Truly, the right to bear firearms is not something that should be in the domain of the psychiatrist, but in our current landscape, it’s fallen into our realm. Personally, (as opposed to professionally), it seems to me that there is no reason that someone needs to own an assault weapon, and Americans somehow survived without them for 10 years from 1994 to 2004 during a national ban on assault weapons, inspired in part by the massacre of children in a 1989 mass shooting at a Stockton, Calif., school, followed in 1993 by a street shooting where eight people were killed in San Francisco.

A CNN poll conducted in 1993 revealed that 73% of those polled opposed the manufacture, sale, or possession of assault weapons, and back then, the politics of gun control were less partisan: Former Republican President Ronald Reagan supported legislation to make them illegal. The ban on assault weapons expired in 2004, and mass shooters have been able to obtain these weapons legally and have used them for many of the highly publicized massacres we read about, now several times a year.

What shocks me is that we manufacture these weapons to allow for rapid and efficient discharge, we make these firearms easily accessible to anyone who wants them in more than 40 states, and then we are surprised when people use them to do exactly what they were designed to do: kill lots of people quickly. Those who oppose bans on these weapons insist that terrorists will find other ways: They will use illegal weapons, bombs made from pressure cookers, biologic agents, or explosives. They may be right; that doesn’t mean our government needs to make it easy for gunmen to massacre innocent people.

Until recently, the discussion about mass murder somehow pitted mental illness against gun control, so like it or not, psychiatry was pulled into the discussion of mass murder. Does this make sense? Very little of gun violence takes the form of these highly publicized mass murders – perhaps 1%. But if you’ve turned on CNN lately, they get a lot of air time, while the deaths of countless others – dozens a day in our gun-drenched cities – are now just part of the routine risks of life. If you hold your definition of mass murders to the deaths of four victims in a public place, then most mass murders are what we see in the news: Aurora, Newtown, Fort Hood, Isla Vista, and the list goes on. Of those shooters, roughly half had some history of some kind of mental illness. If you enlarge the definition, as some do, to include any shooting where four or more victims die, then the association with mental illness drops. Many of these killings are domestic and gang violence, or deaths that occur during the commission of another crime.

Overall, it is estimated that less than 10% of gun murders are caused by mental illness, and the politically correct mantra of the time is to point out that people with mental illness are more likely to be the victims of violence than to perpetrate it. Finally, most gun deaths are suicides and not homicides – a distinction not made by CNN.

Despite the staggering rise in gun deaths in our country, and the clear link between gun availability and gun deaths, our federal legislators are stuck; no new gun legislation has passed. Our Congress has made the quiet statement after Newtown that the National Rifle Association (NRA) is remarkably powerful, and perhaps the story was over when we decided that killing children is acceptable. If that’s not enough, Congress was not propelled to action when one of their own was shot in the head during a massacre.

If I feel frustrated and let off steam by tweeting, how awful former U.S. Rep. Gabby Giffords must feel that her former colleagues have not embraced her advocacy actions with Americans for Responsible Solutions.

Over the last week, we’ve seen Sen. Chris Murphy (D-Conn.) stage a 15-hour filibuster on two gun safety amendments. One would close the terror gap; the other sought to expand background checks for firearms purchases. Both measures failed, as did two other gun control measures in the Senate. We’ve also seen House Democrats conduct a sit-in in an effort to force gun control votes. We can’t even agree that those under FBI surveillance for terrorist activities and those on a no-fly list should not be allowed to purchase firearms of any type, including assault rifles. The response is that the right to own guns is protected by the Constitution and can’t be denied without a judicial process.

In the case of those with mental illnesses, individual states do not allow for such protections. In New York, the NYSAFE Act allows that patients can be reported to the state, then placed on the National Instant Criminal Background Check System, to prevent gun purchases if a therapist believes a patient is at risk of violence. There needs to be no dangerous act and no history of hospitalization to set this in motion, just a therapist’s belief. And all patients who are involuntarily hospitalized in New York are placed in the database.

California is different with its efforts to keep guns from those with mental disorders: Anyone brought in for a psychiatric evaluation by law enforcement or involuntarily hospitalized from an ER on what is commonly known as a “5150 hold,” loses the right to own a gun for 5 years. There is no hearing at that point, and those who are later released at the commitment hearing do not get their gun rights back.

In Maryland, where I live, the restrictions are a mixed bag: Anyone who remains in a psychiatric hospital for more than 30 days, voluntarily or otherwise and without regard to dangerousness, loses his right to own a gun. In addition, more recent legislation has added that at commitment hearings, the administrative law judge determines whether the patient may retain gun rights based on an assessment of his dangerousness toward others.

Each state is different, but for psychiatric patients who are lawful gun owners, seeking help can be a mixed bag, and they certainly do not get the national civil rights protections that we afford terror suspects. Does the fear of losing the right to bear arms play into a hunter’s decision to seek mental health care? It’s hard to imagine that it would not. While we advocate for decreasing stigma and getting care for those who need help, we also erect barriers and increase stigma in this odd mixed-message public health endeavor.

Given the vocal nature of gun control advocates, it’s hard not to wonder whether the unwillingness of Congress to pass laws that might make us safer is about the will of the people or the dollar amount that legislatures receive from the NRA. I am sure there are readers who disagree with me and feel that more guns in the hands of “good guys” make us all safer, but I continue to find it interesting that mental illness does not cause mass murder – at least not with the numbers we see in the United States – in countries with stricter gun control.

Those who advocate for gun rights remain unconcerned about the high incidence of guns and suicide. Many believe that people should have the right to take their own lives, and if a gun were not available, another means would be found. In some cases, there is no doubt that this is true. In others, we worry that an easily accessible gun in the hands of a suicidal person has a very high rate of mortality, and there is no room for second thoughts or chances after an impulsive decision.

Psychiatry has been lassoed here – guns are our domain whether we want them to be or not – and we already are starting to see patients who want us to advocate for their right to retain their firearms. While I can’t imagine taking on the responsibility or liability of saying my patient (or anyone else) is safe with a firearm, there may be moments where it seems there is little choice, especially when a firearm is required for the patient’s employment. In the meantime, I keep hoping our legislators will wake up and come to their senses.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care,” forthcoming from Johns Hopkins University Press in fall 2016.

Truly, the right to bear firearms is not something that should be in the domain of the psychiatrist, but in our current landscape, it’s fallen into our realm. Personally, (as opposed to professionally), it seems to me that there is no reason that someone needs to own an assault weapon, and Americans somehow survived without them for 10 years from 1994 to 2004 during a national ban on assault weapons, inspired in part by the massacre of children in a 1989 mass shooting at a Stockton, Calif., school, followed in 1993 by a street shooting where eight people were killed in San Francisco.

A CNN poll conducted in 1993 revealed that 73% of those polled opposed the manufacture, sale, or possession of assault weapons, and back then, the politics of gun control were less partisan: Former Republican President Ronald Reagan supported legislation to make them illegal. The ban on assault weapons expired in 2004, and mass shooters have been able to obtain these weapons legally and have used them for many of the highly publicized massacres we read about, now several times a year.

What shocks me is that we manufacture these weapons to allow for rapid and efficient discharge, we make these firearms easily accessible to anyone who wants them in more than 40 states, and then we are surprised when people use them to do exactly what they were designed to do: kill lots of people quickly. Those who oppose bans on these weapons insist that terrorists will find other ways: They will use illegal weapons, bombs made from pressure cookers, biologic agents, or explosives. They may be right; that doesn’t mean our government needs to make it easy for gunmen to massacre innocent people.

Until recently, the discussion about mass murder somehow pitted mental illness against gun control, so like it or not, psychiatry was pulled into the discussion of mass murder. Does this make sense? Very little of gun violence takes the form of these highly publicized mass murders – perhaps 1%. But if you’ve turned on CNN lately, they get a lot of air time, while the deaths of countless others – dozens a day in our gun-drenched cities – are now just part of the routine risks of life. If you hold your definition of mass murders to the deaths of four victims in a public place, then most mass murders are what we see in the news: Aurora, Newtown, Fort Hood, Isla Vista, and the list goes on. Of those shooters, roughly half had some history of some kind of mental illness. If you enlarge the definition, as some do, to include any shooting where four or more victims die, then the association with mental illness drops. Many of these killings are domestic and gang violence, or deaths that occur during the commission of another crime.

Overall, it is estimated that less than 10% of gun murders are caused by mental illness, and the politically correct mantra of the time is to point out that people with mental illness are more likely to be the victims of violence than to perpetrate it. Finally, most gun deaths are suicides and not homicides – a distinction not made by CNN.

Despite the staggering rise in gun deaths in our country, and the clear link between gun availability and gun deaths, our federal legislators are stuck; no new gun legislation has passed. Our Congress has made the quiet statement after Newtown that the National Rifle Association (NRA) is remarkably powerful, and perhaps the story was over when we decided that killing children is acceptable. If that’s not enough, Congress was not propelled to action when one of their own was shot in the head during a massacre.

If I feel frustrated and let off steam by tweeting, how awful former U.S. Rep. Gabby Giffords must feel that her former colleagues have not embraced her advocacy actions with Americans for Responsible Solutions.

Over the last week, we’ve seen Sen. Chris Murphy (D-Conn.) stage a 15-hour filibuster on two gun safety amendments. One would close the terror gap; the other sought to expand background checks for firearms purchases. Both measures failed, as did two other gun control measures in the Senate. We’ve also seen House Democrats conduct a sit-in in an effort to force gun control votes. We can’t even agree that those under FBI surveillance for terrorist activities and those on a no-fly list should not be allowed to purchase firearms of any type, including assault rifles. The response is that the right to own guns is protected by the Constitution and can’t be denied without a judicial process.

In the case of those with mental illnesses, individual states do not allow for such protections. In New York, the NYSAFE Act allows that patients can be reported to the state, then placed on the National Instant Criminal Background Check System, to prevent gun purchases if a therapist believes a patient is at risk of violence. There needs to be no dangerous act and no history of hospitalization to set this in motion, just a therapist’s belief. And all patients who are involuntarily hospitalized in New York are placed in the database.

California is different with its efforts to keep guns from those with mental disorders: Anyone brought in for a psychiatric evaluation by law enforcement or involuntarily hospitalized from an ER on what is commonly known as a “5150 hold,” loses the right to own a gun for 5 years. There is no hearing at that point, and those who are later released at the commitment hearing do not get their gun rights back.

In Maryland, where I live, the restrictions are a mixed bag: Anyone who remains in a psychiatric hospital for more than 30 days, voluntarily or otherwise and without regard to dangerousness, loses his right to own a gun. In addition, more recent legislation has added that at commitment hearings, the administrative law judge determines whether the patient may retain gun rights based on an assessment of his dangerousness toward others.

Each state is different, but for psychiatric patients who are lawful gun owners, seeking help can be a mixed bag, and they certainly do not get the national civil rights protections that we afford terror suspects. Does the fear of losing the right to bear arms play into a hunter’s decision to seek mental health care? It’s hard to imagine that it would not. While we advocate for decreasing stigma and getting care for those who need help, we also erect barriers and increase stigma in this odd mixed-message public health endeavor.

Given the vocal nature of gun control advocates, it’s hard not to wonder whether the unwillingness of Congress to pass laws that might make us safer is about the will of the people or the dollar amount that legislatures receive from the NRA. I am sure there are readers who disagree with me and feel that more guns in the hands of “good guys” make us all safer, but I continue to find it interesting that mental illness does not cause mass murder – at least not with the numbers we see in the United States – in countries with stricter gun control.

Those who advocate for gun rights remain unconcerned about the high incidence of guns and suicide. Many believe that people should have the right to take their own lives, and if a gun were not available, another means would be found. In some cases, there is no doubt that this is true. In others, we worry that an easily accessible gun in the hands of a suicidal person has a very high rate of mortality, and there is no room for second thoughts or chances after an impulsive decision.

Psychiatry has been lassoed here – guns are our domain whether we want them to be or not – and we already are starting to see patients who want us to advocate for their right to retain their firearms. While I can’t imagine taking on the responsibility or liability of saying my patient (or anyone else) is safe with a firearm, there may be moments where it seems there is little choice, especially when a firearm is required for the patient’s employment. In the meantime, I keep hoping our legislators will wake up and come to their senses.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care,” forthcoming from Johns Hopkins University Press in fall 2016.

Truly, the right to bear firearms is not something that should be in the domain of the psychiatrist, but in our current landscape, it’s fallen into our realm. Personally, (as opposed to professionally), it seems to me that there is no reason that someone needs to own an assault weapon, and Americans somehow survived without them for 10 years from 1994 to 2004 during a national ban on assault weapons, inspired in part by the massacre of children in a 1989 mass shooting at a Stockton, Calif., school, followed in 1993 by a street shooting where eight people were killed in San Francisco.

A CNN poll conducted in 1993 revealed that 73% of those polled opposed the manufacture, sale, or possession of assault weapons, and back then, the politics of gun control were less partisan: Former Republican President Ronald Reagan supported legislation to make them illegal. The ban on assault weapons expired in 2004, and mass shooters have been able to obtain these weapons legally and have used them for many of the highly publicized massacres we read about, now several times a year.

What shocks me is that we manufacture these weapons to allow for rapid and efficient discharge, we make these firearms easily accessible to anyone who wants them in more than 40 states, and then we are surprised when people use them to do exactly what they were designed to do: kill lots of people quickly. Those who oppose bans on these weapons insist that terrorists will find other ways: They will use illegal weapons, bombs made from pressure cookers, biologic agents, or explosives. They may be right; that doesn’t mean our government needs to make it easy for gunmen to massacre innocent people.

Until recently, the discussion about mass murder somehow pitted mental illness against gun control, so like it or not, psychiatry was pulled into the discussion of mass murder. Does this make sense? Very little of gun violence takes the form of these highly publicized mass murders – perhaps 1%. But if you’ve turned on CNN lately, they get a lot of air time, while the deaths of countless others – dozens a day in our gun-drenched cities – are now just part of the routine risks of life. If you hold your definition of mass murders to the deaths of four victims in a public place, then most mass murders are what we see in the news: Aurora, Newtown, Fort Hood, Isla Vista, and the list goes on. Of those shooters, roughly half had some history of some kind of mental illness. If you enlarge the definition, as some do, to include any shooting where four or more victims die, then the association with mental illness drops. Many of these killings are domestic and gang violence, or deaths that occur during the commission of another crime.

Overall, it is estimated that less than 10% of gun murders are caused by mental illness, and the politically correct mantra of the time is to point out that people with mental illness are more likely to be the victims of violence than to perpetrate it. Finally, most gun deaths are suicides and not homicides – a distinction not made by CNN.

Despite the staggering rise in gun deaths in our country, and the clear link between gun availability and gun deaths, our federal legislators are stuck; no new gun legislation has passed. Our Congress has made the quiet statement after Newtown that the National Rifle Association (NRA) is remarkably powerful, and perhaps the story was over when we decided that killing children is acceptable. If that’s not enough, Congress was not propelled to action when one of their own was shot in the head during a massacre.

If I feel frustrated and let off steam by tweeting, how awful former U.S. Rep. Gabby Giffords must feel that her former colleagues have not embraced her advocacy actions with Americans for Responsible Solutions.

Over the last week, we’ve seen Sen. Chris Murphy (D-Conn.) stage a 15-hour filibuster on two gun safety amendments. One would close the terror gap; the other sought to expand background checks for firearms purchases. Both measures failed, as did two other gun control measures in the Senate. We’ve also seen House Democrats conduct a sit-in in an effort to force gun control votes. We can’t even agree that those under FBI surveillance for terrorist activities and those on a no-fly list should not be allowed to purchase firearms of any type, including assault rifles. The response is that the right to own guns is protected by the Constitution and can’t be denied without a judicial process.

In the case of those with mental illnesses, individual states do not allow for such protections. In New York, the NYSAFE Act allows that patients can be reported to the state, then placed on the National Instant Criminal Background Check System, to prevent gun purchases if a therapist believes a patient is at risk of violence. There needs to be no dangerous act and no history of hospitalization to set this in motion, just a therapist’s belief. And all patients who are involuntarily hospitalized in New York are placed in the database.

California is different with its efforts to keep guns from those with mental disorders: Anyone brought in for a psychiatric evaluation by law enforcement or involuntarily hospitalized from an ER on what is commonly known as a “5150 hold,” loses the right to own a gun for 5 years. There is no hearing at that point, and those who are later released at the commitment hearing do not get their gun rights back.

In Maryland, where I live, the restrictions are a mixed bag: Anyone who remains in a psychiatric hospital for more than 30 days, voluntarily or otherwise and without regard to dangerousness, loses his right to own a gun. In addition, more recent legislation has added that at commitment hearings, the administrative law judge determines whether the patient may retain gun rights based on an assessment of his dangerousness toward others.

Each state is different, but for psychiatric patients who are lawful gun owners, seeking help can be a mixed bag, and they certainly do not get the national civil rights protections that we afford terror suspects. Does the fear of losing the right to bear arms play into a hunter’s decision to seek mental health care? It’s hard to imagine that it would not. While we advocate for decreasing stigma and getting care for those who need help, we also erect barriers and increase stigma in this odd mixed-message public health endeavor.

Given the vocal nature of gun control advocates, it’s hard not to wonder whether the unwillingness of Congress to pass laws that might make us safer is about the will of the people or the dollar amount that legislatures receive from the NRA. I am sure there are readers who disagree with me and feel that more guns in the hands of “good guys” make us all safer, but I continue to find it interesting that mental illness does not cause mass murder – at least not with the numbers we see in the United States – in countries with stricter gun control.

Those who advocate for gun rights remain unconcerned about the high incidence of guns and suicide. Many believe that people should have the right to take their own lives, and if a gun were not available, another means would be found. In some cases, there is no doubt that this is true. In others, we worry that an easily accessible gun in the hands of a suicidal person has a very high rate of mortality, and there is no room for second thoughts or chances after an impulsive decision.

Psychiatry has been lassoed here – guns are our domain whether we want them to be or not – and we already are starting to see patients who want us to advocate for their right to retain their firearms. While I can’t imagine taking on the responsibility or liability of saying my patient (or anyone else) is safe with a firearm, there may be moments where it seems there is little choice, especially when a firearm is required for the patient’s employment. In the meantime, I keep hoping our legislators will wake up and come to their senses.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care,” forthcoming from Johns Hopkins University Press in fall 2016.

United States health care is moving rapidly from volume- to value-based reimbursement. An essential part of this movement will be the development of alternative payment models where a specific bundle of care (colonoscopy), episode of care (a year of care for attributed Crohn’s patients), or ongoing care of a specialty-centric patient population (patients with cirrhosis) are covered within a contract that links health outcomes, quality of care, and payment together. Gastroenterologists are slowly becoming aware of these concepts. Primary care has its patient-centered medical home and now specialists have a patient-centric specialty practice where patient populations are cared for principally by a specialty practice within a well-defined care delivery structure. Previous columns have illustrated these concepts, and this month, Meier and colleagues provide an excellent definition and example of how practices can participate in this new world order.

John I Allen, M.D., MBA, AGAF, Special Section Editor

The Patient Protection and Affordable Care Act secures access to health insurance coverage for many previously uninsured individuals, while transforming the structure of health care delivery to promote high value care that is coordinated and patient-centered.¹ The development of innovative care delivery models is a key feature of this transformation. In turn, patient-centered medical homes (PCMHs) have proliferated in number, with PCMH-related pilot and demonstration projects spanning numerous federal agencies.²

Defining the patient-centered medical home

The concept of the PCMH predates the Patient Protection and Affordable Care Act, with its origins in the American Academy of Pediatrics’ 1967 discussion of the medical home. In 2007, a joint release by the American Academy of Family Physicians, the American Academy of Pediatrics, the American College of Physicians, and the American Osteopathic Association defined the PCMH as “an approach to providing comprehensive primary care for children, youth and adults.” Furthermore, the PCMH would serve as “a health care setting that facilitates partnerships between individual patients, and their personal physicians, and when appropriate, the patient’s family.” Several key principles underscore the PCMH model; the patient has a personal physician, and care is physician-directed at the level of the practice, oriented around the whole person, and coordinated to ensure the highest quality and safety of medical care. The PCMH facilitates enhanced access to care, and the payment structure incentivizes and compensates high-quality care delivery.³

Advent of the patient-centered specialty practice

In 2013 the National Committee for Quality Assurance (NCQA), which operates the Patient Centered Medical Home Recognition program, released a set of standards governing the recognition of the patient-centered specialty practice (PCSP).⁴ Similar to the PCMH model, the PCSP model places the patient at the center of care delivery. Key functions of the PCSP include placing the patient at the center of care, sharing of information, and coordinating across all practices (specialty and primary) for patients.⁵ The NCQA outlines six standards for PCSP recognition; these standards focus on planning, management, tracking and coordination of care, performance measurement, performance improvement, referrals, communication to patients, care access, and coordination and management for populations.⁵

Centering patient care in the specialty practice

With the release of the NCQA PCSP standards, provider groups and regulators should work to identify circumstances under which the PCSP might best operate as an effective model for the populations they serve. For example, in the case of mental illness that is both severe and persistent, the creation of a PCMH may disrupt existing patient-provider relationships, increase fragmentation of medical care, and position poorly equipped providers at the center of a care process that requires greater specialization.⁶

Drawing from this example, we suggest that select patient populations with advanced chronic liver disease may benefit from the development of patient-centered care models that operate such as a PCSP. This may include patients with compensated cirrhosis and other comorbid illnesses such as diabetes mellitus or depression, populations with active complications of portal hypertension, or patients who await or have received liver transplantation.^7,8 We suggest examining the potential value of this model in circumstances where the complexity of patient needs or the sensitivity and vulnerability of the patient circumstance may best be managed by an established, trusted, and specialized provider. In the case of patients with cirrhosis and substance abuse from alcohol, a hybrid specialty model that incorporates addiction medicine, social work, and psychiatry providers in addition to hepatologists and allied health providers may be warranted.⁷

Designing the patient-centered specialty practice for populations with cirrhosis and liver transplant recipients

Practices and providers should carefully assess the context for PCSP adoption, identifying whether the specialty care model will promote greater efficiency and quality than that realized in the absence of a PCSP model. The PCSP model should align with patient needs, considering factors such as cause of disease, disease stage, comorbidities and complications, and socioeconomic factors. Although the NCQA PCSP standards should guide model development, there are specific needs and complexities of cirrhosis and liver transplant populations that may prove highly relevant in identifying one or more ideal model designs. This may entail development of additional PCSP standards beyond what is recognized by NCQA.

Table 1 outlines key questions providers might address when considering the development of the PCSP in this patient population. We divide these questions into three main categories: 1) understanding the context for PCSP model adoption, 2) identifying opportunities to align the PCSP model with the specific needs of the patient population, and 3) selecting a model design. Incorporating careful consideration of the questions highlighted within each of these categories can help inform practitioners on the merits of various PCSP models.

Understanding the context for patient-centered specialty practice adoption

Drawing from Alakeson et al.,⁹ we suggest that providers embarking on PCSP model adoption first consider how the quality of care and strength of patient-provider relationships for the target population will improve. The selection of an appropriate patient population is a key determinant in the answer to this question. Focusing specifically on the cirrhosis population, the PCSP may need to be directed toward a disease stage (i.e., decompensated cirrhosis) where the specialist is the most frequent and continuous point of system access. Similarly, the PCSP might yield the greatest gains in quality when access is a function of requiring specialized knowledge in the day-to-day management of care delivery (i.e., compensated liver disease or long-term post liver transplant recipients).

The case for the PCSP may be particularly strong in instances where the primary care provider lacks sufficient knowledge to appropriately manage patient care. For example, treatment of mental and behavioral health conditions that are comorbid with cirrhosis may best be suited to a specialized and established care team that has secured patient trust. Many transplant centers in the United States have explicitly created teams in this regard in the context of regulatory requirements for being a transplant program.¹⁰

Identifying opportunities to align the patient-centered specialty practice model with the specific needs of the patient population

Liver transplant and cirrhosis patients exhibit variability in the cause of disease, with genetic, social-behavioral, and other causal mechanisms operating as factors in the expression of disease. Developing a model focused on reduction in the risk of need for transplant might differ from these former two examples in target population and specialist team. A relevant example is with hospital readmissions because multiple studies to date have documented at least a 20% frequency of re-hospitalization within 30 days of index readmission.^11,12 Although disease severity indicated by Model for End Stage Liver Disease score explains a significant amount of the variability in risk for readmission, there are other factors including frailty¹³ and complications from index hospitalization14 that also contribute to 30-day readmission. The use of case management and remote monitoring strategies for patients at risk for hospital readmission is likely to be included in a PCSP focused on reducing inpatient utilization.

Variability in the social and economic context surrounding a patient’s daily life should also factor into model design. In the case of Medicaid coverage, a well-designed model might address discontinuities in specific provider and service access arising from churning in Medicaid eligibility and coverage.

Selecting a model design

Three examples of specialty care medical home designs have been described in the literature including the integrated model concept and two variants of the partnership model design. The integrated model concept provides specialty and primary care in one location, whereas the partnership models include an on-site liaison at the specialty practice, either a nurse practitioner who provides some degree of care and is able to draw from the services from an off-site primary care physician or otherwise an on-site nurse care manager who serves as an information source and advocate.⁹

We suggest that selection of model design should consider the number of specialty and primary care providers required to construct a comprehensive care team and whether there is reasonable capacity for patients to access comprehensive care in multiple settings. Providing a spectrum of services through separately located but coordinated PCSP and PCMH care models may be practical for some target populations. In other instances, multisite care programs may place an undesirable and impractical burden on patients with complex needs or low health system literacy.

As the field of PCSP model development moves forward, we suggest that providers learn from shared discussions of experience. If appropriate, innovation and shared learning should inform the development of additional standards to ensure that PCSP development for cirrhosis and transplant patients adheres to meaningful quality standards. As is clear from discussion, cirrhosis and liver transplant patients are a diverse group with a range of needs that fall across a spectrum of complexity. The development of well-structured PCSP models may require a high degree of specialization, where model adaptation acknowledges how specific disease-based needs, clinical comorbidities, and external support networks vary across groups.

