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HHS effort aims to end new HIV cases within 10 years
WASHINGTON – Leaders from five federal agencies came together to announce the framework for a bold new national initiative that aims to eliminate new cases of HIV infection in the United States within 10 years. The announcement came the day after President Trump’s State of the Union address, which highlighted the new effort.
“HIV has cost America too much for too long,” said Adm. Brett Giroir, MD, assistant secretary for health at the Department of Health & Human Services, in a press briefing. In addition to the 700,000 U.S. lives the disease has claimed since 1981, “We are at high risk of another 400,000 becoming infected over the next decade,” with about 40,000 new infections still occurring every year, he said.
Dr. Giroir will lead a coordinated effort among HHS, the Centers for Disease Control, the National Institutes of Health, the Health Resources and Services Administration, and the Indian Health Service. The goals are to reduce new cases of HIV by 50% within 5 years, and by 90% within 10 years.
These 48 counties, together with Washington and San Juan, Puerto Rico, accounted for more than half of the new HIV diagnoses in 2016 and 2017, said Dr. Giroir.
“This is a laser-focused program targeting counties where infection is the highest,” said CDC Director Robert R. Redfield, MD. “We propose to deploy personnel, resources, and strategies” in these targeted areas to maximize not just diagnosis and treatment but also to reach those at risk for HIV to enroll them in preexposure prophylaxis (PrEP) regimens, he said.
In addition to the targeted counties, seven states in the rural South as well as Native American and Alaskan Native populations also will receive intensified education, diagnostic, and treatment services. The targeted states are Alabama, Arkansas, Kentucky, Mississippi, Missouri, Oklahoma, and South Carolina.
George Sigounas, PhD, administrator or the Health Resources and Services Administration, said that existing community health centers will be especially important in reaching rural underserved and marginalized populations. Currently, he said, HRSA supports 12,000 service delivery sites across the country that are already delivering care to 27 million individuals. “These sites will play a major expanded role in providing PrEP to those who are at the greatest risk of contracting HIV,” said Dr. Sigounas.
Among the currently existing resources that will be leveraged are services provided by the Ryan White HIV/AIDS program, which already provides HIV primary medical care and support services through a network of grants to states and local government and community organizations. About half of the people currently diagnosed with HIV in the United States receive services through this program now.
The NIH maintains a geographically distributed network of Centers for AIDS Research that also will be folded into the new initiative.
In his remarks, Anthony S. Fauci, MD, director of the NIH’s National Center for Allergy and Infectious Diseases, pointed out that, “Treatment and detection are wrapped together, because treated individuals can’t transmit HIV” if they are adherent to antiretroviral medication use and achieve an undetectable viral load, he said. “If you get everyone who’s infected on antiretrovirals and give those who need it PrEP, you can theoretically end the epidemic as we know it – and that is our goal.”
Dr. Fauci went on to say that implementation science will play a key role in achieving a targeted and coordinated approach. “We will work closely with our colleagues to make sure the implementation is done well. We have lessons learned; we will do better and better,” he said.
The nuts and bolts of the program include a four-pronged strategy to diagnose individuals as early as possible after infection, to initiate prompt, effective, and sustained treatment, to protect those at risk for HIV by proven means including PrEP, and to provide rapid response when new HIV clusters are identified. A reimagining of current and future personnel into an “HIV health force” will put teams on the ground in each jurisdiction to carry out the initiative.
Though the goal is to provide PrEP to every at-risk individual, Dr. Fauci said that current modeling shows that if PrEP reaches 50%-60% in the at-risk population, new infections can be reduced by 90%. He added, “PrEP works. The efficacy is well over 90%.”
Funding details were not released at the press briefing; Dr. Giroir said that figures will be released by the Office of Management and Budget as part of the 2020 budget cycle. He confirmed, however, that new funds will be allocated for the effort, rather than a mere reshuffling of existing fund and resources.
Several of the leaders acknowledged the problem of stigma and marginalization that many individuals living with or at risk for HIV face, since men who have sex with men, transgender people, sex workers, and those with opioid use disorder all fall into this category.
“Every American deserves to be treated with respect and dignity. We will vigorously enforce all laws on the books about discrimination,” said Rear Adm. Michael Weahkee, MD, principal deputy director of the Indian Health Service. This is especially important in Native American communities “where everybody knows everybody,” he said, and it’s vitally important to include individual and community education in the efforts.
Dr. Redfield concurred, adding that “Dr. Fauci and I have been engaged in HIV since 1981. We have witnessed firsthand the negative impact that stigma can have on our capacity to practice public health. The transgender population, in particular, needs to be reached out to. We need to be able to address in a comprehensive way how to destigmatize the HIV population.”
WASHINGTON – Leaders from five federal agencies came together to announce the framework for a bold new national initiative that aims to eliminate new cases of HIV infection in the United States within 10 years. The announcement came the day after President Trump’s State of the Union address, which highlighted the new effort.
“HIV has cost America too much for too long,” said Adm. Brett Giroir, MD, assistant secretary for health at the Department of Health & Human Services, in a press briefing. In addition to the 700,000 U.S. lives the disease has claimed since 1981, “We are at high risk of another 400,000 becoming infected over the next decade,” with about 40,000 new infections still occurring every year, he said.
Dr. Giroir will lead a coordinated effort among HHS, the Centers for Disease Control, the National Institutes of Health, the Health Resources and Services Administration, and the Indian Health Service. The goals are to reduce new cases of HIV by 50% within 5 years, and by 90% within 10 years.
These 48 counties, together with Washington and San Juan, Puerto Rico, accounted for more than half of the new HIV diagnoses in 2016 and 2017, said Dr. Giroir.
“This is a laser-focused program targeting counties where infection is the highest,” said CDC Director Robert R. Redfield, MD. “We propose to deploy personnel, resources, and strategies” in these targeted areas to maximize not just diagnosis and treatment but also to reach those at risk for HIV to enroll them in preexposure prophylaxis (PrEP) regimens, he said.
In addition to the targeted counties, seven states in the rural South as well as Native American and Alaskan Native populations also will receive intensified education, diagnostic, and treatment services. The targeted states are Alabama, Arkansas, Kentucky, Mississippi, Missouri, Oklahoma, and South Carolina.
George Sigounas, PhD, administrator or the Health Resources and Services Administration, said that existing community health centers will be especially important in reaching rural underserved and marginalized populations. Currently, he said, HRSA supports 12,000 service delivery sites across the country that are already delivering care to 27 million individuals. “These sites will play a major expanded role in providing PrEP to those who are at the greatest risk of contracting HIV,” said Dr. Sigounas.
Among the currently existing resources that will be leveraged are services provided by the Ryan White HIV/AIDS program, which already provides HIV primary medical care and support services through a network of grants to states and local government and community organizations. About half of the people currently diagnosed with HIV in the United States receive services through this program now.
The NIH maintains a geographically distributed network of Centers for AIDS Research that also will be folded into the new initiative.
In his remarks, Anthony S. Fauci, MD, director of the NIH’s National Center for Allergy and Infectious Diseases, pointed out that, “Treatment and detection are wrapped together, because treated individuals can’t transmit HIV” if they are adherent to antiretroviral medication use and achieve an undetectable viral load, he said. “If you get everyone who’s infected on antiretrovirals and give those who need it PrEP, you can theoretically end the epidemic as we know it – and that is our goal.”
Dr. Fauci went on to say that implementation science will play a key role in achieving a targeted and coordinated approach. “We will work closely with our colleagues to make sure the implementation is done well. We have lessons learned; we will do better and better,” he said.
The nuts and bolts of the program include a four-pronged strategy to diagnose individuals as early as possible after infection, to initiate prompt, effective, and sustained treatment, to protect those at risk for HIV by proven means including PrEP, and to provide rapid response when new HIV clusters are identified. A reimagining of current and future personnel into an “HIV health force” will put teams on the ground in each jurisdiction to carry out the initiative.
Though the goal is to provide PrEP to every at-risk individual, Dr. Fauci said that current modeling shows that if PrEP reaches 50%-60% in the at-risk population, new infections can be reduced by 90%. He added, “PrEP works. The efficacy is well over 90%.”
Funding details were not released at the press briefing; Dr. Giroir said that figures will be released by the Office of Management and Budget as part of the 2020 budget cycle. He confirmed, however, that new funds will be allocated for the effort, rather than a mere reshuffling of existing fund and resources.
