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VIDEO: New PsA guideline expected in 2018
SAN DIEGO – For the first time, a forthcoming evidence-based guideline for the management of psoriatic arthritis recommends tumor necrosis factor inhibitor biologics as first-line therapy.
“Guidelines that have been around for the last several years have been skirting around the fact that there’s really no evidence that methotrexate works for PsA,” Dafna D. Gladman, MD, said during a press briefing at the annual meeting of the American College of Rheumatology. “So it’s refreshing and reassuring that when you do an appropriate, evidence-based approach, you finally find the truth in front of you, and you have TNF inhibitors as the first-line treatment. Obviously, they’re not for everybody. There are patients in whom we cannot use TNF inhibitors, either because they don’t like needles, or because they have contraindications to getting these particular needles, but at least we have a recommendation for the use of these drugs as a first-line treatment.”
“At first, I wasn’t a big fan of the idea of the GRADE guidelines because the number of questions blows up so fast, [but] it really makes you focus on what the most common [clinical] settings are,” said another core oversight team member, Alexis Ogdie, MD, a rheumatologist at the University of Pennsylvania, Philadelphia. “These guidelines also reveal the major gap of no head-to-head studies. I think we’ve known that, but this really called that out as important. When we’re making a treatment decision between [drugs] A and B, we need those studies to be able to better understand how to treat our patients, rather than using the data from one trial to make a decision. ... For my patients, I’m excited that I can now use a TNF inhibitor as a first-line agent. When we have patients come in with very severe disease, occasionally they also have severe psoriasis, so we’ve been able to use TNF inhibitors as first-line treatment in some of our patients in Pennsylvania. This differs state by state. But the exciting thing is that they get better so fast and you don’t have to tell them to wait 12 weeks for methotrexate to work.”
The ACR/NPF guideline is currently under peer review and is expected to be published in Arthritis & Rheumatology, Arthritis Care & Research, and the Journal of Psoriasis and Psoriatic Arthritis in the spring or summer of 2018. It focuses on common PsA patients, not exceptional cases. It includes recommendations on the management of patients with active PsA that is defined by the patients’ self-report and judged by the examining clinician to be caused by PsA, based on the on the presence of at least one of the following: actively inflamed joints; dactylitis; enthesitis; axial disease; active skin and/or nail involvement; and/or extra-articular manifestations such as uveitis or inflammatory bowel disease. Authors of the guideline considered cost as one of many possible factors affecting the use of the recommendations, but explicit cost-effectiveness analyses were not conducted. Also, since the NPF and the American Academy of Dermatology are concurrently developing a psoriasis treatment guideline, the treatment of skin psoriasis was not included in the guideline.
According to the guideline’s principal investigator Jasvinder Singh, MD, professor of medicine and epidemiology at the University of Alabama at Birmingham, the guideline will include 80 recommendations, 75 (94%) that are rated as “conditional,” and 5 (6%) that are rated as “strong,” based on the quality of evidence in the existing medical literature. “Most of our treatment guidelines rely on very low-to-moderate quality evidence, which means that there needs to be an active discussion between the physician and the patient with regard to which treatment to choose,” said Dr. Singh, who is also a staff rheumatologist at the Birmingham Veterans Affairs Medical Center and who led development of the 2012 and 2015 ACR treatment guidelines for RA. “When you’re not choosing the preferred treatment, there are defined specific recommendations under which that second treatment may be preferred over the first treatment.”
During a separate session at the meeting, Dr. Singh unveiled a few of the draft recommendations. One calls for using a treat-to-target strategy over not using one. In the setting of immunizing patients who are receiving a biologic, another recommendation calls for clinicians to start the indicated biologic and administer killed vaccines (as indicated) in patients with active PsA rather than delaying the biologic to give the killed vaccines. In addition, delaying the start of the indicated biologic is recommended over not delaying in order to administer a live attenuated vaccine in patients with active PsA. When patients continue to have with active PsA despite being on a TNF inhibitor, the draft guideline recommends switching to a different TNF inhibitor rather than an IL-17 inhibitor, an IL-12/IL-23 inhibitor, abatacept (Orencia), tofacitinib (Xeljanz), or adding methotrexate. If PsA is still active, the guideline recommends switching to an IL-17 inhibitor instead of an IL-12/IL-23 inhibitor, abatacept, or tofacitinib. If PsA is still active, the guideline recommends switching to an IL-12/IL-23 inhibitor over abatacept or tofacitinib.
The guideline also includes suggestions for nonpharmacologic treatments, including recommending low-impact exercise over high-impact exercise, occupational therapy, physical therapy, and weight loss. It also includes a strong recommendation to provide smoking cessation advice to patients.
Dr. Singh acknowledged significant research gaps in the current PsA medical literature, including no head-to-head comparisons of treatments. He said that the field also could benefit from specific studies for enthesitis, axial disease, and arthritis mutilans; randomized trials of nonpharmacologic interventions; more trials of monotherapy vs. combination therapy; vaccination trials for live attenuated vaccines; trials and registry studies of patients with common comorbidities, and studies of NSAIDs and glucocorticoids, to define their role.
Possible topics for future PsA guidelines, he continued, include treatment options for patients for whom biologic medication is not an option; use of therapies in pregnancy and conception; incorporation of high-quality cost or cost-effectiveness analysis into recommendations; and the role of other comorbidities, such as fibromyalgia, hepatitis, depression/anxiety, malignancy, and cardiovascular disease.
“Evidence-based medicine needs to be practiced, even in situations where it’s difficult to get a drug,” Dr. Gladman said. “One of the things we hope will happen in the near future is that companies will start doing head-to-head studies, to help us support evidence-based recommendations in the future.”
None of the speakers reported having relevant financial disclosures.
SAN DIEGO – For the first time, a forthcoming evidence-based guideline for the management of psoriatic arthritis recommends tumor necrosis factor inhibitor biologics as first-line therapy.
“Guidelines that have been around for the last several years have been skirting around the fact that there’s really no evidence that methotrexate works for PsA,” Dafna D. Gladman, MD, said during a press briefing at the annual meeting of the American College of Rheumatology. “So it’s refreshing and reassuring that when you do an appropriate, evidence-based approach, you finally find the truth in front of you, and you have TNF inhibitors as the first-line treatment. Obviously, they’re not for everybody. There are patients in whom we cannot use TNF inhibitors, either because they don’t like needles, or because they have contraindications to getting these particular needles, but at least we have a recommendation for the use of these drugs as a first-line treatment.”
“At first, I wasn’t a big fan of the idea of the GRADE guidelines because the number of questions blows up so fast, [but] it really makes you focus on what the most common [clinical] settings are,” said another core oversight team member, Alexis Ogdie, MD, a rheumatologist at the University of Pennsylvania, Philadelphia. “These guidelines also reveal the major gap of no head-to-head studies. I think we’ve known that, but this really called that out as important. When we’re making a treatment decision between [drugs] A and B, we need those studies to be able to better understand how to treat our patients, rather than using the data from one trial to make a decision. ... For my patients, I’m excited that I can now use a TNF inhibitor as a first-line agent. When we have patients come in with very severe disease, occasionally they also have severe psoriasis, so we’ve been able to use TNF inhibitors as first-line treatment in some of our patients in Pennsylvania. This differs state by state. But the exciting thing is that they get better so fast and you don’t have to tell them to wait 12 weeks for methotrexate to work.”
The ACR/NPF guideline is currently under peer review and is expected to be published in Arthritis & Rheumatology, Arthritis Care & Research, and the Journal of Psoriasis and Psoriatic Arthritis in the spring or summer of 2018. It focuses on common PsA patients, not exceptional cases. It includes recommendations on the management of patients with active PsA that is defined by the patients’ self-report and judged by the examining clinician to be caused by PsA, based on the on the presence of at least one of the following: actively inflamed joints; dactylitis; enthesitis; axial disease; active skin and/or nail involvement; and/or extra-articular manifestations such as uveitis or inflammatory bowel disease. Authors of the guideline considered cost as one of many possible factors affecting the use of the recommendations, but explicit cost-effectiveness analyses were not conducted. Also, since the NPF and the American Academy of Dermatology are concurrently developing a psoriasis treatment guideline, the treatment of skin psoriasis was not included in the guideline.
According to the guideline’s principal investigator Jasvinder Singh, MD, professor of medicine and epidemiology at the University of Alabama at Birmingham, the guideline will include 80 recommendations, 75 (94%) that are rated as “conditional,” and 5 (6%) that are rated as “strong,” based on the quality of evidence in the existing medical literature. “Most of our treatment guidelines rely on very low-to-moderate quality evidence, which means that there needs to be an active discussion between the physician and the patient with regard to which treatment to choose,” said Dr. Singh, who is also a staff rheumatologist at the Birmingham Veterans Affairs Medical Center and who led development of the 2012 and 2015 ACR treatment guidelines for RA. “When you’re not choosing the preferred treatment, there are defined specific recommendations under which that second treatment may be preferred over the first treatment.”
During a separate session at the meeting, Dr. Singh unveiled a few of the draft recommendations. One calls for using a treat-to-target strategy over not using one. In the setting of immunizing patients who are receiving a biologic, another recommendation calls for clinicians to start the indicated biologic and administer killed vaccines (as indicated) in patients with active PsA rather than delaying the biologic to give the killed vaccines. In addition, delaying the start of the indicated biologic is recommended over not delaying in order to administer a live attenuated vaccine in patients with active PsA. When patients continue to have with active PsA despite being on a TNF inhibitor, the draft guideline recommends switching to a different TNF inhibitor rather than an IL-17 inhibitor, an IL-12/IL-23 inhibitor, abatacept (Orencia), tofacitinib (Xeljanz), or adding methotrexate. If PsA is still active, the guideline recommends switching to an IL-17 inhibitor instead of an IL-12/IL-23 inhibitor, abatacept, or tofacitinib. If PsA is still active, the guideline recommends switching to an IL-12/IL-23 inhibitor over abatacept or tofacitinib.
The guideline also includes suggestions for nonpharmacologic treatments, including recommending low-impact exercise over high-impact exercise, occupational therapy, physical therapy, and weight loss. It also includes a strong recommendation to provide smoking cessation advice to patients.
Dr. Singh acknowledged significant research gaps in the current PsA medical literature, including no head-to-head comparisons of treatments. He said that the field also could benefit from specific studies for enthesitis, axial disease, and arthritis mutilans; randomized trials of nonpharmacologic interventions; more trials of monotherapy vs. combination therapy; vaccination trials for live attenuated vaccines; trials and registry studies of patients with common comorbidities, and studies of NSAIDs and glucocorticoids, to define their role.
Possible topics for future PsA guidelines, he continued, include treatment options for patients for whom biologic medication is not an option; use of therapies in pregnancy and conception; incorporation of high-quality cost or cost-effectiveness analysis into recommendations; and the role of other comorbidities, such as fibromyalgia, hepatitis, depression/anxiety, malignancy, and cardiovascular disease.
“Evidence-based medicine needs to be practiced, even in situations where it’s difficult to get a drug,” Dr. Gladman said. “One of the things we hope will happen in the near future is that companies will start doing head-to-head studies, to help us support evidence-based recommendations in the future.”
None of the speakers reported having relevant financial disclosures.
