The crises of opioids and heroin abuse have skyrocketed, but in just 9 years, hospitalizations for women jumped 75%—much higher than the 55% among men and enough to bring hospitalization rates for the 2 sexes neck and neck. According to a report from the Agency for Healthcare Research and Quality, men and women were hospitalized at virtually the same rate in 2014: about 225 hospitalizations per 100,000 people.

The report, which covered data from 44 states and the District of Columbia, highlighted the broad variations in how the epidemic is hitting the U.S. For instance, opioid hospitalization rates among women were highest in West Virginia, Maryland, and Massachusetts (each state reporting rates of more than 350 hospitalizations per 100,000 people). For men, the highest rates were in the District of Columbia, New York, and Maryland (440+ per 100,000). Iowa, Nebraska, Texas, and Wyoming consistently ranked lowest for opioid-related inpatient stays, while Massachusetts consistently had the highest rates.

Men were more likely than women to make opioid-related emergency department (ED) visits, although ED visit rates rose sharply for both sexes between 2005 and 2014. Arkansas and Iowa consistently ranked lowest for opioid-related emergency department visits; Maryland was the highest.

In all states reporting on opioid-related ED visits, the rate was highest among adults aged 25 to 44 years.

The crises of opioids and heroin abuse have skyrocketed, but in just 9 years, hospitalizations for women jumped 75%—much higher than the 55% among men and enough to bring hospitalization rates for the 2 sexes neck and neck. According to a report from the Agency for Healthcare Research and Quality, men and women were hospitalized at virtually the same rate in 2014: about 225 hospitalizations per 100,000 people.

The report, which covered data from 44 states and the District of Columbia, highlighted the broad variations in how the epidemic is hitting the U.S. For instance, opioid hospitalization rates among women were highest in West Virginia, Maryland, and Massachusetts (each state reporting rates of more than 350 hospitalizations per 100,000 people). For men, the highest rates were in the District of Columbia, New York, and Maryland (440+ per 100,000). Iowa, Nebraska, Texas, and Wyoming consistently ranked lowest for opioid-related inpatient stays, while Massachusetts consistently had the highest rates.

Men were more likely than women to make opioid-related emergency department (ED) visits, although ED visit rates rose sharply for both sexes between 2005 and 2014. Arkansas and Iowa consistently ranked lowest for opioid-related emergency department visits; Maryland was the highest.

In all states reporting on opioid-related ED visits, the rate was highest among adults aged 25 to 44 years.

The crises of opioids and heroin abuse have skyrocketed, but in just 9 years, hospitalizations for women jumped 75%—much higher than the 55% among men and enough to bring hospitalization rates for the 2 sexes neck and neck. According to a report from the Agency for Healthcare Research and Quality, men and women were hospitalized at virtually the same rate in 2014: about 225 hospitalizations per 100,000 people.

The report, which covered data from 44 states and the District of Columbia, highlighted the broad variations in how the epidemic is hitting the U.S. For instance, opioid hospitalization rates among women were highest in West Virginia, Maryland, and Massachusetts (each state reporting rates of more than 350 hospitalizations per 100,000 people). For men, the highest rates were in the District of Columbia, New York, and Maryland (440+ per 100,000). Iowa, Nebraska, Texas, and Wyoming consistently ranked lowest for opioid-related inpatient stays, while Massachusetts consistently had the highest rates.

Men were more likely than women to make opioid-related emergency department (ED) visits, although ED visit rates rose sharply for both sexes between 2005 and 2014. Arkansas and Iowa consistently ranked lowest for opioid-related emergency department visits; Maryland was the highest.

In all states reporting on opioid-related ED visits, the rate was highest among adults aged 25 to 44 years.

Anderson Cancer Center

Researchers say they have created guidelines for managing the unique toxicities associated with chimeric antigen receptor (CAR) T-cell therapy.

The guidelines focus on cytokine release syndrome (CRS); neurological toxicity, which the researchers have dubbed “CAR-T-cell-related encephalopathy syndrome (CRES);” and adverse effects related to these syndromes.

“The toxicities are unique, and every member of the care team needs to be trained to recognize them and act accordingly,” said Sattva Neelapu, MD, of University of Texas MD Anderson Cancer Center in Houston.

Dr Neelapu and his colleagues described the toxicities and related recommendations in Nature Reviews Clinical Oncology.

The team’s guidelines include supportive-care considerations for patients receiving CAR T‑cell therapy. For example, they recommend:

• Baseline brain MRI to rule out central nervous system disease
• Cardiac monitoring starting on the day of CAR T‑cell infusion
• Assessing a patient’s vital signs every 4 hours after CAR T-cell infusion
• Assessing and grading CRS at least twice daily and whenever the patient’s status changes
• Assessing and grading CRES at least every 8 hours.

CRS

One section of the guidelines is dedicated to CRS, with subsections on pathophysiology, precautions and supportive care, the use of corticosteroids and IL‑6/IL‑6R antagonists, and grading CRS.

The researchers noted that CRS typically manifests with constitutional symptoms, such as fever, malaise, anorexia, and myalgias. However, CRS can affect any organ system in the body.

The team recommends managing CRS according to grade. For example, patients with grade 1 CRS should typically receive supportive care. However, physicians should consider giving tocilizumab or siltuximab to grade 1 patients who have a refractory fever lasting more than 3 days.

The researchers also noted that CRS can evolve into fulminant hemophagocytic lymphohistiocytosis (HLH), also known as macrophage-activation syndrome (MAS).

The team said HLH/MAS encompasses a group of severe immunological disorders characterized by hyperactivation of macrophages and lymphocytes, proinflammatory cytokine production, lymphohistiocytic tissue infiltration, and immune-mediated multi-organ failure.

The guidelines include diagnostic criteria for CAR T‑cell-related HLH/MAS and recommendations for managing the condition.

CRES

One section of the guidelines is dedicated to the grading and treatment of CRES, which typically mani­fests as a toxic encephalopathy.

The researchers said the earliest signs of CRES are diminished attention, language disturbance, and impaired handwriting. Other symptoms include confusion, disorientation, agitation, apha­sia, somnolence, and tremors.

Patients with severe CRES (grade >2) may experience seizures, motor weakness, incontinence, mental obtundation, increased intracra­nial pressure, papilledema, and cerebral edema.

Therefore, the guidelines include recommendations for the management of status epilepticus and raised intracranial pressure after CAR T‑cell therapy.

The researchers also devised an algorithm, known as CARTOX-10, for identifying neurotoxicity. (An existing general method didn’t effectively quantify the neurological effects caused by CAR T-cell therapies.)

CARTOX-10 is a 10-point test in which patients are asked to do the following:

• Name the current month (1 point) and year (1 point)
• Name the city (1 point) and hospital they are in (1 point)
• Name the president/prime minister of their home country (1 point)
• Name 3 nearby objects (3 points)
• Write a standard sentence (1 point)
• Count backward from 100 by tens (1 point).

A perfect score indicates normal cognitive function. A patient has mild to severe impairment depending on the number of questions or activities missed.

Dr Neelapu and his colleagues believe their recommendations will be applicable to other types of cell-based immunotherapy as well, including CAR natural killer cells, T-cell receptor engineered T cells, and combination drugs that use an antibody to connect T cells to targets on cancer cells.

Researchers involved in this work have received funding from companies developing/marketing CAR T-cell therapies.

Anderson Cancer Center

Researchers say they have created guidelines for managing the unique toxicities associated with chimeric antigen receptor (CAR) T-cell therapy.

The guidelines focus on cytokine release syndrome (CRS); neurological toxicity, which the researchers have dubbed “CAR-T-cell-related encephalopathy syndrome (CRES);” and adverse effects related to these syndromes.

