Click here to download the PDF.

Click here to download the PDF.

Click here to download the PDF.

Photo by Linda Bartlett

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for a biosimilar rituximab product called Rixathon.

The recommended authorization for Rixathon encompasses all the same indications as the reference medicine, MabThera, which includes non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).

The CHMP’s recommendation for Rixathon has been forwarded to the European Commission, which normally decides whether it will grant marketing authorization for a product within 67 days from the time the CHMP adopts its opinion.

The active substance of Rixathon is rituximab, a monoclonal antibody that binds specifically to the transmembrane protein CD20, which is found on both malignant and normal B cells.

In NHL and CLL, this promotes destruction of malignant B cells and controls tumor growth. In RA, GPA, and MPA, it reduces B cells involved in their pathogenesis.

The reference product for Rixathon is Mabthera, which was authorized for use in the European Union in June 1998.

The CHMP says studies have shown Rixathon to have comparable quality, safety, and efficacy to Mabthera.^{1, 2, 3}

The applicant for Rixathon is Sandoz GmbH.

If authorized by the European Commission, Rixathon will be available for the following indications.

NHL

Rixathon is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV follicular lymphoma (FL).

Rixathon maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.

Rixathon monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.

Rixathon is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.

CLL

Rixathon in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory CLL.

The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.

RA, GPA, and MPA 

Rixathon in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.

Rixathon in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.

1. Visser J et al. Physicochemical and Functional Comparability Between the Proposed Biosimilar Rituximab GP2013 and Originator Rituximab. BioDrugs. 2013;27:495-507.

2. Da Silva A et al. Target-directed development and preclinical characterization of the proposed biosimilar rituximab GP2013. Leuk Lymphoma. 2014;55:1609-1617.

3. Jurczak W et al. A Phase III Efficacy and Safety Study of the Proposed Rituximab Biosimilar GP2013 Versus Rituximab in Patients with Previously Untreated Advanced Follicular Lymphoma. ASH Annual Meeting 2016.

Photo by Linda Bartlett

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for a biosimilar rituximab product called Rixathon.

The recommended authorization for Rixathon encompasses all the same indications as the reference medicine, MabThera, which includes non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).

The CHMP’s recommendation for Rixathon has been forwarded to the European Commission, which normally decides whether it will grant marketing authorization for a product within 67 days from the time the CHMP adopts its opinion.

The active substance of Rixathon is rituximab, a monoclonal antibody that binds specifically to the transmembrane protein CD20, which is found on both malignant and normal B cells.

In NHL and CLL, this promotes destruction of malignant B cells and controls tumor growth. In RA, GPA, and MPA, it reduces B cells involved in their pathogenesis.

The reference product for Rixathon is Mabthera, which was authorized for use in the European Union in June 1998.

The CHMP says studies have shown Rixathon to have comparable quality, safety, and efficacy to Mabthera.^{1, 2, 3}

The applicant for Rixathon is Sandoz GmbH.

If authorized by the European Commission, Rixathon will be available for the following indications.

NHL

Rixathon is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV follicular lymphoma (FL).

Rixathon maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.

Rixathon monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.

Rixathon is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.

CLL

Rixathon in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory CLL.

The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.

RA, GPA, and MPA 

Rixathon in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.

Rixathon in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.

1. Visser J et al. Physicochemical and Functional Comparability Between the Proposed Biosimilar Rituximab GP2013 and Originator Rituximab. BioDrugs. 2013;27:495-507.

2. Da Silva A et al. Target-directed development and preclinical characterization of the proposed biosimilar rituximab GP2013. Leuk Lymphoma. 2014;55:1609-1617.

3. Jurczak W et al. A Phase III Efficacy and Safety Study of the Proposed Rituximab Biosimilar GP2013 Versus Rituximab in Patients with Previously Untreated Advanced Follicular Lymphoma. ASH Annual Meeting 2016.

Photo by Linda Bartlett

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for a biosimilar rituximab product called Rixathon.

The recommended authorization for Rixathon encompasses all the same indications as the reference medicine, MabThera, which includes non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).

The CHMP’s recommendation for Rixathon has been forwarded to the European Commission, which normally decides whether it will grant marketing authorization for a product within 67 days from the time the CHMP adopts its opinion.

The active substance of Rixathon is rituximab, a monoclonal antibody that binds specifically to the transmembrane protein CD20, which is found on both malignant and normal B cells.

In NHL and CLL, this promotes destruction of malignant B cells and controls tumor growth. In RA, GPA, and MPA, it reduces B cells involved in their pathogenesis.

The reference product for Rixathon is Mabthera, which was authorized for use in the European Union in June 1998.

The CHMP says studies have shown Rixathon to have comparable quality, safety, and efficacy to Mabthera.^{1, 2, 3}

The applicant for Rixathon is Sandoz GmbH.

If authorized by the European Commission, Rixathon will be available for the following indications.

NHL

Rixathon is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV follicular lymphoma (FL).

Rixathon maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.

Rixathon monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.

Rixathon is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.

CLL

Rixathon in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory CLL.

The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.

RA, GPA, and MPA 

Rixathon in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.

Rixathon in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.

1. Visser J et al. Physicochemical and Functional Comparability Between the Proposed Biosimilar Rituximab GP2013 and Originator Rituximab. BioDrugs. 2013;27:495-507.

2. Da Silva A et al. Target-directed development and preclinical characterization of the proposed biosimilar rituximab GP2013. Leuk Lymphoma. 2014;55:1609-1617.

3. Jurczak W et al. A Phase III Efficacy and Safety Study of the Proposed Rituximab Biosimilar GP2013 Versus Rituximab in Patients with Previously Untreated Advanced Follicular Lymphoma. ASH Annual Meeting 2016.

VIENNA – An investigational antibiotic effective against several types of gram-negative antibiotic-resistant bacteria has proved its mettle against serious infections of the urinary tract, respiratory tract, and bloodstream.

Plazomicin (Achaogen, San Francisco) posted good results in two phase III studies, handily besting comparator drugs considered gold standard for treating complicated urinary tract infections and pyelonephritis, as well as bloodstream infections and hospital- and ventilator-associated bacterial pneumonia.

Both the EPIC (Evaluating Plazomicin In cUTI) and CARE (Combating Antibiotic Resistant Enterobacteriaceae) trials have provided enough positive data for the company to move forward with a new drug application later this year. The company also plans to seek European Medicines Agency approval in 2018.

Plazomicin is an aminoglycoside that has been modified with several side chains that block aminoglycoside-modifying enzymes, Daniel Cloutier, PhD, principal clinical scientist of Achaogen said at the European Society of Clinical Microbiology and Infectious Disease annual congress.

“Aminoglycoside enzymes tend to travel along with beta-lactamases and carbapenemases as well, so this drug retains potent bactericidal activity against extended spectrum beta-lactamase producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and aminoglycoside-resistant Enterobacteriaceae,” said Dr. Cloutier, who presented the results of the EPIC trial. The drug is given once-daily as a 30-minute intravenous infusion.