Several of the leaders acknowledged the problem of stigma and marginalization that many individuals living with or at risk for HIV face, since men who have sex with men, transgender people, sex workers, and those with opioid use disorder all fall into this category.
“Every American deserves to be treated with respect and dignity. We will vigorously enforce all laws on the books about discrimination,” said Rear Adm. Michael Weahkee, MD, principal deputy director of the Indian Health Service. This is especially important in Native American communities “where everybody knows everybody,” he said, and it’s vitally important to include individual and community education in the efforts.
Dr. Redfield concurred, adding that “Dr. Fauci and I have been engaged in HIV since 1981. We have witnessed firsthand the negative impact that stigma can have on our capacity to practice public health. The transgender population, in particular, needs to be reached out to. We need to be able to address in a comprehensive way how to destigmatize the HIV population.”
WASHINGTON – Leaders from five federal agencies came together to announce the framework for a bold new national initiative that aims to eliminate new cases of HIV infection in the United States within 10 years. The announcement came the day after President Trump’s State of the Union address, which highlighted the new effort.
“HIV has cost America too much for too long,” said Adm. Brett Giroir, MD, assistant secretary for health at the Department of Health & Human Services, in a press briefing. In addition to the 700,000 U.S. lives the disease has claimed since 1981, “We are at high risk of another 400,000 becoming infected over the next decade,” with about 40,000 new infections still occurring every year, he said.
Dr. Giroir will lead a coordinated effort among HHS, the Centers for Disease Control, the National Institutes of Health, the Health Resources and Services Administration, and the Indian Health Service. The goals are to reduce new cases of HIV by 50% within 5 years, and by 90% within 10 years.
These 48 counties, together with Washington and San Juan, Puerto Rico, accounted for more than half of the new HIV diagnoses in 2016 and 2017, said Dr. Giroir.
“This is a laser-focused program targeting counties where infection is the highest,” said CDC Director Robert R. Redfield, MD. “We propose to deploy personnel, resources, and strategies” in these targeted areas to maximize not just diagnosis and treatment but also to reach those at risk for HIV to enroll them in preexposure prophylaxis (PrEP) regimens, he said.
In addition to the targeted counties, seven states in the rural South as well as Native American and Alaskan Native populations also will receive intensified education, diagnostic, and treatment services. The targeted states are Alabama, Arkansas, Kentucky, Mississippi, Missouri, Oklahoma, and South Carolina.
George Sigounas, PhD, administrator or the Health Resources and Services Administration, said that existing community health centers will be especially important in reaching rural underserved and marginalized populations. Currently, he said, HRSA supports 12,000 service delivery sites across the country that are already delivering care to 27 million individuals. “These sites will play a major expanded role in providing PrEP to those who are at the greatest risk of contracting HIV,” said Dr. Sigounas.
Among the currently existing resources that will be leveraged are services provided by the Ryan White HIV/AIDS program, which already provides HIV primary medical care and support services through a network of grants to states and local government and community organizations. About half of the people currently diagnosed with HIV in the United States receive services through this program now.
The NIH maintains a geographically distributed network of Centers for AIDS Research that also will be folded into the new initiative.
In his remarks, Anthony S. Fauci, MD, director of the NIH’s National Center for Allergy and Infectious Diseases, pointed out that, “Treatment and detection are wrapped together, because treated individuals can’t transmit HIV” if they are adherent to antiretroviral medication use and achieve an undetectable viral load, he said. “If you get everyone who’s infected on antiretrovirals and give those who need it PrEP, you can theoretically end the epidemic as we know it – and that is our goal.”
Dr. Fauci went on to say that implementation science will play a key role in achieving a targeted and coordinated approach. “We will work closely with our colleagues to make sure the implementation is done well. We have lessons learned; we will do better and better,” he said.
The nuts and bolts of the program include a four-pronged strategy to diagnose individuals as early as possible after infection, to initiate prompt, effective, and sustained treatment, to protect those at risk for HIV by proven means including PrEP, and to provide rapid response when new HIV clusters are identified. A reimagining of current and future personnel into an “HIV health force” will put teams on the ground in each jurisdiction to carry out the initiative.
Though the goal is to provide PrEP to every at-risk individual, Dr. Fauci said that current modeling shows that if PrEP reaches 50%-60% in the at-risk population, new infections can be reduced by 90%. He added, “PrEP works. The efficacy is well over 90%.”
Funding details were not released at the press briefing; Dr. Giroir said that figures will be released by the Office of Management and Budget as part of the 2020 budget cycle. He confirmed, however, that new funds will be allocated for the effort, rather than a mere reshuffling of existing fund and resources.
Several of the leaders acknowledged the problem of stigma and marginalization that many individuals living with or at risk for HIV face, since men who have sex with men, transgender people, sex workers, and those with opioid use disorder all fall into this category.
“Every American deserves to be treated with respect and dignity. We will vigorously enforce all laws on the books about discrimination,” said Rear Adm. Michael Weahkee, MD, principal deputy director of the Indian Health Service. This is especially important in Native American communities “where everybody knows everybody,” he said, and it’s vitally important to include individual and community education in the efforts.
Dr. Redfield concurred, adding that “Dr. Fauci and I have been engaged in HIV since 1981. We have witnessed firsthand the negative impact that stigma can have on our capacity to practice public health. The transgender population, in particular, needs to be reached out to. We need to be able to address in a comprehensive way how to destigmatize the HIV population.”
FROM A HEALTH AND HUMAN SERVICES BRIEFING
Surgeon: Sacral colpopexy can be smart strategy in POP repairs
LAS VEGAS – While research suggests that vaginal mesh grafts are inappropriate for many prolapse repairs, an obstetrician-gynecologist told colleagues that they’re still a valid tool in the repair procedure known as sacral colpopexy, in which mesh is attached via an abdominal route.
Beri M. Ridgeway, MD, of Cleveland Clinic, spoke about the role of mesh grafts and prolapse repairs at the Pelvic Anatomy and Gynecologic Surgery Symposium.
As Dr. Ridgeway noted, vaginal mesh grafts are controversial because of concerns about their safety. Although many women had favorable outcomes, an unacceptable proportion have experienced complications.
In 2011, the Food and Drug Administration warned that urogynecologic surgical mesh had been linked to 2,874 reports of injuries, deaths, and malfunctions, mostly in pelvic organ prolapse (POP) repairs, over 3 years. The other injuries were in stress urinary incontinence repairs. The report focuses on transvaginal mesh for prolapse and not sacral colpopexy or synthetic midurethral slings, which are considered to have a more favorable risk profile.
The FDA declared that “serious adverse events are NOT rare ... and transvaginally placed mesh in POP repair does NOT conclusively improve clinical outcomes over traditional non-mesh repair.” Subsequently, most companies stopped marketing mesh for transvaginal repair of POP.
Since 2011, research has offered new perspective on the use of mesh in specific POP situations.
“We know that mesh does have some slight improvement in medium-term outcome for subjective and objective symptoms,” Dr. Ridgeway said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. “This all comes at a price. There’s more blood loss, and you can actually have prolapse in other compartments and de novo SUI.”
She pointed out that these outcomes were noted in a 2013 Cochrane Review. It found improvements in subjective and objective results after treatment with polypropylene mesh vs. native tissue for anterior compartment POP repairs. But the review found multiple disadvantages for mesh vs. native tissue in operating time, blood loss, and reoperations (Cochrane Database Syst Rev. 2013 Apr 30;[4]:CD004014).
In 2016, an updated Cochrane Review declared that “current evidence does not support the use of mesh repair compared with native tissue repair for anterior compartment prolapse owing to increased morbidity.” The review also cautioned that while new light-weight transvaginal meshes are available, they haven’t been fully studied. “Clinicians and women should be cautious when utilizing these products, as their safety and efficacy have not been established,” according to the review (Cochrane Database of Syst Rev. 2016[11];CD004014).
In a follow-up interview, Dr. Ridgeway said “the data are scarce, so it is hard to have an opinion on this.”
She focused much of her presentation on sacral colpopexy. .
“Compared to native tissue prolapse repair using a vaginal approach, sacral colpopexy does have an increased risk profile but likely is associated with better durability,” she said in the interview. “The long-term outcomes following sacral colpopexy are favorable and the risk profile is acceptably low.”