“The toxicities are unique, and every member of the care team needs to be trained to recognize them and act accordingly,” said Sattva Neelapu, MD, of University of Texas MD Anderson Cancer Center in Houston.

Dr Neelapu and his colleagues described the toxicities and related recommendations in Nature Reviews Clinical Oncology.

The team’s guidelines include supportive-care considerations for patients receiving CAR T‑cell therapy. For example, they recommend:

• Baseline brain MRI to rule out central nervous system disease
• Cardiac monitoring starting on the day of CAR T‑cell infusion
• Assessing a patient’s vital signs every 4 hours after CAR T-cell infusion
• Assessing and grading CRS at least twice daily and whenever the patient’s status changes
• Assessing and grading CRES at least every 8 hours.

CRS

One section of the guidelines is dedicated to CRS, with subsections on pathophysiology, precautions and supportive care, the use of corticosteroids and IL‑6/IL‑6R antagonists, and grading CRS.

The researchers noted that CRS typically manifests with constitutional symptoms, such as fever, malaise, anorexia, and myalgias. However, CRS can affect any organ system in the body.

The team recommends managing CRS according to grade. For example, patients with grade 1 CRS should typically receive supportive care. However, physicians should consider giving tocilizumab or siltuximab to grade 1 patients who have a refractory fever lasting more than 3 days.

The researchers also noted that CRS can evolve into fulminant hemophagocytic lymphohistiocytosis (HLH), also known as macrophage-activation syndrome (MAS).

The team said HLH/MAS encompasses a group of severe immunological disorders characterized by hyperactivation of macrophages and lymphocytes, proinflammatory cytokine production, lymphohistiocytic tissue infiltration, and immune-mediated multi-organ failure.

The guidelines include diagnostic criteria for CAR T‑cell-related HLH/MAS and recommendations for managing the condition.

CRES

One section of the guidelines is dedicated to the grading and treatment of CRES, which typically mani­fests as a toxic encephalopathy.

The researchers said the earliest signs of CRES are diminished attention, language disturbance, and impaired handwriting. Other symptoms include confusion, disorientation, agitation, apha­sia, somnolence, and tremors.

Patients with severe CRES (grade >2) may experience seizures, motor weakness, incontinence, mental obtundation, increased intracra­nial pressure, papilledema, and cerebral edema.

Therefore, the guidelines include recommendations for the management of status epilepticus and raised intracranial pressure after CAR T‑cell therapy.

The researchers also devised an algorithm, known as CARTOX-10, for identifying neurotoxicity. (An existing general method didn’t effectively quantify the neurological effects caused by CAR T-cell therapies.)

CARTOX-10 is a 10-point test in which patients are asked to do the following:

• Name the current month (1 point) and year (1 point)
• Name the city (1 point) and hospital they are in (1 point)
• Name the president/prime minister of their home country (1 point)
• Name 3 nearby objects (3 points)
• Write a standard sentence (1 point)
• Count backward from 100 by tens (1 point).

A perfect score indicates normal cognitive function. A patient has mild to severe impairment depending on the number of questions or activities missed.

Dr Neelapu and his colleagues believe their recommendations will be applicable to other types of cell-based immunotherapy as well, including CAR natural killer cells, T-cell receptor engineered T cells, and combination drugs that use an antibody to connect T cells to targets on cancer cells.

Researchers involved in this work have received funding from companies developing/marketing CAR T-cell therapies.

Anderson Cancer Center

Researchers say they have created guidelines for managing the unique toxicities associated with chimeric antigen receptor (CAR) T-cell therapy.

The guidelines focus on cytokine release syndrome (CRS); neurological toxicity, which the researchers have dubbed “CAR-T-cell-related encephalopathy syndrome (CRES);” and adverse effects related to these syndromes.

“The toxicities are unique, and every member of the care team needs to be trained to recognize them and act accordingly,” said Sattva Neelapu, MD, of University of Texas MD Anderson Cancer Center in Houston.

Dr Neelapu and his colleagues described the toxicities and related recommendations in Nature Reviews Clinical Oncology.

The team’s guidelines include supportive-care considerations for patients receiving CAR T‑cell therapy. For example, they recommend:

• Baseline brain MRI to rule out central nervous system disease
• Cardiac monitoring starting on the day of CAR T‑cell infusion
• Assessing a patient’s vital signs every 4 hours after CAR T-cell infusion
• Assessing and grading CRS at least twice daily and whenever the patient’s status changes
• Assessing and grading CRES at least every 8 hours.

CRS

One section of the guidelines is dedicated to CRS, with subsections on pathophysiology, precautions and supportive care, the use of corticosteroids and IL‑6/IL‑6R antagonists, and grading CRS.

The researchers noted that CRS typically manifests with constitutional symptoms, such as fever, malaise, anorexia, and myalgias. However, CRS can affect any organ system in the body.

The team recommends managing CRS according to grade. For example, patients with grade 1 CRS should typically receive supportive care. However, physicians should consider giving tocilizumab or siltuximab to grade 1 patients who have a refractory fever lasting more than 3 days.

The researchers also noted that CRS can evolve into fulminant hemophagocytic lymphohistiocytosis (HLH), also known as macrophage-activation syndrome (MAS).

The team said HLH/MAS encompasses a group of severe immunological disorders characterized by hyperactivation of macrophages and lymphocytes, proinflammatory cytokine production, lymphohistiocytic tissue infiltration, and immune-mediated multi-organ failure.

The guidelines include diagnostic criteria for CAR T‑cell-related HLH/MAS and recommendations for managing the condition.

CRES

One section of the guidelines is dedicated to the grading and treatment of CRES, which typically mani­fests as a toxic encephalopathy.

The researchers said the earliest signs of CRES are diminished attention, language disturbance, and impaired handwriting. Other symptoms include confusion, disorientation, agitation, apha­sia, somnolence, and tremors.

Patients with severe CRES (grade >2) may experience seizures, motor weakness, incontinence, mental obtundation, increased intracra­nial pressure, papilledema, and cerebral edema.

Therefore, the guidelines include recommendations for the management of status epilepticus and raised intracranial pressure after CAR T‑cell therapy.

The researchers also devised an algorithm, known as CARTOX-10, for identifying neurotoxicity. (An existing general method didn’t effectively quantify the neurological effects caused by CAR T-cell therapies.)

CARTOX-10 is a 10-point test in which patients are asked to do the following:

• Name the current month (1 point) and year (1 point)
• Name the city (1 point) and hospital they are in (1 point)
• Name the president/prime minister of their home country (1 point)
• Name 3 nearby objects (3 points)
• Write a standard sentence (1 point)
• Count backward from 100 by tens (1 point).

A perfect score indicates normal cognitive function. A patient has mild to severe impairment depending on the number of questions or activities missed.

Dr Neelapu and his colleagues believe their recommendations will be applicable to other types of cell-based immunotherapy as well, including CAR natural killer cells, T-cell receptor engineered T cells, and combination drugs that use an antibody to connect T cells to targets on cancer cells.

Researchers involved in this work have received funding from companies developing/marketing CAR T-cell therapies.

Micrograph showing MDS

MADRID—Interim results of a phase 1 study suggest flotetuzumab, a CD123 and CD3 bispecific antibody, may be a feasible treatment option for relapsed or refractory acute myeloid leukemia (AML) or intermediate/high-risk myelodysplastic syndromes (MDS).

Researchers said flotetuzumab demonstrated acceptable tolerability in the dose-escalation portion of the study, with infusion-related reactions (IRRs) and cytokine release syndrome (CRS) being the most common adverse events (AEs).