One suggestion for moving forward is to focus early efforts narrowly on small and highly complex patient groups where the expected value of PCSP is large. This may entail beginning with patient groups whose clinical complexity may otherwise disqualify them from participation in traditional patient-centered care model demonstrations and evaluations. An ideal target population would be patients with decompensated cirrhosis who are ineligible for liver transplantation on the basis of multimorbidity. In addition, specialty providers might consider partnering with state agencies or patient groups in the development, testing, and funding of such programs. These partnerships may help to identify target patient populations with potential to benefit from participation in demonstration projects that innovate through the use of new PCSP model designs.

References

1. Sheen, E., Dorn, S.D., Brill, J.V., et al. Health care reform and the road ahead for gastroenterology. Clin Gastroenterol Hepatol. 2012;10:1062-5.

2. Agency for Healthcare Research and Quality. PCMH activities across federal agencies (Table 1). Available at: http://www.pcmh.ahrq.gov/sites/default/files/attachments/federal-pcmh-activities-table-1.pdf. Accessed May 13, 2015.

3. AAP, AAFP, ACP, and AOA. Joint principles of the patient-centered medical home, March 2007. Available at: http://www.acponline.org/running_practice/delivery_and_payment_models/pcmh/demonstrations/jointprinc_05_17.pdf. Accessed November 24, 2015.

4. Huang, X. Rosenthal, M.B. Transforming specialty practice–the patient-centered medical neighborhood. N Engl J Med. 2014;370:1376-9.

5. National Committee of Quality Assurance. Patient-centered specialty practice recognition: white paper. 2013. Available at: http://www.ncqa.org/Portals/0/Newsroom/2013/PCSP%20Launch/PCSPR%202013%20White%20Paper%203.26.13%20formatted.pdf. Accessed November 24, 2015.

6. National Committee of Quality Assurance. Patient-centered specialty practice frequently asked questions. Available at: http://www.ncqa.org/Programs/Recognition/Practices/PatientCenteredSpecialtyPracticePCSP/PatientCenteredSpecialtyPracticeFAQs.aspx Accessed June 4, 2015.

6. Kanwal, F. Coordinating care in patients with cirrhosis. Clin Gastroenterol Hepatol. 2013;11:859-61.

7. Fortune, B.E., Golus, A., Barsky, C.L., et al. Linking a hepatology clinical service line to quality improvement. Clin Gastroenterol Hepatol. 2015;13:1391-5.

8. Alakeson, V., Frank, R.G., Katz, R.E. Specialty care medical homes for people with severe, persistent mental disorders. Health Affairs. 2010;29:867-73.

9. Talwalkar, J.A. Potential impacts of the Affordable Care Act on the clinical practice of hepatology. Hepatology. 2014;59:1681-7.

9. Volk, M.L., Tocco, R.S., Bazick, J., et al. Hospital readmissions among patients with decompensated cirrhosis. Am J Gastroenterol. 2012;107:247-52.

10. Berman, K., Tandra, S., Forssell, K., et al. Incidence and predictors of 30-day readmission among patients hospitalized for advanced liver disease. Clin Gastroenterol Hepatol. 2011;9:254-9.

11. Tapper, E.B., Finkelstein, D., Mittleman, M.A., et al. Standard assessments of frailty are validated predictors of mortality in hospitalized patients with cirrhosis. Hepatology. 2015;62:584-90.

12. Eappen, S., Lane, B.H., Rosenberg, B., et al. Relationship between occurrence of surgical complications and hospital finances. JAMA. 2013;309:1599-606.

Dr. Meier, Dr. Shah, and Dr. Talwalkar are in the department of health care policy and research, department of health sciences research; Dr. Talwalkar is also in the division of gastroenterology and hepatology and the William von Liebig Center for Transplantation and Regenerative Medicine; Mayo Clinic, Rochester, Minn.

United States health care is moving rapidly from volume- to value-based reimbursement. An essential part of this movement will be the development of alternative payment models where a specific bundle of care (colonoscopy), episode of care (a year of care for attributed Crohn’s patients), or ongoing care of a specialty-centric patient population (patients with cirrhosis) are covered within a contract that links health outcomes, quality of care, and payment together. Gastroenterologists are slowly becoming aware of these concepts. Primary care has its patient-centered medical home and now specialists have a patient-centric specialty practice where patient populations are cared for principally by a specialty practice within a well-defined care delivery structure. Previous columns have illustrated these concepts, and this month, Meier and colleagues provide an excellent definition and example of how practices can participate in this new world order.

John I Allen, M.D., MBA, AGAF, Special Section Editor

The Patient Protection and Affordable Care Act secures access to health insurance coverage for many previously uninsured individuals, while transforming the structure of health care delivery to promote high value care that is coordinated and patient-centered.¹ The development of innovative care delivery models is a key feature of this transformation. In turn, patient-centered medical homes (PCMHs) have proliferated in number, with PCMH-related pilot and demonstration projects spanning numerous federal agencies.²

Defining the patient-centered medical home

The concept of the PCMH predates the Patient Protection and Affordable Care Act, with its origins in the American Academy of Pediatrics’ 1967 discussion of the medical home. In 2007, a joint release by the American Academy of Family Physicians, the American Academy of Pediatrics, the American College of Physicians, and the American Osteopathic Association defined the PCMH as “an approach to providing comprehensive primary care for children, youth and adults.” Furthermore, the PCMH would serve as “a health care setting that facilitates partnerships between individual patients, and their personal physicians, and when appropriate, the patient’s family.” Several key principles underscore the PCMH model; the patient has a personal physician, and care is physician-directed at the level of the practice, oriented around the whole person, and coordinated to ensure the highest quality and safety of medical care. The PCMH facilitates enhanced access to care, and the payment structure incentivizes and compensates high-quality care delivery.³

Advent of the patient-centered specialty practice

In 2013 the National Committee for Quality Assurance (NCQA), which operates the Patient Centered Medical Home Recognition program, released a set of standards governing the recognition of the patient-centered specialty practice (PCSP).⁴ Similar to the PCMH model, the PCSP model places the patient at the center of care delivery. Key functions of the PCSP include placing the patient at the center of care, sharing of information, and coordinating across all practices (specialty and primary) for patients.⁵ The NCQA outlines six standards for PCSP recognition; these standards focus on planning, management, tracking and coordination of care, performance measurement, performance improvement, referrals, communication to patients, care access, and coordination and management for populations.⁵

Centering patient care in the specialty practice

With the release of the NCQA PCSP standards, provider groups and regulators should work to identify circumstances under which the PCSP might best operate as an effective model for the populations they serve. For example, in the case of mental illness that is both severe and persistent, the creation of a PCMH may disrupt existing patient-provider relationships, increase fragmentation of medical care, and position poorly equipped providers at the center of a care process that requires greater specialization.⁶

Drawing from this example, we suggest that select patient populations with advanced chronic liver disease may benefit from the development of patient-centered care models that operate such as a PCSP. This may include patients with compensated cirrhosis and other comorbid illnesses such as diabetes mellitus or depression, populations with active complications of portal hypertension, or patients who await or have received liver transplantation.^7,8 We suggest examining the potential value of this model in circumstances where the complexity of patient needs or the sensitivity and vulnerability of the patient circumstance may best be managed by an established, trusted, and specialized provider. In the case of patients with cirrhosis and substance abuse from alcohol, a hybrid specialty model that incorporates addiction medicine, social work, and psychiatry providers in addition to hepatologists and allied health providers may be warranted.⁷

Designing the patient-centered specialty practice for populations with cirrhosis and liver transplant recipients

Practices and providers should carefully assess the context for PCSP adoption, identifying whether the specialty care model will promote greater efficiency and quality than that realized in the absence of a PCSP model. The PCSP model should align with patient needs, considering factors such as cause of disease, disease stage, comorbidities and complications, and socioeconomic factors. Although the NCQA PCSP standards should guide model development, there are specific needs and complexities of cirrhosis and liver transplant populations that may prove highly relevant in identifying one or more ideal model designs. This may entail development of additional PCSP standards beyond what is recognized by NCQA.

Table 1 outlines key questions providers might address when considering the development of the PCSP in this patient population. We divide these questions into three main categories: 1) understanding the context for PCSP model adoption, 2) identifying opportunities to align the PCSP model with the specific needs of the patient population, and 3) selecting a model design. Incorporating careful consideration of the questions highlighted within each of these categories can help inform practitioners on the merits of various PCSP models.

Understanding the context for patient-centered specialty practice adoption

Drawing from Alakeson et al.,⁹ we suggest that providers embarking on PCSP model adoption first consider how the quality of care and strength of patient-provider relationships for the target population will improve. The selection of an appropriate patient population is a key determinant in the answer to this question. Focusing specifically on the cirrhosis population, the PCSP may need to be directed toward a disease stage (i.e., decompensated cirrhosis) where the specialist is the most frequent and continuous point of system access. Similarly, the PCSP might yield the greatest gains in quality when access is a function of requiring specialized knowledge in the day-to-day management of care delivery (i.e., compensated liver disease or long-term post liver transplant recipients).

The case for the PCSP may be particularly strong in instances where the primary care provider lacks sufficient knowledge to appropriately manage patient care. For example, treatment of mental and behavioral health conditions that are comorbid with cirrhosis may best be suited to a specialized and established care team that has secured patient trust. Many transplant centers in the United States have explicitly created teams in this regard in the context of regulatory requirements for being a transplant program.¹⁰

Identifying opportunities to align the patient-centered specialty practice model with the specific needs of the patient population

Liver transplant and cirrhosis patients exhibit variability in the cause of disease, with genetic, social-behavioral, and other causal mechanisms operating as factors in the expression of disease. Developing a model focused on reduction in the risk of need for transplant might differ from these former two examples in target population and specialist team. A relevant example is with hospital readmissions because multiple studies to date have documented at least a 20% frequency of re-hospitalization within 30 days of index readmission.^11,12 Although disease severity indicated by Model for End Stage Liver Disease score explains a significant amount of the variability in risk for readmission, there are other factors including frailty¹³ and complications from index hospitalization14 that also contribute to 30-day readmission. The use of case management and remote monitoring strategies for patients at risk for hospital readmission is likely to be included in a PCSP focused on reducing inpatient utilization.

Variability in the social and economic context surrounding a patient’s daily life should also factor into model design. In the case of Medicaid coverage, a well-designed model might address discontinuities in specific provider and service access arising from churning in Medicaid eligibility and coverage.

Selecting a model design

Three examples of specialty care medical home designs have been described in the literature including the integrated model concept and two variants of the partnership model design. The integrated model concept provides specialty and primary care in one location, whereas the partnership models include an on-site liaison at the specialty practice, either a nurse practitioner who provides some degree of care and is able to draw from the services from an off-site primary care physician or otherwise an on-site nurse care manager who serves as an information source and advocate.⁹

We suggest that selection of model design should consider the number of specialty and primary care providers required to construct a comprehensive care team and whether there is reasonable capacity for patients to access comprehensive care in multiple settings. Providing a spectrum of services through separately located but coordinated PCSP and PCMH care models may be practical for some target populations. In other instances, multisite care programs may place an undesirable and impractical burden on patients with complex needs or low health system literacy.

As the field of PCSP model development moves forward, we suggest that providers learn from shared discussions of experience. If appropriate, innovation and shared learning should inform the development of additional standards to ensure that PCSP development for cirrhosis and transplant patients adheres to meaningful quality standards. As is clear from discussion, cirrhosis and liver transplant patients are a diverse group with a range of needs that fall across a spectrum of complexity. The development of well-structured PCSP models may require a high degree of specialization, where model adaptation acknowledges how specific disease-based needs, clinical comorbidities, and external support networks vary across groups.

One suggestion for moving forward is to focus early efforts narrowly on small and highly complex patient groups where the expected value of PCSP is large. This may entail beginning with patient groups whose clinical complexity may otherwise disqualify them from participation in traditional patient-centered care model demonstrations and evaluations. An ideal target population would be patients with decompensated cirrhosis who are ineligible for liver transplantation on the basis of multimorbidity. In addition, specialty providers might consider partnering with state agencies or patient groups in the development, testing, and funding of such programs. These partnerships may help to identify target patient populations with potential to benefit from participation in demonstration projects that innovate through the use of new PCSP model designs.

References

1. Sheen, E., Dorn, S.D., Brill, J.V., et al. Health care reform and the road ahead for gastroenterology. Clin Gastroenterol Hepatol. 2012;10:1062-5.

2. Agency for Healthcare Research and Quality. PCMH activities across federal agencies (Table 1). Available at: http://www.pcmh.ahrq.gov/sites/default/files/attachments/federal-pcmh-activities-table-1.pdf. Accessed May 13, 2015.

3. AAP, AAFP, ACP, and AOA. Joint principles of the patient-centered medical home, March 2007. Available at: http://www.acponline.org/running_practice/delivery_and_payment_models/pcmh/demonstrations/jointprinc_05_17.pdf. Accessed November 24, 2015.

4. Huang, X. Rosenthal, M.B. Transforming specialty practice–the patient-centered medical neighborhood. N Engl J Med. 2014;370:1376-9.

5. National Committee of Quality Assurance. Patient-centered specialty practice recognition: white paper. 2013. Available at: http://www.ncqa.org/Portals/0/Newsroom/2013/PCSP%20Launch/PCSPR%202013%20White%20Paper%203.26.13%20formatted.pdf. Accessed November 24, 2015.

6. National Committee of Quality Assurance. Patient-centered specialty practice frequently asked questions. Available at: http://www.ncqa.org/Programs/Recognition/Practices/PatientCenteredSpecialtyPracticePCSP/PatientCenteredSpecialtyPracticeFAQs.aspx Accessed June 4, 2015.

6. Kanwal, F. Coordinating care in patients with cirrhosis. Clin Gastroenterol Hepatol. 2013;11:859-61.

7. Fortune, B.E., Golus, A., Barsky, C.L., et al. Linking a hepatology clinical service line to quality improvement. Clin Gastroenterol Hepatol. 2015;13:1391-5.

8. Alakeson, V., Frank, R.G., Katz, R.E. Specialty care medical homes for people with severe, persistent mental disorders. Health Affairs. 2010;29:867-73.

9. Talwalkar, J.A. Potential impacts of the Affordable Care Act on the clinical practice of hepatology. Hepatology. 2014;59:1681-7.

9. Volk, M.L., Tocco, R.S., Bazick, J., et al. Hospital readmissions among patients with decompensated cirrhosis. Am J Gastroenterol. 2012;107:247-52.

10. Berman, K., Tandra, S., Forssell, K., et al. Incidence and predictors of 30-day readmission among patients hospitalized for advanced liver disease. Clin Gastroenterol Hepatol. 2011;9:254-9.

11. Tapper, E.B., Finkelstein, D., Mittleman, M.A., et al. Standard assessments of frailty are validated predictors of mortality in hospitalized patients with cirrhosis. Hepatology. 2015;62:584-90.

12. Eappen, S., Lane, B.H., Rosenberg, B., et al. Relationship between occurrence of surgical complications and hospital finances. JAMA. 2013;309:1599-606.

Dr. Meier, Dr. Shah, and Dr. Talwalkar are in the department of health care policy and research, department of health sciences research; Dr. Talwalkar is also in the division of gastroenterology and hepatology and the William von Liebig Center for Transplantation and Regenerative Medicine; Mayo Clinic, Rochester, Minn.

United States health care is moving rapidly from volume- to value-based reimbursement. An essential part of this movement will be the development of alternative payment models where a specific bundle of care (colonoscopy), episode of care (a year of care for attributed Crohn’s patients), or ongoing care of a specialty-centric patient population (patients with cirrhosis) are covered within a contract that links health outcomes, quality of care, and payment together. Gastroenterologists are slowly becoming aware of these concepts. Primary care has its patient-centered medical home and now specialists have a patient-centric specialty practice where patient populations are cared for principally by a specialty practice within a well-defined care delivery structure. Previous columns have illustrated these concepts, and this month, Meier and colleagues provide an excellent definition and example of how practices can participate in this new world order.

John I Allen, M.D., MBA, AGAF, Special Section Editor

The Patient Protection and Affordable Care Act secures access to health insurance coverage for many previously uninsured individuals, while transforming the structure of health care delivery to promote high value care that is coordinated and patient-centered.¹ The development of innovative care delivery models is a key feature of this transformation. In turn, patient-centered medical homes (PCMHs) have proliferated in number, with PCMH-related pilot and demonstration projects spanning numerous federal agencies.²

Defining the patient-centered medical home

The concept of the PCMH predates the Patient Protection and Affordable Care Act, with its origins in the American Academy of Pediatrics’ 1967 discussion of the medical home. In 2007, a joint release by the American Academy of Family Physicians, the American Academy of Pediatrics, the American College of Physicians, and the American Osteopathic Association defined the PCMH as “an approach to providing comprehensive primary care for children, youth and adults.” Furthermore, the PCMH would serve as “a health care setting that facilitates partnerships between individual patients, and their personal physicians, and when appropriate, the patient’s family.” Several key principles underscore the PCMH model; the patient has a personal physician, and care is physician-directed at the level of the practice, oriented around the whole person, and coordinated to ensure the highest quality and safety of medical care. The PCMH facilitates enhanced access to care, and the payment structure incentivizes and compensates high-quality care delivery.³

Advent of the patient-centered specialty practice

In 2013 the National Committee for Quality Assurance (NCQA), which operates the Patient Centered Medical Home Recognition program, released a set of standards governing the recognition of the patient-centered specialty practice (PCSP).⁴ Similar to the PCMH model, the PCSP model places the patient at the center of care delivery. Key functions of the PCSP include placing the patient at the center of care, sharing of information, and coordinating across all practices (specialty and primary) for patients.⁵ The NCQA outlines six standards for PCSP recognition; these standards focus on planning, management, tracking and coordination of care, performance measurement, performance improvement, referrals, communication to patients, care access, and coordination and management for populations.⁵

Centering patient care in the specialty practice

With the release of the NCQA PCSP standards, provider groups and regulators should work to identify circumstances under which the PCSP might best operate as an effective model for the populations they serve. For example, in the case of mental illness that is both severe and persistent, the creation of a PCMH may disrupt existing patient-provider relationships, increase fragmentation of medical care, and position poorly equipped providers at the center of a care process that requires greater specialization.⁶

Drawing from this example, we suggest that select patient populations with advanced chronic liver disease may benefit from the development of patient-centered care models that operate such as a PCSP. This may include patients with compensated cirrhosis and other comorbid illnesses such as diabetes mellitus or depression, populations with active complications of portal hypertension, or patients who await or have received liver transplantation.^7,8 We suggest examining the potential value of this model in circumstances where the complexity of patient needs or the sensitivity and vulnerability of the patient circumstance may best be managed by an established, trusted, and specialized provider. In the case of patients with cirrhosis and substance abuse from alcohol, a hybrid specialty model that incorporates addiction medicine, social work, and psychiatry providers in addition to hepatologists and allied health providers may be warranted.⁷

Designing the patient-centered specialty practice for populations with cirrhosis and liver transplant recipients

Practices and providers should carefully assess the context for PCSP adoption, identifying whether the specialty care model will promote greater efficiency and quality than that realized in the absence of a PCSP model. The PCSP model should align with patient needs, considering factors such as cause of disease, disease stage, comorbidities and complications, and socioeconomic factors. Although the NCQA PCSP standards should guide model development, there are specific needs and complexities of cirrhosis and liver transplant populations that may prove highly relevant in identifying one or more ideal model designs. This may entail development of additional PCSP standards beyond what is recognized by NCQA.

Table 1 outlines key questions providers might address when considering the development of the PCSP in this patient population. We divide these questions into three main categories: 1) understanding the context for PCSP model adoption, 2) identifying opportunities to align the PCSP model with the specific needs of the patient population, and 3) selecting a model design. Incorporating careful consideration of the questions highlighted within each of these categories can help inform practitioners on the merits of various PCSP models.

Understanding the context for patient-centered specialty practice adoption

Drawing from Alakeson et al.,⁹ we suggest that providers embarking on PCSP model adoption first consider how the quality of care and strength of patient-provider relationships for the target population will improve. The selection of an appropriate patient population is a key determinant in the answer to this question. Focusing specifically on the cirrhosis population, the PCSP may need to be directed toward a disease stage (i.e., decompensated cirrhosis) where the specialist is the most frequent and continuous point of system access. Similarly, the PCSP might yield the greatest gains in quality when access is a function of requiring specialized knowledge in the day-to-day management of care delivery (i.e., compensated liver disease or long-term post liver transplant recipients).

The case for the PCSP may be particularly strong in instances where the primary care provider lacks sufficient knowledge to appropriately manage patient care. For example, treatment of mental and behavioral health conditions that are comorbid with cirrhosis may best be suited to a specialized and established care team that has secured patient trust. Many transplant centers in the United States have explicitly created teams in this regard in the context of regulatory requirements for being a transplant program.¹⁰

Identifying opportunities to align the patient-centered specialty practice model with the specific needs of the patient population

Liver transplant and cirrhosis patients exhibit variability in the cause of disease, with genetic, social-behavioral, and other causal mechanisms operating as factors in the expression of disease. Developing a model focused on reduction in the risk of need for transplant might differ from these former two examples in target population and specialist team. A relevant example is with hospital readmissions because multiple studies to date have documented at least a 20% frequency of re-hospitalization within 30 days of index readmission.^11,12 Although disease severity indicated by Model for End Stage Liver Disease score explains a significant amount of the variability in risk for readmission, there are other factors including frailty¹³ and complications from index hospitalization14 that also contribute to 30-day readmission. The use of case management and remote monitoring strategies for patients at risk for hospital readmission is likely to be included in a PCSP focused on reducing inpatient utilization.

Variability in the social and economic context surrounding a patient’s daily life should also factor into model design. In the case of Medicaid coverage, a well-designed model might address discontinuities in specific provider and service access arising from churning in Medicaid eligibility and coverage.

Selecting a model design

Three examples of specialty care medical home designs have been described in the literature including the integrated model concept and two variants of the partnership model design. The integrated model concept provides specialty and primary care in one location, whereas the partnership models include an on-site liaison at the specialty practice, either a nurse practitioner who provides some degree of care and is able to draw from the services from an off-site primary care physician or otherwise an on-site nurse care manager who serves as an information source and advocate.⁹

We suggest that selection of model design should consider the number of specialty and primary care providers required to construct a comprehensive care team and whether there is reasonable capacity for patients to access comprehensive care in multiple settings. Providing a spectrum of services through separately located but coordinated PCSP and PCMH care models may be practical for some target populations. In other instances, multisite care programs may place an undesirable and impractical burden on patients with complex needs or low health system literacy.

As the field of PCSP model development moves forward, we suggest that providers learn from shared discussions of experience. If appropriate, innovation and shared learning should inform the development of additional standards to ensure that PCSP development for cirrhosis and transplant patients adheres to meaningful quality standards. As is clear from discussion, cirrhosis and liver transplant patients are a diverse group with a range of needs that fall across a spectrum of complexity. The development of well-structured PCSP models may require a high degree of specialization, where model adaptation acknowledges how specific disease-based needs, clinical comorbidities, and external support networks vary across groups.

One suggestion for moving forward is to focus early efforts narrowly on small and highly complex patient groups where the expected value of PCSP is large. This may entail beginning with patient groups whose clinical complexity may otherwise disqualify them from participation in traditional patient-centered care model demonstrations and evaluations. An ideal target population would be patients with decompensated cirrhosis who are ineligible for liver transplantation on the basis of multimorbidity. In addition, specialty providers might consider partnering with state agencies or patient groups in the development, testing, and funding of such programs. These partnerships may help to identify target patient populations with potential to benefit from participation in demonstration projects that innovate through the use of new PCSP model designs.

References

1. Sheen, E., Dorn, S.D., Brill, J.V., et al. Health care reform and the road ahead for gastroenterology. Clin Gastroenterol Hepatol. 2012;10:1062-5.

2. Agency for Healthcare Research and Quality. PCMH activities across federal agencies (Table 1). Available at: http://www.pcmh.ahrq.gov/sites/default/files/attachments/federal-pcmh-activities-table-1.pdf. Accessed May 13, 2015.

3. AAP, AAFP, ACP, and AOA. Joint principles of the patient-centered medical home, March 2007. Available at: http://www.acponline.org/running_practice/delivery_and_payment_models/pcmh/demonstrations/jointprinc_05_17.pdf. Accessed November 24, 2015.

4. Huang, X. Rosenthal, M.B. Transforming specialty practice–the patient-centered medical neighborhood. N Engl J Med. 2014;370:1376-9.

5. National Committee of Quality Assurance. Patient-centered specialty practice recognition: white paper. 2013. Available at: http://www.ncqa.org/Portals/0/Newsroom/2013/PCSP%20Launch/PCSPR%202013%20White%20Paper%203.26.13%20formatted.pdf. Accessed November 24, 2015.

6. National Committee of Quality Assurance. Patient-centered specialty practice frequently asked questions. Available at: http://www.ncqa.org/Programs/Recognition/Practices/PatientCenteredSpecialtyPracticePCSP/PatientCenteredSpecialtyPracticeFAQs.aspx Accessed June 4, 2015.

6. Kanwal, F. Coordinating care in patients with cirrhosis. Clin Gastroenterol Hepatol. 2013;11:859-61.

7. Fortune, B.E., Golus, A., Barsky, C.L., et al. Linking a hepatology clinical service line to quality improvement. Clin Gastroenterol Hepatol. 2015;13:1391-5.

8. Alakeson, V., Frank, R.G., Katz, R.E. Specialty care medical homes for people with severe, persistent mental disorders. Health Affairs. 2010;29:867-73.

9. Talwalkar, J.A. Potential impacts of the Affordable Care Act on the clinical practice of hepatology. Hepatology. 2014;59:1681-7.

9. Volk, M.L., Tocco, R.S., Bazick, J., et al. Hospital readmissions among patients with decompensated cirrhosis. Am J Gastroenterol. 2012;107:247-52.

