U.S. cardiologists are increasingly opting out of solo or small practices, and joining larger practices, according to a new analysis of U.S. data from 2013 and 2017.

In 2013, 34.2% of U.S. cardiologists worked in practices of five or fewer cardiologists. That number dropped to 27% by 2017. On the flip side, the proportion working in practices with 25 cardiologists or more rose from 26% in 2013 to 35.8% in 2017.

“This is a trend we’re seeing across health care – hospitals are merging and they’re acquiring physician practices, primary care doctors are joining larger practices, too – so to some extent it seems that cardiologists are just responding to changes in the market structure where they practice,” said Jose F. Figueroa, MD, MPH, of Harvard T.H. Chan School of Public Health and Brigham & Women’s Hospital, Boston.

Dr. Figueroa and colleagues published their findings as a research brief for the Aug. 4 issue of the Journal of the American College of Cardiology.

The average number of cardiologists in practice together rose from 3.6 in 2013 to 4.3 in 2017. This trend was less obvious in rural areas (2.05 to 2.20) than in urban areas (3.67 to 4.38).

The smallest change was seen in the mid-size practice tier. In 2013, 22.9% of cardiologists worked in a practice that included 11 to 24 cardiologists, and in 2017, the proportion was 23.2%.

To determine practices sizes, Dr. Figueroa and colleagues used publicly available data from 2013 and 2017 from the Centers for Medicare & Medicaid Services’ Physician Compare, a website that helps patients find and compare clinicians and groups enrolled in Medicare.

Market level variables were obtained from the Dartmouth Atlas Project, which uses CMS data to provide information and analysis about national, regional, and local health care markets, as well as hospitals and their affiliated physicians.

Market forces drive practice patterns

The investigators had no direct data from which to ascertain the reasons why cardiologists have tended to move from smaller to larger practices, but they did conduct a multivariable linear regression analysis to better understand possible market-level factors that may be influencing these trends.

What they found was that as hospital market concentration increased, practice sizes also increased. They found no association between any community-level and physician-level factors and changes in practice size.

So, for example, greater growth in the number of cardiologists in practice together was not associated with age or sex.

“It seems that cardiologists are responding to changes in the market structure where they practice, and in particular, to hospital market concentration. This is all in an effort basically to have more market power, which in part means better bargaining power when they’re negotiating with payers,” said Dr. Figueroa.

He also suggested that joining a large practice is almost a necessity these days given the administrative burdens imposed by value-based care initiatives and their attendant quality measure reporting.

“There are stringent requirements for electronic health records and a huge administrative burden related to requirements to ensure compliance and report on quality measures,” said Dr. Figueroa.

“And then there are also all of these new ‘alternative payment’ models to figure out, like accountable care organizations and bundled payments, so you can imagine that if you’re a solo practitioner, it would be really hard to manage all of these details yourself and still ensure you’re taking care of your patient.

“As a cardiologist you need to invest in a bunch of resources, including a workforce to help you manage all the quality measures and keeping track of patients, ensuring they all get their blood pressures checked on time, etc.,” he said.

Anecdotally, Dr. Figueroa suggests it’s also a quality-of-life decision for many cardiologists. “In terms of physician burnout, when you’re a solo practitioner or in a small practice, it’s really hard to go on vacation and find coverage.”

Larry Sobal, MBA, MHA, the CEO of the Heart and Vascular Institute of Wisconsin, agrees that this consolidation is in large part a reflection of the trend toward consolidation seen across the healthcare system.

“This is because hospitals that purchase cardiology practices often pursue a tactic of consolidating previously separate independent groups into one practice – either legally or virtually – for purposes of controlling cardiology market share,” he said in an interview.

But it also suits the younger cardiology workforce. “My experience has been that cardiologists graduating from fellowships increasingly want to subspecialize and are less likely to join smaller practices where they cannot focus on the area of their training. Positions that allow this type of subspecialization can most easily be found in larger practices.” said Mr. Sobal, cochair of the American College of Cardiology Management Publications Committee. 

And if professional incentives aren’t enough, there is always money. While the study did not look at physician compensation by practice size, Mr. Sobal suspects physicians in larger practices have higher incomes.

Dr. Figueroa has disclosed no relevant financial relationships. Mr. Sobal is the CEO of a midsized cardiology practice (13 cardiologists).
 

A version of this article originally appeared on Medscape.com.

U.S. cardiologists are increasingly opting out of solo or small practices, and joining larger practices, according to a new analysis of U.S. data from 2013 and 2017.

In 2013, 34.2% of U.S. cardiologists worked in practices of five or fewer cardiologists. That number dropped to 27% by 2017. On the flip side, the proportion working in practices with 25 cardiologists or more rose from 26% in 2013 to 35.8% in 2017.

“This is a trend we’re seeing across health care – hospitals are merging and they’re acquiring physician practices, primary care doctors are joining larger practices, too – so to some extent it seems that cardiologists are just responding to changes in the market structure where they practice,” said Jose F. Figueroa, MD, MPH, of Harvard T.H. Chan School of Public Health and Brigham & Women’s Hospital, Boston.

Dr. Figueroa and colleagues published their findings as a research brief for the Aug. 4 issue of the Journal of the American College of Cardiology.

The average number of cardiologists in practice together rose from 3.6 in 2013 to 4.3 in 2017. This trend was less obvious in rural areas (2.05 to 2.20) than in urban areas (3.67 to 4.38).

The smallest change was seen in the mid-size practice tier. In 2013, 22.9% of cardiologists worked in a practice that included 11 to 24 cardiologists, and in 2017, the proportion was 23.2%.

To determine practices sizes, Dr. Figueroa and colleagues used publicly available data from 2013 and 2017 from the Centers for Medicare & Medicaid Services’ Physician Compare, a website that helps patients find and compare clinicians and groups enrolled in Medicare.

Market level variables were obtained from the Dartmouth Atlas Project, which uses CMS data to provide information and analysis about national, regional, and local health care markets, as well as hospitals and their affiliated physicians.

Market forces drive practice patterns

The investigators had no direct data from which to ascertain the reasons why cardiologists have tended to move from smaller to larger practices, but they did conduct a multivariable linear regression analysis to better understand possible market-level factors that may be influencing these trends.

What they found was that as hospital market concentration increased, practice sizes also increased. They found no association between any community-level and physician-level factors and changes in practice size.

So, for example, greater growth in the number of cardiologists in practice together was not associated with age or sex.

“It seems that cardiologists are responding to changes in the market structure where they practice, and in particular, to hospital market concentration. This is all in an effort basically to have more market power, which in part means better bargaining power when they’re negotiating with payers,” said Dr. Figueroa.

He also suggested that joining a large practice is almost a necessity these days given the administrative burdens imposed by value-based care initiatives and their attendant quality measure reporting.

“There are stringent requirements for electronic health records and a huge administrative burden related to requirements to ensure compliance and report on quality measures,” said Dr. Figueroa.

“And then there are also all of these new ‘alternative payment’ models to figure out, like accountable care organizations and bundled payments, so you can imagine that if you’re a solo practitioner, it would be really hard to manage all of these details yourself and still ensure you’re taking care of your patient.

“As a cardiologist you need to invest in a bunch of resources, including a workforce to help you manage all the quality measures and keeping track of patients, ensuring they all get their blood pressures checked on time, etc.,” he said.

Anecdotally, Dr. Figueroa suggests it’s also a quality-of-life decision for many cardiologists. “In terms of physician burnout, when you’re a solo practitioner or in a small practice, it’s really hard to go on vacation and find coverage.”

Larry Sobal, MBA, MHA, the CEO of the Heart and Vascular Institute of Wisconsin, agrees that this consolidation is in large part a reflection of the trend toward consolidation seen across the healthcare system.

“This is because hospitals that purchase cardiology practices often pursue a tactic of consolidating previously separate independent groups into one practice – either legally or virtually – for purposes of controlling cardiology market share,” he said in an interview.

But it also suits the younger cardiology workforce. “My experience has been that cardiologists graduating from fellowships increasingly want to subspecialize and are less likely to join smaller practices where they cannot focus on the area of their training. Positions that allow this type of subspecialization can most easily be found in larger practices.” said Mr. Sobal, cochair of the American College of Cardiology Management Publications Committee. 

And if professional incentives aren’t enough, there is always money. While the study did not look at physician compensation by practice size, Mr. Sobal suspects physicians in larger practices have higher incomes.

Dr. Figueroa has disclosed no relevant financial relationships. Mr. Sobal is the CEO of a midsized cardiology practice (13 cardiologists).
 

A version of this article originally appeared on Medscape.com.

U.S. cardiologists are increasingly opting out of solo or small practices, and joining larger practices, according to a new analysis of U.S. data from 2013 and 2017.

In 2013, 34.2% of U.S. cardiologists worked in practices of five or fewer cardiologists. That number dropped to 27% by 2017. On the flip side, the proportion working in practices with 25 cardiologists or more rose from 26% in 2013 to 35.8% in 2017.

“This is a trend we’re seeing across health care – hospitals are merging and they’re acquiring physician practices, primary care doctors are joining larger practices, too – so to some extent it seems that cardiologists are just responding to changes in the market structure where they practice,” said Jose F. Figueroa, MD, MPH, of Harvard T.H. Chan School of Public Health and Brigham & Women’s Hospital, Boston.

Dr. Figueroa and colleagues published their findings as a research brief for the Aug. 4 issue of the Journal of the American College of Cardiology.

The average number of cardiologists in practice together rose from 3.6 in 2013 to 4.3 in 2017. This trend was less obvious in rural areas (2.05 to 2.20) than in urban areas (3.67 to 4.38).

The smallest change was seen in the mid-size practice tier. In 2013, 22.9% of cardiologists worked in a practice that included 11 to 24 cardiologists, and in 2017, the proportion was 23.2%.

To determine practices sizes, Dr. Figueroa and colleagues used publicly available data from 2013 and 2017 from the Centers for Medicare & Medicaid Services’ Physician Compare, a website that helps patients find and compare clinicians and groups enrolled in Medicare.

Market level variables were obtained from the Dartmouth Atlas Project, which uses CMS data to provide information and analysis about national, regional, and local health care markets, as well as hospitals and their affiliated physicians.

Market forces drive practice patterns

The investigators had no direct data from which to ascertain the reasons why cardiologists have tended to move from smaller to larger practices, but they did conduct a multivariable linear regression analysis to better understand possible market-level factors that may be influencing these trends.

What they found was that as hospital market concentration increased, practice sizes also increased. They found no association between any community-level and physician-level factors and changes in practice size.

So, for example, greater growth in the number of cardiologists in practice together was not associated with age or sex.

“It seems that cardiologists are responding to changes in the market structure where they practice, and in particular, to hospital market concentration. This is all in an effort basically to have more market power, which in part means better bargaining power when they’re negotiating with payers,” said Dr. Figueroa.

He also suggested that joining a large practice is almost a necessity these days given the administrative burdens imposed by value-based care initiatives and their attendant quality measure reporting.

“There are stringent requirements for electronic health records and a huge administrative burden related to requirements to ensure compliance and report on quality measures,” said Dr. Figueroa.

“And then there are also all of these new ‘alternative payment’ models to figure out, like accountable care organizations and bundled payments, so you can imagine that if you’re a solo practitioner, it would be really hard to manage all of these details yourself and still ensure you’re taking care of your patient.

“As a cardiologist you need to invest in a bunch of resources, including a workforce to help you manage all the quality measures and keeping track of patients, ensuring they all get their blood pressures checked on time, etc.,” he said.

Anecdotally, Dr. Figueroa suggests it’s also a quality-of-life decision for many cardiologists. “In terms of physician burnout, when you’re a solo practitioner or in a small practice, it’s really hard to go on vacation and find coverage.”

Larry Sobal, MBA, MHA, the CEO of the Heart and Vascular Institute of Wisconsin, agrees that this consolidation is in large part a reflection of the trend toward consolidation seen across the healthcare system.

“This is because hospitals that purchase cardiology practices often pursue a tactic of consolidating previously separate independent groups into one practice – either legally or virtually – for purposes of controlling cardiology market share,” he said in an interview.

But it also suits the younger cardiology workforce. “My experience has been that cardiologists graduating from fellowships increasingly want to subspecialize and are less likely to join smaller practices where they cannot focus on the area of their training. Positions that allow this type of subspecialization can most easily be found in larger practices.” said Mr. Sobal, cochair of the American College of Cardiology Management Publications Committee. 

And if professional incentives aren’t enough, there is always money. While the study did not look at physician compensation by practice size, Mr. Sobal suspects physicians in larger practices have higher incomes.

Dr. Figueroa has disclosed no relevant financial relationships. Mr. Sobal is the CEO of a midsized cardiology practice (13 cardiologists).
 

A version of this article originally appeared on Medscape.com.

The COVID-19 pandemic has left an indelible mark on the healthcare community, impacting the physical and mental health of healthcare providers, patients, and caregivers alike. For patients managing chronic diseases, their experience with the healthcare system has changed. Whether patients are wary of seeking help because they don’t want to expose themselves to the virus or are uncertain how to engage in telehealth visits with their physician, many patients are struggling with disease management.

Before the pandemic, patients with epilepsy already often experienced physical and psycho-social challenges, which negatively impacted their quality of life.¹ For the 65 million people living with epilepsy worldwide,² failure to effectively manage their condition can have long-lasting and life threatening consequences.^{1, 3, 4} The pandemic has understandably caused anxiety levels to increase, but for patients with epilepsy, the potentially serious impact of having a seizure, coupled with patients’ existing challenges, can make this time even more stressful.

James Wheless, MD, Professor and Chief of Pediatric Neurology at the University of Tennessee Health Science Center and Director of the Comprehensive Epilepsy Program and Neuroscience Institute at Le Bonheur Children’s Hospital, explained that the importance of caring for the emotional health of epilepsy patients cannot be underestimated. “If patients with epilepsy are stressed or anxious, it can impact their sleep, which can then trigger a seizure. Creating a plan to help manage and treat the stress and anxiety that may be intensified amid the pandemic can assist in potentially lessening the uptick of seizures and emergency department use.”

People living with epilepsy, their caregivers and their families, should have a seizure action plan that includes being able to recognize a seizure or a potential seizure emergency, knowing exactly how to act and, if applicable, when to use a prescribed rescue medication, and when to seek emergency care.⁵ A healthcare provider can work with patients and caregivers to help create individualized plans that fit their needs, which will help to ease some of the stress and anxiety often experienced by people living with epilepsy.

UCB’s Focus on the Epilepsy Community During COVID-19

The growing impact of the pandemic on emotional health has made strong and consistent support for patients with epilepsy a necessity. UCB is fully committed to helping all of its patient communities, including people living with epilepsy, navigate this uncharted territory and provide the valuable resources patients need, including access to proper care and treatment.

“We are committed to providing solutions for people living with epilepsy, especially during these challenging times,” said Mike Davis, Head of U.S. Neurology at UCB. “UCB takes great pride in our development of both chronic and acute treatment solutions for people living with epilepsy with the goal of helping them achieve better seizure control and hopefully decrease emergency department visits at such a critical time.”

Access to Medication Remains Top Priority

To date, there has been no shortage of any of UCB's epilepsy medicines, and the company continues to monitor its supply chain to mitigate any possible disruption. In fact, by using the SCORE digital system, UCB’s manufacturing and supply operations data management tool, UCB is able to track the actual quantity of medicines available to serve patients and anticipate any potential transportation delays when shipping its medicines. During the pandemic, SCORE has provided accurate and near real-time information so that UCB has visibility into its continuity of supply for patients across the globe.

“For people living with epilepsy who are experiencing seizures or seizure emergencies, we remain committed to helping patients gain access to UCB medicines,” said Mike Davis. “UCB has also enhanced its affordability solutions for our medications during the pandemic to further support people living with epilepsy.”

Patient Support Programs Provide Valuable Information, Inspiration, and Care                        

Providing patients with ample support and resources takes on an even greater urgency now. UCB has also expanded and extended a number of programs to help the epilepsy community during this unprecedented time. These include:

• Patient Assistance Program (PAP) — UCB has expanded its PAP to help eligible patients who have been impacted by COVID-19 by expediting enrollment to help ensure uninterrupted access to their medicines at no cost. This change will help patients who have previously had difficulty affording UCB medicines due to job loss, job furlough, or loss of insurance coverage.
• ucbCARES^® — UCB’s assistance program is ready to help anyone impacted by COVID-19 find answers to their questions and ensure they receive the respect and care they deserve. Contact ucbCARES at +1-844-599-CARE (2273), via email at UCBCares@ucb.com or visit: https://ucb-usa.com/Patients/Patients
• Epilepsy Advocate™ — UCB supports the Epilepsy Advocate program, enabling a community for people living with epilepsy, their family members, and their caregivers, to share inspirational personal success stories and best practices for topics like telemedicine and other helpful epilepsy resources.

UCB’s commitment to patients is stronger than ever. Through its scientific advances, strategic acquisitions, advocacy partnerships, and other patient-focused programs and resources, UCB is harnessing its strengths to deliver on the company’s promise of meeting and exceeding patient needs. To learn more and access UCB resources, please visit: https://ucb-usa.com/Responsibility/coronavirus-updates.

###

1. The Epilepsy Foundation of America. Challenges with Epilepsy. Accessed on 2nd July 2020 from https://www.epilepsy.com/learn/challenges-epilepsy
2. The Epilepsy Foundation of America . Who gets epilepsy? Accessed on 2nd July 2020 from http://www.epilepsy.com/learn/epilepsy-101/who-gets-epilepsy
3. The Epilepsy Foundation of America. Early Death and Epilepsy. Accessed on 9th July 2020 from https://www.epilepsy.com/learn/early-death-and-sudep
4. Buck D, et al. Patients' Experiences of Injury as a Result of Epilepsy. Epilepsia. 38(4):439-444, 1997.
5. The Epilepsy Foundation of America. Seizure First Aid and Safety. Accessed on 10th July 2020 from https://www.epilepsy.com/learn/seizure-first-aid-and-safety

ucbCARES^® is a registered trademark, and Epilepsy Advocate™ is a trademark, of the UCB Group of Companies.

©2020 UCB, Inc., Smyrna, GA 30080. All rights reserved.

US-P-DA-EPI-2000069

The COVID-19 pandemic has left an indelible mark on the healthcare community, impacting the physical and mental health of healthcare providers, patients, and caregivers alike. For patients managing chronic diseases, their experience with the healthcare system has changed. Whether patients are wary of seeking help because they don’t want to expose themselves to the virus or are uncertain how to engage in telehealth visits with their physician, many patients are struggling with disease management.

Before the pandemic, patients with epilepsy already often experienced physical and psycho-social challenges, which negatively impacted their quality of life.¹ For the 65 million people living with epilepsy worldwide,² failure to effectively manage their condition can have long-lasting and life threatening consequences.^{1, 3, 4} The pandemic has understandably caused anxiety levels to increase, but for patients with epilepsy, the potentially serious impact of having a seizure, coupled with patients’ existing challenges, can make this time even more stressful.

James Wheless, MD, Professor and Chief of Pediatric Neurology at the University of Tennessee Health Science Center and Director of the Comprehensive Epilepsy Program and Neuroscience Institute at Le Bonheur Children’s Hospital, explained that the importance of caring for the emotional health of epilepsy patients cannot be underestimated. “If patients with epilepsy are stressed or anxious, it can impact their sleep, which can then trigger a seizure. Creating a plan to help manage and treat the stress and anxiety that may be intensified amid the pandemic can assist in potentially lessening the uptick of seizures and emergency department use.”