SAN DIEGO – For the first time, a forthcoming evidence-based guideline for the management of psoriatic arthritis recommends tumor necrosis factor inhibitor biologics as first-line therapy.
“Guidelines that have been around for the last several years have been skirting around the fact that there’s really no evidence that methotrexate works for PsA,” Dafna D. Gladman, MD, said during a press briefing at the annual meeting of the American College of Rheumatology. “So it’s refreshing and reassuring that when you do an appropriate, evidence-based approach, you finally find the truth in front of you, and you have TNF inhibitors as the first-line treatment. Obviously, they’re not for everybody. There are patients in whom we cannot use TNF inhibitors, either because they don’t like needles, or because they have contraindications to getting these particular needles, but at least we have a recommendation for the use of these drugs as a first-line treatment.”
“At first, I wasn’t a big fan of the idea of the GRADE guidelines because the number of questions blows up so fast, [but] it really makes you focus on what the most common [clinical] settings are,” said another core oversight team member, Alexis Ogdie, MD, a rheumatologist at the University of Pennsylvania, Philadelphia. “These guidelines also reveal the major gap of no head-to-head studies. I think we’ve known that, but this really called that out as important. When we’re making a treatment decision between [drugs] A and B, we need those studies to be able to better understand how to treat our patients, rather than using the data from one trial to make a decision. ... For my patients, I’m excited that I can now use a TNF inhibitor as a first-line agent. When we have patients come in with very severe disease, occasionally they also have severe psoriasis, so we’ve been able to use TNF inhibitors as first-line treatment in some of our patients in Pennsylvania. This differs state by state. But the exciting thing is that they get better so fast and you don’t have to tell them to wait 12 weeks for methotrexate to work.”
The ACR/NPF guideline is currently under peer review and is expected to be published in Arthritis & Rheumatology, Arthritis Care & Research, and the Journal of Psoriasis and Psoriatic Arthritis in the spring or summer of 2018. It focuses on common PsA patients, not exceptional cases. It includes recommendations on the management of patients with active PsA that is defined by the patients’ self-report and judged by the examining clinician to be caused by PsA, based on the on the presence of at least one of the following: actively inflamed joints; dactylitis; enthesitis; axial disease; active skin and/or nail involvement; and/or extra-articular manifestations such as uveitis or inflammatory bowel disease. Authors of the guideline considered cost as one of many possible factors affecting the use of the recommendations, but explicit cost-effectiveness analyses were not conducted. Also, since the NPF and the American Academy of Dermatology are concurrently developing a psoriasis treatment guideline, the treatment of skin psoriasis was not included in the guideline.
According to the guideline’s principal investigator Jasvinder Singh, MD, professor of medicine and epidemiology at the University of Alabama at Birmingham, the guideline will include 80 recommendations, 75 (94%) that are rated as “conditional,” and 5 (6%) that are rated as “strong,” based on the quality of evidence in the existing medical literature. “Most of our treatment guidelines rely on very low-to-moderate quality evidence, which means that there needs to be an active discussion between the physician and the patient with regard to which treatment to choose,” said Dr. Singh, who is also a staff rheumatologist at the Birmingham Veterans Affairs Medical Center and who led development of the 2012 and 2015 ACR treatment guidelines for RA. “When you’re not choosing the preferred treatment, there are defined specific recommendations under which that second treatment may be preferred over the first treatment.”
During a separate session at the meeting, Dr. Singh unveiled a few of the draft recommendations. One calls for using a treat-to-target strategy over not using one. In the setting of immunizing patients who are receiving a biologic, another recommendation calls for clinicians to start the indicated biologic and administer killed vaccines (as indicated) in patients with active PsA rather than delaying the biologic to give the killed vaccines. In addition, delaying the start of the indicated biologic is recommended over not delaying in order to administer a live attenuated vaccine in patients with active PsA. When patients continue to have with active PsA despite being on a TNF inhibitor, the draft guideline recommends switching to a different TNF inhibitor rather than an IL-17 inhibitor, an IL-12/IL-23 inhibitor, abatacept (Orencia), tofacitinib (Xeljanz), or adding methotrexate. If PsA is still active, the guideline recommends switching to an IL-17 inhibitor instead of an IL-12/IL-23 inhibitor, abatacept, or tofacitinib. If PsA is still active, the guideline recommends switching to an IL-12/IL-23 inhibitor over abatacept or tofacitinib.
The guideline also includes suggestions for nonpharmacologic treatments, including recommending low-impact exercise over high-impact exercise, occupational therapy, physical therapy, and weight loss. It also includes a strong recommendation to provide smoking cessation advice to patients.
Dr. Singh acknowledged significant research gaps in the current PsA medical literature, including no head-to-head comparisons of treatments. He said that the field also could benefit from specific studies for enthesitis, axial disease, and arthritis mutilans; randomized trials of nonpharmacologic interventions; more trials of monotherapy vs. combination therapy; vaccination trials for live attenuated vaccines; trials and registry studies of patients with common comorbidities, and studies of NSAIDs and glucocorticoids, to define their role.
Possible topics for future PsA guidelines, he continued, include treatment options for patients for whom biologic medication is not an option; use of therapies in pregnancy and conception; incorporation of high-quality cost or cost-effectiveness analysis into recommendations; and the role of other comorbidities, such as fibromyalgia, hepatitis, depression/anxiety, malignancy, and cardiovascular disease.
“Evidence-based medicine needs to be practiced, even in situations where it’s difficult to get a drug,” Dr. Gladman said. “One of the things we hope will happen in the near future is that companies will start doing head-to-head studies, to help us support evidence-based recommendations in the future.”
None of the speakers reported having relevant financial disclosures.
AT ACR 2017
Chronicity of obesity provides rationale for physician-surgeon collaboration
NATIONAL HARBOR, MD. – When combined with bariatric surgery, adjunctive therapies for obesity should be individualized for specific drivers of weight gain, which can differ among obesity phenotypes, according to an expert view presented at an annual meeting presented by the American Society for Metabolic and Bariatric Surgery and The Obesity Society .
“Surgery is the most effective therapy we have, but it is only one of multiple treatments that should be considered in a treatment paradigm,” suggested Robert F. Kushner, MD, a professor of endocrinology and specialist in obesity at the Northwestern University, Chicago.
“It is very useful to take a narrative approach to understand the patients in front of us and to understand who they are and how they got to where they are now,” Dr. Kushner explained. Dr. Kushner often asks patients to graph weight history over time. This can connect social, biological, and psychological events with significant weight gains, and these connections can generate insight into the underlying obesity phenotype.
“It is a like a fingerprint. Everyone has his or her own story to tell,” Dr. Kushner explained. A clinical picture of patients’ phenotypes can be developed from observing large jumps in weight connected to such factors as a stressful life event, a period of sustained inactivity, or a pregnancy. Over a weight history, several events may be identified that provide insight into each patient’s “unique weight journey.”
This understanding provides the basis for a systematic approach to combining strategies that may include lifestyle changes, surgery, and pharmacologic management, all tailored for the specific triggers and needs of the patient. Dr. Kushner advised that, even for those who are candidates for surgery, bariatric procedures are just one component of the treatment and must be integrated in a team approach with other modalities.
This approach may include pharmacologic therapy both before and after surgery; Dr. Kushner noted that the availability of drug options has expanded in recent years with approval of such therapies as lorcaserin and liraglutide. According to Dr. Kushner, drug therapy can be used for preoperative weight loss and may be useful for preventing postoperative weight gain in certain patients.
“There are no randomized trials demonstrating efficacy for prevention of postoperative weight gain, but there is supportive evidence from a retrospective study,” said Dr. Kushner, referring to a recently published two-center evaluation (Surg Obes Relat Dis. 2017;13:491-500).
In that study, 258 patients underwent Roux-en-Y gastric bypass, and 61 patients underwent sleeve gastrectomy. Those who received adjunctive drug support, particularly in the RYGB group, had greater sustained weight loss than those who did not, leading to the conclusion that postoperative pharmacotherapy “is a useful adjunct.” The advantage for drug therapy was observed even though patients did not receive the most recently approved and potentially more effective drugs, according to Dr. Kushner. However, he cautioned that information about the optimal timing of treatment after surgery remains “limited.”
The variability in weight loss and weight regain after bariatric procedures is one reason to consider bariatric surgery as only one component in a continuum of care, according to Dr. Kushner. He emphasized that obesity is a chronic condition that requires ongoing and perhaps indefinite treatment. While surgeons may already work with a team that manages preoperative and postoperative lifestyle changes to improve immediate surgical outcomes, Dr. Kushner believes that surgeons and physicians should work more collaboratively toward long-term management plans. By also appreciating obesity phenotypes and the specific mix of treatments that are most likely to help individual patients achieve durable weight loss, surgeons and physicians working together are likely to improve outcomes beyond those that could be expected from either working alone.
Dr. Kushner reports he has financial relationships with Novo Nordisk, Retrofit, Takeda Pharmaceuticals, and Vivus.
NATIONAL HARBOR, MD. – When combined with bariatric surgery, adjunctive therapies for obesity should be individualized for specific drivers of weight gain, which can differ among obesity phenotypes, according to an expert view presented at an annual meeting presented by the American Society for Metabolic and Bariatric Surgery and The Obesity Society .
“Surgery is the most effective therapy we have, but it is only one of multiple treatments that should be considered in a treatment paradigm,” suggested Robert F. Kushner, MD, a professor of endocrinology and specialist in obesity at the Northwestern University, Chicago.
“It is very useful to take a narrative approach to understand the patients in front of us and to understand who they are and how they got to where they are now,” Dr. Kushner explained. Dr. Kushner often asks patients to graph weight history over time. This can connect social, biological, and psychological events with significant weight gains, and these connections can generate insight into the underlying obesity phenotype.
“It is a like a fingerprint. Everyone has his or her own story to tell,” Dr. Kushner explained. A clinical picture of patients’ phenotypes can be developed from observing large jumps in weight connected to such factors as a stressful life event, a period of sustained inactivity, or a pregnancy. Over a weight history, several events may be identified that provide insight into each patient’s “unique weight journey.”
This understanding provides the basis for a systematic approach to combining strategies that may include lifestyle changes, surgery, and pharmacologic management, all tailored for the specific triggers and needs of the patient. Dr. Kushner advised that, even for those who are candidates for surgery, bariatric procedures are just one component of the treatment and must be integrated in a team approach with other modalities.
This approach may include pharmacologic therapy both before and after surgery; Dr. Kushner noted that the availability of drug options has expanded in recent years with approval of such therapies as lorcaserin and liraglutide. According to Dr. Kushner, drug therapy can be used for preoperative weight loss and may be useful for preventing postoperative weight gain in certain patients.
“There are no randomized trials demonstrating efficacy for prevention of postoperative weight gain, but there is supportive evidence from a retrospective study,” said Dr. Kushner, referring to a recently published two-center evaluation (Surg Obes Relat Dis. 2017;13:491-500).
In that study, 258 patients underwent Roux-en-Y gastric bypass, and 61 patients underwent sleeve gastrectomy. Those who received adjunctive drug support, particularly in the RYGB group, had greater sustained weight loss than those who did not, leading to the conclusion that postoperative pharmacotherapy “is a useful adjunct.” The advantage for drug therapy was observed even though patients did not receive the most recently approved and potentially more effective drugs, according to Dr. Kushner. However, he cautioned that information about the optimal timing of treatment after surgery remains “limited.”
