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Fujifilm issues recall to update ED-530XT duodenoscopes
Fujifilm has issued an Urgent Medical Device Correction and Removal notification for all ED-530XT duodenoscopes, according to a Safety Alert from the Food and Drug Administration.
The recall, initiated voluntarily by Fujifilm, includes replacement of the ED-530XT forceps elevator mechanism including the O-ring seal, replacement of the distal end cap, and new operation manuals. The FDA authorized the changes on July 21, 2017.
“Reprocessing is a detailed, multistep process to clean and disinfect or sterilize reusable devices. The FDA has been working with duodenoscope manufacturers as they modify and validate their reprocessing instructions to further enhance the safety margin of their devices and show with a high degree of assurance that their reprocessing instructions, when followed correctly, effectively clean and disinfect the duodenoscopes,” the FDA said in the press release.
Find the full Safety Alert on the FDA website.
Fujifilm has issued an Urgent Medical Device Correction and Removal notification for all ED-530XT duodenoscopes, according to a Safety Alert from the Food and Drug Administration.
The recall, initiated voluntarily by Fujifilm, includes replacement of the ED-530XT forceps elevator mechanism including the O-ring seal, replacement of the distal end cap, and new operation manuals. The FDA authorized the changes on July 21, 2017.
“Reprocessing is a detailed, multistep process to clean and disinfect or sterilize reusable devices. The FDA has been working with duodenoscope manufacturers as they modify and validate their reprocessing instructions to further enhance the safety margin of their devices and show with a high degree of assurance that their reprocessing instructions, when followed correctly, effectively clean and disinfect the duodenoscopes,” the FDA said in the press release.
Find the full Safety Alert on the FDA website.
Fujifilm has issued an Urgent Medical Device Correction and Removal notification for all ED-530XT duodenoscopes, according to a Safety Alert from the Food and Drug Administration.
The recall, initiated voluntarily by Fujifilm, includes replacement of the ED-530XT forceps elevator mechanism including the O-ring seal, replacement of the distal end cap, and new operation manuals. The FDA authorized the changes on July 21, 2017.
“Reprocessing is a detailed, multistep process to clean and disinfect or sterilize reusable devices. The FDA has been working with duodenoscope manufacturers as they modify and validate their reprocessing instructions to further enhance the safety margin of their devices and show with a high degree of assurance that their reprocessing instructions, when followed correctly, effectively clean and disinfect the duodenoscopes,” the FDA said in the press release.
Find the full Safety Alert on the FDA website.
Increased risk of death seen in PPI users
Proton pump inhibitors (PPIs) are associated with a significantly higher risk of death than are H2-receptor antagonists, according to a 5-year longitudinal cohort study.
The study, published online in BMJ Open, found that increased risk of death was evident even in people without gastrointestinal conditions, and it increased with longer duration of use.
Yan Xie, MPH, of the VA Saint Louis Health Care System and coauthors, wrote that PPIs are linked to a range of serious adverse outcomes – such as acute interstitial nephritis, chronic kidney disease, incident dementia, and Clostridium difficile infection – each of which is associated with higher risk of mortality.
Researchers saw a 25% higher risk of death in the 275,977 participants treated with PPIs, compared with that in those who were treated with H2-receptor antagonists (95% confidence interval, 1.23-1.28), after adjusting for factors such as estimated glomerular filtration rate, age, hospitalizations, and a range of comorbidities, including gastrointestinal disorders.When PPI use was compared with no PPI use, there was a 15% increase in the risk of death (95% CI, 1.14-1.15). When compared with no known exposure to any acid suppression therapy, the increased risk of death was 23% (95% CI, 1.22-1.24).
In an attempt to look at the risk of death in a lower-risk cohort, the researchers analyzed a subgroup of participants who did not have the conditions for which PPIs are normally prescribed, such as gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, Helicobacter pylori infection, and Barrett’s esophagus.
However, even in this lower-risk cohort, the study still showed a 24% increase in the risk of death with PPIs, compared with that in H2-receptor antagonists (95% CI, 1.21-1.27); a 19% increase with PPIs, compared with no PPIs; and a 22% increase with PPIs, compared with no acid suppression.
Duration of exposure to PPIs was also associated with increasing risk of death. Participants who had taken PPIs for fewer than 90 days in total had only a 5% increase in risk, while those taking them for 361-720 days had a 51% increased risk of death.