She prefers the approach for recurrent prolapse and post-hysterectomy prolapse, especially in patients with a shorter vagina. She also offers this procedure for younger patients with significant prolapse and those women who are very active or perform repetitive heavy lifting.
In the interview, she offered these tips about the procedure:
- “Identify pertinent anatomy and set yourself up for success. Restore anatomy, retract the colon if necessary, use angled laparoscopes to optimize visualization, and don’t place the vagina on significant tension.”
- “In cases with unusual anatomy, one must recheck anatomic landmarks because it is critical to avoid the middle sacral artery and left common iliac vein, which is often located close to the midline.”
- “The vagina should be well supported but not on tension. One must communicate with assistants to elevate the vagina but not push it too much. I often demonstrate to the assistant how I like it to be.”
- “In regard to closing the peritoneum over the mesh, I like to make sure this dissection is sufficient at the beginning of the case so this part is not a struggle.”
Dr. Ridgeway discloses consulting for Coloplast and serving as an independent contractor (Legal) for Ethicon.
Global Academy and this news organization are owned by the same company.
LAS VEGAS – While research suggests that vaginal mesh grafts are inappropriate for many prolapse repairs, an obstetrician-gynecologist told colleagues that they’re still a valid tool in the repair procedure known as sacral colpopexy, in which mesh is attached via an abdominal route.
Beri M. Ridgeway, MD, of Cleveland Clinic, spoke about the role of mesh grafts and prolapse repairs at the Pelvic Anatomy and Gynecologic Surgery Symposium.
As Dr. Ridgeway noted, vaginal mesh grafts are controversial because of concerns about their safety. Although many women had favorable outcomes, an unacceptable proportion have experienced complications.
In 2011, the Food and Drug Administration warned that urogynecologic surgical mesh had been linked to 2,874 reports of injuries, deaths, and malfunctions, mostly in pelvic organ prolapse (POP) repairs, over 3 years. The other injuries were in stress urinary incontinence repairs. The report focuses on transvaginal mesh for prolapse and not sacral colpopexy or synthetic midurethral slings, which are considered to have a more favorable risk profile.
The FDA declared that “serious adverse events are NOT rare ... and transvaginally placed mesh in POP repair does NOT conclusively improve clinical outcomes over traditional non-mesh repair.” Subsequently, most companies stopped marketing mesh for transvaginal repair of POP.
Since 2011, research has offered new perspective on the use of mesh in specific POP situations.
“We know that mesh does have some slight improvement in medium-term outcome for subjective and objective symptoms,” Dr. Ridgeway said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. “This all comes at a price. There’s more blood loss, and you can actually have prolapse in other compartments and de novo SUI.”
She pointed out that these outcomes were noted in a 2013 Cochrane Review. It found improvements in subjective and objective results after treatment with polypropylene mesh vs. native tissue for anterior compartment POP repairs. But the review found multiple disadvantages for mesh vs. native tissue in operating time, blood loss, and reoperations (Cochrane Database Syst Rev. 2013 Apr 30;[4]:CD004014).
In 2016, an updated Cochrane Review declared that “current evidence does not support the use of mesh repair compared with native tissue repair for anterior compartment prolapse owing to increased morbidity.” The review also cautioned that while new light-weight transvaginal meshes are available, they haven’t been fully studied. “Clinicians and women should be cautious when utilizing these products, as their safety and efficacy have not been established,” according to the review (Cochrane Database of Syst Rev. 2016[11];CD004014).
In a follow-up interview, Dr. Ridgeway said “the data are scarce, so it is hard to have an opinion on this.”
She focused much of her presentation on sacral colpopexy. .
“Compared to native tissue prolapse repair using a vaginal approach, sacral colpopexy does have an increased risk profile but likely is associated with better durability,” she said in the interview. “The long-term outcomes following sacral colpopexy are favorable and the risk profile is acceptably low.”
She prefers the approach for recurrent prolapse and post-hysterectomy prolapse, especially in patients with a shorter vagina. She also offers this procedure for younger patients with significant prolapse and those women who are very active or perform repetitive heavy lifting.
In the interview, she offered these tips about the procedure:
- “Identify pertinent anatomy and set yourself up for success. Restore anatomy, retract the colon if necessary, use angled laparoscopes to optimize visualization, and don’t place the vagina on significant tension.”
- “In cases with unusual anatomy, one must recheck anatomic landmarks because it is critical to avoid the middle sacral artery and left common iliac vein, which is often located close to the midline.”
- “The vagina should be well supported but not on tension. One must communicate with assistants to elevate the vagina but not push it too much. I often demonstrate to the assistant how I like it to be.”
- “In regard to closing the peritoneum over the mesh, I like to make sure this dissection is sufficient at the beginning of the case so this part is not a struggle.”
Dr. Ridgeway discloses consulting for Coloplast and serving as an independent contractor (Legal) for Ethicon.
Global Academy and this news organization are owned by the same company.
LAS VEGAS – While research suggests that vaginal mesh grafts are inappropriate for many prolapse repairs, an obstetrician-gynecologist told colleagues that they’re still a valid tool in the repair procedure known as sacral colpopexy, in which mesh is attached via an abdominal route.
Beri M. Ridgeway, MD, of Cleveland Clinic, spoke about the role of mesh grafts and prolapse repairs at the Pelvic Anatomy and Gynecologic Surgery Symposium.
As Dr. Ridgeway noted, vaginal mesh grafts are controversial because of concerns about their safety. Although many women had favorable outcomes, an unacceptable proportion have experienced complications.
In 2011, the Food and Drug Administration warned that urogynecologic surgical mesh had been linked to 2,874 reports of injuries, deaths, and malfunctions, mostly in pelvic organ prolapse (POP) repairs, over 3 years. The other injuries were in stress urinary incontinence repairs. The report focuses on transvaginal mesh for prolapse and not sacral colpopexy or synthetic midurethral slings, which are considered to have a more favorable risk profile.
The FDA declared that “serious adverse events are NOT rare ... and transvaginally placed mesh in POP repair does NOT conclusively improve clinical outcomes over traditional non-mesh repair.” Subsequently, most companies stopped marketing mesh for transvaginal repair of POP.
Since 2011, research has offered new perspective on the use of mesh in specific POP situations.
“We know that mesh does have some slight improvement in medium-term outcome for subjective and objective symptoms,” Dr. Ridgeway said at the meeting, which was jointly provided by Global Academy for Medical Education and the University of Cincinnati. “This all comes at a price. There’s more blood loss, and you can actually have prolapse in other compartments and de novo SUI.”
She pointed out that these outcomes were noted in a 2013 Cochrane Review. It found improvements in subjective and objective results after treatment with polypropylene mesh vs. native tissue for anterior compartment POP repairs. But the review found multiple disadvantages for mesh vs. native tissue in operating time, blood loss, and reoperations (Cochrane Database Syst Rev. 2013 Apr 30;[4]:CD004014).
In 2016, an updated Cochrane Review declared that “current evidence does not support the use of mesh repair compared with native tissue repair for anterior compartment prolapse owing to increased morbidity.” The review also cautioned that while new light-weight transvaginal meshes are available, they haven’t been fully studied. “Clinicians and women should be cautious when utilizing these products, as their safety and efficacy have not been established,” according to the review (Cochrane Database of Syst Rev. 2016[11];CD004014).
In a follow-up interview, Dr. Ridgeway said “the data are scarce, so it is hard to have an opinion on this.”
She focused much of her presentation on sacral colpopexy. .
“Compared to native tissue prolapse repair using a vaginal approach, sacral colpopexy does have an increased risk profile but likely is associated with better durability,” she said in the interview. “The long-term outcomes following sacral colpopexy are favorable and the risk profile is acceptably low.”
She prefers the approach for recurrent prolapse and post-hysterectomy prolapse, especially in patients with a shorter vagina. She also offers this procedure for younger patients with significant prolapse and those women who are very active or perform repetitive heavy lifting.
In the interview, she offered these tips about the procedure:
- “Identify pertinent anatomy and set yourself up for success. Restore anatomy, retract the colon if necessary, use angled laparoscopes to optimize visualization, and don’t place the vagina on significant tension.”
- “In cases with unusual anatomy, one must recheck anatomic landmarks because it is critical to avoid the middle sacral artery and left common iliac vein, which is often located close to the midline.”