The variability in weight loss and weight regain after bariatric procedures is one reason to consider bariatric surgery as only one component in a continuum of care, according to Dr. Kushner. He emphasized that obesity is a chronic condition that requires ongoing and perhaps indefinite treatment. While surgeons may already work with a team that manages preoperative and postoperative lifestyle changes to improve immediate surgical outcomes, Dr. Kushner believes that surgeons and physicians should work more collaboratively toward long-term management plans. By also appreciating obesity phenotypes and the specific mix of treatments that are most likely to help individual patients achieve durable weight loss, surgeons and physicians working together are likely to improve outcomes beyond those that could be expected from either working alone.
Dr. Kushner reports he has financial relationships with Novo Nordisk, Retrofit, Takeda Pharmaceuticals, and Vivus.
NATIONAL HARBOR, MD. – When combined with bariatric surgery, adjunctive therapies for obesity should be individualized for specific drivers of weight gain, which can differ among obesity phenotypes, according to an expert view presented at an annual meeting presented by the American Society for Metabolic and Bariatric Surgery and The Obesity Society .
“Surgery is the most effective therapy we have, but it is only one of multiple treatments that should be considered in a treatment paradigm,” suggested Robert F. Kushner, MD, a professor of endocrinology and specialist in obesity at the Northwestern University, Chicago.
“It is very useful to take a narrative approach to understand the patients in front of us and to understand who they are and how they got to where they are now,” Dr. Kushner explained. Dr. Kushner often asks patients to graph weight history over time. This can connect social, biological, and psychological events with significant weight gains, and these connections can generate insight into the underlying obesity phenotype.
“It is a like a fingerprint. Everyone has his or her own story to tell,” Dr. Kushner explained. A clinical picture of patients’ phenotypes can be developed from observing large jumps in weight connected to such factors as a stressful life event, a period of sustained inactivity, or a pregnancy. Over a weight history, several events may be identified that provide insight into each patient’s “unique weight journey.”
This understanding provides the basis for a systematic approach to combining strategies that may include lifestyle changes, surgery, and pharmacologic management, all tailored for the specific triggers and needs of the patient. Dr. Kushner advised that, even for those who are candidates for surgery, bariatric procedures are just one component of the treatment and must be integrated in a team approach with other modalities.
This approach may include pharmacologic therapy both before and after surgery; Dr. Kushner noted that the availability of drug options has expanded in recent years with approval of such therapies as lorcaserin and liraglutide. According to Dr. Kushner, drug therapy can be used for preoperative weight loss and may be useful for preventing postoperative weight gain in certain patients.
“There are no randomized trials demonstrating efficacy for prevention of postoperative weight gain, but there is supportive evidence from a retrospective study,” said Dr. Kushner, referring to a recently published two-center evaluation (Surg Obes Relat Dis. 2017;13:491-500).
In that study, 258 patients underwent Roux-en-Y gastric bypass, and 61 patients underwent sleeve gastrectomy. Those who received adjunctive drug support, particularly in the RYGB group, had greater sustained weight loss than those who did not, leading to the conclusion that postoperative pharmacotherapy “is a useful adjunct.” The advantage for drug therapy was observed even though patients did not receive the most recently approved and potentially more effective drugs, according to Dr. Kushner. However, he cautioned that information about the optimal timing of treatment after surgery remains “limited.”
The variability in weight loss and weight regain after bariatric procedures is one reason to consider bariatric surgery as only one component in a continuum of care, according to Dr. Kushner. He emphasized that obesity is a chronic condition that requires ongoing and perhaps indefinite treatment. While surgeons may already work with a team that manages preoperative and postoperative lifestyle changes to improve immediate surgical outcomes, Dr. Kushner believes that surgeons and physicians should work more collaboratively toward long-term management plans. By also appreciating obesity phenotypes and the specific mix of treatments that are most likely to help individual patients achieve durable weight loss, surgeons and physicians working together are likely to improve outcomes beyond those that could be expected from either working alone.
Dr. Kushner reports he has financial relationships with Novo Nordisk, Retrofit, Takeda Pharmaceuticals, and Vivus.
AT OBESITY WEEK 2017
Key clinical point: For treatment of obesity as a chronic disease, bariatric surgery must be incorporated into a continuum of therapies.
Major finding: Obesity phenotypes differ, requiring individualized adjunctive therapies to surgery in order to ensure durable benefit.
Data source: Expert interpretation of published studies.
Disclosures: Dr. Kushner reports he has financial relationships with Novo Nordisk, Retrofit, Takeda Pharmaceuticals, and Vivus.
DACA: Time to act
President Trump recently announced his decision to officially end the Deferred Action for Childhood Arrivals program, also known as DACA. The program has been controversial since its inception, almost as controversial as the decision to end it. What impact has DACA had on the medical community, including hospitalists, and what are the implications of ending it?
DACA is a program started in 2012 by an executive action under the Obama administration. The program currently protects approximately 800,000 undocumented immigrants in the United States from being deported. All DACA recipients were brought to this country illegally as children. When the DACA program began, in order to enroll, recipients had to prove that they had arrived to here before age 16, and that they had been living in the United States continuously since 2007. Once enrolled, the protections they receive from the program include the ability to legally work and to go to school, as well as obtain a social security number and driver’s license. These protections are then afforded for renewable 2-year periods of time.1
When Trump was elected, the controversy over continuing the DACA program accelerated. Understandably, the volume of applications rose substantially, with some estimating ~8,000 renewal requests being filed each week since the election. As such, many estimate the number of illegal immigrants affected by DACA has reached almost 1 million.1
One of the reasons the Trump administration feels compelled to dismantle the program is they contend that DACA is unconstitutional, as it was established purely by executive order. In the meantime, Trump is urging Congress to replace DACA with some type of equivalent legislation. According to his staffers, the dismantling of DACA means:
- No new applications will be accepted.
- All existing permits will be honored until they expire.
- All applications in process will continue to be processed.
They contend that no current DACA recipients will be affected before March 2018. Unfortunately for the Trump administration, this has been a very unpopular move, as two-thirds of Americans support allowing the Dreamers to stay in the United States.1
Impact on health care
The concern for the medical industry is that a “dismantling” of DACA could exacerbate an already existing physician shortage in the United States. For example, the Association of American Medical Colleges estimates the physician shortage will rise as the population ages and medical access increases; they currently estimate a physician shortage of approximately 40,000-104,000 by 2030.
But objectively evaluating the impact of the DACA program on the medical industry is difficult. We do know that most of the DACA recipients arrived from Mexico, El Salvador, Guatemala, and Honduras, as well as from Asia (primarily South Korea and the Philippines). We also know they reside in every state, with the largest numbers in California (222,795), Texas (124,300), New York (41,970), Illinois (42,376), and Florida (32,795). Most appear to be using DACA to work and to go to school; in a recent survey, 91% were employed, and 45% were enrolled in school.1
Pertaining specifically to medical school, during the 2016-2017 school year, there were 113 DACA applicants to U.S. medical schools, 65 of which were accepted and enrolled. The AAMC expects the 2017-2018 enrollment to be even higher. Almost half of medical school enrollees attend Loyola University Chicago, Maywood, Ill.; this year alone, Loyola Stritch Medical School enrolled 32 DACA medical students. This is because, in 2013, Loyola was the first medical school nationwide to openly accept students with DACA status. They did this by creating a mechanism for DACA medical students to get student loans.
One of the biggest challenges for DACA students is paying for school, as they are not eligible for federal student loans. To remove this barrier, Loyola created a loan program through the Illinois Finance Authority, which offers interest-free loans to DACA students if they commit to paying back the principal and working after medical school for 4 years in an underserved area in Illinois. It is clear that no medical school in the country will feel the effects of the DACA dismantling more than will Loyola.3
Another unintended issue that the dismantling of DACA can have on the medical industry is the temptation for undocumented immigrants to avoid seeking medical care, for fear of being discovered and deported. Such delays in seeking care can result in these patients presenting with significant and expensive medical issues.
So what are the options for Congress and what is the likely fate of these DACA recipients whose lives have been placed in limbo? Proposals introduced to date include:
- The Bridge Act, which effectively extends the present DACA program by 3 years.
- Recognizing America’s Children Act, which would allow people who meet DACA eligibility criteria to apply for conditional permanent residence with a path toward citizenship.
- The American Hope Act and updated DREAM Act, both of which propose broader eligibility criteria and faster pathways to citizenship.4
There is great hope that some definitive action can be employed by Congress, as most legislators on both sides of the aisle have expressed some support for at least one of the proposed policies (although that certainly does not guarantee sufficient votes to pass). There also is support from many Americans, given that most DACA recipients have been productive members of society, and most Americans believe that DACA recipients should not be held accountable “for the sins of their parents.”4
It appears that the dismantling of DACA would be quite unsettling and certainly would affect some areas of the country more severely than others. Regardless of political stance, everyone can agree that Congress needs to do something, as the ambiguity and uncertainty caused by a million undocumented immigrants living and working in the United States cannot be ignored or indefinitely deferred. Any of the above options that offer a pathway to citizenship would be welcomed by most Americans. Having Dreamers in limbo is bad for everyone; the time to act is now.
Dr. Scheurer is a hospitalist and chief quality officer at the Medical University of South Carolina in Charleston. She is physician editor of The Hospitalist. Email her at scheured@musc.edu.
References
1. http://www.npr.org/2017/09/05/548754723/5-things-you-should-know-about-daca
2. https://www.forbes.com/sites/brucejapsen/2017/09/05/how-trumps-move-to-end-daca-worsens-the-doctor-shortage/#5143320d5b06
3. http://www.chicagomag.com/city-life/September-2017/DACA-Stritch-Medical-School/
4. http://www.nejm.org/doi/full/10.1056/NEJMp1711416?query=TOC
President Trump recently announced his decision to officially end the Deferred Action for Childhood Arrivals program, also known as DACA. The program has been controversial since its inception, almost as controversial as the decision to end it. What impact has DACA had on the medical community, including hospitalists, and what are the implications of ending it?
DACA is a program started in 2012 by an executive action under the Obama administration. The program currently protects approximately 800,000 undocumented immigrants in the United States from being deported. All DACA recipients were brought to this country illegally as children. When the DACA program began, in order to enroll, recipients had to prove that they had arrived to here before age 16, and that they had been living in the United States continuously since 2007. Once enrolled, the protections they receive from the program include the ability to legally work and to go to school, as well as obtain a social security number and driver’s license. These protections are then afforded for renewable 2-year periods of time.1
When Trump was elected, the controversy over continuing the DACA program accelerated. Understandably, the volume of applications rose substantially, with some estimating ~8,000 renewal requests being filed each week since the election. As such, many estimate the number of illegal immigrants affected by DACA has reached almost 1 million.1
One of the reasons the Trump administration feels compelled to dismantle the program is they contend that DACA is unconstitutional, as it was established purely by executive order. In the meantime, Trump is urging Congress to replace DACA with some type of equivalent legislation. According to his staffers, the dismantling of DACA means:
- No new applications will be accepted.
- All existing permits will be honored until they expire.
- All applications in process will continue to be processed.
