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More Medicaid pay leads to more pediatric participation
If you provide better Medicaid payment, pediatricians will participate.
“Office-based primary care pediatricians, who had historically been more resistant to [Medicaid] participation than either their subspecialist or safety net and institution-based peers, increased their participation in the Medicaid program nationally from before to after the 2013 to 2014 Medicaid payment increase,” noted Suk-fong S. Tang, PhD, research analyst at American Academy of Pediatrics, and colleagues.
“That we found participation increases in 4 of 5 indicators nationally and by different measures in the majority of studied states speaks to the robustness of our conclusions,” they wrote.
The researchers looked at office-based primary care pediatricians’ participation in Medicaid between 2011 to 2012 and 2015 to 2016 (prior to and following the temporary Medicaid pay increases provided by the Affordable Care Act) across 27 states and found that those accepting at least some new patients insured by Medicaid increased by 3% to 77%. Pediatricians accepting all new patients insured by Medicaid increased by 6% to 43% and those accepting these patients at least as often as new privately insured patients increased by 6% to 56%. The average percentage of patients insured by Medicaid per provider panel increased by 6% to 31%.
“In light of such findings, the cost and benefits of recruiting new participants versus incentivizing existing participants to increase their Medicaid capacity merit further investigation and the potential for both strategies to improve access should be considered,” the authors wrote.
The AAP Friends of Children Fund supported the study. The researchers reported no relevant financial conflicts of interest.
SOURCE: Tang S et al. Pediatrics 2018 Jan. doi: 10.1542/peds.2017-2570.
There are a number of ways to use payments as the carrot to increase pediatrician participation in Medicaid: raising rates for preventive care as with private insurance, fully covering the cost of vaccines, paying for developmental screening, and providing incentives for up-to-date immunization rates and meeting targets for developmental and lead screening.
Payments should be done as a per-member-per-month care coordination payment and claims should be simplified so they can be paid in a timely manner.
Stephen Berman, MD, of the University of Colorado, expressed his views in a commentary accompanying Dr. Suk-fong’s study (Pediatrics 2018 Jan. doi: 10.1542/peds.2017-3241 ).
There are a number of ways to use payments as the carrot to increase pediatrician participation in Medicaid: raising rates for preventive care as with private insurance, fully covering the cost of vaccines, paying for developmental screening, and providing incentives for up-to-date immunization rates and meeting targets for developmental and lead screening.
Payments should be done as a per-member-per-month care coordination payment and claims should be simplified so they can be paid in a timely manner.
Stephen Berman, MD, of the University of Colorado, expressed his views in a commentary accompanying Dr. Suk-fong’s study (Pediatrics 2018 Jan. doi: 10.1542/peds.2017-3241 ).
There are a number of ways to use payments as the carrot to increase pediatrician participation in Medicaid: raising rates for preventive care as with private insurance, fully covering the cost of vaccines, paying for developmental screening, and providing incentives for up-to-date immunization rates and meeting targets for developmental and lead screening.
Payments should be done as a per-member-per-month care coordination payment and claims should be simplified so they can be paid in a timely manner.
Stephen Berman, MD, of the University of Colorado, expressed his views in a commentary accompanying Dr. Suk-fong’s study (Pediatrics 2018 Jan. doi: 10.1542/peds.2017-3241 ).
If you provide better Medicaid payment, pediatricians will participate.
“Office-based primary care pediatricians, who had historically been more resistant to [Medicaid] participation than either their subspecialist or safety net and institution-based peers, increased their participation in the Medicaid program nationally from before to after the 2013 to 2014 Medicaid payment increase,” noted Suk-fong S. Tang, PhD, research analyst at American Academy of Pediatrics, and colleagues.
“That we found participation increases in 4 of 5 indicators nationally and by different measures in the majority of studied states speaks to the robustness of our conclusions,” they wrote.
The researchers looked at office-based primary care pediatricians’ participation in Medicaid between 2011 to 2012 and 2015 to 2016 (prior to and following the temporary Medicaid pay increases provided by the Affordable Care Act) across 27 states and found that those accepting at least some new patients insured by Medicaid increased by 3% to 77%. Pediatricians accepting all new patients insured by Medicaid increased by 6% to 43% and those accepting these patients at least as often as new privately insured patients increased by 6% to 56%. The average percentage of patients insured by Medicaid per provider panel increased by 6% to 31%.
“In light of such findings, the cost and benefits of recruiting new participants versus incentivizing existing participants to increase their Medicaid capacity merit further investigation and the potential for both strategies to improve access should be considered,” the authors wrote.
The AAP Friends of Children Fund supported the study. The researchers reported no relevant financial conflicts of interest.
SOURCE: Tang S et al. Pediatrics 2018 Jan. doi: 10.1542/peds.2017-2570.
If you provide better Medicaid payment, pediatricians will participate.
“Office-based primary care pediatricians, who had historically been more resistant to [Medicaid] participation than either their subspecialist or safety net and institution-based peers, increased their participation in the Medicaid program nationally from before to after the 2013 to 2014 Medicaid payment increase,” noted Suk-fong S. Tang, PhD, research analyst at American Academy of Pediatrics, and colleagues.
“That we found participation increases in 4 of 5 indicators nationally and by different measures in the majority of studied states speaks to the robustness of our conclusions,” they wrote.
The researchers looked at office-based primary care pediatricians’ participation in Medicaid between 2011 to 2012 and 2015 to 2016 (prior to and following the temporary Medicaid pay increases provided by the Affordable Care Act) across 27 states and found that those accepting at least some new patients insured by Medicaid increased by 3% to 77%. Pediatricians accepting all new patients insured by Medicaid increased by 6% to 43% and those accepting these patients at least as often as new privately insured patients increased by 6% to 56%. The average percentage of patients insured by Medicaid per provider panel increased by 6% to 31%.
“In light of such findings, the cost and benefits of recruiting new participants versus incentivizing existing participants to increase their Medicaid capacity merit further investigation and the potential for both strategies to improve access should be considered,” the authors wrote.
The AAP Friends of Children Fund supported the study. The researchers reported no relevant financial conflicts of interest.
SOURCE: Tang S et al. Pediatrics 2018 Jan. doi: 10.1542/peds.2017-2570.
FROM PEDIATRICS
Key clinical point: Better Medicaid pay increases physician participation in the program.
Major finding: Percentage of pediatricians accepting some Medicaid patients increased from 3% to 77% during the temporary increase.
Study details: A study of office-based primary care pediatricians’ participation in Medicaid between the periods of 2011-2012 and 2015-2016 in 27 states, before and after temporary Medicaid pay increases provided by the ACA.
Disclosures: The AAP Friends of Children Fund supported the study. The researchers reported no relevant financial conflicts of interest.
Source: Tang S et al. Pediatrics 2018 Jan. doi:10.1542/peds.2017-2570.
Ertugliflozin gets FDA thumbs-up for glucose control
The Food and Drug Administration has approved ertugliflozin for use both as monotherapy and in combination with sitagliptin or metformin to control blood glucose in patients with type 2 diabetes.
The FDA approval covers ertugliflozin monotherapy (Steglatro, Merck and Pfizer) and ertugliflozin plus sitagliptin, a dipeptidyl peptidase–4 (DPP-4) inhibitor, as a fixed-dose combination (Steglujan, Merck) and ertugliflozin plus metformin (Segluromet, Merck).
Ertugliflozin is the third sodium glucose cotransporter 2 (SGLT2) inhibitor to win FDA approval. Another such agent, empagliflozin, recently won a second indication for lowering the risk for cardiovascular death in adults with type 2 diabetes and established heart disease.
The American Diabetes Association recognized the value of SGLT2 inhibitors in patients with type 2 diabetes in its 2018 Standards of Care in Diabetes, now recommending that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the SGLT2 inhibitor empagliflozin or the glucagonlike peptide–1 agonist liraglutide – to the regimens of patients with diabetes and atherosclerotic cardiovascular disease (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
The Food and Drug Administration has approved ertugliflozin for use both as monotherapy and in combination with sitagliptin or metformin to control blood glucose in patients with type 2 diabetes.
The FDA approval covers ertugliflozin monotherapy (Steglatro, Merck and Pfizer) and ertugliflozin plus sitagliptin, a dipeptidyl peptidase–4 (DPP-4) inhibitor, as a fixed-dose combination (Steglujan, Merck) and ertugliflozin plus metformin (Segluromet, Merck).
Ertugliflozin is the third sodium glucose cotransporter 2 (SGLT2) inhibitor to win FDA approval. Another such agent, empagliflozin, recently won a second indication for lowering the risk for cardiovascular death in adults with type 2 diabetes and established heart disease.
The American Diabetes Association recognized the value of SGLT2 inhibitors in patients with type 2 diabetes in its 2018 Standards of Care in Diabetes, now recommending that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the SGLT2 inhibitor empagliflozin or the glucagonlike peptide–1 agonist liraglutide – to the regimens of patients with diabetes and atherosclerotic cardiovascular disease (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
The Food and Drug Administration has approved ertugliflozin for use both as monotherapy and in combination with sitagliptin or metformin to control blood glucose in patients with type 2 diabetes.
The FDA approval covers ertugliflozin monotherapy (Steglatro, Merck and Pfizer) and ertugliflozin plus sitagliptin, a dipeptidyl peptidase–4 (DPP-4) inhibitor, as a fixed-dose combination (Steglujan, Merck) and ertugliflozin plus metformin (Segluromet, Merck).
Ertugliflozin is the third sodium glucose cotransporter 2 (SGLT2) inhibitor to win FDA approval. Another such agent, empagliflozin, recently won a second indication for lowering the risk for cardiovascular death in adults with type 2 diabetes and established heart disease.
The American Diabetes Association recognized the value of SGLT2 inhibitors in patients with type 2 diabetes in its 2018 Standards of Care in Diabetes, now recommending that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the SGLT2 inhibitor empagliflozin or the glucagonlike peptide–1 agonist liraglutide – to the regimens of patients with diabetes and atherosclerotic cardiovascular disease (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
Loneliness is common, and not just in the elderly
MONTREAL – Loneliness is associated with poorer health, but isn’t necessarily more common among older adults; one in five adults in a primary care population reported being lonely, a number higher than previously reported, a study showed.
In a survey of 940 adults seeking care in primary care clinics, 193 (21%) reported loneliness, with women more likely than men to say they were lonely. “Respondents identifying as having poorer health classifications were more likely to report high loneliness scores,” said Rebecca Mullen, MD, and her colleagues in a poster presented at the annual meeting of the North American Primary Care Research Group.
Those who said they were lonely also had a higher level of health care utilization, and reported they had a lower number of healthy days than the respondents who didn’t report loneliness.
The study was conducted in outpatient practice-based research networks in both urban and rural settings in the states of Virginia and Colorado. Participants were adult, English-speaking primary care patients who were given the UCLA Three-Item Loneliness Scale. The scale asks how often respondents feel a lack of companionship, feel left out, and feel isolated from others; responses are “hardly ever,” “sometimes,” and “often.”
