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Precision medicine poised to improve IPF management
SAN ANTONIO – Although the research is in early phases, (IPF), Justin Oldham, MD, said in a plenary presentation at the annual meeting of the American College of Chest Physicians.
“IPF is a highly variable disease,” said Dr. Oldham, director of the Interstitial Lung Disease Program at the University of California, Davis. “Some patients have more rapidly progressive disease than others, and so using precision medicine to identify those who are most likely to have that progressive phenotype is very important, not only for risk stratification but also treatment considerations.”
Some retrospective studies suggest certain subgroups of patients with IPF are genetically predisposed to respond to certain types of therapy, he said in a video interview. Now, researchers are in the process of submitting grants to better study that in a prospective fashion.
Dr. Oldham reported receiving funding from the National Institutes of Health, the American Lung Association, and the ACCP, as well as consulting and speaker fees from Genentech and Boehringer Ingelheim.
SAN ANTONIO – Although the research is in early phases, (IPF), Justin Oldham, MD, said in a plenary presentation at the annual meeting of the American College of Chest Physicians.
“IPF is a highly variable disease,” said Dr. Oldham, director of the Interstitial Lung Disease Program at the University of California, Davis. “Some patients have more rapidly progressive disease than others, and so using precision medicine to identify those who are most likely to have that progressive phenotype is very important, not only for risk stratification but also treatment considerations.”
Some retrospective studies suggest certain subgroups of patients with IPF are genetically predisposed to respond to certain types of therapy, he said in a video interview. Now, researchers are in the process of submitting grants to better study that in a prospective fashion.
Dr. Oldham reported receiving funding from the National Institutes of Health, the American Lung Association, and the ACCP, as well as consulting and speaker fees from Genentech and Boehringer Ingelheim.
SAN ANTONIO – Although the research is in early phases, (IPF), Justin Oldham, MD, said in a plenary presentation at the annual meeting of the American College of Chest Physicians.
“IPF is a highly variable disease,” said Dr. Oldham, director of the Interstitial Lung Disease Program at the University of California, Davis. “Some patients have more rapidly progressive disease than others, and so using precision medicine to identify those who are most likely to have that progressive phenotype is very important, not only for risk stratification but also treatment considerations.”
Some retrospective studies suggest certain subgroups of patients with IPF are genetically predisposed to respond to certain types of therapy, he said in a video interview. Now, researchers are in the process of submitting grants to better study that in a prospective fashion.
Dr. Oldham reported receiving funding from the National Institutes of Health, the American Lung Association, and the ACCP, as well as consulting and speaker fees from Genentech and Boehringer Ingelheim.
EXPERT ANALYSIS FROM CHEST 2018
Low-FODMAP diet improves fecal incontinence in patients with loose stool
PHILADELPHIA – A low fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet was associated with improvement in fecal incontinence in 64.6% of patients who received dietary training, according to recent research presented at the American College of Gastroenterology annual meeting.
“In this case series, the low-FODMAP diet improved fecal incontinence in two-thirds of patients with fecal incontinence and loose stools,” Stacy Menees, MD, MS, assistant professor at the University of Michigan in Ann Arbor, said in her presentation.
Dr. Menees and her colleagues performed a retrospective chart review of 65 patients in the Michigan Bowel Control clinic with fecal incontinence (FI) “without alarming features” who were recommended a low FODMAP diet and received formal dietary teaching between August 2012 and December 2017. Patients received the teaching from a Michigan Medicine gastrointestinal dietitian. The dietitians performed a semi-quantitative analysis of patient response, including complete response, Dr. Menees said.
If we are going to help people with fecal incontinence, the key is to concentrate on the area of their stool consistency,” she explained. “We know that foods high in fermentable oligo-, di-, and monosaccharides and polyols, otherwise known as FODMAPS, can cause diarrhea and urgency.”
These FODMAP foods can include fruits with fructose exceeding glucose, fructan-containing vegetables, wheat-based products, sorbitol- and lactose-containing foods, and raffinose-containing foods, Dr. Menees said.
“We know from observations in data and research from the Monash University and our own group that patients with irritable bowel syndrome who are on a [low-]FODMAP diet [get relief from] their symptoms,” she added.
Most of the patients were female, and most were white. The mean age was 61.9 years, and mean body mass index was 26.7 kg/m2. Among the patients, 27.7% had irritable bowel syndrome (IBS), 9.2% had inflammatory bowel disease (IBD), 16.9% had diabetes mellitus, and 20% had a prior cholecystectomy.
With regard to reports of loose stool and FI, 46.1% of patients said they had loose stool daily with a mean of 2.8 loose bowel movements daily. More than half of the patients (60.5%) reported FI daily; 37.8% said they experienced weekly FI, and 4.6% reported monthly FI. The number of patients reporting FI was higher than 100% because some patients reported in the chart that they had FI daily or weekly, Dr. Menees said.
FI improvement was reported by 64.6% of patients, with 88.1% of responders having a greater than 50% reduction in FI and 35.7% of patients experiencing complete resolution of FI. There were no serious adverse events in the study, Dr. Menees noted.
“The three patients with postinfection IBS and fecal incontinence had no response to a low-FODMAP diet,” she said. “Our dietitians noted that onion and garlic were the triggers that were most often identified.”
Limitations include the retrospective chart review design and small number of patients, which may overestimate or underestimate the study results, and the fact that the study was done at a tertiary care center, Dr. Menees said.
“We are nearing the completion of a confirmatory, prospective, pilot randomized clinical trial to confirm the efficacy of a low-FODMAP diet in patients who suffer from fecal incontinence and loose stools,” she concluded.
Dr. Menees reports being a consultant for Synergy.
SOURCE: Menees SB et al. ACG 2018. Presentation 9.
PHILADELPHIA – A low fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet was associated with improvement in fecal incontinence in 64.6% of patients who received dietary training, according to recent research presented at the American College of Gastroenterology annual meeting.
“In this case series, the low-FODMAP diet improved fecal incontinence in two-thirds of patients with fecal incontinence and loose stools,” Stacy Menees, MD, MS, assistant professor at the University of Michigan in Ann Arbor, said in her presentation.
Dr. Menees and her colleagues performed a retrospective chart review of 65 patients in the Michigan Bowel Control clinic with fecal incontinence (FI) “without alarming features” who were recommended a low FODMAP diet and received formal dietary teaching between August 2012 and December 2017. Patients received the teaching from a Michigan Medicine gastrointestinal dietitian. The dietitians performed a semi-quantitative analysis of patient response, including complete response, Dr. Menees said.
If we are going to help people with fecal incontinence, the key is to concentrate on the area of their stool consistency,” she explained. “We know that foods high in fermentable oligo-, di-, and monosaccharides and polyols, otherwise known as FODMAPS, can cause diarrhea and urgency.”
These FODMAP foods can include fruits with fructose exceeding glucose, fructan-containing vegetables, wheat-based products, sorbitol- and lactose-containing foods, and raffinose-containing foods, Dr. Menees said.
“We know from observations in data and research from the Monash University and our own group that patients with irritable bowel syndrome who are on a [low-]FODMAP diet [get relief from] their symptoms,” she added.
Most of the patients were female, and most were white. The mean age was 61.9 years, and mean body mass index was 26.7 kg/m2. Among the patients, 27.7% had irritable bowel syndrome (IBS), 9.2% had inflammatory bowel disease (IBD), 16.9% had diabetes mellitus, and 20% had a prior cholecystectomy.
With regard to reports of loose stool and FI, 46.1% of patients said they had loose stool daily with a mean of 2.8 loose bowel movements daily. More than half of the patients (60.5%) reported FI daily; 37.8% said they experienced weekly FI, and 4.6% reported monthly FI. The number of patients reporting FI was higher than 100% because some patients reported in the chart that they had FI daily or weekly, Dr. Menees said.
FI improvement was reported by 64.6% of patients, with 88.1% of responders having a greater than 50% reduction in FI and 35.7% of patients experiencing complete resolution of FI. There were no serious adverse events in the study, Dr. Menees noted.
“The three patients with postinfection IBS and fecal incontinence had no response to a low-FODMAP diet,” she said. “Our dietitians noted that onion and garlic were the triggers that were most often identified.”
Limitations include the retrospective chart review design and small number of patients, which may overestimate or underestimate the study results, and the fact that the study was done at a tertiary care center, Dr. Menees said.
“We are nearing the completion of a confirmatory, prospective, pilot randomized clinical trial to confirm the efficacy of a low-FODMAP diet in patients who suffer from fecal incontinence and loose stools,” she concluded.
Dr. Menees reports being a consultant for Synergy.
SOURCE: Menees SB et al. ACG 2018. Presentation 9.
PHILADELPHIA – A low fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet was associated with improvement in fecal incontinence in 64.6% of patients who received dietary training, according to recent research presented at the American College of Gastroenterology annual meeting.
“In this case series, the low-FODMAP diet improved fecal incontinence in two-thirds of patients with fecal incontinence and loose stools,” Stacy Menees, MD, MS, assistant professor at the University of Michigan in Ann Arbor, said in her presentation.
Dr. Menees and her colleagues performed a retrospective chart review of 65 patients in the Michigan Bowel Control clinic with fecal incontinence (FI) “without alarming features” who were recommended a low FODMAP diet and received formal dietary teaching between August 2012 and December 2017. Patients received the teaching from a Michigan Medicine gastrointestinal dietitian. The dietitians performed a semi-quantitative analysis of patient response, including complete response, Dr. Menees said.
If we are going to help people with fecal incontinence, the key is to concentrate on the area of their stool consistency,” she explained. “We know that foods high in fermentable oligo-, di-, and monosaccharides and polyols, otherwise known as FODMAPS, can cause diarrhea and urgency.”
These FODMAP foods can include fruits with fructose exceeding glucose, fructan-containing vegetables, wheat-based products, sorbitol- and lactose-containing foods, and raffinose-containing foods, Dr. Menees said.
“We know from observations in data and research from the Monash University and our own group that patients with irritable bowel syndrome who are on a [low-]FODMAP diet [get relief from] their symptoms,” she added.
Most of the patients were female, and most were white. The mean age was 61.9 years, and mean body mass index was 26.7 kg/m2. Among the patients, 27.7% had irritable bowel syndrome (IBS), 9.2% had inflammatory bowel disease (IBD), 16.9% had diabetes mellitus, and 20% had a prior cholecystectomy.
With regard to reports of loose stool and FI, 46.1% of patients said they had loose stool daily with a mean of 2.8 loose bowel movements daily. More than half of the patients (60.5%) reported FI daily; 37.8% said they experienced weekly FI, and 4.6% reported monthly FI. The number of patients reporting FI was higher than 100% because some patients reported in the chart that they had FI daily or weekly, Dr. Menees said.
FI improvement was reported by 64.6% of patients, with 88.1% of responders having a greater than 50% reduction in FI and 35.7% of patients experiencing complete resolution of FI. There were no serious adverse events in the study, Dr. Menees noted.
“The three patients with postinfection IBS and fecal incontinence had no response to a low-FODMAP diet,” she said. “Our dietitians noted that onion and garlic were the triggers that were most often identified.”
Limitations include the retrospective chart review design and small number of patients, which may overestimate or underestimate the study results, and the fact that the study was done at a tertiary care center, Dr. Menees said.
“We are nearing the completion of a confirmatory, prospective, pilot randomized clinical trial to confirm the efficacy of a low-FODMAP diet in patients who suffer from fecal incontinence and loose stools,” she concluded.
Dr. Menees reports being a consultant for Synergy.
SOURCE: Menees SB et al. ACG 2018. Presentation 9.
REPORTING FROM ACG 2018
Key clinical point: Patients who underwent formal dietary teaching for a fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet showed associated improvements in fecal incontinence.
Major finding: Among patients with fecal incontinence, 64.6% experienced improvement; of these, 88.1% of responders had a greater than 50% reduction in fecal incontinence and 35.7% experienced complete resolution of fecal incontinence.
Study details: A retrospective chart review of 65 patients with fecal incontinence who received formal dietary teaching at the Michigan Bowel Control clinic.
Disclosures: Dr. Menees reports being a consultant for Synergy.
Source: Menees SB et al. ACG 2018. Presentation 9.
Guidelines outline patient-centered approach to type 2 diabetes
issued jointly by the American Diabetes Association and the European Association for the Study of Diabetes.
The 2018 ADA/EASD Consensus Report also addresses clinical inertia and notes that medication adherence and persistence should be facilitated. All patients should be offered ongoing self-management education and support, Melanie J. Davies, MD, one of the two cochairs of the report-writing committee, said during a press conference at the annual meeting of the European Association for the Study of Diabetes.
The report also addresses preferred choices for glucose-lowering medications, largely based on recent findings of large-scale cardiovascular outcomes trials. There also is specific guidance on how to manage hyperglycemia in patients with atherosclerotic cardiovascular disease, chronic kidney disease, and heart failure.
“The consensus report focuses on not what an individual’s glycemic target should be or how to individualize goals but really addresses how each patient can achieve their individualized glycemic target,” Dr. Davies said.
Dr. Davies, who is professor of diabetes medicine at the University of Leicester (England) and an honorary consultant diabetologist at the University Hospitals of Leicester NHS Trust also said that the report looked at taking patient factors and preferences into account but also considered “the ever-increasing complexity around the availability of glucose-lowering agents.”
Practical guide to managing patients
The consensus report, which was simultaneously published in the official journals of the ADA (Diabetes Care 2018 Sep; dci180033) and the EASD (Diabetologia. 2018 Sep. doi: 10.1007/s00125-018-4729-5) to coincide with its presentation at the EASD meeting, is much more visual and aims to be more of a practical aid than was the previous position statement from 2015 (Diabetologia. 2015 Mar;58:429-42; Diabetes Care 2015 Jan;38[1]:140-9), on which it was based, Dr. Davies said.
The patient has been placed firmly at the center of the decision cycle, she observed, which starts with assessment of patient characteristics and consideration of their lifestyle, comorbidities, and clinical parameters. Specific factors that may affect the choice of treatment, such as the individualized glycosylated hemoglobin (HbA1c) target or side effect profiles of medications, are included, as is working together with the patient to make, continually monitor, and reevaluate a shared decision plan.
