Six months of stable international normalized ratio values [INRs] while on warfarin therapy doesn’t predict continued INR stability, according to a Research Letter to the Editor published August 9 in JAMA.

Whether or not to switch patients with atrial fibrillation from warfarin to non–vitamin K anticoagulants remains controversial. “A common belief has been that patients with stable INRs while taking warfarin would continue to be stable and derive less benefit from switching to non–vitamin K oral anticoagulants,” said Sean D. Pokorney, MD, of the division of cardiology, Duke University Medical Center, Durham, N.C., and his associates.

But the results of their observational study of 3,749 patients enrolled in an atrial fibrillation registry show that such stability cannot be predicted, and “challenge the notion that patients who have done well taking warfarin should maintain taking warfarin,” the investigators said (JAMA. 2016;316:661-3).

They assessed INRs over the course of 3 years of follow-up using data from patients enrolled in the registry through 176 clinics. INR stability was defined as having 80% or more of INRs in the therapeutic range (2-3). The mean patient age was 75 years, and 43% were women.

A total of 968 patients showed such INR stability throughout the first 6 months of the study. However, 36% of them went on to have at least one “well out of range” INR during the following year. Even in the subgroup of 376 patients who had 100% of their INRs within the therapeutic range during the first 6 months, 33% went on to have at least one “well out of range” INR during the following year, according to Dr. Pokorney and his associates.

No sponsor was cited for this study. Dr. Pokorney reported ties to AstraZeneca, Boston Scientific, Gilead, Janssen, and Medtronic; his associates reported ties to numerous industry sources.

Six months of stable international normalized ratio values [INRs] while on warfarin therapy doesn’t predict continued INR stability, according to a Research Letter to the Editor published August 9 in JAMA.

Whether or not to switch patients with atrial fibrillation from warfarin to non–vitamin K anticoagulants remains controversial. “A common belief has been that patients with stable INRs while taking warfarin would continue to be stable and derive less benefit from switching to non–vitamin K oral anticoagulants,” said Sean D. Pokorney, MD, of the division of cardiology, Duke University Medical Center, Durham, N.C., and his associates.

But the results of their observational study of 3,749 patients enrolled in an atrial fibrillation registry show that such stability cannot be predicted, and “challenge the notion that patients who have done well taking warfarin should maintain taking warfarin,” the investigators said (JAMA. 2016;316:661-3).

They assessed INRs over the course of 3 years of follow-up using data from patients enrolled in the registry through 176 clinics. INR stability was defined as having 80% or more of INRs in the therapeutic range (2-3). The mean patient age was 75 years, and 43% were women.

A total of 968 patients showed such INR stability throughout the first 6 months of the study. However, 36% of them went on to have at least one “well out of range” INR during the following year. Even in the subgroup of 376 patients who had 100% of their INRs within the therapeutic range during the first 6 months, 33% went on to have at least one “well out of range” INR during the following year, according to Dr. Pokorney and his associates.

No sponsor was cited for this study. Dr. Pokorney reported ties to AstraZeneca, Boston Scientific, Gilead, Janssen, and Medtronic; his associates reported ties to numerous industry sources.

Six months of stable international normalized ratio values [INRs] while on warfarin therapy doesn’t predict continued INR stability, according to a Research Letter to the Editor published August 9 in JAMA.

Whether or not to switch patients with atrial fibrillation from warfarin to non–vitamin K anticoagulants remains controversial. “A common belief has been that patients with stable INRs while taking warfarin would continue to be stable and derive less benefit from switching to non–vitamin K oral anticoagulants,” said Sean D. Pokorney, MD, of the division of cardiology, Duke University Medical Center, Durham, N.C., and his associates.

But the results of their observational study of 3,749 patients enrolled in an atrial fibrillation registry show that such stability cannot be predicted, and “challenge the notion that patients who have done well taking warfarin should maintain taking warfarin,” the investigators said (JAMA. 2016;316:661-3).

They assessed INRs over the course of 3 years of follow-up using data from patients enrolled in the registry through 176 clinics. INR stability was defined as having 80% or more of INRs in the therapeutic range (2-3). The mean patient age was 75 years, and 43% were women.

A total of 968 patients showed such INR stability throughout the first 6 months of the study. However, 36% of them went on to have at least one “well out of range” INR during the following year. Even in the subgroup of 376 patients who had 100% of their INRs within the therapeutic range during the first 6 months, 33% went on to have at least one “well out of range” INR during the following year, according to Dr. Pokorney and his associates.

No sponsor was cited for this study. Dr. Pokorney reported ties to AstraZeneca, Boston Scientific, Gilead, Janssen, and Medtronic; his associates reported ties to numerous industry sources.

According to a report published by AmericanEHR Partners, 61% of respondents in 2010 said they were “satisfied” or “very satisfied” with their electronic health records (EHRs), compared with just 34% in 2014. Additionally, close to half of all respondents reported a negative response to questions related to costs, efficiency, and productivity. SHM’s IT Committee would like to obtain your insight on the EHR within your institution. The findings from the survey will be released in a white paper on how the current state of EHRs affects the quality of patient care and the professional satisfaction of hospitalists.

Please take a few minutes to offer your feedback at www.hospitalmedicine.org/ITEHR.

According to a report published by AmericanEHR Partners, 61% of respondents in 2010 said they were “satisfied” or “very satisfied” with their electronic health records (EHRs), compared with just 34% in 2014. Additionally, close to half of all respondents reported a negative response to questions related to costs, efficiency, and productivity. SHM’s IT Committee would like to obtain your insight on the EHR within your institution. The findings from the survey will be released in a white paper on how the current state of EHRs affects the quality of patient care and the professional satisfaction of hospitalists.

Please take a few minutes to offer your feedback at www.hospitalmedicine.org/ITEHR.

According to a report published by AmericanEHR Partners, 61% of respondents in 2010 said they were “satisfied” or “very satisfied” with their electronic health records (EHRs), compared with just 34% in 2014. Additionally, close to half of all respondents reported a negative response to questions related to costs, efficiency, and productivity. SHM’s IT Committee would like to obtain your insight on the EHR within your institution. The findings from the survey will be released in a white paper on how the current state of EHRs affects the quality of patient care and the professional satisfaction of hospitalists.

Please take a few minutes to offer your feedback at www.hospitalmedicine.org/ITEHR.

• Chicago: Aug. 27
• St. Louis: September
• Philadelphia: October
• Atlanta: Oct. 13
• Denver: Oct. 18
• San Francisco: Oct. 20
• New York City: Nov. 3
• Chicago: December

Visit www.futureofhospitalmedicine.org/events to learn more and see updated schedule details.