10. Berman, K., Tandra, S., Forssell, K., et al. Incidence and predictors of 30-day readmission among patients hospitalized for advanced liver disease. Clin Gastroenterol Hepatol. 2011;9:254-9.

11. Tapper, E.B., Finkelstein, D., Mittleman, M.A., et al. Standard assessments of frailty are validated predictors of mortality in hospitalized patients with cirrhosis. Hepatology. 2015;62:584-90.

12. Eappen, S., Lane, B.H., Rosenberg, B., et al. Relationship between occurrence of surgical complications and hospital finances. JAMA. 2013;309:1599-606.

Dr. Meier, Dr. Shah, and Dr. Talwalkar are in the department of health care policy and research, department of health sciences research; Dr. Talwalkar is also in the division of gastroenterology and hepatology and the William von Liebig Center for Transplantation and Regenerative Medicine; Mayo Clinic, Rochester, Minn.

The clinical management of transgender and gender nonconforming youth is a growing area in pediatric endocrinology and adolescent medicine with multiple questions and challenges. One of the many challenges relates to the decision-making process for transitioning to the self-identified gender. Many medical and ethical aspects surround this issue. What are the risks in delaying transition until adulthood? Can clinicians correctly diagnose gender dysphoria in childhood and adolescence? Are children and adolescents capable of making life-changing decisions? What are the long-term psychological and medical consequences of puberty suppression and cross-sex hormones? Each of these questions may pose a conundrum for patients, families, and clinicians to consider.

What are the risks of delaying transition until adulthood?

Available studies report the incidence of mental health problems among transgender and gender nonconforming youth are higher than the incidence in cisgender youth.¹ This is especially true if they are unable to live as the gender with which they identify. de Vries et al. showed that transgender adults going through transition had worse baseline mental health problems than did transgender adolescents going through transition.² This makes sense, as transgender adults are less likely to have been living as their gender identity, compared with transgender adolescents. This exposes them to longer periods of gender dysphoria and to harassment and discrimination. There are medical risks as well. Some surgical procedures are much more difficult to perform on a fully mature adult. For example, breast removal surgery for a transmale who has fully developed breasts may result in significant scarring, which could have been avoided if the surgery was done when the patient was younger with smaller breasts.³ Furthermore, the secondary sex characteristics that develop during puberty can be much more difficult to remove in adulthood. These characteristics may result in an appearance that can provoke abuse and harassment. Patients can avoid this by the use of hormone blockers at an early age, which would prevent the development of the undesired secondary sex characteristics.

Can gender dysphoria be diagnosed at an early age?

Because of the risks associated with pubertal suppression and cross-sex hormones, there is a concern about making the right diagnosis. Past studies have reported that among children exhibiting gender dysphoria, about 10%-25% will continue to have gender dysphoria after the onset of puberty.^4,5 Because of this low rate of children with persistent gender dysphoria, many feel that making the diagnosis at such a young age, especially if the diagnosis is incorrect, will put them through unnecessary risks.

One potential treatment for some prepubertal children with gender dysphoria is social transition; for example, using the preferred name and pronouns, change of clothing and hairstyle, and so on. This is reversible; however, there are no studies documenting the psychosocial outcomes of children whose gender dysphoria desists in adolescence. Furthermore, the use of pubertal blockers does not begin until the patient reaches Tanner Stage 2,^6,7 and the use of cross-sex hormones typically does not begin until age 16 years old. This allows time for the child to work with a mental health therapist to confirm their gender identity. Finally, children who have gender dysphoria beginning at puberty or persisting after puberty generally have persistent gender dysphoria in adulthood.³

What are the medical risks with pubertal suppression and cross-sex hormones?

One of the risks for puberty suppression with a gonadotropin-releasing hormone agonist (GnRHa) – such as leuprolide – is reduced bone mineral density (BMD).⁷ Most bone accretion occurs during adolescence and cannot be recovered in adulthood. There are no studies on how GnRHa may affect BMD in transgender children and adolescents. The best evidence comes from GnRHa treatment of central precocious puberty in children, which has mixed results. Some studies show that GnRHa may lead to lower BMD,⁸ whereas other studies showed no difference in BMD between those treated with GnRHa versus those who were not,^9,10 especially after resumption of puberty.

What are the medical risks of using cross-sex hormones?

Likewise, use of cross-sex hormones – like estrogen and testosterone – is not risk free. The most likely risks with estrogen are venous thromboembolic events including pulmonary emboli, blood clots, gallstones, elevated liver enzymes, weight gain, and high cholesterol. Polycythemia, weight gain, acne, male pattern baldness, and sleep apnea are risks associated with testosterone use.⁷ Additionally, use of these hormones can induce infertility, and this is not always reversible.⁶ Furthermore, there are some studies in animal and human models that highlight the importance of sex hormones in organizing the brain during the critical period of adolescence.¹¹ There is some concern that pubertal suppression or the use of cross-sex hormones for transition during this time may disrupt this process. However, one prospective study showed that adolescents who received pubertal suppression and cross-sex hormones had no psychopathology as adults and even had improved mental health outcomes.¹² Nevertheless, this is only one study and further studies should confirm that pubertal suppression and sex reassignment are beneficial to the patient.

Can children and adolescents make complex, life-changing decisions?

The ethical issues of managing gender dysphoria in children and adolescents are the avoidance of harm – in both treatment and delaying treatment until the patient is older – and determining if children and adolescents are capable of making important decisions. Many would argue that children are not capable of making complex, life-changing decisions. For example, we wouldn’t expect an 8-year-old recently diagnosed with cancer to decide whether to proceed with treatment, knowing the potential side effects. Nevertheless, the recommended treatment for children is social transition. This process is reversible with little psychological and medical consequences.

However, adolescence can cloud the issue. Depending on the state, teenagers can obtain care for sexually transmitted infections (STIs) and contraception services without parental consent. Prevention of the spread of STIs and unwanted pregnancy are the primary rationales behind this, as adolescents are less likely to obtain these services if doing so required parental consent.¹³ However, underlying this rationale is the belief that adolescents are capable of making some complex decisions. Although the treatment of STIs or preventing unwanted pregnancy is not as complex as pubertal suppression or use of cross-sex hormones, the consequences of foregoing medical care of STIs (for example, the possibility of infertility due to pelvic inflammatory disease) or unexpected pregnancy are also life-changing.

One also must remember that not all adolescents reach their developmental milestones at the same age. A 14-year-old may have cognitive and executive functioning advanced for their age whereas an 18-year-old may lack these skills. Because of this variation, an interdisciplinary team including clinicians and behavioral/mental health experts should help individuals through the process of characterizing their self-identified gender identity and support their eventual transition using, as indicated for each individual, pubertal suppression, cross-sex hormones, and, ultimately, surgery.

The treatment of gender dysphoria in children and adolescents is characterized by ethical, medical, and psychosocial dilemmas. Long-term data are not available to determine the optimal age for transition for each individual. Despite the long-term risks, some children and adolescents are capable of making some important decisions. Furthermore, some treatment recommendations for children and adolescents who have gender dysphoria are reversible. At the end of the day, clinicians must combine the limited evidence with their experience to make the best judgment on how to proceed. Most important of all, they should allow the child to lead because he/she is the best judge of his/her gender identity.

References:

1. Institute of Medicine (U.S.) Committee on Lesbian, Gay, Bisexual, and Transgender Health Issues and Research Gaps and Opportunities. The Health of Lesbian, Gay, Bisexual, and Transgender People: Building a Foundation for Better Understanding. (Washington, D.C.: National Academies Press, 2011).

2. Psychiatry Res. 2011 Apr 30;186(2-3):414-8.

3. Nat Rev Endocrinol. 2011 May 17;7(8):466-72.

4. Dev Psychol. 2008 Jan;44(1):34-45.

5. J Adolesc Health. 2015 Oct;57(4):367-73.

6. J Clin Endocrinol Metab. 2009 Sep;94(9):3132-54.

7. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. 2011; 7th ed.

8. J Clin Endocrinol Metab. 2008 Jan;93(1):190-5.

9. J Clin Endocrinol Metab. 2010 Jan;95(1):109-17.

10. Clinics (Sao Paulo). 2012;67(6):591-6.

11. Front Neuroendocrinol. 2005 Oct-Dec;26(3-4):163-74.

12. Pediatrics. 2014 Oct;134(4):696-704.

13. Arch Pediatr Adolesc Med. 2000;154(9):885-92.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh. Email him at [email protected].

The clinical management of transgender and gender nonconforming youth is a growing area in pediatric endocrinology and adolescent medicine with multiple questions and challenges. One of the many challenges relates to the decision-making process for transitioning to the self-identified gender. Many medical and ethical aspects surround this issue. What are the risks in delaying transition until adulthood? Can clinicians correctly diagnose gender dysphoria in childhood and adolescence? Are children and adolescents capable of making life-changing decisions? What are the long-term psychological and medical consequences of puberty suppression and cross-sex hormones? Each of these questions may pose a conundrum for patients, families, and clinicians to consider.

What are the risks of delaying transition until adulthood?

Available studies report the incidence of mental health problems among transgender and gender nonconforming youth are higher than the incidence in cisgender youth.¹ This is especially true if they are unable to live as the gender with which they identify. de Vries et al. showed that transgender adults going through transition had worse baseline mental health problems than did transgender adolescents going through transition.² This makes sense, as transgender adults are less likely to have been living as their gender identity, compared with transgender adolescents. This exposes them to longer periods of gender dysphoria and to harassment and discrimination. There are medical risks as well. Some surgical procedures are much more difficult to perform on a fully mature adult. For example, breast removal surgery for a transmale who has fully developed breasts may result in significant scarring, which could have been avoided if the surgery was done when the patient was younger with smaller breasts.³ Furthermore, the secondary sex characteristics that develop during puberty can be much more difficult to remove in adulthood. These characteristics may result in an appearance that can provoke abuse and harassment. Patients can avoid this by the use of hormone blockers at an early age, which would prevent the development of the undesired secondary sex characteristics.

Can gender dysphoria be diagnosed at an early age?

Because of the risks associated with pubertal suppression and cross-sex hormones, there is a concern about making the right diagnosis. Past studies have reported that among children exhibiting gender dysphoria, about 10%-25% will continue to have gender dysphoria after the onset of puberty.^4,5 Because of this low rate of children with persistent gender dysphoria, many feel that making the diagnosis at such a young age, especially if the diagnosis is incorrect, will put them through unnecessary risks.

One potential treatment for some prepubertal children with gender dysphoria is social transition; for example, using the preferred name and pronouns, change of clothing and hairstyle, and so on. This is reversible; however, there are no studies documenting the psychosocial outcomes of children whose gender dysphoria desists in adolescence. Furthermore, the use of pubertal blockers does not begin until the patient reaches Tanner Stage 2,^6,7 and the use of cross-sex hormones typically does not begin until age 16 years old. This allows time for the child to work with a mental health therapist to confirm their gender identity. Finally, children who have gender dysphoria beginning at puberty or persisting after puberty generally have persistent gender dysphoria in adulthood.³

What are the medical risks with pubertal suppression and cross-sex hormones?

One of the risks for puberty suppression with a gonadotropin-releasing hormone agonist (GnRHa) – such as leuprolide – is reduced bone mineral density (BMD).⁷ Most bone accretion occurs during adolescence and cannot be recovered in adulthood. There are no studies on how GnRHa may affect BMD in transgender children and adolescents. The best evidence comes from GnRHa treatment of central precocious puberty in children, which has mixed results. Some studies show that GnRHa may lead to lower BMD,⁸ whereas other studies showed no difference in BMD between those treated with GnRHa versus those who were not,^9,10 especially after resumption of puberty.

What are the medical risks of using cross-sex hormones?

Likewise, use of cross-sex hormones – like estrogen and testosterone – is not risk free. The most likely risks with estrogen are venous thromboembolic events including pulmonary emboli, blood clots, gallstones, elevated liver enzymes, weight gain, and high cholesterol. Polycythemia, weight gain, acne, male pattern baldness, and sleep apnea are risks associated with testosterone use.⁷ Additionally, use of these hormones can induce infertility, and this is not always reversible.⁶ Furthermore, there are some studies in animal and human models that highlight the importance of sex hormones in organizing the brain during the critical period of adolescence.¹¹ There is some concern that pubertal suppression or the use of cross-sex hormones for transition during this time may disrupt this process. However, one prospective study showed that adolescents who received pubertal suppression and cross-sex hormones had no psychopathology as adults and even had improved mental health outcomes.¹² Nevertheless, this is only one study and further studies should confirm that pubertal suppression and sex reassignment are beneficial to the patient.

Can children and adolescents make complex, life-changing decisions?

The ethical issues of managing gender dysphoria in children and adolescents are the avoidance of harm – in both treatment and delaying treatment until the patient is older – and determining if children and adolescents are capable of making important decisions. Many would argue that children are not capable of making complex, life-changing decisions. For example, we wouldn’t expect an 8-year-old recently diagnosed with cancer to decide whether to proceed with treatment, knowing the potential side effects. Nevertheless, the recommended treatment for children is social transition. This process is reversible with little psychological and medical consequences.

However, adolescence can cloud the issue. Depending on the state, teenagers can obtain care for sexually transmitted infections (STIs) and contraception services without parental consent. Prevention of the spread of STIs and unwanted pregnancy are the primary rationales behind this, as adolescents are less likely to obtain these services if doing so required parental consent.¹³ However, underlying this rationale is the belief that adolescents are capable of making some complex decisions. Although the treatment of STIs or preventing unwanted pregnancy is not as complex as pubertal suppression or use of cross-sex hormones, the consequences of foregoing medical care of STIs (for example, the possibility of infertility due to pelvic inflammatory disease) or unexpected pregnancy are also life-changing.

One also must remember that not all adolescents reach their developmental milestones at the same age. A 14-year-old may have cognitive and executive functioning advanced for their age whereas an 18-year-old may lack these skills. Because of this variation, an interdisciplinary team including clinicians and behavioral/mental health experts should help individuals through the process of characterizing their self-identified gender identity and support their eventual transition using, as indicated for each individual, pubertal suppression, cross-sex hormones, and, ultimately, surgery.

The treatment of gender dysphoria in children and adolescents is characterized by ethical, medical, and psychosocial dilemmas. Long-term data are not available to determine the optimal age for transition for each individual. Despite the long-term risks, some children and adolescents are capable of making some important decisions. Furthermore, some treatment recommendations for children and adolescents who have gender dysphoria are reversible. At the end of the day, clinicians must combine the limited evidence with their experience to make the best judgment on how to proceed. Most important of all, they should allow the child to lead because he/she is the best judge of his/her gender identity.

References:

1. Institute of Medicine (U.S.) Committee on Lesbian, Gay, Bisexual, and Transgender Health Issues and Research Gaps and Opportunities. The Health of Lesbian, Gay, Bisexual, and Transgender People: Building a Foundation for Better Understanding. (Washington, D.C.: National Academies Press, 2011).

2. Psychiatry Res. 2011 Apr 30;186(2-3):414-8.

3. Nat Rev Endocrinol. 2011 May 17;7(8):466-72.

4. Dev Psychol. 2008 Jan;44(1):34-45.

5. J Adolesc Health. 2015 Oct;57(4):367-73.

6. J Clin Endocrinol Metab. 2009 Sep;94(9):3132-54.

7. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. 2011; 7th ed.

8. J Clin Endocrinol Metab. 2008 Jan;93(1):190-5.

9. J Clin Endocrinol Metab. 2010 Jan;95(1):109-17.

10. Clinics (Sao Paulo). 2012;67(6):591-6.

11. Front Neuroendocrinol. 2005 Oct-Dec;26(3-4):163-74.

12. Pediatrics. 2014 Oct;134(4):696-704.

13. Arch Pediatr Adolesc Med. 2000;154(9):885-92.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh. Email him at [email protected].

The clinical management of transgender and gender nonconforming youth is a growing area in pediatric endocrinology and adolescent medicine with multiple questions and challenges. One of the many challenges relates to the decision-making process for transitioning to the self-identified gender. Many medical and ethical aspects surround this issue. What are the risks in delaying transition until adulthood? Can clinicians correctly diagnose gender dysphoria in childhood and adolescence? Are children and adolescents capable of making life-changing decisions? What are the long-term psychological and medical consequences of puberty suppression and cross-sex hormones? Each of these questions may pose a conundrum for patients, families, and clinicians to consider.

What are the risks of delaying transition until adulthood?

Available studies report the incidence of mental health problems among transgender and gender nonconforming youth are higher than the incidence in cisgender youth.¹ This is especially true if they are unable to live as the gender with which they identify. de Vries et al. showed that transgender adults going through transition had worse baseline mental health problems than did transgender adolescents going through transition.² This makes sense, as transgender adults are less likely to have been living as their gender identity, compared with transgender adolescents. This exposes them to longer periods of gender dysphoria and to harassment and discrimination. There are medical risks as well. Some surgical procedures are much more difficult to perform on a fully mature adult. For example, breast removal surgery for a transmale who has fully developed breasts may result in significant scarring, which could have been avoided if the surgery was done when the patient was younger with smaller breasts.³ Furthermore, the secondary sex characteristics that develop during puberty can be much more difficult to remove in adulthood. These characteristics may result in an appearance that can provoke abuse and harassment. Patients can avoid this by the use of hormone blockers at an early age, which would prevent the development of the undesired secondary sex characteristics.

Can gender dysphoria be diagnosed at an early age?

Because of the risks associated with pubertal suppression and cross-sex hormones, there is a concern about making the right diagnosis. Past studies have reported that among children exhibiting gender dysphoria, about 10%-25% will continue to have gender dysphoria after the onset of puberty.^4,5 Because of this low rate of children with persistent gender dysphoria, many feel that making the diagnosis at such a young age, especially if the diagnosis is incorrect, will put them through unnecessary risks.

One potential treatment for some prepubertal children with gender dysphoria is social transition; for example, using the preferred name and pronouns, change of clothing and hairstyle, and so on. This is reversible; however, there are no studies documenting the psychosocial outcomes of children whose gender dysphoria desists in adolescence. Furthermore, the use of pubertal blockers does not begin until the patient reaches Tanner Stage 2,^6,7 and the use of cross-sex hormones typically does not begin until age 16 years old. This allows time for the child to work with a mental health therapist to confirm their gender identity. Finally, children who have gender dysphoria beginning at puberty or persisting after puberty generally have persistent gender dysphoria in adulthood.³

What are the medical risks with pubertal suppression and cross-sex hormones?

One of the risks for puberty suppression with a gonadotropin-releasing hormone agonist (GnRHa) – such as leuprolide – is reduced bone mineral density (BMD).⁷ Most bone accretion occurs during adolescence and cannot be recovered in adulthood. There are no studies on how GnRHa may affect BMD in transgender children and adolescents. The best evidence comes from GnRHa treatment of central precocious puberty in children, which has mixed results. Some studies show that GnRHa may lead to lower BMD,⁸ whereas other studies showed no difference in BMD between those treated with GnRHa versus those who were not,^9,10 especially after resumption of puberty.

What are the medical risks of using cross-sex hormones?

Likewise, use of cross-sex hormones – like estrogen and testosterone – is not risk free. The most likely risks with estrogen are venous thromboembolic events including pulmonary emboli, blood clots, gallstones, elevated liver enzymes, weight gain, and high cholesterol. Polycythemia, weight gain, acne, male pattern baldness, and sleep apnea are risks associated with testosterone use.⁷ Additionally, use of these hormones can induce infertility, and this is not always reversible.⁶ Furthermore, there are some studies in animal and human models that highlight the importance of sex hormones in organizing the brain during the critical period of adolescence.¹¹ There is some concern that pubertal suppression or the use of cross-sex hormones for transition during this time may disrupt this process. However, one prospective study showed that adolescents who received pubertal suppression and cross-sex hormones had no psychopathology as adults and even had improved mental health outcomes.¹² Nevertheless, this is only one study and further studies should confirm that pubertal suppression and sex reassignment are beneficial to the patient.

Can children and adolescents make complex, life-changing decisions?

The ethical issues of managing gender dysphoria in children and adolescents are the avoidance of harm – in both treatment and delaying treatment until the patient is older – and determining if children and adolescents are capable of making important decisions. Many would argue that children are not capable of making complex, life-changing decisions. For example, we wouldn’t expect an 8-year-old recently diagnosed with cancer to decide whether to proceed with treatment, knowing the potential side effects. Nevertheless, the recommended treatment for children is social transition. This process is reversible with little psychological and medical consequences.

However, adolescence can cloud the issue. Depending on the state, teenagers can obtain care for sexually transmitted infections (STIs) and contraception services without parental consent. Prevention of the spread of STIs and unwanted pregnancy are the primary rationales behind this, as adolescents are less likely to obtain these services if doing so required parental consent.¹³ However, underlying this rationale is the belief that adolescents are capable of making some complex decisions. Although the treatment of STIs or preventing unwanted pregnancy is not as complex as pubertal suppression or use of cross-sex hormones, the consequences of foregoing medical care of STIs (for example, the possibility of infertility due to pelvic inflammatory disease) or unexpected pregnancy are also life-changing.

One also must remember that not all adolescents reach their developmental milestones at the same age. A 14-year-old may have cognitive and executive functioning advanced for their age whereas an 18-year-old may lack these skills. Because of this variation, an interdisciplinary team including clinicians and behavioral/mental health experts should help individuals through the process of characterizing their self-identified gender identity and support their eventual transition using, as indicated for each individual, pubertal suppression, cross-sex hormones, and, ultimately, surgery.

The treatment of gender dysphoria in children and adolescents is characterized by ethical, medical, and psychosocial dilemmas. Long-term data are not available to determine the optimal age for transition for each individual. Despite the long-term risks, some children and adolescents are capable of making some important decisions. Furthermore, some treatment recommendations for children and adolescents who have gender dysphoria are reversible. At the end of the day, clinicians must combine the limited evidence with their experience to make the best judgment on how to proceed. Most important of all, they should allow the child to lead because he/she is the best judge of his/her gender identity.

References:

1. Institute of Medicine (U.S.) Committee on Lesbian, Gay, Bisexual, and Transgender Health Issues and Research Gaps and Opportunities. The Health of Lesbian, Gay, Bisexual, and Transgender People: Building a Foundation for Better Understanding. (Washington, D.C.: National Academies Press, 2011).

2. Psychiatry Res. 2011 Apr 30;186(2-3):414-8.

3. Nat Rev Endocrinol. 2011 May 17;7(8):466-72.

4. Dev Psychol. 2008 Jan;44(1):34-45.

5. J Adolesc Health. 2015 Oct;57(4):367-73.

6. J Clin Endocrinol Metab. 2009 Sep;94(9):3132-54.

7. The World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People. 2011; 7th ed.

8. J Clin Endocrinol Metab. 2008 Jan;93(1):190-5.

9. J Clin Endocrinol Metab. 2010 Jan;95(1):109-17.

10. Clinics (Sao Paulo). 2012;67(6):591-6.

11. Front Neuroendocrinol. 2005 Oct-Dec;26(3-4):163-74.

12. Pediatrics. 2014 Oct;134(4):696-704.

13. Arch Pediatr Adolesc Med. 2000;154(9):885-92.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh. Email him at [email protected].

FLORENCE, ITALY – The 2016 revision of the European Society of Cardiology’s guidelines for diagnosing and treating acute and chronic heart failure highlights the extent to which thinking in the field has changed during the past 4 years, since the prior edition in 2012.

The new European guidelines, unveiled by the ESC’s Heart Failure Association during the group’s annual meeting, also underscore the great dependence that many new approaches have on expert opinion rather than what’s become the keystone of guidelines writing, evidence-based medicine. Frequent reliance on consensus decisions rather than indisputable proof from controlled trials defines what some U.S. specialists see as a divide as wide as the Atlantic between the European and U.S. approaches to guideline writing.

Mitchel L. Zoler/Frontline Medical News

“The guidelines from the ESC are articulated very well; they made their recommendations very clear. But a lot is consensus driven, without new data,” said Dr. Mariell L. Jessup, who serves as both vice chair of the panel currently revising the U.S. heart failure guidelines – expected out later in 2016 – and was also the sole American representative on the panel that produced the ESC guidelines. “The ESC guidelines make clear all the things that need to happen to patients. I hope it will result in better patient care. We are clearly not doing a good job in heart failure. We not only don’t have evidence-based treatments, but people often don’t do a good job [caring for heart failure patients] and they die in the hospital all the time.”

Dr. Javed Butler, another member of the U.S. guidelines panel and professor and chief of cardiology at Stony Brook (N.Y.) University, called the U.S. and European divide a “philosophical perspective of evidence-based medicine.

“U.S. physicians should read the ESC guidelines and make up their own minds. The ESC guidelines are excellent and give you perspective. But U.S. regulatory and payment issues will be driven by U.S. guidelines,” Dr. Butler said in an interview.

Mitchel L. Zoler/Frontline Medical News

But despite their limitations and the limited weight that the ESC guidelines carry for U.S. practice, they have many redeeming features, noted Dr. Mandeep R. Mehra, medical director of the Heart and Vascular Center at Brigham and Women’s Hospital in Boston. The 2016 ESC guidelines “are extraordinarily clear, very practical, and very concise. They are very usable, and provide a fantastic algorithm for managing patients with heart failure with reduced ejection fraction [HFrEF],” he said while discussing the guidelines during the meeting.

U.S. and Europe largely agree on sacubitril/valsartan and ivabradine

Clearly the greatest area of U.S. and European agreement was in the adoption by both guidelines groups of sacubitril/valsartan (Entresto) and ivabradine (Corlanor) as important new components of the basic drug formula for treating patients with HFrEF. In fact, the U.S. guideline writers saw these two additions as so important and timely that they issued a “focused update” in May to the existing, 2013 U.S. heart failure guidelines, and timed release of this update to occur on May 20, 2016, a day before release of the ESC guidelines. But as Dr. Butler noted, this was more of a temporal harmonization than a substantive one, because even here, in a very evidence-based change, the U.S. guidelines for using sacubitril/valsartan differed subtly but importantly from the ESC version.

