There are no benefits from vitamin D supplementation in reducing the risk of major adverse cardiovascular events or all-cause mortality, according to a meta-analysis published in JAMA Cardiology.

copyright istock/Thinkstock

Researchers analyzed data from 83,291 patients enrolled in 21 randomized, placebo-controlled clinical trials of at least 1 year of vitamin D supplementation.

They found the incidence of major adverse cardiovascular events ­was the same among patients taking vitamin D supplements and those taking placebo (risk ratio, 1; P = .85). Even stratifying by age, sex, postmenopausal status, pretreatment vitamin D levels, vitamin D dosage and formulation, chronic kidney disease, or excluding studies that used vitamin D analogues made no significant difference.

However, there was the suggestion of reduced incidence of major adverse cardiovascular events with vitamin D supplementation in individuals of advanced age, but the authors wrote that the finding should be interpreted with caution.

The analysis found no benefit from vitamin D supplementation on the secondary endpoints of MI, stroke, cardiovascular mortality, or all-cause mortality risk.


Mahmoud Barbarawi, MD, from the Hurley Medical Center at Michigan State University, East Lansing, and coauthors commented that previous observational studies have found significant associations between low vitamin D levels and cardiovascular events and all-cause mortality.

“However, observational studies are susceptible to uncontrolled confounding by outdoor physical activity, nutritional status, and prevalent chronic disease, which may influence serum 25-hydroxyvitamin D levels,” they wrote.

This updated analysis extended earlier clinical trial findings and added in some more-recent randomized trial outcomes, including the massive VITAL trial, which showed that neither daily vitamin D nor omega-3 fatty acids reduce cancer or cardiovascular event risk (N Engl J Med. 2019;380[1]:33-44).

Still, the authors noted that most of the trials included in the analysis had not prespecified cardiovascular disease as the primary endpoint and were underpowered to detect an effect on cardiovascular events. They also pointed out that few trials included data on heart failure, and a previous meta-analysis had suggested a potential benefit of supplementation in reducing the risk of this condition.

“Additional trials of higher-dose vitamin D supplementation, perhaps targeting members of older age groups and with attention to other [cardiovascular disease] endpoints such as heart failure, are of interest,” they wrote.

One author reported receiving funding from the National Institutes of Health and in-kind support from the pharmaceutical sector for a vitamin D study. No other disclosures were reported.

SOURCE: Barbarawi M et al. JAMA Cardiol. 2019 Jun 19. doi: 10.1001/jamacardio.2019.1870.

There are no benefits from vitamin D supplementation in reducing the risk of major adverse cardiovascular events or all-cause mortality, according to a meta-analysis published in JAMA Cardiology.

copyright istock/Thinkstock

Researchers analyzed data from 83,291 patients enrolled in 21 randomized, placebo-controlled clinical trials of at least 1 year of vitamin D supplementation.

They found the incidence of major adverse cardiovascular events ­was the same among patients taking vitamin D supplements and those taking placebo (risk ratio, 1; P = .85). Even stratifying by age, sex, postmenopausal status, pretreatment vitamin D levels, vitamin D dosage and formulation, chronic kidney disease, or excluding studies that used vitamin D analogues made no significant difference.

However, there was the suggestion of reduced incidence of major adverse cardiovascular events with vitamin D supplementation in individuals of advanced age, but the authors wrote that the finding should be interpreted with caution.

The analysis found no benefit from vitamin D supplementation on the secondary endpoints of MI, stroke, cardiovascular mortality, or all-cause mortality risk.


Mahmoud Barbarawi, MD, from the Hurley Medical Center at Michigan State University, East Lansing, and coauthors commented that previous observational studies have found significant associations between low vitamin D levels and cardiovascular events and all-cause mortality.

“However, observational studies are susceptible to uncontrolled confounding by outdoor physical activity, nutritional status, and prevalent chronic disease, which may influence serum 25-hydroxyvitamin D levels,” they wrote.

This updated analysis extended earlier clinical trial findings and added in some more-recent randomized trial outcomes, including the massive VITAL trial, which showed that neither daily vitamin D nor omega-3 fatty acids reduce cancer or cardiovascular event risk (N Engl J Med. 2019;380[1]:33-44).

Still, the authors noted that most of the trials included in the analysis had not prespecified cardiovascular disease as the primary endpoint and were underpowered to detect an effect on cardiovascular events. They also pointed out that few trials included data on heart failure, and a previous meta-analysis had suggested a potential benefit of supplementation in reducing the risk of this condition.

“Additional trials of higher-dose vitamin D supplementation, perhaps targeting members of older age groups and with attention to other [cardiovascular disease] endpoints such as heart failure, are of interest,” they wrote.

One author reported receiving funding from the National Institutes of Health and in-kind support from the pharmaceutical sector for a vitamin D study. No other disclosures were reported.

SOURCE: Barbarawi M et al. JAMA Cardiol. 2019 Jun 19. doi: 10.1001/jamacardio.2019.1870.

There are no benefits from vitamin D supplementation in reducing the risk of major adverse cardiovascular events or all-cause mortality, according to a meta-analysis published in JAMA Cardiology.

copyright istock/Thinkstock

Researchers analyzed data from 83,291 patients enrolled in 21 randomized, placebo-controlled clinical trials of at least 1 year of vitamin D supplementation.

They found the incidence of major adverse cardiovascular events ­was the same among patients taking vitamin D supplements and those taking placebo (risk ratio, 1; P = .85). Even stratifying by age, sex, postmenopausal status, pretreatment vitamin D levels, vitamin D dosage and formulation, chronic kidney disease, or excluding studies that used vitamin D analogues made no significant difference.

However, there was the suggestion of reduced incidence of major adverse cardiovascular events with vitamin D supplementation in individuals of advanced age, but the authors wrote that the finding should be interpreted with caution.

The analysis found no benefit from vitamin D supplementation on the secondary endpoints of MI, stroke, cardiovascular mortality, or all-cause mortality risk.


Mahmoud Barbarawi, MD, from the Hurley Medical Center at Michigan State University, East Lansing, and coauthors commented that previous observational studies have found significant associations between low vitamin D levels and cardiovascular events and all-cause mortality.

“However, observational studies are susceptible to uncontrolled confounding by outdoor physical activity, nutritional status, and prevalent chronic disease, which may influence serum 25-hydroxyvitamin D levels,” they wrote.

This updated analysis extended earlier clinical trial findings and added in some more-recent randomized trial outcomes, including the massive VITAL trial, which showed that neither daily vitamin D nor omega-3 fatty acids reduce cancer or cardiovascular event risk (N Engl J Med. 2019;380[1]:33-44).

Still, the authors noted that most of the trials included in the analysis had not prespecified cardiovascular disease as the primary endpoint and were underpowered to detect an effect on cardiovascular events. They also pointed out that few trials included data on heart failure, and a previous meta-analysis had suggested a potential benefit of supplementation in reducing the risk of this condition.

“Additional trials of higher-dose vitamin D supplementation, perhaps targeting members of older age groups and with attention to other [cardiovascular disease] endpoints such as heart failure, are of interest,” they wrote.

One author reported receiving funding from the National Institutes of Health and in-kind support from the pharmaceutical sector for a vitamin D study. No other disclosures were reported.

SOURCE: Barbarawi M et al. JAMA Cardiol. 2019 Jun 19. doi: 10.1001/jamacardio.2019.1870.

Presenter

Patricia Kritek MD, EdM

Session Title

Sepsis update: From screening to refractory shock

Background

Each year 1.7 million adults in America develop sepsis, and 270,000 Americans die from sepsis annually. Sepsis costs U.S. health care over $27 billion dollars each year. Because of the wide range of etiologies and variation in presentation and intensity, it is a challenge to establish homogeneous evidence based guidelines.¹

The definition of sepsis based on the “SIRS” criterion was developed initially in 1992, later revised as Sepsis-2 in 2001. The latest Sepsis-3 definition – “life-threatening organ dysfunction due to a dysregulated host response to infection” – was developed in 2016 by the Third International Consensus Definitions for Sepsis and Septic Shock. This newest definition has renounced the SIRS criterion and adopted the Sequential Organ Failure Assessment (SOFA) score. Treatment guidelines in sepsis were developed by the Surviving Sepsis Campaign starting with the Barcelona Declaration in 2002 and revised multiple times, with the development of 3-hour and 6-hour care bundles in 2012. The latest revision, in 2018, consolidated to a 1-hour bundle.²

Sepsis is a continuum of every severe infection, and with the combined efforts of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine, evidence-based guidelines have been developed over the past 2 decades, with the latest iteration in 2018. The Centers for Medicare & Medicaid Services still uses Sepsis-2 for diagnosis, and the 3-hr/6-hr bundle compliance (2016) for expected care.³

Session summary

Dr. Kritek, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, presented to a room of over 1,000 enthusiastic hospitalists. She was able to capture everyone’s attention with a great presentation. As sepsis is one of the most common and serious conditions we encounter, most hospitalists are fairly well versed in evidence-based practices, and Dr. Kritek was able to keep us engaged, describing in detail the evolving definition, pathophysiology, and screening procedures for sepsis. She also spoke about important studies and the latest evidence that will positively impact each hospitalist’s practice in treating sepsis.

Dr. Kritek explained clearly how the Surviving Sepsis Campaign developed a vital and nontraditional guideline that “recommends health systems have a performance improvement program for sepsis including screening for high-risk patients.” In a 1-hour session, Dr. Kritek did a commendable job untangling this bewildering health care challenge, and aligned each component to explain how to best use available resources and address sepsis in individual hospitals.

She talked about the statistics and historical aspects involved in the definition of sepsis, and the Surviving Sepsis Campaign. With three good case scenarios, Dr. Kritek explained how it was difficult to accurately diagnose sepsis using the Sepsis-2/SIRS criterion, and how the SIRS criterion led to several false positives. This created a need for the new Sepsis-3 definition, which used delta SOFA score of 2 indicating “organ failure.”

Key takeaways: Screening

• Sepsis-3 with delta SOFA score of at least 2 and Quick SOFA (qSOFA) of at least 2 was best at predicting in-hospital death, ICU admission, and long ICU stay in ED.
• qSOFA was not helpful in the admitted ICU population. An increase of at least 2 points in SOFA score within 24 hours of admission to the ICU was the best predictor of in-hospital mortality and long ICU stays.
• SIRS has high sensitivity and low specificity. The Early Warning Score has accuracy similar to qSOFA.
• Understanding that there is no perfect answer regarding screening, but having a process is vital for each organization. This approach led to the Surviving Sepsis Campaign guideline: “Recommend health systems have a performance improvement program for sepsis including screening for high-risk patients.”

Key takeaways: Treatment

• Meta-analysis showed that specifically targeted, early goal–directed treatment (specifically, central venous pressure 8-12 mm Hg, central venous oxygen saturation greater than 70%, packed red blood cell inotropes used) did not show any improvement in 90-day mortality, and actually generated worse outcomes, including cirrhosis, as well as higher costs of care.
• Antibiotics: Though part of the 3-hour bundle, antibiotics are recommended to be administered within 1 hour.
• Intravenous fluids: Patients with sepsis-induced hypoperfusion need 30 mL/kg crystalloids. Normal saline and lactated ringer are preferred. Lactated ringer has the advantage over normal saline, with a reduced incidence of major adverse kidney events.
• Importance of bundle compliance: N.Y. study showed use of protocols cut mortality from 30.2% to 25.4%.