• Chicago: Aug. 27
• St. Louis: September
• Philadelphia: October
• Atlanta: Oct. 13
• Denver: Oct. 18
• San Francisco: Oct. 20
• New York City: Nov. 3
• Chicago: December

Visit www.futureofhospitalmedicine.org/events to learn more and see updated schedule details.

• Chicago: Aug. 27
• St. Louis: September
• Philadelphia: October
• Atlanta: Oct. 13
• Denver: Oct. 18
• San Francisco: Oct. 20
• New York City: Nov. 3
• Chicago: December

Visit www.futureofhospitalmedicine.org/events to learn more and see updated schedule details.

Hydroxyurea

Photo by Zak Hubbard

Researchers say they have uncovered hydroxyurea’s main mechanism of action in sickle cell disease (SCD).

The drug’s mechanism has been a topic of debate, with some researchers claiming hydroxyurea works by reactivating fetal hemoglobin and others saying it increases the volume of red blood cells (RBCs), thereby reducing the concentration of sickle hemoglobin.

Now, research published in PNAS suggests the latter mechanism is the dominant one.

“Our findings shine a light on the mechanism behind hydroxyurea action, which has long been debated in the scientific community,” said study author Ming Dao, PhD, of the Massachusetts Institute of Technology in Cambridge.

“It’s exciting to see that, using the latest optical imaging tools, we can now confirm which one is the dominating mechanism. Understanding the key mechanism of action will allow us to explore novel and improved therapeutic approaches for sickle cell disease.”

For this study, the researchers analyzed blood samples from patients with SCD.

The team used common-path interferometric microscopy to assess the biophysical properties (shape, surface area, and volume) and biomechanical properties (flexibility and stickiness) of RBCs.

The researchers separated RBCs into 4 groups based on their density. Normal, disc-shaped cells were the least dense, while severely sickled cells were the densest.

The team then compares samples from patients who were taking hydroxyurea and those who were not.

The RBCs of patients receiving treatment showed an improvement in all of the biophysical and biomechanical properties tested across all density levels.

Improvement in the physical properties of RBCs from patients treated with hydroxyurea correlated more with an increase in RBC volume than with levels of fetal hemoglobin.

The researchers hope these biophysical markers can be combined with biochemical and molecular-level markers to assess the severity of a patient’s disease, determine whether or not a patient will respond to hydroxyurea, and monitor the effectiveness of that treatment.

“There is a critical need for patient-specific biomarkers that can be used to assess the effectiveness of treatments for sickle cell disease,” said study author Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania.

“This study shows how techniques commonly used in engineering and physics can help us to better understand how the red blood cells in people with sickle cell disease react to treatment, which could lead to improved diagnostics and therapies.”

Hydroxyurea

Photo by Zak Hubbard

Researchers say they have uncovered hydroxyurea’s main mechanism of action in sickle cell disease (SCD).

The drug’s mechanism has been a topic of debate, with some researchers claiming hydroxyurea works by reactivating fetal hemoglobin and others saying it increases the volume of red blood cells (RBCs), thereby reducing the concentration of sickle hemoglobin.

Now, research published in PNAS suggests the latter mechanism is the dominant one.

“Our findings shine a light on the mechanism behind hydroxyurea action, which has long been debated in the scientific community,” said study author Ming Dao, PhD, of the Massachusetts Institute of Technology in Cambridge.

“It’s exciting to see that, using the latest optical imaging tools, we can now confirm which one is the dominating mechanism. Understanding the key mechanism of action will allow us to explore novel and improved therapeutic approaches for sickle cell disease.”

For this study, the researchers analyzed blood samples from patients with SCD.

The team used common-path interferometric microscopy to assess the biophysical properties (shape, surface area, and volume) and biomechanical properties (flexibility and stickiness) of RBCs.

The researchers separated RBCs into 4 groups based on their density. Normal, disc-shaped cells were the least dense, while severely sickled cells were the densest.

The team then compares samples from patients who were taking hydroxyurea and those who were not.

The RBCs of patients receiving treatment showed an improvement in all of the biophysical and biomechanical properties tested across all density levels.

Improvement in the physical properties of RBCs from patients treated with hydroxyurea correlated more with an increase in RBC volume than with levels of fetal hemoglobin.

The researchers hope these biophysical markers can be combined with biochemical and molecular-level markers to assess the severity of a patient’s disease, determine whether or not a patient will respond to hydroxyurea, and monitor the effectiveness of that treatment.

“There is a critical need for patient-specific biomarkers that can be used to assess the effectiveness of treatments for sickle cell disease,” said study author Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania.

“This study shows how techniques commonly used in engineering and physics can help us to better understand how the red blood cells in people with sickle cell disease react to treatment, which could lead to improved diagnostics and therapies.”

Hydroxyurea

Photo by Zak Hubbard

Researchers say they have uncovered hydroxyurea’s main mechanism of action in sickle cell disease (SCD).

The drug’s mechanism has been a topic of debate, with some researchers claiming hydroxyurea works by reactivating fetal hemoglobin and others saying it increases the volume of red blood cells (RBCs), thereby reducing the concentration of sickle hemoglobin.

Now, research published in PNAS suggests the latter mechanism is the dominant one.

“Our findings shine a light on the mechanism behind hydroxyurea action, which has long been debated in the scientific community,” said study author Ming Dao, PhD, of the Massachusetts Institute of Technology in Cambridge.

“It’s exciting to see that, using the latest optical imaging tools, we can now confirm which one is the dominating mechanism. Understanding the key mechanism of action will allow us to explore novel and improved therapeutic approaches for sickle cell disease.”

For this study, the researchers analyzed blood samples from patients with SCD.

The team used common-path interferometric microscopy to assess the biophysical properties (shape, surface area, and volume) and biomechanical properties (flexibility and stickiness) of RBCs.

The researchers separated RBCs into 4 groups based on their density. Normal, disc-shaped cells were the least dense, while severely sickled cells were the densest.

The team then compares samples from patients who were taking hydroxyurea and those who were not.

The RBCs of patients receiving treatment showed an improvement in all of the biophysical and biomechanical properties tested across all density levels.

Improvement in the physical properties of RBCs from patients treated with hydroxyurea correlated more with an increase in RBC volume than with levels of fetal hemoglobin.

The researchers hope these biophysical markers can be combined with biochemical and molecular-level markers to assess the severity of a patient’s disease, determine whether or not a patient will respond to hydroxyurea, and monitor the effectiveness of that treatment.

“There is a critical need for patient-specific biomarkers that can be used to assess the effectiveness of treatments for sickle cell disease,” said study author Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania.

“This study shows how techniques commonly used in engineering and physics can help us to better understand how the red blood cells in people with sickle cell disease react to treatment, which could lead to improved diagnostics and therapies.”

Micrograph showing MM

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Ixazomib is the first oral proteasome inhibitor approved for this indication.

The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceutical Company Limited.

Micrograph showing MM

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Ixazomib is the first oral proteasome inhibitor approved for this indication.