The U.S. focused update says that treatment of patients with stage C (symptomatic heart failure with structural heart disease) HFrEF should receive treatment with sacubitril/valsartan (also know as an angiotensin receptor neprilysin inhibitor, or ARNI), an ACE inhibitor, or an angiotensin receptor blocker (ARB), as well as evidence-based treatment with a beta-blocker and with a mineralocorticoid receptor antagonist (MRA). A subsequent recommendation in the U.S. focused update said that HFrEF patients with chronic symptoms and New York Heart Association class II or III disease should switch from a stable, tolerated regimen with either an ACE inhibitor or ARB to treatment with sacubitril/valsartan.

Courtesy Stony Brook University

In contrast, the new European guideline for sacubitril/valsartan recommends starting patients on this combination formulation only after first demonstrating that patients tolerated treatment with an ACE inhibitor or ARB for at least 30 days and determining that patients remained symptomatic while on one of these treatments. In short, the U.S. guideline gives a green light to starting patients with newly diagnosed, symptomatic HFrEF on sacubitril/valsartan immediately, while the European guideline only sanctions sacubitril/valsartan to start after a patient has spent at least 30 days settling into a multidrug regimen featuring an ACE inhibitor or an ARB when an ACE inhibitor isn’t well tolerated.

“The European guidelines are closely related to the study population enrolled in the PARADIGM-HF trial,” the pivotal trial that showed superiority of sacubitril/valsartan to an ACE inhibitor (N Engl J Med. 2014;371:993-1004), noted Dr. Butler in an interview. “The U.S. guidelines interpreted [the PARADIGM-HF] results in the best interests of a larger patient population. The European guidelines are far more proscriptive in replicating the clinical criteria of the trial. In some patients the sequence of starting a MRA and sacubitril/valsartan matters, but in other patients it is less important.”

Dr. Frank Ruschitzka, a coauthor of the ESC guidelines, said that the reason for the more cautious ESC approach was lack of widespread familiarity with sacubitril/valsartan treatment among cardiologists.

Mitchel L. Zoler/Frontline Medical News

The ESC guidelines on using sacubitril/valsartan “replicated the PARADIGM-HF trial. We have no data right now that it is justifiable to put a [treatment-naive] patient on sacubitril/valsartan to begin with. Another difference between the U.S. and ESC guidelines is when to start a MRA,” said Dr. Ruschitzka, professor and head of cardiology at the Heart Center of the University Hospital in Zurich. “It makes a lot of sense to me to start sacubitril/valsartan early. The PARADIGM trial was positive, but no one has a feel for how to use sacubitril/valsartan. Should we give it to everyone? We said replicate the trial, and gain experience using the drug. We want to bring a life-saving drug to patients, but this is the approach we took. We need more data.”

Dr. Jessup noted that a lot of uncertainty also exists among U.S. clinicians about when to start sacubitril/valsartan. “It’s not been clear which patients to put on sacubitril/valsartan. No guidelines had been out on using it” until mid-May, and “the cost of sacubitril/valsartan is daunting. I have received calls from many people who ask whom am I supposed to use sacubitril/valsartan on? It took years and years to get people to [routinely] start patients on an ACE inhibitor and a beta-blocker, and now we’re telling them to do something else. In my practice it’s a 30-minute conversation with each patient that you need to first stop your ACE inhibitor, and then they often get denied coverage by their insurer,” said Dr. Jessup, professor of medicine at the University of Pennsylvania in Philadelphia. She expressed hope that coverage issues will diminish now that clear guidelines are out endorsing a key role for sacubitril/valsartan.

Mitchel L. Zoler/Frontline Medical News

“We now all have started sacubitril/valsartan on patients” without first starting them on an ACE inhibitor, “but we all need to get a sense of what we can get away with” when using this drug, noted Dr. JoAnn Lindenfeld, professor and director of heart failure and transplant at Vanderbilt University in Nashville.

At least one European cardiologist was skeptical of just how proscriptive the ESC guideline for sacubitril/valsartan will be in actual practice.

“The best treatment [for symptomatic HFrEF] is sacubitril/valsartan, a beta-blocker, and a MRA,” said Dr. John J.V. McMurray, professor of cardiology at Glasgow University and lead investigator for the PARADIGM-HF pivotal trial for sacubitril/valsartan. “The treatment sequence advocated in the guidelines – treat with an ACE inhibitor first and if patients remain symptomatic change to sacubitril/valsartan – is evidence-based medicine. As a guidelines writer and as a promoter of evidence-based medicine, this is absolutely the correct approach. But as a practicing physician I’d go straight for sacubitril/valsartan. Otherwise you’re wasting everybody’s time starting with an ACE inhibitor and then waiting a month to switch,” Dr. McMurray said in an interview.

Mitchel L. Zoler/Frontline Medical News

“It’s pointless to wait. We saw results within 30 days of starting sacubitril/valsartan, so it’s a theoretical risk to wait. Very few patients will become completely asymptomatic on an ACE inhibitor. Everyone who entered PARADIGM-HF was at New York Heart Association class II or higher, and at the time of randomization only a handful of patients were in New York Heart Association class I. Very few patients get to class I. That tells you it’s pretty uncommon for a heart failure patient to become truly asymptomatic with ACE inhibitor treatment. The main problem is that you are inconveniencing everybody with more blood tests and more clinic visits by waiting to start sacubitril/valsartan, said Dr. McMurray, who was not a member of the panel that wrote the new ESC guidelines.

Even less separates the new U.S. focused update and the ESC guidelines for using ivabradine. Both agree on starting the drug on HFrEF patients who remain symptomatic and with a left ventricular ejection fraction of 35% or less despite being on guideline-directed therapy including titration to a maximum beta-blocker dosage and with a persistent heart rate of at least 70 beats/min. The goal of ivabradine treatment is to further reduce heart rate beyond what’s achieved by a maximal beta-blocker dosage.

Perhaps the biggest questions about ivabradine have been why it took so long to enter the U.S. guidelines, and why it is listed in both the U.S. and ESC guidelines as a level II recommendation. Results from the pivotal trial that supported ivabradine’s use in HFrEF patients, SHIFT, first appeared in 2010 (Lancet. 2010 Sep 11;376[9744]:875-95).

Dr. Butler chalked up the drug’s slow entry into U.S. guidelines as the result of a lack of initiative by ivabradine’s initial developer, Servier. “SHIFT did not have any U.S. sites, and Servier never sought Food and Drug Administration approval,” he noted. “Amgen acquired the U.S. rights to ivabradine in 2013,” and the drug received FDA approval in April 2015, Dr. Butler noted, in explaining the drug’s U.S. timeline. As to why its use is a level II recommendation, he noted that the evidence for efficacy came only from the SHIFT trial, questions exist whether the beta-blocker dosages were fully optimized in all patients in this trial, and the benefit was limited to a reduction in heart failure hospitalizations but not in mortality. “I think that patients with persistent heart failure symptoms [and a persistently elevated heart rate] should get ivabradine,” but these caveats limit it to a class II level recommendation, Dr. Butler said.

“There were questions about ivabradine’s benefit in reducing heart failure hospitalization but not mortality, and questions about whether it would benefit patients if their beta-blocker dosage was adequately up titrated. There were also questions about which heart failure patients to use it on,” noted Dr. Lindenfeld, a member of the panel that wrote the U.S. focused update. These concerns in part help explain the delay to integrating ivabradine into U.S. practice guidelines, she said in an interview, but added that additional data and analysis published during the past 3 or so years have clarified ivabradine’s potentially useful role in treating selected HFrEF patients.

New ESC guidelines based on expert opinion

The sections on sacubitril/valsartan and ivabradine occupy a mere 2 pages among more than 55 pages of text and charts that spell out the ESC’s current vision of how physicians should diagnose and manage heart failure patients. While much of what carried over from prior editions of the guidelines is rooted in evidence, many of the new approaches advocated rely on expert opinion or new interpretations of existing data. Here are some of the notable changes and highlights of the 2016 ESC recommendations:

• Heart failure diagnosis. The new ESC guidelines streamline the diagnostic process, which now focuses on five key elements: The patient’s history, physical examination, ECG, serum level of either brain natriuretic peptide (BNP) or N-terminal(NT)-proBNP, and echocardiography. The guidelines specify threshold levels of BNP and NT-proBNP that can effectively rule out heart failure, a BNP level of at least 35 pg/mL or a NT-proBNP level of at least 125 pg/mL.

Mitchel L. Zoler/Frontline Medical News

“The diagnostic minimum levels of BNP and NT-proBNP were designed to rule out heart failure. They both have a high negative predictive value, but at these levels their positive predictive value is low,” explained Dr. Adriaan A. Voors, cochair of the ESC’s guideline-writing panel and professor of cardiology at the University of Groningen, the Netherlands.

But while these levels might be effective for reliable rule out of heart failure, they could mean a large number of patients would qualify for an echocardiographic assessment.

“If we used the ESC’s natriuretic peptide cutoffs, there would be a clear concern about overuse of echo. It’s a cost-effectiveness issue. You wind up doing a lot of echos that will be normal. Echocardiography is very safe, but each echo costs about $400-$500,” commented Dr. Butler.

“The results from the STOP-HF and PONTIAC studies showed that BNP levels can identify people at increased risk for developing heart failure who need more intensive assessment and could also potentially benefit from more attention to heart failure prevention. I suspect the full U.S. guideline update will address this issue, but we have not yet finalized our decisions,” he added.

• Heart failure classification. The new ESC guidelines created a new heart failure category, midrange ejection fraction, that the writing panel positioned squarely between the two more classic heart failure subgroups, HFrEF and heart failure with preserved ejection fraction (HFpEF). The definition of each of the three subgroups depends on left ventricular ejection fraction as determined by echocardiography: A LVEF of less than 40% defined HFrEF, a LVEF of 40%-49% defined heart failure with midrange ejection fraction (HFmrEF), and a LVEF of 50% or higher defined HFpEF. Diagnostic confirmation of both HFmrEF and HFpEF also requires that patients fulfill certain criteria of structural or functional heart abnormalities.

Mitchel L. Zoler/Frontline Medical News

The category of HFmrEF was created “to stimulate research into how to best manage these patients,” explained Dr. Piotr Ponikowski, chair of the ESC guidelines writing panel. For the time being, it remains a category with only theoretical importance as nothing is known to suggest that management of patients with HFmrEF should in any way differ from patients with HFpEF.

• Acute heart failure. Perhaps the most revolutionary element of the new guidelines is the detailed map they provide to managing patients who present with acute decompensated heart failure and the underlying principles cited to justify this radically different approach.

“The acute heart failure section was completely rewritten,” noted Dr. Ponikowski, professor of heart diseases at the Medical University in Wroclaw, Poland. “We don’t yet have evidence-based treatments” to apply to acute heart failure patients, he admitted, “however we strongly recommend the concept that the shorter the better. Shorten the time of diagnosis and for therapeutic decisions. We have borrowed from acute coronary syndrome. Don’t keep patients in the emergency department for another couple of hours just to see if they will respond. We must be aware that we need to do our best to shorten diagnosis and treatment decisions. Time is an issue. Manage a patient’s congestion and impaired peripheral perfusion within a time frame of 1-2 hours.”

The concept that acute heart failure must be quickly managed as an emergency condition similar to acute coronary syndrome first appeared as a European practice recommendation in 2015, a consensus statement from the European Heart Failure Association and two other collaborating organizations (Eur Heart J. 2015 Aug 7;36[30]:1958-66).

Mitchel L. Zoler/Frontline Medical News

“In 2015, the consensus paper talked about how to handle acute heart failure patients in the emergency department. Now, we have focused on defining the patients’ phenotype and how to categorize their treatment options. We built on the 2015 statement, but the algorithms we now have are original to 2016; they were not in the 2015 paper,” said Dr. Veli-Pekka Harjola, a member of the 2015 consensus group and 2016 guidelines panel who spearheaded writing the acute heart failure section of the new ESC guidelines.

An additional new and notable feature of this section in the 2016 guidelines is its creation of an acronym, CHAMP, designed to guide the management of patients with acute heart failure. CHAMP stands for acute Coronary syndrome, Hypertension emergency, Arrhythmia, acute Mechanical cause, and Pulmonary embolism. The CHAMP acronym’s purpose is to “focus attention on these five specific, potential causes of acute heart failure, life-threatening conditions that need immediate treatment,” explained Dr. Ponikowski.

“CHAMP emphasizes the most critical causes of acute heart failure,” added Dr. Harjola, a cardiologist at Helsinki University Central Hospital. “We created this new acronym” to help clinicians keep in mind what to look for in a patient presenting with acute heart failure.

U.S. cardiologists find things to like in what the Europeans say about managing acute heart failure, as well as aspects to question.

“It makes no sense not to aggressively treat a patient who arrives at an emergency department with acute heart failure. But there is a difference between acute MI or stroke and acute heart failure,” said Dr. Butler. “In acute MI there is the ruptured plaque and thrombus that blocks a coronary artery. In stroke there is a thrombus. These are diseases with a specific onset and treatment target. But with acute heart failure we don’t have a thrombus to treat; we don’t have a specific target. What we’ve learned from studying implanted devices [such as CardioMems] is that the congestion that causes acute heart failure can start 2-3 weeks before a patient develops acute decompensated heart failure and goes to the hospital. We have not found a specific pathophysiologic abnormality in the patient with acute heart failure that is any different from chronic heart failure. This begs the question: If a patient who presents with acute heart failure has a congestion process that’s been going on for 2 or 3 weeks what difference will another 3 hours make? Do we need to replicate the concept of an acute stroke team or acute MI response for acute heart failure?”

Dr. Butler stressed that additional data are expected soon that may help clarify this issue.

“Some large outcome trials in patients with acute heart failure are now underway, one testing serelaxin treatment, another testing ularitide treatment, that are also testing the hypothesis that rapid treatment with these drugs can produce more end-organ protection, stop damage to the heart, kidney and liver, and lead to better long-term outcomes. Until we have those data, the jury is still out” on the benefit patients gain from rapid treatment of acute heart failure. “Until then, it’s not that the data say don’t treat acute heart failure patients aggressively. But we have not yet proven it is similar to treating an acute MI or stroke,” said Dr. Butler.

Mitchel L. Zoler/Frontline Medical News

“U.S. guidelines have tended to stay away from areas where there are no evidence-based data. To their credit, the Europeans will take on something like acute heart failure where we don’t have an adequate evidence base. Despite that, they provide guidelines, which is important because clinicians need guidance even when the evidence is not very good, when the guideline is based mostly on experience and expert consensus.” commented Dr. William T. Abraham, professor and director of cardiovascular medicine at the Ohio State University Wexner Medical Center in Columbus.

“It’s absolutely appropriate to think of acute heart failure as an emergency situation. We know from high-sensitivity troponin assays that troponin levels are increased in 90% of patients who present with acute decompensated heart failure. So most acute heart failure patients are losing heart muscle cells and we should treat them like we treat acute coronary syndrome. Time matters in acute heart failure; time is heart muscle. Treatment needs to break the hemodynamic and neurohormonal storm of acute decompensated heart failure; get the patient stabilized; improve vital organ perfusion, including within the heart; and shift the myocardial oxygen supply and demand equation so myocardial necrosis stops. All of this is important, and study results suggest it’s the correct approach. I’m not sure study results prove it, but studies that have looked at the time course of treatment for acute heart failure showed that early initiation of treatment – within the first 6 hours of onset – compared with 12-24 hours of onset makes a difference in outcomes,” Dr. Abraham said in an interview.

But a major limitation to the potential efficacy of a rapidly initiated management strategy is that few interventions currently exist with proven benefits for acute heart failure patients.

For the time being, rapid intervention means using diuretics relatively quickly and, if there is an indication for treating with a vasoactive medication, using that quickly too. “The rapid approach is really more relevant to the future; it’s relevant to the design of future acute heart failure treatment trials. That is where this early treatment paradigm is important,” as it could potentially apply to new, more effective treatments of the future rather than to the marginally effective treatments now available, Dr. Abraham said.

“For a long we time haven’t pushed how quickly we should act when implementing guideline-directed treatment” for patients with acute heart failure, noted Dr. Mehra. “The CHAMP approach is interesting, and the ESC guidelines are a very interesting move in the direction” of faster action. “They speak to the period of time during which one should act. Hopefully this will help the science of acute decompensated heart failure move forward.”

But for other U.S. experts the issue again pivots on the lack of evidence.

“There is nothing new” about managing acute heart failure, said Dr. Jessup. “The ESC guideline was articulated very well; they made their recommendations very clear. But a lot is consensus driven. There are no new data. The problem with acute heart failure is that the recommendations are what we think clinicians should do. CHAMP is a nice acronym; it’s packaged better, but there are not any new data.”

Comorbidities

A dramatic contrast distinguishes the extent to which the ESC guidelines highlight comorbidities, compared with prevailing U.S. guidelines. The new ESC guidelines highlight and discuss with some detail 16 distinct comorbidities for clinicians to keep in mind when managing heart failure patients, compared with three comorbidities (atrial fibrillation, anemia, and depression) discussed with similar detail in the 2013 U.S. guidelines.

Mitchel L. Zoler/Frontline Medical News

“We are targeting comorbidities to personalize medicine, by subgrouping [heart failure] patients into groups that need to receive special attention,” explained Dr. Stefan D. Anker, a coauthor on the ESC guidelines. “We care about comorbidities because they make the diagnosis of heart failure difficult. They aggravate symptoms and contribute to additional hospitalizations. They interfere with [heart failure] treatment, and because comorbidities have led to exclusions of heart failure patients from trials, we lack evidence of treatment efficacy in patients with certain comorbidities,” said Dr. Anker, a professor of innovative clinical trials at the Medical University in Göttingen, Germany.

“The comorbidity discussion in the ESC guidelines is extremely important,” commented Dr. Abraham. “It supports the need for a multidimensional approach to heart failure patients. A cardiologist may not have all the resources to manage all the comorbidities [a heart failure patient might have]. This is why having a sleep medicine specialist, a diabetes specialist, a nephrologist, etc., involved as part of a heart failure management team can be very valuable. We need to involve subspecialists in managing the comorbidities of heart failure because they clearly have an impact on patient outcome.”

But Dr. Butler had a somewhat different take on how comorbidity management fits into the broader picture of heart failure management.

“There is no doubt that heart failure worsens other comorbidities and other comorbidities worsen heart failure. The relationship is bidirectional between heart failure and chronic obstructive pulmonary disease, liver disease, depression, sleep apnea, renal disease, lung disease, diabetes, etc. The problem is that treating a comorbidity does not necessarily translate into improved heart failure outcomes. Comorbidities are important for heart failure patients and worsen their heart failure outcomes. However, management of a comorbidity should be done primarily for the sake of improving the comorbidity. If you treat depression, for example, and it does not improve a patient’s heart failure, that doesn’t mean you shouldn’t have treated the depression. It just means that we don’t have good data that it will improve heart failure.”

Another limitation from a U.S. perspective is what role treatment of various comorbidities can play in benefiting heart failure patients and how compelling the evidence is for this. Dr. Butler gave as an example the problem with treating iron deficiency in heart failure patients who do not have anemia, a strategy endorsed in the ESC guidelines as a level IIa recommendation.

“The data regarding improved exercise capacity from treatment with intravenous ferric carboxymaltose is pretty convincing,” he said. But patients have benefited from this treatment only with improved function and quality of life, and not with improved survival or fewer hospitalizations.

“Is treating patients to improve their function and help them feel better enough?” Dr. Butler asked. “In other diseases it is. In gastrointestinal disease, if a drug helps patients feel better you approve the drug. We value improved functional capacity for patients with pulmonary hypertension, angina, and peripheral vascular disease. All these indications have drugs approved for improving functional capacity and quality of life. But for heart failure the bar has been set higher. There is a lot of interest in changing this” for heart failure.

“There is interest in running a study of ferric carboxymaltose for heart failure with a mortality endpoint. In the meantime, the impact on improving functional capacity is compelling, and it will be interesting to see what happens in the U.S. guidelines. Currently, in U.S. practice if a heart failure patient has iron-deficiency anemia you treat with intravenous iron replacement and the treatment gets reimbursed without a problem. But if the heart failure patient has iron deficiency without anemia then reimbursement for the cost of iron supplementation can be a problem,” Dr. Butler noted. This may change only if the experts who write the next U.S. heart failure guidelines decide to change the rules of what constitutes a useful heart failure treatment, he said.

Dr. Butler has been a consultant to Novartis and Amgen and several other companies. Dr. Jessup had no disclosures. Dr. Mehra has been a consultant to Teva, Johnson & Johnson, Boston Scientific, and St. Jude. Dr. Ruschitzka has been a consultant to Novartis, Servier, Sanofi, Cardiorentis, Heartware, and St. Jude. Dr. McMurray has received research support from Novartis and Amgen. Dr. Lindenfeld has been a consultant to Novartis, Abbott, Janssen, Relypsa, and Resmed. Dr. Voors has been a consultant to Novartis, Amgen, Servier, and several other drug companies. Dr. Ponikowski has been a consultant to Amgen, Novartis, Servier, and several other drug companies. Dr. Harjola has been a consultant to Novartis, Servier, Bayer, Boehringer Ingelheim, Pfizer, and Resmed. Dr. Abraham has been a consultant to Amgen, Novartis, and several device companies. Dr. Anker has been a consultant to Novartis, Servier, and several other companies.

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FLORENCE, ITALY – The 2016 revision of the European Society of Cardiology’s guidelines for diagnosing and treating acute and chronic heart failure highlights the extent to which thinking in the field has changed during the past 4 years, since the prior edition in 2012.

The new European guidelines, unveiled by the ESC’s Heart Failure Association during the group’s annual meeting, also underscore the great dependence that many new approaches have on expert opinion rather than what’s become the keystone of guidelines writing, evidence-based medicine. Frequent reliance on consensus decisions rather than indisputable proof from controlled trials defines what some U.S. specialists see as a divide as wide as the Atlantic between the European and U.S. approaches to guideline writing.

Mitchel L. Zoler/Frontline Medical News

“The guidelines from the ESC are articulated very well; they made their recommendations very clear. But a lot is consensus driven, without new data,” said Dr. Mariell L. Jessup, who serves as both vice chair of the panel currently revising the U.S. heart failure guidelines – expected out later in 2016 – and was also the sole American representative on the panel that produced the ESC guidelines. “The ESC guidelines make clear all the things that need to happen to patients. I hope it will result in better patient care. We are clearly not doing a good job in heart failure. We not only don’t have evidence-based treatments, but people often don’t do a good job [caring for heart failure patients] and they die in the hospital all the time.”

Dr. Javed Butler, another member of the U.S. guidelines panel and professor and chief of cardiology at Stony Brook (N.Y.) University, called the U.S. and European divide a “philosophical perspective of evidence-based medicine.

“U.S. physicians should read the ESC guidelines and make up their own minds. The ESC guidelines are excellent and give you perspective. But U.S. regulatory and payment issues will be driven by U.S. guidelines,” Dr. Butler said in an interview.

Mitchel L. Zoler/Frontline Medical News

But despite their limitations and the limited weight that the ESC guidelines carry for U.S. practice, they have many redeeming features, noted Dr. Mandeep R. Mehra, medical director of the Heart and Vascular Center at Brigham and Women’s Hospital in Boston. The 2016 ESC guidelines “are extraordinarily clear, very practical, and very concise. They are very usable, and provide a fantastic algorithm for managing patients with heart failure with reduced ejection fraction [HFrEF],” he said while discussing the guidelines during the meeting.

U.S. and Europe largely agree on sacubitril/valsartan and ivabradine

Clearly the greatest area of U.S. and European agreement was in the adoption by both guidelines groups of sacubitril/valsartan (Entresto) and ivabradine (Corlanor) as important new components of the basic drug formula for treating patients with HFrEF. In fact, the U.S. guideline writers saw these two additions as so important and timely that they issued a “focused update” in May to the existing, 2013 U.S. heart failure guidelines, and timed release of this update to occur on May 20, 2016, a day before release of the ESC guidelines. But as Dr. Butler noted, this was more of a temporal harmonization than a substantive one, because even here, in a very evidence-based change, the U.S. guidelines for using sacubitril/valsartan differed subtly but importantly from the ESC version.

The U.S. focused update says that treatment of patients with stage C (symptomatic heart failure with structural heart disease) HFrEF should receive treatment with sacubitril/valsartan (also know as an angiotensin receptor neprilysin inhibitor, or ARNI), an ACE inhibitor, or an angiotensin receptor blocker (ARB), as well as evidence-based treatment with a beta-blocker and with a mineralocorticoid receptor antagonist (MRA). A subsequent recommendation in the U.S. focused update said that HFrEF patients with chronic symptoms and New York Heart Association class II or III disease should switch from a stable, tolerated regimen with either an ACE inhibitor or ARB to treatment with sacubitril/valsartan.

Courtesy Stony Brook University

In contrast, the new European guideline for sacubitril/valsartan recommends starting patients on this combination formulation only after first demonstrating that patients tolerated treatment with an ACE inhibitor or ARB for at least 30 days and determining that patients remained symptomatic while on one of these treatments. In short, the U.S. guideline gives a green light to starting patients with newly diagnosed, symptomatic HFrEF on sacubitril/valsartan immediately, while the European guideline only sanctions sacubitril/valsartan to start after a patient has spent at least 30 days settling into a multidrug regimen featuring an ACE inhibitor or an ARB when an ACE inhibitor isn’t well tolerated.

“The European guidelines are closely related to the study population enrolled in the PARADIGM-HF trial,” the pivotal trial that showed superiority of sacubitril/valsartan to an ACE inhibitor (N Engl J Med. 2014;371:993-1004), noted Dr. Butler in an interview. “The U.S. guidelines interpreted [the PARADIGM-HF] results in the best interests of a larger patient population. The European guidelines are far more proscriptive in replicating the clinical criteria of the trial. In some patients the sequence of starting a MRA and sacubitril/valsartan matters, but in other patients it is less important.”