In addition, flotetuzumab exhibited anti-leukemic activity in 8 of 14 response-evaluable patients, with 6 patients achieving a response.

Norbert Vey, MD, of Institut Paoli-Calmettes in Marseille, France, presented these results at the ESMO 2017 Congress (abstract 995O*). The study is sponsored by MacroGenics, Inc., the company developing flotetuzumab.

Flotetuzumab (MGD006) recognizes CD123 and CD3. The primary mechanism of flotetuzumab is thought to be its ability to redirect T cells to kill CD123-expressing cells. To achieve this, the molecule combines a portion of an antibody recognizing CD3 (an activating molecule expressed by T cells) with an arm that recognizes CD123 on the target cancer cells.

In this ongoing phase 1 study of flotetuzumab, researchers have enrolled 47 patients with a median age of 64 (range, 29-84). About 89% of these patients had AML (n=42), and the rest (n=5) had MDS.

Twenty-four percent had relapsed AML (n=10), 55% had refractory AML (n=23), and 21% had failed treatment with hypomethylating agents (n=9). One patient had intermediate-1-risk MDS, 2 had intermediate-2-risk, and 2 had high-risk MDS.

Treatment

The study began with single patients receiving flotetuzumab at escalating doses—3 ng/kg/day, 10 ng/kg/day, 30 ng/kg/day, and 100 ng/kg/day.

Then, patients received a range of doses on 2 different schedules for cycle 1. One group received treatment 7 days a week. The other had a 4-days-on/3-days-off schedule.

All patients received a lead-in dose during the first week of cycle 1. They received 30 ng/kg/day for 3 days, then 100 ng/kg/day for 4 days.

For the rest of cycle 1, patients in the 4 days/3 days group received doses of 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg. Patients in the daily dosing group received doses of 300 ng/kg, 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg.

For cycle 2 and beyond, all patients were on the 4-days-on/3-days-off schedule.

Safety

The maximum tolerated dose and schedule was 500 ng/kg/day for 7 days.

Dose-limiting toxicities occurring at the 700 ng/kg/day dose included grade 2 IRRs/CRS in 2 patients and grade 3 myalgia in 1 patient. There was 1 drug-related central nervous system AE that led to treatment discontinuation.

IRRs/CRS occurred in 77% of patients, with 13% of patients having grade 3 events and 8.5% of patients discontinuing treatment due to IRRs/CRS.

The researchers said they found ways to decrease the incidence and severity of CRS. One is early intervention with tocilizumab. The other is a 2-step lead-in dose during week 1. So patients first receive 30 ng/kg, then 100 ng/kg, and then their target dose.

Other grade 3 AEs occurring in this trial include febrile neutropenia (11%), anemia (11%), and decreases in platelets (13%), white blood cells (11%), and lymphocytes (13%).

Efficacy

The researchers said they observed encouraging anti-leukemic activity in patients treated at 500 ng/kg/day or greater.

As of the data cut-off, 14 patients treated at this dose were evaluable for response. Eight (57%) patients had anti-leukemic activity, with 6 (43%) of these patients experiencing an objective response.

One patient achieved a complete response (CR), 2 had a CR with incomplete count recovery, and 1 had a molecular CR.

In most responders, anti-leukemic activity was observed after a single cycle of therapy.

MacroGenics is currently enrolling patients in dose-expansion cohorts. The company plans to present updated results from this trial at another scientific conference later this year.

*Slides from this presentation are available on the MacroGenics website at http://ir.macrogenics.com/events.cfm.

Micrograph showing MDS

MADRID—Interim results of a phase 1 study suggest flotetuzumab, a CD123 and CD3 bispecific antibody, may be a feasible treatment option for relapsed or refractory acute myeloid leukemia (AML) or intermediate/high-risk myelodysplastic syndromes (MDS).

Researchers said flotetuzumab demonstrated acceptable tolerability in the dose-escalation portion of the study, with infusion-related reactions (IRRs) and cytokine release syndrome (CRS) being the most common adverse events (AEs).

In addition, flotetuzumab exhibited anti-leukemic activity in 8 of 14 response-evaluable patients, with 6 patients achieving a response.

Norbert Vey, MD, of Institut Paoli-Calmettes in Marseille, France, presented these results at the ESMO 2017 Congress (abstract 995O*). The study is sponsored by MacroGenics, Inc., the company developing flotetuzumab.

Flotetuzumab (MGD006) recognizes CD123 and CD3. The primary mechanism of flotetuzumab is thought to be its ability to redirect T cells to kill CD123-expressing cells. To achieve this, the molecule combines a portion of an antibody recognizing CD3 (an activating molecule expressed by T cells) with an arm that recognizes CD123 on the target cancer cells.

In this ongoing phase 1 study of flotetuzumab, researchers have enrolled 47 patients with a median age of 64 (range, 29-84). About 89% of these patients had AML (n=42), and the rest (n=5) had MDS.

Twenty-four percent had relapsed AML (n=10), 55% had refractory AML (n=23), and 21% had failed treatment with hypomethylating agents (n=9). One patient had intermediate-1-risk MDS, 2 had intermediate-2-risk, and 2 had high-risk MDS.

Treatment

The study began with single patients receiving flotetuzumab at escalating doses—3 ng/kg/day, 10 ng/kg/day, 30 ng/kg/day, and 100 ng/kg/day.

Then, patients received a range of doses on 2 different schedules for cycle 1. One group received treatment 7 days a week. The other had a 4-days-on/3-days-off schedule.

All patients received a lead-in dose during the first week of cycle 1. They received 30 ng/kg/day for 3 days, then 100 ng/kg/day for 4 days.

For the rest of cycle 1, patients in the 4 days/3 days group received doses of 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg. Patients in the daily dosing group received doses of 300 ng/kg, 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg.

For cycle 2 and beyond, all patients were on the 4-days-on/3-days-off schedule.

Safety

The maximum tolerated dose and schedule was 500 ng/kg/day for 7 days.

Dose-limiting toxicities occurring at the 700 ng/kg/day dose included grade 2 IRRs/CRS in 2 patients and grade 3 myalgia in 1 patient. There was 1 drug-related central nervous system AE that led to treatment discontinuation.

IRRs/CRS occurred in 77% of patients, with 13% of patients having grade 3 events and 8.5% of patients discontinuing treatment due to IRRs/CRS.

The researchers said they found ways to decrease the incidence and severity of CRS. One is early intervention with tocilizumab. The other is a 2-step lead-in dose during week 1. So patients first receive 30 ng/kg, then 100 ng/kg, and then their target dose.

Other grade 3 AEs occurring in this trial include febrile neutropenia (11%), anemia (11%), and decreases in platelets (13%), white blood cells (11%), and lymphocytes (13%).

Efficacy

The researchers said they observed encouraging anti-leukemic activity in patients treated at 500 ng/kg/day or greater.

As of the data cut-off, 14 patients treated at this dose were evaluable for response. Eight (57%) patients had anti-leukemic activity, with 6 (43%) of these patients experiencing an objective response.

One patient achieved a complete response (CR), 2 had a CR with incomplete count recovery, and 1 had a molecular CR.

In most responders, anti-leukemic activity was observed after a single cycle of therapy.

MacroGenics is currently enrolling patients in dose-expansion cohorts. The company plans to present updated results from this trial at another scientific conference later this year.

*Slides from this presentation are available on the MacroGenics website at http://ir.macrogenics.com/events.cfm.

Micrograph showing MDS

MADRID—Interim results of a phase 1 study suggest flotetuzumab, a CD123 and CD3 bispecific antibody, may be a feasible treatment option for relapsed or refractory acute myeloid leukemia (AML) or intermediate/high-risk myelodysplastic syndromes (MDS).