People living with epilepsy, their caregivers and their families, should have a seizure action plan that includes being able to recognize a seizure or a potential seizure emergency, knowing exactly how to act and, if applicable, when to use a prescribed rescue medication, and when to seek emergency care.⁵ A healthcare provider can work with patients and caregivers to help create individualized plans that fit their needs, which will help to ease some of the stress and anxiety often experienced by people living with epilepsy.

UCB’s Focus on the Epilepsy Community During COVID-19

The growing impact of the pandemic on emotional health has made strong and consistent support for patients with epilepsy a necessity. UCB is fully committed to helping all of its patient communities, including people living with epilepsy, navigate this uncharted territory and provide the valuable resources patients need, including access to proper care and treatment.

“We are committed to providing solutions for people living with epilepsy, especially during these challenging times,” said Mike Davis, Head of U.S. Neurology at UCB. “UCB takes great pride in our development of both chronic and acute treatment solutions for people living with epilepsy with the goal of helping them achieve better seizure control and hopefully decrease emergency department visits at such a critical time.”

Access to Medication Remains Top Priority

To date, there has been no shortage of any of UCB's epilepsy medicines, and the company continues to monitor its supply chain to mitigate any possible disruption. In fact, by using the SCORE digital system, UCB’s manufacturing and supply operations data management tool, UCB is able to track the actual quantity of medicines available to serve patients and anticipate any potential transportation delays when shipping its medicines. During the pandemic, SCORE has provided accurate and near real-time information so that UCB has visibility into its continuity of supply for patients across the globe.

“For people living with epilepsy who are experiencing seizures or seizure emergencies, we remain committed to helping patients gain access to UCB medicines,” said Mike Davis. “UCB has also enhanced its affordability solutions for our medications during the pandemic to further support people living with epilepsy.”

Patient Support Programs Provide Valuable Information, Inspiration, and Care                        

Providing patients with ample support and resources takes on an even greater urgency now. UCB has also expanded and extended a number of programs to help the epilepsy community during this unprecedented time. These include:

• Patient Assistance Program (PAP) — UCB has expanded its PAP to help eligible patients who have been impacted by COVID-19 by expediting enrollment to help ensure uninterrupted access to their medicines at no cost. This change will help patients who have previously had difficulty affording UCB medicines due to job loss, job furlough, or loss of insurance coverage.
• ucbCARES^® — UCB’s assistance program is ready to help anyone impacted by COVID-19 find answers to their questions and ensure they receive the respect and care they deserve. Contact ucbCARES at +1-844-599-CARE (2273), via email at UCBCares@ucb.com or visit: https://ucb-usa.com/Patients/Patients
• Epilepsy Advocate™ — UCB supports the Epilepsy Advocate program, enabling a community for people living with epilepsy, their family members, and their caregivers, to share inspirational personal success stories and best practices for topics like telemedicine and other helpful epilepsy resources.

UCB’s commitment to patients is stronger than ever. Through its scientific advances, strategic acquisitions, advocacy partnerships, and other patient-focused programs and resources, UCB is harnessing its strengths to deliver on the company’s promise of meeting and exceeding patient needs. To learn more and access UCB resources, please visit: https://ucb-usa.com/Responsibility/coronavirus-updates.

###

1. The Epilepsy Foundation of America. Challenges with Epilepsy. Accessed on 2nd July 2020 from https://www.epilepsy.com/learn/challenges-epilepsy
2. The Epilepsy Foundation of America . Who gets epilepsy? Accessed on 2nd July 2020 from http://www.epilepsy.com/learn/epilepsy-101/who-gets-epilepsy
3. The Epilepsy Foundation of America. Early Death and Epilepsy. Accessed on 9th July 2020 from https://www.epilepsy.com/learn/early-death-and-sudep
4. Buck D, et al. Patients' Experiences of Injury as a Result of Epilepsy. Epilepsia. 38(4):439-444, 1997.
5. The Epilepsy Foundation of America. Seizure First Aid and Safety. Accessed on 10th July 2020 from https://www.epilepsy.com/learn/seizure-first-aid-and-safety

ucbCARES^® is a registered trademark, and Epilepsy Advocate™ is a trademark, of the UCB Group of Companies.

©2020 UCB, Inc., Smyrna, GA 30080. All rights reserved.

US-P-DA-EPI-2000069

The COVID-19 pandemic has left an indelible mark on the healthcare community, impacting the physical and mental health of healthcare providers, patients, and caregivers alike. For patients managing chronic diseases, their experience with the healthcare system has changed. Whether patients are wary of seeking help because they don’t want to expose themselves to the virus or are uncertain how to engage in telehealth visits with their physician, many patients are struggling with disease management.

Before the pandemic, patients with epilepsy already often experienced physical and psycho-social challenges, which negatively impacted their quality of life.¹ For the 65 million people living with epilepsy worldwide,² failure to effectively manage their condition can have long-lasting and life threatening consequences.^{1, 3, 4} The pandemic has understandably caused anxiety levels to increase, but for patients with epilepsy, the potentially serious impact of having a seizure, coupled with patients’ existing challenges, can make this time even more stressful.

James Wheless, MD, Professor and Chief of Pediatric Neurology at the University of Tennessee Health Science Center and Director of the Comprehensive Epilepsy Program and Neuroscience Institute at Le Bonheur Children’s Hospital, explained that the importance of caring for the emotional health of epilepsy patients cannot be underestimated. “If patients with epilepsy are stressed or anxious, it can impact their sleep, which can then trigger a seizure. Creating a plan to help manage and treat the stress and anxiety that may be intensified amid the pandemic can assist in potentially lessening the uptick of seizures and emergency department use.”

People living with epilepsy, their caregivers and their families, should have a seizure action plan that includes being able to recognize a seizure or a potential seizure emergency, knowing exactly how to act and, if applicable, when to use a prescribed rescue medication, and when to seek emergency care.⁵ A healthcare provider can work with patients and caregivers to help create individualized plans that fit their needs, which will help to ease some of the stress and anxiety often experienced by people living with epilepsy.

UCB’s Focus on the Epilepsy Community During COVID-19

The growing impact of the pandemic on emotional health has made strong and consistent support for patients with epilepsy a necessity. UCB is fully committed to helping all of its patient communities, including people living with epilepsy, navigate this uncharted territory and provide the valuable resources patients need, including access to proper care and treatment.

“We are committed to providing solutions for people living with epilepsy, especially during these challenging times,” said Mike Davis, Head of U.S. Neurology at UCB. “UCB takes great pride in our development of both chronic and acute treatment solutions for people living with epilepsy with the goal of helping them achieve better seizure control and hopefully decrease emergency department visits at such a critical time.”

Access to Medication Remains Top Priority

To date, there has been no shortage of any of UCB's epilepsy medicines, and the company continues to monitor its supply chain to mitigate any possible disruption. In fact, by using the SCORE digital system, UCB’s manufacturing and supply operations data management tool, UCB is able to track the actual quantity of medicines available to serve patients and anticipate any potential transportation delays when shipping its medicines. During the pandemic, SCORE has provided accurate and near real-time information so that UCB has visibility into its continuity of supply for patients across the globe.

“For people living with epilepsy who are experiencing seizures or seizure emergencies, we remain committed to helping patients gain access to UCB medicines,” said Mike Davis. “UCB has also enhanced its affordability solutions for our medications during the pandemic to further support people living with epilepsy.”

Patient Support Programs Provide Valuable Information, Inspiration, and Care                        

Providing patients with ample support and resources takes on an even greater urgency now. UCB has also expanded and extended a number of programs to help the epilepsy community during this unprecedented time. These include:

• Patient Assistance Program (PAP) — UCB has expanded its PAP to help eligible patients who have been impacted by COVID-19 by expediting enrollment to help ensure uninterrupted access to their medicines at no cost. This change will help patients who have previously had difficulty affording UCB medicines due to job loss, job furlough, or loss of insurance coverage.
• ucbCARES^® — UCB’s assistance program is ready to help anyone impacted by COVID-19 find answers to their questions and ensure they receive the respect and care they deserve. Contact ucbCARES at +1-844-599-CARE (2273), via email at UCBCares@ucb.com or visit: https://ucb-usa.com/Patients/Patients
• Epilepsy Advocate™ — UCB supports the Epilepsy Advocate program, enabling a community for people living with epilepsy, their family members, and their caregivers, to share inspirational personal success stories and best practices for topics like telemedicine and other helpful epilepsy resources.

UCB’s commitment to patients is stronger than ever. Through its scientific advances, strategic acquisitions, advocacy partnerships, and other patient-focused programs and resources, UCB is harnessing its strengths to deliver on the company’s promise of meeting and exceeding patient needs. To learn more and access UCB resources, please visit: https://ucb-usa.com/Responsibility/coronavirus-updates.

###

1. The Epilepsy Foundation of America. Challenges with Epilepsy. Accessed on 2nd July 2020 from https://www.epilepsy.com/learn/challenges-epilepsy
2. The Epilepsy Foundation of America . Who gets epilepsy? Accessed on 2nd July 2020 from http://www.epilepsy.com/learn/epilepsy-101/who-gets-epilepsy
3. The Epilepsy Foundation of America. Early Death and Epilepsy. Accessed on 9th July 2020 from https://www.epilepsy.com/learn/early-death-and-sudep
4. Buck D, et al. Patients' Experiences of Injury as a Result of Epilepsy. Epilepsia. 38(4):439-444, 1997.
5. The Epilepsy Foundation of America. Seizure First Aid and Safety. Accessed on 10th July 2020 from https://www.epilepsy.com/learn/seizure-first-aid-and-safety

ucbCARES^® is a registered trademark, and Epilepsy Advocate™ is a trademark, of the UCB Group of Companies.

©2020 UCB, Inc., Smyrna, GA 30080. All rights reserved.

US-P-DA-EPI-2000069

Vaccinations against influenza and pneumonia may help protect against Alzheimer’s disease,  two large observational studies suggest.

In a cohort study of more than 9,000 older adults, receiving a single influenza vaccination was associated with a 17% lower prevalence of Alzheimer’s disease compared with not receiving the vaccine. In addition, for those who were vaccinated more than once over the years, there was an additional 13% reduction in Alzheimer’s disease incidence.

In another study, which included more than 5,000 older participants, being vaccinated against pneumonia between the ages of 65 and 75 reduced the risk of developing Alzheimer’s disease by 30%.

The subject of vaccines “is obviously very topical with the COVID-19 pandemic,” said Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association. “While these are very preliminary data, these studies do suggest that with vaccination against both respiratory illnesses, there is the potential to lower risk for developing cognitive decline and dementia,” said Dr. Edelmayer, who was not involved in the research.

The findings of both studies were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.

Lower Alzheimer’s disease prevalence

The influenza vaccine study was presented by Albert Amran, a fourth-year medical student at McGovern Medical School at the University of Texas Health Science Center at Houston. The researchers used electronic health record data to create a propensity-matched cohort of 9,066 vaccinated and unvaccinated adults ages 60 and older.

Influenza vaccination, increased frequency of administration, and younger age at time of vaccination were all associated with reduced incidence of Alzheimer’s disease, Mr. Amran reported.

Being vaccinated for influenza was significantly linked to a lower prevalence of Alzheimer’s disease (odds ratio [OR], 0.83; P < .0001) in comparison with not being vaccinated. Receiving more than one vaccination over the years was associated with an additional reduction in AD incidence (OR, 0.87; P = .0342). The protection appeared to be strongest for those who received their first vaccination at a younger age, for example, at age 60 versus 70.

Mr. Amran and research colleagues have two theories as to why influenza vaccination may protect the brain.

One is that vaccination may aid the immune system as people age. “As people get older, their immune systems become less able to control infection. We’ve seen this with the ongoing pandemic, with older people at much higher risk for dying. Giving people the vaccine once a year may help keep the immune system in shape,” Mr. Amran said.

Another theory is that the prevention of influenza itself may be relevant. “Flu infections can be extremely deadly in older patients. Maybe the results of our study will give another reason for people to get vaccinated,” Mr. Amran said.

Pneumonia vaccine

The other study was presented by Svetlana Ukraintseva, PhD, of Duke University, Durham, N.C.

Dr. Ukraintseva and colleagues investigated associations between pneumococcal vaccine, with and without an accompanying influenza vaccine, and the risk for Alzheimer’s disease among 5,146 participants in the Cardiovascular Health Study. Covariates included sex, race, birth cohort, education, smoking, and a known genetic risk factor for Alzheimer’s disease: the rs2075650 G allele in the TOMM40 gene.

In a logistic model with all covariates, vaccination against pneumonia between ages 65 and 75 was significantly associated with reduced risk of developing AD (OR, 0.70; P < .04). The largest reduction in Alzheimer’s disease risk (OR, 0.62; P < .04) was among those vaccinated against pneumonia who were noncarriers of the rs2075650 G allele.

Total number of vaccinations against pneumonia and influenza between ages 65 and 75 was also associated with a lower risk for Alzheimer’s disease (OR, 0.88; P < .01). However, the effect was not evident for the influenza vaccination alone.

“The fact that very different pathogens – viral, bacterial, fungal – have been linked to Alzheimer’s disease indicates a possibility that compromised host immunity may play a role in Alzheimer’s disease through increasing overall brain’s vulnerability to various microbes,” said Dr. Ukraintseva.

The current findings support further investigation of pneumococcal vaccine as a “reasonable candidate for repurposing in personalized AD prevention,” she noted. “These results also support the important role of boosting overall immune robustness/resilience in preventing Alzheimer’s disease,” Dr. Ukraintseva added.

Her group is currently working on confirming the findings in another population.

Brain protective?

“Neither study can prove that the benefit is directly related to the vaccine itself, but what they can indicate is that potentially, vaccines are a way to protect your health and brain,” Dr. Edelmayer said.

In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, noted that more research is needed.

The new data call “for further studies in large, diverse clinical trials to inform whether vaccinations as a public health strategy decrease our risk for developing dementia as we age,” Dr. Carillo said.

Funding for the influenza vaccine study was provided by the Christopher Sarofim Family Professorship in Biomedical Informatics and Bioengineering, a UT STARs Award, the Cancer Prevention and Research Institute of Texas, and the National Institutes of Health. Funding for the pneumonia study was provided by the National Institute on Aging. Dr. Amran, Dr. Ukraintseva, Dr. Edelmayer, and Dr. Carrillo have reported no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

Vaccinations against influenza and pneumonia may help protect against Alzheimer’s disease,  two large observational studies suggest.

In a cohort study of more than 9,000 older adults, receiving a single influenza vaccination was associated with a 17% lower prevalence of Alzheimer’s disease compared with not receiving the vaccine. In addition, for those who were vaccinated more than once over the years, there was an additional 13% reduction in Alzheimer’s disease incidence.

In another study, which included more than 5,000 older participants, being vaccinated against pneumonia between the ages of 65 and 75 reduced the risk of developing Alzheimer’s disease by 30%.

The subject of vaccines “is obviously very topical with the COVID-19 pandemic,” said Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association. “While these are very preliminary data, these studies do suggest that with vaccination against both respiratory illnesses, there is the potential to lower risk for developing cognitive decline and dementia,” said Dr. Edelmayer, who was not involved in the research.

The findings of both studies were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.

Lower Alzheimer’s disease prevalence

The influenza vaccine study was presented by Albert Amran, a fourth-year medical student at McGovern Medical School at the University of Texas Health Science Center at Houston. The researchers used electronic health record data to create a propensity-matched cohort of 9,066 vaccinated and unvaccinated adults ages 60 and older.

Influenza vaccination, increased frequency of administration, and younger age at time of vaccination were all associated with reduced incidence of Alzheimer’s disease, Mr. Amran reported.

Being vaccinated for influenza was significantly linked to a lower prevalence of Alzheimer’s disease (odds ratio [OR], 0.83; P < .0001) in comparison with not being vaccinated. Receiving more than one vaccination over the years was associated with an additional reduction in AD incidence (OR, 0.87; P = .0342). The protection appeared to be strongest for those who received their first vaccination at a younger age, for example, at age 60 versus 70.

Mr. Amran and research colleagues have two theories as to why influenza vaccination may protect the brain.

One is that vaccination may aid the immune system as people age. “As people get older, their immune systems become less able to control infection. We’ve seen this with the ongoing pandemic, with older people at much higher risk for dying. Giving people the vaccine once a year may help keep the immune system in shape,” Mr. Amran said.

Another theory is that the prevention of influenza itself may be relevant. “Flu infections can be extremely deadly in older patients. Maybe the results of our study will give another reason for people to get vaccinated,” Mr. Amran said.

Pneumonia vaccine

The other study was presented by Svetlana Ukraintseva, PhD, of Duke University, Durham, N.C.

Dr. Ukraintseva and colleagues investigated associations between pneumococcal vaccine, with and without an accompanying influenza vaccine, and the risk for Alzheimer’s disease among 5,146 participants in the Cardiovascular Health Study. Covariates included sex, race, birth cohort, education, smoking, and a known genetic risk factor for Alzheimer’s disease: the rs2075650 G allele in the TOMM40 gene.

In a logistic model with all covariates, vaccination against pneumonia between ages 65 and 75 was significantly associated with reduced risk of developing AD (OR, 0.70; P < .04). The largest reduction in Alzheimer’s disease risk (OR, 0.62; P < .04) was among those vaccinated against pneumonia who were noncarriers of the rs2075650 G allele.

Total number of vaccinations against pneumonia and influenza between ages 65 and 75 was also associated with a lower risk for Alzheimer’s disease (OR, 0.88; P < .01). However, the effect was not evident for the influenza vaccination alone.

“The fact that very different pathogens – viral, bacterial, fungal – have been linked to Alzheimer’s disease indicates a possibility that compromised host immunity may play a role in Alzheimer’s disease through increasing overall brain’s vulnerability to various microbes,” said Dr. Ukraintseva.

The current findings support further investigation of pneumococcal vaccine as a “reasonable candidate for repurposing in personalized AD prevention,” she noted. “These results also support the important role of boosting overall immune robustness/resilience in preventing Alzheimer’s disease,” Dr. Ukraintseva added.

Her group is currently working on confirming the findings in another population.

Brain protective?

“Neither study can prove that the benefit is directly related to the vaccine itself, but what they can indicate is that potentially, vaccines are a way to protect your health and brain,” Dr. Edelmayer said.

In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, noted that more research is needed.

The new data call “for further studies in large, diverse clinical trials to inform whether vaccinations as a public health strategy decrease our risk for developing dementia as we age,” Dr. Carillo said.

Funding for the influenza vaccine study was provided by the Christopher Sarofim Family Professorship in Biomedical Informatics and Bioengineering, a UT STARs Award, the Cancer Prevention and Research Institute of Texas, and the National Institutes of Health. Funding for the pneumonia study was provided by the National Institute on Aging. Dr. Amran, Dr. Ukraintseva, Dr. Edelmayer, and Dr. Carrillo have reported no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

Vaccinations against influenza and pneumonia may help protect against Alzheimer’s disease,  two large observational studies suggest.