“Although our results should not deter prescription and use of PPIs where medically indicated, they may be used to encourage and promote pharmacovigilance and emphasize the need to exercise judicious use of PPIs and limit use and duration of therapy to instances where there is a clear medical indication and where benefit outweighs potential risk,” the authors wrote.“Standardized guidelines for initiating PPI prescription may lead to reduced overuse [and] regular review of prescription and over-the-counter medications, and deprescription, where a medical indication for PPI treatment ceases to exist, may be a meritorious approach.”
Examining possible physiologic mechanisms to explain the increased risk of death, the authors noted that animal studies suggested PPIs may limit the liver’s capacity to regenerate.
PPIs are also associated with increased activity of the heme oxygenase-1 enzyme in gastric and endothelial cells and impairment of lysosomal acidification and proteostasis and may alter gene expression in the cellular retinol metabolism pathway and the complement and coagulation cascades pathway.
However, the clinical mediator of the heightened risk of death was likely one of the adverse events linked to PPI use, they said.
The authors declared no relevant financial conflicts of interest.
Review AGA’s “Guide to Conversations About the Latest PPI Research Results” for tips on talking with your patients about this research study.
Proton pump inhibitors (PPIs) are associated with a significantly higher risk of death than are H2-receptor antagonists, according to a 5-year longitudinal cohort study.
The study, published online in BMJ Open, found that increased risk of death was evident even in people without gastrointestinal conditions, and it increased with longer duration of use.
Yan Xie, MPH, of the VA Saint Louis Health Care System and coauthors, wrote that PPIs are linked to a range of serious adverse outcomes – such as acute interstitial nephritis, chronic kidney disease, incident dementia, and Clostridium difficile infection – each of which is associated with higher risk of mortality.
Researchers saw a 25% higher risk of death in the 275,977 participants treated with PPIs, compared with that in those who were treated with H2-receptor antagonists (95% confidence interval, 1.23-1.28), after adjusting for factors such as estimated glomerular filtration rate, age, hospitalizations, and a range of comorbidities, including gastrointestinal disorders.When PPI use was compared with no PPI use, there was a 15% increase in the risk of death (95% CI, 1.14-1.15). When compared with no known exposure to any acid suppression therapy, the increased risk of death was 23% (95% CI, 1.22-1.24).
In an attempt to look at the risk of death in a lower-risk cohort, the researchers analyzed a subgroup of participants who did not have the conditions for which PPIs are normally prescribed, such as gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, Helicobacter pylori infection, and Barrett’s esophagus.
However, even in this lower-risk cohort, the study still showed a 24% increase in the risk of death with PPIs, compared with that in H2-receptor antagonists (95% CI, 1.21-1.27); a 19% increase with PPIs, compared with no PPIs; and a 22% increase with PPIs, compared with no acid suppression.
Duration of exposure to PPIs was also associated with increasing risk of death. Participants who had taken PPIs for fewer than 90 days in total had only a 5% increase in risk, while those taking them for 361-720 days had a 51% increased risk of death.
“Although our results should not deter prescription and use of PPIs where medically indicated, they may be used to encourage and promote pharmacovigilance and emphasize the need to exercise judicious use of PPIs and limit use and duration of therapy to instances where there is a clear medical indication and where benefit outweighs potential risk,” the authors wrote.“Standardized guidelines for initiating PPI prescription may lead to reduced overuse [and] regular review of prescription and over-the-counter medications, and deprescription, where a medical indication for PPI treatment ceases to exist, may be a meritorious approach.”
Examining possible physiologic mechanisms to explain the increased risk of death, the authors noted that animal studies suggested PPIs may limit the liver’s capacity to regenerate.
PPIs are also associated with increased activity of the heme oxygenase-1 enzyme in gastric and endothelial cells and impairment of lysosomal acidification and proteostasis and may alter gene expression in the cellular retinol metabolism pathway and the complement and coagulation cascades pathway.
However, the clinical mediator of the heightened risk of death was likely one of the adverse events linked to PPI use, they said.
The authors declared no relevant financial conflicts of interest.
Review AGA’s “Guide to Conversations About the Latest PPI Research Results” for tips on talking with your patients about this research study.
Proton pump inhibitors (PPIs) are associated with a significantly higher risk of death than are H2-receptor antagonists, according to a 5-year longitudinal cohort study.
The study, published online in BMJ Open, found that increased risk of death was evident even in people without gastrointestinal conditions, and it increased with longer duration of use.