In terms of lifestyle, one of the consensus recommendations is that “an individualized program of medical nutritional therapy should be offered to all patients,” with the more specific recommendation that those who are overweight or obese be advised of the health benefits of weight loss and be encouraged to participate in dietary modifications that may include food substitution. Increasing activity is also highly recommended based on long-established evidence that this can help reduce HbA1c level. Recommendations for when to consider bariatric surgery for weight management also are included.
Clarity on treating comorbidities
Previously discussed in June at the ADA’s annual meeting, the consensus report has undergone fine-tuning and multiple revisions. The report was based on a comprehensive and systematic review of the diabetes literature available from 2014 through February 2018. Overall, more than 6,000 randomized trials, reviews, and meta-analyses were considered and distilled down to a list of around 500 papers that were then thoroughly reviewed by an expert panel.
“I guarantee, there’s never been a paper that’s been more peer reviewed,” said John Buse, MD, PhD, the other cochair of the report’s writing committee. A total of 35 named individuals reviewed and provided more than 800 detailed comments among them, which were considered and reflected in the final version.
Dr. Buse is the Verne S. Caviness Distinguished Professor, chief of the division of endocrinology, and director of the diabetes center at the University of North Carolina at Chapel Hill.
“There’s much more clarity now,” added Dr. Davies, referring to the changes made to how patients with comorbidities are managed. If somebody does have atherosclerotic cardiovascular disease or chronic kidney disease, there is now clear direction on which glucose-lowering therapy should be considered first, and what to do if the HbA1c remains above target.
For example, in patients who have established atherosclerotic cardiovascular disease, the recommendation is, after metformin, to choose either a glucagonlike peptide–1 (GLP-1) receptor agonist or a sodium-glucose cotransporter 2 (SGLT2) inhibitor with proven cardiovascular benefit.
If heart failure or chronic kidney disease coexist, then an SGLT2 inhibitor shown to reduce their progression should be favored, or if contraindicated or not preferred, a GLP-1 receptor agonist with proven cardiovascular benefit should be given.
The main action, pros and cons of interventions, and the various medications are shown in tables to clearly guide clinicians in the decision-making process, Dr. Buse said.
First-line management
The first line recommended glucose-lowering therapy for hyperglycemia in type 2 diabetes remains metformin, together with comprehensive lifestyle advice, Dr. Buse observed.
“A huge controversy in the [diabetes] community asks, ‘Is metformin the first-line therapy because it’s cheap and was the first oral agent studied and has a long history?’ or is it something that really is based on medical evidence?” Dr. Buse acknowledged. Although combinations of glucose-lowering drugs have been proposed upfront, “the evidence for that is largely from small studies, in limited numbers of sites, such that, for now, we generally recommend starting on a single-agent medication if lifestyle management is not enough to control glucose.”
If there is a need to intensify treatment as the patient’s HbA1c remains above their individualized target, then other drugs may be added to step up the treatment. The consensus report then looks at which drugs might be best to add, based on the need to avoid hypoglycemia, promote weight loss, and/or if cost or availability is a major issue.
If patients need the greater glucose-lowering effects of an injectable medication, a GLP-1 receptor agonist – not insulin – is recommended, Dr. Buse observed. However, for patients with extreme and symptomatic hyperglycemia, insulin is then recommended.
There also is guidance on when to consider oral therapies in conjunction with injectable therapies, with the consensus recommendation stating: Patients who are unable to maintain glycemic targets on basal insulin in combination with oral medication can have treatment intensified with GLP-1 receptor agonists, SGLT2 inhibitors, or prandial insulin.
The ADA perspective
William T. Cefalu, MD, chief scientific, medical and mission officer of the ADA observed that the “ADA fully endorses the ADA/EASD Consensus Report” and had already added a statement on the recommendations into its Standards of Medical Care in Diabetes – 2018 as part of the organization’s Living Standards Update. This was a change made last year to allow real-time updates of practice recommendations based on new and evolving evidence released in between the annual process of updating the Society’s Standards.
“Much, if not all, of these recommendations from this paper will be incorporated into our Standards,” said Dr. Cefalu. “We applaud the authors of the consensus paper; we think this was an outstanding group, and we really feel that this is a paradigm change in diabetes management,” he added. “Instead of relying on the [HbA1c] number in an algorithm, this puts the patient at the center; patient-related factors, patient preferences, adherence, compliance, and more importantly, the underlying disease state … this really is a comprehensive approach to management.”
The stratification of patients by cardiovascular disease, kidney disease, or heart failure is a particularly noteworthy, as is the advice on which agent to choose if weight management is an issue. Finally, there are the considerations of costs of therapy, and what to do if there is the risk of hypoglycemia. “The consensus recommendations and approach to glycemic management in adults with type 2 diabetes presented within the report reflects the current view of the ADA,” Dr. Cefalu confirmed.
The EASD perspective
“The EASD was again delighted to go into cooperation with our colleagues and friends at the ADA because is it is so important to bring out a consensus on where we need to go in this forest of glucose-lowering therapies,” said Chantal Mathieu, MD, PhD, vice-president of the EASD.
“The fact that this consensus paper puts the patient front and center, and makes that an integral part of glucose-lowering therapy, and also that lifestyle is being accentuated again, together with education in every patient is crucial,” Dr. Mathieu, who is professor of medicine at the Katholieke Universiteit Leuven (Belgium), and a coauthor of the report, added.
“At EASD, we also believe that it is very important to bring this consensus paper to life,” she added, which is part of her role as the chair of postgraduate education at the EASD. Two of the EASD’s main remits is to ensure that the results of research and education are brought to the diabetes community at large, she said.
In every figure in the paper there is a highlight to say, “please avoid clinical inertia, reassess and modify treatment if necessary, at least every 3-6 months,” Dr. Mathieu noted during the EASD congress.
David Matthews, MD, professor of diabetic medicine at the University of Oxford (England) and president-elect of the EASD, commented on the 2018 ADA/EASD Consensus Report after its presentation at the EASD meeting. “The reality is that you’ve got to think extremely hard with your patients about what the balances between risks and benefits are,” Dr. Matthews said. “We encourage you to do this, what you have here is a wonderful handbook to guide you in your decision making.”
Dr. Davies reported receiving personal fees and/or grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Intarcia Therapeutics/Servier, Janssen, Merck Sharp & Dohme, Mitsubishi Tanabi, Novo Nordisk, Sanofi, and Takeda.
Dr. Buse disclosed acting as a consultant to and/or receiving research support from Adocia, AstraZeneca, Eli Lilly, GI Dynamics, Intarcia Therapeutics, MannKind, NovaTarg, Neurimmune, Novo Nordisk, Senseonics, and vTv Therapeutics with fees paid to the University of North Carolina. He holds stock options in Mellitus Health, PhaseBio and Stability Health.
Dr. Mathieu disclosed relationships with (advisory boards, speakers bureaus, and/or research support) from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Hanmi Pharmaceuticals, Intrexon, Janssen Pharmaceuticals, MannKind, Medtronic, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, Sanofi, and UCB.
Dr. Cefalu had no disclosures and Dr. Matthews had no relevant conflicts of interest other than becoming the EASD president-elect during the meeting.
issued jointly by the American Diabetes Association and the European Association for the Study of Diabetes.
The 2018 ADA/EASD Consensus Report also addresses clinical inertia and notes that medication adherence and persistence should be facilitated. All patients should be offered ongoing self-management education and support, Melanie J. Davies, MD, one of the two cochairs of the report-writing committee, said during a press conference at the annual meeting of the European Association for the Study of Diabetes.
The report also addresses preferred choices for glucose-lowering medications, largely based on recent findings of large-scale cardiovascular outcomes trials. There also is specific guidance on how to manage hyperglycemia in patients with atherosclerotic cardiovascular disease, chronic kidney disease, and heart failure.
“The consensus report focuses on not what an individual’s glycemic target should be or how to individualize goals but really addresses how each patient can achieve their individualized glycemic target,” Dr. Davies said.
Dr. Davies, who is professor of diabetes medicine at the University of Leicester (England) and an honorary consultant diabetologist at the University Hospitals of Leicester NHS Trust also said that the report looked at taking patient factors and preferences into account but also considered “the ever-increasing complexity around the availability of glucose-lowering agents.”
Practical guide to managing patients
The consensus report, which was simultaneously published in the official journals of the ADA (Diabetes Care 2018 Sep; dci180033) and the EASD (Diabetologia. 2018 Sep. doi: 10.1007/s00125-018-4729-5) to coincide with its presentation at the EASD meeting, is much more visual and aims to be more of a practical aid than was the previous position statement from 2015 (Diabetologia. 2015 Mar;58:429-42; Diabetes Care 2015 Jan;38[1]:140-9), on which it was based, Dr. Davies said.
The patient has been placed firmly at the center of the decision cycle, she observed, which starts with assessment of patient characteristics and consideration of their lifestyle, comorbidities, and clinical parameters. Specific factors that may affect the choice of treatment, such as the individualized glycosylated hemoglobin (HbA1c) target or side effect profiles of medications, are included, as is working together with the patient to make, continually monitor, and reevaluate a shared decision plan.
In terms of lifestyle, one of the consensus recommendations is that “an individualized program of medical nutritional therapy should be offered to all patients,” with the more specific recommendation that those who are overweight or obese be advised of the health benefits of weight loss and be encouraged to participate in dietary modifications that may include food substitution. Increasing activity is also highly recommended based on long-established evidence that this can help reduce HbA1c level. Recommendations for when to consider bariatric surgery for weight management also are included.
Clarity on treating comorbidities
Previously discussed in June at the ADA’s annual meeting, the consensus report has undergone fine-tuning and multiple revisions. The report was based on a comprehensive and systematic review of the diabetes literature available from 2014 through February 2018. Overall, more than 6,000 randomized trials, reviews, and meta-analyses were considered and distilled down to a list of around 500 papers that were then thoroughly reviewed by an expert panel.
“I guarantee, there’s never been a paper that’s been more peer reviewed,” said John Buse, MD, PhD, the other cochair of the report’s writing committee. A total of 35 named individuals reviewed and provided more than 800 detailed comments among them, which were considered and reflected in the final version.
Dr. Buse is the Verne S. Caviness Distinguished Professor, chief of the division of endocrinology, and director of the diabetes center at the University of North Carolina at Chapel Hill.
“There’s much more clarity now,” added Dr. Davies, referring to the changes made to how patients with comorbidities are managed. If somebody does have atherosclerotic cardiovascular disease or chronic kidney disease, there is now clear direction on which glucose-lowering therapy should be considered first, and what to do if the HbA1c remains above target.
For example, in patients who have established atherosclerotic cardiovascular disease, the recommendation is, after metformin, to choose either a glucagonlike peptide–1 (GLP-1) receptor agonist or a sodium-glucose cotransporter 2 (SGLT2) inhibitor with proven cardiovascular benefit.
If heart failure or chronic kidney disease coexist, then an SGLT2 inhibitor shown to reduce their progression should be favored, or if contraindicated or not preferred, a GLP-1 receptor agonist with proven cardiovascular benefit should be given.
The main action, pros and cons of interventions, and the various medications are shown in tables to clearly guide clinicians in the decision-making process, Dr. Buse said.
First-line management
The first line recommended glucose-lowering therapy for hyperglycemia in type 2 diabetes remains metformin, together with comprehensive lifestyle advice, Dr. Buse observed.
“A huge controversy in the [diabetes] community asks, ‘Is metformin the first-line therapy because it’s cheap and was the first oral agent studied and has a long history?’ or is it something that really is based on medical evidence?” Dr. Buse acknowledged. Although combinations of glucose-lowering drugs have been proposed upfront, “the evidence for that is largely from small studies, in limited numbers of sites, such that, for now, we generally recommend starting on a single-agent medication if lifestyle management is not enough to control glucose.”
If there is a need to intensify treatment as the patient’s HbA1c remains above their individualized target, then other drugs may be added to step up the treatment. The consensus report then looks at which drugs might be best to add, based on the need to avoid hypoglycemia, promote weight loss, and/or if cost or availability is a major issue.
If patients need the greater glucose-lowering effects of an injectable medication, a GLP-1 receptor agonist – not insulin – is recommended, Dr. Buse observed. However, for patients with extreme and symptomatic hyperglycemia, insulin is then recommended.
There also is guidance on when to consider oral therapies in conjunction with injectable therapies, with the consensus recommendation stating: Patients who are unable to maintain glycemic targets on basal insulin in combination with oral medication can have treatment intensified with GLP-1 receptor agonists, SGLT2 inhibitors, or prandial insulin.
The ADA perspective
William T. Cefalu, MD, chief scientific, medical and mission officer of the ADA observed that the “ADA fully endorses the ADA/EASD Consensus Report” and had already added a statement on the recommendations into its Standards of Medical Care in Diabetes – 2018 as part of the organization’s Living Standards Update. This was a change made last year to allow real-time updates of practice recommendations based on new and evolving evidence released in between the annual process of updating the Society’s Standards.
“Much, if not all, of these recommendations from this paper will be incorporated into our Standards,” said Dr. Cefalu. “We applaud the authors of the consensus paper; we think this was an outstanding group, and we really feel that this is a paradigm change in diabetes management,” he added. “Instead of relying on the [HbA1c] number in an algorithm, this puts the patient at the center; patient-related factors, patient preferences, adherence, compliance, and more importantly, the underlying disease state … this really is a comprehensive approach to management.”
The stratification of patients by cardiovascular disease, kidney disease, or heart failure is a particularly noteworthy, as is the advice on which agent to choose if weight management is an issue. Finally, there are the considerations of costs of therapy, and what to do if there is the risk of hypoglycemia. “The consensus recommendations and approach to glycemic management in adults with type 2 diabetes presented within the report reflects the current view of the ADA,” Dr. Cefalu confirmed.
The EASD perspective
“The EASD was again delighted to go into cooperation with our colleagues and friends at the ADA because is it is so important to bring out a consensus on where we need to go in this forest of glucose-lowering therapies,” said Chantal Mathieu, MD, PhD, vice-president of the EASD.
“The fact that this consensus paper puts the patient front and center, and makes that an integral part of glucose-lowering therapy, and also that lifestyle is being accentuated again, together with education in every patient is crucial,” Dr. Mathieu, who is professor of medicine at the Katholieke Universiteit Leuven (Belgium), and a coauthor of the report, added.