The investigators sought to determine whether high loneliness scores on this scale – the primary outcome – were correlated with health care utilization, the number of healthy days reported by patients, and demographic information. These associations were the study’s secondary outcomes.
After statistical analysis, several variables emerged as being significantly associated with high loneliness scores. These included the number of reported days with poor physical or mental health (odds ratio, 1.06), the number of primary care office visits (OR, 1.06), the number of hospitalizations (OR, 1.16), the number of emergency department or urgent care visits (OR ,1.27), and gender.
When compared with male respondents, females had an OR of 1.56 for reporting loneliness.
Race and ethnicity were not associated with a greater risk of loneliness; neither were disability or employment status, or whether the respondent was in a relationship.
And despite other studies indicating an increased prevalence of loneliness among the elderly, “our findings suggest loneliness is not age related,” wrote Dr. Mullen and her colleagues.
The investigators said they plan to examine their data further, to see if factors such as living in a rural or urban environment are associated with differences in loneliness. Going into still more detail, they plan to use demographic data to plot out respondents’ residences, and then look for spatial associations and links to other comorbidities. Integrating the questionnaire with data from the electronic record will allow Dr. Mullen and her colleagues to search for further associations as well, they said.
Finally, the investigators plan to build partnerships with the community, public health agencies, and those involved in health policy to build interventions against loneliness targeted at both the individual and the community. Some of these interventions, they said, could begin in the clinic: “[T]he primary care health care setting may be an appropriate context to consider intervention delivery.”
Dr. Mullen reported no relevant financial conflicts of interest.
SOURCE: Mullen R et al. Abstract P196.
MONTREAL – Loneliness is associated with poorer health, but isn’t necessarily more common among older adults; one in five adults in a primary care population reported being lonely, a number higher than previously reported, a study showed.
In a survey of 940 adults seeking care in primary care clinics, 193 (21%) reported loneliness, with women more likely than men to say they were lonely. “Respondents identifying as having poorer health classifications were more likely to report high loneliness scores,” said Rebecca Mullen, MD, and her colleagues in a poster presented at the annual meeting of the North American Primary Care Research Group.
Those who said they were lonely also had a higher level of health care utilization, and reported they had a lower number of healthy days than the respondents who didn’t report loneliness.
The study was conducted in outpatient practice-based research networks in both urban and rural settings in the states of Virginia and Colorado. Participants were adult, English-speaking primary care patients who were given the UCLA Three-Item Loneliness Scale. The scale asks how often respondents feel a lack of companionship, feel left out, and feel isolated from others; responses are “hardly ever,” “sometimes,” and “often.”
The investigators sought to determine whether high loneliness scores on this scale – the primary outcome – were correlated with health care utilization, the number of healthy days reported by patients, and demographic information. These associations were the study’s secondary outcomes.
After statistical analysis, several variables emerged as being significantly associated with high loneliness scores. These included the number of reported days with poor physical or mental health (odds ratio, 1.06), the number of primary care office visits (OR, 1.06), the number of hospitalizations (OR, 1.16), the number of emergency department or urgent care visits (OR ,1.27), and gender.
When compared with male respondents, females had an OR of 1.56 for reporting loneliness.
Race and ethnicity were not associated with a greater risk of loneliness; neither were disability or employment status, or whether the respondent was in a relationship.
And despite other studies indicating an increased prevalence of loneliness among the elderly, “our findings suggest loneliness is not age related,” wrote Dr. Mullen and her colleagues.
The investigators said they plan to examine their data further, to see if factors such as living in a rural or urban environment are associated with differences in loneliness. Going into still more detail, they plan to use demographic data to plot out respondents’ residences, and then look for spatial associations and links to other comorbidities. Integrating the questionnaire with data from the electronic record will allow Dr. Mullen and her colleagues to search for further associations as well, they said.
Finally, the investigators plan to build partnerships with the community, public health agencies, and those involved in health policy to build interventions against loneliness targeted at both the individual and the community. Some of these interventions, they said, could begin in the clinic: “[T]he primary care health care setting may be an appropriate context to consider intervention delivery.”
Dr. Mullen reported no relevant financial conflicts of interest.
SOURCE: Mullen R et al. Abstract P196.
MONTREAL – Loneliness is associated with poorer health, but isn’t necessarily more common among older adults; one in five adults in a primary care population reported being lonely, a number higher than previously reported, a study showed.
In a survey of 940 adults seeking care in primary care clinics, 193 (21%) reported loneliness, with women more likely than men to say they were lonely. “Respondents identifying as having poorer health classifications were more likely to report high loneliness scores,” said Rebecca Mullen, MD, and her colleagues in a poster presented at the annual meeting of the North American Primary Care Research Group.
Those who said they were lonely also had a higher level of health care utilization, and reported they had a lower number of healthy days than the respondents who didn’t report loneliness.
The study was conducted in outpatient practice-based research networks in both urban and rural settings in the states of Virginia and Colorado. Participants were adult, English-speaking primary care patients who were given the UCLA Three-Item Loneliness Scale. The scale asks how often respondents feel a lack of companionship, feel left out, and feel isolated from others; responses are “hardly ever,” “sometimes,” and “often.”
The investigators sought to determine whether high loneliness scores on this scale – the primary outcome – were correlated with health care utilization, the number of healthy days reported by patients, and demographic information. These associations were the study’s secondary outcomes.
After statistical analysis, several variables emerged as being significantly associated with high loneliness scores. These included the number of reported days with poor physical or mental health (odds ratio, 1.06), the number of primary care office visits (OR, 1.06), the number of hospitalizations (OR, 1.16), the number of emergency department or urgent care visits (OR ,1.27), and gender.
When compared with male respondents, females had an OR of 1.56 for reporting loneliness.
Race and ethnicity were not associated with a greater risk of loneliness; neither were disability or employment status, or whether the respondent was in a relationship.
And despite other studies indicating an increased prevalence of loneliness among the elderly, “our findings suggest loneliness is not age related,” wrote Dr. Mullen and her colleagues.
The investigators said they plan to examine their data further, to see if factors such as living in a rural or urban environment are associated with differences in loneliness. Going into still more detail, they plan to use demographic data to plot out respondents’ residences, and then look for spatial associations and links to other comorbidities. Integrating the questionnaire with data from the electronic record will allow Dr. Mullen and her colleagues to search for further associations as well, they said.
Finally, the investigators plan to build partnerships with the community, public health agencies, and those involved in health policy to build interventions against loneliness targeted at both the individual and the community. Some of these interventions, they said, could begin in the clinic: “[T]he primary care health care setting may be an appropriate context to consider intervention delivery.”
Dr. Mullen reported no relevant financial conflicts of interest.
SOURCE: Mullen R et al. Abstract P196.
REPORTING FROM NAPCRG 2017
Key clinical point: One in five adults – and more women than men – reported loneliness.
Major finding: Of 940 adults surveyed, 193 (21%) reported being lonely.
Study details: A prospective survey of 940 adults seeking care in primary care clinics.
Disclosures: Dr. Mullen reported no relevant financial conflicts of interest.
Urgent endoscopy is associated with lower mortality in high-risk patients with acute nonvariceal GI bleeding
Clinical question: Is urgent endoscopy (less than 6 hours after ED presentation) better than elective endoscopy (6-48 hours after presentation) to decrease mortality and rebleeding in high-risk patients with acute nonvariceal upper GI bleeding (ANVGIB)?
Background: High-risk ANVGIB patients (Glasgow-Blatchford score greater than 7) are recommended to undergo early endoscopy, within 24 hours of presentation. The impact of urgent endoscopy (less than 6 hours) on patient outcomes is not clear.
Study design: Retrospective observation study.
Setting: Single tertiary referral center in South Korea.
Synopsis: Investigators retrospectively reviewed 961 high-risk ANVGIB patients, 571 patients underwent urgent endoscopy and 390 patients had elective endoscopy (6-48 hours), to compare clinical features and outcomes. The urgent group was slightly older, had a higher Rockall score, lower blood pressure, and higher incidence of shock on admission.
Urgent endoscopy was associated with significantly lower 28-day mortality (1.6% vs 3.8%). Urgent endoscopy also was associated with higher packed red blood cell transfusion volume (2.6 U vs. 2.3 U) and greater need for endoscopic intervention (69.5% vs. 53.5%) and embolization (2.8% vs. 0.5%). There was no significant difference in rebleeding rates, need for ICU admission, vasopressor use, and length of hospital stay between the urgent and elective endoscopy groups. The authors conclude that urgent endoscopy was associated with lower mortality rate but not rebleeding in high-risk patients with ANVGIB.
Despite differences between these two groups, based on this retrospective data, it is reasonable to suggest that urgent endoscopy may be beneficial for reducing mortality in high-risk patients with ANVGIB.
Bottom line: Urgent endoscopy may be beneficial in reducing mortality in high-risk patients with acute nonvariceal gastrointestinal bleeding.
Citation: Cho SH et al. Outcomes and role of urgent endoscopy in high-risk patients with acute nonvariceal gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2017 Jun 19. pii: S1542-3565(17)30736-X.
Dr. Patel is a hospitalist and an assistant professor of medicine, Duke University Health System.
Clinical question: Is urgent endoscopy (less than 6 hours after ED presentation) better than elective endoscopy (6-48 hours after presentation) to decrease mortality and rebleeding in high-risk patients with acute nonvariceal upper GI bleeding (ANVGIB)?
Background: High-risk ANVGIB patients (Glasgow-Blatchford score greater than 7) are recommended to undergo early endoscopy, within 24 hours of presentation. The impact of urgent endoscopy (less than 6 hours) on patient outcomes is not clear.
Study design: Retrospective observation study.
Setting: Single tertiary referral center in South Korea.
Synopsis: Investigators retrospectively reviewed 961 high-risk ANVGIB patients, 571 patients underwent urgent endoscopy and 390 patients had elective endoscopy (6-48 hours), to compare clinical features and outcomes. The urgent group was slightly older, had a higher Rockall score, lower blood pressure, and higher incidence of shock on admission.
Urgent endoscopy was associated with significantly lower 28-day mortality (1.6% vs 3.8%). Urgent endoscopy also was associated with higher packed red blood cell transfusion volume (2.6 U vs. 2.3 U) and greater need for endoscopic intervention (69.5% vs. 53.5%) and embolization (2.8% vs. 0.5%). There was no significant difference in rebleeding rates, need for ICU admission, vasopressor use, and length of hospital stay between the urgent and elective endoscopy groups. The authors conclude that urgent endoscopy was associated with lower mortality rate but not rebleeding in high-risk patients with ANVGIB.
Despite differences between these two groups, based on this retrospective data, it is reasonable to suggest that urgent endoscopy may be beneficial for reducing mortality in high-risk patients with ANVGIB.
Bottom line: Urgent endoscopy may be beneficial in reducing mortality in high-risk patients with acute nonvariceal gastrointestinal bleeding.