- “The vagina should be well supported but not on tension. One must communicate with assistants to elevate the vagina but not push it too much. I often demonstrate to the assistant how I like it to be.”
- “In regard to closing the peritoneum over the mesh, I like to make sure this dissection is sufficient at the beginning of the case so this part is not a struggle.”
Dr. Ridgeway discloses consulting for Coloplast and serving as an independent contractor (Legal) for Ethicon.
Global Academy and this news organization are owned by the same company.
EXPERT ANALYSIS FROM PAGS
Despite concerns, synthetic slings are still ‘standard of care’ in SUI
LAS VEGAS – A few weeks before she was scheduled to speak at the annual Pelvic Anatomy and Gynecologic Surgery Symposium, Beri M. Ridgeway, MD, received an anonymous note about her upcoming presentation. “Someone wanted me to think very carefully about what I’d be talking about during my presentation on synthetics,” she recalled.
The note reflects the deep controversy over the use of transvaginal synthetic mesh products, which have been linked to a long list of serious adverse effects. “There are women who have been harmed, and I take care of a lot of those,” said Dr. Ridgeway, who’s based at Cleveland Clinic. One key distinction is that there is a very different risk profile between transvaginal synthetic mesh prolapse kits and polypropylene midurethral slings. While it’s important to be thoughtful about the use of mesh in synthetic midurethral (MU) slings, she said, they remain well supported as an effective treatment for stress urinary incontinence (SUI).
Even so, she said, the news about the risks of mesh “weighs on our patients’ minds” and spawns fear among physicians. Meanwhile, she said, “there is quite a bit of flux” in the marketplace as companies withdraw products because of their perception of risk.
Even amid the controversy, she said, it’s important to remember how crucial it is to treat women in need. “SUI is a very common problem, and women suffer significantly. With our aging population, the prevalence will increase even more,” she said. “It is critical that we screen patients for SUI and have the ability to offer treatment. Having different treatment options benefit women significantly.”
Dr. Ridgeway offered these pearls about the use of synthetic MU slings and alternative approaches to treating SUI.
It’s helpful to find a single strategy and embrace it.
“For ob.gyn. specialists who treat primary, uncomplicated SUI, I recommend surgeons become comfortable with an approach and focus on becoming high-volume surgeons in that approach,” Dr. Ridgeway said. “It is also good to partner with a female pelvic medicine & reconstructive surgery specialist who can back one up for more complicated cases, complications, or recurrent SUI. These specialists should be able to offer a full array of procedures to treat SUI and tailor the treatment to the individual patient, especially in more complex cases.”
Synthetic MU slings are the “definitive standard of care.”
More than 17 years of research suggest the efficacy of the slings is durable, she said, especially when the goal is to resolve symptoms in patients with pure SUI symptoms. she said, pointing to more than 500 articles and more than 40 randomized controlled trials.
According to her, synthetic slings have similar efficacy to traditional slings but require less time in the operating room and produce less voiding dysfunction and de novo urgency. “The revision rate of synthetic MU slings is very low,” she added. “In large studies, the revision rate at 10 years is 3%-4%.”
It’s important to keep patient consent in mind, she said. “Patients should know and understand the specific risks of any procedure, including MU slings, so that they can share in decision making.”
Transobdurator (TOT) slings offer benefits.
There’s less risk of bladder and vascular injury from the TOT procedure, which is easy to learn and teach, Dr. Ridgeway said. Research suggests the tension-free vaginal tape (TVT) approach is more likely to cause voiding dysfunction, she added.
But TOT is probably less effective in patients with SUI linked to intrinsic sphincter deficiency and in longer-term follow-up, she said. And there are cases of male sex partners injuring their penises during contact with TOT slings during intercourse.
Single-incision slings are up-and-coming options.
These slings offer promising results in short-term studies, but long-term results aren’t available yet. They may be a good option for cases of mild and occult SUI, she said.
Alternative treatments for SUI have limitations.
These include urethral bulking agents, which mainly lead to improvement rather than cure. Autologous fascial pubovaginal slings are another option, especially if patients don’t want a mesh-based treatment or have recurrent SUI following a synthetic mesh complication. However, she noted that research points to morbidity and de novo urinary urgency, she said.
The Pelvic Anatomy & Gynecologic Surgery Symposium was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
Dr. Ridgeway disclosed consulting for Coloplast and having served as an independent contractor (legal) for Ethicon.
LAS VEGAS – A few weeks before she was scheduled to speak at the annual Pelvic Anatomy and Gynecologic Surgery Symposium, Beri M. Ridgeway, MD, received an anonymous note about her upcoming presentation. “Someone wanted me to think very carefully about what I’d be talking about during my presentation on synthetics,” she recalled.
The note reflects the deep controversy over the use of transvaginal synthetic mesh products, which have been linked to a long list of serious adverse effects. “There are women who have been harmed, and I take care of a lot of those,” said Dr. Ridgeway, who’s based at Cleveland Clinic. One key distinction is that there is a very different risk profile between transvaginal synthetic mesh prolapse kits and polypropylene midurethral slings. While it’s important to be thoughtful about the use of mesh in synthetic midurethral (MU) slings, she said, they remain well supported as an effective treatment for stress urinary incontinence (SUI).
Even so, she said, the news about the risks of mesh “weighs on our patients’ minds” and spawns fear among physicians. Meanwhile, she said, “there is quite a bit of flux” in the marketplace as companies withdraw products because of their perception of risk.
Even amid the controversy, she said, it’s important to remember how crucial it is to treat women in need. “SUI is a very common problem, and women suffer significantly. With our aging population, the prevalence will increase even more,” she said. “It is critical that we screen patients for SUI and have the ability to offer treatment. Having different treatment options benefit women significantly.”
Dr. Ridgeway offered these pearls about the use of synthetic MU slings and alternative approaches to treating SUI.
It’s helpful to find a single strategy and embrace it.
“For ob.gyn. specialists who treat primary, uncomplicated SUI, I recommend surgeons become comfortable with an approach and focus on becoming high-volume surgeons in that approach,” Dr. Ridgeway said. “It is also good to partner with a female pelvic medicine & reconstructive surgery specialist who can back one up for more complicated cases, complications, or recurrent SUI. These specialists should be able to offer a full array of procedures to treat SUI and tailor the treatment to the individual patient, especially in more complex cases.”
Synthetic MU slings are the “definitive standard of care.”
More than 17 years of research suggest the efficacy of the slings is durable, she said, especially when the goal is to resolve symptoms in patients with pure SUI symptoms. she said, pointing to more than 500 articles and more than 40 randomized controlled trials.
According to her, synthetic slings have similar efficacy to traditional slings but require less time in the operating room and produce less voiding dysfunction and de novo urgency. “The revision rate of synthetic MU slings is very low,” she added. “In large studies, the revision rate at 10 years is 3%-4%.”
It’s important to keep patient consent in mind, she said. “Patients should know and understand the specific risks of any procedure, including MU slings, so that they can share in decision making.”
Transobdurator (TOT) slings offer benefits.
There’s less risk of bladder and vascular injury from the TOT procedure, which is easy to learn and teach, Dr. Ridgeway said. Research suggests the tension-free vaginal tape (TVT) approach is more likely to cause voiding dysfunction, she added.
But TOT is probably less effective in patients with SUI linked to intrinsic sphincter deficiency and in longer-term follow-up, she said. And there are cases of male sex partners injuring their penises during contact with TOT slings during intercourse.
Single-incision slings are up-and-coming options.
These slings offer promising results in short-term studies, but long-term results aren’t available yet. They may be a good option for cases of mild and occult SUI, she said.
Alternative treatments for SUI have limitations.
These include urethral bulking agents, which mainly lead to improvement rather than cure. Autologous fascial pubovaginal slings are another option, especially if patients don’t want a mesh-based treatment or have recurrent SUI following a synthetic mesh complication. However, she noted that research points to morbidity and de novo urinary urgency, she said.
The Pelvic Anatomy & Gynecologic Surgery Symposium was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
Dr. Ridgeway disclosed consulting for Coloplast and having served as an independent contractor (legal) for Ethicon.
