If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.

Identification of a case of acute hepatitis C virus (HCV) infection in a frequent blood donor without other risk factors should be considered a sentinel event and should prompt public health investigation, according to research published in Morbidity and Mortality Weekly Report, because this could indicate a possible health care–associated infection.

©vchal/Thinkstock

Negative media reports about the safety of the hepatitis B vaccine in China harmed perception of the vaccine’s safety among patients, according to a recent study. Although the reports were erroneous, the failure of public health departments to communicate effectively contributed to a rise in the number of parents refusing to vaccinate their children.

An experimental, highly specific and sensitive HCV core antigen enzyme immunoassay (HCV-Ags EIA) was found to have the lowest limit of detection equivalent to serum HCV RNA levels of 150-250 IU/mL. Investigators found that the HCV-Ags EIA reliably differentiated viremic HCV infection from resolved HCV infection, thus accomplishing screening and diagnosis of viremic HCV infection in one step.

Loss of confidence in the hepatitis B vaccine following disproved allegations that the vaccine caused multiple sclerosis persists in France, according to research published in Human Vaccines & Immunotherapeutics.

The approval of the direct-acting antiviral agents (DAAs) grazoprevir and elbasvir with an indication for all levels of kidney function and dialysis has altered the landscape for the treatment of hepatitis C virus in patients with chronic kidney disease, according to a review in Clinical Liver Disease. The authors say this is because other DAAs are either not approved for use in patients with advanced chronic kidney disease or no safety data are available for the dialysis population.

A study in the Journal of Viral Hepatitis found that insulin resistance was associated with an increased risk for loss of vaccine-acquired anti-HBs (hepatitis B surface antigen) in a large sample of a nondiabetic, general population, indicating a possible role of insulin resistance in vaccine-induced immunity.

Grazoprevir, a second-generation HCV NS3/4A protease inhibitor, combined with ribavirin was associated with a rapid and sustained suppression of HCV RNA in a randomized study. The authors said the results support further evaluation of grazoprevir-based treatment regimens.

HIV–HCV coinfected patients treated with a fixed-dose combination of ledipasvir and sofosbuvir (LDV/SOF) showed significant improvement of their health-related quality of life and other patient-reported outcomes during treatment and after treatment cessation, according to a study in the Journal of Viral Hepatitis.

A Swedish study found that diabetes mellitus and cirrhosis are strong risk factors for hepatocellular carcinoma development after sustained virologic response (SVR) following treatment for chronic HCV has been achieved. However, the risk to develop hepatocellular carcinoma diminished significantly 2 years after SVR.

Chinese investigators said serum levels of platelet-derived growth factor (PDGF) decreased remarkably through fibrosis progression and could be used as a noninvasive biomarker for the assessment of fibrosis stage in patients with chronic hepatitis B virus (HBV).

A genome-wide association study of liver fibrosis progression in patients coinfected with HCV and HIV identified a new locus associated with fibrosis severity on chromosome 3p25. The authors said the results may help define new targets for drug development or new prognostic tests.

The RNA helicase DDX5 and E3 ligase Mex3b are important cellular targets for the design of novel, epigenetic therapies to combat HBV infection and poor-prognosis HBV-associated liver cancer, according to a study in Hepatology.

A Japanese study found that daclatasvir (DCV) and asunaprevir (ASV) dual therapy in hemodialysis patients infected with HCV is effective and safe with similar results, compared with patients with normal renal function.

A study evaluating the antiviral effect of ribavirin priming, and its influence on sustained virologic response after combination treatment, found that the lowest response pattern in HCV-infected patients was observed in prior nonresponder patients to pegylated interferon-alfa plus ribavirin combination therapy. The authors said this suggests that not only the individual interferon, but also the ribavirin sensitivity contributes significantly to the nonresponsive state.

A veterinary study provided evidence that hepatitis E virus is able to damage the blood-brain barrier and replicate in the brain and spinal cord.

An all-oral regimen of ledipasvir and sofosbuvir is an effective and safe treatment for a wide range of HCV genotype 4 subtypes in both treatment-naive and -experienced patients, including those with compensated cirrhosis, according to results of a recent study.

[email protected]

On Twitter @richpizzi

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.

Identification of a case of acute hepatitis C virus (HCV) infection in a frequent blood donor without other risk factors should be considered a sentinel event and should prompt public health investigation, according to research published in Morbidity and Mortality Weekly Report, because this could indicate a possible health care–associated infection.

©vchal/Thinkstock

Negative media reports about the safety of the hepatitis B vaccine in China harmed perception of the vaccine’s safety among patients, according to a recent study. Although the reports were erroneous, the failure of public health departments to communicate effectively contributed to a rise in the number of parents refusing to vaccinate their children.

An experimental, highly specific and sensitive HCV core antigen enzyme immunoassay (HCV-Ags EIA) was found to have the lowest limit of detection equivalent to serum HCV RNA levels of 150-250 IU/mL. Investigators found that the HCV-Ags EIA reliably differentiated viremic HCV infection from resolved HCV infection, thus accomplishing screening and diagnosis of viremic HCV infection in one step.

Loss of confidence in the hepatitis B vaccine following disproved allegations that the vaccine caused multiple sclerosis persists in France, according to research published in Human Vaccines & Immunotherapeutics.

The approval of the direct-acting antiviral agents (DAAs) grazoprevir and elbasvir with an indication for all levels of kidney function and dialysis has altered the landscape for the treatment of hepatitis C virus in patients with chronic kidney disease, according to a review in Clinical Liver Disease. The authors say this is because other DAAs are either not approved for use in patients with advanced chronic kidney disease or no safety data are available for the dialysis population.

A study in the Journal of Viral Hepatitis found that insulin resistance was associated with an increased risk for loss of vaccine-acquired anti-HBs (hepatitis B surface antigen) in a large sample of a nondiabetic, general population, indicating a possible role of insulin resistance in vaccine-induced immunity.

Grazoprevir, a second-generation HCV NS3/4A protease inhibitor, combined with ribavirin was associated with a rapid and sustained suppression of HCV RNA in a randomized study. The authors said the results support further evaluation of grazoprevir-based treatment regimens.

HIV–HCV coinfected patients treated with a fixed-dose combination of ledipasvir and sofosbuvir (LDV/SOF) showed significant improvement of their health-related quality of life and other patient-reported outcomes during treatment and after treatment cessation, according to a study in the Journal of Viral Hepatitis.

A Swedish study found that diabetes mellitus and cirrhosis are strong risk factors for hepatocellular carcinoma development after sustained virologic response (SVR) following treatment for chronic HCV has been achieved. However, the risk to develop hepatocellular carcinoma diminished significantly 2 years after SVR.

Chinese investigators said serum levels of platelet-derived growth factor (PDGF) decreased remarkably through fibrosis progression and could be used as a noninvasive biomarker for the assessment of fibrosis stage in patients with chronic hepatitis B virus (HBV).

A genome-wide association study of liver fibrosis progression in patients coinfected with HCV and HIV identified a new locus associated with fibrosis severity on chromosome 3p25. The authors said the results may help define new targets for drug development or new prognostic tests.

The RNA helicase DDX5 and E3 ligase Mex3b are important cellular targets for the design of novel, epigenetic therapies to combat HBV infection and poor-prognosis HBV-associated liver cancer, according to a study in Hepatology.

A Japanese study found that daclatasvir (DCV) and asunaprevir (ASV) dual therapy in hemodialysis patients infected with HCV is effective and safe with similar results, compared with patients with normal renal function.

A study evaluating the antiviral effect of ribavirin priming, and its influence on sustained virologic response after combination treatment, found that the lowest response pattern in HCV-infected patients was observed in prior nonresponder patients to pegylated interferon-alfa plus ribavirin combination therapy. The authors said this suggests that not only the individual interferon, but also the ribavirin sensitivity contributes significantly to the nonresponsive state.

A veterinary study provided evidence that hepatitis E virus is able to damage the blood-brain barrier and replicate in the brain and spinal cord.