Citation: Cho SH et al. Outcomes and role of urgent endoscopy in high-risk patients with acute nonvariceal gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2017 Jun 19. pii: S1542-3565(17)30736-X.
Dr. Patel is a hospitalist and an assistant professor of medicine, Duke University Health System.
Clinical question: Is urgent endoscopy (less than 6 hours after ED presentation) better than elective endoscopy (6-48 hours after presentation) to decrease mortality and rebleeding in high-risk patients with acute nonvariceal upper GI bleeding (ANVGIB)?
Background: High-risk ANVGIB patients (Glasgow-Blatchford score greater than 7) are recommended to undergo early endoscopy, within 24 hours of presentation. The impact of urgent endoscopy (less than 6 hours) on patient outcomes is not clear.
Study design: Retrospective observation study.
Setting: Single tertiary referral center in South Korea.
Synopsis: Investigators retrospectively reviewed 961 high-risk ANVGIB patients, 571 patients underwent urgent endoscopy and 390 patients had elective endoscopy (6-48 hours), to compare clinical features and outcomes. The urgent group was slightly older, had a higher Rockall score, lower blood pressure, and higher incidence of shock on admission.
Urgent endoscopy was associated with significantly lower 28-day mortality (1.6% vs 3.8%). Urgent endoscopy also was associated with higher packed red blood cell transfusion volume (2.6 U vs. 2.3 U) and greater need for endoscopic intervention (69.5% vs. 53.5%) and embolization (2.8% vs. 0.5%). There was no significant difference in rebleeding rates, need for ICU admission, vasopressor use, and length of hospital stay between the urgent and elective endoscopy groups. The authors conclude that urgent endoscopy was associated with lower mortality rate but not rebleeding in high-risk patients with ANVGIB.
Despite differences between these two groups, based on this retrospective data, it is reasonable to suggest that urgent endoscopy may be beneficial for reducing mortality in high-risk patients with ANVGIB.
Bottom line: Urgent endoscopy may be beneficial in reducing mortality in high-risk patients with acute nonvariceal gastrointestinal bleeding.
Citation: Cho SH et al. Outcomes and role of urgent endoscopy in high-risk patients with acute nonvariceal gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2017 Jun 19. pii: S1542-3565(17)30736-X.
Dr. Patel is a hospitalist and an assistant professor of medicine, Duke University Health System.
Journal of Hospital Medicine – Dec. 2017
BACKGROUND: Identifying hospitals that are both early and consistent adopters of high-value care can help shed light on the culture and practices at those institutions that are necessary to promote high-value care nationwide. The use of troponin testing to diagnose acute myocardial infarction (AMI), and not testing for myoglobin or creatine kinase-MB (CK-MB), is a high-value recommendation of the Choosing Wisely® campaign.
OBJECTIVE: To examine the variation in cardiac biomarker testing and the effect of the Choosing Wisely® troponin-only testing recommendation for the diagnosis of AMI.
DESIGN: A retrospective, observational study using administrative ordering data from Vizient’s Clinical Database/Resource Manager.
PATIENTS: Hospitalized patients with a principal discharge diagnosis of AMI.
INTERVENTION: The Choosing Wisely® recommendation to order troponin-only testing to diagnose AMI was released during the first quarter of 2015.
RESULTS: In 19 hospitals, troponin-only testing was consistently ordered to diagnose AMI before the Choosing Wisely® recommendation and throughout the study period. In 34 hospitals, both troponin testing and myoglobin/CK-MB testing were ordered to diagnose AMI even after the Choosing Wisely® recommendation. In 26 hospitals with low rates of troponin-only testing before the Choosing Wisely® recommendation, the release of the recommendation was associated with a statistically significant increase in the rate of troponin-only testing to diagnose AMI.
CONCLUSION: In institutions with low rates of troponin-only testing prior to the Choosing Wisely® recommendation, the recommendation was associated with a significant increase in the rate of troponin-only testing.
Read the entire article in the Dec. 2017 issue of the Journal of Hospital Medicine.
Also in JHM this month
Hospital perceptions of Medicare’s Sepsis Quality Reporting Initiative
AUTHORS: Ian J. Barbash, MD, MS; Kimberly J. Rak, PhD; Courtney C. Kuza, MPH; and Jeremy M. Kahn, MD, MS
Health literacy and hospital length of stay: An inpatient cohort study
AUTHORS: Ethan G. Jaffee, MD; Vineet M. Arora, MD, MAPP; Madeleine I. Matthiesen, MD; David O. Meltzer, MD, PhD, MHM; and Valerie G. Press, MD, FAAP, FACP, MPH
How exemplary teaching physicians interact with hospitalized patients
AUTHORS: Sanjay Saint, MD, MPH, FHM; Molly Harrod, PhD; Karen E. Fowler, MPH; and Nathan Houchens, MD, FACP, FHM
A randomized cohort controlled trial to compare intern sign-out training interventions
AUTHORS: Soo-Hoon Lee, PhD; Christopher Terndrup, MD; Phillip H. Phan, PhD; Sandra E. Zaeh, MD; Kwame Atsina, MD; Nicole Minkove, MD; Alexander Billioux, MD; DPhil, Souvik Chatterjee, MD; Idoreyin Montague, MD; Bennett Clark, MD; Andrew Hughes, MD; and Sanjay V. Desai, MD
BACKGROUND: Identifying hospitals that are both early and consistent adopters of high-value care can help shed light on the culture and practices at those institutions that are necessary to promote high-value care nationwide. The use of troponin testing to diagnose acute myocardial infarction (AMI), and not testing for myoglobin or creatine kinase-MB (CK-MB), is a high-value recommendation of the Choosing Wisely® campaign.
OBJECTIVE: To examine the variation in cardiac biomarker testing and the effect of the Choosing Wisely® troponin-only testing recommendation for the diagnosis of AMI.
DESIGN: A retrospective, observational study using administrative ordering data from Vizient’s Clinical Database/Resource Manager.
PATIENTS: Hospitalized patients with a principal discharge diagnosis of AMI.
INTERVENTION: The Choosing Wisely® recommendation to order troponin-only testing to diagnose AMI was released during the first quarter of 2015.
RESULTS: In 19 hospitals, troponin-only testing was consistently ordered to diagnose AMI before the Choosing Wisely® recommendation and throughout the study period. In 34 hospitals, both troponin testing and myoglobin/CK-MB testing were ordered to diagnose AMI even after the Choosing Wisely® recommendation. In 26 hospitals with low rates of troponin-only testing before the Choosing Wisely® recommendation, the release of the recommendation was associated with a statistically significant increase in the rate of troponin-only testing to diagnose AMI.
CONCLUSION: In institutions with low rates of troponin-only testing prior to the Choosing Wisely® recommendation, the recommendation was associated with a significant increase in the rate of troponin-only testing.
Read the entire article in the Dec. 2017 issue of the Journal of Hospital Medicine.
Also in JHM this month
Hospital perceptions of Medicare’s Sepsis Quality Reporting Initiative
AUTHORS: Ian J. Barbash, MD, MS; Kimberly J. Rak, PhD; Courtney C. Kuza, MPH; and Jeremy M. Kahn, MD, MS
Health literacy and hospital length of stay: An inpatient cohort study
AUTHORS: Ethan G. Jaffee, MD; Vineet M. Arora, MD, MAPP; Madeleine I. Matthiesen, MD; David O. Meltzer, MD, PhD, MHM; and Valerie G. Press, MD, FAAP, FACP, MPH
How exemplary teaching physicians interact with hospitalized patients
AUTHORS: Sanjay Saint, MD, MPH, FHM; Molly Harrod, PhD; Karen E. Fowler, MPH; and Nathan Houchens, MD, FACP, FHM
A randomized cohort controlled trial to compare intern sign-out training interventions
AUTHORS: Soo-Hoon Lee, PhD; Christopher Terndrup, MD; Phillip H. Phan, PhD; Sandra E. Zaeh, MD; Kwame Atsina, MD; Nicole Minkove, MD; Alexander Billioux, MD; DPhil, Souvik Chatterjee, MD; Idoreyin Montague, MD; Bennett Clark, MD; Andrew Hughes, MD; and Sanjay V. Desai, MD
BACKGROUND: Identifying hospitals that are both early and consistent adopters of high-value care can help shed light on the culture and practices at those institutions that are necessary to promote high-value care nationwide. The use of troponin testing to diagnose acute myocardial infarction (AMI), and not testing for myoglobin or creatine kinase-MB (CK-MB), is a high-value recommendation of the Choosing Wisely® campaign.
OBJECTIVE: To examine the variation in cardiac biomarker testing and the effect of the Choosing Wisely® troponin-only testing recommendation for the diagnosis of AMI.
DESIGN: A retrospective, observational study using administrative ordering data from Vizient’s Clinical Database/Resource Manager.
PATIENTS: Hospitalized patients with a principal discharge diagnosis of AMI.
INTERVENTION: The Choosing Wisely® recommendation to order troponin-only testing to diagnose AMI was released during the first quarter of 2015.
RESULTS: In 19 hospitals, troponin-only testing was consistently ordered to diagnose AMI before the Choosing Wisely® recommendation and throughout the study period. In 34 hospitals, both troponin testing and myoglobin/CK-MB testing were ordered to diagnose AMI even after the Choosing Wisely® recommendation. In 26 hospitals with low rates of troponin-only testing before the Choosing Wisely® recommendation, the release of the recommendation was associated with a statistically significant increase in the rate of troponin-only testing to diagnose AMI.
CONCLUSION: In institutions with low rates of troponin-only testing prior to the Choosing Wisely® recommendation, the recommendation was associated with a significant increase in the rate of troponin-only testing.
Read the entire article in the Dec. 2017 issue of the Journal of Hospital Medicine.
Also in JHM this month
Hospital perceptions of Medicare’s Sepsis Quality Reporting Initiative
AUTHORS: Ian J. Barbash, MD, MS; Kimberly J. Rak, PhD; Courtney C. Kuza, MPH; and Jeremy M. Kahn, MD, MS
Health literacy and hospital length of stay: An inpatient cohort study
AUTHORS: Ethan G. Jaffee, MD; Vineet M. Arora, MD, MAPP; Madeleine I. Matthiesen, MD; David O. Meltzer, MD, PhD, MHM; and Valerie G. Press, MD, FAAP, FACP, MPH
How exemplary teaching physicians interact with hospitalized patients
AUTHORS: Sanjay Saint, MD, MPH, FHM; Molly Harrod, PhD; Karen E. Fowler, MPH; and Nathan Houchens, MD, FACP, FHM
A randomized cohort controlled trial to compare intern sign-out training interventions
AUTHORS: Soo-Hoon Lee, PhD; Christopher Terndrup, MD; Phillip H. Phan, PhD; Sandra E. Zaeh, MD; Kwame Atsina, MD; Nicole Minkove, MD; Alexander Billioux, MD; DPhil, Souvik Chatterjee, MD; Idoreyin Montague, MD; Bennett Clark, MD; Andrew Hughes, MD; and Sanjay V. Desai, MD
Personal omics profiling here to stay
LOS ANGELES – Michael Snyder, PhD, wears his research on his sleeve, so to speak. On any given day, he wears up to eight devices on his body that measure everything from radiation exposure to fasting glucose and sleep activity.