In a cohort study of more than 9,000 older adults, receiving a single influenza vaccination was associated with a 17% lower prevalence of Alzheimer’s disease compared with not receiving the vaccine. In addition, for those who were vaccinated more than once over the years, there was an additional 13% reduction in Alzheimer’s disease incidence.

In another study, which included more than 5,000 older participants, being vaccinated against pneumonia between the ages of 65 and 75 reduced the risk of developing Alzheimer’s disease by 30%.

The subject of vaccines “is obviously very topical with the COVID-19 pandemic,” said Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association. “While these are very preliminary data, these studies do suggest that with vaccination against both respiratory illnesses, there is the potential to lower risk for developing cognitive decline and dementia,” said Dr. Edelmayer, who was not involved in the research.

The findings of both studies were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.

Lower Alzheimer’s disease prevalence

The influenza vaccine study was presented by Albert Amran, a fourth-year medical student at McGovern Medical School at the University of Texas Health Science Center at Houston. The researchers used electronic health record data to create a propensity-matched cohort of 9,066 vaccinated and unvaccinated adults ages 60 and older.

Influenza vaccination, increased frequency of administration, and younger age at time of vaccination were all associated with reduced incidence of Alzheimer’s disease, Mr. Amran reported.

Being vaccinated for influenza was significantly linked to a lower prevalence of Alzheimer’s disease (odds ratio [OR], 0.83; P < .0001) in comparison with not being vaccinated. Receiving more than one vaccination over the years was associated with an additional reduction in AD incidence (OR, 0.87; P = .0342). The protection appeared to be strongest for those who received their first vaccination at a younger age, for example, at age 60 versus 70.

Mr. Amran and research colleagues have two theories as to why influenza vaccination may protect the brain.

One is that vaccination may aid the immune system as people age. “As people get older, their immune systems become less able to control infection. We’ve seen this with the ongoing pandemic, with older people at much higher risk for dying. Giving people the vaccine once a year may help keep the immune system in shape,” Mr. Amran said.

Another theory is that the prevention of influenza itself may be relevant. “Flu infections can be extremely deadly in older patients. Maybe the results of our study will give another reason for people to get vaccinated,” Mr. Amran said.

Pneumonia vaccine

The other study was presented by Svetlana Ukraintseva, PhD, of Duke University, Durham, N.C.

Dr. Ukraintseva and colleagues investigated associations between pneumococcal vaccine, with and without an accompanying influenza vaccine, and the risk for Alzheimer’s disease among 5,146 participants in the Cardiovascular Health Study. Covariates included sex, race, birth cohort, education, smoking, and a known genetic risk factor for Alzheimer’s disease: the rs2075650 G allele in the TOMM40 gene.

In a logistic model with all covariates, vaccination against pneumonia between ages 65 and 75 was significantly associated with reduced risk of developing AD (OR, 0.70; P < .04). The largest reduction in Alzheimer’s disease risk (OR, 0.62; P < .04) was among those vaccinated against pneumonia who were noncarriers of the rs2075650 G allele.

Total number of vaccinations against pneumonia and influenza between ages 65 and 75 was also associated with a lower risk for Alzheimer’s disease (OR, 0.88; P < .01). However, the effect was not evident for the influenza vaccination alone.

“The fact that very different pathogens – viral, bacterial, fungal – have been linked to Alzheimer’s disease indicates a possibility that compromised host immunity may play a role in Alzheimer’s disease through increasing overall brain’s vulnerability to various microbes,” said Dr. Ukraintseva.

The current findings support further investigation of pneumococcal vaccine as a “reasonable candidate for repurposing in personalized AD prevention,” she noted. “These results also support the important role of boosting overall immune robustness/resilience in preventing Alzheimer’s disease,” Dr. Ukraintseva added.

Her group is currently working on confirming the findings in another population.

Brain protective?

“Neither study can prove that the benefit is directly related to the vaccine itself, but what they can indicate is that potentially, vaccines are a way to protect your health and brain,” Dr. Edelmayer said.

In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, noted that more research is needed.

The new data call “for further studies in large, diverse clinical trials to inform whether vaccinations as a public health strategy decrease our risk for developing dementia as we age,” Dr. Carillo said.

Funding for the influenza vaccine study was provided by the Christopher Sarofim Family Professorship in Biomedical Informatics and Bioengineering, a UT STARs Award, the Cancer Prevention and Research Institute of Texas, and the National Institutes of Health. Funding for the pneumonia study was provided by the National Institute on Aging. Dr. Amran, Dr. Ukraintseva, Dr. Edelmayer, and Dr. Carrillo have reported no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors used for the treatment of type 2 diabetes, and for heart failure, are associated with a nearly threefold increased risk for diabetic ketoacidosis (DKA), according to a new large database analysis.

Boarding1Now/Thinkstock

The findings, which include data on the use of three different SGLT2 inhibitors in Canada and the United Kingdom and suggest a class effect, were published online July 27 in Annals of Internal Medicine by Antonios Douros, MD, PhD, of McGill University and the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, and colleagues.

“Our results provide robust evidence that SGLT2 inhibitors are associated with an increased risk for DKA. Of note, increased risks were observed in all molecule-specific analyses, with canagliflozin [Invokana, Janssen] showing the highest effect estimate,” they noted.

And because the beneficial effects of SGLT2 inhibitors in the prevention of cardiovascular and renal disease will probably increase their uptake in the coming years, “Physicians should be aware of DKA as a potential adverse effect,” Dr. Douros and colleagues wrote.
 

Analysis “generally confirms what has already been published”

Asked for comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, said that the study “generally confirms what has already been published” on the topic. He noted that overall “the risk of SGLT2 inhibitor–induced ketoacidosis is quite low in type 2 diabetes, perhaps on the order of 1 episode per 1000 patient-years.”

However, Dr. Taylor cautioned: “Published evidence suggests that the risk of DKA is increased if patients are unable to eat,” such as when hospitalized patients are not permitted to eat.

“In that setting, it is probably prudent to discontinue an SGLT2 inhibitor. Also, it may be prudent not to prescribe SGLT2 inhibitors to patients with a history of DKA,” he added.

Dr. Taylor also advised: “Although not necessarily supported by this publication, I think that caution should be exercised in prescribing SGLT2 inhibitors to insulin-dependent type 2 diabetes patients. ... Some late-stage type 2 diabetes patients may have severe insulin deficiency, and their physiology may resemble that of a type 1 diabetes patient.”

Dr. Taylor has previously advised against using SGLT2 inhibitors altogether in patients with type 1 diabetes.
 

Increased DKA risk seen across all SGLT2 inhibitors

The study involved electronic health care databases from seven Canadian provinces and the United Kingdom, from which 208,757 new users of SGLT2 inhibitors were propensity-matched 1:1 to new dipeptidyl peptidase-4 (DPP-4) inhibitor users.

Of those taking an SGLT2 inhibitor, 42.3% took canagliflozin, 30.7% dapagliflozin (Farxiga/Forxiga, AstraZeneca), and 27.0% empagliflozin (Jardiance, Boehringer Ingelheim).

Over a mean 0.9-year follow-up, 521 patients were hospitalized with DKA, for an overall incidence rate of 1.41 per 1,000 person-years.

The rate with SGLT2 inhibitors, 2.03 per 1,000 person-years, was nearly three times that seen with DPP-4 inhibitors, at 0.75 per 1,000 person-years, a significant difference (hazard ratio, 2.85).

By individual SGLT2 inhibitor, the hazard ratios compared with DPP-4 inhibitors were 1.86 for dapagliflozin, 2.52 for empagliflozin, and 3.58 for canagliflozin, all statistically significant. Stratification by age, sex, and incident versus prevalent user did not change the association between SGLT2 inhibitors and DKA.

Asked about the higher rate for canagliflozin, Dr. Taylor commented: “It is hard to know whether there are real and reproducible differences in the risks of DKA among the various SGLT2 inhibitors. The differences are not huge and the populations are not well matched.”

But, he noted, “If canagliflozin triggers more glucosuria, it is not surprising that it would also induce more ketosis and possibly ketoacidosis.”

He also noted that the threefold relative increase in DKA with canagliflozin versus comparators is consistent with Janssen’s data, published in 2015. 

“It is, of course, reassuring that both [randomized clinical trials] and epidemiology produce similar estimates of the risk of drug-induced adverse events. Interestingly, the incidence of DKA is approximately threefold higher in the Canadian [data] as compared to Janssen’s clinical trials.”

Dr. Taylor also pointed out that, in the Janssen studies, the risk of canagliflozin-induced DKA appeared to be higher among patients with anti-islet antibodies, which suggests that some may have actually had autoimmune (type 1) diabetes. “So the overall risk of SGLT2 inhibitor-induced DKA may depend at least in part on the mix of patients.”

In the current study, individuals who never used insulin had a greater relative increase in risk of DKA with SGLT2 inhibitors, compared with DPP-4 inhibitors, than did those who did use insulin (hazard ratios, 3.96 vs. 2.24, both compared with DPP-4 inhibitors). However, just among those taking SGLT2 inhibitors, the absolute risk for DKA was higher for those with prior insulin use (3.52 vs. 1.43 per 1,000 person-years). 

The results of sensitivity analyses were consistent with those of the primary analysis.

The study was funded by the Canadian Institutes of Health Research and supported by ICES. Dr. Douros has reported receiving a salary support award from Fonds de recherche du Quebec – sante. Dr. Taylor was previously employed at Bristol-Myers Squibb. He is currently a consultant for Ionis Pharmaceuticals and has reported receiving research support provided to the University of Maryland School of Medicine by Regeneron.

A version of this article originally appeared on Medscape.com.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors used for the treatment of type 2 diabetes, and for heart failure, are associated with a nearly threefold increased risk for diabetic ketoacidosis (DKA), according to a new large database analysis.

Boarding1Now/Thinkstock

The findings, which include data on the use of three different SGLT2 inhibitors in Canada and the United Kingdom and suggest a class effect, were published online July 27 in Annals of Internal Medicine by Antonios Douros, MD, PhD, of McGill University and the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, and colleagues.

“Our results provide robust evidence that SGLT2 inhibitors are associated with an increased risk for DKA. Of note, increased risks were observed in all molecule-specific analyses, with canagliflozin [Invokana, Janssen] showing the highest effect estimate,” they noted.

And because the beneficial effects of SGLT2 inhibitors in the prevention of cardiovascular and renal disease will probably increase their uptake in the coming years, “Physicians should be aware of DKA as a potential adverse effect,” Dr. Douros and colleagues wrote.
 

Analysis “generally confirms what has already been published”

Asked for comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, said that the study “generally confirms what has already been published” on the topic. He noted that overall “the risk of SGLT2 inhibitor–induced ketoacidosis is quite low in type 2 diabetes, perhaps on the order of 1 episode per 1000 patient-years.”

However, Dr. Taylor cautioned: “Published evidence suggests that the risk of DKA is increased if patients are unable to eat,” such as when hospitalized patients are not permitted to eat.

“In that setting, it is probably prudent to discontinue an SGLT2 inhibitor. Also, it may be prudent not to prescribe SGLT2 inhibitors to patients with a history of DKA,” he added.

Dr. Taylor also advised: “Although not necessarily supported by this publication, I think that caution should be exercised in prescribing SGLT2 inhibitors to insulin-dependent type 2 diabetes patients. ... Some late-stage type 2 diabetes patients may have severe insulin deficiency, and their physiology may resemble that of a type 1 diabetes patient.”

Dr. Taylor has previously advised against using SGLT2 inhibitors altogether in patients with type 1 diabetes.
 

Increased DKA risk seen across all SGLT2 inhibitors

The study involved electronic health care databases from seven Canadian provinces and the United Kingdom, from which 208,757 new users of SGLT2 inhibitors were propensity-matched 1:1 to new dipeptidyl peptidase-4 (DPP-4) inhibitor users.

Of those taking an SGLT2 inhibitor, 42.3% took canagliflozin, 30.7% dapagliflozin (Farxiga/Forxiga, AstraZeneca), and 27.0% empagliflozin (Jardiance, Boehringer Ingelheim).

Over a mean 0.9-year follow-up, 521 patients were hospitalized with DKA, for an overall incidence rate of 1.41 per 1,000 person-years.

The rate with SGLT2 inhibitors, 2.03 per 1,000 person-years, was nearly three times that seen with DPP-4 inhibitors, at 0.75 per 1,000 person-years, a significant difference (hazard ratio, 2.85).

By individual SGLT2 inhibitor, the hazard ratios compared with DPP-4 inhibitors were 1.86 for dapagliflozin, 2.52 for empagliflozin, and 3.58 for canagliflozin, all statistically significant. Stratification by age, sex, and incident versus prevalent user did not change the association between SGLT2 inhibitors and DKA.

Asked about the higher rate for canagliflozin, Dr. Taylor commented: “It is hard to know whether there are real and reproducible differences in the risks of DKA among the various SGLT2 inhibitors. The differences are not huge and the populations are not well matched.”

But, he noted, “If canagliflozin triggers more glucosuria, it is not surprising that it would also induce more ketosis and possibly ketoacidosis.”

He also noted that the threefold relative increase in DKA with canagliflozin versus comparators is consistent with Janssen’s data, published in 2015. 

“It is, of course, reassuring that both [randomized clinical trials] and epidemiology produce similar estimates of the risk of drug-induced adverse events. Interestingly, the incidence of DKA is approximately threefold higher in the Canadian [data] as compared to Janssen’s clinical trials.”

Dr. Taylor also pointed out that, in the Janssen studies, the risk of canagliflozin-induced DKA appeared to be higher among patients with anti-islet antibodies, which suggests that some may have actually had autoimmune (type 1) diabetes. “So the overall risk of SGLT2 inhibitor-induced DKA may depend at least in part on the mix of patients.”

In the current study, individuals who never used insulin had a greater relative increase in risk of DKA with SGLT2 inhibitors, compared with DPP-4 inhibitors, than did those who did use insulin (hazard ratios, 3.96 vs. 2.24, both compared with DPP-4 inhibitors). However, just among those taking SGLT2 inhibitors, the absolute risk for DKA was higher for those with prior insulin use (3.52 vs. 1.43 per 1,000 person-years). 

The results of sensitivity analyses were consistent with those of the primary analysis.

The study was funded by the Canadian Institutes of Health Research and supported by ICES. Dr. Douros has reported receiving a salary support award from Fonds de recherche du Quebec – sante. Dr. Taylor was previously employed at Bristol-Myers Squibb. He is currently a consultant for Ionis Pharmaceuticals and has reported receiving research support provided to the University of Maryland School of Medicine by Regeneron.

A version of this article originally appeared on Medscape.com.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors used for the treatment of type 2 diabetes, and for heart failure, are associated with a nearly threefold increased risk for diabetic ketoacidosis (DKA), according to a new large database analysis.

Boarding1Now/Thinkstock

The findings, which include data on the use of three different SGLT2 inhibitors in Canada and the United Kingdom and suggest a class effect, were published online July 27 in Annals of Internal Medicine by Antonios Douros, MD, PhD, of McGill University and the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, and colleagues.

“Our results provide robust evidence that SGLT2 inhibitors are associated with an increased risk for DKA. Of note, increased risks were observed in all molecule-specific analyses, with canagliflozin [Invokana, Janssen] showing the highest effect estimate,” they noted.

And because the beneficial effects of SGLT2 inhibitors in the prevention of cardiovascular and renal disease will probably increase their uptake in the coming years, “Physicians should be aware of DKA as a potential adverse effect,” Dr. Douros and colleagues wrote.
 

Analysis “generally confirms what has already been published”

Asked for comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, said that the study “generally confirms what has already been published” on the topic. He noted that overall “the risk of SGLT2 inhibitor–induced ketoacidosis is quite low in type 2 diabetes, perhaps on the order of 1 episode per 1000 patient-years.”

However, Dr. Taylor cautioned: “Published evidence suggests that the risk of DKA is increased if patients are unable to eat,” such as when hospitalized patients are not permitted to eat.

“In that setting, it is probably prudent to discontinue an SGLT2 inhibitor. Also, it may be prudent not to prescribe SGLT2 inhibitors to patients with a history of DKA,” he added.

Dr. Taylor also advised: “Although not necessarily supported by this publication, I think that caution should be exercised in prescribing SGLT2 inhibitors to insulin-dependent type 2 diabetes patients. ... Some late-stage type 2 diabetes patients may have severe insulin deficiency, and their physiology may resemble that of a type 1 diabetes patient.”

Dr. Taylor has previously advised against using SGLT2 inhibitors altogether in patients with type 1 diabetes.
 

Increased DKA risk seen across all SGLT2 inhibitors

The study involved electronic health care databases from seven Canadian provinces and the United Kingdom, from which 208,757 new users of SGLT2 inhibitors were propensity-matched 1:1 to new dipeptidyl peptidase-4 (DPP-4) inhibitor users.

Of those taking an SGLT2 inhibitor, 42.3% took canagliflozin, 30.7% dapagliflozin (Farxiga/Forxiga, AstraZeneca), and 27.0% empagliflozin (Jardiance, Boehringer Ingelheim).

Over a mean 0.9-year follow-up, 521 patients were hospitalized with DKA, for an overall incidence rate of 1.41 per 1,000 person-years.

The rate with SGLT2 inhibitors, 2.03 per 1,000 person-years, was nearly three times that seen with DPP-4 inhibitors, at 0.75 per 1,000 person-years, a significant difference (hazard ratio, 2.85).

By individual SGLT2 inhibitor, the hazard ratios compared with DPP-4 inhibitors were 1.86 for dapagliflozin, 2.52 for empagliflozin, and 3.58 for canagliflozin, all statistically significant. Stratification by age, sex, and incident versus prevalent user did not change the association between SGLT2 inhibitors and DKA.

Asked about the higher rate for canagliflozin, Dr. Taylor commented: “It is hard to know whether there are real and reproducible differences in the risks of DKA among the various SGLT2 inhibitors. The differences are not huge and the populations are not well matched.”

But, he noted, “If canagliflozin triggers more glucosuria, it is not surprising that it would also induce more ketosis and possibly ketoacidosis.”

He also noted that the threefold relative increase in DKA with canagliflozin versus comparators is consistent with Janssen’s data, published in 2015. 

“It is, of course, reassuring that both [randomized clinical trials] and epidemiology produce similar estimates of the risk of drug-induced adverse events. Interestingly, the incidence of DKA is approximately threefold higher in the Canadian [data] as compared to Janssen’s clinical trials.”

Dr. Taylor also pointed out that, in the Janssen studies, the risk of canagliflozin-induced DKA appeared to be higher among patients with anti-islet antibodies, which suggests that some may have actually had autoimmune (type 1) diabetes. “So the overall risk of SGLT2 inhibitor-induced DKA may depend at least in part on the mix of patients.”

In the current study, individuals who never used insulin had a greater relative increase in risk of DKA with SGLT2 inhibitors, compared with DPP-4 inhibitors, than did those who did use insulin (hazard ratios, 3.96 vs. 2.24, both compared with DPP-4 inhibitors). However, just among those taking SGLT2 inhibitors, the absolute risk for DKA was higher for those with prior insulin use (3.52 vs. 1.43 per 1,000 person-years). 

The results of sensitivity analyses were consistent with those of the primary analysis.