The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceutical Company Limited.

Micrograph showing MM

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Ixazomib is the first oral proteasome inhibitor approved for this indication.

The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceutical Company Limited.

Study authors Jianan Gong,

David Segal, and Yuan Yao

Photo from the Walter

and Eliza Hall Institute

A new class of inhibitors may be effective in treating a majority of patients with multiple myeloma (MM), according to research published in Blood.

Experiments in multiple MM cell lines suggested the majority of myelomas rely on the protein MCL1 to stay alive.

And targeting MCL1 inhibited disease progression in mouse models of MM.

Therefore, researchers believe drugs designed to inhibit MCL1 may be a promising treatment option for MM.

“Our research shows that switching off MCL1 has the potential to be an effective new treatment approach for the majority of patients with myeloma,” said Jianan Gong, PhD, of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.

For this study, Dr Gong and her colleagues investigated the survival proteins that keep MM cells alive.

The team found that a majority of MM cell lines—about 70%—died when MCL1 was switched off. This included well-established, immortalized MM cell lines (17/25) and low-passage MM cell lines (5/7).

“In contrast, only around one quarter [of the cell lines] were susceptible to inhibiting BCL2,” Dr Gong said. “This finding is in keeping with earlier research at the Walter and Eliza Hall Institute that pinpointed MCL1 as the likely protein that keeps myeloma cells alive.”

The researchers also found that targeting MCL1 hindered MM growth in vivo.

The team targeted MCL1 by expressing the MCL1-selective ligand BIM2A in mice inoculated with 1 of 2 MM cell lines—AMO1 and H929. In both models, targeting MCL1 resulted in delayed disease progression and reduced disease burden.

Finally, the researchers identified a subtype of MM that is highly dependent upon BCLXL, so they’ve theorized that targeting both MCL1 and BCLXL could prove useful.

The team concluded that MCL1 is pivotal for maintaining the survival of most myelomas, so targeting the protein should be prioritized once validated inhibitors become available.

“As yet, these inhibitors are still in preclinical development,” said study author Andrew Roberts, MBBS, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“Our results suggest that, once necessary laboratory testing for safety is completed, clinical trials of their effectiveness in treating patients with multiple myeloma that is no longer responding to current therapies would be well justified.”

Study authors Jianan Gong,

David Segal, and Yuan Yao

Photo from the Walter

and Eliza Hall Institute

A new class of inhibitors may be effective in treating a majority of patients with multiple myeloma (MM), according to research published in Blood.

Experiments in multiple MM cell lines suggested the majority of myelomas rely on the protein MCL1 to stay alive.

And targeting MCL1 inhibited disease progression in mouse models of MM.

Therefore, researchers believe drugs designed to inhibit MCL1 may be a promising treatment option for MM.

“Our research shows that switching off MCL1 has the potential to be an effective new treatment approach for the majority of patients with myeloma,” said Jianan Gong, PhD, of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.

For this study, Dr Gong and her colleagues investigated the survival proteins that keep MM cells alive.

The team found that a majority of MM cell lines—about 70%—died when MCL1 was switched off. This included well-established, immortalized MM cell lines (17/25) and low-passage MM cell lines (5/7).

“In contrast, only around one quarter [of the cell lines] were susceptible to inhibiting BCL2,” Dr Gong said. “This finding is in keeping with earlier research at the Walter and Eliza Hall Institute that pinpointed MCL1 as the likely protein that keeps myeloma cells alive.”

The researchers also found that targeting MCL1 hindered MM growth in vivo.

The team targeted MCL1 by expressing the MCL1-selective ligand BIM2A in mice inoculated with 1 of 2 MM cell lines—AMO1 and H929. In both models, targeting MCL1 resulted in delayed disease progression and reduced disease burden.

Finally, the researchers identified a subtype of MM that is highly dependent upon BCLXL, so they’ve theorized that targeting both MCL1 and BCLXL could prove useful.

The team concluded that MCL1 is pivotal for maintaining the survival of most myelomas, so targeting the protein should be prioritized once validated inhibitors become available.

“As yet, these inhibitors are still in preclinical development,” said study author Andrew Roberts, MBBS, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“Our results suggest that, once necessary laboratory testing for safety is completed, clinical trials of their effectiveness in treating patients with multiple myeloma that is no longer responding to current therapies would be well justified.”

Study authors Jianan Gong,

David Segal, and Yuan Yao

Photo from the Walter

and Eliza Hall Institute

A new class of inhibitors may be effective in treating a majority of patients with multiple myeloma (MM), according to research published in Blood.

Experiments in multiple MM cell lines suggested the majority of myelomas rely on the protein MCL1 to stay alive.

And targeting MCL1 inhibited disease progression in mouse models of MM.

Therefore, researchers believe drugs designed to inhibit MCL1 may be a promising treatment option for MM.

“Our research shows that switching off MCL1 has the potential to be an effective new treatment approach for the majority of patients with myeloma,” said Jianan Gong, PhD, of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.

For this study, Dr Gong and her colleagues investigated the survival proteins that keep MM cells alive.

The team found that a majority of MM cell lines—about 70%—died when MCL1 was switched off. This included well-established, immortalized MM cell lines (17/25) and low-passage MM cell lines (5/7).

“In contrast, only around one quarter [of the cell lines] were susceptible to inhibiting BCL2,” Dr Gong said. “This finding is in keeping with earlier research at the Walter and Eliza Hall Institute that pinpointed MCL1 as the likely protein that keeps myeloma cells alive.”

The researchers also found that targeting MCL1 hindered MM growth in vivo.

The team targeted MCL1 by expressing the MCL1-selective ligand BIM2A in mice inoculated with 1 of 2 MM cell lines—AMO1 and H929. In both models, targeting MCL1 resulted in delayed disease progression and reduced disease burden.

Finally, the researchers identified a subtype of MM that is highly dependent upon BCLXL, so they’ve theorized that targeting both MCL1 and BCLXL could prove useful.

The team concluded that MCL1 is pivotal for maintaining the survival of most myelomas, so targeting the protein should be prioritized once validated inhibitors become available.

“As yet, these inhibitors are still in preclinical development,” said study author Andrew Roberts, MBBS, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“Our results suggest that, once necessary laboratory testing for safety is completed, clinical trials of their effectiveness in treating patients with multiple myeloma that is no longer responding to current therapies would be well justified.”

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

The US Food and Drug Administration (FDA) is allowing a company to proceed with a field trial of genetically engineered (GE) Aedes aegypti mosquitoes in the Florida Keys.

The FDA said the trial, designed to determine if the GE mosquitoes will suppress the local Aedes aegypti population, will not have a significant impact on the environment.

The FDA’s decision does not mean the GE mosquitoes are approved for commercial use or even that the trial will go ahead.