LAS VEGAS – A few weeks before she was scheduled to speak at the annual Pelvic Anatomy and Gynecologic Surgery Symposium, Beri M. Ridgeway, MD, received an anonymous note about her upcoming presentation. “Someone wanted me to think very carefully about what I’d be talking about during my presentation on synthetics,” she recalled.
The note reflects the deep controversy over the use of transvaginal synthetic mesh products, which have been linked to a long list of serious adverse effects. “There are women who have been harmed, and I take care of a lot of those,” said Dr. Ridgeway, who’s based at Cleveland Clinic. One key distinction is that there is a very different risk profile between transvaginal synthetic mesh prolapse kits and polypropylene midurethral slings. While it’s important to be thoughtful about the use of mesh in synthetic midurethral (MU) slings, she said, they remain well supported as an effective treatment for stress urinary incontinence (SUI).
Even so, she said, the news about the risks of mesh “weighs on our patients’ minds” and spawns fear among physicians. Meanwhile, she said, “there is quite a bit of flux” in the marketplace as companies withdraw products because of their perception of risk.
Even amid the controversy, she said, it’s important to remember how crucial it is to treat women in need. “SUI is a very common problem, and women suffer significantly. With our aging population, the prevalence will increase even more,” she said. “It is critical that we screen patients for SUI and have the ability to offer treatment. Having different treatment options benefit women significantly.”
Dr. Ridgeway offered these pearls about the use of synthetic MU slings and alternative approaches to treating SUI.
It’s helpful to find a single strategy and embrace it.
“For ob.gyn. specialists who treat primary, uncomplicated SUI, I recommend surgeons become comfortable with an approach and focus on becoming high-volume surgeons in that approach,” Dr. Ridgeway said. “It is also good to partner with a female pelvic medicine & reconstructive surgery specialist who can back one up for more complicated cases, complications, or recurrent SUI. These specialists should be able to offer a full array of procedures to treat SUI and tailor the treatment to the individual patient, especially in more complex cases.”
Synthetic MU slings are the “definitive standard of care.”
More than 17 years of research suggest the efficacy of the slings is durable, she said, especially when the goal is to resolve symptoms in patients with pure SUI symptoms. she said, pointing to more than 500 articles and more than 40 randomized controlled trials.
According to her, synthetic slings have similar efficacy to traditional slings but require less time in the operating room and produce less voiding dysfunction and de novo urgency. “The revision rate of synthetic MU slings is very low,” she added. “In large studies, the revision rate at 10 years is 3%-4%.”
It’s important to keep patient consent in mind, she said. “Patients should know and understand the specific risks of any procedure, including MU slings, so that they can share in decision making.”
Transobdurator (TOT) slings offer benefits.
There’s less risk of bladder and vascular injury from the TOT procedure, which is easy to learn and teach, Dr. Ridgeway said. Research suggests the tension-free vaginal tape (TVT) approach is more likely to cause voiding dysfunction, she added.
But TOT is probably less effective in patients with SUI linked to intrinsic sphincter deficiency and in longer-term follow-up, she said. And there are cases of male sex partners injuring their penises during contact with TOT slings during intercourse.
Single-incision slings are up-and-coming options.
These slings offer promising results in short-term studies, but long-term results aren’t available yet. They may be a good option for cases of mild and occult SUI, she said.
Alternative treatments for SUI have limitations.
These include urethral bulking agents, which mainly lead to improvement rather than cure. Autologous fascial pubovaginal slings are another option, especially if patients don’t want a mesh-based treatment or have recurrent SUI following a synthetic mesh complication. However, she noted that research points to morbidity and de novo urinary urgency, she said.
The Pelvic Anatomy & Gynecologic Surgery Symposium was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.
Dr. Ridgeway disclosed consulting for Coloplast and having served as an independent contractor (legal) for Ethicon.
EXPERT ANALYSIS FROM PAGS
Meta-analysis generally supports LI-RADS classification accuracy
Higher (more severe) Liver Imaging Reporting and Data System (LI-RADS) categories contained increasing proportions of hepatocellular carcinomas and overall malignancies, supporting the general reliability of the system, according to a systematic review and meta-analysis of 17 retrospective studies.
But 13% of LR-2 (“probably benign”) observations were actually hepatocellular carcinomas, as were 38% of LR-3 (“intermediate probability of malignancy”) observations, reported Christian B. van der Pol, MD, of McMaster University, Hamilton, Ont., and Christopher S. Lim, BBS, of Harvard Medical School, Boston, and their associates. Thus, clinicians should consider biopsy of many LR-3s, and LR-2s might need “more active management” than the currently recommended “return to surveillance,” including consideration for biopsy of solid LR-2 nodules measuring 1 cm or more, they wrote in Gastroenterology.
Histopathology confirmed that 93% of CT and MRI observations designated as LR-M (“definite or probable malignancy”) were indeed malignancies and that 36% were hepatocellular carcinomas,
The LI-RADS system, like its counterparts in breast and prostate imaging (BI-RADS and PI-RADS), classifies CT and MRI findings based on level of suspicion for malignancy. These categories include LR-M, LR-3, LR-2, LR-1 (“definitely benign”), LR-TIV (“definitely tumor in vein”), and LR-4 and LR-5 (“probably” and “definitely” hepatocellular carcinoma). However, CT and MRI interpretation is only as useful as it is accurate. To calculate actual percentages of hepatocellular carcinomas and overall malignancies within each LI-RADS category, the investigators analyzed aggregate data from studies found by searching MEDLINE, Embase, Cochrane CENTRAL, and Scopus during 2014-2018.
These 17 studies included 2,760 patients and 3,556 imaging observations. Pathology was the reference standard for LR-M, but for other LI-RADS categories, the researchers accepted strong clinical indicators of hepatocellular carcinoma, such as a 50% increase in lesion size within 6 months, or posttreatment recurrence of a previously confirmed malignancy. They classified observations as negative if they stayed stable in size for at least 12 months, spontaneously diminished in size, or disappeared without treatment.
In all, 94% and 97% of LR-5 observations were (respectively) hepatocellular carcinomas and other malignancies, as were 79% and 92% of LR-TIVs, 36% and 93% of LR-Ms, 74% and 80% of LR-4s, 38% and 40% of LR-3s, and 13% and 14% of LR-2s. No LR-1s were confirmed as malignant.
“Our data suggest biopsy of LI-RADS 3 observations should be considered in many patients, as a risk of 38% of HCC would usually provoke biopsy of a lesion elsewhere in the body,” the researchers wrote. They suggested consideration for biopsy of certain LR-2 lesions, but added that many “are small, perfusional alterations caused by arterioportal shunts, which are often not reported” and would be difficult or impossible to biopsy.
The study did not cover the most recent (2018) LI-RADS system, which featured several changes to simplify and better align it with American Association for the Study of Liver Diseases criteria, the researchers noted. They called for prospective studies to help confirm the accuracy of the LI-RADS system, particularly with regard to intermediate categories, such as LR-2.
The researchers disclosed no funding sources. Dr. van der Pol, Dr. Lim, and three other investigators reported having no conflicts of interest. Five researchers reported that they are members of the LI-RADS Steering Committee and four disclosed ties to pharmaceutical companies.
SOURCE: Van der Pol CB et al. Gastroenterology. 2018 Nov 13. doi: 10.1053/j.gastro.2018.11.020.
Higher (more severe) Liver Imaging Reporting and Data System (LI-RADS) categories contained increasing proportions of hepatocellular carcinomas and overall malignancies, supporting the general reliability of the system, according to a systematic review and meta-analysis of 17 retrospective studies.
But 13% of LR-2 (“probably benign”) observations were actually hepatocellular carcinomas, as were 38% of LR-3 (“intermediate probability of malignancy”) observations, reported Christian B. van der Pol, MD, of McMaster University, Hamilton, Ont., and Christopher S. Lim, BBS, of Harvard Medical School, Boston, and their associates. Thus, clinicians should consider biopsy of many LR-3s, and LR-2s might need “more active management” than the currently recommended “return to surveillance,” including consideration for biopsy of solid LR-2 nodules measuring 1 cm or more, they wrote in Gastroenterology.