The way he sees it,wearables to monitor physiomes, plus personal omics profiling technology, give a high-resolution view of how health changes over periods of wellness and disease.
“We know intuitively that your health state is influenced by many things, including your genome and all of the things you’re exposed to, from pathogens to food, stress, and exercise,” Dr. Snyder said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “They all impact your health state, but in a future not far away, people will be born with their genome sequenced, and we will understand in a probabilistic fashion how, with a set of variants in your genome, if you are exposed to certain environmental conditions, you will have certain health outcomes. As an example, if you’re at risk for Parkinson’s disease, you probably shouldn’t be a pesticide worker, because that greatly increases the chances by which you get Parkinson’s.”
About 8 years ago, he and his associates launched an ongoing longitudinal personal omics profiling project of 105 individuals, 55% of whom are prediabetic. After undergoing genome sequencing, each person undergoes measurement of 14 different omics every 3 months, including their RNA, proteins, lipidomics, cytokines, and microbiome (Cell Host Microbe. 2014 Sep 10;16[3]:276-89).
When a perturbation comes along, like a viral infection or positive results from a colonoscopy, the researchers gather additional samples. “We are trying to understand how the different omics relate to one another,” said Dr. Snyder, who in 2012 used his own genome sequence to predict and help diagnose his own type 2 diabetes, a story that received international media attention. “If you know the inputs into a system, you should be able to calculate the outputs, no matter how complex the system is. You should be able to make meaningful associations. In this case, the inputs are your genome, your epigenome and your microbiome, and the foods you eat. The outputs would be the metabolome, and things like that. We try to understand how responses to, say, viral infections or other perturbations are similar to one another, like congestion and fever, but also why some people get more ill than others, or have varying disease-specific symptoms.”
To date, Dr. Snyder and his associates have collected about 1,800 time points and roughly 10,000 samples. The first 1,000 of those time points have been analyzed. Of the first 70 people who underwent genome sequencing, 12 had pathogenic mutations that are clinically actionable, including mutations in BRCA1, which is associated with breast and ovarian cancer; APC and MUTYH, which are associated with colon cancer; SHBD, which is associated with a high frequency of neuroendocrine tumors; and RBM20, which is associated with dilated cardiomyopathy. One such person “underwent stress testing, and it turns out he does have a heart defect,” noted Dr. Snyder, who is also the author of Genomics and Personalized Medicine: What Everyone Needs to Know (New York: Oxford University Press, 2016). “So some of this information is extremely valuable. This is why we argue that genome sequencing, much like family history, will one day move into the clinic for those who want to use it.”
So far, the longitudinal personal omics analysis has revealed other important diagnoses that likely would have flown under the radar of conventional Western medicine, including a heart defect in one person that was detected by a simple wearable device, a case of early lymphoma, and a case of MGUS (monoclonal gammopathy of unknown significance), which is a precancerous condition.
“We have also had many metabolic cases; a lot of folks were prediabetic and others were diabetic,” Dr. Snyder said. “It’s hard to predict exactly what you’re going to see for any one person. But when you collect a lot of this data, you do find things that are important for their health.”
Of the current study participants, 23 underwent a dietary perturbation. Of these, 13 were insulin resistant and 10 were healthy controls, matched for body mass index. The subjects consumed an extra 1,000 calories per day for 30 days, maintained their peak weight for 7 days, and embarked on a weight loss program for 60 days. “We looked at the effects of weight gain and weight loss in incredible molecular detail,” Dr. Snyder explained, noting that the work will appear in a forthcoming edition of Cell Systems. “At baseline, we can tell the insulin-resistant from the -sensitive folks. After people gain and lose weight, we can identify all the compounds and biochemical pathways that change by using integrative c-means clustering to identify pattern recognition across RNA sequencing, proteome, metabolome, microbiome, and cytokines. From blood, we can actually see these compounds changing. We also can tease out differences between resistance and sensitivity in their reaction to weight gain and weight loss. For example, in the microbiome, the insulin-resistant folks were more resistant to changes in weight gain and weight loss, while insulin-sensitive folks go up and down pretty well.”
The researchers also observed that the omics profile of each person who participated in the dietary perturbation study was different at baseline. “So everybody is special, and not just to our mothers,” Dr. Snyder said. “That is to say, if I profile you, you will not look like anyone sitting next to you. If you go through a perturbation, you will still look more like you than the person sitting next to you.” Going forward, he predicted that personal omics profiling “will build a personal dashboard that relays into your smartphone and can measure your health. Just like your car dashboard, we hope that you’ll have indicators of health, which will be your command center of the future.”
He disclosed that he is a scientific adviser to Personalis, Genapsys, SensOmics, and Qbio.
LOS ANGELES – Michael Snyder, PhD, wears his research on his sleeve, so to speak. On any given day, he wears up to eight devices on his body that measure everything from radiation exposure to fasting glucose and sleep activity.
The way he sees it,wearables to monitor physiomes, plus personal omics profiling technology, give a high-resolution view of how health changes over periods of wellness and disease.
“We know intuitively that your health state is influenced by many things, including your genome and all of the things you’re exposed to, from pathogens to food, stress, and exercise,” Dr. Snyder said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “They all impact your health state, but in a future not far away, people will be born with their genome sequenced, and we will understand in a probabilistic fashion how, with a set of variants in your genome, if you are exposed to certain environmental conditions, you will have certain health outcomes. As an example, if you’re at risk for Parkinson’s disease, you probably shouldn’t be a pesticide worker, because that greatly increases the chances by which you get Parkinson’s.”
About 8 years ago, he and his associates launched an ongoing longitudinal personal omics profiling project of 105 individuals, 55% of whom are prediabetic. After undergoing genome sequencing, each person undergoes measurement of 14 different omics every 3 months, including their RNA, proteins, lipidomics, cytokines, and microbiome (Cell Host Microbe. 2014 Sep 10;16[3]:276-89).
When a perturbation comes along, like a viral infection or positive results from a colonoscopy, the researchers gather additional samples. “We are trying to understand how the different omics relate to one another,” said Dr. Snyder, who in 2012 used his own genome sequence to predict and help diagnose his own type 2 diabetes, a story that received international media attention. “If you know the inputs into a system, you should be able to calculate the outputs, no matter how complex the system is. You should be able to make meaningful associations. In this case, the inputs are your genome, your epigenome and your microbiome, and the foods you eat. The outputs would be the metabolome, and things like that. We try to understand how responses to, say, viral infections or other perturbations are similar to one another, like congestion and fever, but also why some people get more ill than others, or have varying disease-specific symptoms.”
To date, Dr. Snyder and his associates have collected about 1,800 time points and roughly 10,000 samples. The first 1,000 of those time points have been analyzed. Of the first 70 people who underwent genome sequencing, 12 had pathogenic mutations that are clinically actionable, including mutations in BRCA1, which is associated with breast and ovarian cancer; APC and MUTYH, which are associated with colon cancer; SHBD, which is associated with a high frequency of neuroendocrine tumors; and RBM20, which is associated with dilated cardiomyopathy. One such person “underwent stress testing, and it turns out he does have a heart defect,” noted Dr. Snyder, who is also the author of Genomics and Personalized Medicine: What Everyone Needs to Know (New York: Oxford University Press, 2016). “So some of this information is extremely valuable. This is why we argue that genome sequencing, much like family history, will one day move into the clinic for those who want to use it.”
So far, the longitudinal personal omics analysis has revealed other important diagnoses that likely would have flown under the radar of conventional Western medicine, including a heart defect in one person that was detected by a simple wearable device, a case of early lymphoma, and a case of MGUS (monoclonal gammopathy of unknown significance), which is a precancerous condition.
“We have also had many metabolic cases; a lot of folks were prediabetic and others were diabetic,” Dr. Snyder said. “It’s hard to predict exactly what you’re going to see for any one person. But when you collect a lot of this data, you do find things that are important for their health.”
Of the current study participants, 23 underwent a dietary perturbation. Of these, 13 were insulin resistant and 10 were healthy controls, matched for body mass index. The subjects consumed an extra 1,000 calories per day for 30 days, maintained their peak weight for 7 days, and embarked on a weight loss program for 60 days. “We looked at the effects of weight gain and weight loss in incredible molecular detail,” Dr. Snyder explained, noting that the work will appear in a forthcoming edition of Cell Systems. “At baseline, we can tell the insulin-resistant from the -sensitive folks. After people gain and lose weight, we can identify all the compounds and biochemical pathways that change by using integrative c-means clustering to identify pattern recognition across RNA sequencing, proteome, metabolome, microbiome, and cytokines. From blood, we can actually see these compounds changing. We also can tease out differences between resistance and sensitivity in their reaction to weight gain and weight loss. For example, in the microbiome, the insulin-resistant folks were more resistant to changes in weight gain and weight loss, while insulin-sensitive folks go up and down pretty well.”
The researchers also observed that the omics profile of each person who participated in the dietary perturbation study was different at baseline. “So everybody is special, and not just to our mothers,” Dr. Snyder said. “That is to say, if I profile you, you will not look like anyone sitting next to you. If you go through a perturbation, you will still look more like you than the person sitting next to you.” Going forward, he predicted that personal omics profiling “will build a personal dashboard that relays into your smartphone and can measure your health. Just like your car dashboard, we hope that you’ll have indicators of health, which will be your command center of the future.”
He disclosed that he is a scientific adviser to Personalis, Genapsys, SensOmics, and Qbio.
LOS ANGELES – Michael Snyder, PhD, wears his research on his sleeve, so to speak. On any given day, he wears up to eight devices on his body that measure everything from radiation exposure to fasting glucose and sleep activity.
The way he sees it,wearables to monitor physiomes, plus personal omics profiling technology, give a high-resolution view of how health changes over periods of wellness and disease.
“We know intuitively that your health state is influenced by many things, including your genome and all of the things you’re exposed to, from pathogens to food, stress, and exercise,” Dr. Snyder said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “They all impact your health state, but in a future not far away, people will be born with their genome sequenced, and we will understand in a probabilistic fashion how, with a set of variants in your genome, if you are exposed to certain environmental conditions, you will have certain health outcomes. As an example, if you’re at risk for Parkinson’s disease, you probably shouldn’t be a pesticide worker, because that greatly increases the chances by which you get Parkinson’s.”
About 8 years ago, he and his associates launched an ongoing longitudinal personal omics profiling project of 105 individuals, 55% of whom are prediabetic. After undergoing genome sequencing, each person undergoes measurement of 14 different omics every 3 months, including their RNA, proteins, lipidomics, cytokines, and microbiome (Cell Host Microbe. 2014 Sep 10;16[3]:276-89).