They contend that no current DACA recipients will be affected before March 2018. Unfortunately for the Trump administration, this has been a very unpopular move, as two-thirds of Americans support allowing the Dreamers to stay in the United States.1
Impact on health care
The concern for the medical industry is that a “dismantling” of DACA could exacerbate an already existing physician shortage in the United States. For example, the Association of American Medical Colleges estimates the physician shortage will rise as the population ages and medical access increases; they currently estimate a physician shortage of approximately 40,000-104,000 by 2030.
But objectively evaluating the impact of the DACA program on the medical industry is difficult. We do know that most of the DACA recipients arrived from Mexico, El Salvador, Guatemala, and Honduras, as well as from Asia (primarily South Korea and the Philippines). We also know they reside in every state, with the largest numbers in California (222,795), Texas (124,300), New York (41,970), Illinois (42,376), and Florida (32,795). Most appear to be using DACA to work and to go to school; in a recent survey, 91% were employed, and 45% were enrolled in school.1
Pertaining specifically to medical school, during the 2016-2017 school year, there were 113 DACA applicants to U.S. medical schools, 65 of which were accepted and enrolled. The AAMC expects the 2017-2018 enrollment to be even higher. Almost half of medical school enrollees attend Loyola University Chicago, Maywood, Ill.; this year alone, Loyola Stritch Medical School enrolled 32 DACA medical students. This is because, in 2013, Loyola was the first medical school nationwide to openly accept students with DACA status. They did this by creating a mechanism for DACA medical students to get student loans.
One of the biggest challenges for DACA students is paying for school, as they are not eligible for federal student loans. To remove this barrier, Loyola created a loan program through the Illinois Finance Authority, which offers interest-free loans to DACA students if they commit to paying back the principal and working after medical school for 4 years in an underserved area in Illinois. It is clear that no medical school in the country will feel the effects of the DACA dismantling more than will Loyola.3
Another unintended issue that the dismantling of DACA can have on the medical industry is the temptation for undocumented immigrants to avoid seeking medical care, for fear of being discovered and deported. Such delays in seeking care can result in these patients presenting with significant and expensive medical issues.
So what are the options for Congress and what is the likely fate of these DACA recipients whose lives have been placed in limbo? Proposals introduced to date include:
- The Bridge Act, which effectively extends the present DACA program by 3 years.
- Recognizing America’s Children Act, which would allow people who meet DACA eligibility criteria to apply for conditional permanent residence with a path toward citizenship.
- The American Hope Act and updated DREAM Act, both of which propose broader eligibility criteria and faster pathways to citizenship.4
There is great hope that some definitive action can be employed by Congress, as most legislators on both sides of the aisle have expressed some support for at least one of the proposed policies (although that certainly does not guarantee sufficient votes to pass). There also is support from many Americans, given that most DACA recipients have been productive members of society, and most Americans believe that DACA recipients should not be held accountable “for the sins of their parents.”4
It appears that the dismantling of DACA would be quite unsettling and certainly would affect some areas of the country more severely than others. Regardless of political stance, everyone can agree that Congress needs to do something, as the ambiguity and uncertainty caused by a million undocumented immigrants living and working in the United States cannot be ignored or indefinitely deferred. Any of the above options that offer a pathway to citizenship would be welcomed by most Americans. Having Dreamers in limbo is bad for everyone; the time to act is now.
Dr. Scheurer is a hospitalist and chief quality officer at the Medical University of South Carolina in Charleston. She is physician editor of The Hospitalist. Email her at scheured@musc.edu.
References
1. http://www.npr.org/2017/09/05/548754723/5-things-you-should-know-about-daca
2. https://www.forbes.com/sites/brucejapsen/2017/09/05/how-trumps-move-to-end-daca-worsens-the-doctor-shortage/#5143320d5b06
3. http://www.chicagomag.com/city-life/September-2017/DACA-Stritch-Medical-School/
4. http://www.nejm.org/doi/full/10.1056/NEJMp1711416?query=TOC
President Trump recently announced his decision to officially end the Deferred Action for Childhood Arrivals program, also known as DACA. The program has been controversial since its inception, almost as controversial as the decision to end it. What impact has DACA had on the medical community, including hospitalists, and what are the implications of ending it?
DACA is a program started in 2012 by an executive action under the Obama administration. The program currently protects approximately 800,000 undocumented immigrants in the United States from being deported. All DACA recipients were brought to this country illegally as children. When the DACA program began, in order to enroll, recipients had to prove that they had arrived to here before age 16, and that they had been living in the United States continuously since 2007. Once enrolled, the protections they receive from the program include the ability to legally work and to go to school, as well as obtain a social security number and driver’s license. These protections are then afforded for renewable 2-year periods of time.1
When Trump was elected, the controversy over continuing the DACA program accelerated. Understandably, the volume of applications rose substantially, with some estimating ~8,000 renewal requests being filed each week since the election. As such, many estimate the number of illegal immigrants affected by DACA has reached almost 1 million.1
One of the reasons the Trump administration feels compelled to dismantle the program is they contend that DACA is unconstitutional, as it was established purely by executive order. In the meantime, Trump is urging Congress to replace DACA with some type of equivalent legislation. According to his staffers, the dismantling of DACA means:
- No new applications will be accepted.
- All existing permits will be honored until they expire.
- All applications in process will continue to be processed.
They contend that no current DACA recipients will be affected before March 2018. Unfortunately for the Trump administration, this has been a very unpopular move, as two-thirds of Americans support allowing the Dreamers to stay in the United States.1
Impact on health care
The concern for the medical industry is that a “dismantling” of DACA could exacerbate an already existing physician shortage in the United States. For example, the Association of American Medical Colleges estimates the physician shortage will rise as the population ages and medical access increases; they currently estimate a physician shortage of approximately 40,000-104,000 by 2030.
But objectively evaluating the impact of the DACA program on the medical industry is difficult. We do know that most of the DACA recipients arrived from Mexico, El Salvador, Guatemala, and Honduras, as well as from Asia (primarily South Korea and the Philippines). We also know they reside in every state, with the largest numbers in California (222,795), Texas (124,300), New York (41,970), Illinois (42,376), and Florida (32,795). Most appear to be using DACA to work and to go to school; in a recent survey, 91% were employed, and 45% were enrolled in school.1
Pertaining specifically to medical school, during the 2016-2017 school year, there were 113 DACA applicants to U.S. medical schools, 65 of which were accepted and enrolled. The AAMC expects the 2017-2018 enrollment to be even higher. Almost half of medical school enrollees attend Loyola University Chicago, Maywood, Ill.; this year alone, Loyola Stritch Medical School enrolled 32 DACA medical students. This is because, in 2013, Loyola was the first medical school nationwide to openly accept students with DACA status. They did this by creating a mechanism for DACA medical students to get student loans.
One of the biggest challenges for DACA students is paying for school, as they are not eligible for federal student loans. To remove this barrier, Loyola created a loan program through the Illinois Finance Authority, which offers interest-free loans to DACA students if they commit to paying back the principal and working after medical school for 4 years in an underserved area in Illinois. It is clear that no medical school in the country will feel the effects of the DACA dismantling more than will Loyola.3
Another unintended issue that the dismantling of DACA can have on the medical industry is the temptation for undocumented immigrants to avoid seeking medical care, for fear of being discovered and deported. Such delays in seeking care can result in these patients presenting with significant and expensive medical issues.
So what are the options for Congress and what is the likely fate of these DACA recipients whose lives have been placed in limbo? Proposals introduced to date include:
- The Bridge Act, which effectively extends the present DACA program by 3 years.
- Recognizing America’s Children Act, which would allow people who meet DACA eligibility criteria to apply for conditional permanent residence with a path toward citizenship.
- The American Hope Act and updated DREAM Act, both of which propose broader eligibility criteria and faster pathways to citizenship.4
There is great hope that some definitive action can be employed by Congress, as most legislators on both sides of the aisle have expressed some support for at least one of the proposed policies (although that certainly does not guarantee sufficient votes to pass). There also is support from many Americans, given that most DACA recipients have been productive members of society, and most Americans believe that DACA recipients should not be held accountable “for the sins of their parents.”4
It appears that the dismantling of DACA would be quite unsettling and certainly would affect some areas of the country more severely than others. Regardless of political stance, everyone can agree that Congress needs to do something, as the ambiguity and uncertainty caused by a million undocumented immigrants living and working in the United States cannot be ignored or indefinitely deferred. Any of the above options that offer a pathway to citizenship would be welcomed by most Americans. Having Dreamers in limbo is bad for everyone; the time to act is now.
Dr. Scheurer is a hospitalist and chief quality officer at the Medical University of South Carolina in Charleston. She is physician editor of The Hospitalist. Email her at scheured@musc.edu.
References
1. http://www.npr.org/2017/09/05/548754723/5-things-you-should-know-about-daca
2. https://www.forbes.com/sites/brucejapsen/2017/09/05/how-trumps-move-to-end-daca-worsens-the-doctor-shortage/#5143320d5b06
3. http://www.chicagomag.com/city-life/September-2017/DACA-Stritch-Medical-School/
4. http://www.nejm.org/doi/full/10.1056/NEJMp1711416?query=TOC
Amyloid imaging changed management for 80% of patients with uncertain dementia diagnosis
BOSTON – Amyloid imaging with the PET agent florbetaben changed the clinical management of 80% of dementia patients with a complicated or uncertain presentation, Mathieu Ceccaldi, MD, reported at the Clinical Trials on Alzheimer’s Disease conference.
The French real-world study also found that 51% of the patients had a medication change after their amyloid imaging study, said Dr. Ceccaldi, a neurologist at the Timone Hospital in Marseille, France.
“In daily practice, we are sometimes faced with complex presentations and diagnostic uncertainty in patients who have early onset dementia, atypical nonamnestic dementia, unusual behavioral symptoms, or an unexpected rate of progression,” he said. “Amyloid imaging can help resolve those issues.”
The results echo – and even exceed – those returned in an interim analysis of the large U.S.-based Imaging Dementia–Evidence for Amyloid Scanning study. The IDEAS study is examining how amyloid imaging with the PET agent florbetapir may change clinical management of dementia patients. According to data presented at last summer’s Alzheimer’s Association International Conference, knowledge of patients’ brain amyloid status changed clinical management in 68% of cases.
In France, as in the United States, amyloid imaging is not routinely available outside of clinical research programs. French patients normally undergo a lumbar puncture (LP) to obtain amyloid biomarkers. However, if an LP isn’t feasible because of the patient’s clinical condition, it’s attempted and fails, the patient refuses, or the results are unclear, then imaging may be employed.
Dr. Ceccaldi’s study comprised 205 such patients seen in any of 18 memory clinics for dementia of uncertain etiology. The study evaluated how often amyloid PET imaging with florbetaben changed the patient’s diagnosis or management and how often it contributed to improving diagnostic uncertainty.
The patients were a mean of 71 years old, with a mean Mini-Mental State Exam score of 22. An LP had been performed in 42%, but those results were either ambiguous or inconsistent with the patient’s clinical presentation. Other patients (37%) refused the procedure, and the rest had a medical contraindication to LP or had a failed procedure.