An all-oral regimen of ledipasvir and sofosbuvir is an effective and safe treatment for a wide range of HCV genotype 4 subtypes in both treatment-naive and -experienced patients, including those with compensated cirrhosis, according to results of a recent study.

[email protected]

On Twitter @richpizzi

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.

Identification of a case of acute hepatitis C virus (HCV) infection in a frequent blood donor without other risk factors should be considered a sentinel event and should prompt public health investigation, according to research published in Morbidity and Mortality Weekly Report, because this could indicate a possible health care–associated infection.

©vchal/Thinkstock

Negative media reports about the safety of the hepatitis B vaccine in China harmed perception of the vaccine’s safety among patients, according to a recent study. Although the reports were erroneous, the failure of public health departments to communicate effectively contributed to a rise in the number of parents refusing to vaccinate their children.

An experimental, highly specific and sensitive HCV core antigen enzyme immunoassay (HCV-Ags EIA) was found to have the lowest limit of detection equivalent to serum HCV RNA levels of 150-250 IU/mL. Investigators found that the HCV-Ags EIA reliably differentiated viremic HCV infection from resolved HCV infection, thus accomplishing screening and diagnosis of viremic HCV infection in one step.

Loss of confidence in the hepatitis B vaccine following disproved allegations that the vaccine caused multiple sclerosis persists in France, according to research published in Human Vaccines & Immunotherapeutics.

The approval of the direct-acting antiviral agents (DAAs) grazoprevir and elbasvir with an indication for all levels of kidney function and dialysis has altered the landscape for the treatment of hepatitis C virus in patients with chronic kidney disease, according to a review in Clinical Liver Disease. The authors say this is because other DAAs are either not approved for use in patients with advanced chronic kidney disease or no safety data are available for the dialysis population.

A study in the Journal of Viral Hepatitis found that insulin resistance was associated with an increased risk for loss of vaccine-acquired anti-HBs (hepatitis B surface antigen) in a large sample of a nondiabetic, general population, indicating a possible role of insulin resistance in vaccine-induced immunity.

Grazoprevir, a second-generation HCV NS3/4A protease inhibitor, combined with ribavirin was associated with a rapid and sustained suppression of HCV RNA in a randomized study. The authors said the results support further evaluation of grazoprevir-based treatment regimens.

HIV–HCV coinfected patients treated with a fixed-dose combination of ledipasvir and sofosbuvir (LDV/SOF) showed significant improvement of their health-related quality of life and other patient-reported outcomes during treatment and after treatment cessation, according to a study in the Journal of Viral Hepatitis.

A Swedish study found that diabetes mellitus and cirrhosis are strong risk factors for hepatocellular carcinoma development after sustained virologic response (SVR) following treatment for chronic HCV has been achieved. However, the risk to develop hepatocellular carcinoma diminished significantly 2 years after SVR.

Chinese investigators said serum levels of platelet-derived growth factor (PDGF) decreased remarkably through fibrosis progression and could be used as a noninvasive biomarker for the assessment of fibrosis stage in patients with chronic hepatitis B virus (HBV).

A genome-wide association study of liver fibrosis progression in patients coinfected with HCV and HIV identified a new locus associated with fibrosis severity on chromosome 3p25. The authors said the results may help define new targets for drug development or new prognostic tests.

The RNA helicase DDX5 and E3 ligase Mex3b are important cellular targets for the design of novel, epigenetic therapies to combat HBV infection and poor-prognosis HBV-associated liver cancer, according to a study in Hepatology.

A Japanese study found that daclatasvir (DCV) and asunaprevir (ASV) dual therapy in hemodialysis patients infected with HCV is effective and safe with similar results, compared with patients with normal renal function.

A study evaluating the antiviral effect of ribavirin priming, and its influence on sustained virologic response after combination treatment, found that the lowest response pattern in HCV-infected patients was observed in prior nonresponder patients to pegylated interferon-alfa plus ribavirin combination therapy. The authors said this suggests that not only the individual interferon, but also the ribavirin sensitivity contributes significantly to the nonresponsive state.

A veterinary study provided evidence that hepatitis E virus is able to damage the blood-brain barrier and replicate in the brain and spinal cord.

An all-oral regimen of ledipasvir and sofosbuvir is an effective and safe treatment for a wide range of HCV genotype 4 subtypes in both treatment-naive and -experienced patients, including those with compensated cirrhosis, according to results of a recent study.

[email protected]

On Twitter @richpizzi

The RADEO toolkit also provides strategies for facilitating policy formation, evaluating current processes, tracking progress against implementation goals, and identifying best practices. Although the RADEO toolkit is designed for the inpatient setting, it also discusses care transitions for patients on opioid therapy to the outpatient setting.

Download the toolkit today at www.hospitalmedicine.org/RADEO. Check out all available quality improvement and patient safety toolkits at www.hospitalmedicine.org/qi.

The RADEO toolkit also provides strategies for facilitating policy formation, evaluating current processes, tracking progress against implementation goals, and identifying best practices. Although the RADEO toolkit is designed for the inpatient setting, it also discusses care transitions for patients on opioid therapy to the outpatient setting.

Download the toolkit today at www.hospitalmedicine.org/RADEO. Check out all available quality improvement and patient safety toolkits at www.hospitalmedicine.org/qi.

The RADEO toolkit also provides strategies for facilitating policy formation, evaluating current processes, tracking progress against implementation goals, and identifying best practices. Although the RADEO toolkit is designed for the inpatient setting, it also discusses care transitions for patients on opioid therapy to the outpatient setting.

Download the toolkit today at www.hospitalmedicine.org/RADEO. Check out all available quality improvement and patient safety toolkits at www.hospitalmedicine.org/qi.

The Commission on Care has issued its final report, which called for the expansion of community care for all veterans through the creation of integrated community-based health care networks similar to TRICARE, expansion of eligibility for veterans, and the creation of a facility and capital asset realignment process based on the DoD Base Realignment and Closure Commission among its 18 recommendations.

Mandated by the Veterans Access, Choice and Accountability Act in the wake of the wait time, the 15-member Commission on Care was charged with providing recommendations for reforming veterans’ health care to President Obama. The commission’s recommendations carry considerable weight. The Choice Act mandated that the VA and other federal agencies “implement each recommendation that the President considers feasible, advisable, and able to implement without further legislation.”

The commission’s first recommendation was to scrap the Choice Program and establish the VHA Care System, a system of “integrated veteran-centric, community-based delivery networks that will optimize the balance of access, quality, and cost-effectiveness.” Local VHA leadership would develop the VHA Care System  and base it on “local needs and veterans’ preferences.” The VHA would be mandated to furnish credentials to community providers, with the highest priority access given to service-connected veterans. The time and distance criteria used by the Choice Program would be eliminated, and veterans would be able to choose any primary care provider from within the system.

The Commission offered 4 possible models for implementing the VHA Care System. In the recommended option (an integrated network of VHA, DoD, other federally funded providers, and community providers, which requires a referral to access specialty care), the commission predicts as many as 60% of veterans would shift to community care for primary care needs, though far fewer would seek referrals in the community. The commission also predicted about a 15% increase in enrollment and an additional $5 billion in cost by FY 2019.

Another recommendation called for a “robust strategy for meeting and managing VHA’s facility and capital-asset needs.” According to the commission, the VA must reevaluate the future of individual facilities “in light of a transformative new delivery model.” A new commission, based on the military closure commissions, would help determine which facilities would remain open and which would close. “If VA could sell, repurpose, or otherwise divest itself of unused or underutilized buildings in a timely, cost-effective manner, it would free funds for the purposes for which they are appropriated,” the commission argued.

The commission also focused on personnel issues in a number of its recommendations, calling for the transformation of VHA culture and staff engagement, performance metrics for all employees, a new personnel system, and increased cultural and military competency, “to embrace diversity, promote cultural sensitivity, and improve veteran health outcomes.”