When a perturbation comes along, like a viral infection or positive results from a colonoscopy, the researchers gather additional samples. “We are trying to understand how the different omics relate to one another,” said Dr. Snyder, who in 2012 used his own genome sequence to predict and help diagnose his own type 2 diabetes, a story that received international media attention. “If you know the inputs into a system, you should be able to calculate the outputs, no matter how complex the system is. You should be able to make meaningful associations. In this case, the inputs are your genome, your epigenome and your microbiome, and the foods you eat. The outputs would be the metabolome, and things like that. We try to understand how responses to, say, viral infections or other perturbations are similar to one another, like congestion and fever, but also why some people get more ill than others, or have varying disease-specific symptoms.”
To date, Dr. Snyder and his associates have collected about 1,800 time points and roughly 10,000 samples. The first 1,000 of those time points have been analyzed. Of the first 70 people who underwent genome sequencing, 12 had pathogenic mutations that are clinically actionable, including mutations in BRCA1, which is associated with breast and ovarian cancer; APC and MUTYH, which are associated with colon cancer; SHBD, which is associated with a high frequency of neuroendocrine tumors; and RBM20, which is associated with dilated cardiomyopathy. One such person “underwent stress testing, and it turns out he does have a heart defect,” noted Dr. Snyder, who is also the author of Genomics and Personalized Medicine: What Everyone Needs to Know (New York: Oxford University Press, 2016). “So some of this information is extremely valuable. This is why we argue that genome sequencing, much like family history, will one day move into the clinic for those who want to use it.”
So far, the longitudinal personal omics analysis has revealed other important diagnoses that likely would have flown under the radar of conventional Western medicine, including a heart defect in one person that was detected by a simple wearable device, a case of early lymphoma, and a case of MGUS (monoclonal gammopathy of unknown significance), which is a precancerous condition.
“We have also had many metabolic cases; a lot of folks were prediabetic and others were diabetic,” Dr. Snyder said. “It’s hard to predict exactly what you’re going to see for any one person. But when you collect a lot of this data, you do find things that are important for their health.”
Of the current study participants, 23 underwent a dietary perturbation. Of these, 13 were insulin resistant and 10 were healthy controls, matched for body mass index. The subjects consumed an extra 1,000 calories per day for 30 days, maintained their peak weight for 7 days, and embarked on a weight loss program for 60 days. “We looked at the effects of weight gain and weight loss in incredible molecular detail,” Dr. Snyder explained, noting that the work will appear in a forthcoming edition of Cell Systems. “At baseline, we can tell the insulin-resistant from the -sensitive folks. After people gain and lose weight, we can identify all the compounds and biochemical pathways that change by using integrative c-means clustering to identify pattern recognition across RNA sequencing, proteome, metabolome, microbiome, and cytokines. From blood, we can actually see these compounds changing. We also can tease out differences between resistance and sensitivity in their reaction to weight gain and weight loss. For example, in the microbiome, the insulin-resistant folks were more resistant to changes in weight gain and weight loss, while insulin-sensitive folks go up and down pretty well.”
The researchers also observed that the omics profile of each person who participated in the dietary perturbation study was different at baseline. “So everybody is special, and not just to our mothers,” Dr. Snyder said. “That is to say, if I profile you, you will not look like anyone sitting next to you. If you go through a perturbation, you will still look more like you than the person sitting next to you.” Going forward, he predicted that personal omics profiling “will build a personal dashboard that relays into your smartphone and can measure your health. Just like your car dashboard, we hope that you’ll have indicators of health, which will be your command center of the future.”
He disclosed that he is a scientific adviser to Personalis, Genapsys, SensOmics, and Qbio.
EXPERT ANALYSIS FROM WCIRDC 2017
Children of moms with RA have higher risk of RA, too
The prevalence of rheumatoid arthritis, as well as thyroid disease and epilepsy, was significantly higher in children whose mothers had RA, according to data from a nationwide cohort study in Denmark.
RA runs in families, and many women with RA are concerned about the possible impact of their disease on a developing fetus, wrote Line R. Jølving of Odense (Denmark) University Hospital and the University of Southern Denmark in Odense and her colleagues in Arthritis Care & Research. “However, we do not have sufficient knowledge on the association between maternal RA and long-term chronic childhood outcomes, and still we do not know which specific chronic diseases to be especially aware of in children of women with RA,” they said.
Overall, the risk of RA was almost three times as high for the children of mothers with RA (hazard ratio, 2.89) as it was for the children of women without RA. In addition, the risk of thyroid disease was more than twice as high (HR, 2.19), and the risk of epilepsy was more than 50% higher (HR, 1.61). Maternal RA during pregnancy had no significant impact on children’s anxiety and personality disorders or on the presence of chronic lung disease.
Mothers with RA were generally older than were those without the condition. The children of mothers with RA were significantly more likely to be born via cesarean section, preterm, and small for gestational age, the researchers said.
The results were limited by the potential inclusion of misclassified diagnoses of child outcomes and by the lack of data on medication use. In addition, the study was not designed to determine the effect of biologic mechanisms or genes, the researchers said. Despite these limitations, “the findings in this study are relevant for pediatricians, rheumatologists, and general practitioners in order to have special awareness of early symptoms of RA, thyroid disease, and epilepsy in offspring of mothers with RA,” they said.
The researchers had no financial conflicts to disclose. The study was funded by several sources, including the Region of Southern Denmark, the University of Southern Denmark in Odense, the Center for Clinical Epidemiology, Odense University Hospital, and the Colitis-Crohn Association in Denmark.
SOURCE: Jølving L et al. Arthritis Care Res. 2017 Dec 11. doi: 10.1002/acr.23461.
The prevalence of rheumatoid arthritis, as well as thyroid disease and epilepsy, was significantly higher in children whose mothers had RA, according to data from a nationwide cohort study in Denmark.
RA runs in families, and many women with RA are concerned about the possible impact of their disease on a developing fetus, wrote Line R. Jølving of Odense (Denmark) University Hospital and the University of Southern Denmark in Odense and her colleagues in Arthritis Care & Research. “However, we do not have sufficient knowledge on the association between maternal RA and long-term chronic childhood outcomes, and still we do not know which specific chronic diseases to be especially aware of in children of women with RA,” they said.
Overall, the risk of RA was almost three times as high for the children of mothers with RA (hazard ratio, 2.89) as it was for the children of women without RA. In addition, the risk of thyroid disease was more than twice as high (HR, 2.19), and the risk of epilepsy was more than 50% higher (HR, 1.61). Maternal RA during pregnancy had no significant impact on children’s anxiety and personality disorders or on the presence of chronic lung disease.
Mothers with RA were generally older than were those without the condition. The children of mothers with RA were significantly more likely to be born via cesarean section, preterm, and small for gestational age, the researchers said.
The results were limited by the potential inclusion of misclassified diagnoses of child outcomes and by the lack of data on medication use. In addition, the study was not designed to determine the effect of biologic mechanisms or genes, the researchers said. Despite these limitations, “the findings in this study are relevant for pediatricians, rheumatologists, and general practitioners in order to have special awareness of early symptoms of RA, thyroid disease, and epilepsy in offspring of mothers with RA,” they said.
The researchers had no financial conflicts to disclose. The study was funded by several sources, including the Region of Southern Denmark, the University of Southern Denmark in Odense, the Center for Clinical Epidemiology, Odense University Hospital, and the Colitis-Crohn Association in Denmark.
SOURCE: Jølving L et al. Arthritis Care Res. 2017 Dec 11. doi: 10.1002/acr.23461.
The prevalence of rheumatoid arthritis, as well as thyroid disease and epilepsy, was significantly higher in children whose mothers had RA, according to data from a nationwide cohort study in Denmark.
RA runs in families, and many women with RA are concerned about the possible impact of their disease on a developing fetus, wrote Line R. Jølving of Odense (Denmark) University Hospital and the University of Southern Denmark in Odense and her colleagues in Arthritis Care & Research. “However, we do not have sufficient knowledge on the association between maternal RA and long-term chronic childhood outcomes, and still we do not know which specific chronic diseases to be especially aware of in children of women with RA,” they said.
Overall, the risk of RA was almost three times as high for the children of mothers with RA (hazard ratio, 2.89) as it was for the children of women without RA. In addition, the risk of thyroid disease was more than twice as high (HR, 2.19), and the risk of epilepsy was more than 50% higher (HR, 1.61). Maternal RA during pregnancy had no significant impact on children’s anxiety and personality disorders or on the presence of chronic lung disease.
Mothers with RA were generally older than were those without the condition. The children of mothers with RA were significantly more likely to be born via cesarean section, preterm, and small for gestational age, the researchers said.
The results were limited by the potential inclusion of misclassified diagnoses of child outcomes and by the lack of data on medication use. In addition, the study was not designed to determine the effect of biologic mechanisms or genes, the researchers said. Despite these limitations, “the findings in this study are relevant for pediatricians, rheumatologists, and general practitioners in order to have special awareness of early symptoms of RA, thyroid disease, and epilepsy in offspring of mothers with RA,” they said.
The researchers had no financial conflicts to disclose. The study was funded by several sources, including the Region of Southern Denmark, the University of Southern Denmark in Odense, the Center for Clinical Epidemiology, Odense University Hospital, and the Colitis-Crohn Association in Denmark.
SOURCE: Jølving L et al. Arthritis Care Res. 2017 Dec 11. doi: 10.1002/acr.23461.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Children whose mothers had RA were significantly more likely to have RA, epilepsy, and thyroid problems than children born to mothers without RA.
Major finding: Children of mothers with RA were almost three times as likely to have RA (hazard ratio, 2.89).
Data source: A nationwide cohort study of live births in Denmark that included 2,106 children born to women with RA and 1,378,539 children born to women without RA.
Disclosures: The researchers had no financial conflicts to disclose. The study was funded by several sources, including the Region of Southern Denmark, the University of Southern Denmark in Odense, the Center for Clinical Epidemiology, Odense University Hospital, and the Colitis-Crohn Association in Denmark.
Source: Jølving L et al. Arthritis Care Res. 2017 Dec 11. doi: 10.1002/acr.23461.
Cardiosphere-derived cells may reverse Duchenne heart scarring
ANAHEIM, CALIF. – One-time infusion of cardiosphere-derived cells into the three major coronary arteries seemed to prevent and perhaps even reverse cardiac scarring, as well as improve arm function, in the open-label phase 1-2 HOPE-Duchenne trial of 25 boys with advanced Duchenne muscular dystrophy.
“Decreased scarring is really a big deal because this is counter to the natural history of Duchenne, where all the scars progress, senior investigator Ronald G. Victor, MD, said at the American Heart Association scientific sessions. “It was gratifying to see that the changes in scar coincided with improved regional systolic wall thickening, particularly in the inferior wall of the left ventricle, which is the very area disproportionately affected early and thus severely in Duchenne.”