EPIC enrolled 609 adult patients with complicated urinary tract infections or acute pyelonephritis; Dr. Cloutier presented a modified intent-to-treat analysis comprising 388 of these. They were randomized to plazomicin 15 mg/kg every 25 hours or to IV meropenem 1 gram every 24 hours. Treatment proceeded for 4-7 days, after which patients could step down to oral therapy (levofloxacin 500 m/day), for a total of 7-10 days of treatment. About 80% of patients had both IV and oral therapy. At 15-19 days from the first dose, patients had a test of cure; at 24-32 days from first dose, they returned for a safety follow-up.

Patients were a mean of 60 years old. About 60% had a complicated UTI; the rest had acute pyelonephritis. About 35% had a mean creatinine clearance of more than 30-60 mL/min; the rest had a mean clearance of more than 60-90 mL/min.

The primary efficacy endpoint was microbial eradication. Plazomicin performed significantly better than meropenem in this measure (87% vs.72%), a mean difference of about 15%. Patients with pyelonephritis responded marginally better than those with complicated UTI, both groups favoring plazomicin (mean treatment differences of 17.5% and 13.7%, respectively).

The results were similar when the investigators examined groups by whether they needed oral step-down treatment. In the IV-only groups, plazomicin bested meropenem in microbiological eradication by almost 19% (84% vs. 65%). In the IV plus oral therapy group, the mean difference was 14%, also in favor of plazomicin (88% vs. 74%).

Plazomicin was significantly more effective then meropenem in all of the resistant Enterobacteriaceae groups (ESBL-positive, and levofloxacin- and aminoglycoside-resistant). It was also significantly more effective against E. coli (17% treatment difference), Klebsiella pneumonia (9%), and Proteus mirabilis (25%). However, it was 20% less effective than meropenem against E. cloacae.

At late follow-up, 2% of the plazomicin group and 8% of the meropenem group had relapsed – a significant difference.

Plazomicin and meropenem had similar safety profiles. Diarrhea and hypertension were the most common adverse events (about 2% in each group). Headache occurred in 3% of the meropenem patients and 1% of the plazomicin patients. Nausea, vomiting, and anemia occurred in about 1% of each group.

More patients taking plazomicin experienced a serum creatinine clearance increase of at least 0.5 mg/dL during treatment (7% vs. 4%). All but two patients taking plazomicin experienced a full recovery by the last follow-up visit.

The CARE trial was much smaller, comprised of 39 patients who had either bloodstream infections, or hospital-acquired or ventilator-associated bacterial pneumonia caused by carbapenem-resistant Enterobacteriaceae. Lynn Connolly, MD, senior medical director and head of late development at Achaogen, presented the data. Recruitment for such a narrow diagnosis was difficult, and hampered patient accrual, she noted.

CARE’s primary endpoints were a combination of all-cause mortality and significant disease-related complications, and all-cause mortality only, both at 28 days.

Patients were randomized 1:1 to either plazomicin 15 mg/kg every 24 hours, or colistin in a 300-mg loading dose, followed by daily infusions of 5 mg/kg. Everyone, regardless of treatment group, could also receive meropenem or tigecycline if deemed necessary. Treatment lasted 7-14 days. There was a test of cure at 7 days from the last IV dose, a safety assessment at 28 days, and a long-term follow-up at 60 days.

The patients’ mean age was about 65 years. Most (about 80%) had a bloodstream infection; bacterial pneumonias were present in the remainder. Most infections (85%) were monomicrobial, with polymicrobial infections making up the balance. Tigecycline was the favored adjunctive therapy (60%), followed by meropenem.

At day 28, plazomicin was associated with significantly better overall outcomes than colistin. It reduced the combination mortality/significant disease complications endpoint by 26% (23% vs. 50% meropenem). This translated to a 53% relative reduction in the risk of death.

Plazomicin also reduced all-cause mortality only by 28% (12% vs. 40% meropenem). This translated to a relative risk reduction of 70.5%.

The study drug performed well in the subgroup of patients with bloodstream infections, reducing the occurrence of the composite endpoint by 39% (14% vs. 53%), and of the mortality-only endpoint by 33% (7% vs. 40%). This translated to a 63% increased chance of 60-day survival in the plazomicin group.

Almost all patients in each group experienced at least one adverse event; 28% were deemed related to plazomicin and 43% to colistin. Many of these events were related to renal function (33% plazomicin, 52% colistin). Serum creatinine increases of at least 0.5 mg/dL during IV treatment occurred in fewer taking plazomicin (1 vs. 6 taking colistin). Full renal recovery occurred in the patient taking plazomicin, but only in three taking colistin.

“These data suggest that plazomicin could offer an important new treatment option for patients with serious infections due to carbapenem-resistant Enterobacteriaceae,” Dr. Connolly said.
 

[email protected]

On Twitter @Alz_gal

VIENNA – An investigational antibiotic effective against several types of gram-negative antibiotic-resistant bacteria has proved its mettle against serious infections of the urinary tract, respiratory tract, and bloodstream.

Plazomicin (Achaogen, San Francisco) posted good results in two phase III studies, handily besting comparator drugs considered gold standard for treating complicated urinary tract infections and pyelonephritis, as well as bloodstream infections and hospital- and ventilator-associated bacterial pneumonia.

Both the EPIC (Evaluating Plazomicin In cUTI) and CARE (Combating Antibiotic Resistant Enterobacteriaceae) trials have provided enough positive data for the company to move forward with a new drug application later this year. The company also plans to seek European Medicines Agency approval in 2018.

Plazomicin is an aminoglycoside that has been modified with several side chains that block aminoglycoside-modifying enzymes, Daniel Cloutier, PhD, principal clinical scientist of Achaogen said at the European Society of Clinical Microbiology and Infectious Disease annual congress.

“Aminoglycoside enzymes tend to travel along with beta-lactamases and carbapenemases as well, so this drug retains potent bactericidal activity against extended spectrum beta-lactamase producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and aminoglycoside-resistant Enterobacteriaceae,” said Dr. Cloutier, who presented the results of the EPIC trial. The drug is given once-daily as a 30-minute intravenous infusion.

EPIC enrolled 609 adult patients with complicated urinary tract infections or acute pyelonephritis; Dr. Cloutier presented a modified intent-to-treat analysis comprising 388 of these. They were randomized to plazomicin 15 mg/kg every 25 hours or to IV meropenem 1 gram every 24 hours. Treatment proceeded for 4-7 days, after which patients could step down to oral therapy (levofloxacin 500 m/day), for a total of 7-10 days of treatment. About 80% of patients had both IV and oral therapy. At 15-19 days from the first dose, patients had a test of cure; at 24-32 days from first dose, they returned for a safety follow-up.

Patients were a mean of 60 years old. About 60% had a complicated UTI; the rest had acute pyelonephritis. About 35% had a mean creatinine clearance of more than 30-60 mL/min; the rest had a mean clearance of more than 60-90 mL/min.

The primary efficacy endpoint was microbial eradication. Plazomicin performed significantly better than meropenem in this measure (87% vs.72%), a mean difference of about 15%. Patients with pyelonephritis responded marginally better than those with complicated UTI, both groups favoring plazomicin (mean treatment differences of 17.5% and 13.7%, respectively).

The results were similar when the investigators examined groups by whether they needed oral step-down treatment. In the IV-only groups, plazomicin bested meropenem in microbiological eradication by almost 19% (84% vs. 65%). In the IV plus oral therapy group, the mean difference was 14%, also in favor of plazomicin (88% vs. 74%).