All but 2 commissioners signed the report. The commission charged that “many profound deficiencies in VHA operations require urgent reform, and that America’s veterans deserve a better organized, high-performing health care system.” While the changes may seem sweeping to many, the 2 dissenting commissioners urged even more significant changes. In a dissent letter acquired by the Washington Free Beacon, these commissioners argue that “the disappointing reality is that the commission’s final report is deeply compromised, disjointed, and incomplete. The report repeatedly invokes the need for a ‘bold transformation’ at the VHA. Yet, with a few exceptions, there is a decided lack of boldness in the Commission’s recommendations.”

Reaction has been slow as officials at the White House, VA, and veterans group digest the 308-page report. Some groups, however, already are raising concerns. The American Legion issued a statement: “Increased privatization of veteran health care services is not in the best interest of veterans or the American taxpayer. While we are still reviewing the complete report, we note that the commission had a very limited interaction with veterans who actually use VA health care, and even less time spent in VA facilities.”

The President also issued a brief noncommittal statement. “The commission's report includes a number of specific proposals that I look forward to reviewing closely over the coming weeks. We will continue to work with veterans, Congress, and our partners in the veteran advocacy community to further our ongoing transformation of the veterans’ health care system. Our veterans deserve nothing less for their sacrifices and their service.”

The VA offered a brief reaction to the report, finding commonalities in its current reform efforts. “While we will examine the report closely over the coming weeks and respond in a more detailed fashion, I am pleased to see that many of their recommendations are in line with our MyVA efforts to transform the VA into a veteran-centric organization,” Secretary of Veterans Affairs Robert A. McDonald said in the statement. “There are some things that can be done right now to help us continue our progress. Congress must act on our proposals to consolidate our Community Care programs, modernize and reform the claims appeals process, and pass the bi-partisan Veterans First Act.”

[Click through to the 18 recommendations offered by the commission.]

The full set of recommendations covers a broad range of issue for the VA:

Recommendation #1: Across the United States, with local input and knowledge, VHA should establish high-performing, integrated community health care networks, to be known as the VHA Care System, from which veterans will access high-quality health care services.

Recommendation #2: Enhance clinical operations through more effective use of providers and other health professionals, and improved data collection and management.

Recommendation #3: Develop a process for appealing clinical decisions that provides veterans protections at least comparable to those afforded patients under other federally supported programs.

Recommendation #4: Adopt a continuous improvement methodology to support VHA transformation, and consolidate best practices and continuous improvement efforts under the Veterans Engineering Resource Center.

Recommendation #5: Eliminate health care disparities among veterans treated in the VHA Care System by committing adequate personnel and monetary resources to address the causes of the problem and ensuring the VHA Health Equity Action Plan is fully implemented.

Recommendation #6: Develop and implement a robust strategy for meeting and managing VHA’s facility and capital-asset needs.

Recommendation #7: Modernize VA’s IT systems and infrastructure to improve veterans’ health and well-being and provide the foundation needed to transform VHA’s clinical and business processes. 

Recommendation #8: Transform the management of the supply chain in VHA.

Recommendation #9: Establish a board of directors to provide overall VHA Care System governance, set long-term strategy, and direct and oversee the transformation process.

Recommendation #10: Require leaders at all levels of the organization to champion a focused, clear, benchmarked strategy to transform VHA culture and sustain staff engagement.

Recommendation #11: Rebuild a system for leadership succession based on a benchmarked health care competency model that is consistently applied to recruitment, development, and advancement within the leadership pipeline.

Recommendation #12: Transform organizational structures and management processes to ensure adherence to national VHA standards, while also promoting decision making at the lowest level of the organization, eliminating waste and redundancy, promoting innovation, and fostering the spread of best practices.

Recommendation #13: Streamline and focus organizational performance measurement in VHA using core metrics that are identical to those used in the private sector, and establish a personnel performance management system for health care leaders in VHA that is distinct from performance measurement, is based on the leadership competency model, assesses leadership ability, and measures the achievement of important organizational strategies.

Recommendation #14: Foster cultural and military competence among all VHA Care System leadership, providers, and staff to embrace diversity, promote cultural sensitivity, and improve veteran health outcomes.

Recommendation #15: Create a simple-to-administer alternative personnel system, in law and regulation, which governs all VHA employees, applies best practices from the private sector to human capital management, and supports pay and benefits that are competitive with the private sector.

Recommendation #16: Require top executives to lead the transformation of HR, commit funds, and assign expert resources to achieve an effective human capital management system.

Recommendation #17: Provide a streamlined path to eligibility for health care for those with an other-than-honorable discharge who have substantial honorable service. 

Recommendation #18: Establish an expert body to develop recommendations for VA care eligibility and benefit design.   

The Commission on Care has issued its final report, which called for the expansion of community care for all veterans through the creation of integrated community-based health care networks similar to TRICARE, expansion of eligibility for veterans, and the creation of a facility and capital asset realignment process based on the DoD Base Realignment and Closure Commission among its 18 recommendations.

Mandated by the Veterans Access, Choice and Accountability Act in the wake of the wait time, the 15-member Commission on Care was charged with providing recommendations for reforming veterans’ health care to President Obama. The commission’s recommendations carry considerable weight. The Choice Act mandated that the VA and other federal agencies “implement each recommendation that the President considers feasible, advisable, and able to implement without further legislation.”

The commission’s first recommendation was to scrap the Choice Program and establish the VHA Care System, a system of “integrated veteran-centric, community-based delivery networks that will optimize the balance of access, quality, and cost-effectiveness.” Local VHA leadership would develop the VHA Care System  and base it on “local needs and veterans’ preferences.” The VHA would be mandated to furnish credentials to community providers, with the highest priority access given to service-connected veterans. The time and distance criteria used by the Choice Program would be eliminated, and veterans would be able to choose any primary care provider from within the system.

The Commission offered 4 possible models for implementing the VHA Care System. In the recommended option (an integrated network of VHA, DoD, other federally funded providers, and community providers, which requires a referral to access specialty care), the commission predicts as many as 60% of veterans would shift to community care for primary care needs, though far fewer would seek referrals in the community. The commission also predicted about a 15% increase in enrollment and an additional $5 billion in cost by FY 2019.

Another recommendation called for a “robust strategy for meeting and managing VHA’s facility and capital-asset needs.” According to the commission, the VA must reevaluate the future of individual facilities “in light of a transformative new delivery model.” A new commission, based on the military closure commissions, would help determine which facilities would remain open and which would close. “If VA could sell, repurpose, or otherwise divest itself of unused or underutilized buildings in a timely, cost-effective manner, it would free funds for the purposes for which they are appropriated,” the commission argued.

The commission also focused on personnel issues in a number of its recommendations, calling for the transformation of VHA culture and staff engagement, performance metrics for all employees, a new personnel system, and increased cultural and military competency, “to embrace diversity, promote cultural sensitivity, and improve veteran health outcomes.”

All but 2 commissioners signed the report. The commission charged that “many profound deficiencies in VHA operations require urgent reform, and that America’s veterans deserve a better organized, high-performing health care system.” While the changes may seem sweeping to many, the 2 dissenting commissioners urged even more significant changes. In a dissent letter acquired by the Washington Free Beacon, these commissioners argue that “the disappointing reality is that the commission’s final report is deeply compromised, disjointed, and incomplete. The report repeatedly invokes the need for a ‘bold transformation’ at the VHA. Yet, with a few exceptions, there is a decided lack of boldness in the Commission’s recommendations.”

Reaction has been slow as officials at the White House, VA, and veterans group digest the 308-page report. Some groups, however, already are raising concerns. The American Legion issued a statement: “Increased privatization of veteran health care services is not in the best interest of veterans or the American taxpayer. While we are still reviewing the complete report, we note that the commission had a very limited interaction with veterans who actually use VA health care, and even less time spent in VA facilities.”

The President also issued a brief noncommittal statement. “The commission's report includes a number of specific proposals that I look forward to reviewing closely over the coming weeks. We will continue to work with veterans, Congress, and our partners in the veteran advocacy community to further our ongoing transformation of the veterans’ health care system. Our veterans deserve nothing less for their sacrifices and their service.”