The most common diagnosis at baseline was Alzheimer’s dementia (72%), which included typical and atypical sporadic AD, young-onset AD, and rapidly progressing AD. In 16% of the cohort, the diagnosis was non-Alzheimer’s dementia, including frontotemporal dementia, primary progressive aphasia, Lewy body dementia, corticobasal degeneration, semantic dementia, and Parkinson’s disease dementia. The diagnosis was mixed dementia in 8% and nonneurodegenerative dementia in the remainder – a catchall that included vascular dementia, psychiatric disorders, and other forms of dementia.
Imaging determined that 73 patients were amyloid negative and that 132 patients were amyloid positive. These results changed diagnosis in 67% of cases overall, in 58% of amyloid-positive patients, and in 84% of amyloid-negative patients.
In the absence of cerebrospinal fluid data, florbetaben imaging significantly improved diagnostic confidence in 81% of the entire cohort (167 patients). Before imaging, clinicians rated fewer than 5% of their diagnoses as very highly confident; this rose to nearly 100% after imaging. Similarly, before imaging, about 40% of clinicians said they had weak confidence in their initial diagnoses; this dropped to fewer than 5% after imaging.
Of the 67% with a changed diagnosis (137 patients), 76 were amyloid positive, and 61 were amyloid negative. Positive scans reclassified 18 patients as having AD; negative scans removed an AD diagnosis for 38 patients.
AD was the most commonly altered diagnosis, dropping from 72% to 62% of the entire cohort. The proportion of those with non-AD dementia increased from 16% before imaging to 18% after. Mixed dementias decreased from 8% to 5%, and the number diagnosed with nonneurodegenerative dementias increased from 5% to 17%.
In particular, Dr. Ceccaldi noted, the number of patients with potentially treatable nonneurodegenerative dementia rose from 10 to 35. These included revised diagnoses for those with psychiatric disorders (from 3 patients before imaging to 11 patients after), vascular dementias (from 2 to 8 patients), and other treatable causes of dementia (from 5 to 16 patients).
All of these altered diagnoses changed management in 80% of both positive and negative patients. Among these changes were the addition of a new medication (50% of amyloid-positive patients, 18% of amyloid-negative patients), the withdrawal of a medication (15% of amyloid-negative cases), additional testing (5% of amyloid-positive cases, 20% of amyloid-negative cases), and referral to another specialist (5% of amyloid-positive patients, 20% of amyloid-negative patients).
“Our results highlight the significant utility of amyloid PET for patients with complex dementia presentations in the context of the existing work-up,” Dr. Ceccaldi said.
He reported financial relationships with a number of pharmaceutical companies, including Piramal, which developed and manufactures florbetaben.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
BOSTON – Amyloid imaging with the PET agent florbetaben changed the clinical management of 80% of dementia patients with a complicated or uncertain presentation, Mathieu Ceccaldi, MD, reported at the Clinical Trials on Alzheimer’s Disease conference.
The French real-world study also found that 51% of the patients had a medication change after their amyloid imaging study, said Dr. Ceccaldi, a neurologist at the Timone Hospital in Marseille, France.
“In daily practice, we are sometimes faced with complex presentations and diagnostic uncertainty in patients who have early onset dementia, atypical nonamnestic dementia, unusual behavioral symptoms, or an unexpected rate of progression,” he said. “Amyloid imaging can help resolve those issues.”
The results echo – and even exceed – those returned in an interim analysis of the large U.S.-based Imaging Dementia–Evidence for Amyloid Scanning study. The IDEAS study is examining how amyloid imaging with the PET agent florbetapir may change clinical management of dementia patients. According to data presented at last summer’s Alzheimer’s Association International Conference, knowledge of patients’ brain amyloid status changed clinical management in 68% of cases.
In France, as in the United States, amyloid imaging is not routinely available outside of clinical research programs. French patients normally undergo a lumbar puncture (LP) to obtain amyloid biomarkers. However, if an LP isn’t feasible because of the patient’s clinical condition, it’s attempted and fails, the patient refuses, or the results are unclear, then imaging may be employed.
Dr. Ceccaldi’s study comprised 205 such patients seen in any of 18 memory clinics for dementia of uncertain etiology. The study evaluated how often amyloid PET imaging with florbetaben changed the patient’s diagnosis or management and how often it contributed to improving diagnostic uncertainty.
The patients were a mean of 71 years old, with a mean Mini-Mental State Exam score of 22. An LP had been performed in 42%, but those results were either ambiguous or inconsistent with the patient’s clinical presentation. Other patients (37%) refused the procedure, and the rest had a medical contraindication to LP or had a failed procedure.
The most common diagnosis at baseline was Alzheimer’s dementia (72%), which included typical and atypical sporadic AD, young-onset AD, and rapidly progressing AD. In 16% of the cohort, the diagnosis was non-Alzheimer’s dementia, including frontotemporal dementia, primary progressive aphasia, Lewy body dementia, corticobasal degeneration, semantic dementia, and Parkinson’s disease dementia. The diagnosis was mixed dementia in 8% and nonneurodegenerative dementia in the remainder – a catchall that included vascular dementia, psychiatric disorders, and other forms of dementia.
Imaging determined that 73 patients were amyloid negative and that 132 patients were amyloid positive. These results changed diagnosis in 67% of cases overall, in 58% of amyloid-positive patients, and in 84% of amyloid-negative patients.
In the absence of cerebrospinal fluid data, florbetaben imaging significantly improved diagnostic confidence in 81% of the entire cohort (167 patients). Before imaging, clinicians rated fewer than 5% of their diagnoses as very highly confident; this rose to nearly 100% after imaging. Similarly, before imaging, about 40% of clinicians said they had weak confidence in their initial diagnoses; this dropped to fewer than 5% after imaging.
Of the 67% with a changed diagnosis (137 patients), 76 were amyloid positive, and 61 were amyloid negative. Positive scans reclassified 18 patients as having AD; negative scans removed an AD diagnosis for 38 patients.
AD was the most commonly altered diagnosis, dropping from 72% to 62% of the entire cohort. The proportion of those with non-AD dementia increased from 16% before imaging to 18% after. Mixed dementias decreased from 8% to 5%, and the number diagnosed with nonneurodegenerative dementias increased from 5% to 17%.
In particular, Dr. Ceccaldi noted, the number of patients with potentially treatable nonneurodegenerative dementia rose from 10 to 35. These included revised diagnoses for those with psychiatric disorders (from 3 patients before imaging to 11 patients after), vascular dementias (from 2 to 8 patients), and other treatable causes of dementia (from 5 to 16 patients).
All of these altered diagnoses changed management in 80% of both positive and negative patients. Among these changes were the addition of a new medication (50% of amyloid-positive patients, 18% of amyloid-negative patients), the withdrawal of a medication (15% of amyloid-negative cases), additional testing (5% of amyloid-positive cases, 20% of amyloid-negative cases), and referral to another specialist (5% of amyloid-positive patients, 20% of amyloid-negative patients).
“Our results highlight the significant utility of amyloid PET for patients with complex dementia presentations in the context of the existing work-up,” Dr. Ceccaldi said.
He reported financial relationships with a number of pharmaceutical companies, including Piramal, which developed and manufactures florbetaben.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
BOSTON – Amyloid imaging with the PET agent florbetaben changed the clinical management of 80% of dementia patients with a complicated or uncertain presentation, Mathieu Ceccaldi, MD, reported at the Clinical Trials on Alzheimer’s Disease conference.
The French real-world study also found that 51% of the patients had a medication change after their amyloid imaging study, said Dr. Ceccaldi, a neurologist at the Timone Hospital in Marseille, France.
“In daily practice, we are sometimes faced with complex presentations and diagnostic uncertainty in patients who have early onset dementia, atypical nonamnestic dementia, unusual behavioral symptoms, or an unexpected rate of progression,” he said. “Amyloid imaging can help resolve those issues.”
The results echo – and even exceed – those returned in an interim analysis of the large U.S.-based Imaging Dementia–Evidence for Amyloid Scanning study. The IDEAS study is examining how amyloid imaging with the PET agent florbetapir may change clinical management of dementia patients. According to data presented at last summer’s Alzheimer’s Association International Conference, knowledge of patients’ brain amyloid status changed clinical management in 68% of cases.
In France, as in the United States, amyloid imaging is not routinely available outside of clinical research programs. French patients normally undergo a lumbar puncture (LP) to obtain amyloid biomarkers. However, if an LP isn’t feasible because of the patient’s clinical condition, it’s attempted and fails, the patient refuses, or the results are unclear, then imaging may be employed.
Dr. Ceccaldi’s study comprised 205 such patients seen in any of 18 memory clinics for dementia of uncertain etiology. The study evaluated how often amyloid PET imaging with florbetaben changed the patient’s diagnosis or management and how often it contributed to improving diagnostic uncertainty.
The patients were a mean of 71 years old, with a mean Mini-Mental State Exam score of 22. An LP had been performed in 42%, but those results were either ambiguous or inconsistent with the patient’s clinical presentation. Other patients (37%) refused the procedure, and the rest had a medical contraindication to LP or had a failed procedure.
The most common diagnosis at baseline was Alzheimer’s dementia (72%), which included typical and atypical sporadic AD, young-onset AD, and rapidly progressing AD. In 16% of the cohort, the diagnosis was non-Alzheimer’s dementia, including frontotemporal dementia, primary progressive aphasia, Lewy body dementia, corticobasal degeneration, semantic dementia, and Parkinson’s disease dementia. The diagnosis was mixed dementia in 8% and nonneurodegenerative dementia in the remainder – a catchall that included vascular dementia, psychiatric disorders, and other forms of dementia.
Imaging determined that 73 patients were amyloid negative and that 132 patients were amyloid positive. These results changed diagnosis in 67% of cases overall, in 58% of amyloid-positive patients, and in 84% of amyloid-negative patients.
In the absence of cerebrospinal fluid data, florbetaben imaging significantly improved diagnostic confidence in 81% of the entire cohort (167 patients). Before imaging, clinicians rated fewer than 5% of their diagnoses as very highly confident; this rose to nearly 100% after imaging. Similarly, before imaging, about 40% of clinicians said they had weak confidence in their initial diagnoses; this dropped to fewer than 5% after imaging.
Of the 67% with a changed diagnosis (137 patients), 76 were amyloid positive, and 61 were amyloid negative. Positive scans reclassified 18 patients as having AD; negative scans removed an AD diagnosis for 38 patients.
AD was the most commonly altered diagnosis, dropping from 72% to 62% of the entire cohort. The proportion of those with non-AD dementia increased from 16% before imaging to 18% after. Mixed dementias decreased from 8% to 5%, and the number diagnosed with nonneurodegenerative dementias increased from 5% to 17%.
In particular, Dr. Ceccaldi noted, the number of patients with potentially treatable nonneurodegenerative dementia rose from 10 to 35. These included revised diagnoses for those with psychiatric disorders (from 3 patients before imaging to 11 patients after), vascular dementias (from 2 to 8 patients), and other treatable causes of dementia (from 5 to 16 patients).
All of these altered diagnoses changed management in 80% of both positive and negative patients. Among these changes were the addition of a new medication (50% of amyloid-positive patients, 18% of amyloid-negative patients), the withdrawal of a medication (15% of amyloid-negative cases), additional testing (5% of amyloid-positive cases, 20% of amyloid-negative cases), and referral to another specialist (5% of amyloid-positive patients, 20% of amyloid-negative patients).