The company developing the mosquitoes, Oxitec, must ensure that all other local, state, and federal requirements are met before conducting the field trial.

Oxitec and its local partner, the Florida Keys Mosquito Control District, will then determine whether and when to begin the trial in Key Haven, Florida.

The goal of the field trial is to reduce the population of Aedes aegypti mosquitoes in the Florida Keys. These non-native mosquitoes spread the Zika virus, dengue fever, and chikungunya.

If it proceeds, the trial will involve male Aedes aegypti mosquitoes that have been genetically engineered so their offspring die before reaching adulthood.

The GE mosquitoes, which do not bite or spread disease, will be released to mate with wild female Aedes aegypti. The resulting offspring are expected to die before they can begin mating themselves, thereby reducing the overall population.

Efficacy trials in Brazil, Panama, and the Cayman Islands have tested this approach, and, in each of these trials, the population of Aedes aegypti was reduced by more than 90%.

“We’ve been developing this approach for many years, and, from these results, we are convinced that our solution is both highly effective and has sound environmental credentials,” said Oxitec’s Chief Executive Officer Hadyn Parry.

“We’re delighted with the announcement today that the FDA, after their extensive review of our dossier and thousands of public comments for a trial in the Florida Keys, have published their final view that this will not have a significant impact on the environment. We are now looking forward to working with the community in the Florida Keys moving forward.”

The FDA published a final finding of no significant impact (FONSI) and a final environmental assessment (EA) regarding the trial on August 5. Both documents are available on the FDA’s website.

More information on Oxitec’s technology and the trial can be found on the company’s website.

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

The US Food and Drug Administration (FDA) is allowing a company to proceed with a field trial of genetically engineered (GE) Aedes aegypti mosquitoes in the Florida Keys.

The FDA said the trial, designed to determine if the GE mosquitoes will suppress the local Aedes aegypti population, will not have a significant impact on the environment.

The FDA’s decision does not mean the GE mosquitoes are approved for commercial use or even that the trial will go ahead.

The company developing the mosquitoes, Oxitec, must ensure that all other local, state, and federal requirements are met before conducting the field trial.

Oxitec and its local partner, the Florida Keys Mosquito Control District, will then determine whether and when to begin the trial in Key Haven, Florida.

The goal of the field trial is to reduce the population of Aedes aegypti mosquitoes in the Florida Keys. These non-native mosquitoes spread the Zika virus, dengue fever, and chikungunya.

If it proceeds, the trial will involve male Aedes aegypti mosquitoes that have been genetically engineered so their offspring die before reaching adulthood.

The GE mosquitoes, which do not bite or spread disease, will be released to mate with wild female Aedes aegypti. The resulting offspring are expected to die before they can begin mating themselves, thereby reducing the overall population.

Efficacy trials in Brazil, Panama, and the Cayman Islands have tested this approach, and, in each of these trials, the population of Aedes aegypti was reduced by more than 90%.

“We’ve been developing this approach for many years, and, from these results, we are convinced that our solution is both highly effective and has sound environmental credentials,” said Oxitec’s Chief Executive Officer Hadyn Parry.

“We’re delighted with the announcement today that the FDA, after their extensive review of our dossier and thousands of public comments for a trial in the Florida Keys, have published their final view that this will not have a significant impact on the environment. We are now looking forward to working with the community in the Florida Keys moving forward.”

The FDA published a final finding of no significant impact (FONSI) and a final environmental assessment (EA) regarding the trial on August 5. Both documents are available on the FDA’s website.

More information on Oxitec’s technology and the trial can be found on the company’s website.

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

The US Food and Drug Administration (FDA) is allowing a company to proceed with a field trial of genetically engineered (GE) Aedes aegypti mosquitoes in the Florida Keys.

The FDA said the trial, designed to determine if the GE mosquitoes will suppress the local Aedes aegypti population, will not have a significant impact on the environment.

The FDA’s decision does not mean the GE mosquitoes are approved for commercial use or even that the trial will go ahead.

The company developing the mosquitoes, Oxitec, must ensure that all other local, state, and federal requirements are met before conducting the field trial.

Oxitec and its local partner, the Florida Keys Mosquito Control District, will then determine whether and when to begin the trial in Key Haven, Florida.

The goal of the field trial is to reduce the population of Aedes aegypti mosquitoes in the Florida Keys. These non-native mosquitoes spread the Zika virus, dengue fever, and chikungunya.

If it proceeds, the trial will involve male Aedes aegypti mosquitoes that have been genetically engineered so their offspring die before reaching adulthood.

The GE mosquitoes, which do not bite or spread disease, will be released to mate with wild female Aedes aegypti. The resulting offspring are expected to die before they can begin mating themselves, thereby reducing the overall population.

Efficacy trials in Brazil, Panama, and the Cayman Islands have tested this approach, and, in each of these trials, the population of Aedes aegypti was reduced by more than 90%.

“We’ve been developing this approach for many years, and, from these results, we are convinced that our solution is both highly effective and has sound environmental credentials,” said Oxitec’s Chief Executive Officer Hadyn Parry.

“We’re delighted with the announcement today that the FDA, after their extensive review of our dossier and thousands of public comments for a trial in the Florida Keys, have published their final view that this will not have a significant impact on the environment. We are now looking forward to working with the community in the Florida Keys moving forward.”

The FDA published a final finding of no significant impact (FONSI) and a final environmental assessment (EA) regarding the trial on August 5. Both documents are available on the FDA’s website.

More information on Oxitec’s technology and the trial can be found on the company’s website.

Disaster Response

Lessons from Orlando

The recent nightclub shootings in Orlando have forced my colleagues and I at our Level I Trauma Center to reexamine the way we do business. Our typical approach to injury involves resource-intense therapy with a gang of clinicians, while anticipating no more than one or two patients at a time. While this model is excellent for training, we would struggle with the scale of casualties seen in Orlando.

Several observations may be made internally and have been made in the press. Triage should take place prior to the emergency department so that patients are appropriately prioritized to high-intensity support. Fundamental high-impact interventions requiring simple application, such as tourniquets, should be part of the training for all medical and nonmedical first responders. Perhaps most importantly, we need to reexamine the concept that health care is provided by competing geographic and economic entities. Evolution of trauma care has “followed the money” but not necessarily the need. An approach viewing trauma care as a right and acute response as a community resource may be necessary.

In 2008, the Republican Party held its convention in St. Paul, Minn. Reports indicated that 20,000-50,000 individuals were expected to enter the city, including protesters and anarchist groups. We prepared together for events ranging from vehicular crashes to biologic agents or explosive events (Dries et al. J Trauma. 2012; 73[6]:1614). Since then, however, there has been little community-wide planning.

Orlando reminds us that we dare not leave these plans on the shelf.