The VA offered a brief reaction to the report, finding commonalities in its current reform efforts. “While we will examine the report closely over the coming weeks and respond in a more detailed fashion, I am pleased to see that many of their recommendations are in line with our MyVA efforts to transform the VA into a veteran-centric organization,” Secretary of Veterans Affairs Robert A. McDonald said in the statement. “There are some things that can be done right now to help us continue our progress. Congress must act on our proposals to consolidate our Community Care programs, modernize and reform the claims appeals process, and pass the bi-partisan Veterans First Act.”

[Click through to the 18 recommendations offered by the commission.]

The full set of recommendations covers a broad range of issue for the VA:

Recommendation #1: Across the United States, with local input and knowledge, VHA should establish high-performing, integrated community health care networks, to be known as the VHA Care System, from which veterans will access high-quality health care services.

Recommendation #2: Enhance clinical operations through more effective use of providers and other health professionals, and improved data collection and management.

Recommendation #3: Develop a process for appealing clinical decisions that provides veterans protections at least comparable to those afforded patients under other federally supported programs.

Recommendation #4: Adopt a continuous improvement methodology to support VHA transformation, and consolidate best practices and continuous improvement efforts under the Veterans Engineering Resource Center.

Recommendation #5: Eliminate health care disparities among veterans treated in the VHA Care System by committing adequate personnel and monetary resources to address the causes of the problem and ensuring the VHA Health Equity Action Plan is fully implemented.

Recommendation #6: Develop and implement a robust strategy for meeting and managing VHA’s facility and capital-asset needs.

Recommendation #7: Modernize VA’s IT systems and infrastructure to improve veterans’ health and well-being and provide the foundation needed to transform VHA’s clinical and business processes. 

Recommendation #8: Transform the management of the supply chain in VHA.

Recommendation #9: Establish a board of directors to provide overall VHA Care System governance, set long-term strategy, and direct and oversee the transformation process.

Recommendation #10: Require leaders at all levels of the organization to champion a focused, clear, benchmarked strategy to transform VHA culture and sustain staff engagement.

Recommendation #11: Rebuild a system for leadership succession based on a benchmarked health care competency model that is consistently applied to recruitment, development, and advancement within the leadership pipeline.

Recommendation #12: Transform organizational structures and management processes to ensure adherence to national VHA standards, while also promoting decision making at the lowest level of the organization, eliminating waste and redundancy, promoting innovation, and fostering the spread of best practices.

Recommendation #13: Streamline and focus organizational performance measurement in VHA using core metrics that are identical to those used in the private sector, and establish a personnel performance management system for health care leaders in VHA that is distinct from performance measurement, is based on the leadership competency model, assesses leadership ability, and measures the achievement of important organizational strategies.

Recommendation #14: Foster cultural and military competence among all VHA Care System leadership, providers, and staff to embrace diversity, promote cultural sensitivity, and improve veteran health outcomes.

Recommendation #15: Create a simple-to-administer alternative personnel system, in law and regulation, which governs all VHA employees, applies best practices from the private sector to human capital management, and supports pay and benefits that are competitive with the private sector.

Recommendation #16: Require top executives to lead the transformation of HR, commit funds, and assign expert resources to achieve an effective human capital management system.

Recommendation #17: Provide a streamlined path to eligibility for health care for those with an other-than-honorable discharge who have substantial honorable service. 

Recommendation #18: Establish an expert body to develop recommendations for VA care eligibility and benefit design.   

The Commission on Care has issued its final report, which called for the expansion of community care for all veterans through the creation of integrated community-based health care networks similar to TRICARE, expansion of eligibility for veterans, and the creation of a facility and capital asset realignment process based on the DoD Base Realignment and Closure Commission among its 18 recommendations.

Mandated by the Veterans Access, Choice and Accountability Act in the wake of the wait time, the 15-member Commission on Care was charged with providing recommendations for reforming veterans’ health care to President Obama. The commission’s recommendations carry considerable weight. The Choice Act mandated that the VA and other federal agencies “implement each recommendation that the President considers feasible, advisable, and able to implement without further legislation.”

The commission’s first recommendation was to scrap the Choice Program and establish the VHA Care System, a system of “integrated veteran-centric, community-based delivery networks that will optimize the balance of access, quality, and cost-effectiveness.” Local VHA leadership would develop the VHA Care System  and base it on “local needs and veterans’ preferences.” The VHA would be mandated to furnish credentials to community providers, with the highest priority access given to service-connected veterans. The time and distance criteria used by the Choice Program would be eliminated, and veterans would be able to choose any primary care provider from within the system.

The Commission offered 4 possible models for implementing the VHA Care System. In the recommended option (an integrated network of VHA, DoD, other federally funded providers, and community providers, which requires a referral to access specialty care), the commission predicts as many as 60% of veterans would shift to community care for primary care needs, though far fewer would seek referrals in the community. The commission also predicted about a 15% increase in enrollment and an additional $5 billion in cost by FY 2019.

Another recommendation called for a “robust strategy for meeting and managing VHA’s facility and capital-asset needs.” According to the commission, the VA must reevaluate the future of individual facilities “in light of a transformative new delivery model.” A new commission, based on the military closure commissions, would help determine which facilities would remain open and which would close. “If VA could sell, repurpose, or otherwise divest itself of unused or underutilized buildings in a timely, cost-effective manner, it would free funds for the purposes for which they are appropriated,” the commission argued.

The commission also focused on personnel issues in a number of its recommendations, calling for the transformation of VHA culture and staff engagement, performance metrics for all employees, a new personnel system, and increased cultural and military competency, “to embrace diversity, promote cultural sensitivity, and improve veteran health outcomes.”

All but 2 commissioners signed the report. The commission charged that “many profound deficiencies in VHA operations require urgent reform, and that America’s veterans deserve a better organized, high-performing health care system.” While the changes may seem sweeping to many, the 2 dissenting commissioners urged even more significant changes. In a dissent letter acquired by the Washington Free Beacon, these commissioners argue that “the disappointing reality is that the commission’s final report is deeply compromised, disjointed, and incomplete. The report repeatedly invokes the need for a ‘bold transformation’ at the VHA. Yet, with a few exceptions, there is a decided lack of boldness in the Commission’s recommendations.”

Reaction has been slow as officials at the White House, VA, and veterans group digest the 308-page report. Some groups, however, already are raising concerns. The American Legion issued a statement: “Increased privatization of veteran health care services is not in the best interest of veterans or the American taxpayer. While we are still reviewing the complete report, we note that the commission had a very limited interaction with veterans who actually use VA health care, and even less time spent in VA facilities.”

The President also issued a brief noncommittal statement. “The commission's report includes a number of specific proposals that I look forward to reviewing closely over the coming weeks. We will continue to work with veterans, Congress, and our partners in the veteran advocacy community to further our ongoing transformation of the veterans’ health care system. Our veterans deserve nothing less for their sacrifices and their service.”

The VA offered a brief reaction to the report, finding commonalities in its current reform efforts. “While we will examine the report closely over the coming weeks and respond in a more detailed fashion, I am pleased to see that many of their recommendations are in line with our MyVA efforts to transform the VA into a veteran-centric organization,” Secretary of Veterans Affairs Robert A. McDonald said in the statement. “There are some things that can be done right now to help us continue our progress. Congress must act on our proposals to consolidate our Community Care programs, modernize and reform the claims appeals process, and pass the bi-partisan Veterans First Act.”

[Click through to the 18 recommendations offered by the commission.]

The full set of recommendations covers a broad range of issue for the VA:

Recommendation #1: Across the United States, with local input and knowledge, VHA should establish high-performing, integrated community health care networks, to be known as the VHA Care System, from which veterans will access high-quality health care services.

Recommendation #2: Enhance clinical operations through more effective use of providers and other health professionals, and improved data collection and management.

Recommendation #3: Develop a process for appealing clinical decisions that provides veterans protections at least comparable to those afforded patients under other federally supported programs.

Recommendation #4: Adopt a continuous improvement methodology to support VHA transformation, and consolidate best practices and continuous improvement efforts under the Veterans Engineering Resource Center.