Dr. Frank Ruschitzka, a coauthor of the ESC guidelines, said that the reason for the more cautious ESC approach was lack of widespread familiarity with sacubitril/valsartan treatment among cardiologists.

Mitchel L. Zoler/Frontline Medical News

The ESC guidelines on using sacubitril/valsartan “replicated the PARADIGM-HF trial. We have no data right now that it is justifiable to put a [treatment-naive] patient on sacubitril/valsartan to begin with. Another difference between the U.S. and ESC guidelines is when to start a MRA,” said Dr. Ruschitzka, professor and head of cardiology at the Heart Center of the University Hospital in Zurich. “It makes a lot of sense to me to start sacubitril/valsartan early. The PARADIGM trial was positive, but no one has a feel for how to use sacubitril/valsartan. Should we give it to everyone? We said replicate the trial, and gain experience using the drug. We want to bring a life-saving drug to patients, but this is the approach we took. We need more data.”

Dr. Jessup noted that a lot of uncertainty also exists among U.S. clinicians about when to start sacubitril/valsartan. “It’s not been clear which patients to put on sacubitril/valsartan. No guidelines had been out on using it” until mid-May, and “the cost of sacubitril/valsartan is daunting. I have received calls from many people who ask whom am I supposed to use sacubitril/valsartan on? It took years and years to get people to [routinely] start patients on an ACE inhibitor and a beta-blocker, and now we’re telling them to do something else. In my practice it’s a 30-minute conversation with each patient that you need to first stop your ACE inhibitor, and then they often get denied coverage by their insurer,” said Dr. Jessup, professor of medicine at the University of Pennsylvania in Philadelphia. She expressed hope that coverage issues will diminish now that clear guidelines are out endorsing a key role for sacubitril/valsartan.

Mitchel L. Zoler/Frontline Medical News

“We now all have started sacubitril/valsartan on patients” without first starting them on an ACE inhibitor, “but we all need to get a sense of what we can get away with” when using this drug, noted Dr. JoAnn Lindenfeld, professor and director of heart failure and transplant at Vanderbilt University in Nashville.

At least one European cardiologist was skeptical of just how proscriptive the ESC guideline for sacubitril/valsartan will be in actual practice.

“The best treatment [for symptomatic HFrEF] is sacubitril/valsartan, a beta-blocker, and a MRA,” said Dr. John J.V. McMurray, professor of cardiology at Glasgow University and lead investigator for the PARADIGM-HF pivotal trial for sacubitril/valsartan. “The treatment sequence advocated in the guidelines – treat with an ACE inhibitor first and if patients remain symptomatic change to sacubitril/valsartan – is evidence-based medicine. As a guidelines writer and as a promoter of evidence-based medicine, this is absolutely the correct approach. But as a practicing physician I’d go straight for sacubitril/valsartan. Otherwise you’re wasting everybody’s time starting with an ACE inhibitor and then waiting a month to switch,” Dr. McMurray said in an interview.

Mitchel L. Zoler/Frontline Medical News

“It’s pointless to wait. We saw results within 30 days of starting sacubitril/valsartan, so it’s a theoretical risk to wait. Very few patients will become completely asymptomatic on an ACE inhibitor. Everyone who entered PARADIGM-HF was at New York Heart Association class II or higher, and at the time of randomization only a handful of patients were in New York Heart Association class I. Very few patients get to class I. That tells you it’s pretty uncommon for a heart failure patient to become truly asymptomatic with ACE inhibitor treatment. The main problem is that you are inconveniencing everybody with more blood tests and more clinic visits by waiting to start sacubitril/valsartan, said Dr. McMurray, who was not a member of the panel that wrote the new ESC guidelines.

Even less separates the new U.S. focused update and the ESC guidelines for using ivabradine. Both agree on starting the drug on HFrEF patients who remain symptomatic and with a left ventricular ejection fraction of 35% or less despite being on guideline-directed therapy including titration to a maximum beta-blocker dosage and with a persistent heart rate of at least 70 beats/min. The goal of ivabradine treatment is to further reduce heart rate beyond what’s achieved by a maximal beta-blocker dosage.

Perhaps the biggest questions about ivabradine have been why it took so long to enter the U.S. guidelines, and why it is listed in both the U.S. and ESC guidelines as a level II recommendation. Results from the pivotal trial that supported ivabradine’s use in HFrEF patients, SHIFT, first appeared in 2010 (Lancet. 2010 Sep 11;376[9744]:875-95).

Dr. Butler chalked up the drug’s slow entry into U.S. guidelines as the result of a lack of initiative by ivabradine’s initial developer, Servier. “SHIFT did not have any U.S. sites, and Servier never sought Food and Drug Administration approval,” he noted. “Amgen acquired the U.S. rights to ivabradine in 2013,” and the drug received FDA approval in April 2015, Dr. Butler noted, in explaining the drug’s U.S. timeline. As to why its use is a level II recommendation, he noted that the evidence for efficacy came only from the SHIFT trial, questions exist whether the beta-blocker dosages were fully optimized in all patients in this trial, and the benefit was limited to a reduction in heart failure hospitalizations but not in mortality. “I think that patients with persistent heart failure symptoms [and a persistently elevated heart rate] should get ivabradine,” but these caveats limit it to a class II level recommendation, Dr. Butler said.

“There were questions about ivabradine’s benefit in reducing heart failure hospitalization but not mortality, and questions about whether it would benefit patients if their beta-blocker dosage was adequately up titrated. There were also questions about which heart failure patients to use it on,” noted Dr. Lindenfeld, a member of the panel that wrote the U.S. focused update. These concerns in part help explain the delay to integrating ivabradine into U.S. practice guidelines, she said in an interview, but added that additional data and analysis published during the past 3 or so years have clarified ivabradine’s potentially useful role in treating selected HFrEF patients.

New ESC guidelines based on expert opinion

The sections on sacubitril/valsartan and ivabradine occupy a mere 2 pages among more than 55 pages of text and charts that spell out the ESC’s current vision of how physicians should diagnose and manage heart failure patients. While much of what carried over from prior editions of the guidelines is rooted in evidence, many of the new approaches advocated rely on expert opinion or new interpretations of existing data. Here are some of the notable changes and highlights of the 2016 ESC recommendations:

• Heart failure diagnosis. The new ESC guidelines streamline the diagnostic process, which now focuses on five key elements: The patient’s history, physical examination, ECG, serum level of either brain natriuretic peptide (BNP) or N-terminal(NT)-proBNP, and echocardiography. The guidelines specify threshold levels of BNP and NT-proBNP that can effectively rule out heart failure, a BNP level of at least 35 pg/mL or a NT-proBNP level of at least 125 pg/mL.

Mitchel L. Zoler/Frontline Medical News

“The diagnostic minimum levels of BNP and NT-proBNP were designed to rule out heart failure. They both have a high negative predictive value, but at these levels their positive predictive value is low,” explained Dr. Adriaan A. Voors, cochair of the ESC’s guideline-writing panel and professor of cardiology at the University of Groningen, the Netherlands.

But while these levels might be effective for reliable rule out of heart failure, they could mean a large number of patients would qualify for an echocardiographic assessment.

“If we used the ESC’s natriuretic peptide cutoffs, there would be a clear concern about overuse of echo. It’s a cost-effectiveness issue. You wind up doing a lot of echos that will be normal. Echocardiography is very safe, but each echo costs about $400-$500,” commented Dr. Butler.

“The results from the STOP-HF and PONTIAC studies showed that BNP levels can identify people at increased risk for developing heart failure who need more intensive assessment and could also potentially benefit from more attention to heart failure prevention. I suspect the full U.S. guideline update will address this issue, but we have not yet finalized our decisions,” he added.

• Heart failure classification. The new ESC guidelines created a new heart failure category, midrange ejection fraction, that the writing panel positioned squarely between the two more classic heart failure subgroups, HFrEF and heart failure with preserved ejection fraction (HFpEF). The definition of each of the three subgroups depends on left ventricular ejection fraction as determined by echocardiography: A LVEF of less than 40% defined HFrEF, a LVEF of 40%-49% defined heart failure with midrange ejection fraction (HFmrEF), and a LVEF of 50% or higher defined HFpEF. Diagnostic confirmation of both HFmrEF and HFpEF also requires that patients fulfill certain criteria of structural or functional heart abnormalities.

Mitchel L. Zoler/Frontline Medical News

The category of HFmrEF was created “to stimulate research into how to best manage these patients,” explained Dr. Piotr Ponikowski, chair of the ESC guidelines writing panel. For the time being, it remains a category with only theoretical importance as nothing is known to suggest that management of patients with HFmrEF should in any way differ from patients with HFpEF.

• Acute heart failure. Perhaps the most revolutionary element of the new guidelines is the detailed map they provide to managing patients who present with acute decompensated heart failure and the underlying principles cited to justify this radically different approach.

“The acute heart failure section was completely rewritten,” noted Dr. Ponikowski, professor of heart diseases at the Medical University in Wroclaw, Poland. “We don’t yet have evidence-based treatments” to apply to acute heart failure patients, he admitted, “however we strongly recommend the concept that the shorter the better. Shorten the time of diagnosis and for therapeutic decisions. We have borrowed from acute coronary syndrome. Don’t keep patients in the emergency department for another couple of hours just to see if they will respond. We must be aware that we need to do our best to shorten diagnosis and treatment decisions. Time is an issue. Manage a patient’s congestion and impaired peripheral perfusion within a time frame of 1-2 hours.”

The concept that acute heart failure must be quickly managed as an emergency condition similar to acute coronary syndrome first appeared as a European practice recommendation in 2015, a consensus statement from the European Heart Failure Association and two other collaborating organizations (Eur Heart J. 2015 Aug 7;36[30]:1958-66).

Mitchel L. Zoler/Frontline Medical News

“In 2015, the consensus paper talked about how to handle acute heart failure patients in the emergency department. Now, we have focused on defining the patients’ phenotype and how to categorize their treatment options. We built on the 2015 statement, but the algorithms we now have are original to 2016; they were not in the 2015 paper,” said Dr. Veli-Pekka Harjola, a member of the 2015 consensus group and 2016 guidelines panel who spearheaded writing the acute heart failure section of the new ESC guidelines.

An additional new and notable feature of this section in the 2016 guidelines is its creation of an acronym, CHAMP, designed to guide the management of patients with acute heart failure. CHAMP stands for acute Coronary syndrome, Hypertension emergency, Arrhythmia, acute Mechanical cause, and Pulmonary embolism. The CHAMP acronym’s purpose is to “focus attention on these five specific, potential causes of acute heart failure, life-threatening conditions that need immediate treatment,” explained Dr. Ponikowski.

“CHAMP emphasizes the most critical causes of acute heart failure,” added Dr. Harjola, a cardiologist at Helsinki University Central Hospital. “We created this new acronym” to help clinicians keep in mind what to look for in a patient presenting with acute heart failure.

U.S. cardiologists find things to like in what the Europeans say about managing acute heart failure, as well as aspects to question.

“It makes no sense not to aggressively treat a patient who arrives at an emergency department with acute heart failure. But there is a difference between acute MI or stroke and acute heart failure,” said Dr. Butler. “In acute MI there is the ruptured plaque and thrombus that blocks a coronary artery. In stroke there is a thrombus. These are diseases with a specific onset and treatment target. But with acute heart failure we don’t have a thrombus to treat; we don’t have a specific target. What we’ve learned from studying implanted devices [such as CardioMems] is that the congestion that causes acute heart failure can start 2-3 weeks before a patient develops acute decompensated heart failure and goes to the hospital. We have not found a specific pathophysiologic abnormality in the patient with acute heart failure that is any different from chronic heart failure. This begs the question: If a patient who presents with acute heart failure has a congestion process that’s been going on for 2 or 3 weeks what difference will another 3 hours make? Do we need to replicate the concept of an acute stroke team or acute MI response for acute heart failure?”

Dr. Butler stressed that additional data are expected soon that may help clarify this issue.

“Some large outcome trials in patients with acute heart failure are now underway, one testing serelaxin treatment, another testing ularitide treatment, that are also testing the hypothesis that rapid treatment with these drugs can produce more end-organ protection, stop damage to the heart, kidney and liver, and lead to better long-term outcomes. Until we have those data, the jury is still out” on the benefit patients gain from rapid treatment of acute heart failure. “Until then, it’s not that the data say don’t treat acute heart failure patients aggressively. But we have not yet proven it is similar to treating an acute MI or stroke,” said Dr. Butler.

Mitchel L. Zoler/Frontline Medical News

“U.S. guidelines have tended to stay away from areas where there are no evidence-based data. To their credit, the Europeans will take on something like acute heart failure where we don’t have an adequate evidence base. Despite that, they provide guidelines, which is important because clinicians need guidance even when the evidence is not very good, when the guideline is based mostly on experience and expert consensus.” commented Dr. William T. Abraham, professor and director of cardiovascular medicine at the Ohio State University Wexner Medical Center in Columbus.

“It’s absolutely appropriate to think of acute heart failure as an emergency situation. We know from high-sensitivity troponin assays that troponin levels are increased in 90% of patients who present with acute decompensated heart failure. So most acute heart failure patients are losing heart muscle cells and we should treat them like we treat acute coronary syndrome. Time matters in acute heart failure; time is heart muscle. Treatment needs to break the hemodynamic and neurohormonal storm of acute decompensated heart failure; get the patient stabilized; improve vital organ perfusion, including within the heart; and shift the myocardial oxygen supply and demand equation so myocardial necrosis stops. All of this is important, and study results suggest it’s the correct approach. I’m not sure study results prove it, but studies that have looked at the time course of treatment for acute heart failure showed that early initiation of treatment – within the first 6 hours of onset – compared with 12-24 hours of onset makes a difference in outcomes,” Dr. Abraham said in an interview.

But a major limitation to the potential efficacy of a rapidly initiated management strategy is that few interventions currently exist with proven benefits for acute heart failure patients.

For the time being, rapid intervention means using diuretics relatively quickly and, if there is an indication for treating with a vasoactive medication, using that quickly too. “The rapid approach is really more relevant to the future; it’s relevant to the design of future acute heart failure treatment trials. That is where this early treatment paradigm is important,” as it could potentially apply to new, more effective treatments of the future rather than to the marginally effective treatments now available, Dr. Abraham said.

“For a long we time haven’t pushed how quickly we should act when implementing guideline-directed treatment” for patients with acute heart failure, noted Dr. Mehra. “The CHAMP approach is interesting, and the ESC guidelines are a very interesting move in the direction” of faster action. “They speak to the period of time during which one should act. Hopefully this will help the science of acute decompensated heart failure move forward.”

But for other U.S. experts the issue again pivots on the lack of evidence.

“There is nothing new” about managing acute heart failure, said Dr. Jessup. “The ESC guideline was articulated very well; they made their recommendations very clear. But a lot is consensus driven. There are no new data. The problem with acute heart failure is that the recommendations are what we think clinicians should do. CHAMP is a nice acronym; it’s packaged better, but there are not any new data.”

Comorbidities

A dramatic contrast distinguishes the extent to which the ESC guidelines highlight comorbidities, compared with prevailing U.S. guidelines. The new ESC guidelines highlight and discuss with some detail 16 distinct comorbidities for clinicians to keep in mind when managing heart failure patients, compared with three comorbidities (atrial fibrillation, anemia, and depression) discussed with similar detail in the 2013 U.S. guidelines.

Mitchel L. Zoler/Frontline Medical News

“We are targeting comorbidities to personalize medicine, by subgrouping [heart failure] patients into groups that need to receive special attention,” explained Dr. Stefan D. Anker, a coauthor on the ESC guidelines. “We care about comorbidities because they make the diagnosis of heart failure difficult. They aggravate symptoms and contribute to additional hospitalizations. They interfere with [heart failure] treatment, and because comorbidities have led to exclusions of heart failure patients from trials, we lack evidence of treatment efficacy in patients with certain comorbidities,” said Dr. Anker, a professor of innovative clinical trials at the Medical University in Göttingen, Germany.

“The comorbidity discussion in the ESC guidelines is extremely important,” commented Dr. Abraham. “It supports the need for a multidimensional approach to heart failure patients. A cardiologist may not have all the resources to manage all the comorbidities [a heart failure patient might have]. This is why having a sleep medicine specialist, a diabetes specialist, a nephrologist, etc., involved as part of a heart failure management team can be very valuable. We need to involve subspecialists in managing the comorbidities of heart failure because they clearly have an impact on patient outcome.”

But Dr. Butler had a somewhat different take on how comorbidity management fits into the broader picture of heart failure management.

“There is no doubt that heart failure worsens other comorbidities and other comorbidities worsen heart failure. The relationship is bidirectional between heart failure and chronic obstructive pulmonary disease, liver disease, depression, sleep apnea, renal disease, lung disease, diabetes, etc. The problem is that treating a comorbidity does not necessarily translate into improved heart failure outcomes. Comorbidities are important for heart failure patients and worsen their heart failure outcomes. However, management of a comorbidity should be done primarily for the sake of improving the comorbidity. If you treat depression, for example, and it does not improve a patient’s heart failure, that doesn’t mean you shouldn’t have treated the depression. It just means that we don’t have good data that it will improve heart failure.”

Another limitation from a U.S. perspective is what role treatment of various comorbidities can play in benefiting heart failure patients and how compelling the evidence is for this. Dr. Butler gave as an example the problem with treating iron deficiency in heart failure patients who do not have anemia, a strategy endorsed in the ESC guidelines as a level IIa recommendation.

“The data regarding improved exercise capacity from treatment with intravenous ferric carboxymaltose is pretty convincing,” he said. But patients have benefited from this treatment only with improved function and quality of life, and not with improved survival or fewer hospitalizations.

“Is treating patients to improve their function and help them feel better enough?” Dr. Butler asked. “In other diseases it is. In gastrointestinal disease, if a drug helps patients feel better you approve the drug. We value improved functional capacity for patients with pulmonary hypertension, angina, and peripheral vascular disease. All these indications have drugs approved for improving functional capacity and quality of life. But for heart failure the bar has been set higher. There is a lot of interest in changing this” for heart failure.

“There is interest in running a study of ferric carboxymaltose for heart failure with a mortality endpoint. In the meantime, the impact on improving functional capacity is compelling, and it will be interesting to see what happens in the U.S. guidelines. Currently, in U.S. practice if a heart failure patient has iron-deficiency anemia you treat with intravenous iron replacement and the treatment gets reimbursed without a problem. But if the heart failure patient has iron deficiency without anemia then reimbursement for the cost of iron supplementation can be a problem,” Dr. Butler noted. This may change only if the experts who write the next U.S. heart failure guidelines decide to change the rules of what constitutes a useful heart failure treatment, he said.

Dr. Butler has been a consultant to Novartis and Amgen and several other companies. Dr. Jessup had no disclosures. Dr. Mehra has been a consultant to Teva, Johnson & Johnson, Boston Scientific, and St. Jude. Dr. Ruschitzka has been a consultant to Novartis, Servier, Sanofi, Cardiorentis, Heartware, and St. Jude. Dr. McMurray has received research support from Novartis and Amgen. Dr. Lindenfeld has been a consultant to Novartis, Abbott, Janssen, Relypsa, and Resmed. Dr. Voors has been a consultant to Novartis, Amgen, Servier, and several other drug companies. Dr. Ponikowski has been a consultant to Amgen, Novartis, Servier, and several other drug companies. Dr. Harjola has been a consultant to Novartis, Servier, Bayer, Boehringer Ingelheim, Pfizer, and Resmed. Dr. Abraham has been a consultant to Amgen, Novartis, and several device companies. Dr. Anker has been a consultant to Novartis, Servier, and several other companies.

[email protected]

On Twitter @mitchelzoler

FLORENCE, ITALY – The 2016 revision of the European Society of Cardiology’s guidelines for diagnosing and treating acute and chronic heart failure highlights the extent to which thinking in the field has changed during the past 4 years, since the prior edition in 2012.

The new European guidelines, unveiled by the ESC’s Heart Failure Association during the group’s annual meeting, also underscore the great dependence that many new approaches have on expert opinion rather than what’s become the keystone of guidelines writing, evidence-based medicine. Frequent reliance on consensus decisions rather than indisputable proof from controlled trials defines what some U.S. specialists see as a divide as wide as the Atlantic between the European and U.S. approaches to guideline writing.

Mitchel L. Zoler/Frontline Medical News

“The guidelines from the ESC are articulated very well; they made their recommendations very clear. But a lot is consensus driven, without new data,” said Dr. Mariell L. Jessup, who serves as both vice chair of the panel currently revising the U.S. heart failure guidelines – expected out later in 2016 – and was also the sole American representative on the panel that produced the ESC guidelines. “The ESC guidelines make clear all the things that need to happen to patients. I hope it will result in better patient care. We are clearly not doing a good job in heart failure. We not only don’t have evidence-based treatments, but people often don’t do a good job [caring for heart failure patients] and they die in the hospital all the time.”

Dr. Javed Butler, another member of the U.S. guidelines panel and professor and chief of cardiology at Stony Brook (N.Y.) University, called the U.S. and European divide a “philosophical perspective of evidence-based medicine.

“U.S. physicians should read the ESC guidelines and make up their own minds. The ESC guidelines are excellent and give you perspective. But U.S. regulatory and payment issues will be driven by U.S. guidelines,” Dr. Butler said in an interview.

Mitchel L. Zoler/Frontline Medical News

But despite their limitations and the limited weight that the ESC guidelines carry for U.S. practice, they have many redeeming features, noted Dr. Mandeep R. Mehra, medical director of the Heart and Vascular Center at Brigham and Women’s Hospital in Boston. The 2016 ESC guidelines “are extraordinarily clear, very practical, and very concise. They are very usable, and provide a fantastic algorithm for managing patients with heart failure with reduced ejection fraction [HFrEF],” he said while discussing the guidelines during the meeting.

U.S. and Europe largely agree on sacubitril/valsartan and ivabradine

Clearly the greatest area of U.S. and European agreement was in the adoption by both guidelines groups of sacubitril/valsartan (Entresto) and ivabradine (Corlanor) as important new components of the basic drug formula for treating patients with HFrEF. In fact, the U.S. guideline writers saw these two additions as so important and timely that they issued a “focused update” in May to the existing, 2013 U.S. heart failure guidelines, and timed release of this update to occur on May 20, 2016, a day before release of the ESC guidelines. But as Dr. Butler noted, this was more of a temporal harmonization than a substantive one, because even here, in a very evidence-based change, the U.S. guidelines for using sacubitril/valsartan differed subtly but importantly from the ESC version.

The U.S. focused update says that treatment of patients with stage C (symptomatic heart failure with structural heart disease) HFrEF should receive treatment with sacubitril/valsartan (also know as an angiotensin receptor neprilysin inhibitor, or ARNI), an ACE inhibitor, or an angiotensin receptor blocker (ARB), as well as evidence-based treatment with a beta-blocker and with a mineralocorticoid receptor antagonist (MRA). A subsequent recommendation in the U.S. focused update said that HFrEF patients with chronic symptoms and New York Heart Association class II or III disease should switch from a stable, tolerated regimen with either an ACE inhibitor or ARB to treatment with sacubitril/valsartan.

Courtesy Stony Brook University

In contrast, the new European guideline for sacubitril/valsartan recommends starting patients on this combination formulation only after first demonstrating that patients tolerated treatment with an ACE inhibitor or ARB for at least 30 days and determining that patients remained symptomatic while on one of these treatments. In short, the U.S. guideline gives a green light to starting patients with newly diagnosed, symptomatic HFrEF on sacubitril/valsartan immediately, while the European guideline only sanctions sacubitril/valsartan to start after a patient has spent at least 30 days settling into a multidrug regimen featuring an ACE inhibitor or an ARB when an ACE inhibitor isn’t well tolerated.

“The European guidelines are closely related to the study population enrolled in the PARADIGM-HF trial,” the pivotal trial that showed superiority of sacubitril/valsartan to an ACE inhibitor (N Engl J Med. 2014;371:993-1004), noted Dr. Butler in an interview. “The U.S. guidelines interpreted [the PARADIGM-HF] results in the best interests of a larger patient population. The European guidelines are far more proscriptive in replicating the clinical criteria of the trial. In some patients the sequence of starting a MRA and sacubitril/valsartan matters, but in other patients it is less important.”

Dr. Frank Ruschitzka, a coauthor of the ESC guidelines, said that the reason for the more cautious ESC approach was lack of widespread familiarity with sacubitril/valsartan treatment among cardiologists.

Mitchel L. Zoler/Frontline Medical News

The ESC guidelines on using sacubitril/valsartan “replicated the PARADIGM-HF trial. We have no data right now that it is justifiable to put a [treatment-naive] patient on sacubitril/valsartan to begin with. Another difference between the U.S. and ESC guidelines is when to start a MRA,” said Dr. Ruschitzka, professor and head of cardiology at the Heart Center of the University Hospital in Zurich. “It makes a lot of sense to me to start sacubitril/valsartan early. The PARADIGM trial was positive, but no one has a feel for how to use sacubitril/valsartan. Should we give it to everyone? We said replicate the trial, and gain experience using the drug. We want to bring a life-saving drug to patients, but this is the approach we took. We need more data.”

Dr. Jessup noted that a lot of uncertainty also exists among U.S. clinicians about when to start sacubitril/valsartan. “It’s not been clear which patients to put on sacubitril/valsartan. No guidelines had been out on using it” until mid-May, and “the cost of sacubitril/valsartan is daunting. I have received calls from many people who ask whom am I supposed to use sacubitril/valsartan on? It took years and years to get people to [routinely] start patients on an ACE inhibitor and a beta-blocker, and now we’re telling them to do something else. In my practice it’s a 30-minute conversation with each patient that you need to first stop your ACE inhibitor, and then they often get denied coverage by their insurer,” said Dr. Jessup, professor of medicine at the University of Pennsylvania in Philadelphia. She expressed hope that coverage issues will diminish now that clear guidelines are out endorsing a key role for sacubitril/valsartan.

Mitchel L. Zoler/Frontline Medical News

“We now all have started sacubitril/valsartan on patients” without first starting them on an ACE inhibitor, “but we all need to get a sense of what we can get away with” when using this drug, noted Dr. JoAnn Lindenfeld, professor and director of heart failure and transplant at Vanderbilt University in Nashville.