David Dries, MD, FCCP

Steering Committee Member

Practice Operations

MACRA, QPP, MIPS, APM: Know these acronyms

In October 2015, Congress passed the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA). A bipartisan legislation, it replaces the flawed Sustainable Growth Rate (SGR) formula that would have forced a 21% cut in Medicare payments to clinicians. MACRA established Quality Payment Program (QPP) that has two paths that link quality to payments: the Merit-Based Incentive Payment System (MIPS) or Advanced Alternative Payment Models (APMs).

MIPS streamlines three currently independent programs – (Physician Quality Reporting Program [PQRS], Value-Based Payment Modifier [VM], and Medicare Electronic Health Records Incentive Program) – into a single program in which eligible professions (EPs) will be measured on quality (50%), resource use/cost (10%), clinical practice improvement activities (15%), and advancing care information (25%). The resulting composite performance score (CPS, scale 0-100) is used to determine and apply a +/- or neutral payment adjustment based on a performance threshold. Payment adjustments will begin in 2019 (based on 2017 performance period). Most physicians will be subject to MIPS, which does not apply to hospitals or facilities.

APMs are new approaches to paying for medical care incentivizing quality and value. As defined by MACRA, APMs include CMS Innovation Center models, the Medicare Shared Saving program, and certain demonstration programs. To qualify for payments, the APMs must also use certified EHR technology, report on certain quality measures, and bear more than nominal financial risk.

Both MIPS and APMs are value-based payment models that incentivize providers on quality, outcomes, and cost containment. Most physicians who see Medicare patients will be required to report either the MIPS or Advanced APM track starting in January 2017.

Editor’s Note – See additional article on MACRA on page in this issue.

Adel Bassily-Marcus, MD, FCCP

Vice-Chair

Transplant

Extracorporeal circulatory support in thoracic medicine and surgery – evolving technology and expanding role

There is growing interest in the use of extracorporeal support (ECS) beyond intraoperative and perioperative utility. This has been driven by improvements in safety and efficacy resulting from corresponding technological advances and enhanced user ability. The paucity of donors, however, remains a significant limiting factor in lung transplantation (LT), and there is a growing number of recipients on the waiting list getting too sick for transplantation. ECS is now commonly used to bridge recipients to LT, and reported outcomes show great promise. Indeed, there is even a growing interest in combining ECS with the ex vivo reconditioning of lungs in a further attempt to broaden the donor pool.

This newly developing paradigm constitutes a confluence of contemporary technologies that should allow more marginal or previously unacceptable donor lungs to be procured and also for the use of cardiopulmonary support to bridge sicker recipients safely. As with most technologies, the prerequisite capital outlay, training, and logistical resources will be required to allow for the acquisition of skill and safety. Furthermore, these trends will likely stimulate development of standards and guidelines to ensure a continuing quest for excellence.

The ongoing use of ECS in transplantation has a ripple effect that may prompt its use in other clinical scenarios, such as a rescue therapy in acute exacerbations of COPD, an alternative to mechanical ventilation following complex thoracic pulmonary or esophageal resections, and in cases of unexpected intraoperative cardiopulmonary collapse. One thing remains likely, however, ECS is here to stay.

Jeremiah Hayanga, MD

Steering Committee Member

Norihisa Shigemura, MD

Steering Committee Member

Women’s Health

Exposure of adolescents to electronic cigarettes: still a cause for alarm despite recent FDA ruling

Developed in 2003, electronic cigarettes (e-cigarettes) have been available in the United States since 2007. Between 2010 and 2013, adult use doubled. By 2013, the major tobacco companies had entered the market, and e-cigarettes were marketed widely (television, Internet, and print) as healthier alternatives to tobacco, useful for quitting smoking, and a way to circumvent smoke-free laws by allowing smokers to “smoke anywhere” (Grana et al. Circulation. 2014;129[19]:1972).

For adolescents, e-cigarette use tripled between 2013 and 2014, from 4.5% (660,000) to 13.4% (2 million) for high school students and from 1.1% (120,000) to 3.9% (450,000) for middle school students (CDC Press Release. http://www.cdc.gov/media/releases/2015/p0416-e-cigarette-use.html). Teenage experimentation, in conjunction with susceptibility to brain-modifying effects of nicotine, places this population at risk for lifelong nicotine addiction. Teenagers who use e-cigarettes are more likely to become regular cigarette smokers than nonusers (Dutra et al. JAMA Pediatr. 2014;168[7]:610; Levanthal et al. JAMA. 2015;314[7]:700). Local and state municipalities have enacted legislation, adding e-cigarettes and other electronic nicotine delivery systems (ENDS) to existing tobacco regulations. On May 5, 2016, a long-anticipated ruling from the FDA extended oversight to include all tobacco products, including e-cigarettes and hookahs, allowing the agency to address public health concerns, such as youth access. However, a key provision of the new tobacco “deeming” rules was subsequently removed less than a month later – one that would have removed flavored e-cigarettes, cigars, hookahs, and other flavored tobacco products from the market in November pending review by the Food and Drug Administration (Boyles. MedPage Today. medpagetoday.com/pulmonology/smoking/58274).

ENDS as a smoking cessation tool, a “safer” alternative to combustible tobacco, is much debated (Green et al. N Engl J Med. 2016;374[14]:1301). There is accumulating evidence of its in vivo and in vitro toxicity (Bhatnagar et al. Circulation. 2014;130[16]:1418; Gibbs et al. Chest. 2016;149[2]:552). Studies have shown that the varied concentration and flavorings used are cytotoxic to human embryonic stem cells as well as mice neural stem cells (Bahl et al. Reprod Toxicol. 2012[4];34:529) and that exposure to propylene glycol and glycerin, main base ingredients in e-liquids, can result in eye and respiratory irritation (Grana et al. Circulation. 2014; 129[19]:1972). Additionally, current evidence does not support e-cigarettes for smoking cessation (Grana et al. Circulation. 2014;129[19]:1972). The accumulating evidence of adverse effects and the increased use in adolescents underscores the need for stricter regulations by the FDA in order to prevent renormalization of the smoking behavior and to protect public health. The rollout of the FDA’s ruling will warrant ongoing evaluation.

Linda S. Efferen, MD, MBA

Consultant

Amanpreet Kaur, MD

Steering Committee Member

Disaster Response

Lessons from Orlando

The recent nightclub shootings in Orlando have forced my colleagues and I at our Level I Trauma Center to reexamine the way we do business. Our typical approach to injury involves resource-intense therapy with a gang of clinicians, while anticipating no more than one or two patients at a time. While this model is excellent for training, we would struggle with the scale of casualties seen in Orlando.