Glucocorticoids are the only thing that help to date, prolonging ambulation by about 3 years, but with Cushingoid features and other well-known side effects.
Cardiosphere-derived cells (CDCs) – cardiac progenitor cells – have shown some promise for heart failure. They don’t seem to engraft and grow, but rather to release extracellular vesicles packed with proteins, RNA, and other bioactive molecules. “They act as a role model to get endogenous cells to do the right thing. That’s what we think,” Dr. Victor said.
The HOPE-Duchenne trial [Halt Cardiomyopathy Progression in Duchenne] randomized 12 boys with Duchenne to usual care and 13 others to usual care plus a single infusion of 75 million CDCs divided equally among the left anterior descending, circumflex, and right coronary arteries. The cells were derived from donated heart muscle. The specific CDC preparation tested was “CAP-1002” from Capricor Therapeutics, the study’s sponsor.
The boys were aged 12-22 years, with a mean age of 17.8 years. They had left ventricle scarring in at least four MRI segments; their mean left ventricle ejection fraction was just below 50%; 68% were wheel-chair bound, and all were on stable steroid regimens.
At 12 months, cardiac scarring had increased about 5% in the control group, but decreased by about 7% in the treatment arm, although with no change ejection fraction improvement (P = .03).
Skeletal muscle was assessed by mid-level and distal performance of upper limb scoring, a measure of arm function developed specifically for Duchenne. “For patients who have lost ambulation, the ability to use a joystick to drive a scooter, the ability to feed themselves and use a computer and cellphone are absolutely key to quality of life,” he said.
At 12 months, performance of upper limb scores were largely unchanged in the control group, but improved in about half of the treated boys. “A couple were quite dramatic,” Dr. Victor said. The differences were statistically significant (P = .007) when limited to subjects who started with scores below 55 points, with 58 points meaning normal function.
On the safety side, nothing unusual happened in the control arm, except a femur fracture.
One boy in the treatment arm went into ventricular fibrillation during the diagnostic angiogram. Five had periprocedural atrial fibrillation. All 13 had periprocedural troponin elevations, versus two boys in the control group over the entire course of the study. Dr. Victor didn’t report any deaths, but safety concerns are probably why Capricor is shifting to intravenous infusion for the next trial, HOPE-2.
Dr. Victor noted that troponin leaks “wax and wane” over time in Duchenne, so the transient increases in the treatment arm “were superimposed on a baseline of abnormal cardiac enzymes.”
The Food and Drug Administration has green-lighted the company’s HOPE-2 trial to start enrollment in early 2018, with a larger number of patients and intravenous CDC delivery at 3 month intervals.
Several investigators were Capricor employees. Others were consultants or reported ownership interests. Dr. Victor was the principal investigator at Cedars-Sinai, and was on the trial’s steering committee. The University of Florida, Gainesville, and Cincinnati Children’s Hospital Medical Center, Ohio, were the other two study sites.
SOURCE: Ronald Victor, MD; 2017 AHA Scientific Sessions abstract number S1177
This is a tough disease, and therapies are desperately needed.
The HOPE-Duchenne data look pretty good, and everything seems to be moving in the same direction, but 13 people treated for even 12 months doesn’t really tell us much about safety.
The pipeline for this disease is filling up, but a lot of therapies are aimed at younger patients with the hopes of keeping them functional for as long as possible. I’m glad to see a treatment aimed at more advanced disease.
In general, when the choice is made to enter a clinical trial, it may mean you can’t enter another clinical trial, and these people are in a desperate situation. We need to sort out what should be tested, not just what can be tested.
Robert M. Califf, MD, is professor of cardiology at Duke University, Durham, N.C. He was the study discussant, and wasn’t involved in the work.
This is a tough disease, and therapies are desperately needed.
The HOPE-Duchenne data look pretty good, and everything seems to be moving in the same direction, but 13 people treated for even 12 months doesn’t really tell us much about safety.
The pipeline for this disease is filling up, but a lot of therapies are aimed at younger patients with the hopes of keeping them functional for as long as possible. I’m glad to see a treatment aimed at more advanced disease.
In general, when the choice is made to enter a clinical trial, it may mean you can’t enter another clinical trial, and these people are in a desperate situation. We need to sort out what should be tested, not just what can be tested.
Robert M. Califf, MD, is professor of cardiology at Duke University, Durham, N.C. He was the study discussant, and wasn’t involved in the work.
This is a tough disease, and therapies are desperately needed.
The HOPE-Duchenne data look pretty good, and everything seems to be moving in the same direction, but 13 people treated for even 12 months doesn’t really tell us much about safety.
The pipeline for this disease is filling up, but a lot of therapies are aimed at younger patients with the hopes of keeping them functional for as long as possible. I’m glad to see a treatment aimed at more advanced disease.
In general, when the choice is made to enter a clinical trial, it may mean you can’t enter another clinical trial, and these people are in a desperate situation. We need to sort out what should be tested, not just what can be tested.
Robert M. Califf, MD, is professor of cardiology at Duke University, Durham, N.C. He was the study discussant, and wasn’t involved in the work.
ANAHEIM, CALIF. – One-time infusion of cardiosphere-derived cells into the three major coronary arteries seemed to prevent and perhaps even reverse cardiac scarring, as well as improve arm function, in the open-label phase 1-2 HOPE-Duchenne trial of 25 boys with advanced Duchenne muscular dystrophy.
“Decreased scarring is really a big deal because this is counter to the natural history of Duchenne, where all the scars progress, senior investigator Ronald G. Victor, MD, said at the American Heart Association scientific sessions. “It was gratifying to see that the changes in scar coincided with improved regional systolic wall thickening, particularly in the inferior wall of the left ventricle, which is the very area disproportionately affected early and thus severely in Duchenne.”
Glucocorticoids are the only thing that help to date, prolonging ambulation by about 3 years, but with Cushingoid features and other well-known side effects.
Cardiosphere-derived cells (CDCs) – cardiac progenitor cells – have shown some promise for heart failure. They don’t seem to engraft and grow, but rather to release extracellular vesicles packed with proteins, RNA, and other bioactive molecules. “They act as a role model to get endogenous cells to do the right thing. That’s what we think,” Dr. Victor said.
The HOPE-Duchenne trial [Halt Cardiomyopathy Progression in Duchenne] randomized 12 boys with Duchenne to usual care and 13 others to usual care plus a single infusion of 75 million CDCs divided equally among the left anterior descending, circumflex, and right coronary arteries. The cells were derived from donated heart muscle. The specific CDC preparation tested was “CAP-1002” from Capricor Therapeutics, the study’s sponsor.
The boys were aged 12-22 years, with a mean age of 17.8 years. They had left ventricle scarring in at least four MRI segments; their mean left ventricle ejection fraction was just below 50%; 68% were wheel-chair bound, and all were on stable steroid regimens.
At 12 months, cardiac scarring had increased about 5% in the control group, but decreased by about 7% in the treatment arm, although with no change ejection fraction improvement (P = .03).
Skeletal muscle was assessed by mid-level and distal performance of upper limb scoring, a measure of arm function developed specifically for Duchenne. “For patients who have lost ambulation, the ability to use a joystick to drive a scooter, the ability to feed themselves and use a computer and cellphone are absolutely key to quality of life,” he said.
At 12 months, performance of upper limb scores were largely unchanged in the control group, but improved in about half of the treated boys. “A couple were quite dramatic,” Dr. Victor said. The differences were statistically significant (P = .007) when limited to subjects who started with scores below 55 points, with 58 points meaning normal function.
On the safety side, nothing unusual happened in the control arm, except a femur fracture.
One boy in the treatment arm went into ventricular fibrillation during the diagnostic angiogram. Five had periprocedural atrial fibrillation. All 13 had periprocedural troponin elevations, versus two boys in the control group over the entire course of the study. Dr. Victor didn’t report any deaths, but safety concerns are probably why Capricor is shifting to intravenous infusion for the next trial, HOPE-2.
Dr. Victor noted that troponin leaks “wax and wane” over time in Duchenne, so the transient increases in the treatment arm “were superimposed on a baseline of abnormal cardiac enzymes.”
The Food and Drug Administration has green-lighted the company’s HOPE-2 trial to start enrollment in early 2018, with a larger number of patients and intravenous CDC delivery at 3 month intervals.
Several investigators were Capricor employees. Others were consultants or reported ownership interests. Dr. Victor was the principal investigator at Cedars-Sinai, and was on the trial’s steering committee. The University of Florida, Gainesville, and Cincinnati Children’s Hospital Medical Center, Ohio, were the other two study sites.
SOURCE: Ronald Victor, MD; 2017 AHA Scientific Sessions abstract number S1177
ANAHEIM, CALIF. – One-time infusion of cardiosphere-derived cells into the three major coronary arteries seemed to prevent and perhaps even reverse cardiac scarring, as well as improve arm function, in the open-label phase 1-2 HOPE-Duchenne trial of 25 boys with advanced Duchenne muscular dystrophy.
“Decreased scarring is really a big deal because this is counter to the natural history of Duchenne, where all the scars progress, senior investigator Ronald G. Victor, MD, said at the American Heart Association scientific sessions. “It was gratifying to see that the changes in scar coincided with improved regional systolic wall thickening, particularly in the inferior wall of the left ventricle, which is the very area disproportionately affected early and thus severely in Duchenne.”
Glucocorticoids are the only thing that help to date, prolonging ambulation by about 3 years, but with Cushingoid features and other well-known side effects.
Cardiosphere-derived cells (CDCs) – cardiac progenitor cells – have shown some promise for heart failure. They don’t seem to engraft and grow, but rather to release extracellular vesicles packed with proteins, RNA, and other bioactive molecules. “They act as a role model to get endogenous cells to do the right thing. That’s what we think,” Dr. Victor said.
The HOPE-Duchenne trial [Halt Cardiomyopathy Progression in Duchenne] randomized 12 boys with Duchenne to usual care and 13 others to usual care plus a single infusion of 75 million CDCs divided equally among the left anterior descending, circumflex, and right coronary arteries. The cells were derived from donated heart muscle. The specific CDC preparation tested was “CAP-1002” from Capricor Therapeutics, the study’s sponsor.
The boys were aged 12-22 years, with a mean age of 17.8 years. They had left ventricle scarring in at least four MRI segments; their mean left ventricle ejection fraction was just below 50%; 68% were wheel-chair bound, and all were on stable steroid regimens.
At 12 months, cardiac scarring had increased about 5% in the control group, but decreased by about 7% in the treatment arm, although with no change ejection fraction improvement (P = .03).
Skeletal muscle was assessed by mid-level and distal performance of upper limb scoring, a measure of arm function developed specifically for Duchenne. “For patients who have lost ambulation, the ability to use a joystick to drive a scooter, the ability to feed themselves and use a computer and cellphone are absolutely key to quality of life,” he said.