Recommendation #5: Eliminate health care disparities among veterans treated in the VHA Care System by committing adequate personnel and monetary resources to address the causes of the problem and ensuring the VHA Health Equity Action Plan is fully implemented.

Recommendation #6: Develop and implement a robust strategy for meeting and managing VHA’s facility and capital-asset needs.

Recommendation #7: Modernize VA’s IT systems and infrastructure to improve veterans’ health and well-being and provide the foundation needed to transform VHA’s clinical and business processes. 

Recommendation #8: Transform the management of the supply chain in VHA.

Recommendation #9: Establish a board of directors to provide overall VHA Care System governance, set long-term strategy, and direct and oversee the transformation process.

Recommendation #10: Require leaders at all levels of the organization to champion a focused, clear, benchmarked strategy to transform VHA culture and sustain staff engagement.

Recommendation #11: Rebuild a system for leadership succession based on a benchmarked health care competency model that is consistently applied to recruitment, development, and advancement within the leadership pipeline.

Recommendation #12: Transform organizational structures and management processes to ensure adherence to national VHA standards, while also promoting decision making at the lowest level of the organization, eliminating waste and redundancy, promoting innovation, and fostering the spread of best practices.

Recommendation #13: Streamline and focus organizational performance measurement in VHA using core metrics that are identical to those used in the private sector, and establish a personnel performance management system for health care leaders in VHA that is distinct from performance measurement, is based on the leadership competency model, assesses leadership ability, and measures the achievement of important organizational strategies.

Recommendation #14: Foster cultural and military competence among all VHA Care System leadership, providers, and staff to embrace diversity, promote cultural sensitivity, and improve veteran health outcomes.

Recommendation #15: Create a simple-to-administer alternative personnel system, in law and regulation, which governs all VHA employees, applies best practices from the private sector to human capital management, and supports pay and benefits that are competitive with the private sector.

Recommendation #16: Require top executives to lead the transformation of HR, commit funds, and assign expert resources to achieve an effective human capital management system.

Recommendation #17: Provide a streamlined path to eligibility for health care for those with an other-than-honorable discharge who have substantial honorable service. 

Recommendation #18: Establish an expert body to develop recommendations for VA care eligibility and benefit design.   

Imatinib tablet

Long-term results from the DASISION trial suggest that dasatinib and imatinib produce similar outcomes in patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML).

Although patients who received dasatinib experienced faster and deeper molecular responses than patients who received imatinib, the overall survival and progression-free survival rates were similar between the treatment arms.

Overall, adverse events (AEs) were similar between the arms as well.

Researchers said these results suggest that dasatinib should continue to be considered an option for patients with newly diagnosed CP-CML.

The team reported the results of this study in the Journal of Clinical Oncology. The research was sponsored by Bristol-Myers Squibb.

The trial enrolled 519 patients with newly diagnosed CP-CML. They were randomized to receive dasatinib at 100 mg once daily (n=259) or imatinib at 400 mg once daily (n=260). Baseline characteristics were well-balanced between the arms.

At 5 years of follow-up, 61% of patients in the dasatinib arm and 63% of patients in the imatinib arm remained on treatment.

Response and survival

The cumulative 5-year rate of major molecular response was 76% in the dasatinib arm and 64% in the imatinib arm (P=0.0022). The rates of MR^4.5 were 42% and 33%, respectively (P=0.0251).

The estimated 5-year overall survival was 91% in the dasatinib arm and 90% in the imatinib arm (hazard ratio=1.01; 95% CI, 0.58 to 1.73).

The estimated 5-year progression-free survival was 85% and 86%, respectively (hazard ratio=1.06; 95% CI, 0.68 to 1.66).

Safety

In both treatment arms, most AEs were grade 1 or 2. Grade 3/4 AEs occurred in 15% of patients in the dasatinib arm and 11% of patients in the imatinib arm.

Rates of grade 3/4 hematologic AEs tended to be higher in the dasatinib arm than the imatinib arm.

But the rates of most drug-related, nonhematologic AEs were lower in the dasatinib arm than the imatinib arm or were comparable between the arms.

The exception was drug-related pleural effusion, which was more common with dasatinib (28%) than with imatinib (0.8%).

Drug-related AEs were largely manageable, although they led to treatment discontinuation in 16% of dasatinib-treated patients and 7% of imatinib-treated patients.

By 5 years, 26 patients (10%) in each treatment arm had died. Nine patients in the dasatinib arm died of disease progression, as did 17 patients in the imatinib arm.

Imatinib tablet

Long-term results from the DASISION trial suggest that dasatinib and imatinib produce similar outcomes in patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML).

Although patients who received dasatinib experienced faster and deeper molecular responses than patients who received imatinib, the overall survival and progression-free survival rates were similar between the treatment arms.

Overall, adverse events (AEs) were similar between the arms as well.

Researchers said these results suggest that dasatinib should continue to be considered an option for patients with newly diagnosed CP-CML.

The team reported the results of this study in the Journal of Clinical Oncology. The research was sponsored by Bristol-Myers Squibb.

The trial enrolled 519 patients with newly diagnosed CP-CML. They were randomized to receive dasatinib at 100 mg once daily (n=259) or imatinib at 400 mg once daily (n=260). Baseline characteristics were well-balanced between the arms.

At 5 years of follow-up, 61% of patients in the dasatinib arm and 63% of patients in the imatinib arm remained on treatment.

Response and survival

The cumulative 5-year rate of major molecular response was 76% in the dasatinib arm and 64% in the imatinib arm (P=0.0022). The rates of MR^4.5 were 42% and 33%, respectively (P=0.0251).

The estimated 5-year overall survival was 91% in the dasatinib arm and 90% in the imatinib arm (hazard ratio=1.01; 95% CI, 0.58 to 1.73).

The estimated 5-year progression-free survival was 85% and 86%, respectively (hazard ratio=1.06; 95% CI, 0.68 to 1.66).

Safety

In both treatment arms, most AEs were grade 1 or 2. Grade 3/4 AEs occurred in 15% of patients in the dasatinib arm and 11% of patients in the imatinib arm.

Rates of grade 3/4 hematologic AEs tended to be higher in the dasatinib arm than the imatinib arm.

But the rates of most drug-related, nonhematologic AEs were lower in the dasatinib arm than the imatinib arm or were comparable between the arms.

The exception was drug-related pleural effusion, which was more common with dasatinib (28%) than with imatinib (0.8%).

Drug-related AEs were largely manageable, although they led to treatment discontinuation in 16% of dasatinib-treated patients and 7% of imatinib-treated patients.

By 5 years, 26 patients (10%) in each treatment arm had died. Nine patients in the dasatinib arm died of disease progression, as did 17 patients in the imatinib arm.

Imatinib tablet

Long-term results from the DASISION trial suggest that dasatinib and imatinib produce similar outcomes in patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML).

Although patients who received dasatinib experienced faster and deeper molecular responses than patients who received imatinib, the overall survival and progression-free survival rates were similar between the treatment arms.

Overall, adverse events (AEs) were similar between the arms as well.

Researchers said these results suggest that dasatinib should continue to be considered an option for patients with newly diagnosed CP-CML.

The team reported the results of this study in the Journal of Clinical Oncology. The research was sponsored by Bristol-Myers Squibb.

The trial enrolled 519 patients with newly diagnosed CP-CML. They were randomized to receive dasatinib at 100 mg once daily (n=259) or imatinib at 400 mg once daily (n=260). Baseline characteristics were well-balanced between the arms.

At 5 years of follow-up, 61% of patients in the dasatinib arm and 63% of patients in the imatinib arm remained on treatment.

Response and survival

The cumulative 5-year rate of major molecular response was 76% in the dasatinib arm and 64% in the imatinib arm (P=0.0022). The rates of MR^4.5 were 42% and 33%, respectively (P=0.0251).

The estimated 5-year overall survival was 91% in the dasatinib arm and 90% in the imatinib arm (hazard ratio=1.01; 95% CI, 0.58 to 1.73).