Histopathology confirmed that 93% of CT and MRI observations designated as LR-M (“definite or probable malignancy”) were indeed malignancies and that 36% were hepatocellular carcinomas,
The LI-RADS system, like its counterparts in breast and prostate imaging (BI-RADS and PI-RADS), classifies CT and MRI findings based on level of suspicion for malignancy. These categories include LR-M, LR-3, LR-2, LR-1 (“definitely benign”), LR-TIV (“definitely tumor in vein”), and LR-4 and LR-5 (“probably” and “definitely” hepatocellular carcinoma). However, CT and MRI interpretation is only as useful as it is accurate. To calculate actual percentages of hepatocellular carcinomas and overall malignancies within each LI-RADS category, the investigators analyzed aggregate data from studies found by searching MEDLINE, Embase, Cochrane CENTRAL, and Scopus during 2014-2018.
These 17 studies included 2,760 patients and 3,556 imaging observations. Pathology was the reference standard for LR-M, but for other LI-RADS categories, the researchers accepted strong clinical indicators of hepatocellular carcinoma, such as a 50% increase in lesion size within 6 months, or posttreatment recurrence of a previously confirmed malignancy. They classified observations as negative if they stayed stable in size for at least 12 months, spontaneously diminished in size, or disappeared without treatment.
In all, 94% and 97% of LR-5 observations were (respectively) hepatocellular carcinomas and other malignancies, as were 79% and 92% of LR-TIVs, 36% and 93% of LR-Ms, 74% and 80% of LR-4s, 38% and 40% of LR-3s, and 13% and 14% of LR-2s. No LR-1s were confirmed as malignant.
“Our data suggest biopsy of LI-RADS 3 observations should be considered in many patients, as a risk of 38% of HCC would usually provoke biopsy of a lesion elsewhere in the body,” the researchers wrote. They suggested consideration for biopsy of certain LR-2 lesions, but added that many “are small, perfusional alterations caused by arterioportal shunts, which are often not reported” and would be difficult or impossible to biopsy.
The study did not cover the most recent (2018) LI-RADS system, which featured several changes to simplify and better align it with American Association for the Study of Liver Diseases criteria, the researchers noted. They called for prospective studies to help confirm the accuracy of the LI-RADS system, particularly with regard to intermediate categories, such as LR-2.
The researchers disclosed no funding sources. Dr. van der Pol, Dr. Lim, and three other investigators reported having no conflicts of interest. Five researchers reported that they are members of the LI-RADS Steering Committee and four disclosed ties to pharmaceutical companies.
SOURCE: Van der Pol CB et al. Gastroenterology. 2018 Nov 13. doi: 10.1053/j.gastro.2018.11.020.
Higher (more severe) Liver Imaging Reporting and Data System (LI-RADS) categories contained increasing proportions of hepatocellular carcinomas and overall malignancies, supporting the general reliability of the system, according to a systematic review and meta-analysis of 17 retrospective studies.
But 13% of LR-2 (“probably benign”) observations were actually hepatocellular carcinomas, as were 38% of LR-3 (“intermediate probability of malignancy”) observations, reported Christian B. van der Pol, MD, of McMaster University, Hamilton, Ont., and Christopher S. Lim, BBS, of Harvard Medical School, Boston, and their associates. Thus, clinicians should consider biopsy of many LR-3s, and LR-2s might need “more active management” than the currently recommended “return to surveillance,” including consideration for biopsy of solid LR-2 nodules measuring 1 cm or more, they wrote in Gastroenterology.
Histopathology confirmed that 93% of CT and MRI observations designated as LR-M (“definite or probable malignancy”) were indeed malignancies and that 36% were hepatocellular carcinomas,
The LI-RADS system, like its counterparts in breast and prostate imaging (BI-RADS and PI-RADS), classifies CT and MRI findings based on level of suspicion for malignancy. These categories include LR-M, LR-3, LR-2, LR-1 (“definitely benign”), LR-TIV (“definitely tumor in vein”), and LR-4 and LR-5 (“probably” and “definitely” hepatocellular carcinoma). However, CT and MRI interpretation is only as useful as it is accurate. To calculate actual percentages of hepatocellular carcinomas and overall malignancies within each LI-RADS category, the investigators analyzed aggregate data from studies found by searching MEDLINE, Embase, Cochrane CENTRAL, and Scopus during 2014-2018.
These 17 studies included 2,760 patients and 3,556 imaging observations. Pathology was the reference standard for LR-M, but for other LI-RADS categories, the researchers accepted strong clinical indicators of hepatocellular carcinoma, such as a 50% increase in lesion size within 6 months, or posttreatment recurrence of a previously confirmed malignancy. They classified observations as negative if they stayed stable in size for at least 12 months, spontaneously diminished in size, or disappeared without treatment.
In all, 94% and 97% of LR-5 observations were (respectively) hepatocellular carcinomas and other malignancies, as were 79% and 92% of LR-TIVs, 36% and 93% of LR-Ms, 74% and 80% of LR-4s, 38% and 40% of LR-3s, and 13% and 14% of LR-2s. No LR-1s were confirmed as malignant.
“Our data suggest biopsy of LI-RADS 3 observations should be considered in many patients, as a risk of 38% of HCC would usually provoke biopsy of a lesion elsewhere in the body,” the researchers wrote. They suggested consideration for biopsy of certain LR-2 lesions, but added that many “are small, perfusional alterations caused by arterioportal shunts, which are often not reported” and would be difficult or impossible to biopsy.
The study did not cover the most recent (2018) LI-RADS system, which featured several changes to simplify and better align it with American Association for the Study of Liver Diseases criteria, the researchers noted. They called for prospective studies to help confirm the accuracy of the LI-RADS system, particularly with regard to intermediate categories, such as LR-2.
The researchers disclosed no funding sources. Dr. van der Pol, Dr. Lim, and three other investigators reported having no conflicts of interest. Five researchers reported that they are members of the LI-RADS Steering Committee and four disclosed ties to pharmaceutical companies.
SOURCE: Van der Pol CB et al. Gastroenterology. 2018 Nov 13. doi: 10.1053/j.gastro.2018.11.020.
FROM GASTROENTEROLOGY
Key clinical point: Consider biopsy of CT/MRI observations classified as LI-RADS 3 (intermediate probability of malignancy), as well as LI-RADS 2 (probably benign) observations that are solid nodules measuring at least 1 cm.
Major finding: In all, 13% of LR-2 observations were confirmed to be hepatocellular carcinomas, as were 38% of LR-3 observations.
Study details: Systematic review and meta-analysis of 17 retrospective studies.
Disclosures: The researchers disclosed no external funding sources. Dr. van der Pol, Dr. Lim, and three other investigators reported having no conflicts of interest. Five researchers reported that they are members of the LI-RADS Steering Committee and four disclosed ties to pharmaceutical companies.
Source: Van der Pol CB et al. Gastroenterology. 2018 Nov 13. doi: 10.1053/j.gastro.2018.11.020.
TNF inhibitors improve BMD in ankylosing spondylitis
Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.
The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.
K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.
After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.
In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.
Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.
“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.
They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.
“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.
No information on study funding or disclosures was available.
SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.
The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.
K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.
After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.
In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.
Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.
“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.
They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.
“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.
No information on study funding or disclosures was available.
SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.
The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.
K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.
After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.
In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.
Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.
“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.
They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.
“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.
No information on study funding or disclosures was available.
SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
FROM THE JOURNAL OF BONE AND MINERAL RESEARCH
Key clinical point: Long-term therapy with tumor necrosis factor inhibitors was shown to benefit bone mineral density in ankylosing spondylitis patients, but not vertebral fracture outcomes or radiographic progression.
Major finding: The proportion of patients with a low bone mineral density of the hip decreased from 40.1% to 31.8% (P = .03) after 4 years of tumor necrosis factor inhibitor treatment.
Study details: A prospective cohort study of 135 patients with ankylosing spondylitis treated with a tumor necrosis factor inhibitor for up to 4 years.
Disclosures: No information on study funding or disclosures was available.
Source: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
Frailty, diabetes increase fragility fracture risk
increasing their risk of fragility fracture, according to findings from a prospective cohort study.
A total of 3,149 participants (70% women) were included in the study, 138 (60% women) of whom had type 2 diabetes. The mean age was 65 years and mean follow-up was 9.2 years. Over the study period, 611 fragility fractures were reported, of which 35 were in patients with diabetes and 576 in patients without diabetes. Overall, 25.4% of patients with diabetes experienced a fragility fracture, compared with 19.1% of control patients. Diabetes was associated with a significantly increased risk of all fragility fractures (hazard ratio, 1.54). It was also significantly associated with risk of hip fracture (HR, 2.60) but not clinical spine fracture.