The study was funded by the Canadian Institutes of Health Research and supported by ICES. Dr. Douros has reported receiving a salary support award from Fonds de recherche du Quebec – sante. Dr. Taylor was previously employed at Bristol-Myers Squibb. He is currently a consultant for Ionis Pharmaceuticals and has reported receiving research support provided to the University of Maryland School of Medicine by Regeneron.

A version of this article originally appeared on Medscape.com.

“Anytime you have a maternal death, it sticks with you for life,” said Elliott Main, MD, a maternal fetal medicine specialist at Stanford (Calif.) University and one of the nation’s leaders in combating maternal mortality.

Courtesy Dr. Elliott Main

Dr. Main has had two maternal deaths in his career, years ago. One woman had a fatal stroke because of severe hypertension, and another died of cardiac complications. “We tried to do everything we possibly could, but you scrounge your memory for years and years [afterward]. To have a young healthy person go into labor and delivery and not come out is a tragedy at all levels. It charged me to not ever want to see that happen again,” he said.

Today, Dr. Main is the medical director of the California Maternal Quality Care Collaborative (CMQCC), a wide-ranging group of clinicians, state officials, hospitals, and others who have come together to address the issue. About 30 states have similar perinatal quality collaboratives (PQCs), and other states are forming them.

They work in collaboration with maternal mortality review committees (MMRCs), state-level groups that review maternal deaths, identify problems to address, and make recommendations to the quality collaboratives on how to prevent maternal deaths.

About 600-800 women die in the United States each year due to pregnancy-related complications, which ranks the United States behind other industrialized nations. Leading causes include hemorrhage and hemorrhagic strokes secondary to hypertension. It’s estimated that the majority of maternal deaths could be prevented with proper care.

To that end, states are enacting safety bundles from the Alliance for Innovation on Maternal Health (AIM), which was established by the American College of Obstetricians and Gynecologist several years ago. There are bundles that address obstetric hypertension, hemorrhage, mental health, venous thromboembolism, opioid use, racial disparities, and other problems. They were developed by experts in the field and published in multiple journals. California and other states have issued toolkits on how to implement them based on local circumstances.

The goal is to standardize best practices nationwide to prevent maternal morbidity and mortality, Dr. Main said.

AIM bundle implementation is “what’s happening in New Mexico and a lot of states, mostly through the efforts of state level quality care collaboratives. Some [states] are further ahead than others,” said Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, and president of the New Mexico PQC.

“Most states now have a [MMRC] that collects maternal mortality and near-miss data. Those data are used by the action arm,” which is the PQC. “If the review committee says” opioid use disorder is a significant contributor “like in our state, the collaborative rolls out the opioid use disorder bundle,” she said.

Beginning next January, the Joint Commission, formerly known as the Joint Commission on Accreditation of Healthcare Organizations, will require that accredited hospitals enact key elements of the AIM bundles for both obstetric hemorrhage and severe hypertension. “Everyone’s [now] motivated to get on that bandwagon,” Dr. Espey said.

“The bundles are here to stay,” and the Joint Commission requirements are “a really important step for sustainability and basic implementation. We really want to get them adopted everywhere,” said Dr. Main, who is also the national implementation director for the AIM initiative.

“The key thing is to work on implementing the hemorrhage and hypertension bundles in your hospital. I would suggest contacting [your] state” PQC, he said.

The California model

California, which has been working to reduce maternal mortality and morbidity since the mid 2000s, has produced among the strongest evidence to date that the efforts make a difference.

By 2013, the state had halved its maternal mortality rate to a 3-year average of 7 deaths per 100,000 live births, which is comparable with the average Western Europe rate of 7.2 deaths. Nationwide, the rate was about 17.4 deaths per 100,000 live births in 2018, according to the Centers for Disease Control and Prevention

The reasons are multifactorial, but “we think” the quality improvement efforts have been “an important contributor,” Dr. Main said.
 

Improvements especially for Black women

Among the success stories has been California’s implementation of the AIM obstetric hemorrhage bundle about 5 years ago. Among other steps, the 17 evidence-based recommendations included early recognition, immediate access to oxytocin and other medications, immediate access to a hemorrhage cart with instructions for intrauterine balloons and compression stitches, the establishment of a hemorrhage response protocol and team, and regular unit-based drills with debriefing sessions afterward.

Mentoring teams consisting of a physician and nurse with maternal quality improvement experience were created to help hospitals come on board, with each team working with five to eight hospitals. Efforts included monthly telephone calls and face-to-face meetings, and providers were held accountable for progress. Hospitals shared data and tips on implementation, under the aegis of the CMQCC.

When the baseline period of 2011-2014 to the postintervention period of October 2015 to December 2016 were compared, the rate of severe maternal morbidity from hemorrhage fell from 22.1% to 18.5% across 99 hospitals and 73,476 women.

The benefit among Black women exceeded that among White women, with a 9% absolute rate reduction versus 2.1%. “If you adjusted for risk factors, [we found] you could eliminate [racial differences] completely,” which is something that hadn’t been shown before. “This is a really big deal,” Dr. Main said, because the risk of maternal morbidity and mortality is three to four times higher among Black women, compared with White women.

Dr. Main and his team found that the biggest clinical risk factor that accounted for racial differences was a higher rate of cesarean deliveries among Black women, followed by higher rates of anemia at hospital admission. “If you have a C-section when you are anemic, you are going to have a transfusion,” he explained.

More recently, there’s been a push in California to reduce the rate of primary cesarean deliveries by enacting the associated AIM bundle with use of the same approach as with the hemorrhage bundle. Dr. Main and his team recently reported a rate reduction from 29.3% to 25% without compromising birth outcomes.

However, “some changes are easier than others. Hemorrhage was an easy one to change because it didn’t deal with physician autonomy as much, and you saw more immediate results” with fewer hemorrhages. Reducing cesarean delivery rates is “a bigger lift” because “it’s really changing the culture of labor and delivery. It involves more group pressure and more reinforcing, but we were able to do that,” he said.
 

Problems in the Show Me State

“We’ve patterned a lot” of what’s being done in New Mexico “after California,” Dr. Espey said.

The AIM hemorrhage bundle, for instance, is being rolled out to New Mexico hospitals, with the help of virtual meetings and mentoring programs, plus outreach to the Navajo and others reservations because, as with Black women, rates of maternal morbidity and mortality are higher among Native American women.

It’s been tougher going, however, in states such as Missouri, which recently ranked 44th in the country for maternal mortality.

“We started a little bit late, and we are a little bit behind,” said ob.gyn. Karen L. Florio, DO, at the University of Missouri–Kansas City and also a leader of the state MMRC and member of its PQC.

The main problem is money. California’s efforts are funded by the Centers for Disease Control and Prevention, the state health department, and hospitals, among others.

But Missouri is “not as well funded as California for our mortality review board, and our [PQC] is mostly not funded. If we could get that funding, we would have more resources to implement these AIM bundles,” she said.

In addition to the issue, Missouri didn’t expand Medicaid under the Accountable Care Act – something that’s been linked to reduced maternal morbidity and mortality – and there are entire rural areas with no maternity care. Plus after generations of mistreatment, “our African American population has a valid distrust of the medical system that contributes to maternal mortality,” she said.

Obesity-related heart disease is also prevalent in Missouri, even among young people. “I cannot tell you how many women I have had who have had a heart attack at the age of 30 and who have had stents placed,” Dr. Florio said.

Dr. Florio and her colleagues are currently using teleconferences and other means to roll out the AIM hypertension bundle but can do so only selectively. “We don’t have the resources to reach every single rural hospital all over the state,” she said; they are working to address the funding issues.
 

For rural hospitals, implementation is “daunting”

Meanwhile, rural hospitals have been a particular concern in South Dakota, said Kimberlee McKay, MD, an ob.gyn. who is the clinical vice president of the ob.gyn. service line at Avera Health, a hospital system based in Sioux Falls, S.D.

She’s been overseeing Avera’s implementation of the hypertension, hemorrhage, and venous thromboembolism bundles. “What’s hard is that” the AIM protocols come “out of academic centers. Implementation of complex algorithms is daunting” for hospitals that only do a couple hundred deliveries a year, she said.

For small hospitals, the approach she’s found that works is to first assess what they can offer, and then have them “do what’s reasonable” for their resources. The second part is making sure high-risk women get to a regional center – with an adequate blood supply, in the case of hemorrhage, for instance – for complications. Dr. McKay and colleagues are working on a system by which regional centers can monitor smaller hospitals for potential maternity problems, and contact them proactively before they emerge.

They’ve also made access to hemorrhage and hypertension drugs easier on labor and delivery units with the help of close-by dedicated medicine boxes, and standardized protocols and order sets across Avera. “We try to make the right thing the easy thing to do,” Dr. McKay said.

Dr. Espey is an editorial adviser for Ob.Gyn. News. The physicians have no relevant financial disclosures.

aotto@mdedge.com

“Anytime you have a maternal death, it sticks with you for life,” said Elliott Main, MD, a maternal fetal medicine specialist at Stanford (Calif.) University and one of the nation’s leaders in combating maternal mortality.

Courtesy Dr. Elliott Main

Dr. Main has had two maternal deaths in his career, years ago. One woman had a fatal stroke because of severe hypertension, and another died of cardiac complications. “We tried to do everything we possibly could, but you scrounge your memory for years and years [afterward]. To have a young healthy person go into labor and delivery and not come out is a tragedy at all levels. It charged me to not ever want to see that happen again,” he said.

Today, Dr. Main is the medical director of the California Maternal Quality Care Collaborative (CMQCC), a wide-ranging group of clinicians, state officials, hospitals, and others who have come together to address the issue. About 30 states have similar perinatal quality collaboratives (PQCs), and other states are forming them.

They work in collaboration with maternal mortality review committees (MMRCs), state-level groups that review maternal deaths, identify problems to address, and make recommendations to the quality collaboratives on how to prevent maternal deaths.

About 600-800 women die in the United States each year due to pregnancy-related complications, which ranks the United States behind other industrialized nations. Leading causes include hemorrhage and hemorrhagic strokes secondary to hypertension. It’s estimated that the majority of maternal deaths could be prevented with proper care.

To that end, states are enacting safety bundles from the Alliance for Innovation on Maternal Health (AIM), which was established by the American College of Obstetricians and Gynecologist several years ago. There are bundles that address obstetric hypertension, hemorrhage, mental health, venous thromboembolism, opioid use, racial disparities, and other problems. They were developed by experts in the field and published in multiple journals. California and other states have issued toolkits on how to implement them based on local circumstances.

The goal is to standardize best practices nationwide to prevent maternal morbidity and mortality, Dr. Main said.

AIM bundle implementation is “what’s happening in New Mexico and a lot of states, mostly through the efforts of state level quality care collaboratives. Some [states] are further ahead than others,” said Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, and president of the New Mexico PQC.

“Most states now have a [MMRC] that collects maternal mortality and near-miss data. Those data are used by the action arm,” which is the PQC. “If the review committee says” opioid use disorder is a significant contributor “like in our state, the collaborative rolls out the opioid use disorder bundle,” she said.

Beginning next January, the Joint Commission, formerly known as the Joint Commission on Accreditation of Healthcare Organizations, will require that accredited hospitals enact key elements of the AIM bundles for both obstetric hemorrhage and severe hypertension. “Everyone’s [now] motivated to get on that bandwagon,” Dr. Espey said.

“The bundles are here to stay,” and the Joint Commission requirements are “a really important step for sustainability and basic implementation. We really want to get them adopted everywhere,” said Dr. Main, who is also the national implementation director for the AIM initiative.

“The key thing is to work on implementing the hemorrhage and hypertension bundles in your hospital. I would suggest contacting [your] state” PQC, he said.

The California model

California, which has been working to reduce maternal mortality and morbidity since the mid 2000s, has produced among the strongest evidence to date that the efforts make a difference.

By 2013, the state had halved its maternal mortality rate to a 3-year average of 7 deaths per 100,000 live births, which is comparable with the average Western Europe rate of 7.2 deaths. Nationwide, the rate was about 17.4 deaths per 100,000 live births in 2018, according to the Centers for Disease Control and Prevention

The reasons are multifactorial, but “we think” the quality improvement efforts have been “an important contributor,” Dr. Main said.
 

Improvements especially for Black women

Among the success stories has been California’s implementation of the AIM obstetric hemorrhage bundle about 5 years ago. Among other steps, the 17 evidence-based recommendations included early recognition, immediate access to oxytocin and other medications, immediate access to a hemorrhage cart with instructions for intrauterine balloons and compression stitches, the establishment of a hemorrhage response protocol and team, and regular unit-based drills with debriefing sessions afterward.

Mentoring teams consisting of a physician and nurse with maternal quality improvement experience were created to help hospitals come on board, with each team working with five to eight hospitals. Efforts included monthly telephone calls and face-to-face meetings, and providers were held accountable for progress. Hospitals shared data and tips on implementation, under the aegis of the CMQCC.

When the baseline period of 2011-2014 to the postintervention period of October 2015 to December 2016 were compared, the rate of severe maternal morbidity from hemorrhage fell from 22.1% to 18.5% across 99 hospitals and 73,476 women.

The benefit among Black women exceeded that among White women, with a 9% absolute rate reduction versus 2.1%. “If you adjusted for risk factors, [we found] you could eliminate [racial differences] completely,” which is something that hadn’t been shown before. “This is a really big deal,” Dr. Main said, because the risk of maternal morbidity and mortality is three to four times higher among Black women, compared with White women.

Dr. Main and his team found that the biggest clinical risk factor that accounted for racial differences was a higher rate of cesarean deliveries among Black women, followed by higher rates of anemia at hospital admission. “If you have a C-section when you are anemic, you are going to have a transfusion,” he explained.

More recently, there’s been a push in California to reduce the rate of primary cesarean deliveries by enacting the associated AIM bundle with use of the same approach as with the hemorrhage bundle. Dr. Main and his team recently reported a rate reduction from 29.3% to 25% without compromising birth outcomes.

However, “some changes are easier than others. Hemorrhage was an easy one to change because it didn’t deal with physician autonomy as much, and you saw more immediate results” with fewer hemorrhages. Reducing cesarean delivery rates is “a bigger lift” because “it’s really changing the culture of labor and delivery. It involves more group pressure and more reinforcing, but we were able to do that,” he said.
 

Problems in the Show Me State

“We’ve patterned a lot” of what’s being done in New Mexico “after California,” Dr. Espey said.

The AIM hemorrhage bundle, for instance, is being rolled out to New Mexico hospitals, with the help of virtual meetings and mentoring programs, plus outreach to the Navajo and others reservations because, as with Black women, rates of maternal morbidity and mortality are higher among Native American women.

It’s been tougher going, however, in states such as Missouri, which recently ranked 44th in the country for maternal mortality.

“We started a little bit late, and we are a little bit behind,” said ob.gyn. Karen L. Florio, DO, at the University of Missouri–Kansas City and also a leader of the state MMRC and member of its PQC.

The main problem is money. California’s efforts are funded by the Centers for Disease Control and Prevention, the state health department, and hospitals, among others.

But Missouri is “not as well funded as California for our mortality review board, and our [PQC] is mostly not funded. If we could get that funding, we would have more resources to implement these AIM bundles,” she said.

In addition to the issue, Missouri didn’t expand Medicaid under the Accountable Care Act – something that’s been linked to reduced maternal morbidity and mortality – and there are entire rural areas with no maternity care. Plus after generations of mistreatment, “our African American population has a valid distrust of the medical system that contributes to maternal mortality,” she said.

Obesity-related heart disease is also prevalent in Missouri, even among young people. “I cannot tell you how many women I have had who have had a heart attack at the age of 30 and who have had stents placed,” Dr. Florio said.

Dr. Florio and her colleagues are currently using teleconferences and other means to roll out the AIM hypertension bundle but can do so only selectively. “We don’t have the resources to reach every single rural hospital all over the state,” she said; they are working to address the funding issues.
 

For rural hospitals, implementation is “daunting”

Meanwhile, rural hospitals have been a particular concern in South Dakota, said Kimberlee McKay, MD, an ob.gyn. who is the clinical vice president of the ob.gyn. service line at Avera Health, a hospital system based in Sioux Falls, S.D.

She’s been overseeing Avera’s implementation of the hypertension, hemorrhage, and venous thromboembolism bundles. “What’s hard is that” the AIM protocols come “out of academic centers. Implementation of complex algorithms is daunting” for hospitals that only do a couple hundred deliveries a year, she said.

For small hospitals, the approach she’s found that works is to first assess what they can offer, and then have them “do what’s reasonable” for their resources. The second part is making sure high-risk women get to a regional center – with an adequate blood supply, in the case of hemorrhage, for instance – for complications. Dr. McKay and colleagues are working on a system by which regional centers can monitor smaller hospitals for potential maternity problems, and contact them proactively before they emerge.

They’ve also made access to hemorrhage and hypertension drugs easier on labor and delivery units with the help of close-by dedicated medicine boxes, and standardized protocols and order sets across Avera. “We try to make the right thing the easy thing to do,” Dr. McKay said.

Dr. Espey is an editorial adviser for Ob.Gyn. News. The physicians have no relevant financial disclosures.

aotto@mdedge.com

“Anytime you have a maternal death, it sticks with you for life,” said Elliott Main, MD, a maternal fetal medicine specialist at Stanford (Calif.) University and one of the nation’s leaders in combating maternal mortality.

Courtesy Dr. Elliott Main

Dr. Main has had two maternal deaths in his career, years ago. One woman had a fatal stroke because of severe hypertension, and another died of cardiac complications. “We tried to do everything we possibly could, but you scrounge your memory for years and years [afterward]. To have a young healthy person go into labor and delivery and not come out is a tragedy at all levels. It charged me to not ever want to see that happen again,” he said.

Today, Dr. Main is the medical director of the California Maternal Quality Care Collaborative (CMQCC), a wide-ranging group of clinicians, state officials, hospitals, and others who have come together to address the issue. About 30 states have similar perinatal quality collaboratives (PQCs), and other states are forming them.

They work in collaboration with maternal mortality review committees (MMRCs), state-level groups that review maternal deaths, identify problems to address, and make recommendations to the quality collaboratives on how to prevent maternal deaths.

About 600-800 women die in the United States each year due to pregnancy-related complications, which ranks the United States behind other industrialized nations. Leading causes include hemorrhage and hemorrhagic strokes secondary to hypertension. It’s estimated that the majority of maternal deaths could be prevented with proper care.

To that end, states are enacting safety bundles from the Alliance for Innovation on Maternal Health (AIM), which was established by the American College of Obstetricians and Gynecologist several years ago. There are bundles that address obstetric hypertension, hemorrhage, mental health, venous thromboembolism, opioid use, racial disparities, and other problems. They were developed by experts in the field and published in multiple journals. California and other states have issued toolkits on how to implement them based on local circumstances.

The goal is to standardize best practices nationwide to prevent maternal morbidity and mortality, Dr. Main said.

AIM bundle implementation is “what’s happening in New Mexico and a lot of states, mostly through the efforts of state level quality care collaboratives. Some [states] are further ahead than others,” said Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, and president of the New Mexico PQC.

“Most states now have a [MMRC] that collects maternal mortality and near-miss data. Those data are used by the action arm,” which is the PQC. “If the review committee says” opioid use disorder is a significant contributor “like in our state, the collaborative rolls out the opioid use disorder bundle,” she said.