Researchers said flotetuzumab demonstrated acceptable tolerability in the dose-escalation portion of the study, with infusion-related reactions (IRRs) and cytokine release syndrome (CRS) being the most common adverse events (AEs).

In addition, flotetuzumab exhibited anti-leukemic activity in 8 of 14 response-evaluable patients, with 6 patients achieving a response.

Norbert Vey, MD, of Institut Paoli-Calmettes in Marseille, France, presented these results at the ESMO 2017 Congress (abstract 995O*). The study is sponsored by MacroGenics, Inc., the company developing flotetuzumab.

Flotetuzumab (MGD006) recognizes CD123 and CD3. The primary mechanism of flotetuzumab is thought to be its ability to redirect T cells to kill CD123-expressing cells. To achieve this, the molecule combines a portion of an antibody recognizing CD3 (an activating molecule expressed by T cells) with an arm that recognizes CD123 on the target cancer cells.

In this ongoing phase 1 study of flotetuzumab, researchers have enrolled 47 patients with a median age of 64 (range, 29-84). About 89% of these patients had AML (n=42), and the rest (n=5) had MDS.

Twenty-four percent had relapsed AML (n=10), 55% had refractory AML (n=23), and 21% had failed treatment with hypomethylating agents (n=9). One patient had intermediate-1-risk MDS, 2 had intermediate-2-risk, and 2 had high-risk MDS.

Treatment

The study began with single patients receiving flotetuzumab at escalating doses—3 ng/kg/day, 10 ng/kg/day, 30 ng/kg/day, and 100 ng/kg/day.

Then, patients received a range of doses on 2 different schedules for cycle 1. One group received treatment 7 days a week. The other had a 4-days-on/3-days-off schedule.

All patients received a lead-in dose during the first week of cycle 1. They received 30 ng/kg/day for 3 days, then 100 ng/kg/day for 4 days.

For the rest of cycle 1, patients in the 4 days/3 days group received doses of 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg. Patients in the daily dosing group received doses of 300 ng/kg, 500 ng/kg, 700 ng/kg, 900 ng/kg, or 1000 ng/kg.

For cycle 2 and beyond, all patients were on the 4-days-on/3-days-off schedule.

Safety

The maximum tolerated dose and schedule was 500 ng/kg/day for 7 days.

Dose-limiting toxicities occurring at the 700 ng/kg/day dose included grade 2 IRRs/CRS in 2 patients and grade 3 myalgia in 1 patient. There was 1 drug-related central nervous system AE that led to treatment discontinuation.

IRRs/CRS occurred in 77% of patients, with 13% of patients having grade 3 events and 8.5% of patients discontinuing treatment due to IRRs/CRS.

The researchers said they found ways to decrease the incidence and severity of CRS. One is early intervention with tocilizumab. The other is a 2-step lead-in dose during week 1. So patients first receive 30 ng/kg, then 100 ng/kg, and then their target dose.

Other grade 3 AEs occurring in this trial include febrile neutropenia (11%), anemia (11%), and decreases in platelets (13%), white blood cells (11%), and lymphocytes (13%).

Efficacy

The researchers said they observed encouraging anti-leukemic activity in patients treated at 500 ng/kg/day or greater.

As of the data cut-off, 14 patients treated at this dose were evaluable for response. Eight (57%) patients had anti-leukemic activity, with 6 (43%) of these patients experiencing an objective response.

One patient achieved a complete response (CR), 2 had a CR with incomplete count recovery, and 1 had a molecular CR.

In most responders, anti-leukemic activity was observed after a single cycle of therapy.

MacroGenics is currently enrolling patients in dose-expansion cohorts. The company plans to present updated results from this trial at another scientific conference later this year.

*Slides from this presentation are available on the MacroGenics website at http://ir.macrogenics.com/events.cfm.

General Medical Sciences

The National Human Genome Research Institute (NHGRI) has created an online toolkit to help nurses integrate genomics into patient care.

The Method for Introducing a New Competency Genomics (MINC) website provides resources for nursing leaders at all levels of genomics competency, ranging from basic knowledge about genomics to its practical impact on healthcare systems and policies.

The resources are intended to help practicing nurses care for patients undergoing genomic testing and treatments, build awareness in their communities, and understand how to prepare their workforce for emerging clinical applications.

“The MINC toolkit is a starting point for healthcare providers who want to promote genomic integration into practice to benefit their patients,” said Laura Lyman Rodriguez, PhD, director of the Division of Policy, Communication and Education at NHGRI.

“It was designed based on the efforts of magnet hospital nurses whose experiences were used in the design and foundation for the toolkit.”

The toolkit is structured in a question and answer format, allowing users to tailor their interventions based on the resources that will work best for them in their clinical setting.

A key feature of the toolkit is “Champion Stories.” These video testimonials from health administrators and educators describe how they overcame barriers as they developed the necessary genomics knowledge to offer personalized care to their patients.

General Medical Sciences

The National Human Genome Research Institute (NHGRI) has created an online toolkit to help nurses integrate genomics into patient care.

The Method for Introducing a New Competency Genomics (MINC) website provides resources for nursing leaders at all levels of genomics competency, ranging from basic knowledge about genomics to its practical impact on healthcare systems and policies.

The resources are intended to help practicing nurses care for patients undergoing genomic testing and treatments, build awareness in their communities, and understand how to prepare their workforce for emerging clinical applications.

“The MINC toolkit is a starting point for healthcare providers who want to promote genomic integration into practice to benefit their patients,” said Laura Lyman Rodriguez, PhD, director of the Division of Policy, Communication and Education at NHGRI.

“It was designed based on the efforts of magnet hospital nurses whose experiences were used in the design and foundation for the toolkit.”

The toolkit is structured in a question and answer format, allowing users to tailor their interventions based on the resources that will work best for them in their clinical setting.

A key feature of the toolkit is “Champion Stories.” These video testimonials from health administrators and educators describe how they overcame barriers as they developed the necessary genomics knowledge to offer personalized care to their patients.

General Medical Sciences

The National Human Genome Research Institute (NHGRI) has created an online toolkit to help nurses integrate genomics into patient care.

The Method for Introducing a New Competency Genomics (MINC) website provides resources for nursing leaders at all levels of genomics competency, ranging from basic knowledge about genomics to its practical impact on healthcare systems and policies.

The resources are intended to help practicing nurses care for patients undergoing genomic testing and treatments, build awareness in their communities, and understand how to prepare their workforce for emerging clinical applications.

“The MINC toolkit is a starting point for healthcare providers who want to promote genomic integration into practice to benefit their patients,” said Laura Lyman Rodriguez, PhD, director of the Division of Policy, Communication and Education at NHGRI.

“It was designed based on the efforts of magnet hospital nurses whose experiences were used in the design and foundation for the toolkit.”

The toolkit is structured in a question and answer format, allowing users to tailor their interventions based on the resources that will work best for them in their clinical setting.

A key feature of the toolkit is “Champion Stories.” These video testimonials from health administrators and educators describe how they overcame barriers as they developed the necessary genomics knowledge to offer personalized care to their patients.

Arthroscopic identification and evaluation of the meniscomeniscal ligament.

Arthroscopic identification and evaluation of the meniscomeniscal ligament.

Arthroscopic identification and evaluation of the meniscomeniscal ligament.

The Food and Drug Administration has approved Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol), a triple-therapy inhaler for the treatment of chronic obstructive pulmonary disease (COPD) in adult patients, according to a press release from GlaxoSmithKline and Innoviva.