Several observations may be made internally and have been made in the press. Triage should take place prior to the emergency department so that patients are appropriately prioritized to high-intensity support. Fundamental high-impact interventions requiring simple application, such as tourniquets, should be part of the training for all medical and nonmedical first responders. Perhaps most importantly, we need to reexamine the concept that health care is provided by competing geographic and economic entities. Evolution of trauma care has “followed the money” but not necessarily the need. An approach viewing trauma care as a right and acute response as a community resource may be necessary.

In 2008, the Republican Party held its convention in St. Paul, Minn. Reports indicated that 20,000-50,000 individuals were expected to enter the city, including protesters and anarchist groups. We prepared together for events ranging from vehicular crashes to biologic agents or explosive events (Dries et al. J Trauma. 2012; 73[6]:1614). Since then, however, there has been little community-wide planning.

Orlando reminds us that we dare not leave these plans on the shelf.

David Dries, MD, FCCP

Steering Committee Member

Practice Operations

MACRA, QPP, MIPS, APM: Know these acronyms

In October 2015, Congress passed the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA). A bipartisan legislation, it replaces the flawed Sustainable Growth Rate (SGR) formula that would have forced a 21% cut in Medicare payments to clinicians. MACRA established Quality Payment Program (QPP) that has two paths that link quality to payments: the Merit-Based Incentive Payment System (MIPS) or Advanced Alternative Payment Models (APMs).

MIPS streamlines three currently independent programs – (Physician Quality Reporting Program [PQRS], Value-Based Payment Modifier [VM], and Medicare Electronic Health Records Incentive Program) – into a single program in which eligible professions (EPs) will be measured on quality (50%), resource use/cost (10%), clinical practice improvement activities (15%), and advancing care information (25%). The resulting composite performance score (CPS, scale 0-100) is used to determine and apply a +/- or neutral payment adjustment based on a performance threshold. Payment adjustments will begin in 2019 (based on 2017 performance period). Most physicians will be subject to MIPS, which does not apply to hospitals or facilities.

APMs are new approaches to paying for medical care incentivizing quality and value. As defined by MACRA, APMs include CMS Innovation Center models, the Medicare Shared Saving program, and certain demonstration programs. To qualify for payments, the APMs must also use certified EHR technology, report on certain quality measures, and bear more than nominal financial risk.

Both MIPS and APMs are value-based payment models that incentivize providers on quality, outcomes, and cost containment. Most physicians who see Medicare patients will be required to report either the MIPS or Advanced APM track starting in January 2017.

Editor’s Note – See additional article on MACRA on page in this issue.

Adel Bassily-Marcus, MD, FCCP

Vice-Chair

Transplant

Extracorporeal circulatory support in thoracic medicine and surgery – evolving technology and expanding role

There is growing interest in the use of extracorporeal support (ECS) beyond intraoperative and perioperative utility. This has been driven by improvements in safety and efficacy resulting from corresponding technological advances and enhanced user ability. The paucity of donors, however, remains a significant limiting factor in lung transplantation (LT), and there is a growing number of recipients on the waiting list getting too sick for transplantation. ECS is now commonly used to bridge recipients to LT, and reported outcomes show great promise. Indeed, there is even a growing interest in combining ECS with the ex vivo reconditioning of lungs in a further attempt to broaden the donor pool.

This newly developing paradigm constitutes a confluence of contemporary technologies that should allow more marginal or previously unacceptable donor lungs to be procured and also for the use of cardiopulmonary support to bridge sicker recipients safely. As with most technologies, the prerequisite capital outlay, training, and logistical resources will be required to allow for the acquisition of skill and safety. Furthermore, these trends will likely stimulate development of standards and guidelines to ensure a continuing quest for excellence.

The ongoing use of ECS in transplantation has a ripple effect that may prompt its use in other clinical scenarios, such as a rescue therapy in acute exacerbations of COPD, an alternative to mechanical ventilation following complex thoracic pulmonary or esophageal resections, and in cases of unexpected intraoperative cardiopulmonary collapse. One thing remains likely, however, ECS is here to stay.

Jeremiah Hayanga, MD

Steering Committee Member

Norihisa Shigemura, MD

Steering Committee Member

Women’s Health

Exposure of adolescents to electronic cigarettes: still a cause for alarm despite recent FDA ruling

Developed in 2003, electronic cigarettes (e-cigarettes) have been available in the United States since 2007. Between 2010 and 2013, adult use doubled. By 2013, the major tobacco companies had entered the market, and e-cigarettes were marketed widely (television, Internet, and print) as healthier alternatives to tobacco, useful for quitting smoking, and a way to circumvent smoke-free laws by allowing smokers to “smoke anywhere” (Grana et al. Circulation. 2014;129[19]:1972).

For adolescents, e-cigarette use tripled between 2013 and 2014, from 4.5% (660,000) to 13.4% (2 million) for high school students and from 1.1% (120,000) to 3.9% (450,000) for middle school students (CDC Press Release. http://www.cdc.gov/media/releases/2015/p0416-e-cigarette-use.html). Teenage experimentation, in conjunction with susceptibility to brain-modifying effects of nicotine, places this population at risk for lifelong nicotine addiction. Teenagers who use e-cigarettes are more likely to become regular cigarette smokers than nonusers (Dutra et al. JAMA Pediatr. 2014;168[7]:610; Levanthal et al. JAMA. 2015;314[7]:700). Local and state municipalities have enacted legislation, adding e-cigarettes and other electronic nicotine delivery systems (ENDS) to existing tobacco regulations. On May 5, 2016, a long-anticipated ruling from the FDA extended oversight to include all tobacco products, including e-cigarettes and hookahs, allowing the agency to address public health concerns, such as youth access. However, a key provision of the new tobacco “deeming” rules was subsequently removed less than a month later – one that would have removed flavored e-cigarettes, cigars, hookahs, and other flavored tobacco products from the market in November pending review by the Food and Drug Administration (Boyles. MedPage Today. medpagetoday.com/pulmonology/smoking/58274).

ENDS as a smoking cessation tool, a “safer” alternative to combustible tobacco, is much debated (Green et al. N Engl J Med. 2016;374[14]:1301). There is accumulating evidence of its in vivo and in vitro toxicity (Bhatnagar et al. Circulation. 2014;130[16]:1418; Gibbs et al. Chest. 2016;149[2]:552). Studies have shown that the varied concentration and flavorings used are cytotoxic to human embryonic stem cells as well as mice neural stem cells (Bahl et al. Reprod Toxicol. 2012[4];34:529) and that exposure to propylene glycol and glycerin, main base ingredients in e-liquids, can result in eye and respiratory irritation (Grana et al. Circulation. 2014; 129[19]:1972). Additionally, current evidence does not support e-cigarettes for smoking cessation (Grana et al. Circulation. 2014;129[19]:1972). The accumulating evidence of adverse effects and the increased use in adolescents underscores the need for stricter regulations by the FDA in order to prevent renormalization of the smoking behavior and to protect public health. The rollout of the FDA’s ruling will warrant ongoing evaluation.