Refractory septic shock

• Adding hydrocortisone and fludrocortisone improved mortality at 28 days, helped patients get off vasopressors sooner, and ultimately resulted in less organ failure. But no difference in 90-day mortality.
• A study of vitamin C use in septic patients needs further studies to validate, as it only included 47 patients.
• Early renal replacement therapy showed no difference in mortality or length of stay.

Dr. Kritek’s presentation made a positive impact by helping to explain the reasoning behind the established and evolving best practices and guidelines for care of patients with sepsis and septic shock. Her approach will help hospitalists provide cost-effective care, by understanding which expensive interventions and practices do not make a difference in patient care.

Dr. Odeti is hospitalist medical director at Johnston Memorial Hospital in Abingdon, Va. JMH is part of Ballad Health, a health system operating 21 hospitals in northeast Tennessee and southwest Virginia.

References

1. https://www.sepsis.org/wp-content/uploads/2017/05/Sepsis-Fact-Sheet-2018.pdf.

2. http://www.survivingsepsis.org/News/Pages/SCCM-and-ACEP-Release-Joint-Statement-About-the-Surviving-Sepsis-Campaign-Hour-1-Bundle.aspx

3. Specifications Manual for National Hospital Inpatient Quality Measures Discharges 01-01-17 (1Q17) through 12-31-17 (4Q17).

Presenter

Patricia Kritek MD, EdM

Session Title

Sepsis update: From screening to refractory shock

Background

Each year 1.7 million adults in America develop sepsis, and 270,000 Americans die from sepsis annually. Sepsis costs U.S. health care over $27 billion dollars each year. Because of the wide range of etiologies and variation in presentation and intensity, it is a challenge to establish homogeneous evidence based guidelines.¹

The definition of sepsis based on the “SIRS” criterion was developed initially in 1992, later revised as Sepsis-2 in 2001. The latest Sepsis-3 definition – “life-threatening organ dysfunction due to a dysregulated host response to infection” – was developed in 2016 by the Third International Consensus Definitions for Sepsis and Septic Shock. This newest definition has renounced the SIRS criterion and adopted the Sequential Organ Failure Assessment (SOFA) score. Treatment guidelines in sepsis were developed by the Surviving Sepsis Campaign starting with the Barcelona Declaration in 2002 and revised multiple times, with the development of 3-hour and 6-hour care bundles in 2012. The latest revision, in 2018, consolidated to a 1-hour bundle.²

Sepsis is a continuum of every severe infection, and with the combined efforts of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine, evidence-based guidelines have been developed over the past 2 decades, with the latest iteration in 2018. The Centers for Medicare & Medicaid Services still uses Sepsis-2 for diagnosis, and the 3-hr/6-hr bundle compliance (2016) for expected care.³

Session summary

Dr. Kritek, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, presented to a room of over 1,000 enthusiastic hospitalists. She was able to capture everyone’s attention with a great presentation. As sepsis is one of the most common and serious conditions we encounter, most hospitalists are fairly well versed in evidence-based practices, and Dr. Kritek was able to keep us engaged, describing in detail the evolving definition, pathophysiology, and screening procedures for sepsis. She also spoke about important studies and the latest evidence that will positively impact each hospitalist’s practice in treating sepsis.

Dr. Kritek explained clearly how the Surviving Sepsis Campaign developed a vital and nontraditional guideline that “recommends health systems have a performance improvement program for sepsis including screening for high-risk patients.” In a 1-hour session, Dr. Kritek did a commendable job untangling this bewildering health care challenge, and aligned each component to explain how to best use available resources and address sepsis in individual hospitals.

She talked about the statistics and historical aspects involved in the definition of sepsis, and the Surviving Sepsis Campaign. With three good case scenarios, Dr. Kritek explained how it was difficult to accurately diagnose sepsis using the Sepsis-2/SIRS criterion, and how the SIRS criterion led to several false positives. This created a need for the new Sepsis-3 definition, which used delta SOFA score of 2 indicating “organ failure.”

Key takeaways: Screening

• Sepsis-3 with delta SOFA score of at least 2 and Quick SOFA (qSOFA) of at least 2 was best at predicting in-hospital death, ICU admission, and long ICU stay in ED.
• qSOFA was not helpful in the admitted ICU population. An increase of at least 2 points in SOFA score within 24 hours of admission to the ICU was the best predictor of in-hospital mortality and long ICU stays.
• SIRS has high sensitivity and low specificity. The Early Warning Score has accuracy similar to qSOFA.
• Understanding that there is no perfect answer regarding screening, but having a process is vital for each organization. This approach led to the Surviving Sepsis Campaign guideline: “Recommend health systems have a performance improvement program for sepsis including screening for high-risk patients.”

Key takeaways: Treatment

• Meta-analysis showed that specifically targeted, early goal–directed treatment (specifically, central venous pressure 8-12 mm Hg, central venous oxygen saturation greater than 70%, packed red blood cell inotropes used) did not show any improvement in 90-day mortality, and actually generated worse outcomes, including cirrhosis, as well as higher costs of care.
• Antibiotics: Though part of the 3-hour bundle, antibiotics are recommended to be administered within 1 hour.
• Intravenous fluids: Patients with sepsis-induced hypoperfusion need 30 mL/kg crystalloids. Normal saline and lactated ringer are preferred. Lactated ringer has the advantage over normal saline, with a reduced incidence of major adverse kidney events.
• Importance of bundle compliance: N.Y. study showed use of protocols cut mortality from 30.2% to 25.4%.

Refractory septic shock

• Adding hydrocortisone and fludrocortisone improved mortality at 28 days, helped patients get off vasopressors sooner, and ultimately resulted in less organ failure. But no difference in 90-day mortality.
• A study of vitamin C use in septic patients needs further studies to validate, as it only included 47 patients.
• Early renal replacement therapy showed no difference in mortality or length of stay.

Dr. Kritek’s presentation made a positive impact by helping to explain the reasoning behind the established and evolving best practices and guidelines for care of patients with sepsis and septic shock. Her approach will help hospitalists provide cost-effective care, by understanding which expensive interventions and practices do not make a difference in patient care.

Dr. Odeti is hospitalist medical director at Johnston Memorial Hospital in Abingdon, Va. JMH is part of Ballad Health, a health system operating 21 hospitals in northeast Tennessee and southwest Virginia.

References

1. https://www.sepsis.org/wp-content/uploads/2017/05/Sepsis-Fact-Sheet-2018.pdf.

2. http://www.survivingsepsis.org/News/Pages/SCCM-and-ACEP-Release-Joint-Statement-About-the-Surviving-Sepsis-Campaign-Hour-1-Bundle.aspx

3. Specifications Manual for National Hospital Inpatient Quality Measures Discharges 01-01-17 (1Q17) through 12-31-17 (4Q17).

Presenter

Patricia Kritek MD, EdM

Session Title

Sepsis update: From screening to refractory shock

Background

Each year 1.7 million adults in America develop sepsis, and 270,000 Americans die from sepsis annually. Sepsis costs U.S. health care over $27 billion dollars each year. Because of the wide range of etiologies and variation in presentation and intensity, it is a challenge to establish homogeneous evidence based guidelines.¹

The definition of sepsis based on the “SIRS” criterion was developed initially in 1992, later revised as Sepsis-2 in 2001. The latest Sepsis-3 definition – “life-threatening organ dysfunction due to a dysregulated host response to infection” – was developed in 2016 by the Third International Consensus Definitions for Sepsis and Septic Shock. This newest definition has renounced the SIRS criterion and adopted the Sequential Organ Failure Assessment (SOFA) score. Treatment guidelines in sepsis were developed by the Surviving Sepsis Campaign starting with the Barcelona Declaration in 2002 and revised multiple times, with the development of 3-hour and 6-hour care bundles in 2012. The latest revision, in 2018, consolidated to a 1-hour bundle.²

Sepsis is a continuum of every severe infection, and with the combined efforts of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine, evidence-based guidelines have been developed over the past 2 decades, with the latest iteration in 2018. The Centers for Medicare & Medicaid Services still uses Sepsis-2 for diagnosis, and the 3-hr/6-hr bundle compliance (2016) for expected care.³

Session summary

Dr. Kritek, of the division of pulmonary, critical care, and sleep medicine at the University of Washington, Seattle, presented to a room of over 1,000 enthusiastic hospitalists. She was able to capture everyone’s attention with a great presentation. As sepsis is one of the most common and serious conditions we encounter, most hospitalists are fairly well versed in evidence-based practices, and Dr. Kritek was able to keep us engaged, describing in detail the evolving definition, pathophysiology, and screening procedures for sepsis. She also spoke about important studies and the latest evidence that will positively impact each hospitalist’s practice in treating sepsis.

Dr. Kritek explained clearly how the Surviving Sepsis Campaign developed a vital and nontraditional guideline that “recommends health systems have a performance improvement program for sepsis including screening for high-risk patients.” In a 1-hour session, Dr. Kritek did a commendable job untangling this bewildering health care challenge, and aligned each component to explain how to best use available resources and address sepsis in individual hospitals.

She talked about the statistics and historical aspects involved in the definition of sepsis, and the Surviving Sepsis Campaign. With three good case scenarios, Dr. Kritek explained how it was difficult to accurately diagnose sepsis using the Sepsis-2/SIRS criterion, and how the SIRS criterion led to several false positives. This created a need for the new Sepsis-3 definition, which used delta SOFA score of 2 indicating “organ failure.”

Key takeaways: Screening

• Sepsis-3 with delta SOFA score of at least 2 and Quick SOFA (qSOFA) of at least 2 was best at predicting in-hospital death, ICU admission, and long ICU stay in ED.
• qSOFA was not helpful in the admitted ICU population. An increase of at least 2 points in SOFA score within 24 hours of admission to the ICU was the best predictor of in-hospital mortality and long ICU stays.
• SIRS has high sensitivity and low specificity. The Early Warning Score has accuracy similar to qSOFA.
• Understanding that there is no perfect answer regarding screening, but having a process is vital for each organization. This approach led to the Surviving Sepsis Campaign guideline: “Recommend health systems have a performance improvement program for sepsis including screening for high-risk patients.”

Key takeaways: Treatment

• Meta-analysis showed that specifically targeted, early goal–directed treatment (specifically, central venous pressure 8-12 mm Hg, central venous oxygen saturation greater than 70%, packed red blood cell inotropes used) did not show any improvement in 90-day mortality, and actually generated worse outcomes, including cirrhosis, as well as higher costs of care.
• Antibiotics: Though part of the 3-hour bundle, antibiotics are recommended to be administered within 1 hour.
• Intravenous fluids: Patients with sepsis-induced hypoperfusion need 30 mL/kg crystalloids. Normal saline and lactated ringer are preferred. Lactated ringer has the advantage over normal saline, with a reduced incidence of major adverse kidney events.
• Importance of bundle compliance: N.Y. study showed use of protocols cut mortality from 30.2% to 25.4%.