The estimated 5-year progression-free survival was 85% and 86%, respectively (hazard ratio=1.06; 95% CI, 0.68 to 1.66).

Safety

In both treatment arms, most AEs were grade 1 or 2. Grade 3/4 AEs occurred in 15% of patients in the dasatinib arm and 11% of patients in the imatinib arm.

Rates of grade 3/4 hematologic AEs tended to be higher in the dasatinib arm than the imatinib arm.

But the rates of most drug-related, nonhematologic AEs were lower in the dasatinib arm than the imatinib arm or were comparable between the arms.

The exception was drug-related pleural effusion, which was more common with dasatinib (28%) than with imatinib (0.8%).

Drug-related AEs were largely manageable, although they led to treatment discontinuation in 16% of dasatinib-treated patients and 7% of imatinib-treated patients.

By 5 years, 26 patients (10%) in each treatment arm had died. Nine patients in the dasatinib arm died of disease progression, as did 17 patients in the imatinib arm.

Carfilzomib (Kyprolis)

Photo from Amgen

The European Commission (EC) has expanded the approved use of the proteasome inhibitor carfilzomib (Kyprolis).

The drug is now approved for use in combination with dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Carfilzomib was previously approved by the EC for use in combination with lenalidomide and dexamethasone to treat adult MM patients who have received at least 1 prior therapy.

The EC approved the extended indication for carfilzomib based on data from the phase 3 ENDEAVOR trial.

The trial included 929 MM patients whose disease had relapsed after 1 to 3 prior therapeutic regimens.

The patients received either carfilzomib plus dexamethasone (n=464) or bortezomib plus dexamethasone (n=465) until disease progression.

The primary endpoint was progression-free survival. The median progression-free survival was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm. The hazard ratio was 0.53 (P<0.0001).

Overall survival data were not yet mature at last follow-up.

Treatment discontinuation due to adverse events and on-study deaths were comparable between the 2 treatment arms.

However, a number of known adverse events were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

Carfilzomib is marketed as Kyprolis by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, with the exception of Japan.

Carfilzomib (Kyprolis)

Photo from Amgen

The European Commission (EC) has expanded the approved use of the proteasome inhibitor carfilzomib (Kyprolis).

The drug is now approved for use in combination with dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Carfilzomib was previously approved by the EC for use in combination with lenalidomide and dexamethasone to treat adult MM patients who have received at least 1 prior therapy.

The EC approved the extended indication for carfilzomib based on data from the phase 3 ENDEAVOR trial.

The trial included 929 MM patients whose disease had relapsed after 1 to 3 prior therapeutic regimens.

The patients received either carfilzomib plus dexamethasone (n=464) or bortezomib plus dexamethasone (n=465) until disease progression.

The primary endpoint was progression-free survival. The median progression-free survival was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm. The hazard ratio was 0.53 (P<0.0001).

Overall survival data were not yet mature at last follow-up.

Treatment discontinuation due to adverse events and on-study deaths were comparable between the 2 treatment arms.

However, a number of known adverse events were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

Carfilzomib is marketed as Kyprolis by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, with the exception of Japan.

Carfilzomib (Kyprolis)

Photo from Amgen

The European Commission (EC) has expanded the approved use of the proteasome inhibitor carfilzomib (Kyprolis).

The drug is now approved for use in combination with dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Carfilzomib was previously approved by the EC for use in combination with lenalidomide and dexamethasone to treat adult MM patients who have received at least 1 prior therapy.

The EC approved the extended indication for carfilzomib based on data from the phase 3 ENDEAVOR trial.

The trial included 929 MM patients whose disease had relapsed after 1 to 3 prior therapeutic regimens.

The patients received either carfilzomib plus dexamethasone (n=464) or bortezomib plus dexamethasone (n=465) until disease progression.

The primary endpoint was progression-free survival. The median progression-free survival was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm. The hazard ratio was 0.53 (P<0.0001).

Overall survival data were not yet mature at last follow-up.

Treatment discontinuation due to adverse events and on-study deaths were comparable between the 2 treatment arms.

However, a number of known adverse events were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

Carfilzomib is marketed as Kyprolis by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, with the exception of Japan.

Plasmodium sporozoite

Image by Ute Frevert

and Margaret Shear

New research suggests that infections with 2 types of malaria parasite lead to greater health risks because 1 species helps the other thrive.

Investigators sought to understand what happens when the 2 most common malaria parasites cause infection at the same time, as they are known to attack the body in different ways.

The team found the first parasite helps provide the second with more of the resources it needs to prosper.

“Immune responses are assumed to determine the outcome of interactions between parasite species, but our study clearly shows that resources can be more important,” said Sarah Reece, of the University of Edinburgh in Scotland.

“Our findings also challenge ideas that 1 species will outcompete the other, which explains why infections involving 2 parasite species can pose a greater health risk to patients.”

Dr Reece and her colleagues recounted these findings in Ecology Letters.

In humans, the malaria parasite Plasmodium falciparum infects red blood cells of all ages, while the Plasmodium vivax parasite attacks only young red blood cells.

The current study, conducted in mice with equivalent malaria parasites (P chabaudi and P yoelii), showed that the body’s response to the first infection produces more of the type of red blood cell the second parasite needs.

In response to the first infection, millions of red blood cells are destroyed. The body responds by replenishing these cells.

The fresh cells then become infected by the second type of parasite, making the infection worse.

The investigators said these results appear to explain why infections with both P falciparum and P vivax often have worse outcomes for patients than infections with a single malaria parasite.

Plasmodium sporozoite

Image by Ute Frevert

and Margaret Shear

New research suggests that infections with 2 types of malaria parasite lead to greater health risks because 1 species helps the other thrive.

Investigators sought to understand what happens when the 2 most common malaria parasites cause infection at the same time, as they are known to attack the body in different ways.

The team found the first parasite helps provide the second with more of the resources it needs to prosper.

“Immune responses are assumed to determine the outcome of interactions between parasite species, but our study clearly shows that resources can be more important,” said Sarah Reece, of the University of Edinburgh in Scotland.

“Our findings also challenge ideas that 1 species will outcompete the other, which explains why infections involving 2 parasite species can pose a greater health risk to patients.”

Dr Reece and her colleagues recounted these findings in Ecology Letters.

In humans, the malaria parasite Plasmodium falciparum infects red blood cells of all ages, while the Plasmodium vivax parasite attacks only young red blood cells.

The current study, conducted in mice with equivalent malaria parasites (P chabaudi and P yoelii), showed that the body’s response to the first infection produces more of the type of red blood cell the second parasite needs.

In response to the first infection, millions of red blood cells are destroyed. The body responds by replenishing these cells.

The fresh cells then become infected by the second type of parasite, making the infection worse.

The investigators said these results appear to explain why infections with both P falciparum and P vivax often have worse outcomes for patients than infections with a single malaria parasite.

Plasmodium sporozoite

Image by Ute Frevert

and Margaret Shear

New research suggests that infections with 2 types of malaria parasite lead to greater health risks because 1 species helps the other thrive.

Investigators sought to understand what happens when the 2 most common malaria parasites cause infection at the same time, as they are known to attack the body in different ways.

The team found the first parasite helps provide the second with more of the resources it needs to prosper.

“Immune responses are assumed to determine the outcome of interactions between parasite species, but our study clearly shows that resources can be more important,” said Sarah Reece, of the University of Edinburgh in Scotland.

“Our findings also challenge ideas that 1 species will outcompete the other, which explains why infections involving 2 parasite species can pose a greater health risk to patients.”

Dr Reece and her colleagues recounted these findings in Ecology Letters.

In humans, the malaria parasite Plasmodium falciparum infects red blood cells of all ages, while the Plasmodium vivax parasite attacks only young red blood cells.

The current study, conducted in mice with equivalent malaria parasites (P chabaudi and P yoelii), showed that the body’s response to the first infection produces more of the type of red blood cell the second parasite needs.

In response to the first infection, millions of red blood cells are destroyed. The body responds by replenishing these cells.