At least one European cardiologist was skeptical of just how proscriptive the ESC guideline for sacubitril/valsartan will be in actual practice.

“The best treatment [for symptomatic HFrEF] is sacubitril/valsartan, a beta-blocker, and a MRA,” said Dr. John J.V. McMurray, professor of cardiology at Glasgow University and lead investigator for the PARADIGM-HF pivotal trial for sacubitril/valsartan. “The treatment sequence advocated in the guidelines – treat with an ACE inhibitor first and if patients remain symptomatic change to sacubitril/valsartan – is evidence-based medicine. As a guidelines writer and as a promoter of evidence-based medicine, this is absolutely the correct approach. But as a practicing physician I’d go straight for sacubitril/valsartan. Otherwise you’re wasting everybody’s time starting with an ACE inhibitor and then waiting a month to switch,” Dr. McMurray said in an interview.

Mitchel L. Zoler/Frontline Medical News

“It’s pointless to wait. We saw results within 30 days of starting sacubitril/valsartan, so it’s a theoretical risk to wait. Very few patients will become completely asymptomatic on an ACE inhibitor. Everyone who entered PARADIGM-HF was at New York Heart Association class II or higher, and at the time of randomization only a handful of patients were in New York Heart Association class I. Very few patients get to class I. That tells you it’s pretty uncommon for a heart failure patient to become truly asymptomatic with ACE inhibitor treatment. The main problem is that you are inconveniencing everybody with more blood tests and more clinic visits by waiting to start sacubitril/valsartan, said Dr. McMurray, who was not a member of the panel that wrote the new ESC guidelines.

Even less separates the new U.S. focused update and the ESC guidelines for using ivabradine. Both agree on starting the drug on HFrEF patients who remain symptomatic and with a left ventricular ejection fraction of 35% or less despite being on guideline-directed therapy including titration to a maximum beta-blocker dosage and with a persistent heart rate of at least 70 beats/min. The goal of ivabradine treatment is to further reduce heart rate beyond what’s achieved by a maximal beta-blocker dosage.

Perhaps the biggest questions about ivabradine have been why it took so long to enter the U.S. guidelines, and why it is listed in both the U.S. and ESC guidelines as a level II recommendation. Results from the pivotal trial that supported ivabradine’s use in HFrEF patients, SHIFT, first appeared in 2010 (Lancet. 2010 Sep 11;376[9744]:875-95).

Dr. Butler chalked up the drug’s slow entry into U.S. guidelines as the result of a lack of initiative by ivabradine’s initial developer, Servier. “SHIFT did not have any U.S. sites, and Servier never sought Food and Drug Administration approval,” he noted. “Amgen acquired the U.S. rights to ivabradine in 2013,” and the drug received FDA approval in April 2015, Dr. Butler noted, in explaining the drug’s U.S. timeline. As to why its use is a level II recommendation, he noted that the evidence for efficacy came only from the SHIFT trial, questions exist whether the beta-blocker dosages were fully optimized in all patients in this trial, and the benefit was limited to a reduction in heart failure hospitalizations but not in mortality. “I think that patients with persistent heart failure symptoms [and a persistently elevated heart rate] should get ivabradine,” but these caveats limit it to a class II level recommendation, Dr. Butler said.

“There were questions about ivabradine’s benefit in reducing heart failure hospitalization but not mortality, and questions about whether it would benefit patients if their beta-blocker dosage was adequately up titrated. There were also questions about which heart failure patients to use it on,” noted Dr. Lindenfeld, a member of the panel that wrote the U.S. focused update. These concerns in part help explain the delay to integrating ivabradine into U.S. practice guidelines, she said in an interview, but added that additional data and analysis published during the past 3 or so years have clarified ivabradine’s potentially useful role in treating selected HFrEF patients.

New ESC guidelines based on expert opinion

The sections on sacubitril/valsartan and ivabradine occupy a mere 2 pages among more than 55 pages of text and charts that spell out the ESC’s current vision of how physicians should diagnose and manage heart failure patients. While much of what carried over from prior editions of the guidelines is rooted in evidence, many of the new approaches advocated rely on expert opinion or new interpretations of existing data. Here are some of the notable changes and highlights of the 2016 ESC recommendations:

• Heart failure diagnosis. The new ESC guidelines streamline the diagnostic process, which now focuses on five key elements: The patient’s history, physical examination, ECG, serum level of either brain natriuretic peptide (BNP) or N-terminal(NT)-proBNP, and echocardiography. The guidelines specify threshold levels of BNP and NT-proBNP that can effectively rule out heart failure, a BNP level of at least 35 pg/mL or a NT-proBNP level of at least 125 pg/mL.

Mitchel L. Zoler/Frontline Medical News

“The diagnostic minimum levels of BNP and NT-proBNP were designed to rule out heart failure. They both have a high negative predictive value, but at these levels their positive predictive value is low,” explained Dr. Adriaan A. Voors, cochair of the ESC’s guideline-writing panel and professor of cardiology at the University of Groningen, the Netherlands.

But while these levels might be effective for reliable rule out of heart failure, they could mean a large number of patients would qualify for an echocardiographic assessment.

“If we used the ESC’s natriuretic peptide cutoffs, there would be a clear concern about overuse of echo. It’s a cost-effectiveness issue. You wind up doing a lot of echos that will be normal. Echocardiography is very safe, but each echo costs about $400-$500,” commented Dr. Butler.

“The results from the STOP-HF and PONTIAC studies showed that BNP levels can identify people at increased risk for developing heart failure who need more intensive assessment and could also potentially benefit from more attention to heart failure prevention. I suspect the full U.S. guideline update will address this issue, but we have not yet finalized our decisions,” he added.

• Heart failure classification. The new ESC guidelines created a new heart failure category, midrange ejection fraction, that the writing panel positioned squarely between the two more classic heart failure subgroups, HFrEF and heart failure with preserved ejection fraction (HFpEF). The definition of each of the three subgroups depends on left ventricular ejection fraction as determined by echocardiography: A LVEF of less than 40% defined HFrEF, a LVEF of 40%-49% defined heart failure with midrange ejection fraction (HFmrEF), and a LVEF of 50% or higher defined HFpEF. Diagnostic confirmation of both HFmrEF and HFpEF also requires that patients fulfill certain criteria of structural or functional heart abnormalities.

Mitchel L. Zoler/Frontline Medical News

The category of HFmrEF was created “to stimulate research into how to best manage these patients,” explained Dr. Piotr Ponikowski, chair of the ESC guidelines writing panel. For the time being, it remains a category with only theoretical importance as nothing is known to suggest that management of patients with HFmrEF should in any way differ from patients with HFpEF.

• Acute heart failure. Perhaps the most revolutionary element of the new guidelines is the detailed map they provide to managing patients who present with acute decompensated heart failure and the underlying principles cited to justify this radically different approach.

“The acute heart failure section was completely rewritten,” noted Dr. Ponikowski, professor of heart diseases at the Medical University in Wroclaw, Poland. “We don’t yet have evidence-based treatments” to apply to acute heart failure patients, he admitted, “however we strongly recommend the concept that the shorter the better. Shorten the time of diagnosis and for therapeutic decisions. We have borrowed from acute coronary syndrome. Don’t keep patients in the emergency department for another couple of hours just to see if they will respond. We must be aware that we need to do our best to shorten diagnosis and treatment decisions. Time is an issue. Manage a patient’s congestion and impaired peripheral perfusion within a time frame of 1-2 hours.”

The concept that acute heart failure must be quickly managed as an emergency condition similar to acute coronary syndrome first appeared as a European practice recommendation in 2015, a consensus statement from the European Heart Failure Association and two other collaborating organizations (Eur Heart J. 2015 Aug 7;36[30]:1958-66).

Mitchel L. Zoler/Frontline Medical News

“In 2015, the consensus paper talked about how to handle acute heart failure patients in the emergency department. Now, we have focused on defining the patients’ phenotype and how to categorize their treatment options. We built on the 2015 statement, but the algorithms we now have are original to 2016; they were not in the 2015 paper,” said Dr. Veli-Pekka Harjola, a member of the 2015 consensus group and 2016 guidelines panel who spearheaded writing the acute heart failure section of the new ESC guidelines.

An additional new and notable feature of this section in the 2016 guidelines is its creation of an acronym, CHAMP, designed to guide the management of patients with acute heart failure. CHAMP stands for acute Coronary syndrome, Hypertension emergency, Arrhythmia, acute Mechanical cause, and Pulmonary embolism. The CHAMP acronym’s purpose is to “focus attention on these five specific, potential causes of acute heart failure, life-threatening conditions that need immediate treatment,” explained Dr. Ponikowski.

“CHAMP emphasizes the most critical causes of acute heart failure,” added Dr. Harjola, a cardiologist at Helsinki University Central Hospital. “We created this new acronym” to help clinicians keep in mind what to look for in a patient presenting with acute heart failure.

U.S. cardiologists find things to like in what the Europeans say about managing acute heart failure, as well as aspects to question.

“It makes no sense not to aggressively treat a patient who arrives at an emergency department with acute heart failure. But there is a difference between acute MI or stroke and acute heart failure,” said Dr. Butler. “In acute MI there is the ruptured plaque and thrombus that blocks a coronary artery. In stroke there is a thrombus. These are diseases with a specific onset and treatment target. But with acute heart failure we don’t have a thrombus to treat; we don’t have a specific target. What we’ve learned from studying implanted devices [such as CardioMems] is that the congestion that causes acute heart failure can start 2-3 weeks before a patient develops acute decompensated heart failure and goes to the hospital. We have not found a specific pathophysiologic abnormality in the patient with acute heart failure that is any different from chronic heart failure. This begs the question: If a patient who presents with acute heart failure has a congestion process that’s been going on for 2 or 3 weeks what difference will another 3 hours make? Do we need to replicate the concept of an acute stroke team or acute MI response for acute heart failure?”

Dr. Butler stressed that additional data are expected soon that may help clarify this issue.

“Some large outcome trials in patients with acute heart failure are now underway, one testing serelaxin treatment, another testing ularitide treatment, that are also testing the hypothesis that rapid treatment with these drugs can produce more end-organ protection, stop damage to the heart, kidney and liver, and lead to better long-term outcomes. Until we have those data, the jury is still out” on the benefit patients gain from rapid treatment of acute heart failure. “Until then, it’s not that the data say don’t treat acute heart failure patients aggressively. But we have not yet proven it is similar to treating an acute MI or stroke,” said Dr. Butler.

Mitchel L. Zoler/Frontline Medical News

“U.S. guidelines have tended to stay away from areas where there are no evidence-based data. To their credit, the Europeans will take on something like acute heart failure where we don’t have an adequate evidence base. Despite that, they provide guidelines, which is important because clinicians need guidance even when the evidence is not very good, when the guideline is based mostly on experience and expert consensus.” commented Dr. William T. Abraham, professor and director of cardiovascular medicine at the Ohio State University Wexner Medical Center in Columbus.

“It’s absolutely appropriate to think of acute heart failure as an emergency situation. We know from high-sensitivity troponin assays that troponin levels are increased in 90% of patients who present with acute decompensated heart failure. So most acute heart failure patients are losing heart muscle cells and we should treat them like we treat acute coronary syndrome. Time matters in acute heart failure; time is heart muscle. Treatment needs to break the hemodynamic and neurohormonal storm of acute decompensated heart failure; get the patient stabilized; improve vital organ perfusion, including within the heart; and shift the myocardial oxygen supply and demand equation so myocardial necrosis stops. All of this is important, and study results suggest it’s the correct approach. I’m not sure study results prove it, but studies that have looked at the time course of treatment for acute heart failure showed that early initiation of treatment – within the first 6 hours of onset – compared with 12-24 hours of onset makes a difference in outcomes,” Dr. Abraham said in an interview.

But a major limitation to the potential efficacy of a rapidly initiated management strategy is that few interventions currently exist with proven benefits for acute heart failure patients.

For the time being, rapid intervention means using diuretics relatively quickly and, if there is an indication for treating with a vasoactive medication, using that quickly too. “The rapid approach is really more relevant to the future; it’s relevant to the design of future acute heart failure treatment trials. That is where this early treatment paradigm is important,” as it could potentially apply to new, more effective treatments of the future rather than to the marginally effective treatments now available, Dr. Abraham said.

“For a long we time haven’t pushed how quickly we should act when implementing guideline-directed treatment” for patients with acute heart failure, noted Dr. Mehra. “The CHAMP approach is interesting, and the ESC guidelines are a very interesting move in the direction” of faster action. “They speak to the period of time during which one should act. Hopefully this will help the science of acute decompensated heart failure move forward.”

But for other U.S. experts the issue again pivots on the lack of evidence.

“There is nothing new” about managing acute heart failure, said Dr. Jessup. “The ESC guideline was articulated very well; they made their recommendations very clear. But a lot is consensus driven. There are no new data. The problem with acute heart failure is that the recommendations are what we think clinicians should do. CHAMP is a nice acronym; it’s packaged better, but there are not any new data.”

Comorbidities

A dramatic contrast distinguishes the extent to which the ESC guidelines highlight comorbidities, compared with prevailing U.S. guidelines. The new ESC guidelines highlight and discuss with some detail 16 distinct comorbidities for clinicians to keep in mind when managing heart failure patients, compared with three comorbidities (atrial fibrillation, anemia, and depression) discussed with similar detail in the 2013 U.S. guidelines.

Mitchel L. Zoler/Frontline Medical News

“We are targeting comorbidities to personalize medicine, by subgrouping [heart failure] patients into groups that need to receive special attention,” explained Dr. Stefan D. Anker, a coauthor on the ESC guidelines. “We care about comorbidities because they make the diagnosis of heart failure difficult. They aggravate symptoms and contribute to additional hospitalizations. They interfere with [heart failure] treatment, and because comorbidities have led to exclusions of heart failure patients from trials, we lack evidence of treatment efficacy in patients with certain comorbidities,” said Dr. Anker, a professor of innovative clinical trials at the Medical University in Göttingen, Germany.

“The comorbidity discussion in the ESC guidelines is extremely important,” commented Dr. Abraham. “It supports the need for a multidimensional approach to heart failure patients. A cardiologist may not have all the resources to manage all the comorbidities [a heart failure patient might have]. This is why having a sleep medicine specialist, a diabetes specialist, a nephrologist, etc., involved as part of a heart failure management team can be very valuable. We need to involve subspecialists in managing the comorbidities of heart failure because they clearly have an impact on patient outcome.”

But Dr. Butler had a somewhat different take on how comorbidity management fits into the broader picture of heart failure management.

“There is no doubt that heart failure worsens other comorbidities and other comorbidities worsen heart failure. The relationship is bidirectional between heart failure and chronic obstructive pulmonary disease, liver disease, depression, sleep apnea, renal disease, lung disease, diabetes, etc. The problem is that treating a comorbidity does not necessarily translate into improved heart failure outcomes. Comorbidities are important for heart failure patients and worsen their heart failure outcomes. However, management of a comorbidity should be done primarily for the sake of improving the comorbidity. If you treat depression, for example, and it does not improve a patient’s heart failure, that doesn’t mean you shouldn’t have treated the depression. It just means that we don’t have good data that it will improve heart failure.”

Another limitation from a U.S. perspective is what role treatment of various comorbidities can play in benefiting heart failure patients and how compelling the evidence is for this. Dr. Butler gave as an example the problem with treating iron deficiency in heart failure patients who do not have anemia, a strategy endorsed in the ESC guidelines as a level IIa recommendation.

“The data regarding improved exercise capacity from treatment with intravenous ferric carboxymaltose is pretty convincing,” he said. But patients have benefited from this treatment only with improved function and quality of life, and not with improved survival or fewer hospitalizations.

“Is treating patients to improve their function and help them feel better enough?” Dr. Butler asked. “In other diseases it is. In gastrointestinal disease, if a drug helps patients feel better you approve the drug. We value improved functional capacity for patients with pulmonary hypertension, angina, and peripheral vascular disease. All these indications have drugs approved for improving functional capacity and quality of life. But for heart failure the bar has been set higher. There is a lot of interest in changing this” for heart failure.

“There is interest in running a study of ferric carboxymaltose for heart failure with a mortality endpoint. In the meantime, the impact on improving functional capacity is compelling, and it will be interesting to see what happens in the U.S. guidelines. Currently, in U.S. practice if a heart failure patient has iron-deficiency anemia you treat with intravenous iron replacement and the treatment gets reimbursed without a problem. But if the heart failure patient has iron deficiency without anemia then reimbursement for the cost of iron supplementation can be a problem,” Dr. Butler noted. This may change only if the experts who write the next U.S. heart failure guidelines decide to change the rules of what constitutes a useful heart failure treatment, he said.

Dr. Butler has been a consultant to Novartis and Amgen and several other companies. Dr. Jessup had no disclosures. Dr. Mehra has been a consultant to Teva, Johnson & Johnson, Boston Scientific, and St. Jude. Dr. Ruschitzka has been a consultant to Novartis, Servier, Sanofi, Cardiorentis, Heartware, and St. Jude. Dr. McMurray has received research support from Novartis and Amgen. Dr. Lindenfeld has been a consultant to Novartis, Abbott, Janssen, Relypsa, and Resmed. Dr. Voors has been a consultant to Novartis, Amgen, Servier, and several other drug companies. Dr. Ponikowski has been a consultant to Amgen, Novartis, Servier, and several other drug companies. Dr. Harjola has been a consultant to Novartis, Servier, Bayer, Boehringer Ingelheim, Pfizer, and Resmed. Dr. Abraham has been a consultant to Amgen, Novartis, and several device companies. Dr. Anker has been a consultant to Novartis, Servier, and several other companies.

[email protected]

On Twitter @mitchelzoler

When too many surgery patients are readmitted, the hospital can be fined by the federal government - but a new study suggests many of those readmissions are not the hospital's fault.

Many readmissions were due to issues like drug abuse or homelessness, the researchers found. Less than one in five patients returned to the hospital due to something doctors could have managed better.

"Very few were due to reasons we could control with better medical care at the index admission," said lead author Dr. Lisa McIntyre, of Harbourview Medical Center in Seattle.

McIntyre and her colleagues noted June 15 in JAMA Surgery that the U.S. government began fining hospitals in 2015 for surgery readmission rates that are higher than expected. Fines were already being imposed since 2012 for readmissions following treatments for various medical conditions.

The researchers studied the medical records of patients who were discharged from their hospital's general surgery department in 2014 or 2015 and readmitted within 30 days.

Out of the 2,100 discharges during that time, there were 173 unplanned readmissions. About 17% of those readmissions were due to injection drug use and about 15% were due to issues like homelessness or difficulty getting to follow-up appointments.

Only about 18% of readmissions - about 2% of all discharges - were due to potentially avoidable problems following surgery.

While the results are only from a single hospital, that hospital is also a safety-net facility for the local area - and McIntyre pointed out that all hospitals have some amount of disadvantaged patients.

"To be able to affect this rate, there are going to need to be new interventions that require money and a more global care package of each individual patient that doesn't stop at discharge," said McIntyre, who is also affiliated with the University of Washington.

Being female, having diabetes, having sepsis upon admission, being in the ICU and being discharged to respite care were all tied to an increased risk of readmission, the researchers found.

The results raise the question of whether readmission rates are valuable measures of surgical quality, write Drs. Alexander Schwed and Christian de Virgilio of the University of California, Los Angeles in an editorial.

Some would argue that readmitting patients is a sound medical decision that is tied to lower risks of death, they write.

"Should such an inexact marker of quality be used to financially penalize hospitals?" they ask. "Health services researchers (need to find) a better marker for surgical quality that is reliably calculable and clinically useful."

SOURCE: http://bit.ly/28Km3aH and http://bit.ly/28Km3Ye JAMA Surgery 2016.

When too many surgery patients are readmitted, the hospital can be fined by the federal government - but a new study suggests many of those readmissions are not the hospital's fault.

Many readmissions were due to issues like drug abuse or homelessness, the researchers found. Less than one in five patients returned to the hospital due to something doctors could have managed better.

"Very few were due to reasons we could control with better medical care at the index admission," said lead author Dr. Lisa McIntyre, of Harbourview Medical Center in Seattle.

McIntyre and her colleagues noted June 15 in JAMA Surgery that the U.S. government began fining hospitals in 2015 for surgery readmission rates that are higher than expected. Fines were already being imposed since 2012 for readmissions following treatments for various medical conditions.

The researchers studied the medical records of patients who were discharged from their hospital's general surgery department in 2014 or 2015 and readmitted within 30 days.

Out of the 2,100 discharges during that time, there were 173 unplanned readmissions. About 17% of those readmissions were due to injection drug use and about 15% were due to issues like homelessness or difficulty getting to follow-up appointments.

Only about 18% of readmissions - about 2% of all discharges - were due to potentially avoidable problems following surgery.

While the results are only from a single hospital, that hospital is also a safety-net facility for the local area - and McIntyre pointed out that all hospitals have some amount of disadvantaged patients.

"To be able to affect this rate, there are going to need to be new interventions that require money and a more global care package of each individual patient that doesn't stop at discharge," said McIntyre, who is also affiliated with the University of Washington.

Being female, having diabetes, having sepsis upon admission, being in the ICU and being discharged to respite care were all tied to an increased risk of readmission, the researchers found.

The results raise the question of whether readmission rates are valuable measures of surgical quality, write Drs. Alexander Schwed and Christian de Virgilio of the University of California, Los Angeles in an editorial.

Some would argue that readmitting patients is a sound medical decision that is tied to lower risks of death, they write.

"Should such an inexact marker of quality be used to financially penalize hospitals?" they ask. "Health services researchers (need to find) a better marker for surgical quality that is reliably calculable and clinically useful."

SOURCE: http://bit.ly/28Km3aH and http://bit.ly/28Km3Ye JAMA Surgery 2016.

When too many surgery patients are readmitted, the hospital can be fined by the federal government - but a new study suggests many of those readmissions are not the hospital's fault.

Many readmissions were due to issues like drug abuse or homelessness, the researchers found. Less than one in five patients returned to the hospital due to something doctors could have managed better.

"Very few were due to reasons we could control with better medical care at the index admission," said lead author Dr. Lisa McIntyre, of Harbourview Medical Center in Seattle.

McIntyre and her colleagues noted June 15 in JAMA Surgery that the U.S. government began fining hospitals in 2015 for surgery readmission rates that are higher than expected. Fines were already being imposed since 2012 for readmissions following treatments for various medical conditions.

The researchers studied the medical records of patients who were discharged from their hospital's general surgery department in 2014 or 2015 and readmitted within 30 days.

Out of the 2,100 discharges during that time, there were 173 unplanned readmissions. About 17% of those readmissions were due to injection drug use and about 15% were due to issues like homelessness or difficulty getting to follow-up appointments.

Only about 18% of readmissions - about 2% of all discharges - were due to potentially avoidable problems following surgery.

While the results are only from a single hospital, that hospital is also a safety-net facility for the local area - and McIntyre pointed out that all hospitals have some amount of disadvantaged patients.

"To be able to affect this rate, there are going to need to be new interventions that require money and a more global care package of each individual patient that doesn't stop at discharge," said McIntyre, who is also affiliated with the University of Washington.

Being female, having diabetes, having sepsis upon admission, being in the ICU and being discharged to respite care were all tied to an increased risk of readmission, the researchers found.

The results raise the question of whether readmission rates are valuable measures of surgical quality, write Drs. Alexander Schwed and Christian de Virgilio of the University of California, Los Angeles in an editorial.

Some would argue that readmitting patients is a sound medical decision that is tied to lower risks of death, they write.

"Should such an inexact marker of quality be used to financially penalize hospitals?" they ask. "Health services researchers (need to find) a better marker for surgical quality that is reliably calculable and clinically useful."

SOURCE: http://bit.ly/28Km3aH and http://bit.ly/28Km3Ye JAMA Surgery 2016.

NEW ORLEANS – Underserved African Americans with type 2 diabetes mellitus who participated in a year-long intensive self-management program did not experience sustained serum glucose control, compared with a control group receiving only two diabetes education classes.

“Relative to non-Hispanic whites, African Americans with type 2 diabetes experience more diabetes-related complications and higher rates of diabetes hospitalization,” lead study author Elizabeth B. Lynch, Ph.D., said at the annual scientific sessions of the American Diabetes Association. “These disparities are even greater for underserved disadvantaged African American populations.”

Dr. Lynch, a psychologist who directs the section of community health in the department of preventive medicine at Rush University Medical Center, Chicago, noted that several self-management interventions for diabetes have demonstrated efficacy at improving glucose control at 6 months. “However, there have not been any diabetes self-management interventions specifically targeting African Americans that have achieved sustained blood glucose control,” she said.

In a trial known as Lifestyle Intervention Through Food and Exercise (LIFE), the researchers examined the effect of a group-based intervention on glucose control at 12 months in a population of low-income African Americans. The intervention components consisted of cognitively tailored nutrition education taught by a registered dietitian, behavioral modification, social support, and peer support. “This education curriculum was based on a series of studies that were done using cognitive anthropological methods with low-income African Americans looking at beliefs and knowledge about the relationship between food and health,” Dr. Lynch said. “We used those studies to design an intervention with the aim of reducing cognitive load among participants when they’re learning new information about nutrition, so essentially making the information easier for people to understand.” Behavioral modification techniques included goal setting, self-monitoring, and problem solving. “We also had social support, and there was a peer supporter who was an individual from the community with type 2 diabetes who was assigned to each of the participants and called them on a regular basis to check in with them on their goals and encourage them,” she said.

The LIFE program consisted of 20 group sessions in the first 6 months and 8 sessions in the second 6 months, while a control group received 2 group-based education classes in the first 6 months only. The researchers conducted assessments at baseline, 6 months, and 12 months.