Refractory septic shock

• Adding hydrocortisone and fludrocortisone improved mortality at 28 days, helped patients get off vasopressors sooner, and ultimately resulted in less organ failure. But no difference in 90-day mortality.
• A study of vitamin C use in septic patients needs further studies to validate, as it only included 47 patients.
• Early renal replacement therapy showed no difference in mortality or length of stay.

Dr. Kritek’s presentation made a positive impact by helping to explain the reasoning behind the established and evolving best practices and guidelines for care of patients with sepsis and septic shock. Her approach will help hospitalists provide cost-effective care, by understanding which expensive interventions and practices do not make a difference in patient care.

Dr. Odeti is hospitalist medical director at Johnston Memorial Hospital in Abingdon, Va. JMH is part of Ballad Health, a health system operating 21 hospitals in northeast Tennessee and southwest Virginia.

References

1. https://www.sepsis.org/wp-content/uploads/2017/05/Sepsis-Fact-Sheet-2018.pdf.

2. http://www.survivingsepsis.org/News/Pages/SCCM-and-ACEP-Release-Joint-Statement-About-the-Surviving-Sepsis-Campaign-Hour-1-Bundle.aspx

3. Specifications Manual for National Hospital Inpatient Quality Measures Discharges 01-01-17 (1Q17) through 12-31-17 (4Q17).

Seventy percent of Americans would like to have conversations about the costs of care with their health care providers, but only 28% do so, according to polling conducted for the Robert Wood Johnson Foundation (RWJF) by Avalere Health.

utah778/Thinkstock

With those polling results in hand, 2 years ago RWJF and Avalere Health launched the Cost Conversation projects to help. Practice briefs for these kinds of conversations are now available on America’s Essential Hospitals’ website (https://essentialhospitals.org/cost-care/practice-briefs/).
 

Reference

1. Ganos E, Steinberg K, Seidman J, Masi D, Gomez-Rexode A, Fraser A. Talking About Costs: Innovation In Clinician-Patient Conversations. Health Affairs. Published online Nov. 27, 2018. doi: 10.1377/hblog20181126.366161. Accessed Dec. 11, 2018.

Seventy percent of Americans would like to have conversations about the costs of care with their health care providers, but only 28% do so, according to polling conducted for the Robert Wood Johnson Foundation (RWJF) by Avalere Health.

utah778/Thinkstock

With those polling results in hand, 2 years ago RWJF and Avalere Health launched the Cost Conversation projects to help. Practice briefs for these kinds of conversations are now available on America’s Essential Hospitals’ website (https://essentialhospitals.org/cost-care/practice-briefs/).
 

Reference

1. Ganos E, Steinberg K, Seidman J, Masi D, Gomez-Rexode A, Fraser A. Talking About Costs: Innovation In Clinician-Patient Conversations. Health Affairs. Published online Nov. 27, 2018. doi: 10.1377/hblog20181126.366161. Accessed Dec. 11, 2018.

Seventy percent of Americans would like to have conversations about the costs of care with their health care providers, but only 28% do so, according to polling conducted for the Robert Wood Johnson Foundation (RWJF) by Avalere Health.

utah778/Thinkstock

With those polling results in hand, 2 years ago RWJF and Avalere Health launched the Cost Conversation projects to help. Practice briefs for these kinds of conversations are now available on America’s Essential Hospitals’ website (https://essentialhospitals.org/cost-care/practice-briefs/).
 

Reference

1. Ganos E, Steinberg K, Seidman J, Masi D, Gomez-Rexode A, Fraser A. Talking About Costs: Innovation In Clinician-Patient Conversations. Health Affairs. Published online Nov. 27, 2018. doi: 10.1377/hblog20181126.366161. Accessed Dec. 11, 2018.

Patients with mild or moderate Alzheimer’s disease who took nilvadipine experienced increases in cerebral blood flow in the hippocampus, according to a new study.

copyright Radboud University Medical Center

Cerebral blood flow in other regions of the brain did not significantly change in patients who took the antihypertensive drug nilvadipine, according to a report on the trial published in Hypertension. Reduced cerebral blood flow is an early marker of Alzheimer’s disease, and the SPRINT MIND study suggests that intensive blood pressure control may reduce the risk of cognitive impairment.

“These findings [of the new study] not only indicate preserved cerebral autoregulation in Alzheimer’s disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment,” said Jurgen A.H.R. Claassen, MD, PhD of Radboud University Medical Center in Nijmegen, the Netherlands, and coauthors. “An important question is whether this observed increase in [cerebral blood flow] translates to clinical benefits. Unfortunately, sample sizes were too small and follow-up time too short to reliably study the effects ... on structural brain measures and cognitive measures.”

Nilvadipine is a dihydropyridine calcium antagonist used to treat hypertension. In the NILVAD trial, investigators assessed the effects of nilvadipine versus placebo in approximately 500 patients with Alzheimer’s disease. The 18-month trial found no beneficial effects of nilvadipine on cognitive function, but subgroup analyses suggested a potential benefit among patients in the early stages of the disease (PLoS Med. 2018 Sep 24;15[9]:e1002660.).

The cerebral blood flow analysis was a preplanned substudy of NILVAD designed to assess how 6 months of treatment with the drug affects cerebral blood flow as measured using MRI arterial spin labeling. The researchers looked at cerebral blood flow in whole-brain gray matter and in specific regions such as the hippocampus.


The substudy analysis included 22 patients who received nilvadipine and 22 who received placebo during the randomized, double-blind study. Participants had a mean age of 72.8 years and a mean Mini-Mental State Examination score of 20.4.

At 6 months, nilvadipine lowered systolic BP by 11.5 mm Hg, and whole-brain gray matter cerebral blood flow remained stable. Blood flow to the hippocampus increased by approximately 20% among patients treated with nilvadipine – by 24.4 mL/100 g per minute to the left hippocampus and by 20.1 mL/100 g per minute to the right hippocampus.

The increased hippocampal cerebral blood flow could be related to nilvadipine’s antihypertensive effects or its effects on amyloid-beta, the authors noted.

“These findings indicate that the known decrease in [cerebral blood flow] in patients with [Alzheimer’s disease] can in some regions be reversed,” they wrote.

“Even though no medical treatment is without risk, getting treatment for high blood pressure could be important to maintain brain health in patients with Alzheimer’s disease,” Dr. Claassen said in a statement. “In the future, we need to find out whether the improvement in blood flow, especially in the hippocampus, can be used as a supportive treatment to slow down progression of Alzheimer’s disease, especially in earlier states of disease.”

The researchers wrote they lacked biomarkers to confirm Alzheimer’s disease pathology. Most of the study participants were white Europeans, which “limits extrapolation [of the findings] to other populations,” they added.

The Alzheimer’s Drug Discovery Foundation and the Dutch Alzheimer Society funded the NILVAD cerebral blood flow substudy. NILVAD was funded by the European Commission Framework 7 Program Health Theme. Dr. Claassen had no disclosures; one coauthor disclosed a pending patent for nilvadipine.

jremaly@mdedge.com

SOURCE: Claassen JAHR et al. Hypertension. 2019 Jun 17. doi: 10.1161/HYPERTENSIONAHA.119.12892.

Patients with mild or moderate Alzheimer’s disease who took nilvadipine experienced increases in cerebral blood flow in the hippocampus, according to a new study.

copyright Radboud University Medical Center

Cerebral blood flow in other regions of the brain did not significantly change in patients who took the antihypertensive drug nilvadipine, according to a report on the trial published in Hypertension. Reduced cerebral blood flow is an early marker of Alzheimer’s disease, and the SPRINT MIND study suggests that intensive blood pressure control may reduce the risk of cognitive impairment.

“These findings [of the new study] not only indicate preserved cerebral autoregulation in Alzheimer’s disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment,” said Jurgen A.H.R. Claassen, MD, PhD of Radboud University Medical Center in Nijmegen, the Netherlands, and coauthors. “An important question is whether this observed increase in [cerebral blood flow] translates to clinical benefits. Unfortunately, sample sizes were too small and follow-up time too short to reliably study the effects ... on structural brain measures and cognitive measures.”

Nilvadipine is a dihydropyridine calcium antagonist used to treat hypertension. In the NILVAD trial, investigators assessed the effects of nilvadipine versus placebo in approximately 500 patients with Alzheimer’s disease. The 18-month trial found no beneficial effects of nilvadipine on cognitive function, but subgroup analyses suggested a potential benefit among patients in the early stages of the disease (PLoS Med. 2018 Sep 24;15[9]:e1002660.).

The cerebral blood flow analysis was a preplanned substudy of NILVAD designed to assess how 6 months of treatment with the drug affects cerebral blood flow as measured using MRI arterial spin labeling. The researchers looked at cerebral blood flow in whole-brain gray matter and in specific regions such as the hippocampus.


The substudy analysis included 22 patients who received nilvadipine and 22 who received placebo during the randomized, double-blind study. Participants had a mean age of 72.8 years and a mean Mini-Mental State Examination score of 20.4.

At 6 months, nilvadipine lowered systolic BP by 11.5 mm Hg, and whole-brain gray matter cerebral blood flow remained stable. Blood flow to the hippocampus increased by approximately 20% among patients treated with nilvadipine – by 24.4 mL/100 g per minute to the left hippocampus and by 20.1 mL/100 g per minute to the right hippocampus.

The increased hippocampal cerebral blood flow could be related to nilvadipine’s antihypertensive effects or its effects on amyloid-beta, the authors noted.

“These findings indicate that the known decrease in [cerebral blood flow] in patients with [Alzheimer’s disease] can in some regions be reversed,” they wrote.

“Even though no medical treatment is without risk, getting treatment for high blood pressure could be important to maintain brain health in patients with Alzheimer’s disease,” Dr. Claassen said in a statement. “In the future, we need to find out whether the improvement in blood flow, especially in the hippocampus, can be used as a supportive treatment to slow down progression of Alzheimer’s disease, especially in earlier states of disease.”

The researchers wrote they lacked biomarkers to confirm Alzheimer’s disease pathology. Most of the study participants were white Europeans, which “limits extrapolation [of the findings] to other populations,” they added.

The Alzheimer’s Drug Discovery Foundation and the Dutch Alzheimer Society funded the NILVAD cerebral blood flow substudy. NILVAD was funded by the European Commission Framework 7 Program Health Theme. Dr. Claassen had no disclosures; one coauthor disclosed a pending patent for nilvadipine.

jremaly@mdedge.com

SOURCE: Claassen JAHR et al. Hypertension. 2019 Jun 17. doi: 10.1161/HYPERTENSIONAHA.119.12892.