Trelegy Ellipta combines an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting beta_2-adrenergic agonist into an inhaler meant for once-daily use in people with COPD. Chronic bronchitis and/or emphysema patients are also indicated for treatment. The FDA-approved dosage is 100 mcg of fluticasone furoate, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

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The Food and Drug Administration has approved Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol), a triple-therapy inhaler for the treatment of chronic obstructive pulmonary disease (COPD) in adult patients, according to a press release from GlaxoSmithKline and Innoviva.

Trelegy Ellipta combines an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting beta_2-adrenergic agonist into an inhaler meant for once-daily use in people with COPD. Chronic bronchitis and/or emphysema patients are also indicated for treatment. The FDA-approved dosage is 100 mcg of fluticasone furoate, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

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The Food and Drug Administration has approved Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol), a triple-therapy inhaler for the treatment of chronic obstructive pulmonary disease (COPD) in adult patients, according to a press release from GlaxoSmithKline and Innoviva.

Trelegy Ellipta combines an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting beta_2-adrenergic agonist into an inhaler meant for once-daily use in people with COPD. Chronic bronchitis and/or emphysema patients are also indicated for treatment. The FDA-approved dosage is 100 mcg of fluticasone furoate, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

BARCELONA – A program promoting broader anticoagulation of patients with atrial fibrillation that used education and feedback from practice audits produced a substantial increase in sustained anticoagulant use and cut strokes in a multinational study with almost 2,300 patients in 48 practices.

Among atrial fibrillation (AF) patients who were not on an anticoagulant at baseline (34% of the enrolled group) 48% of patients in the intervention group began anticoagulant treatment and remained on it for a year with intervention compared with 18% of patients in the control arm without the intervention, Christopher B. Granger, MD, said at the annual congress of the European Society of Cardiology.

The intervention, which highlighted to health care providers the opportunity to start their AF patients on anticoagulant treatment, “transforms how care is provided to this population” of AF patients, Dr. Granger said in a video interview. “Doing something like this can have enormous public health implications.”

IMPACT AF (The Clinical Trial to Improve Treatment With Blood Thinners in Patients With Atrial Fibrillation) randomized 2,281 AF patients in 48 practices in five middle-income countries: Argentina, Brazil, China, India, and Romania. Randomization was by practice, and patients were assigned to either usual care or to an intervention that ran educational sessions for patients and providers on the benefits of and best practices for using anticoagulants. The intervention also monitored anticoagulant use by the patients in each practice and gave providers case-by-case feedback on the care patients received. The educational component customized the feedback to focus on overcoming treatment barriers specific for each patient. This audit and feedback process was a key part of the intervention, Dr. Granger said.

In an adjusted analysis, among patients not on an anticoagulant at baseline, the ones managed in practices that received the intervention had a greater than fourfold likelihood of receiving anticoagulant treatment, compared with patients in practices with no intervention. The intervention was especially successful in transitioning patients off of aspirin treatment, considered ineffective for AF stroke prevention, and onto an anticoagulant, most commonly warfarin.

Overall, anticoagulant use rose by 12 percentage points from baseline among patients in the intervention practices and by 3 percentage points over baseline among the control patients, a statistically significant difference for the study’s primary endpoint.

During 1-year follow-up, 11 strokes occurred among patients managed in practices that received the intervention and 21 in those in control practices, a 52% relative hazard reduction linked with the intervention that was statistically significant, Dr. Granger reported. Concurrently with his talk, the results also appeared online (Lancet. 2017. doi: 10.1016/S0140-6736[17]32165-7).

“How will we take what we have learned [in IMPACT AF] and have it available to people who want to replicate this?” asked Dr. Granger. “We have partnered with several national cardiology societies, and we are working with them to optimize the tools and provide the tools we’ve used,” he said. “We will develop a website for people who want to take this information and use it in their practices.” Dr. Granger and his associates also are working with the Food and Drug Administration and other groups to come up with interventions specially designed for U.S. practice.

IMPACT AF received partial funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Dr. Granger has received honoraria and research funding from all of these companies, and also from Janssen and Medtronic.

[email protected]

On Twitter @mitchelzoler

BARCELONA – A program promoting broader anticoagulation of patients with atrial fibrillation that used education and feedback from practice audits produced a substantial increase in sustained anticoagulant use and cut strokes in a multinational study with almost 2,300 patients in 48 practices.

Among atrial fibrillation (AF) patients who were not on an anticoagulant at baseline (34% of the enrolled group) 48% of patients in the intervention group began anticoagulant treatment and remained on it for a year with intervention compared with 18% of patients in the control arm without the intervention, Christopher B. Granger, MD, said at the annual congress of the European Society of Cardiology.

The intervention, which highlighted to health care providers the opportunity to start their AF patients on anticoagulant treatment, “transforms how care is provided to this population” of AF patients, Dr. Granger said in a video interview. “Doing something like this can have enormous public health implications.”

IMPACT AF (The Clinical Trial to Improve Treatment With Blood Thinners in Patients With Atrial Fibrillation) randomized 2,281 AF patients in 48 practices in five middle-income countries: Argentina, Brazil, China, India, and Romania. Randomization was by practice, and patients were assigned to either usual care or to an intervention that ran educational sessions for patients and providers on the benefits of and best practices for using anticoagulants. The intervention also monitored anticoagulant use by the patients in each practice and gave providers case-by-case feedback on the care patients received. The educational component customized the feedback to focus on overcoming treatment barriers specific for each patient. This audit and feedback process was a key part of the intervention, Dr. Granger said.

In an adjusted analysis, among patients not on an anticoagulant at baseline, the ones managed in practices that received the intervention had a greater than fourfold likelihood of receiving anticoagulant treatment, compared with patients in practices with no intervention. The intervention was especially successful in transitioning patients off of aspirin treatment, considered ineffective for AF stroke prevention, and onto an anticoagulant, most commonly warfarin.

Overall, anticoagulant use rose by 12 percentage points from baseline among patients in the intervention practices and by 3 percentage points over baseline among the control patients, a statistically significant difference for the study’s primary endpoint.

During 1-year follow-up, 11 strokes occurred among patients managed in practices that received the intervention and 21 in those in control practices, a 52% relative hazard reduction linked with the intervention that was statistically significant, Dr. Granger reported. Concurrently with his talk, the results also appeared online (Lancet. 2017. doi: 10.1016/S0140-6736[17]32165-7).

“How will we take what we have learned [in IMPACT AF] and have it available to people who want to replicate this?” asked Dr. Granger. “We have partnered with several national cardiology societies, and we are working with them to optimize the tools and provide the tools we’ve used,” he said. “We will develop a website for people who want to take this information and use it in their practices.” Dr. Granger and his associates also are working with the Food and Drug Administration and other groups to come up with interventions specially designed for U.S. practice.

IMPACT AF received partial funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Dr. Granger has received honoraria and research funding from all of these companies, and also from Janssen and Medtronic.

[email protected]

On Twitter @mitchelzoler

BARCELONA – A program promoting broader anticoagulation of patients with atrial fibrillation that used education and feedback from practice audits produced a substantial increase in sustained anticoagulant use and cut strokes in a multinational study with almost 2,300 patients in 48 practices.

Among atrial fibrillation (AF) patients who were not on an anticoagulant at baseline (34% of the enrolled group) 48% of patients in the intervention group began anticoagulant treatment and remained on it for a year with intervention compared with 18% of patients in the control arm without the intervention, Christopher B. Granger, MD, said at the annual congress of the European Society of Cardiology.

The intervention, which highlighted to health care providers the opportunity to start their AF patients on anticoagulant treatment, “transforms how care is provided to this population” of AF patients, Dr. Granger said in a video interview. “Doing something like this can have enormous public health implications.”