In a Cox model incorporating the interaction between frailty index (FI) scores and diabetes, there was a significant association between FI and overall fracture risk per 0.01-point FI increase (HR, 1.02; 95% confidence interval, 1.01-1.03) and per 0.10-point FI increase (HR, 1.19; 95% CI, 1.10-1.33). However, no interaction between frailty and diabetes was observed for hip or clinical spine fractures.
“Frailty status may aid in the understanding of the paradox and thus enhance the quality of assessment and care for diabetes,” wrote Guowei Li, MBBS, PhD, of McMaster University, Hamilton, Ont., and his colleagues, adding that “particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.”
Four study authors reported conflicts of interest with some pharmaceutical companies that manufacture therapies for osteoporosis.
SOURCE: Li G et al. Diabetes Care. 2019 Jan 28. doi: 10.2337/dc18-1965.
increasing their risk of fragility fracture, according to findings from a prospective cohort study.
A total of 3,149 participants (70% women) were included in the study, 138 (60% women) of whom had type 2 diabetes. The mean age was 65 years and mean follow-up was 9.2 years. Over the study period, 611 fragility fractures were reported, of which 35 were in patients with diabetes and 576 in patients without diabetes. Overall, 25.4% of patients with diabetes experienced a fragility fracture, compared with 19.1% of control patients. Diabetes was associated with a significantly increased risk of all fragility fractures (hazard ratio, 1.54). It was also significantly associated with risk of hip fracture (HR, 2.60) but not clinical spine fracture.
In a Cox model incorporating the interaction between frailty index (FI) scores and diabetes, there was a significant association between FI and overall fracture risk per 0.01-point FI increase (HR, 1.02; 95% confidence interval, 1.01-1.03) and per 0.10-point FI increase (HR, 1.19; 95% CI, 1.10-1.33). However, no interaction between frailty and diabetes was observed for hip or clinical spine fractures.
“Frailty status may aid in the understanding of the paradox and thus enhance the quality of assessment and care for diabetes,” wrote Guowei Li, MBBS, PhD, of McMaster University, Hamilton, Ont., and his colleagues, adding that “particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.”
Four study authors reported conflicts of interest with some pharmaceutical companies that manufacture therapies for osteoporosis.
SOURCE: Li G et al. Diabetes Care. 2019 Jan 28. doi: 10.2337/dc18-1965.
increasing their risk of fragility fracture, according to findings from a prospective cohort study.
A total of 3,149 participants (70% women) were included in the study, 138 (60% women) of whom had type 2 diabetes. The mean age was 65 years and mean follow-up was 9.2 years. Over the study period, 611 fragility fractures were reported, of which 35 were in patients with diabetes and 576 in patients without diabetes. Overall, 25.4% of patients with diabetes experienced a fragility fracture, compared with 19.1% of control patients. Diabetes was associated with a significantly increased risk of all fragility fractures (hazard ratio, 1.54). It was also significantly associated with risk of hip fracture (HR, 2.60) but not clinical spine fracture.
In a Cox model incorporating the interaction between frailty index (FI) scores and diabetes, there was a significant association between FI and overall fracture risk per 0.01-point FI increase (HR, 1.02; 95% confidence interval, 1.01-1.03) and per 0.10-point FI increase (HR, 1.19; 95% CI, 1.10-1.33). However, no interaction between frailty and diabetes was observed for hip or clinical spine fractures.
“Frailty status may aid in the understanding of the paradox and thus enhance the quality of assessment and care for diabetes,” wrote Guowei Li, MBBS, PhD, of McMaster University, Hamilton, Ont., and his colleagues, adding that “particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.”
Four study authors reported conflicts of interest with some pharmaceutical companies that manufacture therapies for osteoporosis.
SOURCE: Li G et al. Diabetes Care. 2019 Jan 28. doi: 10.2337/dc18-1965.
FROM DIABETES CARE
Meet Dr. Vincent DeLeo at AAD
The new MDedge Dermatology podcast will feature Dr. Vincent A. DeLeo talking with colleagues about all things dermatology. The podcast will also feature news highlights.
Stop by our booth at AAD to chat with Dr. DeLeo!
Friday, March 1, 2019
2 pm to 3 pm
Booths 1721 and 1723
The new MDedge Dermatology podcast will feature Dr. Vincent A. DeLeo talking with colleagues about all things dermatology. The podcast will also feature news highlights.
Stop by our booth at AAD to chat with Dr. DeLeo!
Friday, March 1, 2019
2 pm to 3 pm
Booths 1721 and 1723
The new MDedge Dermatology podcast will feature Dr. Vincent A. DeLeo talking with colleagues about all things dermatology. The podcast will also feature news highlights.
Stop by our booth at AAD to chat with Dr. DeLeo!
Friday, March 1, 2019
2 pm to 3 pm
Booths 1721 and 1723
Biomarkers predict VTE risk with menopausal oral hormone therapy
CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.
She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.
“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.
The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.
In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.
Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).
Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.
In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.
In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.
“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.
Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.
The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.
The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.
And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).
At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.
Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.
CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.
She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.
“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.
The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.
In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.
Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).
Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.
In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.
In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.
“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.
Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.
The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.
The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.
And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).
At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.
Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.
CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.
She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.
“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.
The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.
In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.
Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).
Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.
In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.
In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.
“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.
Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.
The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.
The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.
And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).
At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.
Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Women in the top 25% for D-dimer level before going on menopausal hormone therapy had a 6% incidence of venous thromboembolism over 5 years.
Study details: This was a nested case-control study focused on identifying biomarkers for venous thromboembolism risk which included 1,082 participants in the Women’s Health Initiative randomized to menopausal hormone therapy or placebo.
Disclosures: The presenter reported having no financial conflicts regarding the study, which was funded by the National Institutes of Health.
Cerdulatinib yields ‘encouraging’ results in CTCL, PTCL
LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).
The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).
The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.
“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.
Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.
Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.
PTCL cohort
The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.
The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.
Responses according to subtype were as follows:
- 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
- 2 CRs in PTCL not otherwise specified.
- 1 CR in gamma-delta T-cell lymphoma.
- 1 PR in ALK-negative anaplastic large-cell lymphoma.
- 1 CR and 1 PR in adult T-cell leukemia/lymphoma.
Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.
The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).
There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
CTCL cohort
The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.
The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.
Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.
“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.
The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).
“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”
She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.
“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.
She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).
The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).
The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.
“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.
Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.
Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.
PTCL cohort
The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.
The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.
Responses according to subtype were as follows:
- 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
- 2 CRs in PTCL not otherwise specified.
- 1 CR in gamma-delta T-cell lymphoma.
- 1 PR in ALK-negative anaplastic large-cell lymphoma.
- 1 CR and 1 PR in adult T-cell leukemia/lymphoma.
Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.
The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).
There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
CTCL cohort
The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.
The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.
Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.
“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.
The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).
“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”
She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.
“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.
She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).
The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).
The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.
“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.
Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.
Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.
PTCL cohort
The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.
The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.
Responses according to subtype were as follows:
- 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
- 2 CRs in PTCL not otherwise specified.
- 1 CR in gamma-delta T-cell lymphoma.
- 1 PR in ALK-negative anaplastic large-cell lymphoma.
- 1 CR and 1 PR in adult T-cell leukemia/lymphoma.
Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.
The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).
There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
CTCL cohort
The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.
The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.
Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.
“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.
The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).
“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”
She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.
“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.
She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Key clinical point:
Major finding: The overall response rate was 34% in patients with peripheral T-cell lymphoma (PTCL) and 26% in patients with cutaneous T-cell lymphoma (CTCL).
Study details: Expansion cohorts of a phase 2 trial including 45 PTCL patients and 29 CTCL patients
Disclosures: The study was funded by Portola Pharmaceuticals. The investigator reported having no relevant conflicts.
President Trump calls for end to HIV/AIDS, pediatric cancer
HIV/AIDS, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights of President Donald Trump’s second State of the Union address Feb. 5.
Mr. Trump promised to push for funds to end HIV/AIDS and childhood cancer within in 10 years. “In recent years, we have made remarkable progress in the fight against HIV and AIDS. Scientific breakthroughs have brought a once-distant dream within reach,” he said to assembled members of Congress and leaders of the executive and judicial branches of government. “My budget will ask Democrats and Republicans to make the needed commitment to eliminate the HIV epidemic in the United States within 10 years.”