“Our results highlight the significant utility of amyloid PET for patients with complex dementia presentations in the context of the existing work-up,” Dr. Ceccaldi said.
He reported financial relationships with a number of pharmaceutical companies, including Piramal, which developed and manufactures florbetaben.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT CTAD
Key clinical point:
Major finding: A majority of patients (80%) experienced a change in management, including drugs added or withdrawn, or referral to another specialist.
Data source: A naturalistic, clinic-based study comprising 205 patients.
Disclosures: Dr. Ceccaldi reported financial relationships with several pharmaceutical companies, including Piramal, which developed and manufactures florbetaben.
Renal dosing of non–vitamin K antagonist oral anticoagulants in atrial fibrillation is important in preventing thrombotic and bleeding complications
Clinical question: Does renal underdosing and overdosing of non–vitamin K antagonist oral anticoagulants (NOACs) impact the risk of thrombotic and bleeding complications?
Background: All of the NOACs have at least partial renal clearance, but compliance with Food and Drug Administration–labeled renal dosing recommendations is inconsistent. This study examines the risk of adverse thrombotic and bleeding events in patients with improper anticoagulant dosing.
Study design: Retrospective cohort study.
Setting: United States (OptumLabs data warehouse, a database of over 100 million patients hospitalized in the United States in the last 20 years).
Synopsis: With use of data from the OptumLabs data warehouse of privately insured and Medicare Advantage enrollees, 14,865 patients with nonvalvular atrial fibrillation who were started on NOACs (apixaban, dabigatran, or rivaroxaban) were identified. Creatinine values within the year before treatment were used to calculate an estimated glomerular filtration rate (eGFR).
Of patients qualifying for renal dose reduction, 43% received the standard dosing (overdose). Of patients not qualifying for renal dose reduction, 13% received a reduced dose (underdose). The overdosed group had a higher rate of bleeding events, compared with controls (hazard ratio, 2.19; 95% CI, 1.07-4.46). The underdosed group had a higher rate of stroke (HR, 4.87; 95% CI, 1.30-18.26).
Bottom line: Excessive dosing of NOACs in patients with renal insufficiency is common and is associated with bleeding.Citation: Yao X, Shah ND, Sangaralingham LR, Gersh BJ, and Noseworthy PA. Non–vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. JACC. 2017;69(23):2779-90.
Dr. Portnoy is hospitalist and instructor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
Clinical question: Does renal underdosing and overdosing of non–vitamin K antagonist oral anticoagulants (NOACs) impact the risk of thrombotic and bleeding complications?
Background: All of the NOACs have at least partial renal clearance, but compliance with Food and Drug Administration–labeled renal dosing recommendations is inconsistent. This study examines the risk of adverse thrombotic and bleeding events in patients with improper anticoagulant dosing.
Study design: Retrospective cohort study.
Setting: United States (OptumLabs data warehouse, a database of over 100 million patients hospitalized in the United States in the last 20 years).
Synopsis: With use of data from the OptumLabs data warehouse of privately insured and Medicare Advantage enrollees, 14,865 patients with nonvalvular atrial fibrillation who were started on NOACs (apixaban, dabigatran, or rivaroxaban) were identified. Creatinine values within the year before treatment were used to calculate an estimated glomerular filtration rate (eGFR).
Of patients qualifying for renal dose reduction, 43% received the standard dosing (overdose). Of patients not qualifying for renal dose reduction, 13% received a reduced dose (underdose). The overdosed group had a higher rate of bleeding events, compared with controls (hazard ratio, 2.19; 95% CI, 1.07-4.46). The underdosed group had a higher rate of stroke (HR, 4.87; 95% CI, 1.30-18.26).
Bottom line: Excessive dosing of NOACs in patients with renal insufficiency is common and is associated with bleeding.Citation: Yao X, Shah ND, Sangaralingham LR, Gersh BJ, and Noseworthy PA. Non–vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. JACC. 2017;69(23):2779-90.
Dr. Portnoy is hospitalist and instructor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
Clinical question: Does renal underdosing and overdosing of non–vitamin K antagonist oral anticoagulants (NOACs) impact the risk of thrombotic and bleeding complications?
Background: All of the NOACs have at least partial renal clearance, but compliance with Food and Drug Administration–labeled renal dosing recommendations is inconsistent. This study examines the risk of adverse thrombotic and bleeding events in patients with improper anticoagulant dosing.
Study design: Retrospective cohort study.
Setting: United States (OptumLabs data warehouse, a database of over 100 million patients hospitalized in the United States in the last 20 years).
Synopsis: With use of data from the OptumLabs data warehouse of privately insured and Medicare Advantage enrollees, 14,865 patients with nonvalvular atrial fibrillation who were started on NOACs (apixaban, dabigatran, or rivaroxaban) were identified. Creatinine values within the year before treatment were used to calculate an estimated glomerular filtration rate (eGFR).
Of patients qualifying for renal dose reduction, 43% received the standard dosing (overdose). Of patients not qualifying for renal dose reduction, 13% received a reduced dose (underdose). The overdosed group had a higher rate of bleeding events, compared with controls (hazard ratio, 2.19; 95% CI, 1.07-4.46). The underdosed group had a higher rate of stroke (HR, 4.87; 95% CI, 1.30-18.26).
Bottom line: Excessive dosing of NOACs in patients with renal insufficiency is common and is associated with bleeding.Citation: Yao X, Shah ND, Sangaralingham LR, Gersh BJ, and Noseworthy PA. Non–vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. JACC. 2017;69(23):2779-90.
Dr. Portnoy is hospitalist and instructor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
CABG and PCI with drug-eluting stents for left main coronary disease have superior outcomes to medical therapy alone
Clinical question: Does coronary artery bypass grafting (CABG) have superior mortality outcomes to percutaneous coronary intervention (PCI) for left main coronary disease, and how do these interventions compare with medical therapy alone?
Background: Optimal therapy for left main coronary disease is a highly researched topic with CABG having been standard therapy of choice for several decades. However, most studies have not included data comparing CABG to newer drug-eluting stent (DES) generations and no studies have directly compared PCI with DES to medical therapy alone (MTA).
Study design: Meta-analysis.
Setting: Largely European acute care hospitals as well as some VA hospitals.
Synopsis: With PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a review of PubMed and Cochrane databases was conducted, yielding eight RCTs, including a total of 4,850 patients. Six of the RCTs compared CABG with DES, while two compared CABG with MTA. Network meta-analysis was used to compare DES with MTA. At 5 years there were no differences in all-cause mortality between CABG and DES groups (RR, 0.94; 95% CI, 0.68-1.32), though both groups had lower mortality than MTA (RR, 0.21; 95% CI, 0.09-0.47 for CABG vs. MTA and RR, 0.20; 95% CI, 0.08-0.46 for DES vs MTA).
PCI did have higher risk of revascularization at 5 years (RR, 1.68; 95% CI, 1.36-2.08) and lower risk of stroke at 1 year (RR, 0.21; 95% CI, 0.07-0.63), compared with CABG, suggesting younger patients might prefer CABG to avoid revascularization, and older patients may prefer PCI to avoid postprocedural morbidity.
Bottom line: For patients with left main disease, CABG and PCI with DES appear equally effective with regards to prevention of all-cause mortality and both are superior to MTA.
Citation: Shah R, Morsy MS, Weiman DS, and Vetrovec GW. Meta-analysis comparing coronary artery bypass grafting to drug-eluting stents. Am J Cardiol. 2017;120:63-8.
Dr. Portnoy is hospitalist and instructor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
Clinical question: Does coronary artery bypass grafting (CABG) have superior mortality outcomes to percutaneous coronary intervention (PCI) for left main coronary disease, and how do these interventions compare with medical therapy alone?
Background: Optimal therapy for left main coronary disease is a highly researched topic with CABG having been standard therapy of choice for several decades. However, most studies have not included data comparing CABG to newer drug-eluting stent (DES) generations and no studies have directly compared PCI with DES to medical therapy alone (MTA).
Study design: Meta-analysis.
Setting: Largely European acute care hospitals as well as some VA hospitals.
Synopsis: With PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a review of PubMed and Cochrane databases was conducted, yielding eight RCTs, including a total of 4,850 patients. Six of the RCTs compared CABG with DES, while two compared CABG with MTA. Network meta-analysis was used to compare DES with MTA. At 5 years there were no differences in all-cause mortality between CABG and DES groups (RR, 0.94; 95% CI, 0.68-1.32), though both groups had lower mortality than MTA (RR, 0.21; 95% CI, 0.09-0.47 for CABG vs. MTA and RR, 0.20; 95% CI, 0.08-0.46 for DES vs MTA).
PCI did have higher risk of revascularization at 5 years (RR, 1.68; 95% CI, 1.36-2.08) and lower risk of stroke at 1 year (RR, 0.21; 95% CI, 0.07-0.63), compared with CABG, suggesting younger patients might prefer CABG to avoid revascularization, and older patients may prefer PCI to avoid postprocedural morbidity.
Bottom line: For patients with left main disease, CABG and PCI with DES appear equally effective with regards to prevention of all-cause mortality and both are superior to MTA.
Citation: Shah R, Morsy MS, Weiman DS, and Vetrovec GW. Meta-analysis comparing coronary artery bypass grafting to drug-eluting stents. Am J Cardiol. 2017;120:63-8.
Dr. Portnoy is hospitalist and instructor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
Clinical question: Does coronary artery bypass grafting (CABG) have superior mortality outcomes to percutaneous coronary intervention (PCI) for left main coronary disease, and how do these interventions compare with medical therapy alone?
Background: Optimal therapy for left main coronary disease is a highly researched topic with CABG having been standard therapy of choice for several decades. However, most studies have not included data comparing CABG to newer drug-eluting stent (DES) generations and no studies have directly compared PCI with DES to medical therapy alone (MTA).
Study design: Meta-analysis.
Setting: Largely European acute care hospitals as well as some VA hospitals.
Synopsis: With PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a review of PubMed and Cochrane databases was conducted, yielding eight RCTs, including a total of 4,850 patients. Six of the RCTs compared CABG with DES, while two compared CABG with MTA. Network meta-analysis was used to compare DES with MTA. At 5 years there were no differences in all-cause mortality between CABG and DES groups (RR, 0.94; 95% CI, 0.68-1.32), though both groups had lower mortality than MTA (RR, 0.21; 95% CI, 0.09-0.47 for CABG vs. MTA and RR, 0.20; 95% CI, 0.08-0.46 for DES vs MTA).
PCI did have higher risk of revascularization at 5 years (RR, 1.68; 95% CI, 1.36-2.08) and lower risk of stroke at 1 year (RR, 0.21; 95% CI, 0.07-0.63), compared with CABG, suggesting younger patients might prefer CABG to avoid revascularization, and older patients may prefer PCI to avoid postprocedural morbidity.
Bottom line: For patients with left main disease, CABG and PCI with DES appear equally effective with regards to prevention of all-cause mortality and both are superior to MTA.
Citation: Shah R, Morsy MS, Weiman DS, and Vetrovec GW. Meta-analysis comparing coronary artery bypass grafting to drug-eluting stents. Am J Cardiol. 2017;120:63-8.