Beginning next January, the Joint Commission, formerly known as the Joint Commission on Accreditation of Healthcare Organizations, will require that accredited hospitals enact key elements of the AIM bundles for both obstetric hemorrhage and severe hypertension. “Everyone’s [now] motivated to get on that bandwagon,” Dr. Espey said.

“The bundles are here to stay,” and the Joint Commission requirements are “a really important step for sustainability and basic implementation. We really want to get them adopted everywhere,” said Dr. Main, who is also the national implementation director for the AIM initiative.

“The key thing is to work on implementing the hemorrhage and hypertension bundles in your hospital. I would suggest contacting [your] state” PQC, he said.

The California model

California, which has been working to reduce maternal mortality and morbidity since the mid 2000s, has produced among the strongest evidence to date that the efforts make a difference.

By 2013, the state had halved its maternal mortality rate to a 3-year average of 7 deaths per 100,000 live births, which is comparable with the average Western Europe rate of 7.2 deaths. Nationwide, the rate was about 17.4 deaths per 100,000 live births in 2018, according to the Centers for Disease Control and Prevention

The reasons are multifactorial, but “we think” the quality improvement efforts have been “an important contributor,” Dr. Main said.
 

Improvements especially for Black women

Among the success stories has been California’s implementation of the AIM obstetric hemorrhage bundle about 5 years ago. Among other steps, the 17 evidence-based recommendations included early recognition, immediate access to oxytocin and other medications, immediate access to a hemorrhage cart with instructions for intrauterine balloons and compression stitches, the establishment of a hemorrhage response protocol and team, and regular unit-based drills with debriefing sessions afterward.

Mentoring teams consisting of a physician and nurse with maternal quality improvement experience were created to help hospitals come on board, with each team working with five to eight hospitals. Efforts included monthly telephone calls and face-to-face meetings, and providers were held accountable for progress. Hospitals shared data and tips on implementation, under the aegis of the CMQCC.

When the baseline period of 2011-2014 to the postintervention period of October 2015 to December 2016 were compared, the rate of severe maternal morbidity from hemorrhage fell from 22.1% to 18.5% across 99 hospitals and 73,476 women.

The benefit among Black women exceeded that among White women, with a 9% absolute rate reduction versus 2.1%. “If you adjusted for risk factors, [we found] you could eliminate [racial differences] completely,” which is something that hadn’t been shown before. “This is a really big deal,” Dr. Main said, because the risk of maternal morbidity and mortality is three to four times higher among Black women, compared with White women.

Dr. Main and his team found that the biggest clinical risk factor that accounted for racial differences was a higher rate of cesarean deliveries among Black women, followed by higher rates of anemia at hospital admission. “If you have a C-section when you are anemic, you are going to have a transfusion,” he explained.

More recently, there’s been a push in California to reduce the rate of primary cesarean deliveries by enacting the associated AIM bundle with use of the same approach as with the hemorrhage bundle. Dr. Main and his team recently reported a rate reduction from 29.3% to 25% without compromising birth outcomes.

However, “some changes are easier than others. Hemorrhage was an easy one to change because it didn’t deal with physician autonomy as much, and you saw more immediate results” with fewer hemorrhages. Reducing cesarean delivery rates is “a bigger lift” because “it’s really changing the culture of labor and delivery. It involves more group pressure and more reinforcing, but we were able to do that,” he said.
 

Problems in the Show Me State

“We’ve patterned a lot” of what’s being done in New Mexico “after California,” Dr. Espey said.

The AIM hemorrhage bundle, for instance, is being rolled out to New Mexico hospitals, with the help of virtual meetings and mentoring programs, plus outreach to the Navajo and others reservations because, as with Black women, rates of maternal morbidity and mortality are higher among Native American women.

It’s been tougher going, however, in states such as Missouri, which recently ranked 44th in the country for maternal mortality.

“We started a little bit late, and we are a little bit behind,” said ob.gyn. Karen L. Florio, DO, at the University of Missouri–Kansas City and also a leader of the state MMRC and member of its PQC.

The main problem is money. California’s efforts are funded by the Centers for Disease Control and Prevention, the state health department, and hospitals, among others.

But Missouri is “not as well funded as California for our mortality review board, and our [PQC] is mostly not funded. If we could get that funding, we would have more resources to implement these AIM bundles,” she said.

In addition to the issue, Missouri didn’t expand Medicaid under the Accountable Care Act – something that’s been linked to reduced maternal morbidity and mortality – and there are entire rural areas with no maternity care. Plus after generations of mistreatment, “our African American population has a valid distrust of the medical system that contributes to maternal mortality,” she said.

Obesity-related heart disease is also prevalent in Missouri, even among young people. “I cannot tell you how many women I have had who have had a heart attack at the age of 30 and who have had stents placed,” Dr. Florio said.

Dr. Florio and her colleagues are currently using teleconferences and other means to roll out the AIM hypertension bundle but can do so only selectively. “We don’t have the resources to reach every single rural hospital all over the state,” she said; they are working to address the funding issues.
 

For rural hospitals, implementation is “daunting”

Meanwhile, rural hospitals have been a particular concern in South Dakota, said Kimberlee McKay, MD, an ob.gyn. who is the clinical vice president of the ob.gyn. service line at Avera Health, a hospital system based in Sioux Falls, S.D.

She’s been overseeing Avera’s implementation of the hypertension, hemorrhage, and venous thromboembolism bundles. “What’s hard is that” the AIM protocols come “out of academic centers. Implementation of complex algorithms is daunting” for hospitals that only do a couple hundred deliveries a year, she said.

For small hospitals, the approach she’s found that works is to first assess what they can offer, and then have them “do what’s reasonable” for their resources. The second part is making sure high-risk women get to a regional center – with an adequate blood supply, in the case of hemorrhage, for instance – for complications. Dr. McKay and colleagues are working on a system by which regional centers can monitor smaller hospitals for potential maternity problems, and contact them proactively before they emerge.

They’ve also made access to hemorrhage and hypertension drugs easier on labor and delivery units with the help of close-by dedicated medicine boxes, and standardized protocols and order sets across Avera. “We try to make the right thing the easy thing to do,” Dr. McKay said.

Dr. Espey is an editorial adviser for Ob.Gyn. News. The physicians have no relevant financial disclosures.

aotto@mdedge.com

When children and adolescents first present to George Hightower, MD, PhD, with suspected primary hyperhidrosis, he tries to gauge their level of impairment and distress.

Miyuki-3

“I ask my patients directly: ‘Does this get in the way of doing things you enjoy?’ ” Dr. Hightower said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. If they say yes, he then asks, “‘What are those things that it gets in the way of?’ Also, so that I can develop a rapport with them, I ask, ‘Is it causing you to view yourself negatively?’ I also ask them how they anticipate treatment is going to change that.”

Dr. Hightower, of the departments of dermatology and pediatrics, University of California, San Diego, and a pediatric dermatologist at Rady Children’s Hospital, defined focal primary hyperhidrosis as focal, visible, excessive sweating for at least 6 months without an apparent cause, plus at least two of the following characteristics: bilateral and relatively symmetric, sweating that impairs daily activities, onset before age 25, at least one episode per week, family history of idiopathic hyperhidrosis, and focal sweating that stops during sleep.

“Based on their prominence in the popular media, armpits relative to body surface area play an oversized role in our patients’ perception of well-being,” he said. “Most of all, patients’ concerns regarding their armpits include one more of the following symptoms: smelly, sweaty, red, and itchy or painful.”

The differential diagnosis for disorders of the axilla includes irritant/contact dermatitis, folliculitis, seborrheic dermatitis, hyperhidrosis, and hidradenitis suppurativa.

Topical antiperspirants are the preferred initial treatment. “They’re widely available, inexpensive, and well-tolerated therapies,” Dr. Hightower said. Most commercially available antiperspirants contain low-dose aluminum or other metal that keeps the sweat gland ducts from opening.

“Most patients referred to me have failed to improve with over-the-counter antiperspirants or aluminum chloride 20%,” he said. “We start by reviewing the appropriate use of aluminum chloride 20%. If they’re using it appropriately and fail to achieve adequate control, I open the discussion to use glycopyrronium tosylate cloth 2.4%, applied daily. This can be cost prohibitive or not covered by insurance.” Other options include glycopyrrolate 1-6 mg daily and microwave-based procedural intervention.

In a post hoc analysis, researchers examined the efficacy and safety findings by age from two phase three randomized, controlled trials of glycopyrronium tosylate in pediatric primary axillary hyperhidrosis (Pediatr Dermatol. 2019 Jan-Feb;36[1]:89-99). It was well tolerated in the 19 patients aged 9-16 years. “No patients discontinued from the study in this age group [because of] symptomatology,” said Dr. Hightower, who was not involved with the study. “The concerns related to this medication are related to anticholinergic effects such as blurry vision and dry mouth, but overall, randomized clinical trial data support the benefit of this medication in helping patients improve the symptoms of hyperhidrosis.”

In an earlier study, researchers retrospectively studied children with hyperhidrosis who were treated with a mean dosage of 2 mg glycopyrronium tosylate daily (J Am Acad Dermatol 2012 Nov;67[5]:918-23). The average age of patients was 15 years. Most (90%) experienced some improvement and 71% of those who responded saw major improvement. This occurred within hours of administration and disappeared within a day of discontinuation. The two most common side effects were dry mouth (26%) and dry eyes (10%). More worrisome side effects were associated with higher dosing, including blurring of vision (3%) and sensation of palpitations (3%).

When patients return for their first follow-up appointment after starting a treatment plan, Dr. Hightower revisits their level of impairment and distress with hyperhidrosis. “I ask, ‘Remember that activity that you were doing before that this was getting in the way of? Are you doing that more? Do you feel like you can do that in a way that you weren’t able to do before, whether it’s playing an instrument or spending time with friends?’ ”

He also sets expectations with patients and their families with comments such as, “If this treatment does not work for you after 2 months, the next option I would consider is ...” and, “for most people there is no cure, but treatment is helpful.” He also emphasizes the importance of follow-up care, so they “come back to assess the next steps.”

Dr. Hightower reported having no financial disclosures.

dbrunk@mdedge.com

When children and adolescents first present to George Hightower, MD, PhD, with suspected primary hyperhidrosis, he tries to gauge their level of impairment and distress.

Miyuki-3

“I ask my patients directly: ‘Does this get in the way of doing things you enjoy?’ ” Dr. Hightower said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. If they say yes, he then asks, “‘What are those things that it gets in the way of?’ Also, so that I can develop a rapport with them, I ask, ‘Is it causing you to view yourself negatively?’ I also ask them how they anticipate treatment is going to change that.”

Dr. Hightower, of the departments of dermatology and pediatrics, University of California, San Diego, and a pediatric dermatologist at Rady Children’s Hospital, defined focal primary hyperhidrosis as focal, visible, excessive sweating for at least 6 months without an apparent cause, plus at least two of the following characteristics: bilateral and relatively symmetric, sweating that impairs daily activities, onset before age 25, at least one episode per week, family history of idiopathic hyperhidrosis, and focal sweating that stops during sleep.

“Based on their prominence in the popular media, armpits relative to body surface area play an oversized role in our patients’ perception of well-being,” he said. “Most of all, patients’ concerns regarding their armpits include one more of the following symptoms: smelly, sweaty, red, and itchy or painful.”

The differential diagnosis for disorders of the axilla includes irritant/contact dermatitis, folliculitis, seborrheic dermatitis, hyperhidrosis, and hidradenitis suppurativa.

Topical antiperspirants are the preferred initial treatment. “They’re widely available, inexpensive, and well-tolerated therapies,” Dr. Hightower said. Most commercially available antiperspirants contain low-dose aluminum or other metal that keeps the sweat gland ducts from opening.

“Most patients referred to me have failed to improve with over-the-counter antiperspirants or aluminum chloride 20%,” he said. “We start by reviewing the appropriate use of aluminum chloride 20%. If they’re using it appropriately and fail to achieve adequate control, I open the discussion to use glycopyrronium tosylate cloth 2.4%, applied daily. This can be cost prohibitive or not covered by insurance.” Other options include glycopyrrolate 1-6 mg daily and microwave-based procedural intervention.

In a post hoc analysis, researchers examined the efficacy and safety findings by age from two phase three randomized, controlled trials of glycopyrronium tosylate in pediatric primary axillary hyperhidrosis (Pediatr Dermatol. 2019 Jan-Feb;36[1]:89-99). It was well tolerated in the 19 patients aged 9-16 years. “No patients discontinued from the study in this age group [because of] symptomatology,” said Dr. Hightower, who was not involved with the study. “The concerns related to this medication are related to anticholinergic effects such as blurry vision and dry mouth, but overall, randomized clinical trial data support the benefit of this medication in helping patients improve the symptoms of hyperhidrosis.”

In an earlier study, researchers retrospectively studied children with hyperhidrosis who were treated with a mean dosage of 2 mg glycopyrronium tosylate daily (J Am Acad Dermatol 2012 Nov;67[5]:918-23). The average age of patients was 15 years. Most (90%) experienced some improvement and 71% of those who responded saw major improvement. This occurred within hours of administration and disappeared within a day of discontinuation. The two most common side effects were dry mouth (26%) and dry eyes (10%). More worrisome side effects were associated with higher dosing, including blurring of vision (3%) and sensation of palpitations (3%).

When patients return for their first follow-up appointment after starting a treatment plan, Dr. Hightower revisits their level of impairment and distress with hyperhidrosis. “I ask, ‘Remember that activity that you were doing before that this was getting in the way of? Are you doing that more? Do you feel like you can do that in a way that you weren’t able to do before, whether it’s playing an instrument or spending time with friends?’ ”

He also sets expectations with patients and their families with comments such as, “If this treatment does not work for you after 2 months, the next option I would consider is ...” and, “for most people there is no cure, but treatment is helpful.” He also emphasizes the importance of follow-up care, so they “come back to assess the next steps.”

Dr. Hightower reported having no financial disclosures.

dbrunk@mdedge.com

When children and adolescents first present to George Hightower, MD, PhD, with suspected primary hyperhidrosis, he tries to gauge their level of impairment and distress.

Miyuki-3

“I ask my patients directly: ‘Does this get in the way of doing things you enjoy?’ ” Dr. Hightower said during the virtual Pediatric Dermatology 2020: Best Practices and Innovations Conference. If they say yes, he then asks, “‘What are those things that it gets in the way of?’ Also, so that I can develop a rapport with them, I ask, ‘Is it causing you to view yourself negatively?’ I also ask them how they anticipate treatment is going to change that.”

Dr. Hightower, of the departments of dermatology and pediatrics, University of California, San Diego, and a pediatric dermatologist at Rady Children’s Hospital, defined focal primary hyperhidrosis as focal, visible, excessive sweating for at least 6 months without an apparent cause, plus at least two of the following characteristics: bilateral and relatively symmetric, sweating that impairs daily activities, onset before age 25, at least one episode per week, family history of idiopathic hyperhidrosis, and focal sweating that stops during sleep.

“Based on their prominence in the popular media, armpits relative to body surface area play an oversized role in our patients’ perception of well-being,” he said. “Most of all, patients’ concerns regarding their armpits include one more of the following symptoms: smelly, sweaty, red, and itchy or painful.”

The differential diagnosis for disorders of the axilla includes irritant/contact dermatitis, folliculitis, seborrheic dermatitis, hyperhidrosis, and hidradenitis suppurativa.

Topical antiperspirants are the preferred initial treatment. “They’re widely available, inexpensive, and well-tolerated therapies,” Dr. Hightower said. Most commercially available antiperspirants contain low-dose aluminum or other metal that keeps the sweat gland ducts from opening.

“Most patients referred to me have failed to improve with over-the-counter antiperspirants or aluminum chloride 20%,” he said. “We start by reviewing the appropriate use of aluminum chloride 20%. If they’re using it appropriately and fail to achieve adequate control, I open the discussion to use glycopyrronium tosylate cloth 2.4%, applied daily. This can be cost prohibitive or not covered by insurance.” Other options include glycopyrrolate 1-6 mg daily and microwave-based procedural intervention.

In a post hoc analysis, researchers examined the efficacy and safety findings by age from two phase three randomized, controlled trials of glycopyrronium tosylate in pediatric primary axillary hyperhidrosis (Pediatr Dermatol. 2019 Jan-Feb;36[1]:89-99). It was well tolerated in the 19 patients aged 9-16 years. “No patients discontinued from the study in this age group [because of] symptomatology,” said Dr. Hightower, who was not involved with the study. “The concerns related to this medication are related to anticholinergic effects such as blurry vision and dry mouth, but overall, randomized clinical trial data support the benefit of this medication in helping patients improve the symptoms of hyperhidrosis.”

In an earlier study, researchers retrospectively studied children with hyperhidrosis who were treated with a mean dosage of 2 mg glycopyrronium tosylate daily (J Am Acad Dermatol 2012 Nov;67[5]:918-23). The average age of patients was 15 years. Most (90%) experienced some improvement and 71% of those who responded saw major improvement. This occurred within hours of administration and disappeared within a day of discontinuation. The two most common side effects were dry mouth (26%) and dry eyes (10%). More worrisome side effects were associated with higher dosing, including blurring of vision (3%) and sensation of palpitations (3%).

When patients return for their first follow-up appointment after starting a treatment plan, Dr. Hightower revisits their level of impairment and distress with hyperhidrosis. “I ask, ‘Remember that activity that you were doing before that this was getting in the way of? Are you doing that more? Do you feel like you can do that in a way that you weren’t able to do before, whether it’s playing an instrument or spending time with friends?’ ”

He also sets expectations with patients and their families with comments such as, “If this treatment does not work for you after 2 months, the next option I would consider is ...” and, “for most people there is no cure, but treatment is helpful.” He also emphasizes the importance of follow-up care, so they “come back to assess the next steps.”

Dr. Hightower reported having no financial disclosures.

dbrunk@mdedge.com

Continued use of the nonsteroidal drug (NSAID) meloxicam was associated with less reported knee osteoarthritis (OA) pain at 4 weeks compared with switching to a placebo in a randomized trial.

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.

Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).

“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.

They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.

“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.

The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.

The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.

The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.

Courtesy Dr. David Walsh

“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.

Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).

“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.

“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.

Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.

“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.

He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.

“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”

Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.

It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”

Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.

SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.

Continued use of the nonsteroidal drug (NSAID) meloxicam was associated with less reported knee osteoarthritis (OA) pain at 4 weeks compared with switching to a placebo in a randomized trial.

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.

Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).

“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.

They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.

“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.

The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.

The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.

The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.

Courtesy Dr. David Walsh

“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.

Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).

“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.

“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.

Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.

“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.

He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.

“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”

Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.

It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”

Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.

SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.

Continued use of the nonsteroidal drug (NSAID) meloxicam was associated with less reported knee osteoarthritis (OA) pain at 4 weeks compared with switching to a placebo in a randomized trial.

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.

Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).

“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.

They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.

“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.

The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.

The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.

The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.

Courtesy Dr. David Walsh

“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.

Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).

“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.

“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.

Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.

“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.

He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.

“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”

Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.

It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”

Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.

SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.

Two-year outcomes following transcatheter mitral valve replacement with the Tendyne prosthesis showed durable control of mitral regurgitation, sustained improvement in quality of life and functional capacity, and a marked drop-off in the rate of hospitalization for heart failure, David W.M. Muller, MBBS, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“The outcomes can be considered very acceptable considering the advanced age and underlying comorbidities. The data show that, at 2 years, we still have excellent control of the MR [mitral regurgitation], with more than 93% of patients having no MR at all, and there were no patients with 1+ or greater MR,” said Dr. Muller, director of cardiac catheterization laboratories at St. Vincent’s Hospital in Sydney.