“At EASD, we also believe that it is very important to bring this consensus paper to life,” she added, which is part of her role as the chair of postgraduate education at the EASD. Two of the EASD’s main remits is to ensure that the results of research and education are brought to the diabetes community at large, she said.
In every figure in the paper there is a highlight to say, “please avoid clinical inertia, reassess and modify treatment if necessary, at least every 3-6 months,” Dr. Mathieu noted during the EASD congress.
David Matthews, MD, professor of diabetic medicine at the University of Oxford (England) and president-elect of the EASD, commented on the 2018 ADA/EASD Consensus Report after its presentation at the EASD meeting. “The reality is that you’ve got to think extremely hard with your patients about what the balances between risks and benefits are,” Dr. Matthews said. “We encourage you to do this, what you have here is a wonderful handbook to guide you in your decision making.”
Dr. Davies reported receiving personal fees and/or grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Intarcia Therapeutics/Servier, Janssen, Merck Sharp & Dohme, Mitsubishi Tanabi, Novo Nordisk, Sanofi, and Takeda.
Dr. Buse disclosed acting as a consultant to and/or receiving research support from Adocia, AstraZeneca, Eli Lilly, GI Dynamics, Intarcia Therapeutics, MannKind, NovaTarg, Neurimmune, Novo Nordisk, Senseonics, and vTv Therapeutics with fees paid to the University of North Carolina. He holds stock options in Mellitus Health, PhaseBio and Stability Health.
Dr. Mathieu disclosed relationships with (advisory boards, speakers bureaus, and/or research support) from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Hanmi Pharmaceuticals, Intrexon, Janssen Pharmaceuticals, MannKind, Medtronic, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, Sanofi, and UCB.
Dr. Cefalu had no disclosures and Dr. Matthews had no relevant conflicts of interest other than becoming the EASD president-elect during the meeting.
issued jointly by the American Diabetes Association and the European Association for the Study of Diabetes.
The 2018 ADA/EASD Consensus Report also addresses clinical inertia and notes that medication adherence and persistence should be facilitated. All patients should be offered ongoing self-management education and support, Melanie J. Davies, MD, one of the two cochairs of the report-writing committee, said during a press conference at the annual meeting of the European Association for the Study of Diabetes.
The report also addresses preferred choices for glucose-lowering medications, largely based on recent findings of large-scale cardiovascular outcomes trials. There also is specific guidance on how to manage hyperglycemia in patients with atherosclerotic cardiovascular disease, chronic kidney disease, and heart failure.
“The consensus report focuses on not what an individual’s glycemic target should be or how to individualize goals but really addresses how each patient can achieve their individualized glycemic target,” Dr. Davies said.
Dr. Davies, who is professor of diabetes medicine at the University of Leicester (England) and an honorary consultant diabetologist at the University Hospitals of Leicester NHS Trust also said that the report looked at taking patient factors and preferences into account but also considered “the ever-increasing complexity around the availability of glucose-lowering agents.”
Practical guide to managing patients
The consensus report, which was simultaneously published in the official journals of the ADA (Diabetes Care 2018 Sep; dci180033) and the EASD (Diabetologia. 2018 Sep. doi: 10.1007/s00125-018-4729-5) to coincide with its presentation at the EASD meeting, is much more visual and aims to be more of a practical aid than was the previous position statement from 2015 (Diabetologia. 2015 Mar;58:429-42; Diabetes Care 2015 Jan;38[1]:140-9), on which it was based, Dr. Davies said.
The patient has been placed firmly at the center of the decision cycle, she observed, which starts with assessment of patient characteristics and consideration of their lifestyle, comorbidities, and clinical parameters. Specific factors that may affect the choice of treatment, such as the individualized glycosylated hemoglobin (HbA1c) target or side effect profiles of medications, are included, as is working together with the patient to make, continually monitor, and reevaluate a shared decision plan.
In terms of lifestyle, one of the consensus recommendations is that “an individualized program of medical nutritional therapy should be offered to all patients,” with the more specific recommendation that those who are overweight or obese be advised of the health benefits of weight loss and be encouraged to participate in dietary modifications that may include food substitution. Increasing activity is also highly recommended based on long-established evidence that this can help reduce HbA1c level. Recommendations for when to consider bariatric surgery for weight management also are included.
Clarity on treating comorbidities
Previously discussed in June at the ADA’s annual meeting, the consensus report has undergone fine-tuning and multiple revisions. The report was based on a comprehensive and systematic review of the diabetes literature available from 2014 through February 2018. Overall, more than 6,000 randomized trials, reviews, and meta-analyses were considered and distilled down to a list of around 500 papers that were then thoroughly reviewed by an expert panel.
“I guarantee, there’s never been a paper that’s been more peer reviewed,” said John Buse, MD, PhD, the other cochair of the report’s writing committee. A total of 35 named individuals reviewed and provided more than 800 detailed comments among them, which were considered and reflected in the final version.
Dr. Buse is the Verne S. Caviness Distinguished Professor, chief of the division of endocrinology, and director of the diabetes center at the University of North Carolina at Chapel Hill.
“There’s much more clarity now,” added Dr. Davies, referring to the changes made to how patients with comorbidities are managed. If somebody does have atherosclerotic cardiovascular disease or chronic kidney disease, there is now clear direction on which glucose-lowering therapy should be considered first, and what to do if the HbA1c remains above target.
For example, in patients who have established atherosclerotic cardiovascular disease, the recommendation is, after metformin, to choose either a glucagonlike peptide–1 (GLP-1) receptor agonist or a sodium-glucose cotransporter 2 (SGLT2) inhibitor with proven cardiovascular benefit.
If heart failure or chronic kidney disease coexist, then an SGLT2 inhibitor shown to reduce their progression should be favored, or if contraindicated or not preferred, a GLP-1 receptor agonist with proven cardiovascular benefit should be given.
The main action, pros and cons of interventions, and the various medications are shown in tables to clearly guide clinicians in the decision-making process, Dr. Buse said.
First-line management
The first line recommended glucose-lowering therapy for hyperglycemia in type 2 diabetes remains metformin, together with comprehensive lifestyle advice, Dr. Buse observed.
“A huge controversy in the [diabetes] community asks, ‘Is metformin the first-line therapy because it’s cheap and was the first oral agent studied and has a long history?’ or is it something that really is based on medical evidence?” Dr. Buse acknowledged. Although combinations of glucose-lowering drugs have been proposed upfront, “the evidence for that is largely from small studies, in limited numbers of sites, such that, for now, we generally recommend starting on a single-agent medication if lifestyle management is not enough to control glucose.”
If there is a need to intensify treatment as the patient’s HbA1c remains above their individualized target, then other drugs may be added to step up the treatment. The consensus report then looks at which drugs might be best to add, based on the need to avoid hypoglycemia, promote weight loss, and/or if cost or availability is a major issue.
If patients need the greater glucose-lowering effects of an injectable medication, a GLP-1 receptor agonist – not insulin – is recommended, Dr. Buse observed. However, for patients with extreme and symptomatic hyperglycemia, insulin is then recommended.
There also is guidance on when to consider oral therapies in conjunction with injectable therapies, with the consensus recommendation stating: Patients who are unable to maintain glycemic targets on basal insulin in combination with oral medication can have treatment intensified with GLP-1 receptor agonists, SGLT2 inhibitors, or prandial insulin.
The ADA perspective
William T. Cefalu, MD, chief scientific, medical and mission officer of the ADA observed that the “ADA fully endorses the ADA/EASD Consensus Report” and had already added a statement on the recommendations into its Standards of Medical Care in Diabetes – 2018 as part of the organization’s Living Standards Update. This was a change made last year to allow real-time updates of practice recommendations based on new and evolving evidence released in between the annual process of updating the Society’s Standards.
“Much, if not all, of these recommendations from this paper will be incorporated into our Standards,” said Dr. Cefalu. “We applaud the authors of the consensus paper; we think this was an outstanding group, and we really feel that this is a paradigm change in diabetes management,” he added. “Instead of relying on the [HbA1c] number in an algorithm, this puts the patient at the center; patient-related factors, patient preferences, adherence, compliance, and more importantly, the underlying disease state … this really is a comprehensive approach to management.”
The stratification of patients by cardiovascular disease, kidney disease, or heart failure is a particularly noteworthy, as is the advice on which agent to choose if weight management is an issue. Finally, there are the considerations of costs of therapy, and what to do if there is the risk of hypoglycemia. “The consensus recommendations and approach to glycemic management in adults with type 2 diabetes presented within the report reflects the current view of the ADA,” Dr. Cefalu confirmed.
The EASD perspective
“The EASD was again delighted to go into cooperation with our colleagues and friends at the ADA because is it is so important to bring out a consensus on where we need to go in this forest of glucose-lowering therapies,” said Chantal Mathieu, MD, PhD, vice-president of the EASD.
“The fact that this consensus paper puts the patient front and center, and makes that an integral part of glucose-lowering therapy, and also that lifestyle is being accentuated again, together with education in every patient is crucial,” Dr. Mathieu, who is professor of medicine at the Katholieke Universiteit Leuven (Belgium), and a coauthor of the report, added.
“At EASD, we also believe that it is very important to bring this consensus paper to life,” she added, which is part of her role as the chair of postgraduate education at the EASD. Two of the EASD’s main remits is to ensure that the results of research and education are brought to the diabetes community at large, she said.
In every figure in the paper there is a highlight to say, “please avoid clinical inertia, reassess and modify treatment if necessary, at least every 3-6 months,” Dr. Mathieu noted during the EASD congress.
David Matthews, MD, professor of diabetic medicine at the University of Oxford (England) and president-elect of the EASD, commented on the 2018 ADA/EASD Consensus Report after its presentation at the EASD meeting. “The reality is that you’ve got to think extremely hard with your patients about what the balances between risks and benefits are,” Dr. Matthews said. “We encourage you to do this, what you have here is a wonderful handbook to guide you in your decision making.”
Dr. Davies reported receiving personal fees and/or grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Intarcia Therapeutics/Servier, Janssen, Merck Sharp & Dohme, Mitsubishi Tanabi, Novo Nordisk, Sanofi, and Takeda.
Dr. Buse disclosed acting as a consultant to and/or receiving research support from Adocia, AstraZeneca, Eli Lilly, GI Dynamics, Intarcia Therapeutics, MannKind, NovaTarg, Neurimmune, Novo Nordisk, Senseonics, and vTv Therapeutics with fees paid to the University of North Carolina. He holds stock options in Mellitus Health, PhaseBio and Stability Health.
Dr. Mathieu disclosed relationships with (advisory boards, speakers bureaus, and/or research support) from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Hanmi Pharmaceuticals, Intrexon, Janssen Pharmaceuticals, MannKind, Medtronic, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, Sanofi, and UCB.
Dr. Cefalu had no disclosures and Dr. Matthews had no relevant conflicts of interest other than becoming the EASD president-elect during the meeting.
REPORTING FROM EASD 2018
Association between hospice length of stay and health care costs
Background: Early hospice referral among Medicare patients is associated with lower rates of hospital admission, intensive care unit admission, and in-hospital death. However, it is not known whether there is association between early hospice referral and health care costs among patients with maintenance hemodialysis.
Study design: Cross-sectional observational study.
Setting: Using the United States Renal Data System registry.
Synopsis: With the use of data from the United States Renal Data System from 2000-2014, the study examined the relationship between health care utilization during the last month and that of the last week of life among patients with maintenance hemodialysis. The investigators used patients who had renal failure as a primary hospice diagnosis regardless of the decision to discontinue hemodialysis before death. Hospital admission, ICU admission, death in the hospital, and one or more inpatient intensive procedures were used as measures for health care utilization.
Among 154,186 (20%) patients receiving hospice service at the time of death, 41.5% enrolled in hospice within 3 days of death. Because more patients were referred to hospice very close to the time of death, the Medicare cost for hospice patients was similar to those patients not referred to hospice ($10,756 vs. $10,871; P = .08). Longer lengths of stay in hospice beyond 3 days were associated with lower rates of health care utilization and costs. Late hospice referral was also associated with inadequate pain control and emotional needs.
The study was not able to capture patients who had end-stage renal disease but were on hemodialysis. Patients with private insurance or those covered by Veterans Affairs were not included.
Bottom line: Half of hospice referrals among patients with maintenance hemodialysis occur within the last 3 day of life, which has no significant effect on end-of-life costs and health care utilization.
Citation: Wachterman MW et al. Association between hospice length of stay, health care utilization, and Medicare costs at the end of life among patients who received maintenance hemodialysis. Jama Intern Med. 2018;178(6):792-9.
Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.
Background: Early hospice referral among Medicare patients is associated with lower rates of hospital admission, intensive care unit admission, and in-hospital death. However, it is not known whether there is association between early hospice referral and health care costs among patients with maintenance hemodialysis.
Study design: Cross-sectional observational study.
Setting: Using the United States Renal Data System registry.
Synopsis: With the use of data from the United States Renal Data System from 2000-2014, the study examined the relationship between health care utilization during the last month and that of the last week of life among patients with maintenance hemodialysis. The investigators used patients who had renal failure as a primary hospice diagnosis regardless of the decision to discontinue hemodialysis before death. Hospital admission, ICU admission, death in the hospital, and one or more inpatient intensive procedures were used as measures for health care utilization.
Among 154,186 (20%) patients receiving hospice service at the time of death, 41.5% enrolled in hospice within 3 days of death. Because more patients were referred to hospice very close to the time of death, the Medicare cost for hospice patients was similar to those patients not referred to hospice ($10,756 vs. $10,871; P = .08). Longer lengths of stay in hospice beyond 3 days were associated with lower rates of health care utilization and costs. Late hospice referral was also associated with inadequate pain control and emotional needs.
The study was not able to capture patients who had end-stage renal disease but were on hemodialysis. Patients with private insurance or those covered by Veterans Affairs were not included.
Bottom line: Half of hospice referrals among patients with maintenance hemodialysis occur within the last 3 day of life, which has no significant effect on end-of-life costs and health care utilization.
Citation: Wachterman MW et al. Association between hospice length of stay, health care utilization, and Medicare costs at the end of life among patients who received maintenance hemodialysis. Jama Intern Med. 2018;178(6):792-9.
Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.