Dr. Portnoy is hospitalist and instructor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
Antiplatelet therapy can be continued through surgery without increased risk of reintervention for bleeding
Clinical question: Does continuing antiplatelet therapy through noncardiac surgery increase the risk of postoperative blood transfusion or surgical reintervention for bleeding?
Background: Many prior studies have analyzed the risks and benefits of holding versus continuing antiplatelet therapy in the perioperative setting, but heterogeneity in outcome reporting has limited the ability to compare and contrast studies.
Study design: Meta-analysis.
Setting: Both domestic and international studies were included in the meta-analysis.
Synopsis: With a MEDLINE search, 37 studies with over 30,000 patients total were identified and included in the meta-analysis. Studies compared outcomes of transfusion and surgical reintervention for bleeding in patients receiving noncardiac surgery. Patients were either on no antiplatelet therapy, single therapy, or dual-antiplatelet therapy (DAPT). Relative risk of transfusion escalated in proportion to the amount of antiplatelet therapy; there was a 14% increased risk (95% confidence interval, 1.03-1.26) with aspirin over control and a 33% (95% CI, 1.15-1.55) increased risk with DAPT over control.
Risk of surgical reintervention for bleeding, however, was not increased above control whether on aspirin (relative risk, 0.96; 95% CI, 0.76-1.22), clopidogrel (RR, 1.84; 95% CI, 0.87-3.87), or DAPT (RR, 1.51; (95% CI, 0.92-2.49).
Bottom line: In noncardiac surgery, continuing aspirin or DAPT perioperatively increases the need for transfusion, but not the need for surgical reintervention for bleeding.
Citation: Columbo JA, Lambour AJ, Sundling RA, et. al. A meta-analysis of the impact of aspirin, clopidogrel, and dual-antiplatelet therapy on bleeding complications in noncardiac surgery. Ann Surg. 2017;20(20):1-9.
Dr. Portnoy is hospitalist and instructor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
Clinical question: Does continuing antiplatelet therapy through noncardiac surgery increase the risk of postoperative blood transfusion or surgical reintervention for bleeding?
Background: Many prior studies have analyzed the risks and benefits of holding versus continuing antiplatelet therapy in the perioperative setting, but heterogeneity in outcome reporting has limited the ability to compare and contrast studies.
Study design: Meta-analysis.
Setting: Both domestic and international studies were included in the meta-analysis.
Synopsis: With a MEDLINE search, 37 studies with over 30,000 patients total were identified and included in the meta-analysis. Studies compared outcomes of transfusion and surgical reintervention for bleeding in patients receiving noncardiac surgery. Patients were either on no antiplatelet therapy, single therapy, or dual-antiplatelet therapy (DAPT). Relative risk of transfusion escalated in proportion to the amount of antiplatelet therapy; there was a 14% increased risk (95% confidence interval, 1.03-1.26) with aspirin over control and a 33% (95% CI, 1.15-1.55) increased risk with DAPT over control.
Risk of surgical reintervention for bleeding, however, was not increased above control whether on aspirin (relative risk, 0.96; 95% CI, 0.76-1.22), clopidogrel (RR, 1.84; 95% CI, 0.87-3.87), or DAPT (RR, 1.51; (95% CI, 0.92-2.49).
Bottom line: In noncardiac surgery, continuing aspirin or DAPT perioperatively increases the need for transfusion, but not the need for surgical reintervention for bleeding.
Citation: Columbo JA, Lambour AJ, Sundling RA, et. al. A meta-analysis of the impact of aspirin, clopidogrel, and dual-antiplatelet therapy on bleeding complications in noncardiac surgery. Ann Surg. 2017;20(20):1-9.
Dr. Portnoy is hospitalist and instructor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
Clinical question: Does continuing antiplatelet therapy through noncardiac surgery increase the risk of postoperative blood transfusion or surgical reintervention for bleeding?
Background: Many prior studies have analyzed the risks and benefits of holding versus continuing antiplatelet therapy in the perioperative setting, but heterogeneity in outcome reporting has limited the ability to compare and contrast studies.
Study design: Meta-analysis.
Setting: Both domestic and international studies were included in the meta-analysis.
Synopsis: With a MEDLINE search, 37 studies with over 30,000 patients total were identified and included in the meta-analysis. Studies compared outcomes of transfusion and surgical reintervention for bleeding in patients receiving noncardiac surgery. Patients were either on no antiplatelet therapy, single therapy, or dual-antiplatelet therapy (DAPT). Relative risk of transfusion escalated in proportion to the amount of antiplatelet therapy; there was a 14% increased risk (95% confidence interval, 1.03-1.26) with aspirin over control and a 33% (95% CI, 1.15-1.55) increased risk with DAPT over control.
Risk of surgical reintervention for bleeding, however, was not increased above control whether on aspirin (relative risk, 0.96; 95% CI, 0.76-1.22), clopidogrel (RR, 1.84; 95% CI, 0.87-3.87), or DAPT (RR, 1.51; (95% CI, 0.92-2.49).
Bottom line: In noncardiac surgery, continuing aspirin or DAPT perioperatively increases the need for transfusion, but not the need for surgical reintervention for bleeding.
Citation: Columbo JA, Lambour AJ, Sundling RA, et. al. A meta-analysis of the impact of aspirin, clopidogrel, and dual-antiplatelet therapy on bleeding complications in noncardiac surgery. Ann Surg. 2017;20(20):1-9.
Dr. Portnoy is hospitalist and instructor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
NIH Researchers Find Lymph Drainage in Brain
In 1816, an Italian anatomist reported finding lymphatic vessels on the surface of the brain—but the information went nowhere. However, 200 years later, NIH researchers believe they have confirmed that report with evidence that the human brain may drain some waste out through the body’s lymphatic “sewer system.”
Two animal studies in 2015 had showed evidence of a lymphatic system in the brain. Building on that, the researchers used magnetic resonance imaging to scan the brains of 5 healthy volunteers who had been injected with gadobutrol, typically used to visualize brain blood vessels. The dye molecules are small enough to leak out of blood vessels in the dura but too big to pass through the blood-brain barrier.
At first, the researchers say, the dura lit up brightly, but no lymphatic vessels were visible. When they turned the scanner differently, the blood vessels “disappeared,” and they saw that the dura also had smaller but almost equally bright spots and lines—possibly lymph vessels. The researchers’ results suggested that the dye leaked from the blood vessels and flowed through the dura into neighboring lymphatic vessels. “We literally watched people’s brains drain fluid into these vessels,” said Daniel Reich, MD, PhD, senior author of the study.
The VA/DoD Chronic Effects of Neurotrauma Consortium: An Overview at Year 1
The researchers tested the findings by doing another round of scans, using a dye made of larger molecules. This time they saw blood vessels but no lymph vessels, no matter how the scanner was turned.
The researchers also found evidence for blood and lymph vessels in autopsied human brain tissue. “For years, we knew how fluid entered the brain. Now we may finally see that, like other organs in the body, brain fluid can drain out through the lymphatic system,” said Dr. Reich.
“These results could fundamentally change the way we think about how the brain and immune system interrelate,” said Walter Koroshetz, MD, the director of the National Institute of Neurological Disorders and Stroke.
In 1816, an Italian anatomist reported finding lymphatic vessels on the surface of the brain—but the information went nowhere. However, 200 years later, NIH researchers believe they have confirmed that report with evidence that the human brain may drain some waste out through the body’s lymphatic “sewer system.”
Two animal studies in 2015 had showed evidence of a lymphatic system in the brain. Building on that, the researchers used magnetic resonance imaging to scan the brains of 5 healthy volunteers who had been injected with gadobutrol, typically used to visualize brain blood vessels. The dye molecules are small enough to leak out of blood vessels in the dura but too big to pass through the blood-brain barrier.
At first, the researchers say, the dura lit up brightly, but no lymphatic vessels were visible. When they turned the scanner differently, the blood vessels “disappeared,” and they saw that the dura also had smaller but almost equally bright spots and lines—possibly lymph vessels. The researchers’ results suggested that the dye leaked from the blood vessels and flowed through the dura into neighboring lymphatic vessels. “We literally watched people’s brains drain fluid into these vessels,” said Daniel Reich, MD, PhD, senior author of the study.
The VA/DoD Chronic Effects of Neurotrauma Consortium: An Overview at Year 1
The researchers tested the findings by doing another round of scans, using a dye made of larger molecules. This time they saw blood vessels but no lymph vessels, no matter how the scanner was turned.
The researchers also found evidence for blood and lymph vessels in autopsied human brain tissue. “For years, we knew how fluid entered the brain. Now we may finally see that, like other organs in the body, brain fluid can drain out through the lymphatic system,” said Dr. Reich.
“These results could fundamentally change the way we think about how the brain and immune system interrelate,” said Walter Koroshetz, MD, the director of the National Institute of Neurological Disorders and Stroke.
In 1816, an Italian anatomist reported finding lymphatic vessels on the surface of the brain—but the information went nowhere. However, 200 years later, NIH researchers believe they have confirmed that report with evidence that the human brain may drain some waste out through the body’s lymphatic “sewer system.”
Two animal studies in 2015 had showed evidence of a lymphatic system in the brain. Building on that, the researchers used magnetic resonance imaging to scan the brains of 5 healthy volunteers who had been injected with gadobutrol, typically used to visualize brain blood vessels. The dye molecules are small enough to leak out of blood vessels in the dura but too big to pass through the blood-brain barrier.
At first, the researchers say, the dura lit up brightly, but no lymphatic vessels were visible. When they turned the scanner differently, the blood vessels “disappeared,” and they saw that the dura also had smaller but almost equally bright spots and lines—possibly lymph vessels. The researchers’ results suggested that the dye leaked from the blood vessels and flowed through the dura into neighboring lymphatic vessels. “We literally watched people’s brains drain fluid into these vessels,” said Daniel Reich, MD, PhD, senior author of the study.
The VA/DoD Chronic Effects of Neurotrauma Consortium: An Overview at Year 1
The researchers tested the findings by doing another round of scans, using a dye made of larger molecules. This time they saw blood vessels but no lymph vessels, no matter how the scanner was turned.
The researchers also found evidence for blood and lymph vessels in autopsied human brain tissue. “For years, we knew how fluid entered the brain. Now we may finally see that, like other organs in the body, brain fluid can drain out through the lymphatic system,” said Dr. Reich.
“These results could fundamentally change the way we think about how the brain and immune system interrelate,” said Walter Koroshetz, MD, the director of the National Institute of Neurological Disorders and Stroke.
Warfarin may decrease risk of cancer
New research suggests warfarin use may reduce the risk of cancer among people over the age of 50.
An observational study of more than 1 million people in Norway revealed that individuals who took warfarin had a lower incidence of cancers overall, as well as certain types of cancers, than people who did not take warfarin.
James B. Lorens, PhD, of the University of Bergen in Norway, and his colleagues reported these findings in JAMA Internal Medicine.
The researchers analyzed data from the Norwegian National Registry, the Norwegian Prescription Database, and the Cancer Registry of Norway.
This included data for all individuals ages 52 to 82 who were living in Norway from January 1, 2006, through December 31, 2012, (n=1,256,725).
The researchers looked for cancer diagnoses in this group during the 7-year observation period. They compared the incidence of any new cancer (including certain cancer types) between warfarin users and non-users.