Patients with mild or moderate Alzheimer’s disease who took nilvadipine experienced increases in cerebral blood flow in the hippocampus, according to a new study.

copyright Radboud University Medical Center

Cerebral blood flow in other regions of the brain did not significantly change in patients who took the antihypertensive drug nilvadipine, according to a report on the trial published in Hypertension. Reduced cerebral blood flow is an early marker of Alzheimer’s disease, and the SPRINT MIND study suggests that intensive blood pressure control may reduce the risk of cognitive impairment.

“These findings [of the new study] not only indicate preserved cerebral autoregulation in Alzheimer’s disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment,” said Jurgen A.H.R. Claassen, MD, PhD of Radboud University Medical Center in Nijmegen, the Netherlands, and coauthors. “An important question is whether this observed increase in [cerebral blood flow] translates to clinical benefits. Unfortunately, sample sizes were too small and follow-up time too short to reliably study the effects ... on structural brain measures and cognitive measures.”

Nilvadipine is a dihydropyridine calcium antagonist used to treat hypertension. In the NILVAD trial, investigators assessed the effects of nilvadipine versus placebo in approximately 500 patients with Alzheimer’s disease. The 18-month trial found no beneficial effects of nilvadipine on cognitive function, but subgroup analyses suggested a potential benefit among patients in the early stages of the disease (PLoS Med. 2018 Sep 24;15[9]:e1002660.).

The cerebral blood flow analysis was a preplanned substudy of NILVAD designed to assess how 6 months of treatment with the drug affects cerebral blood flow as measured using MRI arterial spin labeling. The researchers looked at cerebral blood flow in whole-brain gray matter and in specific regions such as the hippocampus.


The substudy analysis included 22 patients who received nilvadipine and 22 who received placebo during the randomized, double-blind study. Participants had a mean age of 72.8 years and a mean Mini-Mental State Examination score of 20.4.

At 6 months, nilvadipine lowered systolic BP by 11.5 mm Hg, and whole-brain gray matter cerebral blood flow remained stable. Blood flow to the hippocampus increased by approximately 20% among patients treated with nilvadipine – by 24.4 mL/100 g per minute to the left hippocampus and by 20.1 mL/100 g per minute to the right hippocampus.

The increased hippocampal cerebral blood flow could be related to nilvadipine’s antihypertensive effects or its effects on amyloid-beta, the authors noted.

“These findings indicate that the known decrease in [cerebral blood flow] in patients with [Alzheimer’s disease] can in some regions be reversed,” they wrote.

“Even though no medical treatment is without risk, getting treatment for high blood pressure could be important to maintain brain health in patients with Alzheimer’s disease,” Dr. Claassen said in a statement. “In the future, we need to find out whether the improvement in blood flow, especially in the hippocampus, can be used as a supportive treatment to slow down progression of Alzheimer’s disease, especially in earlier states of disease.”

The researchers wrote they lacked biomarkers to confirm Alzheimer’s disease pathology. Most of the study participants were white Europeans, which “limits extrapolation [of the findings] to other populations,” they added.

The Alzheimer’s Drug Discovery Foundation and the Dutch Alzheimer Society funded the NILVAD cerebral blood flow substudy. NILVAD was funded by the European Commission Framework 7 Program Health Theme. Dr. Claassen had no disclosures; one coauthor disclosed a pending patent for nilvadipine.

jremaly@mdedge.com

SOURCE: Claassen JAHR et al. Hypertension. 2019 Jun 17. doi: 10.1161/HYPERTENSIONAHA.119.12892.

In this issue of the Journal of Hospital Medicine, McAlister et al.¹ compared the ability of the Clinical Frailty Scale (CFS) and the Hospital Frailty Risk Score (HFRS) to predict 30-day readmission or death. The authors prospectively assessed adult patients aged ≥18 years without cognitive impairment being discharged back to the community after medical admissions. They demonstrated only modest overlap in frailty designation between HFRS and CFS and concluded that CFS is better than HFRS for predicting the outcomes of interest.

Before a prediction rule is widely adopted for use in routine practice, robust external validation is needed.² Factors such as the prevalence of disease in a population, the clinical competencies of a health system, the socioeconomic status, and the ethnicity of the population can all affect how well a clinical rule performs, but may not become apparent until a prospective validation in a different population is attempted.

In developing the HFRS, Gilbert et al. aimed to create a low-cost, highly generalizable method of identifying frailty using International Classification of Diseases (ICD) 10 billing codes.³ The derivation and validation cohorts for HFRS included older adults aged >75 years in the United Kingdom, many of whom had cognitive impairment. Therefore, it is not surprising that the tool behaved very differently in the younger Canadian cohort described by McAlister et al. where persons with cognitive impairment were excluded. That the HFRS had less predictability in the Canadian cohort may simply indicate that it performs better in an older population with cognitive vulnerabilities; given the frailty constructs of the CFS, it may provide less insights in older populations.

We applaud the efforts to find a way to better identify high-risk groups of adults. We also appreciate the increasing attention to function and other frailty-related domains in risk prediction models. Nevertheless, we recommend caution in using any of the many existing frailty indices⁴ in risk prediction tools unless it is clear what domains of frailty are most relevant for the predicted outcome and what population is the subject of interest.

One of the challenges of choosing an appropriate frailty tool is that different tools are measuring different domains or constructs of frailty. Most consider frailty either as a physical phenotype⁵ or as a more multifaceted construct with impairments in physical and mental health, function, and social interaction.⁶ There is often poor overlap between those individuals identified as frail by different measures, highlighting that they are in fact identifying different people within the population studied and have different predictive abilities.

An ideal frailty tool for clinical use would allow clinicians to identify high-risk patients relative to specific outcome(s) in real time prior to discharge from hospital or prior to a sentinel event in the community. CFS can be calculated at the bedside, but HFRS calculation can only be done retrospectively when medical records are coded for claims after discharge. This makes HFRS more suited to research or post hoc quality measure work and CFS more suited to clinical use as the authors describe.

Although using a frailty indicator to help determine those at high risk of early readmission is an important objective, the presence of frailty accounts for only part of a person’s risk for readmission or other untoward events. Reasons for readmissions are complex and often heavily weighted on a lack of social and community supports. A deeper understanding of the reasons for readmission is needed to establish whether readmission of these complex patients has more to do with frailty or other drivers such as poor transitions of care.

The prevalence of frailty will continue to increase as our population ages. Definitions of frailty vary, but there is a broad agreement that frailty, regardless of how it is constructed, increases with age, results in multisystem changes, and leads to increased healthcare utilization and costs. Preventing the development of frailty, identifying frailty, and developing interventions to address frailty in and out of the hospital setting are all vital. We welcome further research regarding the biopsychosocial constructs of frailty, how they overlap with the frailty phenotype, and how these constructs inform both our understanding of frailty and the use of frailty tools.

Disclosures

The authors have no conflicts of interest to report.

In this issue of the Journal of Hospital Medicine, McAlister et al.¹ compared the ability of the Clinical Frailty Scale (CFS) and the Hospital Frailty Risk Score (HFRS) to predict 30-day readmission or death. The authors prospectively assessed adult patients aged ≥18 years without cognitive impairment being discharged back to the community after medical admissions. They demonstrated only modest overlap in frailty designation between HFRS and CFS and concluded that CFS is better than HFRS for predicting the outcomes of interest.

Before a prediction rule is widely adopted for use in routine practice, robust external validation is needed.² Factors such as the prevalence of disease in a population, the clinical competencies of a health system, the socioeconomic status, and the ethnicity of the population can all affect how well a clinical rule performs, but may not become apparent until a prospective validation in a different population is attempted.

In developing the HFRS, Gilbert et al. aimed to create a low-cost, highly generalizable method of identifying frailty using International Classification of Diseases (ICD) 10 billing codes.³ The derivation and validation cohorts for HFRS included older adults aged >75 years in the United Kingdom, many of whom had cognitive impairment. Therefore, it is not surprising that the tool behaved very differently in the younger Canadian cohort described by McAlister et al. where persons with cognitive impairment were excluded. That the HFRS had less predictability in the Canadian cohort may simply indicate that it performs better in an older population with cognitive vulnerabilities; given the frailty constructs of the CFS, it may provide less insights in older populations.

We applaud the efforts to find a way to better identify high-risk groups of adults. We also appreciate the increasing attention to function and other frailty-related domains in risk prediction models. Nevertheless, we recommend caution in using any of the many existing frailty indices⁴ in risk prediction tools unless it is clear what domains of frailty are most relevant for the predicted outcome and what population is the subject of interest.

One of the challenges of choosing an appropriate frailty tool is that different tools are measuring different domains or constructs of frailty. Most consider frailty either as a physical phenotype⁵ or as a more multifaceted construct with impairments in physical and mental health, function, and social interaction.⁶ There is often poor overlap between those individuals identified as frail by different measures, highlighting that they are in fact identifying different people within the population studied and have different predictive abilities.

An ideal frailty tool for clinical use would allow clinicians to identify high-risk patients relative to specific outcome(s) in real time prior to discharge from hospital or prior to a sentinel event in the community. CFS can be calculated at the bedside, but HFRS calculation can only be done retrospectively when medical records are coded for claims after discharge. This makes HFRS more suited to research or post hoc quality measure work and CFS more suited to clinical use as the authors describe.

Although using a frailty indicator to help determine those at high risk of early readmission is an important objective, the presence of frailty accounts for only part of a person’s risk for readmission or other untoward events. Reasons for readmissions are complex and often heavily weighted on a lack of social and community supports. A deeper understanding of the reasons for readmission is needed to establish whether readmission of these complex patients has more to do with frailty or other drivers such as poor transitions of care.

The prevalence of frailty will continue to increase as our population ages. Definitions of frailty vary, but there is a broad agreement that frailty, regardless of how it is constructed, increases with age, results in multisystem changes, and leads to increased healthcare utilization and costs. Preventing the development of frailty, identifying frailty, and developing interventions to address frailty in and out of the hospital setting are all vital. We welcome further research regarding the biopsychosocial constructs of frailty, how they overlap with the frailty phenotype, and how these constructs inform both our understanding of frailty and the use of frailty tools.

Disclosures

The authors have no conflicts of interest to report.

In this issue of the Journal of Hospital Medicine, McAlister et al.¹ compared the ability of the Clinical Frailty Scale (CFS) and the Hospital Frailty Risk Score (HFRS) to predict 30-day readmission or death. The authors prospectively assessed adult patients aged ≥18 years without cognitive impairment being discharged back to the community after medical admissions. They demonstrated only modest overlap in frailty designation between HFRS and CFS and concluded that CFS is better than HFRS for predicting the outcomes of interest.

Before a prediction rule is widely adopted for use in routine practice, robust external validation is needed.² Factors such as the prevalence of disease in a population, the clinical competencies of a health system, the socioeconomic status, and the ethnicity of the population can all affect how well a clinical rule performs, but may not become apparent until a prospective validation in a different population is attempted.

In developing the HFRS, Gilbert et al. aimed to create a low-cost, highly generalizable method of identifying frailty using International Classification of Diseases (ICD) 10 billing codes.³ The derivation and validation cohorts for HFRS included older adults aged >75 years in the United Kingdom, many of whom had cognitive impairment. Therefore, it is not surprising that the tool behaved very differently in the younger Canadian cohort described by McAlister et al. where persons with cognitive impairment were excluded. That the HFRS had less predictability in the Canadian cohort may simply indicate that it performs better in an older population with cognitive vulnerabilities; given the frailty constructs of the CFS, it may provide less insights in older populations.