He presented for the first time the 2-year results for the first 100 patients enrolled in the long-term Tendyne Expanded Clinical Study. The 1-year outcomes were reported previously (J Am Coll Cardiol. 2019 Mar 26;73[11]:1250-60).

The transcatheter Tendyne mitral valve system received European marketing approval in early 2020 for commercial use in patients with severe symptomatic MR who aren’t candidates for open surgery or transcatheter mitral repair using the MitraClip device. The Tendyne remains investigational in the United States, where a large phase 3 randomized head-to-head trial of the Tendyne device and the FDA-approved MitraClip is ongoing.

At enrollment, the first 100 patients in the long-term prospective Tendyne study averaged 75 years of age, 66% were New York Heart Association functional class III or IV, 89% had secondary or mixed etiology MR, and 39% had been hospitalized for heart failure during the preceding 6 months. Ninety-two percent of participants had 4+ MR before implantation. The group’s average Society of Thoracic Surgeons Predicted Risk of Mortality score was 7.8%.

The all-cause mortality rate was 27% at 1 year and 39% at 2 years, with 87% of deaths being attributable to cardiovascular causes. At 2 years, 82% of survivors were NYHA class I or II. Their Kansas City Cardiomyopathy Questionnaire score improved by 19.1 points from an average of 49 at baseline. There was no evidence of structural valve dysfunction. Their heart failure hospitalization rate improved from 1.3 events per patient per year to 0.6 per patient-year at 1 year and 0.51 at 2 years.

Discussant Francesco Maisano, MD, was favorably impressed by the acute outcomes of transcatheter mitral valve replacement with the Tendyne device.

“There were very few procedural or in-hospital complications. Success was obtained in almost every patient. There was no procedural mortality. The 30-day mortality of 6.0% was reasonable in patients with a baseline STS score of 7.8%; that’s pretty good, I would say,” observed Dr. Maisano, professor of cardiac surgery at the University of Zürich and a pioneer of catheter-based mitral and tricuspid interventions.

However, he voiced concerns about the 35% incidence of major bleeding and 5% rate of disabling stroke at 2 years, which he deemed “pretty high.”

“This underlies the open issue of anticoagulation following these kinds of procedures. This obviously requires further work in the next years,” he said.

Dr. Muller reported receiving research grants from and serving as a consultant to Abbott, which markets the MitraClip and is developing the Tendyne system. He also serves as a consultant to Edwards Lifesciences and Medtronic. Dr. Maisano also reported serving as a consultant to several medical device companies.

bjancin@mdedge.com

Two-year outcomes following transcatheter mitral valve replacement with the Tendyne prosthesis showed durable control of mitral regurgitation, sustained improvement in quality of life and functional capacity, and a marked drop-off in the rate of hospitalization for heart failure, David W.M. Muller, MBBS, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“The outcomes can be considered very acceptable considering the advanced age and underlying comorbidities. The data show that, at 2 years, we still have excellent control of the MR [mitral regurgitation], with more than 93% of patients having no MR at all, and there were no patients with 1+ or greater MR,” said Dr. Muller, director of cardiac catheterization laboratories at St. Vincent’s Hospital in Sydney.

He presented for the first time the 2-year results for the first 100 patients enrolled in the long-term Tendyne Expanded Clinical Study. The 1-year outcomes were reported previously (J Am Coll Cardiol. 2019 Mar 26;73[11]:1250-60).

The transcatheter Tendyne mitral valve system received European marketing approval in early 2020 for commercial use in patients with severe symptomatic MR who aren’t candidates for open surgery or transcatheter mitral repair using the MitraClip device. The Tendyne remains investigational in the United States, where a large phase 3 randomized head-to-head trial of the Tendyne device and the FDA-approved MitraClip is ongoing.

At enrollment, the first 100 patients in the long-term prospective Tendyne study averaged 75 years of age, 66% were New York Heart Association functional class III or IV, 89% had secondary or mixed etiology MR, and 39% had been hospitalized for heart failure during the preceding 6 months. Ninety-two percent of participants had 4+ MR before implantation. The group’s average Society of Thoracic Surgeons Predicted Risk of Mortality score was 7.8%.

The all-cause mortality rate was 27% at 1 year and 39% at 2 years, with 87% of deaths being attributable to cardiovascular causes. At 2 years, 82% of survivors were NYHA class I or II. Their Kansas City Cardiomyopathy Questionnaire score improved by 19.1 points from an average of 49 at baseline. There was no evidence of structural valve dysfunction. Their heart failure hospitalization rate improved from 1.3 events per patient per year to 0.6 per patient-year at 1 year and 0.51 at 2 years.

Discussant Francesco Maisano, MD, was favorably impressed by the acute outcomes of transcatheter mitral valve replacement with the Tendyne device.

“There were very few procedural or in-hospital complications. Success was obtained in almost every patient. There was no procedural mortality. The 30-day mortality of 6.0% was reasonable in patients with a baseline STS score of 7.8%; that’s pretty good, I would say,” observed Dr. Maisano, professor of cardiac surgery at the University of Zürich and a pioneer of catheter-based mitral and tricuspid interventions.

However, he voiced concerns about the 35% incidence of major bleeding and 5% rate of disabling stroke at 2 years, which he deemed “pretty high.”

“This underlies the open issue of anticoagulation following these kinds of procedures. This obviously requires further work in the next years,” he said.

Dr. Muller reported receiving research grants from and serving as a consultant to Abbott, which markets the MitraClip and is developing the Tendyne system. He also serves as a consultant to Edwards Lifesciences and Medtronic. Dr. Maisano also reported serving as a consultant to several medical device companies.

bjancin@mdedge.com

Two-year outcomes following transcatheter mitral valve replacement with the Tendyne prosthesis showed durable control of mitral regurgitation, sustained improvement in quality of life and functional capacity, and a marked drop-off in the rate of hospitalization for heart failure, David W.M. Muller, MBBS, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“The outcomes can be considered very acceptable considering the advanced age and underlying comorbidities. The data show that, at 2 years, we still have excellent control of the MR [mitral regurgitation], with more than 93% of patients having no MR at all, and there were no patients with 1+ or greater MR,” said Dr. Muller, director of cardiac catheterization laboratories at St. Vincent’s Hospital in Sydney.

He presented for the first time the 2-year results for the first 100 patients enrolled in the long-term Tendyne Expanded Clinical Study. The 1-year outcomes were reported previously (J Am Coll Cardiol. 2019 Mar 26;73[11]:1250-60).

The transcatheter Tendyne mitral valve system received European marketing approval in early 2020 for commercial use in patients with severe symptomatic MR who aren’t candidates for open surgery or transcatheter mitral repair using the MitraClip device. The Tendyne remains investigational in the United States, where a large phase 3 randomized head-to-head trial of the Tendyne device and the FDA-approved MitraClip is ongoing.

At enrollment, the first 100 patients in the long-term prospective Tendyne study averaged 75 years of age, 66% were New York Heart Association functional class III or IV, 89% had secondary or mixed etiology MR, and 39% had been hospitalized for heart failure during the preceding 6 months. Ninety-two percent of participants had 4+ MR before implantation. The group’s average Society of Thoracic Surgeons Predicted Risk of Mortality score was 7.8%.

The all-cause mortality rate was 27% at 1 year and 39% at 2 years, with 87% of deaths being attributable to cardiovascular causes. At 2 years, 82% of survivors were NYHA class I or II. Their Kansas City Cardiomyopathy Questionnaire score improved by 19.1 points from an average of 49 at baseline. There was no evidence of structural valve dysfunction. Their heart failure hospitalization rate improved from 1.3 events per patient per year to 0.6 per patient-year at 1 year and 0.51 at 2 years.

Discussant Francesco Maisano, MD, was favorably impressed by the acute outcomes of transcatheter mitral valve replacement with the Tendyne device.

“There were very few procedural or in-hospital complications. Success was obtained in almost every patient. There was no procedural mortality. The 30-day mortality of 6.0% was reasonable in patients with a baseline STS score of 7.8%; that’s pretty good, I would say,” observed Dr. Maisano, professor of cardiac surgery at the University of Zürich and a pioneer of catheter-based mitral and tricuspid interventions.

However, he voiced concerns about the 35% incidence of major bleeding and 5% rate of disabling stroke at 2 years, which he deemed “pretty high.”

“This underlies the open issue of anticoagulation following these kinds of procedures. This obviously requires further work in the next years,” he said.

Dr. Muller reported receiving research grants from and serving as a consultant to Abbott, which markets the MitraClip and is developing the Tendyne system. He also serves as a consultant to Edwards Lifesciences and Medtronic. Dr. Maisano also reported serving as a consultant to several medical device companies.

bjancin@mdedge.com

From the Department of Medicine, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL.

Abstract

Objective: To review selected process-of-care interventions that can be applied both during the hospitalization and during the transitional care period to help address the persistent challenge of heart failure readmissions.

Methods: Review of the literature.

Results: Process-of-care interventions that can be implemented to reduce readmissions of heart failure patients include: accurately identifying heart failure patients; providing disease education; titrating guideline-directed medical therapy; ensuring discharge readiness; arranging close discharge follow-up; identifying and addressing social barriers; following up by telephone; using home health; and addressing comorbidities. Importantly, the heart failure hospitalization is an opportunity to set up outpatient success, and setting up feedback loops can aid in post-discharge monitoring.

Conclusion: We encourage teams to consider local capabilities when selecting processes to improve; begin by improving something small to build capacity and team morale, and continually iterate and reexamine processes, as health care systems are continually evolving.

Keywords: heart failure; process improvement; quality improvement; readmission; rehospitalization; transitional care.

The growing population of patients affected by heart failure continues to challenge health systems. The increasing prevalence is paralleled by the rising costs of managing heart failure, which are projected to grow from $30.7 billion in 2012 to $69.8 billion in 2030.¹ A significant portion of these costs relate to readmission after an index heart failure hospitalization. The statistics are staggering: for patients hospitalized with heart failure, approximately 15% to 20% are readmitted within 30 days.^2,3 Though recent temporal trends suggest a modest reduction in readmission rates, there is a concerning correlation with increasing mortality,³ and a recognition that readmission rate decreases may relate to subtle changes in coding-based risk adjustment.⁴ Despite these concerns, efforts to reduce readmissions after heart failure hospitalization command significant attention.

Process improvement methodologies may be helpful in reducing hospital readmissions. Various approaches have been employed, and results have been mixed. An analysis of 70 participating hospitals in the American Heart Association’s Get With the Guidelines initiative found that, while overall readmission rates declined by 1.0% over 3 years, only 1 hospital achieved a 20% reduction in readmission rates.⁵

It is notably difficult to reduce readmissions after heart failure hospitalization. One challenge is that patients with heart failure often have multiple comorbidities, and approximately 50% to 60% of 30-day readmissions after heart failure hospitalization arise from noncardiac causes.¹ Another challenge is that a significant fraction of readmissions in general—perhaps 75%—may not be avoidable.⁶

Recent excellent systematic reviews and meta-analyses provide comprehensive overviews of process improvement strategies that can be used to reduce readmissions after heart failure hospitalizations.^7-9 Yet despite this extensive knowledge, few reports discuss the process of actually implementing these changes: the process of process improvement. Here, we seek to not only highlight some of the most promising potential interventions to reduce heart failure readmissions, but also to discuss a process improvement framework to help engender success, using our experience as a case study. We schematize process improvement efforts as having several distinct phases (Figure 1): processes delivered during the hospitalization and prior to discharge; feedback loops set up to maintain clinical stability at home; and the postdischarge clinic visit as an opportunity to further stabilize the patient and advance the plan of care. The discussion of these interventions follows this organization.

During Hospitalization

The heart failure hospitalization can be used as an opportunity to set up outpatient success, with several goals to target during the index admission. One goal is identifying the root causes of the heart failure syndrome and correcting those root causes, if possible. For example, patients in whom the heart failure syndrome is secondary to valvular heart disease may benefit from transcatheter aortic valve replacement.¹⁰ Another clinical goal is decongesting the patient, which is associated with lower readmission rates.^11,12 These goals focus on the medical aspects of heart failure care. However, beyond these medical aspects, a patient must be equipped to successfully manage the disease at home.

To support medical and nonmedical interventions for hospitalized heart failure patients, a critical first step is identifying patients with heart failure. This accomplishes at least 2 objectives. First, early identification allows early initiation of interventions, such as heart failure education and social work evaluation. Early initiation of these interventions allows sufficient time during the hospitalization to make meaningful progress on these fronts. Second, early identification allows an opportunity for the delivery of cardiology specialty care, which may help with identifying and correcting root causes of the heart failure syndrome. Such access to cardiology has been shown to improve inpatient mortality and readmission rates.¹³

In smaller hospitals, identification of patients with heart failure can be as simple as reviewing overnight admissions. More advanced strategies, such as screeners based on brain natriuretic peptide (BNP) levels and administration of intravenous diuretics, can be employed.^14,15 In the near future, deep learning-based natural language processing will be applied to mine full-text data in the electronic health record to identify heart failure hospitalizations.¹⁶

In the hospital, patients can also receive education about heart failure disease management. This education is a cornerstone of reducing heart failure readmissions. A recent systematic review of nurse education interventions demonstrated reductions in readmissions, hospitalizations, and costs.¹⁷ However, the efficacy of heart failure education hinges on many other variables. For patients to adhere to water restriction and daily weights, for example, there must also be patient understanding, compliance, and accessibility to providers to recommend how to strike the fluid balance. Education is therefore necessary, but not sufficient, for setting up outpatient success.

The hospitalization also represents an important time to start or uptitrate guideline-directed medical therapy (GDMT) for heart failure. Doing so takes advantage of an important opportunity to reduce the risk of readmission and even reverse the disease process.¹⁸ Uptitration of GDMT in patients with heart failure with reduced ejection fraction is associated with a decreased risk of mortality, while discontinuation is associated with an increased risk of mortality.¹⁹ However, recent registry data indicate that intensity of GDMT is just as likely to be decreased as increased during the hospitalization.²⁰ Nevertheless, predischarge initiation of medications may be associated with higher attained doses in follow-up.²¹

Preparing for Discharge

Preparing a patient for discharge after a heart failure hospitalization involves stabilizing the medical condition as well as ensuring that the patient and caregivers have the medication, equipment, and self-care resources at home necessary to manage the condition. Several frameworks have been put forth to help care teams analyze a patient’s readiness for discharge. One is the B-PREPARED score,²² a validated instrument to discriminate among patients with regard to their readiness to discharge from the hospital. This instrument highlights the importance of several key factors that should be addressed during the discharge process, including counseling and written instructions about medications and their side effects; information about equipment needs and community resources; and information on activity levels and restrictions. Nurse education and discharge coordination can improve patients’ perception of discharge readiness,²³ although whether this discharge readiness translates into improved readmission rates appears to depend on the specific follow-up intervention design.⁹

Prior to discharge, it is important to arrange postdischarge follow-up appointments, as emphasized by the American College of Cardiology/American Heart Association (ACC/AHA) guidelines.²⁴ The use of nurse navigators can help with planning follow-up appointments. For example, the ACC Patient Navigator Program was applied in a single-center study of 120 patients randomized to the program versus usual care.²⁵ This study found a significant increase in patient education and follow-up appointments compared to usual care, and a numerical decrease in hospital readmissions, although the finding was not statistically significant.²⁵

A third critical component of preparing for discharge is identifying and addressing social barriers to care. In a study of patients stratified by household income, patients in the lowest income quartile had a higher readmission rate than patients in the highest income quartile.²⁶ Poverty also correlates with heart failure mortality.²⁷ Social factors play an important role in many aspects of patients’ ability to manage their health, including self-care, medication adherence, and ability to follow-up. Identifying these social factors prior to discharge is the first step to addressing them. While few studies specifically address the role of social workers in the management of heart failure care, the general medical literature suggests that social workers embedded in transitional care teams can augment readmission reduction efforts.²⁸

After Discharge

Patients recently discharged from the hospital who have not yet attended their postdischarge appointment are in an incredibly vulnerable phase of care. Patients who are discharged from the hospital may not yet be connected with outpatient care. During this initial transitional care period, feedback loops involving patient communication back to the clinic, and clinic communication back to the patient, are critical to helping patients remain stable. For example, consider monitoring weights daily after hospital discharge. A patient at home can report increasing weights to a provider, who can then recommend an increased dose of diuretic. The patient can complete the feedback loop by taking the extra medication and monitoring the return of weight back to normal.

While daily weight monitoring is a simple process improvement that relies on the principle of establishing feedback loops, many other strategies exist. One commonly employed tool is the postdischarge telephone follow-up call, which is often coupled with other interventions in a comprehensive care bundle.⁸ During the telephone call, several process-of-care defects can be corrected, including missing medications or missing information on appointment times.

Beyond the telephone, newer technologies show promise for helping develop feedback loops for patients at home. One such technology is telemonitoring, whereby physiologic information such as weight, heart rate, and blood pressure is collected and sent back to a monitoring center. While the principle holds promise, several studies have not demonstrated significantly different outcomes as compared to usual care.^13,29 Another promising technology is the CardioMEMS device (Abbott, Inc., Atlanta, GA), which can remotely transmit the pulmonary artery pressure, a physiologic signal which correlates with volume overload. There is now strong evidence supporting the efficacy of pulmonary artery pressure–guided heart failure management.^30,31

Finally, home visits can be an efficient way to communicate symptoms, enable clinical assessment, and provide recommendations. One program that implemented home visits, 24-hour nurses available by call, and telephone follow-up showed a statistically significant reduction in readmissions.³² Furthermore, a meta-analysis of randomized controlled trials comparing home health to usual care showed decreased readmissions and mortality.³³ The efficacy may be in strengthening the feedback loop—home care improves compliance with weight monitoring, fluid restriction, and medications.³⁴ These studies provide a strong rationale for the benefits of home health in stabilizing heart failure patients postdischarge. Indeed, nurse home visits were 1 of the 2 process interventions in a Cochrane review of randomized controlled trials that were shown to statistically significantly decrease readmissions and mortality.⁹ These data underscore the importance of feedback loops for helping ensure patients are clinically stable.

Postdischarge Follow-Up Clinic Visit

The first clinic appointment postdischarge is an important check-in to help advance patient care. Several key tasks can be achieved during the postdischarge visit. First, the patient can be clinically stabilized by adjusting diuretic therapy. If the patient is clinically stable, GDMT can be uptitrated. Second, education around symptoms, medications, diet, and exercise can be reinforced. Finally, clinicians can help connect patients to other members of the multidisciplinary care team, including specialist care, home health, or cardiac rehabilitation.

Achieving 7-day follow-up visits after discharge has been a point of emphasis in national guidelines.²⁴ The ACC promotes a “See You in 7” challenge, advising that all patients discharged with a diagnosis of heart failure have a follow-up appointment within 7 days. Yet based on the latest available data, arrival rates to the postdischarge clinic are dismal, hovering around 30%.³⁵ In a multicenter observational study of hospitals participating in the “See You in 7” collaborative, hospitals were able to increase their 7-day follow-up appointment rates by 2% to 3%, and also noted an absolute decrease in readmission rates by 1% to 2%.³⁶ We have demonstrated, using a mathematical approach called queuing theory, that discharge appointment wait times and clinic access can be significantly improved by providing a modest capacity buffer to clinic availability.³⁷ Those interested in applying this model to their own clinical practice may do so with a free online calculator at http://hfresearch.org.