Individuals were eligible for the trial if they were African American, were a patient of a community clinic affiliated with Cook County Healthcare System, had a clinical diagnosis of type 2 diabetes, and had a hemoglobin A_1c level of 7% or greater. Of 1,403 initially screened for the trial, 603 were found to be eligible. Of these, 211 were randomized and enrolled: 106 to the treatment group and 105 to the control group. There was 94% follow-up at 6 and 12 months.

At baseline, the mean age of study participants was 55 years, 70% were female, 46% had a high school education or less, 60% had an annual income of less than $24,000, 65% were uninsured, and 39% had limited health literacy. Baseline food intake as reported by two 24-hour food recalls consisted of a diet high in saturated fat and low in fiber, with a moderate intake of carbohydrates and underconsumption of fruits, vegetables, and dairy products. The baseline level of daily physical activity as measured by accelerometry revealed sedentary activity that exceeded 7 hours per day, 3,614 steps per day, and only 14 minutes per day of moderate-level activity. Study enrollees had a baseline HbA_1c level of 9% and a diabetes duration of 11 years; 45% used insulin, and 48% had poor medication adherence. Their mean body mass index was 35.6 kg/m², and 91% had hypertension.

More than half of individuals in the intervention group attended each of the 20 group sessions, and 90% attended at least 1. At the same time, 68% of individuals in the control group attended both educational sessions. Dr. Lynch reported that compared with the control group, the intervention group had a significantly greater reduction in HbA_1c at 6 months (–0.76 vs. –0.21, respectively; P = .026) but not at 12 months (–0.63 vs. –0.45; P = .47). In addition, a higher percentage of individuals in the treatment group had a 0.5% or more decline in HbA_1c level at 6 months (63% vs. 42%, P = .005) but not at 12 months (53% vs. 51%, P = .89). The fact that the control group also had a reduction in HbA_1c presented a conundrum for the researchers. “One possible explanation for the decrease in A_1c in the control group is that medication adherence increased in this group, relative to the intervention group,” Dr. Lynch explained in a press release. “Additional research is needed to identify the most effective strategies to achieve sustained A_1c control in African Americans with type 2 diabetes.”

No changes were observed in blood pressure, weight, or physical activity over the course of 12 months in either group.

Although LIFE lacked a third study arm that received usual care, one possible implication of the current findings “may be that diabetes education of any type may be helpful in improving glycemic control, especially in a population that does not normally receive any education,” she said. “Medication adherence may be an easier and more effective strategy to improve glycemic control in this population.”

LIFE was supported by grants from the National Institutes of Health. Dr. Lynch reported having no relevant financial disclosures.

[email protected]

NEW ORLEANS – Underserved African Americans with type 2 diabetes mellitus who participated in a year-long intensive self-management program did not experience sustained serum glucose control, compared with a control group receiving only two diabetes education classes.

“Relative to non-Hispanic whites, African Americans with type 2 diabetes experience more diabetes-related complications and higher rates of diabetes hospitalization,” lead study author Elizabeth B. Lynch, Ph.D., said at the annual scientific sessions of the American Diabetes Association. “These disparities are even greater for underserved disadvantaged African American populations.”

Dr. Lynch, a psychologist who directs the section of community health in the department of preventive medicine at Rush University Medical Center, Chicago, noted that several self-management interventions for diabetes have demonstrated efficacy at improving glucose control at 6 months. “However, there have not been any diabetes self-management interventions specifically targeting African Americans that have achieved sustained blood glucose control,” she said.

In a trial known as Lifestyle Intervention Through Food and Exercise (LIFE), the researchers examined the effect of a group-based intervention on glucose control at 12 months in a population of low-income African Americans. The intervention components consisted of cognitively tailored nutrition education taught by a registered dietitian, behavioral modification, social support, and peer support. “This education curriculum was based on a series of studies that were done using cognitive anthropological methods with low-income African Americans looking at beliefs and knowledge about the relationship between food and health,” Dr. Lynch said. “We used those studies to design an intervention with the aim of reducing cognitive load among participants when they’re learning new information about nutrition, so essentially making the information easier for people to understand.” Behavioral modification techniques included goal setting, self-monitoring, and problem solving. “We also had social support, and there was a peer supporter who was an individual from the community with type 2 diabetes who was assigned to each of the participants and called them on a regular basis to check in with them on their goals and encourage them,” she said.

The LIFE program consisted of 20 group sessions in the first 6 months and 8 sessions in the second 6 months, while a control group received 2 group-based education classes in the first 6 months only. The researchers conducted assessments at baseline, 6 months, and 12 months.

Individuals were eligible for the trial if they were African American, were a patient of a community clinic affiliated with Cook County Healthcare System, had a clinical diagnosis of type 2 diabetes, and had a hemoglobin A_1c level of 7% or greater. Of 1,403 initially screened for the trial, 603 were found to be eligible. Of these, 211 were randomized and enrolled: 106 to the treatment group and 105 to the control group. There was 94% follow-up at 6 and 12 months.

At baseline, the mean age of study participants was 55 years, 70% were female, 46% had a high school education or less, 60% had an annual income of less than $24,000, 65% were uninsured, and 39% had limited health literacy. Baseline food intake as reported by two 24-hour food recalls consisted of a diet high in saturated fat and low in fiber, with a moderate intake of carbohydrates and underconsumption of fruits, vegetables, and dairy products. The baseline level of daily physical activity as measured by accelerometry revealed sedentary activity that exceeded 7 hours per day, 3,614 steps per day, and only 14 minutes per day of moderate-level activity. Study enrollees had a baseline HbA_1c level of 9% and a diabetes duration of 11 years; 45% used insulin, and 48% had poor medication adherence. Their mean body mass index was 35.6 kg/m², and 91% had hypertension.

More than half of individuals in the intervention group attended each of the 20 group sessions, and 90% attended at least 1. At the same time, 68% of individuals in the control group attended both educational sessions. Dr. Lynch reported that compared with the control group, the intervention group had a significantly greater reduction in HbA_1c at 6 months (–0.76 vs. –0.21, respectively; P = .026) but not at 12 months (–0.63 vs. –0.45; P = .47). In addition, a higher percentage of individuals in the treatment group had a 0.5% or more decline in HbA_1c level at 6 months (63% vs. 42%, P = .005) but not at 12 months (53% vs. 51%, P = .89). The fact that the control group also had a reduction in HbA_1c presented a conundrum for the researchers. “One possible explanation for the decrease in A_1c in the control group is that medication adherence increased in this group, relative to the intervention group,” Dr. Lynch explained in a press release. “Additional research is needed to identify the most effective strategies to achieve sustained A_1c control in African Americans with type 2 diabetes.”

No changes were observed in blood pressure, weight, or physical activity over the course of 12 months in either group.

Although LIFE lacked a third study arm that received usual care, one possible implication of the current findings “may be that diabetes education of any type may be helpful in improving glycemic control, especially in a population that does not normally receive any education,” she said. “Medication adherence may be an easier and more effective strategy to improve glycemic control in this population.”

LIFE was supported by grants from the National Institutes of Health. Dr. Lynch reported having no relevant financial disclosures.

[email protected]

NEW ORLEANS – Underserved African Americans with type 2 diabetes mellitus who participated in a year-long intensive self-management program did not experience sustained serum glucose control, compared with a control group receiving only two diabetes education classes.

“Relative to non-Hispanic whites, African Americans with type 2 diabetes experience more diabetes-related complications and higher rates of diabetes hospitalization,” lead study author Elizabeth B. Lynch, Ph.D., said at the annual scientific sessions of the American Diabetes Association. “These disparities are even greater for underserved disadvantaged African American populations.”

Dr. Lynch, a psychologist who directs the section of community health in the department of preventive medicine at Rush University Medical Center, Chicago, noted that several self-management interventions for diabetes have demonstrated efficacy at improving glucose control at 6 months. “However, there have not been any diabetes self-management interventions specifically targeting African Americans that have achieved sustained blood glucose control,” she said.

In a trial known as Lifestyle Intervention Through Food and Exercise (LIFE), the researchers examined the effect of a group-based intervention on glucose control at 12 months in a population of low-income African Americans. The intervention components consisted of cognitively tailored nutrition education taught by a registered dietitian, behavioral modification, social support, and peer support. “This education curriculum was based on a series of studies that were done using cognitive anthropological methods with low-income African Americans looking at beliefs and knowledge about the relationship between food and health,” Dr. Lynch said. “We used those studies to design an intervention with the aim of reducing cognitive load among participants when they’re learning new information about nutrition, so essentially making the information easier for people to understand.” Behavioral modification techniques included goal setting, self-monitoring, and problem solving. “We also had social support, and there was a peer supporter who was an individual from the community with type 2 diabetes who was assigned to each of the participants and called them on a regular basis to check in with them on their goals and encourage them,” she said.

The LIFE program consisted of 20 group sessions in the first 6 months and 8 sessions in the second 6 months, while a control group received 2 group-based education classes in the first 6 months only. The researchers conducted assessments at baseline, 6 months, and 12 months.

Individuals were eligible for the trial if they were African American, were a patient of a community clinic affiliated with Cook County Healthcare System, had a clinical diagnosis of type 2 diabetes, and had a hemoglobin A_1c level of 7% or greater. Of 1,403 initially screened for the trial, 603 were found to be eligible. Of these, 211 were randomized and enrolled: 106 to the treatment group and 105 to the control group. There was 94% follow-up at 6 and 12 months.

At baseline, the mean age of study participants was 55 years, 70% were female, 46% had a high school education or less, 60% had an annual income of less than $24,000, 65% were uninsured, and 39% had limited health literacy. Baseline food intake as reported by two 24-hour food recalls consisted of a diet high in saturated fat and low in fiber, with a moderate intake of carbohydrates and underconsumption of fruits, vegetables, and dairy products. The baseline level of daily physical activity as measured by accelerometry revealed sedentary activity that exceeded 7 hours per day, 3,614 steps per day, and only 14 minutes per day of moderate-level activity. Study enrollees had a baseline HbA_1c level of 9% and a diabetes duration of 11 years; 45% used insulin, and 48% had poor medication adherence. Their mean body mass index was 35.6 kg/m², and 91% had hypertension.

More than half of individuals in the intervention group attended each of the 20 group sessions, and 90% attended at least 1. At the same time, 68% of individuals in the control group attended both educational sessions. Dr. Lynch reported that compared with the control group, the intervention group had a significantly greater reduction in HbA_1c at 6 months (–0.76 vs. –0.21, respectively; P = .026) but not at 12 months (–0.63 vs. –0.45; P = .47). In addition, a higher percentage of individuals in the treatment group had a 0.5% or more decline in HbA_1c level at 6 months (63% vs. 42%, P = .005) but not at 12 months (53% vs. 51%, P = .89). The fact that the control group also had a reduction in HbA_1c presented a conundrum for the researchers. “One possible explanation for the decrease in A_1c in the control group is that medication adherence increased in this group, relative to the intervention group,” Dr. Lynch explained in a press release. “Additional research is needed to identify the most effective strategies to achieve sustained A_1c control in African Americans with type 2 diabetes.”

No changes were observed in blood pressure, weight, or physical activity over the course of 12 months in either group.

Although LIFE lacked a third study arm that received usual care, one possible implication of the current findings “may be that diabetes education of any type may be helpful in improving glycemic control, especially in a population that does not normally receive any education,” she said. “Medication adherence may be an easier and more effective strategy to improve glycemic control in this population.”

LIFE was supported by grants from the National Institutes of Health. Dr. Lynch reported having no relevant financial disclosures.

[email protected]

In discussion of pregnancy prevention, a great deal of time is spent on female birth control, and the use of condoms is like a tag line “Oh! And, of course, use a condom.” But are we really educating our teens on condoms, their proper use, and their prevention of sexually transmitted infections (STIs). Condoms are our basic entry level birth control, but despite their relative ease of use and accessibility, their use is on the decline.

When we evaluate unintended pregnancies among teens, it is down almost 20% since 1981, according to data from the Guttmacher Institute, but compared with other developed nations, our rates are high.

In 2013, the AAP published a statement encouraging schools and pediatricians to discuss and make condoms more accessible. Fifty-four studies were done on early education of condom use, and reported a 48% increase in their use and a 42% delay in the initiation of sexual activity by 6 months.¹ Despite these positive findings , condom use is still declining.

Many factors that affect their use are lack of formal education, availability, and the perception that they decrease sexual pleasure. Condom manufacturers have started campaigns that promote the image of escalating sexual pleasure, but they are competing with the media and music industry, which inundate teens with all kinds of sexual images. In review of the media, 77% showed sexual content, compared with 14% that showed risk and responsible sexual activity.

Before educating teens about condoms, we first must educate ourselves. Condoms are available in three forms: latex (80%), lamb’s cecum (15%), and synthetic (5%). Latex is considered the most effective condom in protecting against STIs and birth control. Synthetic is a good alternative to latex when a latex allergy is present, but is more prone to breakage and slippage. Lamb’s cecum prevents spread of some STIs, but because of its porous nature it does not provide protection against viruses such as HIV, hepatitis B, and herpes simplex virus (HSV). Nonlatex has a longer shelf life and is more compatible with lubricants.

Spermicide-coated condoms have fallen out of favor because the spermicide shortens the shelf life of the condom, as well as can cause mucosal irritation. When the mucosa is irritated, there is an associated increase of contracting STIs, particularly HIV.²

Make patients are aware that condoms do expire and that it is important to check the expiration date. Educating patients on the proper technique of putting a condom on is likely an awkward conversation for most, so consider directing them to the website Bedsiders.org, which has great explanations on how to use and put condoms on, along with comparisons of all types of birth control and which one is best for them.

Making condoms easily accessible is the most-important intervention. Studies show that when condoms are readily available, their use increases. The AAP advocates for schools and primary care doctors to hand them out freely.

Education is key in increasing usage of condoms and reducing spread of STIs. Encouraging parents to talk with their teen and provide access to condoms is crucial in lowering STI statistics. Although abstinence is the only 100% proof of protection, proper use of contraception is an alternative.

References

1. “Condom Use by Adolescents,” Pediatrics. 2013 Nov. doi: 10.1542/peds.2013-2821

2. “Contraception for Adolescents,” Pediatrics. 2014 Oct 10;134:e1244-56.

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

In discussion of pregnancy prevention, a great deal of time is spent on female birth control, and the use of condoms is like a tag line “Oh! And, of course, use a condom.” But are we really educating our teens on condoms, their proper use, and their prevention of sexually transmitted infections (STIs). Condoms are our basic entry level birth control, but despite their relative ease of use and accessibility, their use is on the decline.

When we evaluate unintended pregnancies among teens, it is down almost 20% since 1981, according to data from the Guttmacher Institute, but compared with other developed nations, our rates are high.

In 2013, the AAP published a statement encouraging schools and pediatricians to discuss and make condoms more accessible. Fifty-four studies were done on early education of condom use, and reported a 48% increase in their use and a 42% delay in the initiation of sexual activity by 6 months.¹ Despite these positive findings , condom use is still declining.

Many factors that affect their use are lack of formal education, availability, and the perception that they decrease sexual pleasure. Condom manufacturers have started campaigns that promote the image of escalating sexual pleasure, but they are competing with the media and music industry, which inundate teens with all kinds of sexual images. In review of the media, 77% showed sexual content, compared with 14% that showed risk and responsible sexual activity.

Before educating teens about condoms, we first must educate ourselves. Condoms are available in three forms: latex (80%), lamb’s cecum (15%), and synthetic (5%). Latex is considered the most effective condom in protecting against STIs and birth control. Synthetic is a good alternative to latex when a latex allergy is present, but is more prone to breakage and slippage. Lamb’s cecum prevents spread of some STIs, but because of its porous nature it does not provide protection against viruses such as HIV, hepatitis B, and herpes simplex virus (HSV). Nonlatex has a longer shelf life and is more compatible with lubricants.

Spermicide-coated condoms have fallen out of favor because the spermicide shortens the shelf life of the condom, as well as can cause mucosal irritation. When the mucosa is irritated, there is an associated increase of contracting STIs, particularly HIV.²

Make patients are aware that condoms do expire and that it is important to check the expiration date. Educating patients on the proper technique of putting a condom on is likely an awkward conversation for most, so consider directing them to the website Bedsiders.org, which has great explanations on how to use and put condoms on, along with comparisons of all types of birth control and which one is best for them.

Making condoms easily accessible is the most-important intervention. Studies show that when condoms are readily available, their use increases. The AAP advocates for schools and primary care doctors to hand them out freely.

Education is key in increasing usage of condoms and reducing spread of STIs. Encouraging parents to talk with their teen and provide access to condoms is crucial in lowering STI statistics. Although abstinence is the only 100% proof of protection, proper use of contraception is an alternative.

References

1. “Condom Use by Adolescents,” Pediatrics. 2013 Nov. doi: 10.1542/peds.2013-2821

2. “Contraception for Adolescents,” Pediatrics. 2014 Oct 10;134:e1244-56.

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

In discussion of pregnancy prevention, a great deal of time is spent on female birth control, and the use of condoms is like a tag line “Oh! And, of course, use a condom.” But are we really educating our teens on condoms, their proper use, and their prevention of sexually transmitted infections (STIs). Condoms are our basic entry level birth control, but despite their relative ease of use and accessibility, their use is on the decline.

When we evaluate unintended pregnancies among teens, it is down almost 20% since 1981, according to data from the Guttmacher Institute, but compared with other developed nations, our rates are high.

In 2013, the AAP published a statement encouraging schools and pediatricians to discuss and make condoms more accessible. Fifty-four studies were done on early education of condom use, and reported a 48% increase in their use and a 42% delay in the initiation of sexual activity by 6 months.¹ Despite these positive findings , condom use is still declining.

Many factors that affect their use are lack of formal education, availability, and the perception that they decrease sexual pleasure. Condom manufacturers have started campaigns that promote the image of escalating sexual pleasure, but they are competing with the media and music industry, which inundate teens with all kinds of sexual images. In review of the media, 77% showed sexual content, compared with 14% that showed risk and responsible sexual activity.

Before educating teens about condoms, we first must educate ourselves. Condoms are available in three forms: latex (80%), lamb’s cecum (15%), and synthetic (5%). Latex is considered the most effective condom in protecting against STIs and birth control. Synthetic is a good alternative to latex when a latex allergy is present, but is more prone to breakage and slippage. Lamb’s cecum prevents spread of some STIs, but because of its porous nature it does not provide protection against viruses such as HIV, hepatitis B, and herpes simplex virus (HSV). Nonlatex has a longer shelf life and is more compatible with lubricants.

Spermicide-coated condoms have fallen out of favor because the spermicide shortens the shelf life of the condom, as well as can cause mucosal irritation. When the mucosa is irritated, there is an associated increase of contracting STIs, particularly HIV.²

Make patients are aware that condoms do expire and that it is important to check the expiration date. Educating patients on the proper technique of putting a condom on is likely an awkward conversation for most, so consider directing them to the website Bedsiders.org, which has great explanations on how to use and put condoms on, along with comparisons of all types of birth control and which one is best for them.

Making condoms easily accessible is the most-important intervention. Studies show that when condoms are readily available, their use increases. The AAP advocates for schools and primary care doctors to hand them out freely.

Education is key in increasing usage of condoms and reducing spread of STIs. Encouraging parents to talk with their teen and provide access to condoms is crucial in lowering STI statistics. Although abstinence is the only 100% proof of protection, proper use of contraception is an alternative.

References

1. “Condom Use by Adolescents,” Pediatrics. 2013 Nov. doi: 10.1542/peds.2013-2821

2. “Contraception for Adolescents,” Pediatrics. 2014 Oct 10;134:e1244-56.

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

LONDON – A single, intravenous infusion of 1,000 mg of rituximab to people with arthralgia and a high risk for developing rheumatoid arthritis cut the subsequent rate of rheumatoid arthritis development roughly in half during more than 18 months of follow-up in a proof-of-concept, placebo-controlled study that randomized 81 people.

“This is the first study to evaluate the effects of a biopharmaceutical in subjects at risk of developing RA [rheumatoid arthritis],” Dr. Daniëlle M. Gerlag said at the European Congress of Rheumatology. “These results strongly support the rationale for future clinical trials aimed at prevention of RA by a targeted intervention,” added Dr. Gerlag, a rheumatologist at the Academic Medical Center in Amsterdam.

Mitchel L. Zoler/Frontline Medical News

Additional studies are needed to confirm this effect and to examine whether the period of protection against RA development can be extended by administration of additional rituximab (Rituxan) doses. In the current study, the protective effect from the single dose administered appeared to wane over time, she noted.

The idea behind this strategy is that a window of opportunity exists in people at high risk for developing RA to prevent the disease by blocking production of the autoantibodies that trigger the development of a subclinical synovitis that eventually leads to RA. Rituximab is a cytolytic antibody directed against the CD20 antigen on B cells that already has regulatory approval for treating moderately to severely active RA as well as certain other diseases.

Dr. Gerlag and her associates recently published an analysis that detailed their rationale for hypothesizing that prophylactic treatment with rituximab might prove effective at delaying or preventing the development of RA in susceptible people (Rheumatology [Oxford]. 2016 April;55[4]:607-14).

The Prevention of RA by Rituximab (PRAIRI) study ran at three Dutch centers. The investigators enrolled people with arthralgia who had never been diagnosed with arthritis, had never used a disease-modifying antirheumatic drug, and had at least one of these two risk factors: a serum level of IgM rheumatoid factor of more than 12.5 IU/mL and a serum level of anticitrullinated peptide antibodies of more than 25 IU/mL. Enrolled participants also needed to have at least one of the following: a serum level of C-reactive protein greater than 3 mg/L, an erythrocyte sedimentation rate of greater than 28 mm/hr, and evidence of subclinical synovitis identified by either ultrasound or MRI.

The researchers found these participants largely through screening sessions run at health fairs and by publicizing the study during television appearances, Dr. Gerlag said. About three-quarters of the participants were first-degree relatives of patients already diagnosed with RA, but this was not a criterion for enrollment. The participants averaged about 53 years old, and nearly two-thirds were women.

Among the 81 people who underwent treatment, 41 received a single, 1,000-mg infusion of rituximab, and 40 received a placebo infusion. The researchers then followed the participants with scheduled, periodic examinations during a median of 29 months.

During follow-up, 16 of the 40 people in the placebo group (40%) developed RA after a median of 12 months, and 14 of the 41 in the treated arm (34%) developed RA after a median of 17 months.

The researchers performed two different statistical analyses on these outcomes. They used a Kaplan-Meier survival analysis to determine the time until 25% of people in each arm developed RA. Among the placebo patients, this occurred after 12 months, while in the intervention arm, it did not occur until 24 months, a statistically significant doubling of the time to this outcome with rituximab treatment, Dr. Gerlag reported.

The second analysis calculated a Cox proportional hazard ratio based on the time to development of rheumatoid arthritis among those in each of the treatment groups. This determined a 55% reduced hazard ratio after 12 months among people treated with rituximab, compared with the placebo-treated controls, and a 53% reduced hazard after 18 months, both statistically significant differences.

A safety analysis showed that some people treated with rituximab had mild infusion-related symptoms, but no participants had serious infections. Serious adverse events occurred in 11 people in the rituximab group and in 3 in the placebo arm, but none of these serious adverse events was judged to be related to treatment by the study’s data safety monitoring board, said Dr. Gerlag, who is also on the staff of GlaxoSmithKline in Cambridge, England.

The PRAIRI study received no commercial funding. Dr. Gerlag is also a shareholder in GlaxoSmithKline, but the company played no role in the study.

[email protected]

On Twitter@mitchelzoler

LONDON – A single, intravenous infusion of 1,000 mg of rituximab to people with arthralgia and a high risk for developing rheumatoid arthritis cut the subsequent rate of rheumatoid arthritis development roughly in half during more than 18 months of follow-up in a proof-of-concept, placebo-controlled study that randomized 81 people.

“This is the first study to evaluate the effects of a biopharmaceutical in subjects at risk of developing RA [rheumatoid arthritis],” Dr. Daniëlle M. Gerlag said at the European Congress of Rheumatology. “These results strongly support the rationale for future clinical trials aimed at prevention of RA by a targeted intervention,” added Dr. Gerlag, a rheumatologist at the Academic Medical Center in Amsterdam.

Mitchel L. Zoler/Frontline Medical News

Additional studies are needed to confirm this effect and to examine whether the period of protection against RA development can be extended by administration of additional rituximab (Rituxan) doses. In the current study, the protective effect from the single dose administered appeared to wane over time, she noted.

The idea behind this strategy is that a window of opportunity exists in people at high risk for developing RA to prevent the disease by blocking production of the autoantibodies that trigger the development of a subclinical synovitis that eventually leads to RA. Rituximab is a cytolytic antibody directed against the CD20 antigen on B cells that already has regulatory approval for treating moderately to severely active RA as well as certain other diseases.

Dr. Gerlag and her associates recently published an analysis that detailed their rationale for hypothesizing that prophylactic treatment with rituximab might prove effective at delaying or preventing the development of RA in susceptible people (Rheumatology [Oxford]. 2016 April;55[4]:607-14).

The Prevention of RA by Rituximab (PRAIRI) study ran at three Dutch centers. The investigators enrolled people with arthralgia who had never been diagnosed with arthritis, had never used a disease-modifying antirheumatic drug, and had at least one of these two risk factors: a serum level of IgM rheumatoid factor of more than 12.5 IU/mL and a serum level of anticitrullinated peptide antibodies of more than 25 IU/mL. Enrolled participants also needed to have at least one of the following: a serum level of C-reactive protein greater than 3 mg/L, an erythrocyte sedimentation rate of greater than 28 mm/hr, and evidence of subclinical synovitis identified by either ultrasound or MRI.

The researchers found these participants largely through screening sessions run at health fairs and by publicizing the study during television appearances, Dr. Gerlag said. About three-quarters of the participants were first-degree relatives of patients already diagnosed with RA, but this was not a criterion for enrollment. The participants averaged about 53 years old, and nearly two-thirds were women.

Among the 81 people who underwent treatment, 41 received a single, 1,000-mg infusion of rituximab, and 40 received a placebo infusion. The researchers then followed the participants with scheduled, periodic examinations during a median of 29 months.