Plazomicin was significantly more effective then meropenem in all of the resistant Enterobacteriaceae groups (ESBL-positive, and levofloxacin- and aminoglycoside-resistant). It was also significantly more effective against E. coli (17% treatment difference), Klebsiella pneumonia (9%), and Proteus mirabilis (25%). However, it was 20% less effective than meropenem against E. cloacae.

At late follow-up, 2% of the plazomicin group and 8% of the meropenem group had relapsed – a significant difference.

Plazomicin and meropenem had similar safety profiles. Diarrhea and hypertension were the most common adverse events (about 2% in each group). Headache occurred in 3% of the meropenem patients and 1% of the plazomicin patients. Nausea, vomiting, and anemia occurred in about 1% of each group.

More patients taking plazomicin experienced a serum creatinine clearance increase of at least 0.5 mg/dL during treatment (7% vs. 4%). All but two patients taking plazomicin experienced a full recovery by the last follow-up visit.

The CARE trial was much smaller, comprised of 39 patients who had either bloodstream infections, or hospital-acquired or ventilator-associated bacterial pneumonia caused by carbapenem-resistant Enterobacteriaceae. Lynn Connolly, MD, senior medical director and head of late development at Achaogen, presented the data. Recruitment for such a narrow diagnosis was difficult, and hampered patient accrual, she noted.

CARE’s primary endpoints were a combination of all-cause mortality and significant disease-related complications, and all-cause mortality only, both at 28 days.

Patients were randomized 1:1 to either plazomicin 15 mg/kg every 24 hours, or colistin in a 300-mg loading dose, followed by daily infusions of 5 mg/kg. Everyone, regardless of treatment group, could also receive meropenem or tigecycline if deemed necessary. Treatment lasted 7-14 days. There was a test of cure at 7 days from the last IV dose, a safety assessment at 28 days, and a long-term follow-up at 60 days.

The patients’ mean age was about 65 years. Most (about 80%) had a bloodstream infection; bacterial pneumonias were present in the remainder. Most infections (85%) were monomicrobial, with polymicrobial infections making up the balance. Tigecycline was the favored adjunctive therapy (60%), followed by meropenem.

At day 28, plazomicin was associated with significantly better overall outcomes than colistin. It reduced the combination mortality/significant disease complications endpoint by 26% (23% vs. 50% meropenem). This translated to a 53% relative reduction in the risk of death.

Plazomicin also reduced all-cause mortality only by 28% (12% vs. 40% meropenem). This translated to a relative risk reduction of 70.5%.

The study drug performed well in the subgroup of patients with bloodstream infections, reducing the occurrence of the composite endpoint by 39% (14% vs. 53%), and of the mortality-only endpoint by 33% (7% vs. 40%). This translated to a 63% increased chance of 60-day survival in the plazomicin group.

Almost all patients in each group experienced at least one adverse event; 28% were deemed related to plazomicin and 43% to colistin. Many of these events were related to renal function (33% plazomicin, 52% colistin). Serum creatinine increases of at least 0.5 mg/dL during IV treatment occurred in fewer taking plazomicin (1 vs. 6 taking colistin). Full renal recovery occurred in the patient taking plazomicin, but only in three taking colistin.

“These data suggest that plazomicin could offer an important new treatment option for patients with serious infections due to carbapenem-resistant Enterobacteriaceae,” Dr. Connolly said.
 

[email protected]

On Twitter @Alz_gal

VIENNA – An investigational antibiotic effective against several types of gram-negative antibiotic-resistant bacteria has proved its mettle against serious infections of the urinary tract, respiratory tract, and bloodstream.

Plazomicin (Achaogen, San Francisco) posted good results in two phase III studies, handily besting comparator drugs considered gold standard for treating complicated urinary tract infections and pyelonephritis, as well as bloodstream infections and hospital- and ventilator-associated bacterial pneumonia.

Both the EPIC (Evaluating Plazomicin In cUTI) and CARE (Combating Antibiotic Resistant Enterobacteriaceae) trials have provided enough positive data for the company to move forward with a new drug application later this year. The company also plans to seek European Medicines Agency approval in 2018.

Plazomicin is an aminoglycoside that has been modified with several side chains that block aminoglycoside-modifying enzymes, Daniel Cloutier, PhD, principal clinical scientist of Achaogen said at the European Society of Clinical Microbiology and Infectious Disease annual congress.

“Aminoglycoside enzymes tend to travel along with beta-lactamases and carbapenemases as well, so this drug retains potent bactericidal activity against extended spectrum beta-lactamase producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and aminoglycoside-resistant Enterobacteriaceae,” said Dr. Cloutier, who presented the results of the EPIC trial. The drug is given once-daily as a 30-minute intravenous infusion.

EPIC enrolled 609 adult patients with complicated urinary tract infections or acute pyelonephritis; Dr. Cloutier presented a modified intent-to-treat analysis comprising 388 of these. They were randomized to plazomicin 15 mg/kg every 25 hours or to IV meropenem 1 gram every 24 hours. Treatment proceeded for 4-7 days, after which patients could step down to oral therapy (levofloxacin 500 m/day), for a total of 7-10 days of treatment. About 80% of patients had both IV and oral therapy. At 15-19 days from the first dose, patients had a test of cure; at 24-32 days from first dose, they returned for a safety follow-up.

Patients were a mean of 60 years old. About 60% had a complicated UTI; the rest had acute pyelonephritis. About 35% had a mean creatinine clearance of more than 30-60 mL/min; the rest had a mean clearance of more than 60-90 mL/min.

The primary efficacy endpoint was microbial eradication. Plazomicin performed significantly better than meropenem in this measure (87% vs.72%), a mean difference of about 15%. Patients with pyelonephritis responded marginally better than those with complicated UTI, both groups favoring plazomicin (mean treatment differences of 17.5% and 13.7%, respectively).

The results were similar when the investigators examined groups by whether they needed oral step-down treatment. In the IV-only groups, plazomicin bested meropenem in microbiological eradication by almost 19% (84% vs. 65%). In the IV plus oral therapy group, the mean difference was 14%, also in favor of plazomicin (88% vs. 74%).

Plazomicin was significantly more effective then meropenem in all of the resistant Enterobacteriaceae groups (ESBL-positive, and levofloxacin- and aminoglycoside-resistant). It was also significantly more effective against E. coli (17% treatment difference), Klebsiella pneumonia (9%), and Proteus mirabilis (25%). However, it was 20% less effective than meropenem against E. cloacae.

At late follow-up, 2% of the plazomicin group and 8% of the meropenem group had relapsed – a significant difference.

Plazomicin and meropenem had similar safety profiles. Diarrhea and hypertension were the most common adverse events (about 2% in each group). Headache occurred in 3% of the meropenem patients and 1% of the plazomicin patients. Nausea, vomiting, and anemia occurred in about 1% of each group.

More patients taking plazomicin experienced a serum creatinine clearance increase of at least 0.5 mg/dL during treatment (7% vs. 4%). All but two patients taking plazomicin experienced a full recovery by the last follow-up visit.