At 12 months, performance of upper limb scores were largely unchanged in the control group, but improved in about half of the treated boys. “A couple were quite dramatic,” Dr. Victor said. The differences were statistically significant (P = .007) when limited to subjects who started with scores below 55 points, with 58 points meaning normal function.
On the safety side, nothing unusual happened in the control arm, except a femur fracture.
One boy in the treatment arm went into ventricular fibrillation during the diagnostic angiogram. Five had periprocedural atrial fibrillation. All 13 had periprocedural troponin elevations, versus two boys in the control group over the entire course of the study. Dr. Victor didn’t report any deaths, but safety concerns are probably why Capricor is shifting to intravenous infusion for the next trial, HOPE-2.
Dr. Victor noted that troponin leaks “wax and wane” over time in Duchenne, so the transient increases in the treatment arm “were superimposed on a baseline of abnormal cardiac enzymes.”
The Food and Drug Administration has green-lighted the company’s HOPE-2 trial to start enrollment in early 2018, with a larger number of patients and intravenous CDC delivery at 3 month intervals.
Several investigators were Capricor employees. Others were consultants or reported ownership interests. Dr. Victor was the principal investigator at Cedars-Sinai, and was on the trial’s steering committee. The University of Florida, Gainesville, and Cincinnati Children’s Hospital Medical Center, Ohio, were the other two study sites.
SOURCE: Ronald Victor, MD; 2017 AHA Scientific Sessions abstract number S1177
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: One-time infusion of cardiosphere-derived cells (CDCs) into the three major coronary arteries seemed to prevent and perhaps even reverse cardiac scarring, as well as improve arm function, in boys with advanced Duchenne muscular dystrophy.
Major finding: At 12 months, cardiac scarring increased about 5% in the control group, but decreased about 7% in the treatment arm, although with no change in ejection fraction (P = .03).
Study details: HOPE-Duchenne, an open-label, phase 1-2 trial involving 25 boys
Disclosures: The study was funded by Capricor Therapeutics, makers of the CDC preparation tested. Several investigators were Capricor employees. Others were consultants or reported ownership interests. The senior investigator and presenter was on the trial’s steering committee.
Source: Victor R, et al. 2017 AHA Scientific Sessions abstract number S1177.
Brain structural changes on MRI predict sudden death in epilepsy
WASHINGTON – It has long been hypothesized that sudden unexpected death in epilepsy (SUDEP) is the result of damage to areas of the brain that control breathing and heart rate, but two studies presented at the American Epilepsy Society annual meeting identified specific areas where structural changes correlate with SUDEP, suggesting the potential for screening.
In one of two studies that evaluated MRI images in patients who subsequently died of SUDEP and compared them to patients with epilepsy or normal healthy individuals, brainstem volume loss was not only greater in those with SUDEP but there was a correlation between greater volume loss and a shorter period of survival, reported Susanne G. Mueller, MD, a radiologist affiliated with the Center for Imaging of Neurodegenerative Diseases at the San Francisco Veterans Affairs Medical Center.
“This is the first evidence that brainstem damage, one of the mechanisms that has been shown to cause SUDEP in animals, could also play a role in people with epilepsy,” Dr. Mueller reported. Although more work is needed, volume loss observed on MRI “could be used as a potential biomarker to assess the individual SUDEP risk in epilepsy patients.”
In one of two populations studied, investigators analyzed MRI scans from 27 SUDEP patients taken prior to death. Focusing on brainstem areas involved in autonomic function, deformation morphometry generated profile maps that isolated areas of volume loss. The changes suggested that focal epilepsy produced structural changes in the mesencephalic region of the lower brainstem.
Damage to nuclei involved in control of heart rate variability and other autonomic functions would be consistent with increased risk of SUDEP.
“We can just report what we see on imaging. These data do not tell us the cause of SUDEP, but they do show correlations that are consistent with current theories,” Dr. Mueller explained.
In a second study that compared 18 patients with focal epilepsy to 11 controls, greater volume loss in patients with epilepsy correlated negatively with heart rate variability, a relationship not seen in the controls. The volume loss in periventricular gray and medulla oblongata nuclei was most closely associated with heart rate variability, which is considered a surrogate for altered autonomic function, Dr. Mueller reported.
Similar conclusions were reached in a different study conducted at a separate institution. In this study, MRI scans from 237 patients with epilepsy and 110 healthy controls were evaluated. Four of the epilepsy patients subsequently died of SUDEP.
“These are all areas that can be involved in autonomic function potentially involved in SUDEP,” Mr. George said. Like Dr. Mueller, Mr. George cautioned that clinically viable algorithms that would allow MRI to assess SUDEP risk may be years away, but these studies provide preliminary evidence that structural changes on MRI could eventually serve as a SUDEP biomarker.
There was limited overlap between the areas of structural change potentially associated with SUDEP in the studies presented by Dr. Mueller and Mr. George, but Dr. Mueller said that SUDEP might not stem from a single epilepsy-induced brain abnormality. She reported that more MRI scans to trace structural changes in SUDEP patients are likely to identify more areas of interest. Acquiring a large number of MRI scans is a challenge, but Dr. Mueller envisions a registry where routine scans could be submitted. This would permit this research to be conducted on a larger scale.
“There is a similar initiative to collect MRI brain images of patients with Alzheimer’s disease,” said Dr. Mueller, noting that this provides a precedent for the type of research needed in epilepsy. If a similar program could be undertaken in epilepsy, Dr. Mueller believes it might substantially accelerate the effort to understand and recognize risk of SUDEP.
Mr. George’s study was funded by FACES (Finding a CURE for Epilepsy/Seizures). Dr. Mueller’s study was funded by grants from UCSF, the Epilepsy Foundation, and the National Institutes of Health.
Dr. Mueller and Mr. George reported no potential conflicts of interest related to this topic.
SOURCE: Mueller S et al., AES 2017 abstract 3.205 and George A et al., AES 2017 abstract 3.214
WASHINGTON – It has long been hypothesized that sudden unexpected death in epilepsy (SUDEP) is the result of damage to areas of the brain that control breathing and heart rate, but two studies presented at the American Epilepsy Society annual meeting identified specific areas where structural changes correlate with SUDEP, suggesting the potential for screening.
In one of two studies that evaluated MRI images in patients who subsequently died of SUDEP and compared them to patients with epilepsy or normal healthy individuals, brainstem volume loss was not only greater in those with SUDEP but there was a correlation between greater volume loss and a shorter period of survival, reported Susanne G. Mueller, MD, a radiologist affiliated with the Center for Imaging of Neurodegenerative Diseases at the San Francisco Veterans Affairs Medical Center.
“This is the first evidence that brainstem damage, one of the mechanisms that has been shown to cause SUDEP in animals, could also play a role in people with epilepsy,” Dr. Mueller reported. Although more work is needed, volume loss observed on MRI “could be used as a potential biomarker to assess the individual SUDEP risk in epilepsy patients.”
In one of two populations studied, investigators analyzed MRI scans from 27 SUDEP patients taken prior to death. Focusing on brainstem areas involved in autonomic function, deformation morphometry generated profile maps that isolated areas of volume loss. The changes suggested that focal epilepsy produced structural changes in the mesencephalic region of the lower brainstem.
Damage to nuclei involved in control of heart rate variability and other autonomic functions would be consistent with increased risk of SUDEP.
“We can just report what we see on imaging. These data do not tell us the cause of SUDEP, but they do show correlations that are consistent with current theories,” Dr. Mueller explained.
In a second study that compared 18 patients with focal epilepsy to 11 controls, greater volume loss in patients with epilepsy correlated negatively with heart rate variability, a relationship not seen in the controls. The volume loss in periventricular gray and medulla oblongata nuclei was most closely associated with heart rate variability, which is considered a surrogate for altered autonomic function, Dr. Mueller reported.
Similar conclusions were reached in a different study conducted at a separate institution. In this study, MRI scans from 237 patients with epilepsy and 110 healthy controls were evaluated. Four of the epilepsy patients subsequently died of SUDEP.
“These are all areas that can be involved in autonomic function potentially involved in SUDEP,” Mr. George said. Like Dr. Mueller, Mr. George cautioned that clinically viable algorithms that would allow MRI to assess SUDEP risk may be years away, but these studies provide preliminary evidence that structural changes on MRI could eventually serve as a SUDEP biomarker.
There was limited overlap between the areas of structural change potentially associated with SUDEP in the studies presented by Dr. Mueller and Mr. George, but Dr. Mueller said that SUDEP might not stem from a single epilepsy-induced brain abnormality. She reported that more MRI scans to trace structural changes in SUDEP patients are likely to identify more areas of interest. Acquiring a large number of MRI scans is a challenge, but Dr. Mueller envisions a registry where routine scans could be submitted. This would permit this research to be conducted on a larger scale.
“There is a similar initiative to collect MRI brain images of patients with Alzheimer’s disease,” said Dr. Mueller, noting that this provides a precedent for the type of research needed in epilepsy. If a similar program could be undertaken in epilepsy, Dr. Mueller believes it might substantially accelerate the effort to understand and recognize risk of SUDEP.
Mr. George’s study was funded by FACES (Finding a CURE for Epilepsy/Seizures). Dr. Mueller’s study was funded by grants from UCSF, the Epilepsy Foundation, and the National Institutes of Health.
Dr. Mueller and Mr. George reported no potential conflicts of interest related to this topic.
SOURCE: Mueller S et al., AES 2017 abstract 3.205 and George A et al., AES 2017 abstract 3.214
WASHINGTON – It has long been hypothesized that sudden unexpected death in epilepsy (SUDEP) is the result of damage to areas of the brain that control breathing and heart rate, but two studies presented at the American Epilepsy Society annual meeting identified specific areas where structural changes correlate with SUDEP, suggesting the potential for screening.
In one of two studies that evaluated MRI images in patients who subsequently died of SUDEP and compared them to patients with epilepsy or normal healthy individuals, brainstem volume loss was not only greater in those with SUDEP but there was a correlation between greater volume loss and a shorter period of survival, reported Susanne G. Mueller, MD, a radiologist affiliated with the Center for Imaging of Neurodegenerative Diseases at the San Francisco Veterans Affairs Medical Center.
“This is the first evidence that brainstem damage, one of the mechanisms that has been shown to cause SUDEP in animals, could also play a role in people with epilepsy,” Dr. Mueller reported. Although more work is needed, volume loss observed on MRI “could be used as a potential biomarker to assess the individual SUDEP risk in epilepsy patients.”
In one of two populations studied, investigators analyzed MRI scans from 27 SUDEP patients taken prior to death. Focusing on brainstem areas involved in autonomic function, deformation morphometry generated profile maps that isolated areas of volume loss. The changes suggested that focal epilepsy produced structural changes in the mesencephalic region of the lower brainstem.
Damage to nuclei involved in control of heart rate variability and other autonomic functions would be consistent with increased risk of SUDEP.
“We can just report what we see on imaging. These data do not tell us the cause of SUDEP, but they do show correlations that are consistent with current theories,” Dr. Mueller explained.