Another important aspect of postdischarge follow-up is appropriate management of the comorbidity burden, which, as noted, is often significant in patients hospitalized with heart failure.³⁸ For instance, in recent cohorts of hospitalized heart failure patients, the incidence of hypertension was 78%, coronary artery disease was more than 50%, atrial fibrillation was more than 40%, and diabetes was nearly 40%.³⁹ Given this burden of comorbidity, it is not surprising that only 35% of readmissions after an index heart failure hospitalization are for recurrent heart failure.⁴⁰ Coordinating care among primary care physicians and relevant subspecialists is thus essential. Phone calls and secure electronic messages are very helpful in achieving this. There is increasing interest in more nimble care models, such as the patient-centered specialty practice⁴¹ or the dyspnea clinic, to help bring coordinated resources to the patient.⁴²

Process of Process Improvement: Our Experiences

The previous sections outline a series of potential process improvements clinical teams and health systems can implement to impact heart failure readmissions. A plan on paper, however, does not equal a plan in actuality. How does one go about implementing these changes? We offer our local experience starting a heart failure transitional care program as a case study, then draw lessons learned as a set of practical tips for local teams to employ. What we hope to highlight is that there is a large difference between a completed process for transitional care of heart failure patients, and the process of developing that process itself. The former is the hardware, the latter is the software. The latter does not typically get highlighted, but it is absolutely critical to unlocking the capabilities of a team and the institution.

In 2015, Northwestern Memorial Hospital adopted a novel payment arrangement from the Center for Medicare and Medicaid Services for Medicare patients being discharged from the hospital with heart failure. Known as Bundled Payments for Care Improvement,⁴³ this bundled payment model incentivized Northwestern Memorial Hospital charge, principally by reducing hospital readmissions and by collaborating with skilled nursing facilities to control length of stay.

We approached this problem by drawing on the available literature,^44,45 and by first creating a schematic of our high-level approach, which comprised 3 major elements (Figure 2): identification of hospitalized heart failure patients, delivery of a care bundle to hospitalized heart failure patients in hospital, and coordinating postdischarge care, centered on a telephone call and a postdischarge visit.

We then proceeded by building out, in stepwise fashion, each component of our value chain, using Agile techniques as a guiding principle.⁴⁶ Agile, a productivity and process improvement mindset with roots in software development, emphasizes tackling 1 problem at a time, building out new features sequentially and completely, recognizing that the end user does not derive value from a program until new functionality is available for use. Rather than wholesale monolithic change, Agile emphasizes rapid iteration, prototyping, and discarding innovations not found to be helpful. The notion is to stand up new, incremental features rapidly, with each incremental improvement delivering value and helping to accelerate overall change.

Our experience building a robust way to identify heart failure cases is a good example of Agile process improvement in practice. At our hospital, identification of patients with heart failure was a challenge because more than half of heart failure patients are admitted to noncardiology floors. We developed a simple electronic health record query to detect heart failure patients, relying on parameters such as administration of intravenous diuretic or levels of BNP exceeding 100 ng/dL. We deployed this query, finding very high sensitivity for detection of heart failure patients.¹⁴ Patients found to have heart failure were then populated into a list in the electronic health record, which made patients’ heart failure status visible to all members of the health care team. Using this list, we were able to automate several processes necessary for heart failure care. For example, the list made it possible for cardiologists to know if there was a patient who perhaps needed cardiology consultation. Nurse navigators could know which patients needed heart failure education without having to be actively consulted by the admitting team. The same nurse navigators could then know upon discharge which patients needed a follow-up telephone call at 48 hours.

This list of heart failure patients was the end product, which was built through prototyping and iteration. For example, with our initial BNP cutoff of 300 ng/dL, we recognized we were missing several cases, and lowered the cutoff for the screener to 100 ng/dL. When we were satisfied this process was working well, we moved on to the next problem to tackle, avoiding trying to work on too many things at once. By doing so, we were able to focus our process improvement resources on 1 problem at a time, building up a suite of interventions. For our hospital, we settled on a bundle of interventions, captured by the mnemonic HEART:

Heart doctor sees patient in the hospital

Education about heart failure in the hospital

After-visit summary with 7-day appointment printed

Reach out to the patient by telephone within 72 hours

Treat the patient in clinic by the 7-day visit

Conclusion

We would like to emphasize that the elements of our heart failure readmissions interventions were not all put in place at once. This was an iterative process that proceeded in a stepwise fashion, with each step improving the care of our patients. We learned a number of lessons from our experience. First, we would advise that teams not try to do everything. One program simply cannot implement all possible readmission reduction interventions, and certainly not all at once. Trade-offs should be made, and interventions more likely to succeed in the local environment should be prioritized. In addition, interventions that do not fit and do not create synergy with the local practice environment should not be pursued.

Second, we would advise teams to start small, tackling a known problem in heart failure transitions of care first. This initial intuition is often right. An example might be improving 7-day appointments upon discharge. Starting with a problem that can be tackled builds process improvement muscle and improves team morale. Third, we would advise teams to consistently iterate on designs, tweaking and improving performance. Complex organizations always evolve; processes that work 1 year may fail the next because another element of the organization may have changed.

Finally, the framework presented in Figure 1 may be helpful in guiding how to structure interventions. Considering interventions to be delivered in the hospital, interventions to be delivered in the clinic, and how to set up feedback loops to support patients as outpatients help develop a comprehensive heart failure readmissions reduction program.

Corresponding author: R. Kannan Mutharasan, MD, Northwestern University Feinberg School of Medicine, 676 North Saint Clair St., Arkes Pavilion, Suite 7-038, Chicago, IL 60611;kannanm@northwestern.edu.

Financial disclosures: None.

From the Department of Medicine, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL.

Abstract

Objective: To review selected process-of-care interventions that can be applied both during the hospitalization and during the transitional care period to help address the persistent challenge of heart failure readmissions.

Methods: Review of the literature.

Results: Process-of-care interventions that can be implemented to reduce readmissions of heart failure patients include: accurately identifying heart failure patients; providing disease education; titrating guideline-directed medical therapy; ensuring discharge readiness; arranging close discharge follow-up; identifying and addressing social barriers; following up by telephone; using home health; and addressing comorbidities. Importantly, the heart failure hospitalization is an opportunity to set up outpatient success, and setting up feedback loops can aid in post-discharge monitoring.

Conclusion: We encourage teams to consider local capabilities when selecting processes to improve; begin by improving something small to build capacity and team morale, and continually iterate and reexamine processes, as health care systems are continually evolving.

Keywords: heart failure; process improvement; quality improvement; readmission; rehospitalization; transitional care.

The growing population of patients affected by heart failure continues to challenge health systems. The increasing prevalence is paralleled by the rising costs of managing heart failure, which are projected to grow from $30.7 billion in 2012 to $69.8 billion in 2030.¹ A significant portion of these costs relate to readmission after an index heart failure hospitalization. The statistics are staggering: for patients hospitalized with heart failure, approximately 15% to 20% are readmitted within 30 days.^2,3 Though recent temporal trends suggest a modest reduction in readmission rates, there is a concerning correlation with increasing mortality,³ and a recognition that readmission rate decreases may relate to subtle changes in coding-based risk adjustment.⁴ Despite these concerns, efforts to reduce readmissions after heart failure hospitalization command significant attention.

Process improvement methodologies may be helpful in reducing hospital readmissions. Various approaches have been employed, and results have been mixed. An analysis of 70 participating hospitals in the American Heart Association’s Get With the Guidelines initiative found that, while overall readmission rates declined by 1.0% over 3 years, only 1 hospital achieved a 20% reduction in readmission rates.⁵

It is notably difficult to reduce readmissions after heart failure hospitalization. One challenge is that patients with heart failure often have multiple comorbidities, and approximately 50% to 60% of 30-day readmissions after heart failure hospitalization arise from noncardiac causes.¹ Another challenge is that a significant fraction of readmissions in general—perhaps 75%—may not be avoidable.⁶

Recent excellent systematic reviews and meta-analyses provide comprehensive overviews of process improvement strategies that can be used to reduce readmissions after heart failure hospitalizations.^7-9 Yet despite this extensive knowledge, few reports discuss the process of actually implementing these changes: the process of process improvement. Here, we seek to not only highlight some of the most promising potential interventions to reduce heart failure readmissions, but also to discuss a process improvement framework to help engender success, using our experience as a case study. We schematize process improvement efforts as having several distinct phases (Figure 1): processes delivered during the hospitalization and prior to discharge; feedback loops set up to maintain clinical stability at home; and the postdischarge clinic visit as an opportunity to further stabilize the patient and advance the plan of care. The discussion of these interventions follows this organization.

During Hospitalization

The heart failure hospitalization can be used as an opportunity to set up outpatient success, with several goals to target during the index admission. One goal is identifying the root causes of the heart failure syndrome and correcting those root causes, if possible. For example, patients in whom the heart failure syndrome is secondary to valvular heart disease may benefit from transcatheter aortic valve replacement.¹⁰ Another clinical goal is decongesting the patient, which is associated with lower readmission rates.^11,12 These goals focus on the medical aspects of heart failure care. However, beyond these medical aspects, a patient must be equipped to successfully manage the disease at home.

To support medical and nonmedical interventions for hospitalized heart failure patients, a critical first step is identifying patients with heart failure. This accomplishes at least 2 objectives. First, early identification allows early initiation of interventions, such as heart failure education and social work evaluation. Early initiation of these interventions allows sufficient time during the hospitalization to make meaningful progress on these fronts. Second, early identification allows an opportunity for the delivery of cardiology specialty care, which may help with identifying and correcting root causes of the heart failure syndrome. Such access to cardiology has been shown to improve inpatient mortality and readmission rates.¹³

In smaller hospitals, identification of patients with heart failure can be as simple as reviewing overnight admissions. More advanced strategies, such as screeners based on brain natriuretic peptide (BNP) levels and administration of intravenous diuretics, can be employed.^14,15 In the near future, deep learning-based natural language processing will be applied to mine full-text data in the electronic health record to identify heart failure hospitalizations.¹⁶

In the hospital, patients can also receive education about heart failure disease management. This education is a cornerstone of reducing heart failure readmissions. A recent systematic review of nurse education interventions demonstrated reductions in readmissions, hospitalizations, and costs.¹⁷ However, the efficacy of heart failure education hinges on many other variables. For patients to adhere to water restriction and daily weights, for example, there must also be patient understanding, compliance, and accessibility to providers to recommend how to strike the fluid balance. Education is therefore necessary, but not sufficient, for setting up outpatient success.

The hospitalization also represents an important time to start or uptitrate guideline-directed medical therapy (GDMT) for heart failure. Doing so takes advantage of an important opportunity to reduce the risk of readmission and even reverse the disease process.¹⁸ Uptitration of GDMT in patients with heart failure with reduced ejection fraction is associated with a decreased risk of mortality, while discontinuation is associated with an increased risk of mortality.¹⁹ However, recent registry data indicate that intensity of GDMT is just as likely to be decreased as increased during the hospitalization.²⁰ Nevertheless, predischarge initiation of medications may be associated with higher attained doses in follow-up.²¹

Preparing for Discharge

Preparing a patient for discharge after a heart failure hospitalization involves stabilizing the medical condition as well as ensuring that the patient and caregivers have the medication, equipment, and self-care resources at home necessary to manage the condition. Several frameworks have been put forth to help care teams analyze a patient’s readiness for discharge. One is the B-PREPARED score,²² a validated instrument to discriminate among patients with regard to their readiness to discharge from the hospital. This instrument highlights the importance of several key factors that should be addressed during the discharge process, including counseling and written instructions about medications and their side effects; information about equipment needs and community resources; and information on activity levels and restrictions. Nurse education and discharge coordination can improve patients’ perception of discharge readiness,²³ although whether this discharge readiness translates into improved readmission rates appears to depend on the specific follow-up intervention design.⁹

Prior to discharge, it is important to arrange postdischarge follow-up appointments, as emphasized by the American College of Cardiology/American Heart Association (ACC/AHA) guidelines.²⁴ The use of nurse navigators can help with planning follow-up appointments. For example, the ACC Patient Navigator Program was applied in a single-center study of 120 patients randomized to the program versus usual care.²⁵ This study found a significant increase in patient education and follow-up appointments compared to usual care, and a numerical decrease in hospital readmissions, although the finding was not statistically significant.²⁵

A third critical component of preparing for discharge is identifying and addressing social barriers to care. In a study of patients stratified by household income, patients in the lowest income quartile had a higher readmission rate than patients in the highest income quartile.²⁶ Poverty also correlates with heart failure mortality.²⁷ Social factors play an important role in many aspects of patients’ ability to manage their health, including self-care, medication adherence, and ability to follow-up. Identifying these social factors prior to discharge is the first step to addressing them. While few studies specifically address the role of social workers in the management of heart failure care, the general medical literature suggests that social workers embedded in transitional care teams can augment readmission reduction efforts.²⁸

After Discharge

Patients recently discharged from the hospital who have not yet attended their postdischarge appointment are in an incredibly vulnerable phase of care. Patients who are discharged from the hospital may not yet be connected with outpatient care. During this initial transitional care period, feedback loops involving patient communication back to the clinic, and clinic communication back to the patient, are critical to helping patients remain stable. For example, consider monitoring weights daily after hospital discharge. A patient at home can report increasing weights to a provider, who can then recommend an increased dose of diuretic. The patient can complete the feedback loop by taking the extra medication and monitoring the return of weight back to normal.

While daily weight monitoring is a simple process improvement that relies on the principle of establishing feedback loops, many other strategies exist. One commonly employed tool is the postdischarge telephone follow-up call, which is often coupled with other interventions in a comprehensive care bundle.⁸ During the telephone call, several process-of-care defects can be corrected, including missing medications or missing information on appointment times.

Beyond the telephone, newer technologies show promise for helping develop feedback loops for patients at home. One such technology is telemonitoring, whereby physiologic information such as weight, heart rate, and blood pressure is collected and sent back to a monitoring center. While the principle holds promise, several studies have not demonstrated significantly different outcomes as compared to usual care.^13,29 Another promising technology is the CardioMEMS device (Abbott, Inc., Atlanta, GA), which can remotely transmit the pulmonary artery pressure, a physiologic signal which correlates with volume overload. There is now strong evidence supporting the efficacy of pulmonary artery pressure–guided heart failure management.^30,31

Finally, home visits can be an efficient way to communicate symptoms, enable clinical assessment, and provide recommendations. One program that implemented home visits, 24-hour nurses available by call, and telephone follow-up showed a statistically significant reduction in readmissions.³² Furthermore, a meta-analysis of randomized controlled trials comparing home health to usual care showed decreased readmissions and mortality.³³ The efficacy may be in strengthening the feedback loop—home care improves compliance with weight monitoring, fluid restriction, and medications.³⁴ These studies provide a strong rationale for the benefits of home health in stabilizing heart failure patients postdischarge. Indeed, nurse home visits were 1 of the 2 process interventions in a Cochrane review of randomized controlled trials that were shown to statistically significantly decrease readmissions and mortality.⁹ These data underscore the importance of feedback loops for helping ensure patients are clinically stable.

Postdischarge Follow-Up Clinic Visit

The first clinic appointment postdischarge is an important check-in to help advance patient care. Several key tasks can be achieved during the postdischarge visit. First, the patient can be clinically stabilized by adjusting diuretic therapy. If the patient is clinically stable, GDMT can be uptitrated. Second, education around symptoms, medications, diet, and exercise can be reinforced. Finally, clinicians can help connect patients to other members of the multidisciplinary care team, including specialist care, home health, or cardiac rehabilitation.

Achieving 7-day follow-up visits after discharge has been a point of emphasis in national guidelines.²⁴ The ACC promotes a “See You in 7” challenge, advising that all patients discharged with a diagnosis of heart failure have a follow-up appointment within 7 days. Yet based on the latest available data, arrival rates to the postdischarge clinic are dismal, hovering around 30%.³⁵ In a multicenter observational study of hospitals participating in the “See You in 7” collaborative, hospitals were able to increase their 7-day follow-up appointment rates by 2% to 3%, and also noted an absolute decrease in readmission rates by 1% to 2%.³⁶ We have demonstrated, using a mathematical approach called queuing theory, that discharge appointment wait times and clinic access can be significantly improved by providing a modest capacity buffer to clinic availability.³⁷ Those interested in applying this model to their own clinical practice may do so with a free online calculator at http://hfresearch.org.

Another important aspect of postdischarge follow-up is appropriate management of the comorbidity burden, which, as noted, is often significant in patients hospitalized with heart failure.³⁸ For instance, in recent cohorts of hospitalized heart failure patients, the incidence of hypertension was 78%, coronary artery disease was more than 50%, atrial fibrillation was more than 40%, and diabetes was nearly 40%.³⁹ Given this burden of comorbidity, it is not surprising that only 35% of readmissions after an index heart failure hospitalization are for recurrent heart failure.⁴⁰ Coordinating care among primary care physicians and relevant subspecialists is thus essential. Phone calls and secure electronic messages are very helpful in achieving this. There is increasing interest in more nimble care models, such as the patient-centered specialty practice⁴¹ or the dyspnea clinic, to help bring coordinated resources to the patient.⁴²

Process of Process Improvement: Our Experiences

The previous sections outline a series of potential process improvements clinical teams and health systems can implement to impact heart failure readmissions. A plan on paper, however, does not equal a plan in actuality. How does one go about implementing these changes? We offer our local experience starting a heart failure transitional care program as a case study, then draw lessons learned as a set of practical tips for local teams to employ. What we hope to highlight is that there is a large difference between a completed process for transitional care of heart failure patients, and the process of developing that process itself. The former is the hardware, the latter is the software. The latter does not typically get highlighted, but it is absolutely critical to unlocking the capabilities of a team and the institution.

In 2015, Northwestern Memorial Hospital adopted a novel payment arrangement from the Center for Medicare and Medicaid Services for Medicare patients being discharged from the hospital with heart failure. Known as Bundled Payments for Care Improvement,⁴³ this bundled payment model incentivized Northwestern Memorial Hospital charge, principally by reducing hospital readmissions and by collaborating with skilled nursing facilities to control length of stay.

We approached this problem by drawing on the available literature,^44,45 and by first creating a schematic of our high-level approach, which comprised 3 major elements (Figure 2): identification of hospitalized heart failure patients, delivery of a care bundle to hospitalized heart failure patients in hospital, and coordinating postdischarge care, centered on a telephone call and a postdischarge visit.

We then proceeded by building out, in stepwise fashion, each component of our value chain, using Agile techniques as a guiding principle.⁴⁶ Agile, a productivity and process improvement mindset with roots in software development, emphasizes tackling 1 problem at a time, building out new features sequentially and completely, recognizing that the end user does not derive value from a program until new functionality is available for use. Rather than wholesale monolithic change, Agile emphasizes rapid iteration, prototyping, and discarding innovations not found to be helpful. The notion is to stand up new, incremental features rapidly, with each incremental improvement delivering value and helping to accelerate overall change.