The CARE trial was much smaller, comprised of 39 patients who had either bloodstream infections, or hospital-acquired or ventilator-associated bacterial pneumonia caused by carbapenem-resistant Enterobacteriaceae. Lynn Connolly, MD, senior medical director and head of late development at Achaogen, presented the data. Recruitment for such a narrow diagnosis was difficult, and hampered patient accrual, she noted.

CARE’s primary endpoints were a combination of all-cause mortality and significant disease-related complications, and all-cause mortality only, both at 28 days.

Patients were randomized 1:1 to either plazomicin 15 mg/kg every 24 hours, or colistin in a 300-mg loading dose, followed by daily infusions of 5 mg/kg. Everyone, regardless of treatment group, could also receive meropenem or tigecycline if deemed necessary. Treatment lasted 7-14 days. There was a test of cure at 7 days from the last IV dose, a safety assessment at 28 days, and a long-term follow-up at 60 days.

The patients’ mean age was about 65 years. Most (about 80%) had a bloodstream infection; bacterial pneumonias were present in the remainder. Most infections (85%) were monomicrobial, with polymicrobial infections making up the balance. Tigecycline was the favored adjunctive therapy (60%), followed by meropenem.

At day 28, plazomicin was associated with significantly better overall outcomes than colistin. It reduced the combination mortality/significant disease complications endpoint by 26% (23% vs. 50% meropenem). This translated to a 53% relative reduction in the risk of death.

Plazomicin also reduced all-cause mortality only by 28% (12% vs. 40% meropenem). This translated to a relative risk reduction of 70.5%.

The study drug performed well in the subgroup of patients with bloodstream infections, reducing the occurrence of the composite endpoint by 39% (14% vs. 53%), and of the mortality-only endpoint by 33% (7% vs. 40%). This translated to a 63% increased chance of 60-day survival in the plazomicin group.

Almost all patients in each group experienced at least one adverse event; 28% were deemed related to plazomicin and 43% to colistin. Many of these events were related to renal function (33% plazomicin, 52% colistin). Serum creatinine increases of at least 0.5 mg/dL during IV treatment occurred in fewer taking plazomicin (1 vs. 6 taking colistin). Full renal recovery occurred in the patient taking plazomicin, but only in three taking colistin.

“These data suggest that plazomicin could offer an important new treatment option for patients with serious infections due to carbapenem-resistant Enterobacteriaceae,” Dr. Connolly said.
 

[email protected]

On Twitter @Alz_gal

Gastric bypass surgery was associated with more than a 50% drop in baseline rates of psoriasis, and with about a 70% decrease in the incidence of psoriatic arthritis, investigators reported.

In contrast, gastric banding did not appear to affect baselines rates of either of these autoimmune conditions, Alexander Egeberg, MD, of Herlev and Gentofte Hospital, Hellerup, Denmark, and associates reported in JAMA Surgery. “Although speculative, these findings may be the result of post-operative differences in weight loss and nutrient uptake, as well as differences in the postsurgical secretion of a number of gut hormones, including [glucagon-like peptide-1],” they wrote.

Psoriasis strongly correlates with obesity, and weight loss appears to mitigate psoriatic symptoms, the investigators noted. Previously, small studies and case series indicated that bariatric surgery might induce remission of psoriasis. To further investigate this possibility, Dr. Egeberg and his associates conducted a longitudinal cohort study of all 12,364 patients who underwent gastric bypass surgery and all 1,071 patients who underwent gastric banding in Denmark between 1997 and 2012 (JAMA Surg. 2017;152:344-349). No patient had psoriasis symptoms at the start of the study. A total of 272 (2%) gastric bypass patients developed psoriasis before their surgery, while only 0.5% did so afterward. In contrast, gastric banding was not tied to a significant change in the incidence of psoriasis – the preoperative rate was 0.5%, and the postoperative rate was 0.4%. Similarly, respective rates of psoriatic arthritis were 0.5% and 0.1% before and after gastric bypass, but were 0.3% and 0.6% before and after gastric banding. Additionally, respective rates of severe psoriasis were 0.8% and 0% before and after gastric bypass, but were about 0.2% and 0.5% before and after gastric banding.

After adjusting for age, sex, alcohol abuse, socioeconomic status, smoking, and diabetes status, gastric bypass was associated with about a 48% drop in the incidence of any type of psoriasis (P = .004), with about a 56% drop in the rate of severe psoriasis (P = .02), and with about a 71% drop in the rate of psoriatic arthritis (P = .01). In contrast, neither crude nor adjusted models linked gastric banding to a decrease in the incidence of psoriasis, severe psoriasis, or psoriatic arthritis, the researchers said.

Gastric banding is “a purely restrictive procedure,” while gastric bypass – especially Roux-en-Y bypass – diverts nutrients to the distal small intestine, where enteroendocrine cells secrete GLP-1, the researchers wrote.

“These postoperative hormonal changes may, in addition to the weight loss, be important for the antipsoriatic effect of gastric bypass,” they added. “Both gastric bypass and gastric banding have been shown to lead to sustained weight loss, suggesting that the observed differences in our study might be caused by factors other than weight loss.”

An unrestricted research grant from the Novo Nordisk Foundation funded the work. Dr. Egeberg disclosed ties to Pfizer and Eli Lilly. One coinvestigator disclosed ties to these and several other pharmaceutical companies.

Gastric bypass surgery was associated with more than a 50% drop in baseline rates of psoriasis, and with about a 70% decrease in the incidence of psoriatic arthritis, investigators reported.

In contrast, gastric banding did not appear to affect baselines rates of either of these autoimmune conditions, Alexander Egeberg, MD, of Herlev and Gentofte Hospital, Hellerup, Denmark, and associates reported in JAMA Surgery. “Although speculative, these findings may be the result of post-operative differences in weight loss and nutrient uptake, as well as differences in the postsurgical secretion of a number of gut hormones, including [glucagon-like peptide-1],” they wrote.

Psoriasis strongly correlates with obesity, and weight loss appears to mitigate psoriatic symptoms, the investigators noted. Previously, small studies and case series indicated that bariatric surgery might induce remission of psoriasis. To further investigate this possibility, Dr. Egeberg and his associates conducted a longitudinal cohort study of all 12,364 patients who underwent gastric bypass surgery and all 1,071 patients who underwent gastric banding in Denmark between 1997 and 2012 (JAMA Surg. 2017;152:344-349). No patient had psoriasis symptoms at the start of the study. A total of 272 (2%) gastric bypass patients developed psoriasis before their surgery, while only 0.5% did so afterward. In contrast, gastric banding was not tied to a significant change in the incidence of psoriasis – the preoperative rate was 0.5%, and the postoperative rate was 0.4%. Similarly, respective rates of psoriatic arthritis were 0.5% and 0.1% before and after gastric bypass, but were 0.3% and 0.6% before and after gastric banding. Additionally, respective rates of severe psoriasis were 0.8% and 0% before and after gastric bypass, but were about 0.2% and 0.5% before and after gastric banding.

After adjusting for age, sex, alcohol abuse, socioeconomic status, smoking, and diabetes status, gastric bypass was associated with about a 48% drop in the incidence of any type of psoriasis (P = .004), with about a 56% drop in the rate of severe psoriasis (P = .02), and with about a 71% drop in the rate of psoriatic arthritis (P = .01). In contrast, neither crude nor adjusted models linked gastric banding to a decrease in the incidence of psoriasis, severe psoriasis, or psoriatic arthritis, the researchers said.