IMPACT AF (The Clinical Trial to Improve Treatment With Blood Thinners in Patients With Atrial Fibrillation) randomized 2,281 AF patients in 48 practices in five middle-income countries: Argentina, Brazil, China, India, and Romania. Randomization was by practice, and patients were assigned to either usual care or to an intervention that ran educational sessions for patients and providers on the benefits of and best practices for using anticoagulants. The intervention also monitored anticoagulant use by the patients in each practice and gave providers case-by-case feedback on the care patients received. The educational component customized the feedback to focus on overcoming treatment barriers specific for each patient. This audit and feedback process was a key part of the intervention, Dr. Granger said.

In an adjusted analysis, among patients not on an anticoagulant at baseline, the ones managed in practices that received the intervention had a greater than fourfold likelihood of receiving anticoagulant treatment, compared with patients in practices with no intervention. The intervention was especially successful in transitioning patients off of aspirin treatment, considered ineffective for AF stroke prevention, and onto an anticoagulant, most commonly warfarin.

Overall, anticoagulant use rose by 12 percentage points from baseline among patients in the intervention practices and by 3 percentage points over baseline among the control patients, a statistically significant difference for the study’s primary endpoint.

During 1-year follow-up, 11 strokes occurred among patients managed in practices that received the intervention and 21 in those in control practices, a 52% relative hazard reduction linked with the intervention that was statistically significant, Dr. Granger reported. Concurrently with his talk, the results also appeared online (Lancet. 2017. doi: 10.1016/S0140-6736[17]32165-7).

“How will we take what we have learned [in IMPACT AF] and have it available to people who want to replicate this?” asked Dr. Granger. “We have partnered with several national cardiology societies, and we are working with them to optimize the tools and provide the tools we’ve used,” he said. “We will develop a website for people who want to take this information and use it in their practices.” Dr. Granger and his associates also are working with the Food and Drug Administration and other groups to come up with interventions specially designed for U.S. practice.

IMPACT AF received partial funding from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. Dr. Granger has received honoraria and research funding from all of these companies, and also from Janssen and Medtronic.

[email protected]

On Twitter @mitchelzoler

Over 15% of adults have used electronic cigarettes at some time, and about 3% reported current use when they were surveyed in 2016, according to the Centers for Disease Control and Prevention.

When those numbers are broken down by age group, the youngest adults are the most likely e-cigarette users: 23.5% of those aged 18-24 years had ever vaped and 4.5% were currently vaping either every day or on some days, the CDC reported (MMWR. 2017;66[33]:892).

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Over 15% of adults have used electronic cigarettes at some time, and about 3% reported current use when they were surveyed in 2016, according to the Centers for Disease Control and Prevention.

When those numbers are broken down by age group, the youngest adults are the most likely e-cigarette users: 23.5% of those aged 18-24 years had ever vaped and 4.5% were currently vaping either every day or on some days, the CDC reported (MMWR. 2017;66[33]:892).

[email protected]

Over 15% of adults have used electronic cigarettes at some time, and about 3% reported current use when they were surveyed in 2016, according to the Centers for Disease Control and Prevention.

When those numbers are broken down by age group, the youngest adults are the most likely e-cigarette users: 23.5% of those aged 18-24 years had ever vaped and 4.5% were currently vaping either every day or on some days, the CDC reported (MMWR. 2017;66[33]:892).

[email protected]

SAN DIEGO – Hyperbaric oxygen therapy, a mainstay of wound care, has a long and controversial history as a treatment for diabetic foot ulcers. Conflicting studies have spawned plenty of debate, and the most recent Cochrane Library review of existing research didn’t shed much light on the value of the treatment because the evidence was weak (Cochrane Database Syst Rev. 2015 Jun 24;[6]:CD004123).

But William H. Tettelbach, MD, a wound care specialist, told an audience at the annual scientific sessions of the American Diabetic Association that hyperbaric treatments are worth a try in certain cases. And he brought evidence to prove it – a 2015 report he coauthored that reviewed studies and offered clinical practice guidelines for hyperbaric oxygen therapy for the treatment of diabetic foot ulcers (DFUs) (Undersea Hyperb Med. 2015 May-Jun;42[3]:205-47).

Question: What did your review of research tell you about the value of hyperbaric oxygen treatment for DFUs?

Answer: We came to the same conclusion that most of the papers have indicated over the years: Hyperbaric oxygen is effective and attains goals such as reducing rates of amputation in a select population of diabetic ulcer patients.

Patients who have Wagner grade 3 or greater ulcers or admitted for surgery due to a septic diabetic foot benefit from an evaluation by a hyperbaric medicine–trained physician and treatment when indicated. There is evidence and years of clinical experience indicating that these patients benefit and have improved outcomes when evaluated and treated appropriately with hyperbaric oxygen therapy.

In the United States, hyperbaric oxygen therapy is not indicated in Wagner grade 2, 1 or 0 diabetic foot ulcers, the ulcers that involve soft tissue but not deep structure like bone.
 

Q: Why has there been so much controversy over the value of this treatment? 

A: In the past, there have been problems with commercial outpatient wound centers that are heavily driven by profits. Financial margins in wound care clinics can be tight, and the need to remain profitable has at times resulted in patients being treated inappropriately with hyperbaric oxygen therapy (Adv Skin Wound Care. 2017 Apr;30[4]:181-90).

Q: Why does hyperbaric oxygen treatment work in some cases?

A: When you place a patient in a hyperbaric chamber where they breathe 100% oxygen under pressure, you increase the percentage of oxygen in the blood. At such a high percentage, oxygen saturates the plasma versus just being carried by red blood cells, thereby allowing the oxygen to penetrate farther into hypoxic tissues. By increasing the oxygen, you have the ability to make the environment unfavorable for rapid proliferation of anaerobic or microaerophilic bacteria that do not survive a highly oxygen-rich environment. Increasing tissue oxygen tension to 30 mm Hg or greater increases the macrophages’ ability to have an oxidative burst needed to kill bacteria. Furthermore, there are antibiotics that require certain levels of oxygen for transport across the bacterial cell wall.

Q: What should physicians understand about hyperbaric oxygen therapy for DFUs?

A: Overall, hyperbaric practitioners need to be more selective in identifying and treating patients according to what the evidence supports. Poorly designed trials with misleading results should not drive medical decisions. We should revisit diabetic foot ulcers through well-thought-out studies that target those who would benefit as suggested by current evidence. Prior trials have been heavily weighted with Wagner grade 1 and 2 candidates or ischemic diabetic ulcers that are not revascularized. These are biased toward poor outcomes since the current evidence does not strongly support treating these types of individuals with adjunctive hyperbaric oxygen therapy (Ont Health Technol Assess Ser. 2017 May 12;17[5]:1-142. eCollection 2017).

Q: What conditions should trigger endocrinologists to think about hyperbaric oxygen therapy for their DFU patients?

A: Candidates for the therapy include diabetic ulcers that have persisted for longer than 30 days, since these ulcers are at a significantly higher risk of a complicating infection, along with those that have failed treatment or are becoming more symptomatic over time (Undersea Hyperb Med. 2017 Mar-Apr;44[2]:157-60). 

At that point, it might make sense to refer those patients to a wound and hyperbaric specialist for further evaluation and management, especially to a wound center that offers hyperbaric oxygen therapy.  

These wound centers can be found in smaller towns. But some folks will have to travel, perhaps to a wound center at a hospital that has room and board like they do for cancer patients. 
 

Q: What about treatment after surgery?

A: Using hyperbariatric oxygen therapy to treat inpatients with septic diabetic foot ulcers – Wagner grade 3 or higher – immediately after surgery may reduce length of stay as well as lower the risk of requiring multiple surgical debridements. 

Q: What are the best-case scenarios for treatment?