Background: Early hospice referral among Medicare patients is associated with lower rates of hospital admission, intensive care unit admission, and in-hospital death. However, it is not known whether there is association between early hospice referral and health care costs among patients with maintenance hemodialysis.
Study design: Cross-sectional observational study.
Setting: Using the United States Renal Data System registry.
Synopsis: With the use of data from the United States Renal Data System from 2000-2014, the study examined the relationship between health care utilization during the last month and that of the last week of life among patients with maintenance hemodialysis. The investigators used patients who had renal failure as a primary hospice diagnosis regardless of the decision to discontinue hemodialysis before death. Hospital admission, ICU admission, death in the hospital, and one or more inpatient intensive procedures were used as measures for health care utilization.
Among 154,186 (20%) patients receiving hospice service at the time of death, 41.5% enrolled in hospice within 3 days of death. Because more patients were referred to hospice very close to the time of death, the Medicare cost for hospice patients was similar to those patients not referred to hospice ($10,756 vs. $10,871; P = .08). Longer lengths of stay in hospice beyond 3 days were associated with lower rates of health care utilization and costs. Late hospice referral was also associated with inadequate pain control and emotional needs.
The study was not able to capture patients who had end-stage renal disease but were on hemodialysis. Patients with private insurance or those covered by Veterans Affairs were not included.
Bottom line: Half of hospice referrals among patients with maintenance hemodialysis occur within the last 3 day of life, which has no significant effect on end-of-life costs and health care utilization.
Citation: Wachterman MW et al. Association between hospice length of stay, health care utilization, and Medicare costs at the end of life among patients who received maintenance hemodialysis. Jama Intern Med. 2018;178(6):792-9.
Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.
With more mindfulness, menopausal symptoms wane
An observational Furthermore, mindfulness had the greatest positive effect on menopausal symptoms for those women with the highest self-reported stress levels.
“In this cross-sectional study, mindfulness was associated with lower menopausal symptom burden. In women with higher stress, the magnitude of association between mindfulness and menopausal symptoms appeared more robust,” said Richa Sood, MD, speaking at the annual meeting of the North American Menopause Society.
Menopausal symptoms can exist alongside many other midlife issues because women often are trying to keep many balls in the air: This age group may be facing aging parents, a household with teenagers, and work-related pressures, she noted.
Thus, menopausal symptoms can be amplified by stressors. New mood problems – or worsening of preexisting ones – can interfere with work productivity and negatively affect relationships. Life satisfaction can take a steep dive during midlife for some women, said Dr. Sood of the Mayo Clinic, Rochester, Minn.
Could mindfulness be effective for stress management in this complex landscape of physiological and lifespan changes? “Mindfulness is paying attention,” said Dr. Sood. Practitioners of mindfulness focus on purposeful attention, staying in the present moment, and avoiding judgment.
Mindfulness may work as a stress-management tool for a variety of reasons, said Dr. Sood. The technique can help retrain people with tendencies for emotional reactivity in stressful situations; additionally, the focus on the present and on observation, rather than judgment, may help avoid maladaptive rumination.
To see how mindfulness in everyday life could affect the burden of menopausal symptoms, Dr. Sood and her collaborators designed an observational, cross-sectional study of 1,744 women aged 40-64 years.
The investigators used three scales in their assessments. The first, the Menopause Rating Scale (MRS), is an 11-item scale ranging from 0 to 44 that assesses psychological, somatovegetative, and urogenital domains. The second, the Perceived Stress Scale 4 (PSS-4), is a four-item scale that is a global measure of stress over the last 4 weeks, with tallied scores in the 0-16 range. Finally, the Mindful Attention Awareness Scale (MAAS) is a 15-item scale that captures how frequently respondents are in a mindful state during their daily life, with higher scores meaning more mindfulness.
The 1,744 women were seen in a women’s health clinic over the period of one year. Participants were a mean 53.4 years old (standard deviation, 6.1 years). Almost all were white (93%), most were married (82.7%), and most also had at least a 4-year college degree (64.6%) and were employed (65.3%).
The investigators mapped each scale against each of the others, which yielded three plots. In the first, higher MAAS scores were correlated with lower MRS scores (correlation, –0.49; P less than .001), which means that more time in a mindful state was associated with less severe menopausal symptoms.
In the second plot, lower MRS scores were associated with lower PSS-4 scores (correlation, 0.55; P less than .001). The last plot mapped PSS-4 scores against MAAS scores, showing that higher MAAS scores were correlated with lower PSS-4 scores, which means that more time in a mindful state was also associated with less perceived stress (correlation, –0.53; P less than .001).
Most of these associations remained statistically significant after multivariable linear regression analysis and breaking out the subscales of the MRS. Only the association between higher MAAS scores and the somatovegetative domain of the PSS-4 lost significance (P = 0.44).
Next, Dr. Sood and her collaborators probed how higher perceived stress, as measured by higher PSS-4 scores, altered the effects that mindful activity had on menopausal symptoms (as measured by the MRS).
The effect of mindfulness became stronger in the milieu of higher perceived stress. At a relatively low PSS-4 value of 4, the MRS score dropped 1.53 points for each one-point increase in the MAAS total score. However, with a PSS-4 score of 12, the decrease in MRS was 2.27 points for each one-point increase in MAAS, and with the maximum perceived stress score of 16, the MRS fell 2.64 points for each one-point increase in the MAAS score.
These findings are set against the backdrop of previous literature linking mindfulness to positive health behaviors and outcomes, she said, noting that work looking specifically at mindfulness-based stress reduction in peri- and postmenopausal women showed a halving of symptoms and improved quality of life.
Dr. Sood said that the present study was observational only, noting that it looked only at time spent in a mindful state in an untrained cohort of women in midlife. “Trait, or dispositional, mindfulness appears to be protective against stress and symptoms in midlife women,” she commented. “More mindful women may be choosing to shift their attention to more pleasant aspects of life, rather than their symptoms.”
“If you allow me to speculate a bit,” Dr. Sood continued, “the underpinnings of psychological symptoms rest in threat-focused attention and emotional reactivity – so the mindfulness approach appears to fit very well to impact such a change.”
Mindfulness, she added, “might be a tool to impact the emotional component of the overall experience, thereby decreasing the total suffering.” However, she noted that what’s needed are studies with a more heterogeneous population, as well as ones designed to tease out causality. Still, “the current study adds to the wealth of data supporting the role of mindfulness in various settings for impacting positive change in health and behaviors.”
Dr. Sood reported that she has ownership stake in the Global Center for Resiliency and Well-Being.
SOURCE: Sood R et al. NAMS 2018, Top-Scoring Abstract Session.
An observational Furthermore, mindfulness had the greatest positive effect on menopausal symptoms for those women with the highest self-reported stress levels.
“In this cross-sectional study, mindfulness was associated with lower menopausal symptom burden. In women with higher stress, the magnitude of association between mindfulness and menopausal symptoms appeared more robust,” said Richa Sood, MD, speaking at the annual meeting of the North American Menopause Society.
Menopausal symptoms can exist alongside many other midlife issues because women often are trying to keep many balls in the air: This age group may be facing aging parents, a household with teenagers, and work-related pressures, she noted.
Thus, menopausal symptoms can be amplified by stressors. New mood problems – or worsening of preexisting ones – can interfere with work productivity and negatively affect relationships. Life satisfaction can take a steep dive during midlife for some women, said Dr. Sood of the Mayo Clinic, Rochester, Minn.
Could mindfulness be effective for stress management in this complex landscape of physiological and lifespan changes? “Mindfulness is paying attention,” said Dr. Sood. Practitioners of mindfulness focus on purposeful attention, staying in the present moment, and avoiding judgment.
Mindfulness may work as a stress-management tool for a variety of reasons, said Dr. Sood. The technique can help retrain people with tendencies for emotional reactivity in stressful situations; additionally, the focus on the present and on observation, rather than judgment, may help avoid maladaptive rumination.
To see how mindfulness in everyday life could affect the burden of menopausal symptoms, Dr. Sood and her collaborators designed an observational, cross-sectional study of 1,744 women aged 40-64 years.
The investigators used three scales in their assessments. The first, the Menopause Rating Scale (MRS), is an 11-item scale ranging from 0 to 44 that assesses psychological, somatovegetative, and urogenital domains. The second, the Perceived Stress Scale 4 (PSS-4), is a four-item scale that is a global measure of stress over the last 4 weeks, with tallied scores in the 0-16 range. Finally, the Mindful Attention Awareness Scale (MAAS) is a 15-item scale that captures how frequently respondents are in a mindful state during their daily life, with higher scores meaning more mindfulness.
The 1,744 women were seen in a women’s health clinic over the period of one year. Participants were a mean 53.4 years old (standard deviation, 6.1 years). Almost all were white (93%), most were married (82.7%), and most also had at least a 4-year college degree (64.6%) and were employed (65.3%).
The investigators mapped each scale against each of the others, which yielded three plots. In the first, higher MAAS scores were correlated with lower MRS scores (correlation, –0.49; P less than .001), which means that more time in a mindful state was associated with less severe menopausal symptoms.
In the second plot, lower MRS scores were associated with lower PSS-4 scores (correlation, 0.55; P less than .001). The last plot mapped PSS-4 scores against MAAS scores, showing that higher MAAS scores were correlated with lower PSS-4 scores, which means that more time in a mindful state was also associated with less perceived stress (correlation, –0.53; P less than .001).
Most of these associations remained statistically significant after multivariable linear regression analysis and breaking out the subscales of the MRS. Only the association between higher MAAS scores and the somatovegetative domain of the PSS-4 lost significance (P = 0.44).
Next, Dr. Sood and her collaborators probed how higher perceived stress, as measured by higher PSS-4 scores, altered the effects that mindful activity had on menopausal symptoms (as measured by the MRS).
The effect of mindfulness became stronger in the milieu of higher perceived stress. At a relatively low PSS-4 value of 4, the MRS score dropped 1.53 points for each one-point increase in the MAAS total score. However, with a PSS-4 score of 12, the decrease in MRS was 2.27 points for each one-point increase in MAAS, and with the maximum perceived stress score of 16, the MRS fell 2.64 points for each one-point increase in the MAAS score.
These findings are set against the backdrop of previous literature linking mindfulness to positive health behaviors and outcomes, she said, noting that work looking specifically at mindfulness-based stress reduction in peri- and postmenopausal women showed a halving of symptoms and improved quality of life.
Dr. Sood said that the present study was observational only, noting that it looked only at time spent in a mindful state in an untrained cohort of women in midlife. “Trait, or dispositional, mindfulness appears to be protective against stress and symptoms in midlife women,” she commented. “More mindful women may be choosing to shift their attention to more pleasant aspects of life, rather than their symptoms.”
“If you allow me to speculate a bit,” Dr. Sood continued, “the underpinnings of psychological symptoms rest in threat-focused attention and emotional reactivity – so the mindfulness approach appears to fit very well to impact such a change.”
Mindfulness, she added, “might be a tool to impact the emotional component of the overall experience, thereby decreasing the total suffering.” However, she noted that what’s needed are studies with a more heterogeneous population, as well as ones designed to tease out causality. Still, “the current study adds to the wealth of data supporting the role of mindfulness in various settings for impacting positive change in health and behaviors.”
Dr. Sood reported that she has ownership stake in the Global Center for Resiliency and Well-Being.
SOURCE: Sood R et al. NAMS 2018, Top-Scoring Abstract Session.
An observational Furthermore, mindfulness had the greatest positive effect on menopausal symptoms for those women with the highest self-reported stress levels.
“In this cross-sectional study, mindfulness was associated with lower menopausal symptom burden. In women with higher stress, the magnitude of association between mindfulness and menopausal symptoms appeared more robust,” said Richa Sood, MD, speaking at the annual meeting of the North American Menopause Society.
Menopausal symptoms can exist alongside many other midlife issues because women often are trying to keep many balls in the air: This age group may be facing aging parents, a household with teenagers, and work-related pressures, she noted.
Thus, menopausal symptoms can be amplified by stressors. New mood problems – or worsening of preexisting ones – can interfere with work productivity and negatively affect relationships. Life satisfaction can take a steep dive during midlife for some women, said Dr. Sood of the Mayo Clinic, Rochester, Minn.
Could mindfulness be effective for stress management in this complex landscape of physiological and lifespan changes? “Mindfulness is paying attention,” said Dr. Sood. Practitioners of mindfulness focus on purposeful attention, staying in the present moment, and avoiding judgment.
Mindfulness may work as a stress-management tool for a variety of reasons, said Dr. Sood. The technique can help retrain people with tendencies for emotional reactivity in stressful situations; additionally, the focus on the present and on observation, rather than judgment, may help avoid maladaptive rumination.
To see how mindfulness in everyday life could affect the burden of menopausal symptoms, Dr. Sood and her collaborators designed an observational, cross-sectional study of 1,744 women aged 40-64 years.
The investigators used three scales in their assessments. The first, the Menopause Rating Scale (MRS), is an 11-item scale ranging from 0 to 44 that assesses psychological, somatovegetative, and urogenital domains. The second, the Perceived Stress Scale 4 (PSS-4), is a four-item scale that is a global measure of stress over the last 4 weeks, with tallied scores in the 0-16 range. Finally, the Mindful Attention Awareness Scale (MAAS) is a 15-item scale that captures how frequently respondents are in a mindful state during their daily life, with higher scores meaning more mindfulness.
The 1,744 women were seen in a women’s health clinic over the period of one year. Participants were a mean 53.4 years old (standard deviation, 6.1 years). Almost all were white (93%), most were married (82.7%), and most also had at least a 4-year college degree (64.6%) and were employed (65.3%).
The investigators mapped each scale against each of the others, which yielded three plots. In the first, higher MAAS scores were correlated with lower MRS scores (correlation, –0.49; P less than .001), which means that more time in a mindful state was associated with less severe menopausal symptoms.
In the second plot, lower MRS scores were associated with lower PSS-4 scores (correlation, 0.55; P less than .001). The last plot mapped PSS-4 scores against MAAS scores, showing that higher MAAS scores were correlated with lower PSS-4 scores, which means that more time in a mindful state was also associated with less perceived stress (correlation, –0.53; P less than .001).
Most of these associations remained statistically significant after multivariable linear regression analysis and breaking out the subscales of the MRS. Only the association between higher MAAS scores and the somatovegetative domain of the PSS-4 lost significance (P = 0.44).