Gastric banding is “a purely restrictive procedure,” while gastric bypass – especially Roux-en-Y bypass – diverts nutrients to the distal small intestine, where enteroendocrine cells secrete GLP-1, the researchers wrote.

“These postoperative hormonal changes may, in addition to the weight loss, be important for the antipsoriatic effect of gastric bypass,” they added. “Both gastric bypass and gastric banding have been shown to lead to sustained weight loss, suggesting that the observed differences in our study might be caused by factors other than weight loss.”

An unrestricted research grant from the Novo Nordisk Foundation funded the work. Dr. Egeberg disclosed ties to Pfizer and Eli Lilly. One coinvestigator disclosed ties to these and several other pharmaceutical companies.

Gastric bypass surgery was associated with more than a 50% drop in baseline rates of psoriasis, and with about a 70% decrease in the incidence of psoriatic arthritis, investigators reported.

In contrast, gastric banding did not appear to affect baselines rates of either of these autoimmune conditions, Alexander Egeberg, MD, of Herlev and Gentofte Hospital, Hellerup, Denmark, and associates reported in JAMA Surgery. “Although speculative, these findings may be the result of post-operative differences in weight loss and nutrient uptake, as well as differences in the postsurgical secretion of a number of gut hormones, including [glucagon-like peptide-1],” they wrote.

Psoriasis strongly correlates with obesity, and weight loss appears to mitigate psoriatic symptoms, the investigators noted. Previously, small studies and case series indicated that bariatric surgery might induce remission of psoriasis. To further investigate this possibility, Dr. Egeberg and his associates conducted a longitudinal cohort study of all 12,364 patients who underwent gastric bypass surgery and all 1,071 patients who underwent gastric banding in Denmark between 1997 and 2012 (JAMA Surg. 2017;152:344-349). No patient had psoriasis symptoms at the start of the study. A total of 272 (2%) gastric bypass patients developed psoriasis before their surgery, while only 0.5% did so afterward. In contrast, gastric banding was not tied to a significant change in the incidence of psoriasis – the preoperative rate was 0.5%, and the postoperative rate was 0.4%. Similarly, respective rates of psoriatic arthritis were 0.5% and 0.1% before and after gastric bypass, but were 0.3% and 0.6% before and after gastric banding. Additionally, respective rates of severe psoriasis were 0.8% and 0% before and after gastric bypass, but were about 0.2% and 0.5% before and after gastric banding.

After adjusting for age, sex, alcohol abuse, socioeconomic status, smoking, and diabetes status, gastric bypass was associated with about a 48% drop in the incidence of any type of psoriasis (P = .004), with about a 56% drop in the rate of severe psoriasis (P = .02), and with about a 71% drop in the rate of psoriatic arthritis (P = .01). In contrast, neither crude nor adjusted models linked gastric banding to a decrease in the incidence of psoriasis, severe psoriasis, or psoriatic arthritis, the researchers said.

Gastric banding is “a purely restrictive procedure,” while gastric bypass – especially Roux-en-Y bypass – diverts nutrients to the distal small intestine, where enteroendocrine cells secrete GLP-1, the researchers wrote.

“These postoperative hormonal changes may, in addition to the weight loss, be important for the antipsoriatic effect of gastric bypass,” they added. “Both gastric bypass and gastric banding have been shown to lead to sustained weight loss, suggesting that the observed differences in our study might be caused by factors other than weight loss.”

An unrestricted research grant from the Novo Nordisk Foundation funded the work. Dr. Egeberg disclosed ties to Pfizer and Eli Lilly. One coinvestigator disclosed ties to these and several other pharmaceutical companies.

Displaying Medicare allowable fees in the electronic health record at the time of order entry did not significantly reduce the number of inpatient lab tests at three Philadelphia hospitals.

In a study involving 98,529 patients and 142,921 admissions, Medicare payment information popped up randomly in the EHR when standard tests including complete blood cell counts, metabolic panels, and liver function tests were ordered. The costs of the labs varied depending on their extent. The message mentioned that “the dollar amount represents Medicare reimbursement for the test. Actual costs to the consumer may vary by patient insurance status.” Just over a third of the patients were actually on Medicare; most had private insurance.

The idea of the study was to see if cost information would curb unnecessary testing, and save money. “There is growing interest in using price transparency to influence medical decision-making toward higher value care,” Mina Sedrak, MD, and her colleagues said in a paper presented at the annual meeting of the Society of General Internal Medicine.

It didn’t work out that way. Four tests ordered per patient day when the messages appeared, and 2.34 when they did not. With messaging, the mean lab fee per patient day was $38.85, versus $27.59 without it. In an adjusted analyses comparing the intervention to the control group, there were no significant changes in overall test ordering (0.05 tests ordered per patient day, P = .06) or associated fees when pricing information was displayed ($0.24 per patient day; P = .47).

In a subset analysis, the investigators did find a small decrease orders for the most expensive labs and a small but significant increase in orders for the least expensive ones when physicians aware of cost (top quartile of tests based on fee value: -0.01; P = .04; bottom quartile: 0.03, P = .04).

Despite the overall negative results, there’s still a likely role for cost information in value improvement programs; what the study shows is that there’s a better way to use it, according to Dr. Sedrak, currently of the City of Hope Comprehensive Cancer Center in Duarte, Calif., and colleagues.

The investigators made several suggestions when reviewing their work.

“First, the price transparency intervention in this study was always displayed regardless of the clinical scenario. The presence of this information for appropriate tests may have diminished its impact when tests were inappropriate. Future efforts may consider more selective targeting of price transparency.” It might also be a good idea to price out different testing options for providers, and use actual charges and other more on-point forms of cost estimates, they said, instead of Medicare fees that have little to do with what many patients are actually charged. Targeting only the most expensive tests might also help (JAMA Intern Med. 2017 April 21. doi: 10.1001/jamainternmed.2017.1144).

The investigators also noticed a problem when labs are ordered to repeat automatically; clinicians did not see the price information every day, and so missed cost information “when it would be most salient.”

The mean age in the study was 54.7 years; 52% of the patients were white, 39% black, and 57% women. The mean length of stay was about 6 days, and over 80% of the patients were discharged home.
 

[email protected]
 

Displaying Medicare allowable fees in the electronic health record at the time of order entry did not significantly reduce the number of inpatient lab tests at three Philadelphia hospitals.

In a study involving 98,529 patients and 142,921 admissions, Medicare payment information popped up randomly in the EHR when standard tests including complete blood cell counts, metabolic panels, and liver function tests were ordered. The costs of the labs varied depending on their extent. The message mentioned that “the dollar amount represents Medicare reimbursement for the test. Actual costs to the consumer may vary by patient insurance status.” Just over a third of the patients were actually on Medicare; most had private insurance.

The idea of the study was to see if cost information would curb unnecessary testing, and save money. “There is growing interest in using price transparency to influence medical decision-making toward higher value care,” Mina Sedrak, MD, and her colleagues said in a paper presented at the annual meeting of the Society of General Internal Medicine.

It didn’t work out that way. Four tests ordered per patient day when the messages appeared, and 2.34 when they did not. With messaging, the mean lab fee per patient day was $38.85, versus $27.59 without it. In an adjusted analyses comparing the intervention to the control group, there were no significant changes in overall test ordering (0.05 tests ordered per patient day, P = .06) or associated fees when pricing information was displayed ($0.24 per patient day; P = .47).