A: A significant portion of what we do is limb preservation. Hyperbaric oxygen therapy often can help save a digit, forefoot, or even an extremity. 

But it’s not something that just happens overnight. It’s a long-term process. Underlying complicating osteomyelitis may require up to 40-60 adjunctive hyperbaric oxygen treatments, 5 days a week with weekends off, along with concurrent antibiotics, wound care, and vascular interventions when indicated. 
 

Q: Is insurance ever an issue for this treatment?

A: Typically, not if one follows the indications set by the Centers for Medicare & Medicaid Services and the Undersea and Hyperbaric Medical Society.

Medicare lists 15 medical indications that it will cover, and a majority of commercial insurers will cover the same 15 indications and possibly more. But commercial insurers may require prior authorization of medical necessity before preceding with hyperbaric oxygen therapy (Diving Hyperb Med. 2016 Sep;46[3]:133-4).

SAN DIEGO – Hyperbaric oxygen therapy, a mainstay of wound care, has a long and controversial history as a treatment for diabetic foot ulcers. Conflicting studies have spawned plenty of debate, and the most recent Cochrane Library review of existing research didn’t shed much light on the value of the treatment because the evidence was weak (Cochrane Database Syst Rev. 2015 Jun 24;[6]:CD004123).

But William H. Tettelbach, MD, a wound care specialist, told an audience at the annual scientific sessions of the American Diabetic Association that hyperbaric treatments are worth a try in certain cases. And he brought evidence to prove it – a 2015 report he coauthored that reviewed studies and offered clinical practice guidelines for hyperbaric oxygen therapy for the treatment of diabetic foot ulcers (DFUs) (Undersea Hyperb Med. 2015 May-Jun;42[3]:205-47).

Question: What did your review of research tell you about the value of hyperbaric oxygen treatment for DFUs?

Answer: We came to the same conclusion that most of the papers have indicated over the years: Hyperbaric oxygen is effective and attains goals such as reducing rates of amputation in a select population of diabetic ulcer patients.

Patients who have Wagner grade 3 or greater ulcers or admitted for surgery due to a septic diabetic foot benefit from an evaluation by a hyperbaric medicine–trained physician and treatment when indicated. There is evidence and years of clinical experience indicating that these patients benefit and have improved outcomes when evaluated and treated appropriately with hyperbaric oxygen therapy.

In the United States, hyperbaric oxygen therapy is not indicated in Wagner grade 2, 1 or 0 diabetic foot ulcers, the ulcers that involve soft tissue but not deep structure like bone.
 

Q: Why has there been so much controversy over the value of this treatment? 

A: In the past, there have been problems with commercial outpatient wound centers that are heavily driven by profits. Financial margins in wound care clinics can be tight, and the need to remain profitable has at times resulted in patients being treated inappropriately with hyperbaric oxygen therapy (Adv Skin Wound Care. 2017 Apr;30[4]:181-90).

Q: Why does hyperbaric oxygen treatment work in some cases?

A: When you place a patient in a hyperbaric chamber where they breathe 100% oxygen under pressure, you increase the percentage of oxygen in the blood. At such a high percentage, oxygen saturates the plasma versus just being carried by red blood cells, thereby allowing the oxygen to penetrate farther into hypoxic tissues. By increasing the oxygen, you have the ability to make the environment unfavorable for rapid proliferation of anaerobic or microaerophilic bacteria that do not survive a highly oxygen-rich environment. Increasing tissue oxygen tension to 30 mm Hg or greater increases the macrophages’ ability to have an oxidative burst needed to kill bacteria. Furthermore, there are antibiotics that require certain levels of oxygen for transport across the bacterial cell wall.

Q: What should physicians understand about hyperbaric oxygen therapy for DFUs?

A: Overall, hyperbaric practitioners need to be more selective in identifying and treating patients according to what the evidence supports. Poorly designed trials with misleading results should not drive medical decisions. We should revisit diabetic foot ulcers through well-thought-out studies that target those who would benefit as suggested by current evidence. Prior trials have been heavily weighted with Wagner grade 1 and 2 candidates or ischemic diabetic ulcers that are not revascularized. These are biased toward poor outcomes since the current evidence does not strongly support treating these types of individuals with adjunctive hyperbaric oxygen therapy (Ont Health Technol Assess Ser. 2017 May 12;17[5]:1-142. eCollection 2017).

Q: What conditions should trigger endocrinologists to think about hyperbaric oxygen therapy for their DFU patients?

A: Candidates for the therapy include diabetic ulcers that have persisted for longer than 30 days, since these ulcers are at a significantly higher risk of a complicating infection, along with those that have failed treatment or are becoming more symptomatic over time (Undersea Hyperb Med. 2017 Mar-Apr;44[2]:157-60). 

At that point, it might make sense to refer those patients to a wound and hyperbaric specialist for further evaluation and management, especially to a wound center that offers hyperbaric oxygen therapy.  

These wound centers can be found in smaller towns. But some folks will have to travel, perhaps to a wound center at a hospital that has room and board like they do for cancer patients. 
 

Q: What about treatment after surgery?

A: Using hyperbariatric oxygen therapy to treat inpatients with septic diabetic foot ulcers – Wagner grade 3 or higher – immediately after surgery may reduce length of stay as well as lower the risk of requiring multiple surgical debridements. 

Q: What are the best-case scenarios for treatment?

A: A significant portion of what we do is limb preservation. Hyperbaric oxygen therapy often can help save a digit, forefoot, or even an extremity. 

But it’s not something that just happens overnight. It’s a long-term process. Underlying complicating osteomyelitis may require up to 40-60 adjunctive hyperbaric oxygen treatments, 5 days a week with weekends off, along with concurrent antibiotics, wound care, and vascular interventions when indicated. 
 

Q: Is insurance ever an issue for this treatment?

A: Typically, not if one follows the indications set by the Centers for Medicare & Medicaid Services and the Undersea and Hyperbaric Medical Society.

Medicare lists 15 medical indications that it will cover, and a majority of commercial insurers will cover the same 15 indications and possibly more. But commercial insurers may require prior authorization of medical necessity before preceding with hyperbaric oxygen therapy (Diving Hyperb Med. 2016 Sep;46[3]:133-4).

SAN DIEGO – Hyperbaric oxygen therapy, a mainstay of wound care, has a long and controversial history as a treatment for diabetic foot ulcers. Conflicting studies have spawned plenty of debate, and the most recent Cochrane Library review of existing research didn’t shed much light on the value of the treatment because the evidence was weak (Cochrane Database Syst Rev. 2015 Jun 24;[6]:CD004123).

But William H. Tettelbach, MD, a wound care specialist, told an audience at the annual scientific sessions of the American Diabetic Association that hyperbaric treatments are worth a try in certain cases. And he brought evidence to prove it – a 2015 report he coauthored that reviewed studies and offered clinical practice guidelines for hyperbaric oxygen therapy for the treatment of diabetic foot ulcers (DFUs) (Undersea Hyperb Med. 2015 May-Jun;42[3]:205-47).

Question: What did your review of research tell you about the value of hyperbaric oxygen treatment for DFUs?

Answer: We came to the same conclusion that most of the papers have indicated over the years: Hyperbaric oxygen is effective and attains goals such as reducing rates of amputation in a select population of diabetic ulcer patients.

Patients who have Wagner grade 3 or greater ulcers or admitted for surgery due to a septic diabetic foot benefit from an evaluation by a hyperbaric medicine–trained physician and treatment when indicated. There is evidence and years of clinical experience indicating that these patients benefit and have improved outcomes when evaluated and treated appropriately with hyperbaric oxygen therapy.