Next, Dr. Sood and her collaborators probed how higher perceived stress, as measured by higher PSS-4 scores, altered the effects that mindful activity had on menopausal symptoms (as measured by the MRS).
The effect of mindfulness became stronger in the milieu of higher perceived stress. At a relatively low PSS-4 value of 4, the MRS score dropped 1.53 points for each one-point increase in the MAAS total score. However, with a PSS-4 score of 12, the decrease in MRS was 2.27 points for each one-point increase in MAAS, and with the maximum perceived stress score of 16, the MRS fell 2.64 points for each one-point increase in the MAAS score.
These findings are set against the backdrop of previous literature linking mindfulness to positive health behaviors and outcomes, she said, noting that work looking specifically at mindfulness-based stress reduction in peri- and postmenopausal women showed a halving of symptoms and improved quality of life.
Dr. Sood said that the present study was observational only, noting that it looked only at time spent in a mindful state in an untrained cohort of women in midlife. “Trait, or dispositional, mindfulness appears to be protective against stress and symptoms in midlife women,” she commented. “More mindful women may be choosing to shift their attention to more pleasant aspects of life, rather than their symptoms.”
“If you allow me to speculate a bit,” Dr. Sood continued, “the underpinnings of psychological symptoms rest in threat-focused attention and emotional reactivity – so the mindfulness approach appears to fit very well to impact such a change.”
Mindfulness, she added, “might be a tool to impact the emotional component of the overall experience, thereby decreasing the total suffering.” However, she noted that what’s needed are studies with a more heterogeneous population, as well as ones designed to tease out causality. Still, “the current study adds to the wealth of data supporting the role of mindfulness in various settings for impacting positive change in health and behaviors.”
Dr. Sood reported that she has ownership stake in the Global Center for Resiliency and Well-Being.
SOURCE: Sood R et al. NAMS 2018, Top-Scoring Abstract Session.
FROM NAMS 2018
Key clinical point: Time spent in a mindful state was associated with fewer menopause symptoms.
Major finding: With maximum stress, each 1-point increase in mindfulness was associated with a 2.64-point drop in menopausal symptoms.
Study details: A cross-sectional, single-center study of 1,744 women aged 40-64 years.
Disclosures: Dr. Sood reported that she has ownership stake in the Global Center for Resiliency and Well-Being.
Source: Sood R et al. NAMS 2018, Top-Scoring Abstract Session.
Myeloperoxidase elevated in HCV-related liver cancer
Myeloperoxidase (MPO) expression was significantly higher in hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC) cases when compared with cirrhotic patients, according to a study of 59 patients with HCV-related liver disease.
HCV is the main cause of liver disease, wrote Mohamed Abdel-Hamed, MD, of Minia University in Egypt, and his colleagues. In addition, HCV is associated with significant oxidative stress, which has been identified as a significant metabolic pathway culminating in hepatic cirrhosis, liver failure, and liver cancer. Thus the researchers studied the role of MPO, an oxidative enzyme released at sites of inflammation, in the possible etiology of HCV-related liver cancer.
The patients were divided into two groups, 25 with HCC and 34 with chronic liver diseases with cirrhosis. All patients were examined immunohistochemically to demonstrate the expression of myeloperoxidase, according to the report published in Meta Gene.
Subjects with HCC showed markedly increased MPO expression when compared with MPO expression in hepatocytes of subjects with liver cirrhosis, who mostly showed a mild degree of expression. In addition, no mild expression of MPO was detected in the subjects with HCC. These findings were highly statistically significant (P less than .0001), according to Dr. Abdel-Hamed and his colleagues.
“The present study showed that marked expression of MPO plays an important role in the pathogenesis of HCV-associated HCC,” the authors stated. “This study could provide valuable, predictive parameters that can be used clinically in the prognosis of HCC patients.”
The authors did not report any disclosures.
SOURCE: Abdel-Hamid M et al. Meta Gene. 2018 Dec;18:1-8.
Myeloperoxidase (MPO) expression was significantly higher in hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC) cases when compared with cirrhotic patients, according to a study of 59 patients with HCV-related liver disease.
HCV is the main cause of liver disease, wrote Mohamed Abdel-Hamed, MD, of Minia University in Egypt, and his colleagues. In addition, HCV is associated with significant oxidative stress, which has been identified as a significant metabolic pathway culminating in hepatic cirrhosis, liver failure, and liver cancer. Thus the researchers studied the role of MPO, an oxidative enzyme released at sites of inflammation, in the possible etiology of HCV-related liver cancer.
The patients were divided into two groups, 25 with HCC and 34 with chronic liver diseases with cirrhosis. All patients were examined immunohistochemically to demonstrate the expression of myeloperoxidase, according to the report published in Meta Gene.
Subjects with HCC showed markedly increased MPO expression when compared with MPO expression in hepatocytes of subjects with liver cirrhosis, who mostly showed a mild degree of expression. In addition, no mild expression of MPO was detected in the subjects with HCC. These findings were highly statistically significant (P less than .0001), according to Dr. Abdel-Hamed and his colleagues.
“The present study showed that marked expression of MPO plays an important role in the pathogenesis of HCV-associated HCC,” the authors stated. “This study could provide valuable, predictive parameters that can be used clinically in the prognosis of HCC patients.”
The authors did not report any disclosures.
SOURCE: Abdel-Hamid M et al. Meta Gene. 2018 Dec;18:1-8.
Myeloperoxidase (MPO) expression was significantly higher in hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC) cases when compared with cirrhotic patients, according to a study of 59 patients with HCV-related liver disease.
HCV is the main cause of liver disease, wrote Mohamed Abdel-Hamed, MD, of Minia University in Egypt, and his colleagues. In addition, HCV is associated with significant oxidative stress, which has been identified as a significant metabolic pathway culminating in hepatic cirrhosis, liver failure, and liver cancer. Thus the researchers studied the role of MPO, an oxidative enzyme released at sites of inflammation, in the possible etiology of HCV-related liver cancer.
The patients were divided into two groups, 25 with HCC and 34 with chronic liver diseases with cirrhosis. All patients were examined immunohistochemically to demonstrate the expression of myeloperoxidase, according to the report published in Meta Gene.
Subjects with HCC showed markedly increased MPO expression when compared with MPO expression in hepatocytes of subjects with liver cirrhosis, who mostly showed a mild degree of expression. In addition, no mild expression of MPO was detected in the subjects with HCC. These findings were highly statistically significant (P less than .0001), according to Dr. Abdel-Hamed and his colleagues.
“The present study showed that marked expression of MPO plays an important role in the pathogenesis of HCV-associated HCC,” the authors stated. “This study could provide valuable, predictive parameters that can be used clinically in the prognosis of HCC patients.”
The authors did not report any disclosures.
SOURCE: Abdel-Hamid M et al. Meta Gene. 2018 Dec;18:1-8.
FROM META GENE
Key clinical point:
Major finding: Hepatocellular carcinoma subjects showed a marked increase of myeloperoxidase expression when compared with subjects with liver cirrhosis (P less than .0001).
Study details: An immunohistochemical analysis of 59 patients infected with hepatitis C virus.
Disclosures: The authors did not report any disclosures.
Source: Abdel-Hamid M et al. Meta Gene. 2018 Dec;18:1-8.
Federal changes in GI payment models most likely through CMS
DALLAS – With the approaching midterm elections and Congress’ relative silence on health care policy this year, new health care legislation is unlikely in the immediate foreseeable future. But that does not mean the door to federal changes in health care policy is completely closed, according to Robert S. Saunders, PhD, of the Duke–Margolis Center for Health Policy, Durham, N.C.
It’s simply more likely to come from the new leadership at the Department of Health & Human Services including Secretary Alex Azar, Center for Medicare & Medicaid Services Administrator Seema Verma, and Center for Medicare & Medicaid Innovation Director Adam Boehler. In his keynote address for the American Gastroenterological Association’s Partners in Value meeting, Dr. Saunders gave attendees an overview of the current landscape in Washington and what they might expect in the coming months.
“Assuming congressional gridlock continues, HHS is a primary outlet for policy,” Dr. Saunders said, also noting CMMI’s pledge to make value-based payment a priority.
Broadly speaking, six goals comprise the current administration’s future vision within CMS, Dr. Saunders said. CMS has been encouraging payment reform innovation and benefit flexibility in Medicare Advantage and promoting private sector leadership with payment reform.
Three other goals include using CMMI to increase alternative payment model availability to specialists, expanding patients’ access to their own health data, and adding more outcomes measures but reducing the total number of measures.
- CMS is also collecting information on how it might reform the Stark Law to streamline value-based payment (VBP) arrangements or establish a mechanism for direct provider contracting.
Dr. Saunders highlighted two health policy developments already announced. First, CMS will continue to offer bundled payment options through the Bundled Payments for Care Improvement Advanced initiative, Dr. Saunders said. That program presents opportunities related to treatment of GI hemorrhage, GI obstruction, and most liver disorders (excepting cancer, cirrhosis, and alcoholic hepatitis).
Then, CMS is proposing several changes to existing programs, though it remains to be seen how those will develop. One of those is the proposed modification of the Accountable Care Organization program to shorten the period ACOs can spend in upside risk, thereby pushing for more downside risk taking. Instead of having 6 years in upside risk getting 50% of savings, the proposed Pathways to Success would reduce that period to 2 years of upside risk, after which the ACOs would be responsible for shared losses in adddition to potentially receiving savings.
Another proposed change is to make payments sites neutral so that Medicare clinical visits are charged the same regardless of whether they occur at a doctor’s office or in a hospital outpatient setting. Currently, hospital outpatient visits are reimbursed at a higher amount than are those in private physicians offices.
Finally, a new proposed rule would collapse payments for evaluation and management services into two tiers, which would apply only to office and outpatient E/M codes.
But it’s not clear yet how hard CMS will push for implementation of these changes. For example, the proposed rule on E/M policy is the most significant push so far to reduce documentation from this administration, Dr. Saunders said, but medical groups, particularly specialists, oppose the rule because they argue it incentivizes short, repeat visits.
The three probable scenarios are that CMS moves forward with the new rule, that CMS scales back and retains the existing system, or that the “medical community pushes for an alternative to E/M with a framework that rewards doctors for their time,” Dr. Saunders said. The final rule, likely to come down by November, will also offer some insight into how forcefully CMS will promote its agenda, according to Dr. Saunders.
Hearing these points “helps confirm that we are all headed toward this value-based world, and so we should start to ready our practices in the way that we internally compensate physicians and the way we engage with patients toward that value-based world,” Michael Weinstein, MD, president of the Digestive Health Physicians Association, said in an interview following the keynote.
But Dr. Weinstein expressed skepticism about CMS’ power to alter regulations sufficiently to really move forward into value-based care more broadly. He pointed out the various obstacles in the private sector that simply require legislative fixes, such as Stark Law modernization; increased transparency on price, outcomes, and quality measures; and interoperability between systems; among others.
“You have to keep knocking CMS to make the changes, but if CMS makes changes, it only makes changes for Medicare,” Dr. Weinstein said. Many states have laws requiring commercial carriers to follow the same federal rules that are set up for Medicare, but those are not universal and remain limited in scope.
Dr. Saunders also discussed the Physician-Focused Payment Model Technical Advisory Committee (PTAC), created by the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) to review new options for alternative payment models.
Since beginning to accept submissions in December 2016, PTAC has reviewed two GI models in 2017: Project Sonar and a comprehensive colonoscopy APM. Project Sonar focuses on creation of an IBD/Crohn’s medical home. Despite reservations about proprietary technology and about the evidence on Project Sonar, PTAC has recommended the program for further testing. The comprehensive colonoscopy APM, however, was withdrawn after preliminary reviews because the PTAC was concerned the proposal “was too reliant on site-of-service shift and wanted more information on how it would lead to better integrated care,” Dr. Saunders explained.
Though PTAC’s existence led to hope early on that it might stimulate the creation of APMs and help them spread, the reality has been much shakier.
“CMS has not implemented any of the models PTAC has approved for use, and CMS has also not yet created a formal pathway for limited testing,” Dr. Saunders said. That has left members uncertain about the future.
DALLAS – With the approaching midterm elections and Congress’ relative silence on health care policy this year, new health care legislation is unlikely in the immediate foreseeable future. But that does not mean the door to federal changes in health care policy is completely closed, according to Robert S. Saunders, PhD, of the Duke–Margolis Center for Health Policy, Durham, N.C.
It’s simply more likely to come from the new leadership at the Department of Health & Human Services including Secretary Alex Azar, Center for Medicare & Medicaid Services Administrator Seema Verma, and Center for Medicare & Medicaid Innovation Director Adam Boehler. In his keynote address for the American Gastroenterological Association’s Partners in Value meeting, Dr. Saunders gave attendees an overview of the current landscape in Washington and what they might expect in the coming months.
“Assuming congressional gridlock continues, HHS is a primary outlet for policy,” Dr. Saunders said, also noting CMMI’s pledge to make value-based payment a priority.
Broadly speaking, six goals comprise the current administration’s future vision within CMS, Dr. Saunders said. CMS has been encouraging payment reform innovation and benefit flexibility in Medicare Advantage and promoting private sector leadership with payment reform.
Three other goals include using CMMI to increase alternative payment model availability to specialists, expanding patients’ access to their own health data, and adding more outcomes measures but reducing the total number of measures.
- CMS is also collecting information on how it might reform the Stark Law to streamline value-based payment (VBP) arrangements or establish a mechanism for direct provider contracting.
Dr. Saunders highlighted two health policy developments already announced. First, CMS will continue to offer bundled payment options through the Bundled Payments for Care Improvement Advanced initiative, Dr. Saunders said. That program presents opportunities related to treatment of GI hemorrhage, GI obstruction, and most liver disorders (excepting cancer, cirrhosis, and alcoholic hepatitis).
Then, CMS is proposing several changes to existing programs, though it remains to be seen how those will develop. One of those is the proposed modification of the Accountable Care Organization program to shorten the period ACOs can spend in upside risk, thereby pushing for more downside risk taking. Instead of having 6 years in upside risk getting 50% of savings, the proposed Pathways to Success would reduce that period to 2 years of upside risk, after which the ACOs would be responsible for shared losses in adddition to potentially receiving savings.