Linda S. Efferen, MD, MBA

Consultant

Amanpreet Kaur, MD

Steering Committee Member

Disaster Response

Lessons from Orlando

The recent nightclub shootings in Orlando have forced my colleagues and I at our Level I Trauma Center to reexamine the way we do business. Our typical approach to injury involves resource-intense therapy with a gang of clinicians, while anticipating no more than one or two patients at a time. While this model is excellent for training, we would struggle with the scale of casualties seen in Orlando.

Several observations may be made internally and have been made in the press. Triage should take place prior to the emergency department so that patients are appropriately prioritized to high-intensity support. Fundamental high-impact interventions requiring simple application, such as tourniquets, should be part of the training for all medical and nonmedical first responders. Perhaps most importantly, we need to reexamine the concept that health care is provided by competing geographic and economic entities. Evolution of trauma care has “followed the money” but not necessarily the need. An approach viewing trauma care as a right and acute response as a community resource may be necessary.

In 2008, the Republican Party held its convention in St. Paul, Minn. Reports indicated that 20,000-50,000 individuals were expected to enter the city, including protesters and anarchist groups. We prepared together for events ranging from vehicular crashes to biologic agents or explosive events (Dries et al. J Trauma. 2012; 73[6]:1614). Since then, however, there has been little community-wide planning.

Orlando reminds us that we dare not leave these plans on the shelf.

David Dries, MD, FCCP

Steering Committee Member

Practice Operations

MACRA, QPP, MIPS, APM: Know these acronyms

In October 2015, Congress passed the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA). A bipartisan legislation, it replaces the flawed Sustainable Growth Rate (SGR) formula that would have forced a 21% cut in Medicare payments to clinicians. MACRA established Quality Payment Program (QPP) that has two paths that link quality to payments: the Merit-Based Incentive Payment System (MIPS) or Advanced Alternative Payment Models (APMs).

MIPS streamlines three currently independent programs – (Physician Quality Reporting Program [PQRS], Value-Based Payment Modifier [VM], and Medicare Electronic Health Records Incentive Program) – into a single program in which eligible professions (EPs) will be measured on quality (50%), resource use/cost (10%), clinical practice improvement activities (15%), and advancing care information (25%). The resulting composite performance score (CPS, scale 0-100) is used to determine and apply a +/- or neutral payment adjustment based on a performance threshold. Payment adjustments will begin in 2019 (based on 2017 performance period). Most physicians will be subject to MIPS, which does not apply to hospitals or facilities.

APMs are new approaches to paying for medical care incentivizing quality and value. As defined by MACRA, APMs include CMS Innovation Center models, the Medicare Shared Saving program, and certain demonstration programs. To qualify for payments, the APMs must also use certified EHR technology, report on certain quality measures, and bear more than nominal financial risk.

Both MIPS and APMs are value-based payment models that incentivize providers on quality, outcomes, and cost containment. Most physicians who see Medicare patients will be required to report either the MIPS or Advanced APM track starting in January 2017.

Editor’s Note – See additional article on MACRA on page in this issue.

Adel Bassily-Marcus, MD, FCCP

Vice-Chair

Transplant

Extracorporeal circulatory support in thoracic medicine and surgery – evolving technology and expanding role

There is growing interest in the use of extracorporeal support (ECS) beyond intraoperative and perioperative utility. This has been driven by improvements in safety and efficacy resulting from corresponding technological advances and enhanced user ability. The paucity of donors, however, remains a significant limiting factor in lung transplantation (LT), and there is a growing number of recipients on the waiting list getting too sick for transplantation. ECS is now commonly used to bridge recipients to LT, and reported outcomes show great promise. Indeed, there is even a growing interest in combining ECS with the ex vivo reconditioning of lungs in a further attempt to broaden the donor pool.

This newly developing paradigm constitutes a confluence of contemporary technologies that should allow more marginal or previously unacceptable donor lungs to be procured and also for the use of cardiopulmonary support to bridge sicker recipients safely. As with most technologies, the prerequisite capital outlay, training, and logistical resources will be required to allow for the acquisition of skill and safety. Furthermore, these trends will likely stimulate development of standards and guidelines to ensure a continuing quest for excellence.

The ongoing use of ECS in transplantation has a ripple effect that may prompt its use in other clinical scenarios, such as a rescue therapy in acute exacerbations of COPD, an alternative to mechanical ventilation following complex thoracic pulmonary or esophageal resections, and in cases of unexpected intraoperative cardiopulmonary collapse. One thing remains likely, however, ECS is here to stay.

Jeremiah Hayanga, MD

Steering Committee Member

Norihisa Shigemura, MD

Steering Committee Member

Women’s Health

Exposure of adolescents to electronic cigarettes: still a cause for alarm despite recent FDA ruling

Developed in 2003, electronic cigarettes (e-cigarettes) have been available in the United States since 2007. Between 2010 and 2013, adult use doubled. By 2013, the major tobacco companies had entered the market, and e-cigarettes were marketed widely (television, Internet, and print) as healthier alternatives to tobacco, useful for quitting smoking, and a way to circumvent smoke-free laws by allowing smokers to “smoke anywhere” (Grana et al. Circulation. 2014;129[19]:1972).

For adolescents, e-cigarette use tripled between 2013 and 2014, from 4.5% (660,000) to 13.4% (2 million) for high school students and from 1.1% (120,000) to 3.9% (450,000) for middle school students (CDC Press Release. http://www.cdc.gov/media/releases/2015/p0416-e-cigarette-use.html). Teenage experimentation, in conjunction with susceptibility to brain-modifying effects of nicotine, places this population at risk for lifelong nicotine addiction. Teenagers who use e-cigarettes are more likely to become regular cigarette smokers than nonusers (Dutra et al. JAMA Pediatr. 2014;168[7]:610; Levanthal et al. JAMA. 2015;314[7]:700). Local and state municipalities have enacted legislation, adding e-cigarettes and other electronic nicotine delivery systems (ENDS) to existing tobacco regulations. On May 5, 2016, a long-anticipated ruling from the FDA extended oversight to include all tobacco products, including e-cigarettes and hookahs, allowing the agency to address public health concerns, such as youth access. However, a key provision of the new tobacco “deeming” rules was subsequently removed less than a month later – one that would have removed flavored e-cigarettes, cigars, hookahs, and other flavored tobacco products from the market in November pending review by the Food and Drug Administration (Boyles. MedPage Today. medpagetoday.com/pulmonology/smoking/58274).