In the United States, hyperbaric oxygen therapy is not indicated in Wagner grade 2, 1 or 0 diabetic foot ulcers, the ulcers that involve soft tissue but not deep structure like bone.
 

Q: Why has there been so much controversy over the value of this treatment? 

A: In the past, there have been problems with commercial outpatient wound centers that are heavily driven by profits. Financial margins in wound care clinics can be tight, and the need to remain profitable has at times resulted in patients being treated inappropriately with hyperbaric oxygen therapy (Adv Skin Wound Care. 2017 Apr;30[4]:181-90).

Q: Why does hyperbaric oxygen treatment work in some cases?

A: When you place a patient in a hyperbaric chamber where they breathe 100% oxygen under pressure, you increase the percentage of oxygen in the blood. At such a high percentage, oxygen saturates the plasma versus just being carried by red blood cells, thereby allowing the oxygen to penetrate farther into hypoxic tissues. By increasing the oxygen, you have the ability to make the environment unfavorable for rapid proliferation of anaerobic or microaerophilic bacteria that do not survive a highly oxygen-rich environment. Increasing tissue oxygen tension to 30 mm Hg or greater increases the macrophages’ ability to have an oxidative burst needed to kill bacteria. Furthermore, there are antibiotics that require certain levels of oxygen for transport across the bacterial cell wall.

Q: What should physicians understand about hyperbaric oxygen therapy for DFUs?

A: Overall, hyperbaric practitioners need to be more selective in identifying and treating patients according to what the evidence supports. Poorly designed trials with misleading results should not drive medical decisions. We should revisit diabetic foot ulcers through well-thought-out studies that target those who would benefit as suggested by current evidence. Prior trials have been heavily weighted with Wagner grade 1 and 2 candidates or ischemic diabetic ulcers that are not revascularized. These are biased toward poor outcomes since the current evidence does not strongly support treating these types of individuals with adjunctive hyperbaric oxygen therapy (Ont Health Technol Assess Ser. 2017 May 12;17[5]:1-142. eCollection 2017).

Q: What conditions should trigger endocrinologists to think about hyperbaric oxygen therapy for their DFU patients?

A: Candidates for the therapy include diabetic ulcers that have persisted for longer than 30 days, since these ulcers are at a significantly higher risk of a complicating infection, along with those that have failed treatment or are becoming more symptomatic over time (Undersea Hyperb Med. 2017 Mar-Apr;44[2]:157-60). 

At that point, it might make sense to refer those patients to a wound and hyperbaric specialist for further evaluation and management, especially to a wound center that offers hyperbaric oxygen therapy.  

These wound centers can be found in smaller towns. But some folks will have to travel, perhaps to a wound center at a hospital that has room and board like they do for cancer patients. 
 

Q: What about treatment after surgery?

A: Using hyperbariatric oxygen therapy to treat inpatients with septic diabetic foot ulcers – Wagner grade 3 or higher – immediately after surgery may reduce length of stay as well as lower the risk of requiring multiple surgical debridements. 

Q: What are the best-case scenarios for treatment?

A: A significant portion of what we do is limb preservation. Hyperbaric oxygen therapy often can help save a digit, forefoot, or even an extremity. 

But it’s not something that just happens overnight. It’s a long-term process. Underlying complicating osteomyelitis may require up to 40-60 adjunctive hyperbaric oxygen treatments, 5 days a week with weekends off, along with concurrent antibiotics, wound care, and vascular interventions when indicated. 
 

Q: Is insurance ever an issue for this treatment?

A: Typically, not if one follows the indications set by the Centers for Medicare & Medicaid Services and the Undersea and Hyperbaric Medical Society.

Medicare lists 15 medical indications that it will cover, and a majority of commercial insurers will cover the same 15 indications and possibly more. But commercial insurers may require prior authorization of medical necessity before preceding with hyperbaric oxygen therapy (Diving Hyperb Med. 2016 Sep;46[3]:133-4).

Madrid – A combination of the investigational cyclin-dependent kinase 4/6 (CDK4/6) agent abemaciclib and a nonsteroidal aromatase inhibitor (AI) was associated with a near doubling of progression-free survival in postmenopausal women with previously untreated hormone-receptor positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) advanced breast cancer.

At a planned 18-month interim analysis of the MONARCH 3 trial, the median investigator-assessed progression free survival (PFS), the primary endpoint, had not been reached for 328 patients assigned to receive abemaciclib with either anastrozole (Arimidex) or letrozole (Femara). In contrast, the median PFS for 165 patients assigned to an AI and a placebo was 14.7 months, translating into a hazard ratio (HR) of 0.543 (P = .000021), reported Angelo Di Leo, MD, of Hospital of Prato, Istituto Toscano Tumori, Prato, Italy.

“Abemaciclib in combination with a nonsteroidal aromatase inhibitor is superior to a nonsteroidal aromatase inhibitor alone in terms of progression-free survival, but also in terms of the objective response rate as the initial treatment of HER2-negative, endocrine sensitive advanced breast cancer,” he said at a briefing prior to his presentation of the data in a presidential symposium at the European Society for Medical Oncology Congress.

Neil Osterweil/Frontline Medical News

[email protected]

Madrid – A combination of the investigational cyclin-dependent kinase 4/6 (CDK4/6) agent abemaciclib and a nonsteroidal aromatase inhibitor (AI) was associated with a near doubling of progression-free survival in postmenopausal women with previously untreated hormone-receptor positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) advanced breast cancer.

At a planned 18-month interim analysis of the MONARCH 3 trial, the median investigator-assessed progression free survival (PFS), the primary endpoint, had not been reached for 328 patients assigned to receive abemaciclib with either anastrozole (Arimidex) or letrozole (Femara). In contrast, the median PFS for 165 patients assigned to an AI and a placebo was 14.7 months, translating into a hazard ratio (HR) of 0.543 (P = .000021), reported Angelo Di Leo, MD, of Hospital of Prato, Istituto Toscano Tumori, Prato, Italy.

“Abemaciclib in combination with a nonsteroidal aromatase inhibitor is superior to a nonsteroidal aromatase inhibitor alone in terms of progression-free survival, but also in terms of the objective response rate as the initial treatment of HER2-negative, endocrine sensitive advanced breast cancer,” he said at a briefing prior to his presentation of the data in a presidential symposium at the European Society for Medical Oncology Congress.

Neil Osterweil/Frontline Medical News

[email protected]

Madrid – A combination of the investigational cyclin-dependent kinase 4/6 (CDK4/6) agent abemaciclib and a nonsteroidal aromatase inhibitor (AI) was associated with a near doubling of progression-free survival in postmenopausal women with previously untreated hormone-receptor positive, human epidermal growth factor receptor 2–negative (HR+/HER2-) advanced breast cancer.

At a planned 18-month interim analysis of the MONARCH 3 trial, the median investigator-assessed progression free survival (PFS), the primary endpoint, had not been reached for 328 patients assigned to receive abemaciclib with either anastrozole (Arimidex) or letrozole (Femara). In contrast, the median PFS for 165 patients assigned to an AI and a placebo was 14.7 months, translating into a hazard ratio (HR) of 0.543 (P = .000021), reported Angelo Di Leo, MD, of Hospital of Prato, Istituto Toscano Tumori, Prato, Italy.

“Abemaciclib in combination with a nonsteroidal aromatase inhibitor is superior to a nonsteroidal aromatase inhibitor alone in terms of progression-free survival, but also in terms of the objective response rate as the initial treatment of HER2-negative, endocrine sensitive advanced breast cancer,” he said at a briefing prior to his presentation of the data in a presidential symposium at the European Society for Medical Oncology Congress.

Neil Osterweil/Frontline Medical News

[email protected]