In a subset analysis, the investigators did find a small decrease orders for the most expensive labs and a small but significant increase in orders for the least expensive ones when physicians aware of cost (top quartile of tests based on fee value: -0.01; P = .04; bottom quartile: 0.03, P = .04).

Despite the overall negative results, there’s still a likely role for cost information in value improvement programs; what the study shows is that there’s a better way to use it, according to Dr. Sedrak, currently of the City of Hope Comprehensive Cancer Center in Duarte, Calif., and colleagues.

The investigators made several suggestions when reviewing their work.

“First, the price transparency intervention in this study was always displayed regardless of the clinical scenario. The presence of this information for appropriate tests may have diminished its impact when tests were inappropriate. Future efforts may consider more selective targeting of price transparency.” It might also be a good idea to price out different testing options for providers, and use actual charges and other more on-point forms of cost estimates, they said, instead of Medicare fees that have little to do with what many patients are actually charged. Targeting only the most expensive tests might also help (JAMA Intern Med. 2017 April 21. doi: 10.1001/jamainternmed.2017.1144).

The investigators also noticed a problem when labs are ordered to repeat automatically; clinicians did not see the price information every day, and so missed cost information “when it would be most salient.”

The mean age in the study was 54.7 years; 52% of the patients were white, 39% black, and 57% women. The mean length of stay was about 6 days, and over 80% of the patients were discharged home.
 

[email protected]
 

Displaying Medicare allowable fees in the electronic health record at the time of order entry did not significantly reduce the number of inpatient lab tests at three Philadelphia hospitals.

In a study involving 98,529 patients and 142,921 admissions, Medicare payment information popped up randomly in the EHR when standard tests including complete blood cell counts, metabolic panels, and liver function tests were ordered. The costs of the labs varied depending on their extent. The message mentioned that “the dollar amount represents Medicare reimbursement for the test. Actual costs to the consumer may vary by patient insurance status.” Just over a third of the patients were actually on Medicare; most had private insurance.

The idea of the study was to see if cost information would curb unnecessary testing, and save money. “There is growing interest in using price transparency to influence medical decision-making toward higher value care,” Mina Sedrak, MD, and her colleagues said in a paper presented at the annual meeting of the Society of General Internal Medicine.

It didn’t work out that way. Four tests ordered per patient day when the messages appeared, and 2.34 when they did not. With messaging, the mean lab fee per patient day was $38.85, versus $27.59 without it. In an adjusted analyses comparing the intervention to the control group, there were no significant changes in overall test ordering (0.05 tests ordered per patient day, P = .06) or associated fees when pricing information was displayed ($0.24 per patient day; P = .47).

In a subset analysis, the investigators did find a small decrease orders for the most expensive labs and a small but significant increase in orders for the least expensive ones when physicians aware of cost (top quartile of tests based on fee value: -0.01; P = .04; bottom quartile: 0.03, P = .04).

Despite the overall negative results, there’s still a likely role for cost information in value improvement programs; what the study shows is that there’s a better way to use it, according to Dr. Sedrak, currently of the City of Hope Comprehensive Cancer Center in Duarte, Calif., and colleagues.

The investigators made several suggestions when reviewing their work.

“First, the price transparency intervention in this study was always displayed regardless of the clinical scenario. The presence of this information for appropriate tests may have diminished its impact when tests were inappropriate. Future efforts may consider more selective targeting of price transparency.” It might also be a good idea to price out different testing options for providers, and use actual charges and other more on-point forms of cost estimates, they said, instead of Medicare fees that have little to do with what many patients are actually charged. Targeting only the most expensive tests might also help (JAMA Intern Med. 2017 April 21. doi: 10.1001/jamainternmed.2017.1144).

The investigators also noticed a problem when labs are ordered to repeat automatically; clinicians did not see the price information every day, and so missed cost information “when it would be most salient.”

The mean age in the study was 54.7 years; 52% of the patients were white, 39% black, and 57% women. The mean length of stay was about 6 days, and over 80% of the patients were discharged home.
 

[email protected]
 

The number of people living with diagnosed HIV in the United States will increase to 1,232,054 by 2045, up from 917,294 in 2013, according to projections based on the National HIV Surveillance System and U.S. census data.

The number of people with HIV over age 55 will more than double from 232,113 to 470,221, though the annual growth rate will slow from 1.8% to 0.8%. By 2025, older people will comprise about 38% of the entire HIV population, said investigators led by epidemiologist Julia Hood, of the University of Washington Department of Epidemiology, Seattle.

NIAID

[email protected]

The number of people living with diagnosed HIV in the United States will increase to 1,232,054 by 2045, up from 917,294 in 2013, according to projections based on the National HIV Surveillance System and U.S. census data.

The number of people with HIV over age 55 will more than double from 232,113 to 470,221, though the annual growth rate will slow from 1.8% to 0.8%. By 2025, older people will comprise about 38% of the entire HIV population, said investigators led by epidemiologist Julia Hood, of the University of Washington Department of Epidemiology, Seattle.

NIAID

[email protected]

The number of people living with diagnosed HIV in the United States will increase to 1,232,054 by 2045, up from 917,294 in 2013, according to projections based on the National HIV Surveillance System and U.S. census data.

The number of people with HIV over age 55 will more than double from 232,113 to 470,221, though the annual growth rate will slow from 1.8% to 0.8%. By 2025, older people will comprise about 38% of the entire HIV population, said investigators led by epidemiologist Julia Hood, of the University of Washington Department of Epidemiology, Seattle.

NIAID

[email protected]

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has added 9 disease sites to its NCCN Radiation Therapy Compendium™, a resource that provides a single access point for NCCN recommendations pertaining to radiation therapy (RT).

The compendium provides guidance on all RT modalities recommended within NCCN guidelines, including intensity modulated RT, intra-operative RT, stereotactic radiosurgery/stereotactic body RT/stereotactic ablative RT, image-guided RT, low dose-rate brachytherapy/high dose-rate brachytherapy, radioisotope, and particle therapy.

The NCCN Radiation Therapy Compendium was launched with recommendations pertaining to 24 cancer types.

Now, NCCN has added RT recommendations from an additional 9 NCCN Clinical Practice Guidelines in Oncology:

Acute lymphoblastic leukemia (ALL), Version 2.2016

Basal cell skin cancer, Version 1.2017

Dermatofibrosarcoma protuberans, Version 1.2017

Gastric cancer, Version 1.2017

Hodgkin lymphoma (HL), Version 1.2017

Merkel cell carcinoma, Version 1.2017

Ovarian cancer, Version 1.2017

Squamous cell skin cancer, Version 1.2017

Thymomas and thymic carcinomas, Version 1.2017

The first 24 disease sites included in the NCCN Radiation Therapy Compendium were:

Acute myeloid leukemia

Anal cancer

B-cell lymphomas

Bladder cancer

Breast cancer

Chronic lymphocytic leukemia/small lymphoblastic lymphoma

Colon cancer

Hepatobiliary cancers

Kidney cancer

Malignant pleural mesothelioma

Melanoma

Multiple myeloma

Neuroendocrine tumors

Non-small cell lung cancer

Occult primary cancer

Pancreatic adenocarcinoma

Penile cancer

Primary cutaneous B-cell lymphomas

Prostate cancer

Rectal cancer

Small cell lung cancer

Soft tissue sarcoma

T-cell lymphomas

Testicular cancer

The NCCN said additional cancer types will be added to the NCCN Radiation Therapy Compendium on a rolling basis over the coming months.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium.