People were considered warfarin users if they had taken at least 6 months of a warfarin prescription and at least 2 years had elapsed from their first prescription to any cancer diagnosis.
Most study subjects were non-users (92.6%, n=1,163,783), but 7.4% (n=92,942) were warfarin users.
The researchers noted that warfarin users were older than non-users, with mean ages of 70.2 and 63.9, respectively. Warfarin users were also more likely to be male (61.7%; n=57,370) and non-users female (52.7%; n=613,803).
The incidence of cancer was 10.6% (n=132,687) in the entire study cohort, 9.4% (n=8754) among warfarin users, and 10.6% (n=123,933) among non-users. The most common cancer types were prostate, lung, colon, and breast.
The researchers found a significantly lower age- and sex-adjusted incidence rate ratio (IRR) for all cancers among warfarin users than nonusers. The IRR was 0.84 (95% CI, 0.82-0.86).
The IRR was also significantly lower among users than non-users for 3 of the 4 most common cancers. The IRR was 0.69 (95% CI, 0.65-0.72) for prostate cancer, 0.80 (95% CI, 0.75-0.86) for lung cancer, and 0.90 (95% CI, 0.82-1.00) for female breast cancer.
The researchers said there was no significant difference between users and non-users for colon cancer. The IRR was 0.99 (95% CI, 0.93-1.06).
The team also assessed hematologic malignancies. The IRRs, for users compared to non-users, were as follows:
- 0.99 (95% CI, 0.89-1.11) for leukemia
- 0.89 (95% CI, 0.71-1.11) for chronic lymphocytic leukemia
- 0.70 (95% CI, 0.51-0.98) for acute myeloid leukemia
- 0.92 (95% CI, 0.82-1.04) for lymphoma
- 0.66 (95% CI, 0.34-1.26) for Hodgkin lymphoma
- 0.92 (95% CI, 0.81-1.04) for non-Hodgkin lymphoma.
The researchers noted that they did not collect information on other medications subjects were taking or risk factors that might influence cancer development, and new cancers may have been cancer recurrences.
In addition, the team said the prescription of warfarin may be a marker for other healthcare factors that lead to cancer prevention.
Still, the researchers said warfarin appeared to be associated with reduced cancer risk in this study.
They therefore believe this finding could have implications for choosing anticoagulants, although additional research is needed. 
New research suggests warfarin use may reduce the risk of cancer among people over the age of 50.
An observational study of more than 1 million people in Norway revealed that individuals who took warfarin had a lower incidence of cancers overall, as well as certain types of cancers, than people who did not take warfarin.
James B. Lorens, PhD, of the University of Bergen in Norway, and his colleagues reported these findings in JAMA Internal Medicine.
The researchers analyzed data from the Norwegian National Registry, the Norwegian Prescription Database, and the Cancer Registry of Norway.
This included data for all individuals ages 52 to 82 who were living in Norway from January 1, 2006, through December 31, 2012, (n=1,256,725).
The researchers looked for cancer diagnoses in this group during the 7-year observation period. They compared the incidence of any new cancer (including certain cancer types) between warfarin users and non-users.
People were considered warfarin users if they had taken at least 6 months of a warfarin prescription and at least 2 years had elapsed from their first prescription to any cancer diagnosis.
Most study subjects were non-users (92.6%, n=1,163,783), but 7.4% (n=92,942) were warfarin users.
The researchers noted that warfarin users were older than non-users, with mean ages of 70.2 and 63.9, respectively. Warfarin users were also more likely to be male (61.7%; n=57,370) and non-users female (52.7%; n=613,803).
The incidence of cancer was 10.6% (n=132,687) in the entire study cohort, 9.4% (n=8754) among warfarin users, and 10.6% (n=123,933) among non-users. The most common cancer types were prostate, lung, colon, and breast.
The researchers found a significantly lower age- and sex-adjusted incidence rate ratio (IRR) for all cancers among warfarin users than nonusers. The IRR was 0.84 (95% CI, 0.82-0.86).
The IRR was also significantly lower among users than non-users for 3 of the 4 most common cancers. The IRR was 0.69 (95% CI, 0.65-0.72) for prostate cancer, 0.80 (95% CI, 0.75-0.86) for lung cancer, and 0.90 (95% CI, 0.82-1.00) for female breast cancer.
The researchers said there was no significant difference between users and non-users for colon cancer. The IRR was 0.99 (95% CI, 0.93-1.06).
The team also assessed hematologic malignancies. The IRRs, for users compared to non-users, were as follows:
- 0.99 (95% CI, 0.89-1.11) for leukemia
- 0.89 (95% CI, 0.71-1.11) for chronic lymphocytic leukemia
- 0.70 (95% CI, 0.51-0.98) for acute myeloid leukemia
- 0.92 (95% CI, 0.82-1.04) for lymphoma
- 0.66 (95% CI, 0.34-1.26) for Hodgkin lymphoma
- 0.92 (95% CI, 0.81-1.04) for non-Hodgkin lymphoma.
The researchers noted that they did not collect information on other medications subjects were taking or risk factors that might influence cancer development, and new cancers may have been cancer recurrences.
In addition, the team said the prescription of warfarin may be a marker for other healthcare factors that lead to cancer prevention.
Still, the researchers said warfarin appeared to be associated with reduced cancer risk in this study.
They therefore believe this finding could have implications for choosing anticoagulants, although additional research is needed.
New research suggests warfarin use may reduce the risk of cancer among people over the age of 50.
An observational study of more than 1 million people in Norway revealed that individuals who took warfarin had a lower incidence of cancers overall, as well as certain types of cancers, than people who did not take warfarin.
James B. Lorens, PhD, of the University of Bergen in Norway, and his colleagues reported these findings in JAMA Internal Medicine.
The researchers analyzed data from the Norwegian National Registry, the Norwegian Prescription Database, and the Cancer Registry of Norway.
This included data for all individuals ages 52 to 82 who were living in Norway from January 1, 2006, through December 31, 2012, (n=1,256,725).
The researchers looked for cancer diagnoses in this group during the 7-year observation period. They compared the incidence of any new cancer (including certain cancer types) between warfarin users and non-users.
People were considered warfarin users if they had taken at least 6 months of a warfarin prescription and at least 2 years had elapsed from their first prescription to any cancer diagnosis.
Most study subjects were non-users (92.6%, n=1,163,783), but 7.4% (n=92,942) were warfarin users.
The researchers noted that warfarin users were older than non-users, with mean ages of 70.2 and 63.9, respectively. Warfarin users were also more likely to be male (61.7%; n=57,370) and non-users female (52.7%; n=613,803).
The incidence of cancer was 10.6% (n=132,687) in the entire study cohort, 9.4% (n=8754) among warfarin users, and 10.6% (n=123,933) among non-users. The most common cancer types were prostate, lung, colon, and breast.
The researchers found a significantly lower age- and sex-adjusted incidence rate ratio (IRR) for all cancers among warfarin users than nonusers. The IRR was 0.84 (95% CI, 0.82-0.86).
The IRR was also significantly lower among users than non-users for 3 of the 4 most common cancers. The IRR was 0.69 (95% CI, 0.65-0.72) for prostate cancer, 0.80 (95% CI, 0.75-0.86) for lung cancer, and 0.90 (95% CI, 0.82-1.00) for female breast cancer.
The researchers said there was no significant difference between users and non-users for colon cancer. The IRR was 0.99 (95% CI, 0.93-1.06).
The team also assessed hematologic malignancies. The IRRs, for users compared to non-users, were as follows:
- 0.99 (95% CI, 0.89-1.11) for leukemia
- 0.89 (95% CI, 0.71-1.11) for chronic lymphocytic leukemia
- 0.70 (95% CI, 0.51-0.98) for acute myeloid leukemia
- 0.92 (95% CI, 0.82-1.04) for lymphoma
- 0.66 (95% CI, 0.34-1.26) for Hodgkin lymphoma
- 0.92 (95% CI, 0.81-1.04) for non-Hodgkin lymphoma.
The researchers noted that they did not collect information on other medications subjects were taking or risk factors that might influence cancer development, and new cancers may have been cancer recurrences.
In addition, the team said the prescription of warfarin may be a marker for other healthcare factors that lead to cancer prevention.
Still, the researchers said warfarin appeared to be associated with reduced cancer risk in this study.
They therefore believe this finding could have implications for choosing anticoagulants, although additional research is needed.
FDA grants drug orphan designation for treatment of malaria
The US Food and Drug Administration (FDA) has granted orphan drug designation to artemisone, a product candidate for the treatment of malaria.
Artemisone is a synthetic derivative of the antimalarial drug artemisinin, which “has been optimized for potency, stability, and safety,” according to Artemis Therapeutics, Inc., the company developing artemisone.
The company said phase 2 trial data suggest artemisone is effective against Plasmodium falciparum malaria.
Ninety-five patients were enrolled in the trial, and they received a 2-day or 3-day course of artemisone. Patients also received a second antimalarial drug on the final day of artemisone treatment (in compliance with recommendations from the World Health Organization).
At 28 days, the cure rates were 100% in both the 2-day and 3-day course groups. However, parasite clearance time was 25% faster with the 2-day course.
Artemis Therapeutics, Inc. has not yet released safety data from this trial.
Phase 1 data suggested artemisone was well tolerated by healthy subjects. There were no serious adverse events in the trial and no clinically relevant changes in laboratory and vital parameters, according to researchers.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to artemisone, a product candidate for the treatment of malaria.
Artemisone is a synthetic derivative of the antimalarial drug artemisinin, which “has been optimized for potency, stability, and safety,” according to Artemis Therapeutics, Inc., the company developing artemisone.
The company said phase 2 trial data suggest artemisone is effective against Plasmodium falciparum malaria.
Ninety-five patients were enrolled in the trial, and they received a 2-day or 3-day course of artemisone. Patients also received a second antimalarial drug on the final day of artemisone treatment (in compliance with recommendations from the World Health Organization).
At 28 days, the cure rates were 100% in both the 2-day and 3-day course groups. However, parasite clearance time was 25% faster with the 2-day course.
Artemis Therapeutics, Inc. has not yet released safety data from this trial.
Phase 1 data suggested artemisone was well tolerated by healthy subjects. There were no serious adverse events in the trial and no clinically relevant changes in laboratory and vital parameters, according to researchers.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to artemisone, a product candidate for the treatment of malaria.
Artemisone is a synthetic derivative of the antimalarial drug artemisinin, which “has been optimized for potency, stability, and safety,” according to Artemis Therapeutics, Inc., the company developing artemisone.
The company said phase 2 trial data suggest artemisone is effective against Plasmodium falciparum malaria.
Ninety-five patients were enrolled in the trial, and they received a 2-day or 3-day course of artemisone. Patients also received a second antimalarial drug on the final day of artemisone treatment (in compliance with recommendations from the World Health Organization).
At 28 days, the cure rates were 100% in both the 2-day and 3-day course groups. However, parasite clearance time was 25% faster with the 2-day course.
Artemis Therapeutics, Inc. has not yet released safety data from this trial.
Phase 1 data suggested artemisone was well tolerated by healthy subjects. There were no serious adverse events in the trial and no clinically relevant changes in laboratory and vital parameters, according to researchers.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.