Another proposed change is to make payments sites neutral so that Medicare clinical visits are charged the same regardless of whether they occur at a doctor’s office or in a hospital outpatient setting. Currently, hospital outpatient visits are reimbursed at a higher amount than are those in private physicians offices.
Finally, a new proposed rule would collapse payments for evaluation and management services into two tiers, which would apply only to office and outpatient E/M codes.
But it’s not clear yet how hard CMS will push for implementation of these changes. For example, the proposed rule on E/M policy is the most significant push so far to reduce documentation from this administration, Dr. Saunders said, but medical groups, particularly specialists, oppose the rule because they argue it incentivizes short, repeat visits.
The three probable scenarios are that CMS moves forward with the new rule, that CMS scales back and retains the existing system, or that the “medical community pushes for an alternative to E/M with a framework that rewards doctors for their time,” Dr. Saunders said. The final rule, likely to come down by November, will also offer some insight into how forcefully CMS will promote its agenda, according to Dr. Saunders.
Hearing these points “helps confirm that we are all headed toward this value-based world, and so we should start to ready our practices in the way that we internally compensate physicians and the way we engage with patients toward that value-based world,” Michael Weinstein, MD, president of the Digestive Health Physicians Association, said in an interview following the keynote.
But Dr. Weinstein expressed skepticism about CMS’ power to alter regulations sufficiently to really move forward into value-based care more broadly. He pointed out the various obstacles in the private sector that simply require legislative fixes, such as Stark Law modernization; increased transparency on price, outcomes, and quality measures; and interoperability between systems; among others.
“You have to keep knocking CMS to make the changes, but if CMS makes changes, it only makes changes for Medicare,” Dr. Weinstein said. Many states have laws requiring commercial carriers to follow the same federal rules that are set up for Medicare, but those are not universal and remain limited in scope.
Dr. Saunders also discussed the Physician-Focused Payment Model Technical Advisory Committee (PTAC), created by the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) to review new options for alternative payment models.
Since beginning to accept submissions in December 2016, PTAC has reviewed two GI models in 2017: Project Sonar and a comprehensive colonoscopy APM. Project Sonar focuses on creation of an IBD/Crohn’s medical home. Despite reservations about proprietary technology and about the evidence on Project Sonar, PTAC has recommended the program for further testing. The comprehensive colonoscopy APM, however, was withdrawn after preliminary reviews because the PTAC was concerned the proposal “was too reliant on site-of-service shift and wanted more information on how it would lead to better integrated care,” Dr. Saunders explained.
Though PTAC’s existence led to hope early on that it might stimulate the creation of APMs and help them spread, the reality has been much shakier.
“CMS has not implemented any of the models PTAC has approved for use, and CMS has also not yet created a formal pathway for limited testing,” Dr. Saunders said. That has left members uncertain about the future.
DALLAS – With the approaching midterm elections and Congress’ relative silence on health care policy this year, new health care legislation is unlikely in the immediate foreseeable future. But that does not mean the door to federal changes in health care policy is completely closed, according to Robert S. Saunders, PhD, of the Duke–Margolis Center for Health Policy, Durham, N.C.
It’s simply more likely to come from the new leadership at the Department of Health & Human Services including Secretary Alex Azar, Center for Medicare & Medicaid Services Administrator Seema Verma, and Center for Medicare & Medicaid Innovation Director Adam Boehler. In his keynote address for the American Gastroenterological Association’s Partners in Value meeting, Dr. Saunders gave attendees an overview of the current landscape in Washington and what they might expect in the coming months.
“Assuming congressional gridlock continues, HHS is a primary outlet for policy,” Dr. Saunders said, also noting CMMI’s pledge to make value-based payment a priority.
Broadly speaking, six goals comprise the current administration’s future vision within CMS, Dr. Saunders said. CMS has been encouraging payment reform innovation and benefit flexibility in Medicare Advantage and promoting private sector leadership with payment reform.
Three other goals include using CMMI to increase alternative payment model availability to specialists, expanding patients’ access to their own health data, and adding more outcomes measures but reducing the total number of measures.
- CMS is also collecting information on how it might reform the Stark Law to streamline value-based payment (VBP) arrangements or establish a mechanism for direct provider contracting.
Dr. Saunders highlighted two health policy developments already announced. First, CMS will continue to offer bundled payment options through the Bundled Payments for Care Improvement Advanced initiative, Dr. Saunders said. That program presents opportunities related to treatment of GI hemorrhage, GI obstruction, and most liver disorders (excepting cancer, cirrhosis, and alcoholic hepatitis).
Then, CMS is proposing several changes to existing programs, though it remains to be seen how those will develop. One of those is the proposed modification of the Accountable Care Organization program to shorten the period ACOs can spend in upside risk, thereby pushing for more downside risk taking. Instead of having 6 years in upside risk getting 50% of savings, the proposed Pathways to Success would reduce that period to 2 years of upside risk, after which the ACOs would be responsible for shared losses in adddition to potentially receiving savings.
Another proposed change is to make payments sites neutral so that Medicare clinical visits are charged the same regardless of whether they occur at a doctor’s office or in a hospital outpatient setting. Currently, hospital outpatient visits are reimbursed at a higher amount than are those in private physicians offices.
Finally, a new proposed rule would collapse payments for evaluation and management services into two tiers, which would apply only to office and outpatient E/M codes.
But it’s not clear yet how hard CMS will push for implementation of these changes. For example, the proposed rule on E/M policy is the most significant push so far to reduce documentation from this administration, Dr. Saunders said, but medical groups, particularly specialists, oppose the rule because they argue it incentivizes short, repeat visits.
The three probable scenarios are that CMS moves forward with the new rule, that CMS scales back and retains the existing system, or that the “medical community pushes for an alternative to E/M with a framework that rewards doctors for their time,” Dr. Saunders said. The final rule, likely to come down by November, will also offer some insight into how forcefully CMS will promote its agenda, according to Dr. Saunders.
Hearing these points “helps confirm that we are all headed toward this value-based world, and so we should start to ready our practices in the way that we internally compensate physicians and the way we engage with patients toward that value-based world,” Michael Weinstein, MD, president of the Digestive Health Physicians Association, said in an interview following the keynote.
But Dr. Weinstein expressed skepticism about CMS’ power to alter regulations sufficiently to really move forward into value-based care more broadly. He pointed out the various obstacles in the private sector that simply require legislative fixes, such as Stark Law modernization; increased transparency on price, outcomes, and quality measures; and interoperability between systems; among others.
“You have to keep knocking CMS to make the changes, but if CMS makes changes, it only makes changes for Medicare,” Dr. Weinstein said. Many states have laws requiring commercial carriers to follow the same federal rules that are set up for Medicare, but those are not universal and remain limited in scope.
Dr. Saunders also discussed the Physician-Focused Payment Model Technical Advisory Committee (PTAC), created by the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) to review new options for alternative payment models.
Since beginning to accept submissions in December 2016, PTAC has reviewed two GI models in 2017: Project Sonar and a comprehensive colonoscopy APM. Project Sonar focuses on creation of an IBD/Crohn’s medical home. Despite reservations about proprietary technology and about the evidence on Project Sonar, PTAC has recommended the program for further testing. The comprehensive colonoscopy APM, however, was withdrawn after preliminary reviews because the PTAC was concerned the proposal “was too reliant on site-of-service shift and wanted more information on how it would lead to better integrated care,” Dr. Saunders explained.
Though PTAC’s existence led to hope early on that it might stimulate the creation of APMs and help them spread, the reality has been much shakier.
“CMS has not implemented any of the models PTAC has approved for use, and CMS has also not yet created a formal pathway for limited testing,” Dr. Saunders said. That has left members uncertain about the future.
REPORTING FROM 2018 AGA PARTNERS IN VALUE
Delayed pushing during labor does not benefit mother or baby, study finds
according to the results of a randomized trial.
“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”
They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.
The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.
Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).
The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).
In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.
Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.
“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”
They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.
The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.
SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.
Of the almost 4 million births in the United States each year, 68% are vaginal deliveries, which illustrates how important it is to have additional evidence to guide the management of labor, Jeffrey D. Sperling, MD, and Dana R. Gossett, MD, wrote in an accompanying editorial. They noted that, despite a lack of blinding and other limitations, as well as the fact there is no one risk-free solution regarding labor management or route of delivery, the results of this study have improved the understanding “of the risks and benefits of different strategies of labor management.”
The study, they added, “presents the only contemporary level 1 evidence available on the topic of whether the timing of pushing in the second stage of labor can have an effect on outcomes.”
The data “contribute to a growing body of literature on how to optimally manage labor in an evidenced-based fashion and improve perinatal outcomes without compromising maternal satisfaction,” they wrote. They recommended that future research should include exploring the effects and outcomes of delaying pushing among multiparous women, women with a previous cesarean delivery, and women who have not received epidural analgesia.
Dr. Sperling and Dr. Gossett are with the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. Dr. Gossett reported serving as a consultant to Bayer Pharmaceuticals. No other disclosures were reported (JAMA. 2018;320[14]:1439-40).
Of the almost 4 million births in the United States each year, 68% are vaginal deliveries, which illustrates how important it is to have additional evidence to guide the management of labor, Jeffrey D. Sperling, MD, and Dana R. Gossett, MD, wrote in an accompanying editorial. They noted that, despite a lack of blinding and other limitations, as well as the fact there is no one risk-free solution regarding labor management or route of delivery, the results of this study have improved the understanding “of the risks and benefits of different strategies of labor management.”
The study, they added, “presents the only contemporary level 1 evidence available on the topic of whether the timing of pushing in the second stage of labor can have an effect on outcomes.”
The data “contribute to a growing body of literature on how to optimally manage labor in an evidenced-based fashion and improve perinatal outcomes without compromising maternal satisfaction,” they wrote. They recommended that future research should include exploring the effects and outcomes of delaying pushing among multiparous women, women with a previous cesarean delivery, and women who have not received epidural analgesia.
Dr. Sperling and Dr. Gossett are with the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. Dr. Gossett reported serving as a consultant to Bayer Pharmaceuticals. No other disclosures were reported (JAMA. 2018;320[14]:1439-40).
Of the almost 4 million births in the United States each year, 68% are vaginal deliveries, which illustrates how important it is to have additional evidence to guide the management of labor, Jeffrey D. Sperling, MD, and Dana R. Gossett, MD, wrote in an accompanying editorial. They noted that, despite a lack of blinding and other limitations, as well as the fact there is no one risk-free solution regarding labor management or route of delivery, the results of this study have improved the understanding “of the risks and benefits of different strategies of labor management.”
The study, they added, “presents the only contemporary level 1 evidence available on the topic of whether the timing of pushing in the second stage of labor can have an effect on outcomes.”
The data “contribute to a growing body of literature on how to optimally manage labor in an evidenced-based fashion and improve perinatal outcomes without compromising maternal satisfaction,” they wrote. They recommended that future research should include exploring the effects and outcomes of delaying pushing among multiparous women, women with a previous cesarean delivery, and women who have not received epidural analgesia.
Dr. Sperling and Dr. Gossett are with the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. Dr. Gossett reported serving as a consultant to Bayer Pharmaceuticals. No other disclosures were reported (JAMA. 2018;320[14]:1439-40).
according to the results of a randomized trial.
“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”
They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.
The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.
Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).
The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).
In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.
Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.
“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”
They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.
The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.
SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.
according to the results of a randomized trial.
“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”
They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.
The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.
Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).
The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).
In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.
Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.
“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”
They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.
The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.
SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.
FROM JAMA
Key clinical point: Delayed pushing during the second stage of labor may not reduce the risk of cesarean delivery and may lengthen the duration of labor.
Major finding: The rate of spontaneous vaginal delivery did not differ between groups (85.9% in the immediate pushing group versus 86.5% in the delayed pushing group).
Study details: A multicenter trial involving 2,414 nulliparous women receiving neuraxial analgesia, who were randomized to immediate pushing or delayed pushing during the second stage of labor.
Disclosures: The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.
Source: Cahill AG et al. JAMA. 2018;320(14):1444-54.
Third trimester Tdap vaccination raises antibodies in newborns
Immunization of pregnant women with the Tdap vaccine during weeks 27-30 of pregnancy yielded the higher concentration of protective pertussis toxin antibodies in neonates, compared with neonates not exposed to the vaccine, based on data from more than 600 pregnancies.
The Centers for Disease Control and Prevention recommends Tdap vaccination for pregnant women between 27 and 35 weeks’ gestation, but “data on pertussis antibody concentrations following maternal Tdap immunization are limited because of small cohort size or differing immunization schedules,” wrote C. Mary Healy, MD, of Baylor College of Medicine, Houston and her colleagues.
In an observational study published in JAMA, the researchers reviewed data from 626 pregnancies and births at a single tertiary care center in Texas. The average age of the mothers was 30 years; 41% were white, 27% Hispanic, 26% black, 5% Asian, and 1% another ethnicity. Of these, 312 received the Tdap vaccine at an average gestation of 31 weeks, while 314 women were not immunized.
Overall, the geometric mean concentration (GMC) of neonatal umbilical cord pertussis toxin antibodies among infants exposed to Tdap was 47.3 IU/mL, compared with 12.9 IU/mL for unexposed infants, yielding a GMC ratio of 3.6 (P less than .001).
In addition, pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher were significantly more common in Tdap-exposed vs. Tdap-unexposed neonates (86% vs. 37%, 72% vs. 17%, 59% vs. 12%, respectively).
The GMC of pertussis toxin antibodies was highest when the vaccine was given during weeks 27-30, after which the GMC declined, the researchers noted.
The study was limited by several factors including the observational design, which does not support causes and effect analysis, the use of data from a single center, and the lack of pre- and postimmunization serum samples for comparison, and the absence of data on women immunized during the second trimester, the researchers wrote.
However, the results support data from previous studies, and were strengthened by the large study population. The findings suggest that “following U.S. immunization recommendations and in accordance with current understanding of the kinetics of placental transfer, optimal time to administer Tdap vaccine to maximize pertussis toxin antibodies at birth may be early in the third trimester, with the window of 27 through 30 weeks of gestation yielding the highest cord blood levels,” the researchers said.
The study was supported in part by the Centers for Disease Control and Prevention. Dr. Healy disclosed relationships with Sanofi Pasteur, Novartis Vaccines, Pfizer, and Novavax.