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has added 9 disease sites to its NCCN Radiation Therapy Compendium™, a resource that provides a single access point for NCCN recommendations pertaining to radiation therapy (RT).

The compendium provides guidance on all RT modalities recommended within NCCN guidelines, including intensity modulated RT, intra-operative RT, stereotactic radiosurgery/stereotactic body RT/stereotactic ablative RT, image-guided RT, low dose-rate brachytherapy/high dose-rate brachytherapy, radioisotope, and particle therapy.

The NCCN Radiation Therapy Compendium was launched with recommendations pertaining to 24 cancer types.

Now, NCCN has added RT recommendations from an additional 9 NCCN Clinical Practice Guidelines in Oncology:

Acute lymphoblastic leukemia (ALL), Version 2.2016

Basal cell skin cancer, Version 1.2017

Dermatofibrosarcoma protuberans, Version 1.2017

Gastric cancer, Version 1.2017

Hodgkin lymphoma (HL), Version 1.2017

Merkel cell carcinoma, Version 1.2017

Ovarian cancer, Version 1.2017

Squamous cell skin cancer, Version 1.2017

Thymomas and thymic carcinomas, Version 1.2017

The first 24 disease sites included in the NCCN Radiation Therapy Compendium were:

Acute myeloid leukemia

Anal cancer

B-cell lymphomas

Bladder cancer

Breast cancer

Chronic lymphocytic leukemia/small lymphoblastic lymphoma

Colon cancer

Hepatobiliary cancers

Kidney cancer

Malignant pleural mesothelioma

Melanoma

Multiple myeloma

Neuroendocrine tumors

Non-small cell lung cancer

Occult primary cancer

Pancreatic adenocarcinoma

Penile cancer

Primary cutaneous B-cell lymphomas

Prostate cancer

Rectal cancer

Small cell lung cancer

Soft tissue sarcoma

T-cell lymphomas

Testicular cancer

The NCCN said additional cancer types will be added to the NCCN Radiation Therapy Compendium on a rolling basis over the coming months.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium.

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has added 9 disease sites to its NCCN Radiation Therapy Compendium™, a resource that provides a single access point for NCCN recommendations pertaining to radiation therapy (RT).

The compendium provides guidance on all RT modalities recommended within NCCN guidelines, including intensity modulated RT, intra-operative RT, stereotactic radiosurgery/stereotactic body RT/stereotactic ablative RT, image-guided RT, low dose-rate brachytherapy/high dose-rate brachytherapy, radioisotope, and particle therapy.

The NCCN Radiation Therapy Compendium was launched with recommendations pertaining to 24 cancer types.

Now, NCCN has added RT recommendations from an additional 9 NCCN Clinical Practice Guidelines in Oncology:

Acute lymphoblastic leukemia (ALL), Version 2.2016

Basal cell skin cancer, Version 1.2017

Dermatofibrosarcoma protuberans, Version 1.2017

Gastric cancer, Version 1.2017

Hodgkin lymphoma (HL), Version 1.2017

Merkel cell carcinoma, Version 1.2017

Ovarian cancer, Version 1.2017

Squamous cell skin cancer, Version 1.2017

Thymomas and thymic carcinomas, Version 1.2017

The first 24 disease sites included in the NCCN Radiation Therapy Compendium were:

Acute myeloid leukemia

Anal cancer

B-cell lymphomas

Bladder cancer

Breast cancer

Chronic lymphocytic leukemia/small lymphoblastic lymphoma

Colon cancer

Hepatobiliary cancers

Kidney cancer

Malignant pleural mesothelioma

Melanoma

Multiple myeloma

Neuroendocrine tumors

Non-small cell lung cancer

Occult primary cancer

Pancreatic adenocarcinoma

Penile cancer

Primary cutaneous B-cell lymphomas

Prostate cancer

Rectal cancer

Small cell lung cancer

Soft tissue sarcoma

T-cell lymphomas

Testicular cancer

The NCCN said additional cancer types will be added to the NCCN Radiation Therapy Compendium on a rolling basis over the coming months.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium.

Clinical question: Is withholding angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) prior to noncardiac surgery associated with a lower risk of a 30-day composite outcome of all-cause death, myocardial injury after noncardiac surgery, and stroke when compared with continuing them on the day of surgery?

Background: The current American College of Cardiology/American Heart Association guidelines recommend continuing ACEI and ARBs for noncardiac surgery. However, many clinicians, including anesthesiologists, withhold these medications to prevent intraoperative hypotension. Because of the lack of strong evidence regarding clinical outcomes, the decision to withhold ACEI and ARBs prior to noncardiac surgery is currently dictated by physician preference and local policy.

Study Design: Prospective cohort study.

Setting: Analysis sample from the VISION study (Vascular Events in Noncardiac Surgery Patients Cohort Evaluation), which included 12 centers in eight countries.

Synopsis: A sample analysis was performed on 14,687 patients from the VISION study, who were at least 45 years old and undergoing noncardiac surgery and who required an overnight hospital admission. A total of 4,802 patients were taking ACEI/ARBs at baseline, and, for 1,245 (25.9%) of those patients, ACEI/ARBs were withheld at least 24 hours before surgery. Using multivariable regression models, the authors found that patients for whom ACEI/ARBs were withheld were less likely to suffer from the primary composite outcome of 30-day all-cause death, myocardial injury after noncardiac surgery, and stroke (12% vs 12.9%; adjusted relative risk, 0.82; 95% confidence interval, 0.7-0.96; P = .01). Withholding ACEI/ARBs prior to surgery was also associated with less risk of clinically important intraoperative hypotension, while the risk of postoperative hypotension was similar between the two groups.

Given that this was an observational study, analysis is limited because of the inability to account for every potential confounding factor.

Bottom Line: The study suggests a lower risk of postoperative death, stroke, and myocardial injury in patients for whom ACEI/ARBs were withheld prior to noncardiac surgery. A large randomized trial is needed to confirm the findings suggested by this analysis.

Citation: Roshanov PS, Rochwerg B, Patel A, et al. Withholding versus continuing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers before noncardiac surgery.” Anesthesiology. 2017 Jan;126(1):16-27.
 

Dr. Libot is assistant professor in the division of hospital medicine, Loyola University Chicago, Maywood, Ill.

Clinical question: Is withholding angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) prior to noncardiac surgery associated with a lower risk of a 30-day composite outcome of all-cause death, myocardial injury after noncardiac surgery, and stroke when compared with continuing them on the day of surgery?

Background: The current American College of Cardiology/American Heart Association guidelines recommend continuing ACEI and ARBs for noncardiac surgery. However, many clinicians, including anesthesiologists, withhold these medications to prevent intraoperative hypotension. Because of the lack of strong evidence regarding clinical outcomes, the decision to withhold ACEI and ARBs prior to noncardiac surgery is currently dictated by physician preference and local policy.