ENDS as a smoking cessation tool, a “safer” alternative to combustible tobacco, is much debated (Green et al. N Engl J Med. 2016;374[14]:1301). There is accumulating evidence of its in vivo and in vitro toxicity (Bhatnagar et al. Circulation. 2014;130[16]:1418; Gibbs et al. Chest. 2016;149[2]:552). Studies have shown that the varied concentration and flavorings used are cytotoxic to human embryonic stem cells as well as mice neural stem cells (Bahl et al. Reprod Toxicol. 2012[4];34:529) and that exposure to propylene glycol and glycerin, main base ingredients in e-liquids, can result in eye and respiratory irritation (Grana et al. Circulation. 2014; 129[19]:1972). Additionally, current evidence does not support e-cigarettes for smoking cessation (Grana et al. Circulation. 2014;129[19]:1972). The accumulating evidence of adverse effects and the increased use in adolescents underscores the need for stricter regulations by the FDA in order to prevent renormalization of the smoking behavior and to protect public health. The rollout of the FDA’s ruling will warrant ongoing evaluation.

Linda S. Efferen, MD, MBA

Consultant

Amanpreet Kaur, MD

Steering Committee Member

Where are they now? What have they been up to? CHEST’s Past Presidents each forged the way for the many successes of the American College of Chest Physicians (CHEST), leading to enhanced patient care around the globe. Their outstanding leadership and vision are evidenced today in many of CHEST’s current initiatives, and now it is time to check in with these past leaders to give us a look at what’s new.

Alex G. Little, MD, FCCP

President 1990-1991

Being President of the American College of Chest Physicians was a remarkable and exhilarating experience beginning with my inauguration in San Francisco in 1990. Although I had been active with the College for several years, the responsibility of the presidency entailed a much closer relationship with the organization, the excellent staff, the physician leaders, the greater membership, and notably, Dr. Al Soffer. As the Executive Director, Al was my go to advisor and guide for questions and advice. He and his wife Izzy became good personal friends and that relationship is one of the major benefits of my presidency (although it never resulted in him showing any mercy on the tennis courts).

For me, as a surgeon, one of the appealing aspects of the College, and, in particular, its annual meeting, was its interdisciplinary nature with pulmonologists, surgeons, and cardiologists interacting in a way that more narrowly focused specialty societies rarely provide. Learning alternative perspectives and hearing from other disciplines is always interesting and occasionally critically important for progress toward maximal patient care.

During my tenure, there were several noteworthy events. The College continued to exhibit robust growth in membership, strengthening its role in supporting chest physicians. We opened the new (amazingly, now the old) headquarters building in Northbrook, signaling a commitment to remain state of the art and joined the challenge of providing continuing medical education for our members.

I retired from clinical practice and as Chair of Surgery at Wright State in 2010 when my wife Louise and I settled in Tucson. I am involved with teaching and mentoring general and cardiothoracic residents at the University of Arizona and also keep active with ongoing clinical research projects. With my leisure time, I play tennis, read books I should have gotten to in earlier years, look for a publisher for a book I have written on the evolution of thoracic surgery (for the general reader), and admire my wife’s expertise in making glass beads and jewelry.

Where are they now? What have they been up to? CHEST’s Past Presidents each forged the way for the many successes of the American College of Chest Physicians (CHEST), leading to enhanced patient care around the globe. Their outstanding leadership and vision are evidenced today in many of CHEST’s current initiatives, and now it is time to check in with these past leaders to give us a look at what’s new.

Alex G. Little, MD, FCCP

President 1990-1991

Being President of the American College of Chest Physicians was a remarkable and exhilarating experience beginning with my inauguration in San Francisco in 1990. Although I had been active with the College for several years, the responsibility of the presidency entailed a much closer relationship with the organization, the excellent staff, the physician leaders, the greater membership, and notably, Dr. Al Soffer. As the Executive Director, Al was my go to advisor and guide for questions and advice. He and his wife Izzy became good personal friends and that relationship is one of the major benefits of my presidency (although it never resulted in him showing any mercy on the tennis courts).

For me, as a surgeon, one of the appealing aspects of the College, and, in particular, its annual meeting, was its interdisciplinary nature with pulmonologists, surgeons, and cardiologists interacting in a way that more narrowly focused specialty societies rarely provide. Learning alternative perspectives and hearing from other disciplines is always interesting and occasionally critically important for progress toward maximal patient care.

During my tenure, there were several noteworthy events. The College continued to exhibit robust growth in membership, strengthening its role in supporting chest physicians. We opened the new (amazingly, now the old) headquarters building in Northbrook, signaling a commitment to remain state of the art and joined the challenge of providing continuing medical education for our members.

I retired from clinical practice and as Chair of Surgery at Wright State in 2010 when my wife Louise and I settled in Tucson. I am involved with teaching and mentoring general and cardiothoracic residents at the University of Arizona and also keep active with ongoing clinical research projects. With my leisure time, I play tennis, read books I should have gotten to in earlier years, look for a publisher for a book I have written on the evolution of thoracic surgery (for the general reader), and admire my wife’s expertise in making glass beads and jewelry.

Where are they now? What have they been up to? CHEST’s Past Presidents each forged the way for the many successes of the American College of Chest Physicians (CHEST), leading to enhanced patient care around the globe. Their outstanding leadership and vision are evidenced today in many of CHEST’s current initiatives, and now it is time to check in with these past leaders to give us a look at what’s new.

Alex G. Little, MD, FCCP

President 1990-1991

Being President of the American College of Chest Physicians was a remarkable and exhilarating experience beginning with my inauguration in San Francisco in 1990. Although I had been active with the College for several years, the responsibility of the presidency entailed a much closer relationship with the organization, the excellent staff, the physician leaders, the greater membership, and notably, Dr. Al Soffer. As the Executive Director, Al was my go to advisor and guide for questions and advice. He and his wife Izzy became good personal friends and that relationship is one of the major benefits of my presidency (although it never resulted in him showing any mercy on the tennis courts).

For me, as a surgeon, one of the appealing aspects of the College, and, in particular, its annual meeting, was its interdisciplinary nature with pulmonologists, surgeons, and cardiologists interacting in a way that more narrowly focused specialty societies rarely provide. Learning alternative perspectives and hearing from other disciplines is always interesting and occasionally critically important for progress toward maximal patient care.

During my tenure, there were several noteworthy events. The College continued to exhibit robust growth in membership, strengthening its role in supporting chest physicians. We opened the new (amazingly, now the old) headquarters building in Northbrook, signaling a commitment to remain state of the art and joined the challenge of providing continuing medical education for our members.

I retired from clinical practice and as Chair of Surgery at Wright State in 2010 when my wife Louise and I settled in Tucson. I am involved with teaching and mentoring general and cardiothoracic residents at the University of Arizona and also keep active with ongoing clinical research projects. With my leisure time, I play tennis, read books I should have gotten to in earlier years, look for a publisher for a book I have written on the evolution of thoracic surgery (for the general reader), and admire my wife’s expertise in making glass beads and jewelry.