The fresh cells then become infected by the second type of parasite, making the infection worse.

The investigators said these results appear to explain why infections with both P falciparum and P vivax often have worse outcomes for patients than infections with a single malaria parasite.

Lab mouse

A new study helps explain why some patients with malignant hyperthermia may suffer from excessive bleeding.

The findings suggest a mutation that causes malignant hyperthermia can disrupt calcium signaling in vascular smooth muscle cells, leading to bleeding abnormalities.

What’s more, researchers found that a drug clinically approved to treat muscle-related symptoms in malignant hyperthermia helped stop bleeding.

Rubén Lopez, of Basel University Hospital in Switzerland, and his colleagues conducted this research and reported their findings in Science Signaling.

Patients with malignant hyperthermia experience dangerously high fever and severe muscle contractions when exposed to general anesthesia.

Malignant hyperthermia is often caused by mutations in the RYR1 gene, which encodes a calcium channel in skeletal muscle called ryanodine receptor type 1 (RyR1).

For some patients with these mutations, malignant hyperthermia is accompanied by a mild bleeding disorder, but whether the 2 conditions are connected has not been clear.

Working in a mouse model of malignant hyperthermia, researchers found that vascular smooth muscle cells with mutated RyR1 displayed frequent spikes in calcium levels, known as calcium sparks. These sparks led to excessive vasodilation and prolonged bleeding.

Blocking the receptor with dantrolene, a drug used to treat malignant hyperthermia, helped reduce bleeding in the mice and in a single human patient, pointing to an unexpected benefit from the drug.

The findings suggest that mutations in RyR1, which is also found in other types of smooth muscle cells such as those in the bladder and uterus, may have a wider range of effects than previously thought.

Lab mouse

A new study helps explain why some patients with malignant hyperthermia may suffer from excessive bleeding.

The findings suggest a mutation that causes malignant hyperthermia can disrupt calcium signaling in vascular smooth muscle cells, leading to bleeding abnormalities.

What’s more, researchers found that a drug clinically approved to treat muscle-related symptoms in malignant hyperthermia helped stop bleeding.

Rubén Lopez, of Basel University Hospital in Switzerland, and his colleagues conducted this research and reported their findings in Science Signaling.

Patients with malignant hyperthermia experience dangerously high fever and severe muscle contractions when exposed to general anesthesia.

Malignant hyperthermia is often caused by mutations in the RYR1 gene, which encodes a calcium channel in skeletal muscle called ryanodine receptor type 1 (RyR1).

For some patients with these mutations, malignant hyperthermia is accompanied by a mild bleeding disorder, but whether the 2 conditions are connected has not been clear.

Working in a mouse model of malignant hyperthermia, researchers found that vascular smooth muscle cells with mutated RyR1 displayed frequent spikes in calcium levels, known as calcium sparks. These sparks led to excessive vasodilation and prolonged bleeding.

Blocking the receptor with dantrolene, a drug used to treat malignant hyperthermia, helped reduce bleeding in the mice and in a single human patient, pointing to an unexpected benefit from the drug.

The findings suggest that mutations in RyR1, which is also found in other types of smooth muscle cells such as those in the bladder and uterus, may have a wider range of effects than previously thought.

Lab mouse

A new study helps explain why some patients with malignant hyperthermia may suffer from excessive bleeding.

The findings suggest a mutation that causes malignant hyperthermia can disrupt calcium signaling in vascular smooth muscle cells, leading to bleeding abnormalities.

What’s more, researchers found that a drug clinically approved to treat muscle-related symptoms in malignant hyperthermia helped stop bleeding.

Rubén Lopez, of Basel University Hospital in Switzerland, and his colleagues conducted this research and reported their findings in Science Signaling.

Patients with malignant hyperthermia experience dangerously high fever and severe muscle contractions when exposed to general anesthesia.

Malignant hyperthermia is often caused by mutations in the RYR1 gene, which encodes a calcium channel in skeletal muscle called ryanodine receptor type 1 (RyR1).

For some patients with these mutations, malignant hyperthermia is accompanied by a mild bleeding disorder, but whether the 2 conditions are connected has not been clear.

Working in a mouse model of malignant hyperthermia, researchers found that vascular smooth muscle cells with mutated RyR1 displayed frequent spikes in calcium levels, known as calcium sparks. These sparks led to excessive vasodilation and prolonged bleeding.

Blocking the receptor with dantrolene, a drug used to treat malignant hyperthermia, helped reduce bleeding in the mice and in a single human patient, pointing to an unexpected benefit from the drug.

The findings suggest that mutations in RyR1, which is also found in other types of smooth muscle cells such as those in the bladder and uterus, may have a wider range of effects than previously thought.

In the July podcast for The Journal of Community and Supportive Oncology, Dr David Henry discusses an editorial by Dr Linda bosserman, in which she presents the case for pathways and the importance of processes and team work in paving the way for value-based care. Survivor care is the focus of 2 Original Reports in which investigators report on adolescent and young adult perceptions of cancer survivor care and supportive programming and on the symptoms, unmet need, and quality of life among recent breast cancer survivors. Also in the Original Report section are reports on the impact of loss of income and medicine costs on the financial burden for cancer patients in Australia and the use of a gene-panel for testing for hereditary ovarian cancer. Dr Henry also looks at 2 Case Reports, one in which a patient undergoes multivisceral resection for growing teratoma syndrome and another in which a patient presents with aleukemic acute lymphoblastic leukemia with unusual clinical features. Diabetes management in cancer patients is the topic of a lengthy and informative interview between Dr Henry and Dr Todd Brown.

Listen to the podcast below.

In the July podcast for The Journal of Community and Supportive Oncology, Dr David Henry discusses an editorial by Dr Linda bosserman, in which she presents the case for pathways and the importance of processes and team work in paving the way for value-based care. Survivor care is the focus of 2 Original Reports in which investigators report on adolescent and young adult perceptions of cancer survivor care and supportive programming and on the symptoms, unmet need, and quality of life among recent breast cancer survivors. Also in the Original Report section are reports on the impact of loss of income and medicine costs on the financial burden for cancer patients in Australia and the use of a gene-panel for testing for hereditary ovarian cancer. Dr Henry also looks at 2 Case Reports, one in which a patient undergoes multivisceral resection for growing teratoma syndrome and another in which a patient presents with aleukemic acute lymphoblastic leukemia with unusual clinical features. Diabetes management in cancer patients is the topic of a lengthy and informative interview between Dr Henry and Dr Todd Brown.

Listen to the podcast below.

In the July podcast for The Journal of Community and Supportive Oncology, Dr David Henry discusses an editorial by Dr Linda bosserman, in which she presents the case for pathways and the importance of processes and team work in paving the way for value-based care. Survivor care is the focus of 2 Original Reports in which investigators report on adolescent and young adult perceptions of cancer survivor care and supportive programming and on the symptoms, unmet need, and quality of life among recent breast cancer survivors. Also in the Original Report section are reports on the impact of loss of income and medicine costs on the financial burden for cancer patients in Australia and the use of a gene-panel for testing for hereditary ovarian cancer. Dr Henry also looks at 2 Case Reports, one in which a patient undergoes multivisceral resection for growing teratoma syndrome and another in which a patient presents with aleukemic acute lymphoblastic leukemia with unusual clinical features. Diabetes management in cancer patients is the topic of a lengthy and informative interview between Dr Henry and Dr Todd Brown.

Listen to the podcast below.

The Food and Drug Administration approved the first fully absorbable vascular scaffold designed for use in coronary arteries, the Absorb GT1 bioresorbable vascular scaffold system, made by Abbott.

Concurrent with the FDA’s announcement on July 5, the company said that it plans to start immediate commercial rollout of the Absorb bioresorbable vascular scaffold (BVS). Initial availability will be limited to the roughly 100 most active sites that participated in the ABSORB III trial, the pivotal study that established noninferiority of the BVS, compared with a state-of-the-art metallic coronary stent during 1-year follow-up, according to a company spokesman.