We applaud the efforts to find a way to better identify high-risk groups of adults. We also appreciate the increasing attention to function and other frailty-related domains in risk prediction models. Nevertheless, we recommend caution in using any of the many existing frailty indices⁴ in risk prediction tools unless it is clear what domains of frailty are most relevant for the predicted outcome and what population is the subject of interest.

One of the challenges of choosing an appropriate frailty tool is that different tools are measuring different domains or constructs of frailty. Most consider frailty either as a physical phenotype⁵ or as a more multifaceted construct with impairments in physical and mental health, function, and social interaction.⁶ There is often poor overlap between those individuals identified as frail by different measures, highlighting that they are in fact identifying different people within the population studied and have different predictive abilities.

An ideal frailty tool for clinical use would allow clinicians to identify high-risk patients relative to specific outcome(s) in real time prior to discharge from hospital or prior to a sentinel event in the community. CFS can be calculated at the bedside, but HFRS calculation can only be done retrospectively when medical records are coded for claims after discharge. This makes HFRS more suited to research or post hoc quality measure work and CFS more suited to clinical use as the authors describe.

Although using a frailty indicator to help determine those at high risk of early readmission is an important objective, the presence of frailty accounts for only part of a person’s risk for readmission or other untoward events. Reasons for readmissions are complex and often heavily weighted on a lack of social and community supports. A deeper understanding of the reasons for readmission is needed to establish whether readmission of these complex patients has more to do with frailty or other drivers such as poor transitions of care.

The prevalence of frailty will continue to increase as our population ages. Definitions of frailty vary, but there is a broad agreement that frailty, regardless of how it is constructed, increases with age, results in multisystem changes, and leads to increased healthcare utilization and costs. Preventing the development of frailty, identifying frailty, and developing interventions to address frailty in and out of the hospital setting are all vital. We welcome further research regarding the biopsychosocial constructs of frailty, how they overlap with the frailty phenotype, and how these constructs inform both our understanding of frailty and the use of frailty tools.

Disclosures

The authors have no conflicts of interest to report.

SAN ANTONIO – Prescription opioid abuse has continued declining since 2011, but opioids remain far more commonly abused than other prescription drugs, including gabapentin and pregabalin, new research shows.

“Both gabapentin and pregabalin are abused but at rates that are 6-56 times less frequent than for opioid analgesics,” wrote Kofi Asomaning, DSci, of Pfizer, and associates at Pfizer and Denver Health’s Rocky Mountain Poison and Drug Center.

“Gabapentin is generally more frequently abused than pregabalin,” they reported in a research poster at the annual meeting of the College on Problems of Drug Dependence.

The researchers analyzed data from the RADARS System Survey of Non-Medical Use of Prescription Drugs Program (NMURx), the RADARS System Treatment Center Programs Combined, and the American Association of Poison Control Centers National Poison Data System (NPDS).

All those use self-reported data. The first is a confidential, anonymous web-based survey used to estimate population-level prevalence, and the second surveys patients with opioid use disorder entering treatment. The NPDS tracks all cases reported to poison control centers nationally.


Analysis of the NMURx data revealed similar lifetime abuse prevalence rates for gabapentin and pregabalin at 0.4%, several magnitudes lower than the 5.3% rate identified with opioids.

Gabapentin, however, had higher rates of abuse in the past month in the Treatment Center Programs Combined. For the third to fourth quarter of 2017, 0.12 per 100,000 population reportedly abused gabapentin, compared with 0.01 per 100,000 for pregabalin. The rate for past-month abuse of opioids was 0.79 per 100,000.

A similar pattern for the same quarter emerged from the NPDS data: Rate of gabapentin abuse was 0.06 per 100,000, rate for pregabalin was 0.01 per 100,000, and rate for opioids was 0.40 per 100,000.

Both pregabalin and opioids were predominantly ingested, though a very small amount of each was inhaled and a similarly small amount of opioids was injected. Data on exposure route for gabapentin were not provided, though it was used more frequently than pregabalin.

The research was funded by Pfizer. The RADARS system is owned by Denver Health and Hospital Authority under the Colorado state government. RADARS receives some funding from pharmaceutical industry subscriptions. Dr. Asomaning and Diane L. Martire, MD, MPH, are Pfizer employees who have financial interests with Pfizer.

SAN ANTONIO – Prescription opioid abuse has continued declining since 2011, but opioids remain far more commonly abused than other prescription drugs, including gabapentin and pregabalin, new research shows.

“Both gabapentin and pregabalin are abused but at rates that are 6-56 times less frequent than for opioid analgesics,” wrote Kofi Asomaning, DSci, of Pfizer, and associates at Pfizer and Denver Health’s Rocky Mountain Poison and Drug Center.

“Gabapentin is generally more frequently abused than pregabalin,” they reported in a research poster at the annual meeting of the College on Problems of Drug Dependence.

The researchers analyzed data from the RADARS System Survey of Non-Medical Use of Prescription Drugs Program (NMURx), the RADARS System Treatment Center Programs Combined, and the American Association of Poison Control Centers National Poison Data System (NPDS).

All those use self-reported data. The first is a confidential, anonymous web-based survey used to estimate population-level prevalence, and the second surveys patients with opioid use disorder entering treatment. The NPDS tracks all cases reported to poison control centers nationally.


Analysis of the NMURx data revealed similar lifetime abuse prevalence rates for gabapentin and pregabalin at 0.4%, several magnitudes lower than the 5.3% rate identified with opioids.

Gabapentin, however, had higher rates of abuse in the past month in the Treatment Center Programs Combined. For the third to fourth quarter of 2017, 0.12 per 100,000 population reportedly abused gabapentin, compared with 0.01 per 100,000 for pregabalin. The rate for past-month abuse of opioids was 0.79 per 100,000.

A similar pattern for the same quarter emerged from the NPDS data: Rate of gabapentin abuse was 0.06 per 100,000, rate for pregabalin was 0.01 per 100,000, and rate for opioids was 0.40 per 100,000.

Both pregabalin and opioids were predominantly ingested, though a very small amount of each was inhaled and a similarly small amount of opioids was injected. Data on exposure route for gabapentin were not provided, though it was used more frequently than pregabalin.

The research was funded by Pfizer. The RADARS system is owned by Denver Health and Hospital Authority under the Colorado state government. RADARS receives some funding from pharmaceutical industry subscriptions. Dr. Asomaning and Diane L. Martire, MD, MPH, are Pfizer employees who have financial interests with Pfizer.

SAN ANTONIO – Prescription opioid abuse has continued declining since 2011, but opioids remain far more commonly abused than other prescription drugs, including gabapentin and pregabalin, new research shows.

“Both gabapentin and pregabalin are abused but at rates that are 6-56 times less frequent than for opioid analgesics,” wrote Kofi Asomaning, DSci, of Pfizer, and associates at Pfizer and Denver Health’s Rocky Mountain Poison and Drug Center.

“Gabapentin is generally more frequently abused than pregabalin,” they reported in a research poster at the annual meeting of the College on Problems of Drug Dependence.

The researchers analyzed data from the RADARS System Survey of Non-Medical Use of Prescription Drugs Program (NMURx), the RADARS System Treatment Center Programs Combined, and the American Association of Poison Control Centers National Poison Data System (NPDS).

All those use self-reported data. The first is a confidential, anonymous web-based survey used to estimate population-level prevalence, and the second surveys patients with opioid use disorder entering treatment. The NPDS tracks all cases reported to poison control centers nationally.


Analysis of the NMURx data revealed similar lifetime abuse prevalence rates for gabapentin and pregabalin at 0.4%, several magnitudes lower than the 5.3% rate identified with opioids.

Gabapentin, however, had higher rates of abuse in the past month in the Treatment Center Programs Combined. For the third to fourth quarter of 2017, 0.12 per 100,000 population reportedly abused gabapentin, compared with 0.01 per 100,000 for pregabalin. The rate for past-month abuse of opioids was 0.79 per 100,000.

A similar pattern for the same quarter emerged from the NPDS data: Rate of gabapentin abuse was 0.06 per 100,000, rate for pregabalin was 0.01 per 100,000, and rate for opioids was 0.40 per 100,000.

Both pregabalin and opioids were predominantly ingested, though a very small amount of each was inhaled and a similarly small amount of opioids was injected. Data on exposure route for gabapentin were not provided, though it was used more frequently than pregabalin.

The research was funded by Pfizer. The RADARS system is owned by Denver Health and Hospital Authority under the Colorado state government. RADARS receives some funding from pharmaceutical industry subscriptions. Dr. Asomaning and Diane L. Martire, MD, MPH, are Pfizer employees who have financial interests with Pfizer.

Anticoagulant use to prevent ischemic strokes in patients with atrial fibrillation (AF) continues to be one of the most challenging decisions facing patients and their physicians, in large part due to significant patient-to-patient variation in both AF-related stroke risk and anticoagulant-associated hemorrhage risk. Now, add a layer of complexity—.how should one approach anticoagulant use following an adverse event such as an acute upper gastrointestinal (GI) hemorrhage? On the one side, the risk of ischemic stroke, and on the other, the risk of recurrent bleeding, either of which can lead to death or disability. Making this decision requires humility, clinical acumen, shared decision-making, and data.

Data on this subject are sparse.^1,2 Observational studies show that patients who restart anticoagulants after GI hemorrhage experience fewer ischemic strokes. These studies also show that patients who restart anticoagulant therapy are healthier than those who do not—in measurable ways and, importantly, in unmeasurable ways. Thus far, observational studies have not sufficiently dealt with confounding by indication; that is, patients who restart anticoagulants are fundamentally different than patients who do not.

In this issue of the Journal of Hospital Medicine^®, Pappas et al. focus on the optimal timing of resuming oral anticoagulation in patients who have sustained acute upper GI bleeds while receiving oral anticoagulation for AF.³ They use a microsimulation modeling approach to address this question, by creating a synthetic population of patients reflective of age, gender, and comorbidities in a United States population of patients with AF. Using data from epidemiologic studies that describe the risk of rebleeding, hemorrhagic complications, and ischemic stroke as well as the quality of life associated with each of these events, the authors have constructed a decision analytic model to determine the optimal day to restart anticoagulation. This modeling approach mitigates confounding by indication, a limitation of observational studies. They report that the optimal day to restart anticoagulant therapy is in the range of 32-51 days. As one would predict, when using direct-acting anticoagulants and for patients with high stroke risk, the investigators find that restarting therapy earlier is associated with greater benefit. These findings help to untangle a knot of risk and benefits facing patients with AF following an acute GI hemorrhage.