Study Design: Prospective cohort study.

Setting: Analysis sample from the VISION study (Vascular Events in Noncardiac Surgery Patients Cohort Evaluation), which included 12 centers in eight countries.

Synopsis: A sample analysis was performed on 14,687 patients from the VISION study, who were at least 45 years old and undergoing noncardiac surgery and who required an overnight hospital admission. A total of 4,802 patients were taking ACEI/ARBs at baseline, and, for 1,245 (25.9%) of those patients, ACEI/ARBs were withheld at least 24 hours before surgery. Using multivariable regression models, the authors found that patients for whom ACEI/ARBs were withheld were less likely to suffer from the primary composite outcome of 30-day all-cause death, myocardial injury after noncardiac surgery, and stroke (12% vs 12.9%; adjusted relative risk, 0.82; 95% confidence interval, 0.7-0.96; P = .01). Withholding ACEI/ARBs prior to surgery was also associated with less risk of clinically important intraoperative hypotension, while the risk of postoperative hypotension was similar between the two groups.

Given that this was an observational study, analysis is limited because of the inability to account for every potential confounding factor.

Bottom Line: The study suggests a lower risk of postoperative death, stroke, and myocardial injury in patients for whom ACEI/ARBs were withheld prior to noncardiac surgery. A large randomized trial is needed to confirm the findings suggested by this analysis.

Citation: Roshanov PS, Rochwerg B, Patel A, et al. Withholding versus continuing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers before noncardiac surgery.” Anesthesiology. 2017 Jan;126(1):16-27.
 

Dr. Libot is assistant professor in the division of hospital medicine, Loyola University Chicago, Maywood, Ill.

Clinical question: Is withholding angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) prior to noncardiac surgery associated with a lower risk of a 30-day composite outcome of all-cause death, myocardial injury after noncardiac surgery, and stroke when compared with continuing them on the day of surgery?

Background: The current American College of Cardiology/American Heart Association guidelines recommend continuing ACEI and ARBs for noncardiac surgery. However, many clinicians, including anesthesiologists, withhold these medications to prevent intraoperative hypotension. Because of the lack of strong evidence regarding clinical outcomes, the decision to withhold ACEI and ARBs prior to noncardiac surgery is currently dictated by physician preference and local policy.

Study Design: Prospective cohort study.

Setting: Analysis sample from the VISION study (Vascular Events in Noncardiac Surgery Patients Cohort Evaluation), which included 12 centers in eight countries.

Synopsis: A sample analysis was performed on 14,687 patients from the VISION study, who were at least 45 years old and undergoing noncardiac surgery and who required an overnight hospital admission. A total of 4,802 patients were taking ACEI/ARBs at baseline, and, for 1,245 (25.9%) of those patients, ACEI/ARBs were withheld at least 24 hours before surgery. Using multivariable regression models, the authors found that patients for whom ACEI/ARBs were withheld were less likely to suffer from the primary composite outcome of 30-day all-cause death, myocardial injury after noncardiac surgery, and stroke (12% vs 12.9%; adjusted relative risk, 0.82; 95% confidence interval, 0.7-0.96; P = .01). Withholding ACEI/ARBs prior to surgery was also associated with less risk of clinically important intraoperative hypotension, while the risk of postoperative hypotension was similar between the two groups.

Given that this was an observational study, analysis is limited because of the inability to account for every potential confounding factor.

Bottom Line: The study suggests a lower risk of postoperative death, stroke, and myocardial injury in patients for whom ACEI/ARBs were withheld prior to noncardiac surgery. A large randomized trial is needed to confirm the findings suggested by this analysis.

Citation: Roshanov PS, Rochwerg B, Patel A, et al. Withholding versus continuing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers before noncardiac surgery.” Anesthesiology. 2017 Jan;126(1):16-27.
 

Dr. Libot is assistant professor in the division of hospital medicine, Loyola University Chicago, Maywood, Ill.

The struggle to defeat Ebola virus disease continues globally, although it may not always make the headlines. To catch up on what you may have missed, here are some notable news items and journal articles published over the past few weeks that are worth a second look.

Malaria parasite coinfections were common in patients presenting to Ebola treatment units in Sierra Leone and conferred an increased mortality risk in patients infected with Ebola virus, according to a study in the Lancet Infectious Diseases.

CDC/Daniel J. DeNoon

[email protected]

On Twitter @richpizzi

The struggle to defeat Ebola virus disease continues globally, although it may not always make the headlines. To catch up on what you may have missed, here are some notable news items and journal articles published over the past few weeks that are worth a second look.

Malaria parasite coinfections were common in patients presenting to Ebola treatment units in Sierra Leone and conferred an increased mortality risk in patients infected with Ebola virus, according to a study in the Lancet Infectious Diseases.

CDC/Daniel J. DeNoon

[email protected]

On Twitter @richpizzi

The struggle to defeat Ebola virus disease continues globally, although it may not always make the headlines. To catch up on what you may have missed, here are some notable news items and journal articles published over the past few weeks that are worth a second look.

Malaria parasite coinfections were common in patients presenting to Ebola treatment units in Sierra Leone and conferred an increased mortality risk in patients infected with Ebola virus, according to a study in the Lancet Infectious Diseases.

CDC/Daniel J. DeNoon

[email protected]

On Twitter @richpizzi

The percentage of uninsured veterans dropped by almost 40% in the first 2 years after the Affordable Care Act’s major coverage provisions were implemented, according to a report from the Robert Wood Johnson Foundation and the Urban Institute.

In 2015, 5.9% of the almost 9.4 million veterans aged 19-64 years were uninsured, down from 9.6% in 2013 – the statistically significant difference of 3.8 percentage points representing a relative decline of 38.5%. The difference was even greater for veterans living in the states that had expanded Medicaid by mid-2015, who saw their uninsured rate fall from 9% to 4.8%, compared with those in states that had not, whose uninsured rate declined from 10.3% to 7.1%, the report’s authors said.

[email protected]

The percentage of uninsured veterans dropped by almost 40% in the first 2 years after the Affordable Care Act’s major coverage provisions were implemented, according to a report from the Robert Wood Johnson Foundation and the Urban Institute.

In 2015, 5.9% of the almost 9.4 million veterans aged 19-64 years were uninsured, down from 9.6% in 2013 – the statistically significant difference of 3.8 percentage points representing a relative decline of 38.5%. The difference was even greater for veterans living in the states that had expanded Medicaid by mid-2015, who saw their uninsured rate fall from 9% to 4.8%, compared with those in states that had not, whose uninsured rate declined from 10.3% to 7.1%, the report’s authors said.

[email protected]

The percentage of uninsured veterans dropped by almost 40% in the first 2 years after the Affordable Care Act’s major coverage provisions were implemented, according to a report from the Robert Wood Johnson Foundation and the Urban Institute.

In 2015, 5.9% of the almost 9.4 million veterans aged 19-64 years were uninsured, down from 9.6% in 2013 – the statistically significant difference of 3.8 percentage points representing a relative decline of 38.5%. The difference was even greater for veterans living in the states that had expanded Medicaid by mid-2015, who saw their uninsured rate fall from 9% to 4.8%, compared with those in states that had not, whose uninsured rate declined from 10.3% to 7.1%, the report’s authors said.

[email protected]