However, the ABSORB III results, reported in October 2015, failed to document any superiority of the BVS, compared with a metallic stent. The potential advantages of a BVS remain for now unproven, and are based on the potential long-term advantages of using devices in percutaneous coronary interventions that slowly degrade away and thereby eliminate a residual metallic structure in a patient’s coronaries and the long-term threat they could pose for thrombosis or interference with subsequent coronary procedures.

“All the potential advantages are hypothetical at this point,” said Hiram G. Bezerra, MD, an investigator in the ABSORB III trial and director of the cardiac catheterization laboratory at University Hospitals Case Medical Center in Cleveland. However, “if you have a metallic stent it lasts a lifetime, creating a metallic cage” that could interfere with a possible later coronary procedure or be the site for thrombus formation. Disappearance of the BVS also creates the possibility for eventual restoration of more normal vasomotion in the coronary wall, said Dr. Bezerra, a self-professed “enthusiast” for the BVS alternative.

A major limiting factor for BVS use today is coronary diameter because the Absorb BVS is bulkier than metallic stents. The ABSORB III trial limited use of the BVS to coronary vessels with a reference-vessel diameter by visual assessment of at least 2.5 mm, with an upper limit of 3.75 mm. Other limiting factors can be coronary calcification and tortuosity, although Dr. Bezerra said that these obstacles are usually overcome with a more time-consuming procedure if the operator is committed to placing a BVS.

Another variable will be the cost of the BVS. According to the Abbott spokesman, the device “will be priced so that it will be broadly accessible to hospitals.” Also, the Absorb BVS will receive payer reimbursement comparable to a drug-eluting stent using existing reimbursement codes, the spokesman said. Abbott will require inexperienced operators to take a training course to learn proper placement technique.

Dr. Bezerra admitted that he is probably an outlier in his plan to quickly make the BVS a mainstay of his practice. “I think adoption will be slow in the beginning” for most U.S. operators, he predicted. One of his Cleveland colleagues who spoke about the near-term prospects BVS use last October when the ABSORB III results came out predicted that immediate use might occur in about 10%-15% of patients undergoing percutaneous coronary interventions, similar to the usage level in Europe where this BVS has been available for several years.

Dr. Bezerra has been a consultant to Abbott and St. Jude. He was an investigator on the ABSORB III trial.

[email protected]

On Twitter @mitchelzoler

The Food and Drug Administration approved the first fully absorbable vascular scaffold designed for use in coronary arteries, the Absorb GT1 bioresorbable vascular scaffold system, made by Abbott.

Concurrent with the FDA’s announcement on July 5, the company said that it plans to start immediate commercial rollout of the Absorb bioresorbable vascular scaffold (BVS). Initial availability will be limited to the roughly 100 most active sites that participated in the ABSORB III trial, the pivotal study that established noninferiority of the BVS, compared with a state-of-the-art metallic coronary stent during 1-year follow-up, according to a company spokesman.

However, the ABSORB III results, reported in October 2015, failed to document any superiority of the BVS, compared with a metallic stent. The potential advantages of a BVS remain for now unproven, and are based on the potential long-term advantages of using devices in percutaneous coronary interventions that slowly degrade away and thereby eliminate a residual metallic structure in a patient’s coronaries and the long-term threat they could pose for thrombosis or interference with subsequent coronary procedures.

“All the potential advantages are hypothetical at this point,” said Hiram G. Bezerra, MD, an investigator in the ABSORB III trial and director of the cardiac catheterization laboratory at University Hospitals Case Medical Center in Cleveland. However, “if you have a metallic stent it lasts a lifetime, creating a metallic cage” that could interfere with a possible later coronary procedure or be the site for thrombus formation. Disappearance of the BVS also creates the possibility for eventual restoration of more normal vasomotion in the coronary wall, said Dr. Bezerra, a self-professed “enthusiast” for the BVS alternative.

A major limiting factor for BVS use today is coronary diameter because the Absorb BVS is bulkier than metallic stents. The ABSORB III trial limited use of the BVS to coronary vessels with a reference-vessel diameter by visual assessment of at least 2.5 mm, with an upper limit of 3.75 mm. Other limiting factors can be coronary calcification and tortuosity, although Dr. Bezerra said that these obstacles are usually overcome with a more time-consuming procedure if the operator is committed to placing a BVS.

Another variable will be the cost of the BVS. According to the Abbott spokesman, the device “will be priced so that it will be broadly accessible to hospitals.” Also, the Absorb BVS will receive payer reimbursement comparable to a drug-eluting stent using existing reimbursement codes, the spokesman said. Abbott will require inexperienced operators to take a training course to learn proper placement technique.

Dr. Bezerra admitted that he is probably an outlier in his plan to quickly make the BVS a mainstay of his practice. “I think adoption will be slow in the beginning” for most U.S. operators, he predicted. One of his Cleveland colleagues who spoke about the near-term prospects BVS use last October when the ABSORB III results came out predicted that immediate use might occur in about 10%-15% of patients undergoing percutaneous coronary interventions, similar to the usage level in Europe where this BVS has been available for several years.

Dr. Bezerra has been a consultant to Abbott and St. Jude. He was an investigator on the ABSORB III trial.

[email protected]

On Twitter @mitchelzoler

The Food and Drug Administration approved the first fully absorbable vascular scaffold designed for use in coronary arteries, the Absorb GT1 bioresorbable vascular scaffold system, made by Abbott.

Concurrent with the FDA’s announcement on July 5, the company said that it plans to start immediate commercial rollout of the Absorb bioresorbable vascular scaffold (BVS). Initial availability will be limited to the roughly 100 most active sites that participated in the ABSORB III trial, the pivotal study that established noninferiority of the BVS, compared with a state-of-the-art metallic coronary stent during 1-year follow-up, according to a company spokesman.

However, the ABSORB III results, reported in October 2015, failed to document any superiority of the BVS, compared with a metallic stent. The potential advantages of a BVS remain for now unproven, and are based on the potential long-term advantages of using devices in percutaneous coronary interventions that slowly degrade away and thereby eliminate a residual metallic structure in a patient’s coronaries and the long-term threat they could pose for thrombosis or interference with subsequent coronary procedures.

“All the potential advantages are hypothetical at this point,” said Hiram G. Bezerra, MD, an investigator in the ABSORB III trial and director of the cardiac catheterization laboratory at University Hospitals Case Medical Center in Cleveland. However, “if you have a metallic stent it lasts a lifetime, creating a metallic cage” that could interfere with a possible later coronary procedure or be the site for thrombus formation. Disappearance of the BVS also creates the possibility for eventual restoration of more normal vasomotion in the coronary wall, said Dr. Bezerra, a self-professed “enthusiast” for the BVS alternative.

A major limiting factor for BVS use today is coronary diameter because the Absorb BVS is bulkier than metallic stents. The ABSORB III trial limited use of the BVS to coronary vessels with a reference-vessel diameter by visual assessment of at least 2.5 mm, with an upper limit of 3.75 mm. Other limiting factors can be coronary calcification and tortuosity, although Dr. Bezerra said that these obstacles are usually overcome with a more time-consuming procedure if the operator is committed to placing a BVS.

Another variable will be the cost of the BVS. According to the Abbott spokesman, the device “will be priced so that it will be broadly accessible to hospitals.” Also, the Absorb BVS will receive payer reimbursement comparable to a drug-eluting stent using existing reimbursement codes, the spokesman said. Abbott will require inexperienced operators to take a training course to learn proper placement technique.

Dr. Bezerra admitted that he is probably an outlier in his plan to quickly make the BVS a mainstay of his practice. “I think adoption will be slow in the beginning” for most U.S. operators, he predicted. One of his Cleveland colleagues who spoke about the near-term prospects BVS use last October when the ABSORB III results came out predicted that immediate use might occur in about 10%-15% of patients undergoing percutaneous coronary interventions, similar to the usage level in Europe where this BVS has been available for several years.

Dr. Bezerra has been a consultant to Abbott and St. Jude. He was an investigator on the ABSORB III trial.

[email protected]

On Twitter @mitchelzoler