Interpreting the results relies on an understanding of the strengths and weaknesses of simulation modeling and the data used in the analysis. Like any research method, the devil is in the details. Stitching together event rates and outcomes from multiple studies, the results of a simulation model are only as good as the studies the model draws from. In particular, assumptions regarding the time-dependent decline in rebleeding risk are a critical component of determining the optimal time to resume anticoagulation. The authors had to make multiple assumptions to project the 24-hour risk of rebleeding determined from the Rockall score to estimate the risk of rebleeding over the next days to months.⁴ Consequently, the results are likely overly precise. Practically, 30-50 days or four to eight weeks may better reflect the precision of the study findings.

Results on optimal timing of resuming anticoagulation therapy are most applicable for patients when the decision to restart anticoagulants has already been made. We part ways with the authors in their conclusion that these results confirm that anticoagulants should be restarted. There are multiple appropriate reasons why anticoagulant therapy should not be restarted following an acute upper GI hemorrhage. For example, in observational studies, patients not restarted on anticoagulant therapy were more likely to have a history of falls and to have had severe bleeds.¹ Furthermore, patients who do not restart therapy are more likely to die in follow-up. It is tempting to use this fact to support restarting anticoagulants. However, when the causes of death are examined, the vast majority of deaths were unrelated to thrombosis or hemorrhage.² Patients with AF are older and have multiple comorbidities and life-limiting conditions. Accordingly, the results of this study are better used to engage patients in shared decision-making and contextualized in the broader picture of patients’ health and goals.⁵

Restarting anticoagulants after a GI hemorrhage is a difficult and high-stakes clinical decision. The study by Pappas et al. uses a simulation model to advance our understanding about the optimal timing to restart anticoagulants. By integrating the dynamic risk of ischemic stroke and recurrent hemorrhage following GI hemorrhage, they estimate the maximal benefit when anticoagulants are restarted between 30 days and 50 days after hemorrhage. The results of their analysis are best used to inform timing among patients where the decision to restart anticoagulants has already been made. The analysis also provides a useful starting point for shared decision-making by highlighting that the optimal net benefit is influenced by patient-to-patient variation in the underlying AF-related stroke risk and anticoagulant-associated rebleeding risk.

Disclosures: Dr. Shah has nothing to disclose. Dr. Eckman reports grants from Heart Rhythm Society/Boehringer-Ingelheim and grants from Bristol-Myers Squibb/Pfizer Education Consortium, outside the submitted work.

Anticoagulant use to prevent ischemic strokes in patients with atrial fibrillation (AF) continues to be one of the most challenging decisions facing patients and their physicians, in large part due to significant patient-to-patient variation in both AF-related stroke risk and anticoagulant-associated hemorrhage risk. Now, add a layer of complexity—.how should one approach anticoagulant use following an adverse event such as an acute upper gastrointestinal (GI) hemorrhage? On the one side, the risk of ischemic stroke, and on the other, the risk of recurrent bleeding, either of which can lead to death or disability. Making this decision requires humility, clinical acumen, shared decision-making, and data.

Data on this subject are sparse.^1,2 Observational studies show that patients who restart anticoagulants after GI hemorrhage experience fewer ischemic strokes. These studies also show that patients who restart anticoagulant therapy are healthier than those who do not—in measurable ways and, importantly, in unmeasurable ways. Thus far, observational studies have not sufficiently dealt with confounding by indication; that is, patients who restart anticoagulants are fundamentally different than patients who do not.

In this issue of the Journal of Hospital Medicine^®, Pappas et al. focus on the optimal timing of resuming oral anticoagulation in patients who have sustained acute upper GI bleeds while receiving oral anticoagulation for AF.³ They use a microsimulation modeling approach to address this question, by creating a synthetic population of patients reflective of age, gender, and comorbidities in a United States population of patients with AF. Using data from epidemiologic studies that describe the risk of rebleeding, hemorrhagic complications, and ischemic stroke as well as the quality of life associated with each of these events, the authors have constructed a decision analytic model to determine the optimal day to restart anticoagulation. This modeling approach mitigates confounding by indication, a limitation of observational studies. They report that the optimal day to restart anticoagulant therapy is in the range of 32-51 days. As one would predict, when using direct-acting anticoagulants and for patients with high stroke risk, the investigators find that restarting therapy earlier is associated with greater benefit. These findings help to untangle a knot of risk and benefits facing patients with AF following an acute GI hemorrhage.

Interpreting the results relies on an understanding of the strengths and weaknesses of simulation modeling and the data used in the analysis. Like any research method, the devil is in the details. Stitching together event rates and outcomes from multiple studies, the results of a simulation model are only as good as the studies the model draws from. In particular, assumptions regarding the time-dependent decline in rebleeding risk are a critical component of determining the optimal time to resume anticoagulation. The authors had to make multiple assumptions to project the 24-hour risk of rebleeding determined from the Rockall score to estimate the risk of rebleeding over the next days to months.⁴ Consequently, the results are likely overly precise. Practically, 30-50 days or four to eight weeks may better reflect the precision of the study findings.

Results on optimal timing of resuming anticoagulation therapy are most applicable for patients when the decision to restart anticoagulants has already been made. We part ways with the authors in their conclusion that these results confirm that anticoagulants should be restarted. There are multiple appropriate reasons why anticoagulant therapy should not be restarted following an acute upper GI hemorrhage. For example, in observational studies, patients not restarted on anticoagulant therapy were more likely to have a history of falls and to have had severe bleeds.¹ Furthermore, patients who do not restart therapy are more likely to die in follow-up. It is tempting to use this fact to support restarting anticoagulants. However, when the causes of death are examined, the vast majority of deaths were unrelated to thrombosis or hemorrhage.² Patients with AF are older and have multiple comorbidities and life-limiting conditions. Accordingly, the results of this study are better used to engage patients in shared decision-making and contextualized in the broader picture of patients’ health and goals.⁵

Restarting anticoagulants after a GI hemorrhage is a difficult and high-stakes clinical decision. The study by Pappas et al. uses a simulation model to advance our understanding about the optimal timing to restart anticoagulants. By integrating the dynamic risk of ischemic stroke and recurrent hemorrhage following GI hemorrhage, they estimate the maximal benefit when anticoagulants are restarted between 30 days and 50 days after hemorrhage. The results of their analysis are best used to inform timing among patients where the decision to restart anticoagulants has already been made. The analysis also provides a useful starting point for shared decision-making by highlighting that the optimal net benefit is influenced by patient-to-patient variation in the underlying AF-related stroke risk and anticoagulant-associated rebleeding risk.

Disclosures: Dr. Shah has nothing to disclose. Dr. Eckman reports grants from Heart Rhythm Society/Boehringer-Ingelheim and grants from Bristol-Myers Squibb/Pfizer Education Consortium, outside the submitted work.

Anticoagulant use to prevent ischemic strokes in patients with atrial fibrillation (AF) continues to be one of the most challenging decisions facing patients and their physicians, in large part due to significant patient-to-patient variation in both AF-related stroke risk and anticoagulant-associated hemorrhage risk. Now, add a layer of complexity—.how should one approach anticoagulant use following an adverse event such as an acute upper gastrointestinal (GI) hemorrhage? On the one side, the risk of ischemic stroke, and on the other, the risk of recurrent bleeding, either of which can lead to death or disability. Making this decision requires humility, clinical acumen, shared decision-making, and data.

Data on this subject are sparse.^1,2 Observational studies show that patients who restart anticoagulants after GI hemorrhage experience fewer ischemic strokes. These studies also show that patients who restart anticoagulant therapy are healthier than those who do not—in measurable ways and, importantly, in unmeasurable ways. Thus far, observational studies have not sufficiently dealt with confounding by indication; that is, patients who restart anticoagulants are fundamentally different than patients who do not.

In this issue of the Journal of Hospital Medicine^®, Pappas et al. focus on the optimal timing of resuming oral anticoagulation in patients who have sustained acute upper GI bleeds while receiving oral anticoagulation for AF.³ They use a microsimulation modeling approach to address this question, by creating a synthetic population of patients reflective of age, gender, and comorbidities in a United States population of patients with AF. Using data from epidemiologic studies that describe the risk of rebleeding, hemorrhagic complications, and ischemic stroke as well as the quality of life associated with each of these events, the authors have constructed a decision analytic model to determine the optimal day to restart anticoagulation. This modeling approach mitigates confounding by indication, a limitation of observational studies. They report that the optimal day to restart anticoagulant therapy is in the range of 32-51 days. As one would predict, when using direct-acting anticoagulants and for patients with high stroke risk, the investigators find that restarting therapy earlier is associated with greater benefit. These findings help to untangle a knot of risk and benefits facing patients with AF following an acute GI hemorrhage.

Interpreting the results relies on an understanding of the strengths and weaknesses of simulation modeling and the data used in the analysis. Like any research method, the devil is in the details. Stitching together event rates and outcomes from multiple studies, the results of a simulation model are only as good as the studies the model draws from. In particular, assumptions regarding the time-dependent decline in rebleeding risk are a critical component of determining the optimal time to resume anticoagulation. The authors had to make multiple assumptions to project the 24-hour risk of rebleeding determined from the Rockall score to estimate the risk of rebleeding over the next days to months.⁴ Consequently, the results are likely overly precise. Practically, 30-50 days or four to eight weeks may better reflect the precision of the study findings.

Results on optimal timing of resuming anticoagulation therapy are most applicable for patients when the decision to restart anticoagulants has already been made. We part ways with the authors in their conclusion that these results confirm that anticoagulants should be restarted. There are multiple appropriate reasons why anticoagulant therapy should not be restarted following an acute upper GI hemorrhage. For example, in observational studies, patients not restarted on anticoagulant therapy were more likely to have a history of falls and to have had severe bleeds.¹ Furthermore, patients who do not restart therapy are more likely to die in follow-up. It is tempting to use this fact to support restarting anticoagulants. However, when the causes of death are examined, the vast majority of deaths were unrelated to thrombosis or hemorrhage.² Patients with AF are older and have multiple comorbidities and life-limiting conditions. Accordingly, the results of this study are better used to engage patients in shared decision-making and contextualized in the broader picture of patients’ health and goals.⁵

Restarting anticoagulants after a GI hemorrhage is a difficult and high-stakes clinical decision. The study by Pappas et al. uses a simulation model to advance our understanding about the optimal timing to restart anticoagulants. By integrating the dynamic risk of ischemic stroke and recurrent hemorrhage following GI hemorrhage, they estimate the maximal benefit when anticoagulants are restarted between 30 days and 50 days after hemorrhage. The results of their analysis are best used to inform timing among patients where the decision to restart anticoagulants has already been made. The analysis also provides a useful starting point for shared decision-making by highlighting that the optimal net benefit is influenced by patient-to-patient variation in the underlying AF-related stroke risk and anticoagulant-associated rebleeding risk.

Disclosures: Dr. Shah has nothing to disclose. Dr. Eckman reports grants from Heart Rhythm Society/Boehringer-Ingelheim and grants from Bristol-Myers Squibb/Pfizer Education Consortium, outside the submitted work.

MADRID – The first consensus recommendations for the identification and management of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) place particular emphasis on routine screening in all systemic sclerosis patients for early detection, monitoring, and, when warranted, treatment, Anna-Maria Hoffmann-Vold, MD, PhD, reported at the European Congress of Rheumatology.