Our experience building a robust way to identify heart failure cases is a good example of Agile process improvement in practice. At our hospital, identification of patients with heart failure was a challenge because more than half of heart failure patients are admitted to noncardiology floors. We developed a simple electronic health record query to detect heart failure patients, relying on parameters such as administration of intravenous diuretic or levels of BNP exceeding 100 ng/dL. We deployed this query, finding very high sensitivity for detection of heart failure patients.¹⁴ Patients found to have heart failure were then populated into a list in the electronic health record, which made patients’ heart failure status visible to all members of the health care team. Using this list, we were able to automate several processes necessary for heart failure care. For example, the list made it possible for cardiologists to know if there was a patient who perhaps needed cardiology consultation. Nurse navigators could know which patients needed heart failure education without having to be actively consulted by the admitting team. The same nurse navigators could then know upon discharge which patients needed a follow-up telephone call at 48 hours.

This list of heart failure patients was the end product, which was built through prototyping and iteration. For example, with our initial BNP cutoff of 300 ng/dL, we recognized we were missing several cases, and lowered the cutoff for the screener to 100 ng/dL. When we were satisfied this process was working well, we moved on to the next problem to tackle, avoiding trying to work on too many things at once. By doing so, we were able to focus our process improvement resources on 1 problem at a time, building up a suite of interventions. For our hospital, we settled on a bundle of interventions, captured by the mnemonic HEART:

Heart doctor sees patient in the hospital

Education about heart failure in the hospital

After-visit summary with 7-day appointment printed

Reach out to the patient by telephone within 72 hours

Treat the patient in clinic by the 7-day visit

Conclusion

We would like to emphasize that the elements of our heart failure readmissions interventions were not all put in place at once. This was an iterative process that proceeded in a stepwise fashion, with each step improving the care of our patients. We learned a number of lessons from our experience. First, we would advise that teams not try to do everything. One program simply cannot implement all possible readmission reduction interventions, and certainly not all at once. Trade-offs should be made, and interventions more likely to succeed in the local environment should be prioritized. In addition, interventions that do not fit and do not create synergy with the local practice environment should not be pursued.

Second, we would advise teams to start small, tackling a known problem in heart failure transitions of care first. This initial intuition is often right. An example might be improving 7-day appointments upon discharge. Starting with a problem that can be tackled builds process improvement muscle and improves team morale. Third, we would advise teams to consistently iterate on designs, tweaking and improving performance. Complex organizations always evolve; processes that work 1 year may fail the next because another element of the organization may have changed.

Finally, the framework presented in Figure 1 may be helpful in guiding how to structure interventions. Considering interventions to be delivered in the hospital, interventions to be delivered in the clinic, and how to set up feedback loops to support patients as outpatients help develop a comprehensive heart failure readmissions reduction program.

Corresponding author: R. Kannan Mutharasan, MD, Northwestern University Feinberg School of Medicine, 676 North Saint Clair St., Arkes Pavilion, Suite 7-038, Chicago, IL 60611;kannanm@northwestern.edu.

Financial disclosures: None.

From the Department of Medicine, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL.

Abstract

Objective: To review selected process-of-care interventions that can be applied both during the hospitalization and during the transitional care period to help address the persistent challenge of heart failure readmissions.

Methods: Review of the literature.

Results: Process-of-care interventions that can be implemented to reduce readmissions of heart failure patients include: accurately identifying heart failure patients; providing disease education; titrating guideline-directed medical therapy; ensuring discharge readiness; arranging close discharge follow-up; identifying and addressing social barriers; following up by telephone; using home health; and addressing comorbidities. Importantly, the heart failure hospitalization is an opportunity to set up outpatient success, and setting up feedback loops can aid in post-discharge monitoring.

Conclusion: We encourage teams to consider local capabilities when selecting processes to improve; begin by improving something small to build capacity and team morale, and continually iterate and reexamine processes, as health care systems are continually evolving.

Keywords: heart failure; process improvement; quality improvement; readmission; rehospitalization; transitional care.

The growing population of patients affected by heart failure continues to challenge health systems. The increasing prevalence is paralleled by the rising costs of managing heart failure, which are projected to grow from $30.7 billion in 2012 to $69.8 billion in 2030.¹ A significant portion of these costs relate to readmission after an index heart failure hospitalization. The statistics are staggering: for patients hospitalized with heart failure, approximately 15% to 20% are readmitted within 30 days.^2,3 Though recent temporal trends suggest a modest reduction in readmission rates, there is a concerning correlation with increasing mortality,³ and a recognition that readmission rate decreases may relate to subtle changes in coding-based risk adjustment.⁴ Despite these concerns, efforts to reduce readmissions after heart failure hospitalization command significant attention.

Process improvement methodologies may be helpful in reducing hospital readmissions. Various approaches have been employed, and results have been mixed. An analysis of 70 participating hospitals in the American Heart Association’s Get With the Guidelines initiative found that, while overall readmission rates declined by 1.0% over 3 years, only 1 hospital achieved a 20% reduction in readmission rates.⁵

It is notably difficult to reduce readmissions after heart failure hospitalization. One challenge is that patients with heart failure often have multiple comorbidities, and approximately 50% to 60% of 30-day readmissions after heart failure hospitalization arise from noncardiac causes.¹ Another challenge is that a significant fraction of readmissions in general—perhaps 75%—may not be avoidable.⁶

Recent excellent systematic reviews and meta-analyses provide comprehensive overviews of process improvement strategies that can be used to reduce readmissions after heart failure hospitalizations.^7-9 Yet despite this extensive knowledge, few reports discuss the process of actually implementing these changes: the process of process improvement. Here, we seek to not only highlight some of the most promising potential interventions to reduce heart failure readmissions, but also to discuss a process improvement framework to help engender success, using our experience as a case study. We schematize process improvement efforts as having several distinct phases (Figure 1): processes delivered during the hospitalization and prior to discharge; feedback loops set up to maintain clinical stability at home; and the postdischarge clinic visit as an opportunity to further stabilize the patient and advance the plan of care. The discussion of these interventions follows this organization.

During Hospitalization

The heart failure hospitalization can be used as an opportunity to set up outpatient success, with several goals to target during the index admission. One goal is identifying the root causes of the heart failure syndrome and correcting those root causes, if possible. For example, patients in whom the heart failure syndrome is secondary to valvular heart disease may benefit from transcatheter aortic valve replacement.¹⁰ Another clinical goal is decongesting the patient, which is associated with lower readmission rates.^11,12 These goals focus on the medical aspects of heart failure care. However, beyond these medical aspects, a patient must be equipped to successfully manage the disease at home.

To support medical and nonmedical interventions for hospitalized heart failure patients, a critical first step is identifying patients with heart failure. This accomplishes at least 2 objectives. First, early identification allows early initiation of interventions, such as heart failure education and social work evaluation. Early initiation of these interventions allows sufficient time during the hospitalization to make meaningful progress on these fronts. Second, early identification allows an opportunity for the delivery of cardiology specialty care, which may help with identifying and correcting root causes of the heart failure syndrome. Such access to cardiology has been shown to improve inpatient mortality and readmission rates.¹³

In smaller hospitals, identification of patients with heart failure can be as simple as reviewing overnight admissions. More advanced strategies, such as screeners based on brain natriuretic peptide (BNP) levels and administration of intravenous diuretics, can be employed.^14,15 In the near future, deep learning-based natural language processing will be applied to mine full-text data in the electronic health record to identify heart failure hospitalizations.¹⁶

In the hospital, patients can also receive education about heart failure disease management. This education is a cornerstone of reducing heart failure readmissions. A recent systematic review of nurse education interventions demonstrated reductions in readmissions, hospitalizations, and costs.¹⁷ However, the efficacy of heart failure education hinges on many other variables. For patients to adhere to water restriction and daily weights, for example, there must also be patient understanding, compliance, and accessibility to providers to recommend how to strike the fluid balance. Education is therefore necessary, but not sufficient, for setting up outpatient success.

The hospitalization also represents an important time to start or uptitrate guideline-directed medical therapy (GDMT) for heart failure. Doing so takes advantage of an important opportunity to reduce the risk of readmission and even reverse the disease process.¹⁸ Uptitration of GDMT in patients with heart failure with reduced ejection fraction is associated with a decreased risk of mortality, while discontinuation is associated with an increased risk of mortality.¹⁹ However, recent registry data indicate that intensity of GDMT is just as likely to be decreased as increased during the hospitalization.²⁰ Nevertheless, predischarge initiation of medications may be associated with higher attained doses in follow-up.²¹

Preparing for Discharge

Preparing a patient for discharge after a heart failure hospitalization involves stabilizing the medical condition as well as ensuring that the patient and caregivers have the medication, equipment, and self-care resources at home necessary to manage the condition. Several frameworks have been put forth to help care teams analyze a patient’s readiness for discharge. One is the B-PREPARED score,²² a validated instrument to discriminate among patients with regard to their readiness to discharge from the hospital. This instrument highlights the importance of several key factors that should be addressed during the discharge process, including counseling and written instructions about medications and their side effects; information about equipment needs and community resources; and information on activity levels and restrictions. Nurse education and discharge coordination can improve patients’ perception of discharge readiness,²³ although whether this discharge readiness translates into improved readmission rates appears to depend on the specific follow-up intervention design.⁹

Prior to discharge, it is important to arrange postdischarge follow-up appointments, as emphasized by the American College of Cardiology/American Heart Association (ACC/AHA) guidelines.²⁴ The use of nurse navigators can help with planning follow-up appointments. For example, the ACC Patient Navigator Program was applied in a single-center study of 120 patients randomized to the program versus usual care.²⁵ This study found a significant increase in patient education and follow-up appointments compared to usual care, and a numerical decrease in hospital readmissions, although the finding was not statistically significant.²⁵

A third critical component of preparing for discharge is identifying and addressing social barriers to care. In a study of patients stratified by household income, patients in the lowest income quartile had a higher readmission rate than patients in the highest income quartile.²⁶ Poverty also correlates with heart failure mortality.²⁷ Social factors play an important role in many aspects of patients’ ability to manage their health, including self-care, medication adherence, and ability to follow-up. Identifying these social factors prior to discharge is the first step to addressing them. While few studies specifically address the role of social workers in the management of heart failure care, the general medical literature suggests that social workers embedded in transitional care teams can augment readmission reduction efforts.²⁸

After Discharge

Patients recently discharged from the hospital who have not yet attended their postdischarge appointment are in an incredibly vulnerable phase of care. Patients who are discharged from the hospital may not yet be connected with outpatient care. During this initial transitional care period, feedback loops involving patient communication back to the clinic, and clinic communication back to the patient, are critical to helping patients remain stable. For example, consider monitoring weights daily after hospital discharge. A patient at home can report increasing weights to a provider, who can then recommend an increased dose of diuretic. The patient can complete the feedback loop by taking the extra medication and monitoring the return of weight back to normal.

While daily weight monitoring is a simple process improvement that relies on the principle of establishing feedback loops, many other strategies exist. One commonly employed tool is the postdischarge telephone follow-up call, which is often coupled with other interventions in a comprehensive care bundle.⁸ During the telephone call, several process-of-care defects can be corrected, including missing medications or missing information on appointment times.

Beyond the telephone, newer technologies show promise for helping develop feedback loops for patients at home. One such technology is telemonitoring, whereby physiologic information such as weight, heart rate, and blood pressure is collected and sent back to a monitoring center. While the principle holds promise, several studies have not demonstrated significantly different outcomes as compared to usual care.^13,29 Another promising technology is the CardioMEMS device (Abbott, Inc., Atlanta, GA), which can remotely transmit the pulmonary artery pressure, a physiologic signal which correlates with volume overload. There is now strong evidence supporting the efficacy of pulmonary artery pressure–guided heart failure management.^30,31

Finally, home visits can be an efficient way to communicate symptoms, enable clinical assessment, and provide recommendations. One program that implemented home visits, 24-hour nurses available by call, and telephone follow-up showed a statistically significant reduction in readmissions.³² Furthermore, a meta-analysis of randomized controlled trials comparing home health to usual care showed decreased readmissions and mortality.³³ The efficacy may be in strengthening the feedback loop—home care improves compliance with weight monitoring, fluid restriction, and medications.³⁴ These studies provide a strong rationale for the benefits of home health in stabilizing heart failure patients postdischarge. Indeed, nurse home visits were 1 of the 2 process interventions in a Cochrane review of randomized controlled trials that were shown to statistically significantly decrease readmissions and mortality.⁹ These data underscore the importance of feedback loops for helping ensure patients are clinically stable.

Postdischarge Follow-Up Clinic Visit

The first clinic appointment postdischarge is an important check-in to help advance patient care. Several key tasks can be achieved during the postdischarge visit. First, the patient can be clinically stabilized by adjusting diuretic therapy. If the patient is clinically stable, GDMT can be uptitrated. Second, education around symptoms, medications, diet, and exercise can be reinforced. Finally, clinicians can help connect patients to other members of the multidisciplinary care team, including specialist care, home health, or cardiac rehabilitation.

Achieving 7-day follow-up visits after discharge has been a point of emphasis in national guidelines.²⁴ The ACC promotes a “See You in 7” challenge, advising that all patients discharged with a diagnosis of heart failure have a follow-up appointment within 7 days. Yet based on the latest available data, arrival rates to the postdischarge clinic are dismal, hovering around 30%.³⁵ In a multicenter observational study of hospitals participating in the “See You in 7” collaborative, hospitals were able to increase their 7-day follow-up appointment rates by 2% to 3%, and also noted an absolute decrease in readmission rates by 1% to 2%.³⁶ We have demonstrated, using a mathematical approach called queuing theory, that discharge appointment wait times and clinic access can be significantly improved by providing a modest capacity buffer to clinic availability.³⁷ Those interested in applying this model to their own clinical practice may do so with a free online calculator at http://hfresearch.org.

Another important aspect of postdischarge follow-up is appropriate management of the comorbidity burden, which, as noted, is often significant in patients hospitalized with heart failure.³⁸ For instance, in recent cohorts of hospitalized heart failure patients, the incidence of hypertension was 78%, coronary artery disease was more than 50%, atrial fibrillation was more than 40%, and diabetes was nearly 40%.³⁹ Given this burden of comorbidity, it is not surprising that only 35% of readmissions after an index heart failure hospitalization are for recurrent heart failure.⁴⁰ Coordinating care among primary care physicians and relevant subspecialists is thus essential. Phone calls and secure electronic messages are very helpful in achieving this. There is increasing interest in more nimble care models, such as the patient-centered specialty practice⁴¹ or the dyspnea clinic, to help bring coordinated resources to the patient.⁴²

Process of Process Improvement: Our Experiences

The previous sections outline a series of potential process improvements clinical teams and health systems can implement to impact heart failure readmissions. A plan on paper, however, does not equal a plan in actuality. How does one go about implementing these changes? We offer our local experience starting a heart failure transitional care program as a case study, then draw lessons learned as a set of practical tips for local teams to employ. What we hope to highlight is that there is a large difference between a completed process for transitional care of heart failure patients, and the process of developing that process itself. The former is the hardware, the latter is the software. The latter does not typically get highlighted, but it is absolutely critical to unlocking the capabilities of a team and the institution.

In 2015, Northwestern Memorial Hospital adopted a novel payment arrangement from the Center for Medicare and Medicaid Services for Medicare patients being discharged from the hospital with heart failure. Known as Bundled Payments for Care Improvement,⁴³ this bundled payment model incentivized Northwestern Memorial Hospital charge, principally by reducing hospital readmissions and by collaborating with skilled nursing facilities to control length of stay.

We approached this problem by drawing on the available literature,^44,45 and by first creating a schematic of our high-level approach, which comprised 3 major elements (Figure 2): identification of hospitalized heart failure patients, delivery of a care bundle to hospitalized heart failure patients in hospital, and coordinating postdischarge care, centered on a telephone call and a postdischarge visit.

We then proceeded by building out, in stepwise fashion, each component of our value chain, using Agile techniques as a guiding principle.⁴⁶ Agile, a productivity and process improvement mindset with roots in software development, emphasizes tackling 1 problem at a time, building out new features sequentially and completely, recognizing that the end user does not derive value from a program until new functionality is available for use. Rather than wholesale monolithic change, Agile emphasizes rapid iteration, prototyping, and discarding innovations not found to be helpful. The notion is to stand up new, incremental features rapidly, with each incremental improvement delivering value and helping to accelerate overall change.

Our experience building a robust way to identify heart failure cases is a good example of Agile process improvement in practice. At our hospital, identification of patients with heart failure was a challenge because more than half of heart failure patients are admitted to noncardiology floors. We developed a simple electronic health record query to detect heart failure patients, relying on parameters such as administration of intravenous diuretic or levels of BNP exceeding 100 ng/dL. We deployed this query, finding very high sensitivity for detection of heart failure patients.¹⁴ Patients found to have heart failure were then populated into a list in the electronic health record, which made patients’ heart failure status visible to all members of the health care team. Using this list, we were able to automate several processes necessary for heart failure care. For example, the list made it possible for cardiologists to know if there was a patient who perhaps needed cardiology consultation. Nurse navigators could know which patients needed heart failure education without having to be actively consulted by the admitting team. The same nurse navigators could then know upon discharge which patients needed a follow-up telephone call at 48 hours.

This list of heart failure patients was the end product, which was built through prototyping and iteration. For example, with our initial BNP cutoff of 300 ng/dL, we recognized we were missing several cases, and lowered the cutoff for the screener to 100 ng/dL. When we were satisfied this process was working well, we moved on to the next problem to tackle, avoiding trying to work on too many things at once. By doing so, we were able to focus our process improvement resources on 1 problem at a time, building up a suite of interventions. For our hospital, we settled on a bundle of interventions, captured by the mnemonic HEART:

Heart doctor sees patient in the hospital

Education about heart failure in the hospital

After-visit summary with 7-day appointment printed

Reach out to the patient by telephone within 72 hours

Treat the patient in clinic by the 7-day visit

Conclusion

We would like to emphasize that the elements of our heart failure readmissions interventions were not all put in place at once. This was an iterative process that proceeded in a stepwise fashion, with each step improving the care of our patients. We learned a number of lessons from our experience. First, we would advise that teams not try to do everything. One program simply cannot implement all possible readmission reduction interventions, and certainly not all at once. Trade-offs should be made, and interventions more likely to succeed in the local environment should be prioritized. In addition, interventions that do not fit and do not create synergy with the local practice environment should not be pursued.

Second, we would advise teams to start small, tackling a known problem in heart failure transitions of care first. This initial intuition is often right. An example might be improving 7-day appointments upon discharge. Starting with a problem that can be tackled builds process improvement muscle and improves team morale. Third, we would advise teams to consistently iterate on designs, tweaking and improving performance. Complex organizations always evolve; processes that work 1 year may fail the next because another element of the organization may have changed.

Finally, the framework presented in Figure 1 may be helpful in guiding how to structure interventions. Considering interventions to be delivered in the hospital, interventions to be delivered in the clinic, and how to set up feedback loops to support patients as outpatients help develop a comprehensive heart failure readmissions reduction program.

Corresponding author: R. Kannan Mutharasan, MD, Northwestern University Feinberg School of Medicine, 676 North Saint Clair St., Arkes Pavilion, Suite 7-038, Chicago, IL 60611;kannanm@northwestern.edu.

Financial disclosures: None.