Following the speech, Alex Azar, secretary of the Department of Health and Human Services, offered more details in a blog post on the agency’s website.
Funding for the initiative, dubbed “Ending the HIV Epidemic: A Plan for America,” will have three components.
The first involves increasing investments in “geographic hotspots” though existing programs like the Ryan White HIV/AIDS Program and a new community health center–based program to provide antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) to those at the highest risk of contracting the disease.
Second is the use of data to track where the disease is spreading most rapidly to help target prevention, care, and treatment at the local level. The third will provide funds for the creation of a local HIV HealthForce in these targeted areas to expand HIV prevention and treatment efforts.
A fact sheet on this initiative called for a 75% reduction in new cases of HIV infection in 5 years and at least a 90% reduction within 10 years.
President Trump called for similar efforts to address pediatric cancer.
“Tonight I am also asking you to join me in another fight that all American can get behind – the fight against childhood cancer,” he said, adding that his budget request will come with a line item of $500 million over 10 years to fund research. “Many childhood cancers have not seen new therapies in decades.”
President Trump also asked Congress to legislate a prohibition of late-term abortion.
“There could be no greater contrast to the beautiful image of a mother holding her infant child than the chilling displays our nation saw in recent days,” he said. “Lawmakers in New York cheered with delight upon the passage of legislation that would allow a baby to be ripped from the mother’s womb moments from birth. These are living, feeling beautiful babies who will never get the chance to share their love and their dreams with the world. ... Let us work together to build a culture that cherishes innocent life.”
He also touched on the recurring themes regarding lowering the cost of health care and prescription drugs, as well as protecting those with preexisting conditions, something he called a major priority.
“It’s unacceptable that Americans pay vastly more than people in other countries for the exact same drugs, often made in the exact same place. This is wrong. This is unfair and together we will stop it, and we will stop it fast,” he said.
He did not offer any specific policy recommendation on how to address prescription drug costs, other than a comment on the need for greater price transparency.
“I am asking Congress to pass legislation that finally takes on the problem of global freeloading and delivers fairness and price transparency for American patients,” he said.
“We should also require drug companies, insurance companies, and hospitals to disclose real prices to foster competition and bring costs way down.”
SOURCE: Trump D. State of the Union Address, Feb. 5, 2019.
HIV/AIDS, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights of President Donald Trump’s second State of the Union address Feb. 5.
Mr. Trump promised to push for funds to end HIV/AIDS and childhood cancer within in 10 years. “In recent years, we have made remarkable progress in the fight against HIV and AIDS. Scientific breakthroughs have brought a once-distant dream within reach,” he said to assembled members of Congress and leaders of the executive and judicial branches of government. “My budget will ask Democrats and Republicans to make the needed commitment to eliminate the HIV epidemic in the United States within 10 years.”
Following the speech, Alex Azar, secretary of the Department of Health and Human Services, offered more details in a blog post on the agency’s website.
Funding for the initiative, dubbed “Ending the HIV Epidemic: A Plan for America,” will have three components.
The first involves increasing investments in “geographic hotspots” though existing programs like the Ryan White HIV/AIDS Program and a new community health center–based program to provide antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) to those at the highest risk of contracting the disease.
Second is the use of data to track where the disease is spreading most rapidly to help target prevention, care, and treatment at the local level. The third will provide funds for the creation of a local HIV HealthForce in these targeted areas to expand HIV prevention and treatment efforts.
A fact sheet on this initiative called for a 75% reduction in new cases of HIV infection in 5 years and at least a 90% reduction within 10 years.
President Trump called for similar efforts to address pediatric cancer.
“Tonight I am also asking you to join me in another fight that all American can get behind – the fight against childhood cancer,” he said, adding that his budget request will come with a line item of $500 million over 10 years to fund research. “Many childhood cancers have not seen new therapies in decades.”
President Trump also asked Congress to legislate a prohibition of late-term abortion.
“There could be no greater contrast to the beautiful image of a mother holding her infant child than the chilling displays our nation saw in recent days,” he said. “Lawmakers in New York cheered with delight upon the passage of legislation that would allow a baby to be ripped from the mother’s womb moments from birth. These are living, feeling beautiful babies who will never get the chance to share their love and their dreams with the world. ... Let us work together to build a culture that cherishes innocent life.”
He also touched on the recurring themes regarding lowering the cost of health care and prescription drugs, as well as protecting those with preexisting conditions, something he called a major priority.
“It’s unacceptable that Americans pay vastly more than people in other countries for the exact same drugs, often made in the exact same place. This is wrong. This is unfair and together we will stop it, and we will stop it fast,” he said.
He did not offer any specific policy recommendation on how to address prescription drug costs, other than a comment on the need for greater price transparency.
“I am asking Congress to pass legislation that finally takes on the problem of global freeloading and delivers fairness and price transparency for American patients,” he said.
“We should also require drug companies, insurance companies, and hospitals to disclose real prices to foster competition and bring costs way down.”
SOURCE: Trump D. State of the Union Address, Feb. 5, 2019.
HIV/AIDS, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights of President Donald Trump’s second State of the Union address Feb. 5.
Mr. Trump promised to push for funds to end HIV/AIDS and childhood cancer within in 10 years. “In recent years, we have made remarkable progress in the fight against HIV and AIDS. Scientific breakthroughs have brought a once-distant dream within reach,” he said to assembled members of Congress and leaders of the executive and judicial branches of government. “My budget will ask Democrats and Republicans to make the needed commitment to eliminate the HIV epidemic in the United States within 10 years.”
Following the speech, Alex Azar, secretary of the Department of Health and Human Services, offered more details in a blog post on the agency’s website.
Funding for the initiative, dubbed “Ending the HIV Epidemic: A Plan for America,” will have three components.
The first involves increasing investments in “geographic hotspots” though existing programs like the Ryan White HIV/AIDS Program and a new community health center–based program to provide antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) to those at the highest risk of contracting the disease.
Second is the use of data to track where the disease is spreading most rapidly to help target prevention, care, and treatment at the local level. The third will provide funds for the creation of a local HIV HealthForce in these targeted areas to expand HIV prevention and treatment efforts.
A fact sheet on this initiative called for a 75% reduction in new cases of HIV infection in 5 years and at least a 90% reduction within 10 years.
President Trump called for similar efforts to address pediatric cancer.
“Tonight I am also asking you to join me in another fight that all American can get behind – the fight against childhood cancer,” he said, adding that his budget request will come with a line item of $500 million over 10 years to fund research. “Many childhood cancers have not seen new therapies in decades.”
President Trump also asked Congress to legislate a prohibition of late-term abortion.
“There could be no greater contrast to the beautiful image of a mother holding her infant child than the chilling displays our nation saw in recent days,” he said. “Lawmakers in New York cheered with delight upon the passage of legislation that would allow a baby to be ripped from the mother’s womb moments from birth. These are living, feeling beautiful babies who will never get the chance to share their love and their dreams with the world. ... Let us work together to build a culture that cherishes innocent life.”
He also touched on the recurring themes regarding lowering the cost of health care and prescription drugs, as well as protecting those with preexisting conditions, something he called a major priority.
“It’s unacceptable that Americans pay vastly more than people in other countries for the exact same drugs, often made in the exact same place. This is wrong. This is unfair and together we will stop it, and we will stop it fast,” he said.
He did not offer any specific policy recommendation on how to address prescription drug costs, other than a comment on the need for greater price transparency.
“I am asking Congress to pass legislation that finally takes on the problem of global freeloading and delivers fairness and price transparency for American patients,” he said.
“We should also require drug companies, insurance companies, and hospitals to disclose real prices to foster competition and bring costs way down.”
SOURCE: Trump D. State of the Union Address, Feb. 5, 2019.
Key clinical point: President Trump calls for an end to HIV/AIDS and pediatric cancer in 10 years.
Major finding: His budget will request $500 million for cancer research and as yet undisclosed amount for HIV/AIDS research.
Study details: More specific details on the proposals will likely come when the president makes his budget submission to Congress in the coming weeks.
Disclosures: There are no disclosures.
Source: Trump D. State of the Union Address, Feb. 5, 2019.