“Everyone with systemic sclerosis needs to be screened because this is the most important risk factor for ILD,” said Dr. Hoffmann-Vold, a clinical scientist in the division of rheumatology at the University of Oslo and head of scleroderma research at Oslo University Hospital.

Although the frequency of screening is not specified based on the opinion that this should be based on risk factors and other clinical characteristics, there was unanimous agreement that lung function tests do not represent an adequate screening tool or method for assessing ILD severity. Rather, the recommendations make clear that lung function studies are adjunctive to high-resolution computed tomography (HRCT).

“HRCT is the primary tool for evaluating ILD, but there was 100% agreement that assessment should include more than one measure, including lung function tests and clinical assessment,” Dr. Hoffmann-Vold reported.

There was a strong opinion that the numerous potential biomarkers described for ILD, although promising, are not yet ready for clinical use.

In developing these new recommendations, 95 potential statements were considered by the panel of 27 rheumatologists, pulmonologists, and others with experience in this field. A Delphi process was used for members of the panel to identify areas of agreement to produce consensus statements.

The result has been more than 50 statements issued in six major domains. These include statements on risk factors, appropriate methodology for diagnosis and severity assessment, when to initiate therapy, and when and how to initiate treatment escalation.

“We want to increase clinician awareness and provide standardized guidance for evaluating patients for the presence and medical management of ILD-SSc,” Dr. Hoffmann-Vold explained.

ILD occurs in about half of all patients with systemic sclerosis. Among these, approximately one out of three will experience lung disease progression. Although these high prevalence rates are well recognized and associated with high morbidity and mortality, Dr. Hoffmann-Vold said that there has been uncertainty about how to screen systemic sclerosis patients for ILD and what steps to take when it was found. It is this uncertainty that prompted the present initiative.

The consensus recommendations are an initial step to guide clinicians, but Dr. Hoffmann-Vold noted that the many statements are based on expert opinion, suggesting more studies are needed to compare strategies for objective severity grading and prediction of which patients are most at risk for ILD progression.

“There are still huge knowledge gaps we need to fill,” she stated. Still, she believes these recommendations represent progress in this field. While they are likely “to increase the standard of care” for those who develop ILD-SSc, they also have identified where to concentrate further research.

Dr. Hoffmann-Vold reported financial relationships with Actelion, Boehringer Ingelheim, and GlaxoSmithKline.

SOURCE: Hoffmann-Vold A-M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):104, Abstract OPO064, doi: 10.1136/annrheumdis-2019-eular.3225.

MADRID – The first consensus recommendations for the identification and management of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) place particular emphasis on routine screening in all systemic sclerosis patients for early detection, monitoring, and, when warranted, treatment, Anna-Maria Hoffmann-Vold, MD, PhD, reported at the European Congress of Rheumatology.

“Everyone with systemic sclerosis needs to be screened because this is the most important risk factor for ILD,” said Dr. Hoffmann-Vold, a clinical scientist in the division of rheumatology at the University of Oslo and head of scleroderma research at Oslo University Hospital.

Although the frequency of screening is not specified based on the opinion that this should be based on risk factors and other clinical characteristics, there was unanimous agreement that lung function tests do not represent an adequate screening tool or method for assessing ILD severity. Rather, the recommendations make clear that lung function studies are adjunctive to high-resolution computed tomography (HRCT).

“HRCT is the primary tool for evaluating ILD, but there was 100% agreement that assessment should include more than one measure, including lung function tests and clinical assessment,” Dr. Hoffmann-Vold reported.

There was a strong opinion that the numerous potential biomarkers described for ILD, although promising, are not yet ready for clinical use.

In developing these new recommendations, 95 potential statements were considered by the panel of 27 rheumatologists, pulmonologists, and others with experience in this field. A Delphi process was used for members of the panel to identify areas of agreement to produce consensus statements.

The result has been more than 50 statements issued in six major domains. These include statements on risk factors, appropriate methodology for diagnosis and severity assessment, when to initiate therapy, and when and how to initiate treatment escalation.

“We want to increase clinician awareness and provide standardized guidance for evaluating patients for the presence and medical management of ILD-SSc,” Dr. Hoffmann-Vold explained.

ILD occurs in about half of all patients with systemic sclerosis. Among these, approximately one out of three will experience lung disease progression. Although these high prevalence rates are well recognized and associated with high morbidity and mortality, Dr. Hoffmann-Vold said that there has been uncertainty about how to screen systemic sclerosis patients for ILD and what steps to take when it was found. It is this uncertainty that prompted the present initiative.

The consensus recommendations are an initial step to guide clinicians, but Dr. Hoffmann-Vold noted that the many statements are based on expert opinion, suggesting more studies are needed to compare strategies for objective severity grading and prediction of which patients are most at risk for ILD progression.

“There are still huge knowledge gaps we need to fill,” she stated. Still, she believes these recommendations represent progress in this field. While they are likely “to increase the standard of care” for those who develop ILD-SSc, they also have identified where to concentrate further research.

Dr. Hoffmann-Vold reported financial relationships with Actelion, Boehringer Ingelheim, and GlaxoSmithKline.

SOURCE: Hoffmann-Vold A-M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):104, Abstract OPO064, doi: 10.1136/annrheumdis-2019-eular.3225.

MADRID – The first consensus recommendations for the identification and management of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) place particular emphasis on routine screening in all systemic sclerosis patients for early detection, monitoring, and, when warranted, treatment, Anna-Maria Hoffmann-Vold, MD, PhD, reported at the European Congress of Rheumatology.

“Everyone with systemic sclerosis needs to be screened because this is the most important risk factor for ILD,” said Dr. Hoffmann-Vold, a clinical scientist in the division of rheumatology at the University of Oslo and head of scleroderma research at Oslo University Hospital.

Although the frequency of screening is not specified based on the opinion that this should be based on risk factors and other clinical characteristics, there was unanimous agreement that lung function tests do not represent an adequate screening tool or method for assessing ILD severity. Rather, the recommendations make clear that lung function studies are adjunctive to high-resolution computed tomography (HRCT).

“HRCT is the primary tool for evaluating ILD, but there was 100% agreement that assessment should include more than one measure, including lung function tests and clinical assessment,” Dr. Hoffmann-Vold reported.

There was a strong opinion that the numerous potential biomarkers described for ILD, although promising, are not yet ready for clinical use.

In developing these new recommendations, 95 potential statements were considered by the panel of 27 rheumatologists, pulmonologists, and others with experience in this field. A Delphi process was used for members of the panel to identify areas of agreement to produce consensus statements.

The result has been more than 50 statements issued in six major domains. These include statements on risk factors, appropriate methodology for diagnosis and severity assessment, when to initiate therapy, and when and how to initiate treatment escalation.

“We want to increase clinician awareness and provide standardized guidance for evaluating patients for the presence and medical management of ILD-SSc,” Dr. Hoffmann-Vold explained.

ILD occurs in about half of all patients with systemic sclerosis. Among these, approximately one out of three will experience lung disease progression. Although these high prevalence rates are well recognized and associated with high morbidity and mortality, Dr. Hoffmann-Vold said that there has been uncertainty about how to screen systemic sclerosis patients for ILD and what steps to take when it was found. It is this uncertainty that prompted the present initiative.

The consensus recommendations are an initial step to guide clinicians, but Dr. Hoffmann-Vold noted that the many statements are based on expert opinion, suggesting more studies are needed to compare strategies for objective severity grading and prediction of which patients are most at risk for ILD progression.

“There are still huge knowledge gaps we need to fill,” she stated. Still, she believes these recommendations represent progress in this field. While they are likely “to increase the standard of care” for those who develop ILD-SSc, they also have identified where to concentrate further research.

Dr. Hoffmann-Vold reported financial relationships with Actelion, Boehringer Ingelheim, and GlaxoSmithKline.

SOURCE: Hoffmann-Vold A-M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):104, Abstract OPO064, doi: 10.1136/annrheumdis-2019-eular.3225.

CHICAGO – Tumor protein 53 (TP53) mutation, fibroblast growth factor receptor 1 (FGFR1) amplification, and tumor purity in plasma each predict early progression on palbociclib and/or fulvestrant in patients with advanced estrogen receptor–positive (ER+) breast cancer, according to genomic analyses of PALOMA-3 trial data.

Sharon Worcester/MDedge News

Overall, the presence of one or more of these genomic changes identified 131 out of 310 patients from the phase 3 trial who had baseline samples available, Ben O’Leary, MBBS, said at the annual meeting of the American Society of Clinical Oncology.

“So, a significant minority of patients – 42.3% – potentially who fall into a more poor-prognosis group,” said Dr. O’Leary of the Institute of Cancer Research at the Royal Marsden Hospital in London.

The findings suggest that a “liquid biopsy” at the start of treatment could identify patients at risk for progression.

The PALOMA-3 trial randomized 521 patients with ER+, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer who had previously progressed on endocrine therapy 2:1 to CDK4/CDK6 inhibition with palbociclib plus fulvestrant (P+F) or placebo plus fulvestrant (F), and it showed that adding palbociclib significantly improved progression-free survival (PFS) (N Engl J Med. Jul 16 2015;373:209-19).

For the current analysis, the investigators assessed circulating tumor DNA (ctDNA) in baseline plasma samples from 459 study participants in an effort to identify genomic biomarkers for progression, to examine the association between baseline tumor fraction and clinical outcome, and to explore differences in predictive markers by treatment arm. A custom amplicon-sequencing analysis was performed to look for mutations in 17 different relevant genes, and another was used to estimate tumor fraction by looking at about 800 common germline single-nucleotide polymorphisms and to assess copy-number gain in the amplification status in 11 different genes, Dr. O’Leary said.


Results for mutations and circulating nucleic acids were available in 203 and 107 patients from the P+F and F groups, respectively, and on multivariable analysis of all 310 patients (including palbociclib as a variable in the model and with ctDNA fraction as a continuous variable), higher baseline tumor purity in plasma was associated with highly significantly worse PFS (HR 1.2 per 10% increase in purity), and baseline TP53 mutation and FGFR1 amplification each were associated with significantly shorter PFS (HRs, 1.8 and 2.9, respectively).

“[It is] very important to note ... that we did look specifically for interaction between our genomic changes and treatment, and we didn’t find any evidence of a significant interaction, so these genomic markers [are] prognostic rather than predictive in terms of the two treatment arms of the trial,” he said.

A survival analysis showed a median PFS of 3.7 vs. 12.7 months in patients with vs. without TP53 mutation in the P+F arm, and 1.8 vs. 5.4 months, respectively, in the F arm, with similar HRs of 2.0 and 2.3 in the arms, respectively.

“Even in the [P+F] arm, you see almost half of the patients with a TP53 mutation ... have relapsed by 2 months, the earliest clinical assessment in the trial,” he noted.

For FGFR1, the PFS was 3.9 vs. 12 months with vs. without amplification in the P+F arms, and 1.8 vs. 5.8 months, respectively in th F arm, with HRs of 3.4 and 3.6, respectively.