SOURCE: Healy C et al. JAMA. 2018 Oct 9;320(14):1464-70.
Immunization of pregnant women with the Tdap vaccine during weeks 27-30 of pregnancy yielded the higher concentration of protective pertussis toxin antibodies in neonates, compared with neonates not exposed to the vaccine, based on data from more than 600 pregnancies.
The Centers for Disease Control and Prevention recommends Tdap vaccination for pregnant women between 27 and 35 weeks’ gestation, but “data on pertussis antibody concentrations following maternal Tdap immunization are limited because of small cohort size or differing immunization schedules,” wrote C. Mary Healy, MD, of Baylor College of Medicine, Houston and her colleagues.
In an observational study published in JAMA, the researchers reviewed data from 626 pregnancies and births at a single tertiary care center in Texas. The average age of the mothers was 30 years; 41% were white, 27% Hispanic, 26% black, 5% Asian, and 1% another ethnicity. Of these, 312 received the Tdap vaccine at an average gestation of 31 weeks, while 314 women were not immunized.
Overall, the geometric mean concentration (GMC) of neonatal umbilical cord pertussis toxin antibodies among infants exposed to Tdap was 47.3 IU/mL, compared with 12.9 IU/mL for unexposed infants, yielding a GMC ratio of 3.6 (P less than .001).
In addition, pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher were significantly more common in Tdap-exposed vs. Tdap-unexposed neonates (86% vs. 37%, 72% vs. 17%, 59% vs. 12%, respectively).
The GMC of pertussis toxin antibodies was highest when the vaccine was given during weeks 27-30, after which the GMC declined, the researchers noted.
The study was limited by several factors including the observational design, which does not support causes and effect analysis, the use of data from a single center, and the lack of pre- and postimmunization serum samples for comparison, and the absence of data on women immunized during the second trimester, the researchers wrote.
However, the results support data from previous studies, and were strengthened by the large study population. The findings suggest that “following U.S. immunization recommendations and in accordance with current understanding of the kinetics of placental transfer, optimal time to administer Tdap vaccine to maximize pertussis toxin antibodies at birth may be early in the third trimester, with the window of 27 through 30 weeks of gestation yielding the highest cord blood levels,” the researchers said.
The study was supported in part by the Centers for Disease Control and Prevention. Dr. Healy disclosed relationships with Sanofi Pasteur, Novartis Vaccines, Pfizer, and Novavax.
SOURCE: Healy C et al. JAMA. 2018 Oct 9;320(14):1464-70.
Immunization of pregnant women with the Tdap vaccine during weeks 27-30 of pregnancy yielded the higher concentration of protective pertussis toxin antibodies in neonates, compared with neonates not exposed to the vaccine, based on data from more than 600 pregnancies.
The Centers for Disease Control and Prevention recommends Tdap vaccination for pregnant women between 27 and 35 weeks’ gestation, but “data on pertussis antibody concentrations following maternal Tdap immunization are limited because of small cohort size or differing immunization schedules,” wrote C. Mary Healy, MD, of Baylor College of Medicine, Houston and her colleagues.
In an observational study published in JAMA, the researchers reviewed data from 626 pregnancies and births at a single tertiary care center in Texas. The average age of the mothers was 30 years; 41% were white, 27% Hispanic, 26% black, 5% Asian, and 1% another ethnicity. Of these, 312 received the Tdap vaccine at an average gestation of 31 weeks, while 314 women were not immunized.
Overall, the geometric mean concentration (GMC) of neonatal umbilical cord pertussis toxin antibodies among infants exposed to Tdap was 47.3 IU/mL, compared with 12.9 IU/mL for unexposed infants, yielding a GMC ratio of 3.6 (P less than .001).
In addition, pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher were significantly more common in Tdap-exposed vs. Tdap-unexposed neonates (86% vs. 37%, 72% vs. 17%, 59% vs. 12%, respectively).
The GMC of pertussis toxin antibodies was highest when the vaccine was given during weeks 27-30, after which the GMC declined, the researchers noted.
The study was limited by several factors including the observational design, which does not support causes and effect analysis, the use of data from a single center, and the lack of pre- and postimmunization serum samples for comparison, and the absence of data on women immunized during the second trimester, the researchers wrote.
However, the results support data from previous studies, and were strengthened by the large study population. The findings suggest that “following U.S. immunization recommendations and in accordance with current understanding of the kinetics of placental transfer, optimal time to administer Tdap vaccine to maximize pertussis toxin antibodies at birth may be early in the third trimester, with the window of 27 through 30 weeks of gestation yielding the highest cord blood levels,” the researchers said.
The study was supported in part by the Centers for Disease Control and Prevention. Dr. Healy disclosed relationships with Sanofi Pasteur, Novartis Vaccines, Pfizer, and Novavax.
SOURCE: Healy C et al. JAMA. 2018 Oct 9;320(14):1464-70.
FROM JAMA
Key clinical point:
Major finding: The geometric mean concentration of neonatal cord pertussis toxin antibodies was 47.3 IU/mL among newborns exposed to Tdap, compared with 12.9 IU/mL among unexposed (P less than .001).
Study details: The data come from an observational study of 626 pregnancies.
Disclosures: The study was supported in part by the Centers for Disease Control and Prevention. Dr. Healy disclosed relationships with Sanofi Pasteur, Novartis Vaccines, Pfizer, and Novavax.
Source: Healy C et al. JAMA. 2018 Oct 9;320(14):1464-70.
ALTA-1L: Brigatinib beats crizotinib for PFS in ALK-positive NSCLC
TORONTO – in the first interim results from the multicenter, open-label, phase 3 ALTA-1L trial.
In fact, the primary endpoint of the study – blinded independent review committee–assessed progression-free survival (PFS) – was met at this first analysis. The next-generation ALK inhibitor brigatinib reduced the chance of progression or death by 51% as compared with crizotinib – the current first-line standard of care in this population, D. Ross Camidge, MD, reported at the World Conference on Lung Cancer.
“At a median follow-up of 9-11 months, 26% [of 137 patients] on the brigatinib arm and 46% [of 138 patients] on the crizotinib arm had experienced a PFS event. Median PFS was not reached for the brigatinib arm and was 9.8 months for the crizotinib arm; the hazard ratio for progression or death was 0.49 and highly statistically significant,” said Dr. Camidge, director of thoracic oncology and the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, Aurora, at the meeting sponsored by the International Association for the Study of Lung Cancer.
The findings were published simultaneously in the New England Journal of Medicine.
The 12-month PFS rate estimate was 67% for brigatinib and 43% for crizotinib, and the investigator-assessed hazard ratio for PFS was 0.45. Overall survival data are immature, Dr. Camidge added, noting that the PFS hazard ratios for those with versus those without prior chemotherapy were 0.35 and 0.55, respectively.
“PFS consistently favored brigatinib across all other subgroups,” he said. “Although the confidence intervals overlap, the effect size appears greater among those with baseline [CNS] disease than among those without [HR, 0.2 vs. 0.72].”
Data suggest that CNS progression among those with CNS disease at baseline tends to be an earlier event than either extra-CNS progression in general or CNS progression in those without baseline CNS disease. “Consequently, this first interim analysis may be preferentially emphasizing drug efficacy differences within the subgroup in whom the earlier progression events are occurring,” Dr. Camidge said.
As for overall objective responses, the rates were numerically higher with brigatinib versus crizotinib (70% vs. 60%), but were not statistically different in the two groups. “However, the median duration of confirmed responses was not reached for brigatinib and [was] 11.1 months with crizotinib, with the 12-month [probability] of sustained response being 75% for brigatinib and 41% for crizotinib,” he added.
Further, among those with measurable CNS lesions, brigatinib demonstrated a significantly higher intracranial response rate of 78% versus 29% (odds ratio, 10.42), and when those with nonmeasurable CNS disease were included in the intracranial response assessment, the odds ratio was 13.
Median intracranial PFS among those with CNS involvement at baseline was not reached in the brigatinib arm versus 5.6 months with crizotinib, for a highly statistically significant hazard ratio of 0.27. “Which, given that the median PFS for crizotinib in the overall population ... was 9.8 months, again emphasizes how CNS events in this subgroup tend to occur early,” he noted.
Study subjects had stage IIIB/IV ALK-positive non–small cell lung cancer (NSCLC) based on local ALK testing, Eastern Cooperative Oncology Group performance status of 0-2, no more than one prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor therapy, Dr. Camidge said, noting that asymptomatic, untreated brain metastases were allowed and crossover to the brigatinib arm was permitted for those with blinded independent review committee–assessed progression on crizotinib.
Those randomized to the brigatinib arm had a median age of 58 years and received 180 mg daily with a 7-day lead-in at 90 mg. Those randomized to the crizotinib group had a median age of 60 years and received 250 mg twice daily. Prior chemotherapy for advanced disease was received by 26% and 27% and brain metastasis was present in 29% and 30% of patients in the arms, respectively.
The most common treatment-emergent adverse events of grade 3 or higher in the brigatinib patients were laboratory abnormalities such as creatinine phosphokinase, lipase, and amylase increases, and the most common in the crizotinib group were gastrointestinal effects, transaminitis, bradycardia, peripheral edema, and vision disturbances.
Discontinuations caused by adverse events occurred in 12% and 9% of the brigatinib and crizotinib patients, respectively, he said. No clinical cases of pancreatitis occurred in either arm, there was no difference in the incidence of any grade myalgia or musculoskeletal pain between arms, and there was no grade 3 or greater myalgia or musculoskeletal pain reported.
Early-onset interstitial lung disease, however, “appears to be a unique side effect of brigatinib,” Dr. Camidge noted.
Although interstitial lung disease/pneumonitis occurred in both groups, onset at days 3-8 after treatment initiation occurred only with brigatinib, he said, adding that “it only occurred in 3% of cases – half the rate seen in the postcrizotinib setting.”
The PROFILE 1014 study established crizotinib as the standard first-line therapy for advanced ALK-rearranged NSCLC, showing superior PFS versus pemetrexed doublet chemotherapy (HR, 0.45), but median PFS with crizotinib in that trial was only 10.9 months, Dr. Camidge said.
The next-generation ALK inhibitor brigatinib, however, has demonstrated broad preclinical activity against ALK resistance mutations, has excellent CNS penetration, and is the only ALK inhibitor with marked activity against multiple epidermal growth factor receptor–mutant cell lines, he said. “It has already shown significant activity both within the CNS and extracranially in the postcrizotinib setting, where it has consistently demonstrated the longest reported median PFS [up to 16.7 months] of any licensed or experimental ALK inhibitor.”
The ALTA-1L study provides a head-to-head comparison of brigatinib and crizotinib in a real-world setting, and the findings demonstrate that “brigatinib represents a promising new treatment for inhibitor-naive, ALK-rearranged NSCLC,” he said.
In a press statement, Dr. Camidge further stated that, based on these findings, brigatinib is set to become a first-line treatment option for ALK-positive lung cancer, adding that, “even with only 9-11 months of follow-up, the efficacy of brigatinib is clearly superior to crizotinib. A lot of the initial difference is driven by an effect on brain metastases, which tend to be an earlier progression event. However, once differences in control of disease outside the brain have time to manifest, it is possible the PFS improvement may increase.”
Both Dr. Camidge and invited discussant Fiona Blackhall, PhD, noted that the tolerability of brigatinib may be “even better in the real world,” as most of the 29% of patients on the brigatinib arm with adverse event–related dose reductions had “paper toxicities” for which the clinical impact is not well understood.
The rate of dose reductions for adverse events with brigatinib was higher in ALTA-1L than that seen in earlier studies of the second-generation ALK inhibitor alectinib, said Dr. Blackhall, professor and chair in thoracic oncology at the University of Manchester (England).
“We need to be sure that these dose reductions are appropriate and not potentially compromising efficacy,” she added.
Dr. Blackhall also suggested that sequential use of crizotinib and other ALK inhibitors like brigatinib should be evaluated and that the potential impact of ALK inhibitor selection “on the spectrum and type of resistance mutations and mechanisms” should be considered.
“Brigatinib is a new first-line treatment option for patients with ALK-positive non–small cell lung cancer. ... But in the absence of direct comparison of next-generation ALK inhibitors, it is going to take some time before we can determine whether there is indeed – if there ever will be – a ‘best’ ALK inhibitor for our patients,” she said.
Dr. Camidge has received honoraria from Arrys/Kyn, AstraZeneca, Biothera, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Medicines, Roche/Genentech, and Takeda, and has received research funding from ARIADTakeda. Dr. Blackhall reported research funding from Amgen, AstraZeneca, Novartis, and Pfizer, and has served has an advisory board member, consultant, or speaker for AbbVie, Boehringer Ingelheim, Cell Medica, Medivation, Merck, Regeneron, Roche, and Takeda.
SOURCE: Camidge DR et al. WCLC 2018, Abstract PL02.03.
TORONTO – in the first interim results from the multicenter, open-label, phase 3 ALTA-1L trial.
In fact, the primary endpoint of the study – blinded independent review committee–assessed progression-free survival (PFS) – was met at this first analysis. The next-generation ALK inhibitor brigatinib reduced the chance of progression or death by 51% as compared with crizotinib – the current first-line standard of care in this population, D. Ross Camidge, MD, reported at the World Conference on Lung Cancer.
“At a median follow-up of 9-11 months, 26% [of 137 patients] on the brigatinib arm and 46% [of 138 patients] on the crizotinib arm had experienced a PFS event. Median PFS was not reached for the brigatinib arm and was 9.8 months for the crizotinib arm; the hazard ratio for progression or death was 0.49 and highly statistically significant,” said Dr. Camidge, director of thoracic oncology and the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, Aurora, at the meeting sponsored by the International Association for the Study of Lung Cancer.
The findings were published simultaneously in the New England Journal of Medicine.
The 12-month PFS rate estimate was 67% for brigatinib and 43% for crizotinib, and the investigator-assessed hazard ratio for PFS was 0.45. Overall survival data are immature, Dr. Camidge added, noting that the PFS hazard ratios for those with versus those without prior chemotherapy were 0.35 and 0.55, respectively.
“PFS consistently favored brigatinib across all other subgroups,” he said. “Although the confidence intervals overlap, the effect size appears greater among those with baseline [CNS] disease than among those without [HR, 0.2 vs. 0.72].”