In a second study that compared 18 patients with focal epilepsy to 11 controls, greater volume loss in patients with epilepsy correlated negatively with heart rate variability, a relationship not seen in the controls. The volume loss in periventricular gray and medulla oblongata nuclei was most closely associated with heart rate variability, which is considered a surrogate for altered autonomic function, Dr. Mueller reported.
Similar conclusions were reached in a different study conducted at a separate institution. In this study, MRI scans from 237 patients with epilepsy and 110 healthy controls were evaluated. Four of the epilepsy patients subsequently died of SUDEP.
“These are all areas that can be involved in autonomic function potentially involved in SUDEP,” Mr. George said. Like Dr. Mueller, Mr. George cautioned that clinically viable algorithms that would allow MRI to assess SUDEP risk may be years away, but these studies provide preliminary evidence that structural changes on MRI could eventually serve as a SUDEP biomarker.
There was limited overlap between the areas of structural change potentially associated with SUDEP in the studies presented by Dr. Mueller and Mr. George, but Dr. Mueller said that SUDEP might not stem from a single epilepsy-induced brain abnormality. She reported that more MRI scans to trace structural changes in SUDEP patients are likely to identify more areas of interest. Acquiring a large number of MRI scans is a challenge, but Dr. Mueller envisions a registry where routine scans could be submitted. This would permit this research to be conducted on a larger scale.
“There is a similar initiative to collect MRI brain images of patients with Alzheimer’s disease,” said Dr. Mueller, noting that this provides a precedent for the type of research needed in epilepsy. If a similar program could be undertaken in epilepsy, Dr. Mueller believes it might substantially accelerate the effort to understand and recognize risk of SUDEP.
Mr. George’s study was funded by FACES (Finding a CURE for Epilepsy/Seizures). Dr. Mueller’s study was funded by grants from UCSF, the Epilepsy Foundation, and the National Institutes of Health.
Dr. Mueller and Mr. George reported no potential conflicts of interest related to this topic.
SOURCE: Mueller S et al., AES 2017 abstract 3.205 and George A et al., AES 2017 abstract 3.214
REPORTING FROM AES 2017
Key clinical point: MRI-detected damage to brain areas mediating autonomic function is implicated in sudden unexpected death in epilepsy (SUDEP).
Major finding: Two separate studies drew the conclusion that brain structural difference seen on MRI may become an effective screening tool for identifying epilepsy patients at high risk for SUDEP.
Data source: Prospective studies.
Disclosures: Dr. Mueller’s study was funded by grants from UCSF, the Epilepsy Foundation, and the National Institutes of Health. Mr. George’s study was funded by FACES (Finding a CURE for Epilepsy/Seizures). Dr. Mueller and Mr. George reported no potential conflicts of interest related to this topic.
Source: Mueller S et al., AES 2017 abstract 3.205 and George A et al., AES 2017 abstract 3.214
A three-track concept proposed for regulating fecal microbiota transplantation
FROM SCIENCE
Researchers are proposing a three-track regulatory framework to help ensure that using fecal microbiota transplantations (FMTs) to treat recurring Clostridium difficile infection (CDI) can be done in a more safe and effective manner.
The need for better regulation is arising because, although FMT is considered by many to be the standard of care, samples are inconsistently screened for infectious pathogens.
“The use of prescreened stool obtained from a stool bank and shipped to a physician is increasing, but the stool banks are not regulated,” Diane Hoffmann, the Jacob A. France Professor of Health Care Law at the University of Maryland, Baltimore, and her colleagues wrote in Science.
The authors noted that the Food and Drug Administration has struggled with regulating FMT; so far, it has tried to use the drug approval pathway as a tool to oversee FMT.
However, the authors note that the transplanted material “is not a ‘typical’ drug, and thus may not be appropriate for the drug regulatory pathway.” To that end, Ms. Hoffmann and her colleagues offered three paths that the FDA could implement to regulate FMT.
The first track would cover instances in which a physician obtains the stool from a donor the patient or physician already know. In this case, “FMT would be regulated as the ‘practice of medicine’ subject primarily to state regulation,” the authors proposed. “Physicians performing FMT for CDI would be able to do so based on their scope of practice using clinical judgment and the relevant standard of care.” In this track, the investigational new drug (IND) pathway would be applied when FMT is used for any indication other than CDI unless the use meets clinical innovation requirements.
The second track covers stool obtained from stool banks. In this scenario, it would be “regulated in the same manner as human cell-tissue establishments with some additional oversight,” Ms. Hoffmann and her colleagues wrote. “This would include registering annually with the FDA and complying with rules for donor screening and testing and ‘good manufacturing processes.’ ” Physicians using stool from these banks would be required to report back any adverse events stemming from stool supplied by the banks, and the banks would submit that data to the FDA. Unless operating under an IND, stool banks would only be able to provide samples to treat CDI.
The third track deals with “modified stool-based products” (stool processed in such a way that the original relevant characteristics of the transferred community of microorganisms have been altered). “These products would be regulated as biological products or drugs with some alteration of IND requirements (i.e., elimination of some phase I IND requirements and modification of characterization specifications),” the authors wrote.
“Our proposal improves on the FDA’s current and proposed regulatory scheme as it allows stool banks to continue to provide stool but only under an approved regulatory framework,” Ms. Hoffmann and her colleagues wrote.
They believe that implementation of this three-track structure would not be difficult: “FDA would need to change its position and determine that microbiota derived from stool is a tissue, not a drug or biological product. The framework could be implemented through new guidance or by issuing formal regulations and no statutory changes would be required. The scheme would serve as a useful starting point for regulation of other types of [microbiota transplants].”
FROM SCIENCE
Researchers are proposing a three-track regulatory framework to help ensure that using fecal microbiota transplantations (FMTs) to treat recurring Clostridium difficile infection (CDI) can be done in a more safe and effective manner.
The need for better regulation is arising because, although FMT is considered by many to be the standard of care, samples are inconsistently screened for infectious pathogens.
“The use of prescreened stool obtained from a stool bank and shipped to a physician is increasing, but the stool banks are not regulated,” Diane Hoffmann, the Jacob A. France Professor of Health Care Law at the University of Maryland, Baltimore, and her colleagues wrote in Science.
The authors noted that the Food and Drug Administration has struggled with regulating FMT; so far, it has tried to use the drug approval pathway as a tool to oversee FMT.
However, the authors note that the transplanted material “is not a ‘typical’ drug, and thus may not be appropriate for the drug regulatory pathway.” To that end, Ms. Hoffmann and her colleagues offered three paths that the FDA could implement to regulate FMT.
The first track would cover instances in which a physician obtains the stool from a donor the patient or physician already know. In this case, “FMT would be regulated as the ‘practice of medicine’ subject primarily to state regulation,” the authors proposed. “Physicians performing FMT for CDI would be able to do so based on their scope of practice using clinical judgment and the relevant standard of care.” In this track, the investigational new drug (IND) pathway would be applied when FMT is used for any indication other than CDI unless the use meets clinical innovation requirements.
The second track covers stool obtained from stool banks. In this scenario, it would be “regulated in the same manner as human cell-tissue establishments with some additional oversight,” Ms. Hoffmann and her colleagues wrote. “This would include registering annually with the FDA and complying with rules for donor screening and testing and ‘good manufacturing processes.’ ” Physicians using stool from these banks would be required to report back any adverse events stemming from stool supplied by the banks, and the banks would submit that data to the FDA. Unless operating under an IND, stool banks would only be able to provide samples to treat CDI.
The third track deals with “modified stool-based products” (stool processed in such a way that the original relevant characteristics of the transferred community of microorganisms have been altered). “These products would be regulated as biological products or drugs with some alteration of IND requirements (i.e., elimination of some phase I IND requirements and modification of characterization specifications),” the authors wrote.
“Our proposal improves on the FDA’s current and proposed regulatory scheme as it allows stool banks to continue to provide stool but only under an approved regulatory framework,” Ms. Hoffmann and her colleagues wrote.
They believe that implementation of this three-track structure would not be difficult: “FDA would need to change its position and determine that microbiota derived from stool is a tissue, not a drug or biological product. The framework could be implemented through new guidance or by issuing formal regulations and no statutory changes would be required. The scheme would serve as a useful starting point for regulation of other types of [microbiota transplants].”
FROM SCIENCE
Researchers are proposing a three-track regulatory framework to help ensure that using fecal microbiota transplantations (FMTs) to treat recurring Clostridium difficile infection (CDI) can be done in a more safe and effective manner.
The need for better regulation is arising because, although FMT is considered by many to be the standard of care, samples are inconsistently screened for infectious pathogens.
“The use of prescreened stool obtained from a stool bank and shipped to a physician is increasing, but the stool banks are not regulated,” Diane Hoffmann, the Jacob A. France Professor of Health Care Law at the University of Maryland, Baltimore, and her colleagues wrote in Science.
The authors noted that the Food and Drug Administration has struggled with regulating FMT; so far, it has tried to use the drug approval pathway as a tool to oversee FMT.
However, the authors note that the transplanted material “is not a ‘typical’ drug, and thus may not be appropriate for the drug regulatory pathway.” To that end, Ms. Hoffmann and her colleagues offered three paths that the FDA could implement to regulate FMT.
The first track would cover instances in which a physician obtains the stool from a donor the patient or physician already know. In this case, “FMT would be regulated as the ‘practice of medicine’ subject primarily to state regulation,” the authors proposed. “Physicians performing FMT for CDI would be able to do so based on their scope of practice using clinical judgment and the relevant standard of care.” In this track, the investigational new drug (IND) pathway would be applied when FMT is used for any indication other than CDI unless the use meets clinical innovation requirements.
The second track covers stool obtained from stool banks. In this scenario, it would be “regulated in the same manner as human cell-tissue establishments with some additional oversight,” Ms. Hoffmann and her colleagues wrote. “This would include registering annually with the FDA and complying with rules for donor screening and testing and ‘good manufacturing processes.’ ” Physicians using stool from these banks would be required to report back any adverse events stemming from stool supplied by the banks, and the banks would submit that data to the FDA. Unless operating under an IND, stool banks would only be able to provide samples to treat CDI.
The third track deals with “modified stool-based products” (stool processed in such a way that the original relevant characteristics of the transferred community of microorganisms have been altered). “These products would be regulated as biological products or drugs with some alteration of IND requirements (i.e., elimination of some phase I IND requirements and modification of characterization specifications),” the authors wrote.
“Our proposal improves on the FDA’s current and proposed regulatory scheme as it allows stool banks to continue to provide stool but only under an approved regulatory framework,” Ms. Hoffmann and her colleagues wrote.
They believe that implementation of this three-track structure would not be difficult: “FDA would need to change its position and determine that microbiota derived from stool is a tissue, not a drug or biological product. The framework could be implemented through new guidance or by issuing formal regulations and no statutory changes would be required. The scheme would serve as a useful starting point for regulation of other types of [microbiota transplants].”