These findings are notable because markers of early progression on endocrine therapy in combination with CDK4/6 inhibitors remain limited – despite the key role of these combinations in treating ER+ advanced breast cancer, Dr. O’Leary explained.

“Although many patients derive a great deal of benefit from these combinations, there are a subset of patients who will relapse relatively early, and ... we don’t have an established means of identifying those patients at the present,” he said. “From the technical perspective, liquid biopsies have emerged in recent years as a promising means of genotyping patients’ cancers from circulating tumor DNA, and in addition, the overall level of circulating tumor DNA – the fractional purity – has been associated with poor prognosis, specifically in the triple-negative breast cancer setting.”

The results, which require independent validation, could potentially inform future clinical trials of CDK4/6 inhibitor combinations in advanced ER+ breast cancer to identify a high-risk group of patients who require escalation of therapy, he concluded.

Dr. O’Leary reported receiving research funding from Pfizer to his institution.

SOURCE: O’Leary B et al. ASCO 2019, Abstract 1010.

CHICAGO – Tumor protein 53 (TP53) mutation, fibroblast growth factor receptor 1 (FGFR1) amplification, and tumor purity in plasma each predict early progression on palbociclib and/or fulvestrant in patients with advanced estrogen receptor–positive (ER+) breast cancer, according to genomic analyses of PALOMA-3 trial data.

Sharon Worcester/MDedge News

Overall, the presence of one or more of these genomic changes identified 131 out of 310 patients from the phase 3 trial who had baseline samples available, Ben O’Leary, MBBS, said at the annual meeting of the American Society of Clinical Oncology.

“So, a significant minority of patients – 42.3% – potentially who fall into a more poor-prognosis group,” said Dr. O’Leary of the Institute of Cancer Research at the Royal Marsden Hospital in London.

The findings suggest that a “liquid biopsy” at the start of treatment could identify patients at risk for progression.

The PALOMA-3 trial randomized 521 patients with ER+, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer who had previously progressed on endocrine therapy 2:1 to CDK4/CDK6 inhibition with palbociclib plus fulvestrant (P+F) or placebo plus fulvestrant (F), and it showed that adding palbociclib significantly improved progression-free survival (PFS) (N Engl J Med. Jul 16 2015;373:209-19).

For the current analysis, the investigators assessed circulating tumor DNA (ctDNA) in baseline plasma samples from 459 study participants in an effort to identify genomic biomarkers for progression, to examine the association between baseline tumor fraction and clinical outcome, and to explore differences in predictive markers by treatment arm. A custom amplicon-sequencing analysis was performed to look for mutations in 17 different relevant genes, and another was used to estimate tumor fraction by looking at about 800 common germline single-nucleotide polymorphisms and to assess copy-number gain in the amplification status in 11 different genes, Dr. O’Leary said.


Results for mutations and circulating nucleic acids were available in 203 and 107 patients from the P+F and F groups, respectively, and on multivariable analysis of all 310 patients (including palbociclib as a variable in the model and with ctDNA fraction as a continuous variable), higher baseline tumor purity in plasma was associated with highly significantly worse PFS (HR 1.2 per 10% increase in purity), and baseline TP53 mutation and FGFR1 amplification each were associated with significantly shorter PFS (HRs, 1.8 and 2.9, respectively).

“[It is] very important to note ... that we did look specifically for interaction between our genomic changes and treatment, and we didn’t find any evidence of a significant interaction, so these genomic markers [are] prognostic rather than predictive in terms of the two treatment arms of the trial,” he said.

A survival analysis showed a median PFS of 3.7 vs. 12.7 months in patients with vs. without TP53 mutation in the P+F arm, and 1.8 vs. 5.4 months, respectively, in the F arm, with similar HRs of 2.0 and 2.3 in the arms, respectively.

“Even in the [P+F] arm, you see almost half of the patients with a TP53 mutation ... have relapsed by 2 months, the earliest clinical assessment in the trial,” he noted.

For FGFR1, the PFS was 3.9 vs. 12 months with vs. without amplification in the P+F arms, and 1.8 vs. 5.8 months, respectively in th F arm, with HRs of 3.4 and 3.6, respectively.

These findings are notable because markers of early progression on endocrine therapy in combination with CDK4/6 inhibitors remain limited – despite the key role of these combinations in treating ER+ advanced breast cancer, Dr. O’Leary explained.

“Although many patients derive a great deal of benefit from these combinations, there are a subset of patients who will relapse relatively early, and ... we don’t have an established means of identifying those patients at the present,” he said. “From the technical perspective, liquid biopsies have emerged in recent years as a promising means of genotyping patients’ cancers from circulating tumor DNA, and in addition, the overall level of circulating tumor DNA – the fractional purity – has been associated with poor prognosis, specifically in the triple-negative breast cancer setting.”

The results, which require independent validation, could potentially inform future clinical trials of CDK4/6 inhibitor combinations in advanced ER+ breast cancer to identify a high-risk group of patients who require escalation of therapy, he concluded.

Dr. O’Leary reported receiving research funding from Pfizer to his institution.

SOURCE: O’Leary B et al. ASCO 2019, Abstract 1010.

CHICAGO – Tumor protein 53 (TP53) mutation, fibroblast growth factor receptor 1 (FGFR1) amplification, and tumor purity in plasma each predict early progression on palbociclib and/or fulvestrant in patients with advanced estrogen receptor–positive (ER+) breast cancer, according to genomic analyses of PALOMA-3 trial data.

Sharon Worcester/MDedge News

Overall, the presence of one or more of these genomic changes identified 131 out of 310 patients from the phase 3 trial who had baseline samples available, Ben O’Leary, MBBS, said at the annual meeting of the American Society of Clinical Oncology.

“So, a significant minority of patients – 42.3% – potentially who fall into a more poor-prognosis group,” said Dr. O’Leary of the Institute of Cancer Research at the Royal Marsden Hospital in London.

The findings suggest that a “liquid biopsy” at the start of treatment could identify patients at risk for progression.

The PALOMA-3 trial randomized 521 patients with ER+, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer who had previously progressed on endocrine therapy 2:1 to CDK4/CDK6 inhibition with palbociclib plus fulvestrant (P+F) or placebo plus fulvestrant (F), and it showed that adding palbociclib significantly improved progression-free survival (PFS) (N Engl J Med. Jul 16 2015;373:209-19).

For the current analysis, the investigators assessed circulating tumor DNA (ctDNA) in baseline plasma samples from 459 study participants in an effort to identify genomic biomarkers for progression, to examine the association between baseline tumor fraction and clinical outcome, and to explore differences in predictive markers by treatment arm. A custom amplicon-sequencing analysis was performed to look for mutations in 17 different relevant genes, and another was used to estimate tumor fraction by looking at about 800 common germline single-nucleotide polymorphisms and to assess copy-number gain in the amplification status in 11 different genes, Dr. O’Leary said.


Results for mutations and circulating nucleic acids were available in 203 and 107 patients from the P+F and F groups, respectively, and on multivariable analysis of all 310 patients (including palbociclib as a variable in the model and with ctDNA fraction as a continuous variable), higher baseline tumor purity in plasma was associated with highly significantly worse PFS (HR 1.2 per 10% increase in purity), and baseline TP53 mutation and FGFR1 amplification each were associated with significantly shorter PFS (HRs, 1.8 and 2.9, respectively).

“[It is] very important to note ... that we did look specifically for interaction between our genomic changes and treatment, and we didn’t find any evidence of a significant interaction, so these genomic markers [are] prognostic rather than predictive in terms of the two treatment arms of the trial,” he said.

A survival analysis showed a median PFS of 3.7 vs. 12.7 months in patients with vs. without TP53 mutation in the P+F arm, and 1.8 vs. 5.4 months, respectively, in the F arm, with similar HRs of 2.0 and 2.3 in the arms, respectively.

“Even in the [P+F] arm, you see almost half of the patients with a TP53 mutation ... have relapsed by 2 months, the earliest clinical assessment in the trial,” he noted.

For FGFR1, the PFS was 3.9 vs. 12 months with vs. without amplification in the P+F arms, and 1.8 vs. 5.8 months, respectively in th F arm, with HRs of 3.4 and 3.6, respectively.

These findings are notable because markers of early progression on endocrine therapy in combination with CDK4/6 inhibitors remain limited – despite the key role of these combinations in treating ER+ advanced breast cancer, Dr. O’Leary explained.

“Although many patients derive a great deal of benefit from these combinations, there are a subset of patients who will relapse relatively early, and ... we don’t have an established means of identifying those patients at the present,” he said. “From the technical perspective, liquid biopsies have emerged in recent years as a promising means of genotyping patients’ cancers from circulating tumor DNA, and in addition, the overall level of circulating tumor DNA – the fractional purity – has been associated with poor prognosis, specifically in the triple-negative breast cancer setting.”

The results, which require independent validation, could potentially inform future clinical trials of CDK4/6 inhibitor combinations in advanced ER+ breast cancer to identify a high-risk group of patients who require escalation of therapy, he concluded.

Dr. O’Leary reported receiving research funding from Pfizer to his institution.

SOURCE: O’Leary B et al. ASCO 2019, Abstract 1010.

The inability to be in two places at one time makes VAM On Demand an essential component of the Vascular Annual Meeting.

ISerg Creative/Getty Images

VAM on Demand lets people review — in depth and on their own timeline —sessions they attended and “attend” electronically the ones they couldn’t in person. VAM on Demand will include hundreds of individual presentations, with accompanying PowerPoint slides and audio. Select video sessions will be available.

The fee is $199 for attendees after the meeting ends. (Non-attendees may purchase VAM on Demand for $499.) All purchasers receive unlimited access, plus downloads to the library, for up to one year. Access begins several weeks after VAM ends and will be available on the SVS website vascular.org.

Contact education@vascularsociety.org with questions.




 

The inability to be in two places at one time makes VAM On Demand an essential component of the Vascular Annual Meeting.

ISerg Creative/Getty Images

VAM on Demand lets people review — in depth and on their own timeline —sessions they attended and “attend” electronically the ones they couldn’t in person. VAM on Demand will include hundreds of individual presentations, with accompanying PowerPoint slides and audio. Select video sessions will be available.

The fee is $199 for attendees after the meeting ends. (Non-attendees may purchase VAM on Demand for $499.) All purchasers receive unlimited access, plus downloads to the library, for up to one year. Access begins several weeks after VAM ends and will be available on the SVS website vascular.org.

Contact education@vascularsociety.org with questions.




 

The inability to be in two places at one time makes VAM On Demand an essential component of the Vascular Annual Meeting.

ISerg Creative/Getty Images

VAM on Demand lets people review — in depth and on their own timeline —sessions they attended and “attend” electronically the ones they couldn’t in person. VAM on Demand will include hundreds of individual presentations, with accompanying PowerPoint slides and audio. Select video sessions will be available.

The fee is $199 for attendees after the meeting ends. (Non-attendees may purchase VAM on Demand for $499.) All purchasers receive unlimited access, plus downloads to the library, for up to one year. Access begins several weeks after VAM ends and will be available on the SVS website vascular.org.

Contact education@vascularsociety.org with questions.