Data suggest that CNS progression among those with CNS disease at baseline tends to be an earlier event than either extra-CNS progression in general or CNS progression in those without baseline CNS disease. “Consequently, this first interim analysis may be preferentially emphasizing drug efficacy differences within the subgroup in whom the earlier progression events are occurring,” Dr. Camidge said.
As for overall objective responses, the rates were numerically higher with brigatinib versus crizotinib (70% vs. 60%), but were not statistically different in the two groups. “However, the median duration of confirmed responses was not reached for brigatinib and [was] 11.1 months with crizotinib, with the 12-month [probability] of sustained response being 75% for brigatinib and 41% for crizotinib,” he added.
Further, among those with measurable CNS lesions, brigatinib demonstrated a significantly higher intracranial response rate of 78% versus 29% (odds ratio, 10.42), and when those with nonmeasurable CNS disease were included in the intracranial response assessment, the odds ratio was 13.
Median intracranial PFS among those with CNS involvement at baseline was not reached in the brigatinib arm versus 5.6 months with crizotinib, for a highly statistically significant hazard ratio of 0.27. “Which, given that the median PFS for crizotinib in the overall population ... was 9.8 months, again emphasizes how CNS events in this subgroup tend to occur early,” he noted.
Study subjects had stage IIIB/IV ALK-positive non–small cell lung cancer (NSCLC) based on local ALK testing, Eastern Cooperative Oncology Group performance status of 0-2, no more than one prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor therapy, Dr. Camidge said, noting that asymptomatic, untreated brain metastases were allowed and crossover to the brigatinib arm was permitted for those with blinded independent review committee–assessed progression on crizotinib.
Those randomized to the brigatinib arm had a median age of 58 years and received 180 mg daily with a 7-day lead-in at 90 mg. Those randomized to the crizotinib group had a median age of 60 years and received 250 mg twice daily. Prior chemotherapy for advanced disease was received by 26% and 27% and brain metastasis was present in 29% and 30% of patients in the arms, respectively.
The most common treatment-emergent adverse events of grade 3 or higher in the brigatinib patients were laboratory abnormalities such as creatinine phosphokinase, lipase, and amylase increases, and the most common in the crizotinib group were gastrointestinal effects, transaminitis, bradycardia, peripheral edema, and vision disturbances.
Discontinuations caused by adverse events occurred in 12% and 9% of the brigatinib and crizotinib patients, respectively, he said. No clinical cases of pancreatitis occurred in either arm, there was no difference in the incidence of any grade myalgia or musculoskeletal pain between arms, and there was no grade 3 or greater myalgia or musculoskeletal pain reported.
Early-onset interstitial lung disease, however, “appears to be a unique side effect of brigatinib,” Dr. Camidge noted.
Although interstitial lung disease/pneumonitis occurred in both groups, onset at days 3-8 after treatment initiation occurred only with brigatinib, he said, adding that “it only occurred in 3% of cases – half the rate seen in the postcrizotinib setting.”
The PROFILE 1014 study established crizotinib as the standard first-line therapy for advanced ALK-rearranged NSCLC, showing superior PFS versus pemetrexed doublet chemotherapy (HR, 0.45), but median PFS with crizotinib in that trial was only 10.9 months, Dr. Camidge said.
The next-generation ALK inhibitor brigatinib, however, has demonstrated broad preclinical activity against ALK resistance mutations, has excellent CNS penetration, and is the only ALK inhibitor with marked activity against multiple epidermal growth factor receptor–mutant cell lines, he said. “It has already shown significant activity both within the CNS and extracranially in the postcrizotinib setting, where it has consistently demonstrated the longest reported median PFS [up to 16.7 months] of any licensed or experimental ALK inhibitor.”
The ALTA-1L study provides a head-to-head comparison of brigatinib and crizotinib in a real-world setting, and the findings demonstrate that “brigatinib represents a promising new treatment for inhibitor-naive, ALK-rearranged NSCLC,” he said.
In a press statement, Dr. Camidge further stated that, based on these findings, brigatinib is set to become a first-line treatment option for ALK-positive lung cancer, adding that, “even with only 9-11 months of follow-up, the efficacy of brigatinib is clearly superior to crizotinib. A lot of the initial difference is driven by an effect on brain metastases, which tend to be an earlier progression event. However, once differences in control of disease outside the brain have time to manifest, it is possible the PFS improvement may increase.”
Both Dr. Camidge and invited discussant Fiona Blackhall, PhD, noted that the tolerability of brigatinib may be “even better in the real world,” as most of the 29% of patients on the brigatinib arm with adverse event–related dose reductions had “paper toxicities” for which the clinical impact is not well understood.
The rate of dose reductions for adverse events with brigatinib was higher in ALTA-1L than that seen in earlier studies of the second-generation ALK inhibitor alectinib, said Dr. Blackhall, professor and chair in thoracic oncology at the University of Manchester (England).
“We need to be sure that these dose reductions are appropriate and not potentially compromising efficacy,” she added.
Dr. Blackhall also suggested that sequential use of crizotinib and other ALK inhibitors like brigatinib should be evaluated and that the potential impact of ALK inhibitor selection “on the spectrum and type of resistance mutations and mechanisms” should be considered.
“Brigatinib is a new first-line treatment option for patients with ALK-positive non–small cell lung cancer. ... But in the absence of direct comparison of next-generation ALK inhibitors, it is going to take some time before we can determine whether there is indeed – if there ever will be – a ‘best’ ALK inhibitor for our patients,” she said.
Dr. Camidge has received honoraria from Arrys/Kyn, AstraZeneca, Biothera, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Medicines, Roche/Genentech, and Takeda, and has received research funding from ARIADTakeda. Dr. Blackhall reported research funding from Amgen, AstraZeneca, Novartis, and Pfizer, and has served has an advisory board member, consultant, or speaker for AbbVie, Boehringer Ingelheim, Cell Medica, Medivation, Merck, Regeneron, Roche, and Takeda.
SOURCE: Camidge DR et al. WCLC 2018, Abstract PL02.03.
TORONTO – in the first interim results from the multicenter, open-label, phase 3 ALTA-1L trial.
In fact, the primary endpoint of the study – blinded independent review committee–assessed progression-free survival (PFS) – was met at this first analysis. The next-generation ALK inhibitor brigatinib reduced the chance of progression or death by 51% as compared with crizotinib – the current first-line standard of care in this population, D. Ross Camidge, MD, reported at the World Conference on Lung Cancer.
“At a median follow-up of 9-11 months, 26% [of 137 patients] on the brigatinib arm and 46% [of 138 patients] on the crizotinib arm had experienced a PFS event. Median PFS was not reached for the brigatinib arm and was 9.8 months for the crizotinib arm; the hazard ratio for progression or death was 0.49 and highly statistically significant,” said Dr. Camidge, director of thoracic oncology and the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, Aurora, at the meeting sponsored by the International Association for the Study of Lung Cancer.
The findings were published simultaneously in the New England Journal of Medicine.
The 12-month PFS rate estimate was 67% for brigatinib and 43% for crizotinib, and the investigator-assessed hazard ratio for PFS was 0.45. Overall survival data are immature, Dr. Camidge added, noting that the PFS hazard ratios for those with versus those without prior chemotherapy were 0.35 and 0.55, respectively.
“PFS consistently favored brigatinib across all other subgroups,” he said. “Although the confidence intervals overlap, the effect size appears greater among those with baseline [CNS] disease than among those without [HR, 0.2 vs. 0.72].”
Data suggest that CNS progression among those with CNS disease at baseline tends to be an earlier event than either extra-CNS progression in general or CNS progression in those without baseline CNS disease. “Consequently, this first interim analysis may be preferentially emphasizing drug efficacy differences within the subgroup in whom the earlier progression events are occurring,” Dr. Camidge said.
As for overall objective responses, the rates were numerically higher with brigatinib versus crizotinib (70% vs. 60%), but were not statistically different in the two groups. “However, the median duration of confirmed responses was not reached for brigatinib and [was] 11.1 months with crizotinib, with the 12-month [probability] of sustained response being 75% for brigatinib and 41% for crizotinib,” he added.
Further, among those with measurable CNS lesions, brigatinib demonstrated a significantly higher intracranial response rate of 78% versus 29% (odds ratio, 10.42), and when those with nonmeasurable CNS disease were included in the intracranial response assessment, the odds ratio was 13.
Median intracranial PFS among those with CNS involvement at baseline was not reached in the brigatinib arm versus 5.6 months with crizotinib, for a highly statistically significant hazard ratio of 0.27. “Which, given that the median PFS for crizotinib in the overall population ... was 9.8 months, again emphasizes how CNS events in this subgroup tend to occur early,” he noted.
Study subjects had stage IIIB/IV ALK-positive non–small cell lung cancer (NSCLC) based on local ALK testing, Eastern Cooperative Oncology Group performance status of 0-2, no more than one prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor therapy, Dr. Camidge said, noting that asymptomatic, untreated brain metastases were allowed and crossover to the brigatinib arm was permitted for those with blinded independent review committee–assessed progression on crizotinib.
Those randomized to the brigatinib arm had a median age of 58 years and received 180 mg daily with a 7-day lead-in at 90 mg. Those randomized to the crizotinib group had a median age of 60 years and received 250 mg twice daily. Prior chemotherapy for advanced disease was received by 26% and 27% and brain metastasis was present in 29% and 30% of patients in the arms, respectively.
The most common treatment-emergent adverse events of grade 3 or higher in the brigatinib patients were laboratory abnormalities such as creatinine phosphokinase, lipase, and amylase increases, and the most common in the crizotinib group were gastrointestinal effects, transaminitis, bradycardia, peripheral edema, and vision disturbances.
Discontinuations caused by adverse events occurred in 12% and 9% of the brigatinib and crizotinib patients, respectively, he said. No clinical cases of pancreatitis occurred in either arm, there was no difference in the incidence of any grade myalgia or musculoskeletal pain between arms, and there was no grade 3 or greater myalgia or musculoskeletal pain reported.
Early-onset interstitial lung disease, however, “appears to be a unique side effect of brigatinib,” Dr. Camidge noted.
Although interstitial lung disease/pneumonitis occurred in both groups, onset at days 3-8 after treatment initiation occurred only with brigatinib, he said, adding that “it only occurred in 3% of cases – half the rate seen in the postcrizotinib setting.”
The PROFILE 1014 study established crizotinib as the standard first-line therapy for advanced ALK-rearranged NSCLC, showing superior PFS versus pemetrexed doublet chemotherapy (HR, 0.45), but median PFS with crizotinib in that trial was only 10.9 months, Dr. Camidge said.
The next-generation ALK inhibitor brigatinib, however, has demonstrated broad preclinical activity against ALK resistance mutations, has excellent CNS penetration, and is the only ALK inhibitor with marked activity against multiple epidermal growth factor receptor–mutant cell lines, he said. “It has already shown significant activity both within the CNS and extracranially in the postcrizotinib setting, where it has consistently demonstrated the longest reported median PFS [up to 16.7 months] of any licensed or experimental ALK inhibitor.”
The ALTA-1L study provides a head-to-head comparison of brigatinib and crizotinib in a real-world setting, and the findings demonstrate that “brigatinib represents a promising new treatment for inhibitor-naive, ALK-rearranged NSCLC,” he said.
In a press statement, Dr. Camidge further stated that, based on these findings, brigatinib is set to become a first-line treatment option for ALK-positive lung cancer, adding that, “even with only 9-11 months of follow-up, the efficacy of brigatinib is clearly superior to crizotinib. A lot of the initial difference is driven by an effect on brain metastases, which tend to be an earlier progression event. However, once differences in control of disease outside the brain have time to manifest, it is possible the PFS improvement may increase.”
Both Dr. Camidge and invited discussant Fiona Blackhall, PhD, noted that the tolerability of brigatinib may be “even better in the real world,” as most of the 29% of patients on the brigatinib arm with adverse event–related dose reductions had “paper toxicities” for which the clinical impact is not well understood.
The rate of dose reductions for adverse events with brigatinib was higher in ALTA-1L than that seen in earlier studies of the second-generation ALK inhibitor alectinib, said Dr. Blackhall, professor and chair in thoracic oncology at the University of Manchester (England).
“We need to be sure that these dose reductions are appropriate and not potentially compromising efficacy,” she added.
Dr. Blackhall also suggested that sequential use of crizotinib and other ALK inhibitors like brigatinib should be evaluated and that the potential impact of ALK inhibitor selection “on the spectrum and type of resistance mutations and mechanisms” should be considered.
“Brigatinib is a new first-line treatment option for patients with ALK-positive non–small cell lung cancer. ... But in the absence of direct comparison of next-generation ALK inhibitors, it is going to take some time before we can determine whether there is indeed – if there ever will be – a ‘best’ ALK inhibitor for our patients,” she said.
Dr. Camidge has received honoraria from Arrys/Kyn, AstraZeneca, Biothera, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Medicines, Roche/Genentech, and Takeda, and has received research funding from ARIADTakeda. Dr. Blackhall reported research funding from Amgen, AstraZeneca, Novartis, and Pfizer, and has served has an advisory board member, consultant, or speaker for AbbVie, Boehringer Ingelheim, Cell Medica, Medivation, Merck, Regeneron, Roche, and Takeda.
SOURCE: Camidge DR et al. WCLC 2018, Abstract PL02.03.
REPORTING FROM WCLC 2018
Key clinical point: Brigatinib improves progression-free survival versus crizotinib in anaplastic lymphoma kinase–positive non–small cell lung cancer.
Major finding: Brigatinib reduced the chance of progression or death by 51% versus crizotinib.
Study details: The multicenter, open-label, phase 3 ALTA-1L trial of 275 patients.
Disclosures: Dr. Camidge has received honoraria from Arrys/Kyn, AstraZeneca, Biothera, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Medicines, Roche/Genentech, and Takeda, and has received research funding from ARIAD/Takeda. Dr. Blackhall reported research funding from Amgen, AstraZeneca, Novartis, and Pfizer, and has served has an advisory board member, consultant, or speaker for AbbVie, Boehringer Ingelheim, Cell Medica, Medivation, Merck, Regeneron, Roche, and Takeda.
Source: Camidge DR et al. WCLC 2018, Abstract PL02.03.