During follow-up, 16 of the 40 people in the placebo group (40%) developed RA after a median of 12 months, and 14 of the 41 in the treated arm (34%) developed RA after a median of 17 months.

The researchers performed two different statistical analyses on these outcomes. They used a Kaplan-Meier survival analysis to determine the time until 25% of people in each arm developed RA. Among the placebo patients, this occurred after 12 months, while in the intervention arm, it did not occur until 24 months, a statistically significant doubling of the time to this outcome with rituximab treatment, Dr. Gerlag reported.

The second analysis calculated a Cox proportional hazard ratio based on the time to development of rheumatoid arthritis among those in each of the treatment groups. This determined a 55% reduced hazard ratio after 12 months among people treated with rituximab, compared with the placebo-treated controls, and a 53% reduced hazard after 18 months, both statistically significant differences.

A safety analysis showed that some people treated with rituximab had mild infusion-related symptoms, but no participants had serious infections. Serious adverse events occurred in 11 people in the rituximab group and in 3 in the placebo arm, but none of these serious adverse events was judged to be related to treatment by the study’s data safety monitoring board, said Dr. Gerlag, who is also on the staff of GlaxoSmithKline in Cambridge, England.

The PRAIRI study received no commercial funding. Dr. Gerlag is also a shareholder in GlaxoSmithKline, but the company played no role in the study.

[email protected]

On Twitter@mitchelzoler

LONDON – A single, intravenous infusion of 1,000 mg of rituximab to people with arthralgia and a high risk for developing rheumatoid arthritis cut the subsequent rate of rheumatoid arthritis development roughly in half during more than 18 months of follow-up in a proof-of-concept, placebo-controlled study that randomized 81 people.

“This is the first study to evaluate the effects of a biopharmaceutical in subjects at risk of developing RA [rheumatoid arthritis],” Dr. Daniëlle M. Gerlag said at the European Congress of Rheumatology. “These results strongly support the rationale for future clinical trials aimed at prevention of RA by a targeted intervention,” added Dr. Gerlag, a rheumatologist at the Academic Medical Center in Amsterdam.

Mitchel L. Zoler/Frontline Medical News

Additional studies are needed to confirm this effect and to examine whether the period of protection against RA development can be extended by administration of additional rituximab (Rituxan) doses. In the current study, the protective effect from the single dose administered appeared to wane over time, she noted.

The idea behind this strategy is that a window of opportunity exists in people at high risk for developing RA to prevent the disease by blocking production of the autoantibodies that trigger the development of a subclinical synovitis that eventually leads to RA. Rituximab is a cytolytic antibody directed against the CD20 antigen on B cells that already has regulatory approval for treating moderately to severely active RA as well as certain other diseases.

Dr. Gerlag and her associates recently published an analysis that detailed their rationale for hypothesizing that prophylactic treatment with rituximab might prove effective at delaying or preventing the development of RA in susceptible people (Rheumatology [Oxford]. 2016 April;55[4]:607-14).

The Prevention of RA by Rituximab (PRAIRI) study ran at three Dutch centers. The investigators enrolled people with arthralgia who had never been diagnosed with arthritis, had never used a disease-modifying antirheumatic drug, and had at least one of these two risk factors: a serum level of IgM rheumatoid factor of more than 12.5 IU/mL and a serum level of anticitrullinated peptide antibodies of more than 25 IU/mL. Enrolled participants also needed to have at least one of the following: a serum level of C-reactive protein greater than 3 mg/L, an erythrocyte sedimentation rate of greater than 28 mm/hr, and evidence of subclinical synovitis identified by either ultrasound or MRI.

The researchers found these participants largely through screening sessions run at health fairs and by publicizing the study during television appearances, Dr. Gerlag said. About three-quarters of the participants were first-degree relatives of patients already diagnosed with RA, but this was not a criterion for enrollment. The participants averaged about 53 years old, and nearly two-thirds were women.

Among the 81 people who underwent treatment, 41 received a single, 1,000-mg infusion of rituximab, and 40 received a placebo infusion. The researchers then followed the participants with scheduled, periodic examinations during a median of 29 months.

During follow-up, 16 of the 40 people in the placebo group (40%) developed RA after a median of 12 months, and 14 of the 41 in the treated arm (34%) developed RA after a median of 17 months.

The researchers performed two different statistical analyses on these outcomes. They used a Kaplan-Meier survival analysis to determine the time until 25% of people in each arm developed RA. Among the placebo patients, this occurred after 12 months, while in the intervention arm, it did not occur until 24 months, a statistically significant doubling of the time to this outcome with rituximab treatment, Dr. Gerlag reported.

The second analysis calculated a Cox proportional hazard ratio based on the time to development of rheumatoid arthritis among those in each of the treatment groups. This determined a 55% reduced hazard ratio after 12 months among people treated with rituximab, compared with the placebo-treated controls, and a 53% reduced hazard after 18 months, both statistically significant differences.

A safety analysis showed that some people treated with rituximab had mild infusion-related symptoms, but no participants had serious infections. Serious adverse events occurred in 11 people in the rituximab group and in 3 in the placebo arm, but none of these serious adverse events was judged to be related to treatment by the study’s data safety monitoring board, said Dr. Gerlag, who is also on the staff of GlaxoSmithKline in Cambridge, England.

The PRAIRI study received no commercial funding. Dr. Gerlag is also a shareholder in GlaxoSmithKline, but the company played no role in the study.

[email protected]

On Twitter@mitchelzoler

LONDON – Early clinical data show that a novel injectable drug holds promise for becoming the first disease-modifying osteoarthritis drug.

The results of a randomized, placebo-controlled, double-blind phase I trial involving 61 patients showed that a single intra-articular injection of SM04690 was associated with improved Western Ontario and McMaster Universities Arthritis Index (WOMAC) function and pain scores. The investigational drug also seemed to slow joint-space narrowing, compared with baseline values, with the suggestion that it may even increase joint space width.

However, those were exploratory efficacy analyses because the primary objective of the trial was to examine the safety of SM04690, a small molecule that inhibits the Wnt signaling pathway.

“The Wnt pathway has been implicated in the development of osteoarthritis [OA],” said Dr. Yusuf Yazici during a poster presentation at the European Congress of Rheumatology.

“Overactivity of Wnt signaling leads to stem cells constantly differentiating into osteoblasts, leading to osteophyte formation,” he explained, noting that Wnt signaling also stimulates the secretion of cartilage-destroying metalloproteases (Osteoarthritis Cartilage. 2012;20:162-71). “It has been very well established in the literature that if you could somehow turn that off you, could maybe improve some of the things that are happening in osteoarthritis.”

SM04690 works by “pushing the lineage fate of progenitor stem cells in the knee towards chondrocyte formation and away from osteoblast formation,” said Dr. Yazici of New York University Langone Medical Center, New York, and the chief medical officer of Samumed, the San Diego–based company developing the novel Wnt inhibitor.

He noted preclinical data had been presented orally at the EULAR congress showing that there was cartilage growth, suppressed protease production, and reduced proinflammatory cytokine (interleukin-6 and tumor necrosis factor–alpha) production.

The phase I data represent the first in-human results, with three doses of SM04690 evaluated (0.03 mg, 0.07 mg, and 0.23 mg) versus placebo in patients with moderate to severe symptomatic OA. For inclusion, patients had to have a WOMAC total score of between 36 and 72 and Kellgren-Lawrence (KL) grade 2 or 3 knee OA, and be willing to forgo pain medication for 24 hours prior to pain assessments being performed.

At baseline, the mean age of patients ranged from 60 to 64 years, their body mass index ranged from 28.7 kg/m² to 31.4 kg/m², and 41%-69% had KL grade 3 knee OA.

In terms of safety, the primary objective of the trial, there were no reports of serious adverse events related to the study drug. One patient who had reported increased knee pain and paroxysmal tachycardia 2 months after the injection was found to have a history of the condition, and after unblinding, none of the patients had detectable drug levels outside of the knee.

Overall, the number of adverse events was low and no different from placebo, Dr. Yazici said. The percentage of patients reporting an adverse event with the three rising doses of SM04690 were 53%, 35%, and 44%, respectively, compared with 55% of those given placebo.

WOMAC function scores for the 0.03-mg dose declined by a mean of –18.4 at week 12 and by –20.1 at week 24 from a baseline of 39.1; for 0.07 mg, by –19.5 at week 12 and by –18.9 at 24 weeks from 37.5; for 0.23 mg, by –17.8 at week 12 and by –12.4 at week 24 from 40.4; and for placebo, by –14.9 at week 12 and by –16.0 at week 24 from 34.4.

WOMAC pain scores at baseline were a respective 10.8, 10.8, 11.4, and 9.9, and the mean changes at week 12 were –4.4, –5.8, –5.7, and –4.2. At week 24, the mean declines were –5.6, –5.3, –4.3, and –4.8.

Medial joint space width was a mean of 4.5, 3.72, 3.62, and 3.74 mm at baseline in the four treatment groups, with mean changes from baseline to 24 weeks of 0.00, 0.49, –0.15, and –0.33 for the 0.03-mg, 0.07-mg, and 0.23-mg SM04690 and placebo groups, respectively.

Although the trial was not powered to detect any statistically significant differences between the active treatment dose and placebo, there was an indication that more patients treated with SM04690 than with placebo were likely to achieve an OMERACT-OARSI strict response.

These data support the ongoing phase II trial that is being conducted in 455 patients, Dr. Yazici said. The results of that trial are expected around October 2016, which should be in time for their presentation at the annual meeting of the American College of Rheumatology.

LONDON – Early clinical data show that a novel injectable drug holds promise for becoming the first disease-modifying osteoarthritis drug.

The results of a randomized, placebo-controlled, double-blind phase I trial involving 61 patients showed that a single intra-articular injection of SM04690 was associated with improved Western Ontario and McMaster Universities Arthritis Index (WOMAC) function and pain scores. The investigational drug also seemed to slow joint-space narrowing, compared with baseline values, with the suggestion that it may even increase joint space width.

However, those were exploratory efficacy analyses because the primary objective of the trial was to examine the safety of SM04690, a small molecule that inhibits the Wnt signaling pathway.

“The Wnt pathway has been implicated in the development of osteoarthritis [OA],” said Dr. Yusuf Yazici during a poster presentation at the European Congress of Rheumatology.

“Overactivity of Wnt signaling leads to stem cells constantly differentiating into osteoblasts, leading to osteophyte formation,” he explained, noting that Wnt signaling also stimulates the secretion of cartilage-destroying metalloproteases (Osteoarthritis Cartilage. 2012;20:162-71). “It has been very well established in the literature that if you could somehow turn that off you, could maybe improve some of the things that are happening in osteoarthritis.”

SM04690 works by “pushing the lineage fate of progenitor stem cells in the knee towards chondrocyte formation and away from osteoblast formation,” said Dr. Yazici of New York University Langone Medical Center, New York, and the chief medical officer of Samumed, the San Diego–based company developing the novel Wnt inhibitor.

He noted preclinical data had been presented orally at the EULAR congress showing that there was cartilage growth, suppressed protease production, and reduced proinflammatory cytokine (interleukin-6 and tumor necrosis factor–alpha) production.

The phase I data represent the first in-human results, with three doses of SM04690 evaluated (0.03 mg, 0.07 mg, and 0.23 mg) versus placebo in patients with moderate to severe symptomatic OA. For inclusion, patients had to have a WOMAC total score of between 36 and 72 and Kellgren-Lawrence (KL) grade 2 or 3 knee OA, and be willing to forgo pain medication for 24 hours prior to pain assessments being performed.

At baseline, the mean age of patients ranged from 60 to 64 years, their body mass index ranged from 28.7 kg/m² to 31.4 kg/m², and 41%-69% had KL grade 3 knee OA.

In terms of safety, the primary objective of the trial, there were no reports of serious adverse events related to the study drug. One patient who had reported increased knee pain and paroxysmal tachycardia 2 months after the injection was found to have a history of the condition, and after unblinding, none of the patients had detectable drug levels outside of the knee.

Overall, the number of adverse events was low and no different from placebo, Dr. Yazici said. The percentage of patients reporting an adverse event with the three rising doses of SM04690 were 53%, 35%, and 44%, respectively, compared with 55% of those given placebo.

WOMAC function scores for the 0.03-mg dose declined by a mean of –18.4 at week 12 and by –20.1 at week 24 from a baseline of 39.1; for 0.07 mg, by –19.5 at week 12 and by –18.9 at 24 weeks from 37.5; for 0.23 mg, by –17.8 at week 12 and by –12.4 at week 24 from 40.4; and for placebo, by –14.9 at week 12 and by –16.0 at week 24 from 34.4.

WOMAC pain scores at baseline were a respective 10.8, 10.8, 11.4, and 9.9, and the mean changes at week 12 were –4.4, –5.8, –5.7, and –4.2. At week 24, the mean declines were –5.6, –5.3, –4.3, and –4.8.

Medial joint space width was a mean of 4.5, 3.72, 3.62, and 3.74 mm at baseline in the four treatment groups, with mean changes from baseline to 24 weeks of 0.00, 0.49, –0.15, and –0.33 for the 0.03-mg, 0.07-mg, and 0.23-mg SM04690 and placebo groups, respectively.

Although the trial was not powered to detect any statistically significant differences between the active treatment dose and placebo, there was an indication that more patients treated with SM04690 than with placebo were likely to achieve an OMERACT-OARSI strict response.

These data support the ongoing phase II trial that is being conducted in 455 patients, Dr. Yazici said. The results of that trial are expected around October 2016, which should be in time for their presentation at the annual meeting of the American College of Rheumatology.

LONDON – Early clinical data show that a novel injectable drug holds promise for becoming the first disease-modifying osteoarthritis drug.

The results of a randomized, placebo-controlled, double-blind phase I trial involving 61 patients showed that a single intra-articular injection of SM04690 was associated with improved Western Ontario and McMaster Universities Arthritis Index (WOMAC) function and pain scores. The investigational drug also seemed to slow joint-space narrowing, compared with baseline values, with the suggestion that it may even increase joint space width.

However, those were exploratory efficacy analyses because the primary objective of the trial was to examine the safety of SM04690, a small molecule that inhibits the Wnt signaling pathway.

“The Wnt pathway has been implicated in the development of osteoarthritis [OA],” said Dr. Yusuf Yazici during a poster presentation at the European Congress of Rheumatology.

“Overactivity of Wnt signaling leads to stem cells constantly differentiating into osteoblasts, leading to osteophyte formation,” he explained, noting that Wnt signaling also stimulates the secretion of cartilage-destroying metalloproteases (Osteoarthritis Cartilage. 2012;20:162-71). “It has been very well established in the literature that if you could somehow turn that off you, could maybe improve some of the things that are happening in osteoarthritis.”

SM04690 works by “pushing the lineage fate of progenitor stem cells in the knee towards chondrocyte formation and away from osteoblast formation,” said Dr. Yazici of New York University Langone Medical Center, New York, and the chief medical officer of Samumed, the San Diego–based company developing the novel Wnt inhibitor.

He noted preclinical data had been presented orally at the EULAR congress showing that there was cartilage growth, suppressed protease production, and reduced proinflammatory cytokine (interleukin-6 and tumor necrosis factor–alpha) production.

The phase I data represent the first in-human results, with three doses of SM04690 evaluated (0.03 mg, 0.07 mg, and 0.23 mg) versus placebo in patients with moderate to severe symptomatic OA. For inclusion, patients had to have a WOMAC total score of between 36 and 72 and Kellgren-Lawrence (KL) grade 2 or 3 knee OA, and be willing to forgo pain medication for 24 hours prior to pain assessments being performed.

At baseline, the mean age of patients ranged from 60 to 64 years, their body mass index ranged from 28.7 kg/m² to 31.4 kg/m², and 41%-69% had KL grade 3 knee OA.

In terms of safety, the primary objective of the trial, there were no reports of serious adverse events related to the study drug. One patient who had reported increased knee pain and paroxysmal tachycardia 2 months after the injection was found to have a history of the condition, and after unblinding, none of the patients had detectable drug levels outside of the knee.

Overall, the number of adverse events was low and no different from placebo, Dr. Yazici said. The percentage of patients reporting an adverse event with the three rising doses of SM04690 were 53%, 35%, and 44%, respectively, compared with 55% of those given placebo.

WOMAC function scores for the 0.03-mg dose declined by a mean of –18.4 at week 12 and by –20.1 at week 24 from a baseline of 39.1; for 0.07 mg, by –19.5 at week 12 and by –18.9 at 24 weeks from 37.5; for 0.23 mg, by –17.8 at week 12 and by –12.4 at week 24 from 40.4; and for placebo, by –14.9 at week 12 and by –16.0 at week 24 from 34.4.

WOMAC pain scores at baseline were a respective 10.8, 10.8, 11.4, and 9.9, and the mean changes at week 12 were –4.4, –5.8, –5.7, and –4.2. At week 24, the mean declines were –5.6, –5.3, –4.3, and –4.8.

Medial joint space width was a mean of 4.5, 3.72, 3.62, and 3.74 mm at baseline in the four treatment groups, with mean changes from baseline to 24 weeks of 0.00, 0.49, –0.15, and –0.33 for the 0.03-mg, 0.07-mg, and 0.23-mg SM04690 and placebo groups, respectively.

Although the trial was not powered to detect any statistically significant differences between the active treatment dose and placebo, there was an indication that more patients treated with SM04690 than with placebo were likely to achieve an OMERACT-OARSI strict response.

These data support the ongoing phase II trial that is being conducted in 455 patients, Dr. Yazici said. The results of that trial are expected around October 2016, which should be in time for their presentation at the annual meeting of the American College of Rheumatology.

NEW ORLEANS – The use of metformin for at least 2 years had a protective effect on the incidence of neurodegenerative disease among elderly veterans, according to results from a large analysis of Veterans Affairs data.

At the annual scientific sessions of the American Diabetes Association, lead study author Qian Shi said that according to the current medical literature, diabetes increases one’s risk of Alzheimer’s disease (by 1.46- to 1.56-fold), all types of dementia (by 1.51- to 1.73-fold), vascular dementia (by 2.27- to 2.48-fold), and mild cognitive impairment (by 1.21-fold). “Metformin can cross the blood-brain barrier having specific effects on the central nervous system. But the exact mechanism and sites of its action remain unknown, and there are conflicting results,” said Ms. Shi, a PhD candidate in the department of global health policy and management at Tulane University School of Public Health and Tropical Medicine, New Orleans.

In an effort to examine the impact of receiving metformin treatment on the incidence of neurodegenerative disease and the association between length of metformin exposure and the risk of neurodegenerative diseases, the researchers used the Veterans Affairs database from 2004 to 2010 to study 6,046 patients who were at least 50 years of age with type 2 diabetes mellitus and were receiving long-term insulin treatment.

The length of metformin exposure was categorized by exposure years over the study period from baseline to the time of the first diagnosis of neurodegenerative disease, which included Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, dementia, and cognitive impairment. The five categories of metformin exposure time were no metformin treatment, less than 1 year, 1-2 years, 2-4 years, and 4 years or more. The mean age of patients was 63 years, 98% were male, and they were followed for a median of 5.3 years.

Of the 6,046 patients, 433 developed neurodegenerative disease during the study period, primarily dementia (334 cases). Other diagnoses included Parkinson’s disease (100 cases), Alzheimer’s disease (71 cases), and cognitive impairment (19 cases).

Ms. Shi reported that the adjusted incidence rates of neurodegenerative disease by cohort were 2.08 cases per 100 person-years for those who received no metformin treatment, 2.47 per 100 person-years for those treated with metformin for less than 1 year, 1.61 per 100 person-years for those treated 1-2 years, 1.30 per 100 person-years for those treated 2-4 years, and 0.49 person-years for those treated 4 years or more. The longer patients took metformin, the less likely they were to develop neurodegenerative disease, she said.

When comparing patients who received metformin treatment with those who did not on Cox regression analysis, the hazard ratio was 0.686 for neurodegenerative disease, 0.644 for dementia, and 0.611 for Parkinson’s disease. The risk reduction was not as robust for those with Alzheimer’s disease and cognitive impairment, most likely because of the limited number of cases, Ms. Shi said. Renal disease had no significant association with the risk of neurodegenerative disease, and it was balanced across metformin exposure groups.

She acknowledged certain limitations of the study, including its retrospective design, the high proportion of males, and the fact that data on diabetes duration and serum vitamin B level were not available.

The researchers reported having no relevant financial disclosures.

[email protected]

NEW ORLEANS – The use of metformin for at least 2 years had a protective effect on the incidence of neurodegenerative disease among elderly veterans, according to results from a large analysis of Veterans Affairs data.

At the annual scientific sessions of the American Diabetes Association, lead study author Qian Shi said that according to the current medical literature, diabetes increases one’s risk of Alzheimer’s disease (by 1.46- to 1.56-fold), all types of dementia (by 1.51- to 1.73-fold), vascular dementia (by 2.27- to 2.48-fold), and mild cognitive impairment (by 1.21-fold). “Metformin can cross the blood-brain barrier having specific effects on the central nervous system. But the exact mechanism and sites of its action remain unknown, and there are conflicting results,” said Ms. Shi, a PhD candidate in the department of global health policy and management at Tulane University School of Public Health and Tropical Medicine, New Orleans.

In an effort to examine the impact of receiving metformin treatment on the incidence of neurodegenerative disease and the association between length of metformin exposure and the risk of neurodegenerative diseases, the researchers used the Veterans Affairs database from 2004 to 2010 to study 6,046 patients who were at least 50 years of age with type 2 diabetes mellitus and were receiving long-term insulin treatment.

The length of metformin exposure was categorized by exposure years over the study period from baseline to the time of the first diagnosis of neurodegenerative disease, which included Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, dementia, and cognitive impairment. The five categories of metformin exposure time were no metformin treatment, less than 1 year, 1-2 years, 2-4 years, and 4 years or more. The mean age of patients was 63 years, 98% were male, and they were followed for a median of 5.3 years.

Of the 6,046 patients, 433 developed neurodegenerative disease during the study period, primarily dementia (334 cases). Other diagnoses included Parkinson’s disease (100 cases), Alzheimer’s disease (71 cases), and cognitive impairment (19 cases).

Ms. Shi reported that the adjusted incidence rates of neurodegenerative disease by cohort were 2.08 cases per 100 person-years for those who received no metformin treatment, 2.47 per 100 person-years for those treated with metformin for less than 1 year, 1.61 per 100 person-years for those treated 1-2 years, 1.30 per 100 person-years for those treated 2-4 years, and 0.49 person-years for those treated 4 years or more. The longer patients took metformin, the less likely they were to develop neurodegenerative disease, she said.

When comparing patients who received metformin treatment with those who did not on Cox regression analysis, the hazard ratio was 0.686 for neurodegenerative disease, 0.644 for dementia, and 0.611 for Parkinson’s disease. The risk reduction was not as robust for those with Alzheimer’s disease and cognitive impairment, most likely because of the limited number of cases, Ms. Shi said. Renal disease had no significant association with the risk of neurodegenerative disease, and it was balanced across metformin exposure groups.

She acknowledged certain limitations of the study, including its retrospective design, the high proportion of males, and the fact that data on diabetes duration and serum vitamin B level were not available.

The researchers reported having no relevant financial disclosures.

[email protected]

NEW ORLEANS – The use of metformin for at least 2 years had a protective effect on the incidence of neurodegenerative disease among elderly veterans, according to results from a large analysis of Veterans Affairs data.

At the annual scientific sessions of the American Diabetes Association, lead study author Qian Shi said that according to the current medical literature, diabetes increases one’s risk of Alzheimer’s disease (by 1.46- to 1.56-fold), all types of dementia (by 1.51- to 1.73-fold), vascular dementia (by 2.27- to 2.48-fold), and mild cognitive impairment (by 1.21-fold). “Metformin can cross the blood-brain barrier having specific effects on the central nervous system. But the exact mechanism and sites of its action remain unknown, and there are conflicting results,” said Ms. Shi, a PhD candidate in the department of global health policy and management at Tulane University School of Public Health and Tropical Medicine, New Orleans.

In an effort to examine the impact of receiving metformin treatment on the incidence of neurodegenerative disease and the association between length of metformin exposure and the risk of neurodegenerative diseases, the researchers used the Veterans Affairs database from 2004 to 2010 to study 6,046 patients who were at least 50 years of age with type 2 diabetes mellitus and were receiving long-term insulin treatment.

The length of metformin exposure was categorized by exposure years over the study period from baseline to the time of the first diagnosis of neurodegenerative disease, which included Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, dementia, and cognitive impairment. The five categories of metformin exposure time were no metformin treatment, less than 1 year, 1-2 years, 2-4 years, and 4 years or more. The mean age of patients was 63 years, 98% were male, and they were followed for a median of 5.3 years.

Of the 6,046 patients, 433 developed neurodegenerative disease during the study period, primarily dementia (334 cases). Other diagnoses included Parkinson’s disease (100 cases), Alzheimer’s disease (71 cases), and cognitive impairment (19 cases).

Ms. Shi reported that the adjusted incidence rates of neurodegenerative disease by cohort were 2.08 cases per 100 person-years for those who received no metformin treatment, 2.47 per 100 person-years for those treated with metformin for less than 1 year, 1.61 per 100 person-years for those treated 1-2 years, 1.30 per 100 person-years for those treated 2-4 years, and 0.49 person-years for those treated 4 years or more. The longer patients took metformin, the less likely they were to develop neurodegenerative disease, she said.

When comparing patients who received metformin treatment with those who did not on Cox regression analysis, the hazard ratio was 0.686 for neurodegenerative disease, 0.644 for dementia, and 0.611 for Parkinson’s disease. The risk reduction was not as robust for those with Alzheimer’s disease and cognitive impairment, most likely because of the limited number of cases, Ms. Shi said. Renal disease had no significant association with the risk of neurodegenerative disease, and it was balanced across metformin exposure groups.

She acknowledged certain limitations of the study, including its retrospective design, the high proportion of males, and the fact that data on diabetes duration and serum vitamin B level were not available.

The researchers reported having no relevant financial disclosures.

[email protected]