Yan Xie, MPH, of the VA Saint Louis Health Care System and coauthors, wrote that PPIs are linked to a range of serious adverse outcomes – such as acute interstitial nephritis, chronic kidney disease, incident dementia, and Clostridium difficile infection – each of which is associated with higher risk of mortality.
Researchers saw a 25% higher risk of death in the 275,977 participants treated with PPIs, compared with that in those who were treated with H2-receptor antagonists (95% confidence interval, 1.23-1.28), after adjusting for factors such as estimated glomerular filtration rate, age, hospitalizations, and a range of comorbidities, including gastrointestinal disorders.When PPI use was compared with no PPI use, there was a 15% increase in the risk of death (95% CI, 1.14-1.15). When compared with no known exposure to any acid suppression therapy, the increased risk of death was 23% (95% CI, 1.22-1.24).
In an attempt to look at the risk of death in a lower-risk cohort, the researchers analyzed a subgroup of participants who did not have the conditions for which PPIs are normally prescribed, such as gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, Helicobacter pylori infection, and Barrett’s esophagus.
However, even in this lower-risk cohort, the study still showed a 24% increase in the risk of death with PPIs, compared with that in H2-receptor antagonists (95% CI, 1.21-1.27); a 19% increase with PPIs, compared with no PPIs; and a 22% increase with PPIs, compared with no acid suppression.
Duration of exposure to PPIs was also associated with increasing risk of death. Participants who had taken PPIs for fewer than 90 days in total had only a 5% increase in risk, while those taking them for 361-720 days had a 51% increased risk of death.
“Although our results should not deter prescription and use of PPIs where medically indicated, they may be used to encourage and promote pharmacovigilance and emphasize the need to exercise judicious use of PPIs and limit use and duration of therapy to instances where there is a clear medical indication and where benefit outweighs potential risk,” the authors wrote.“Standardized guidelines for initiating PPI prescription may lead to reduced overuse [and] regular review of prescription and over-the-counter medications, and deprescription, where a medical indication for PPI treatment ceases to exist, may be a meritorious approach.”
Examining possible physiologic mechanisms to explain the increased risk of death, the authors noted that animal studies suggested PPIs may limit the liver’s capacity to regenerate.
PPIs are also associated with increased activity of the heme oxygenase-1 enzyme in gastric and endothelial cells and impairment of lysosomal acidification and proteostasis and may alter gene expression in the cellular retinol metabolism pathway and the complement and coagulation cascades pathway.
However, the clinical mediator of the heightened risk of death was likely one of the adverse events linked to PPI use, they said.
The authors declared no relevant financial conflicts of interest.
Review AGA’s “Guide to Conversations About the Latest PPI Research Results” for tips on talking with your patients about this research study.
EUS beats MRCP on sensitivity for bile duct stones
Endoscopic ultrasound (EUS) beat magnetic resonance cholangiopancreatography (MRCP) on diagnostic accuracy for choledocholithiasis, but both provided similar specificity, according to data from a meta-analysis of head-to-head comparisons. The findings were published in Gastrointestinal Endoscopy.
EUS and MRCP can provide accurate diagnosis of choledocholithiasis with lower adverse event rates than the clinical standards of endoscopic retrograde cholangiopancreatography and intraoperative cholangiography, but a meta-analysis of the diagnostic test accuracy (DTA) of the two methods was lacking, wrote Mohammad Yaghoobi, MD, of McMaster University, Hamilton, Ont., and his colleagues (Gastrointest Endosc. 2017. doi: 10.1016/j.gie.2017.06.009).
“The methodology of a meta-analysis of DTA is different from a conventional meta-analysis in several aspects, including statistical analysis and quality assessment of the included trials,” the researchers wrote.
They reviewed data from studies conducted between 1980 and January 2017 and identified five studies of head-to-head comparisons of EUS and MRCP. Studies involving children, and those with insufficient data, no reference standards, and a gap of more than 48 hours between two index tests were excluded.
Overall, the diagnostic odds ratio was significantly higher for EUS than MRCP (P = .008). This difference was mainly a factor of the significantly higher sensitivity of EUS vs. MRCP (P = .006). Specificity was not significantly different between the two tests.
The results were limited by several factors, including inadequate data for a subgroup analysis based on stone size and the relatively small number of studies included in the analysis, but the strict inclusion criteria add to the strength of the findings, the researchers noted.
“EUS should be incorporated in the diagnostic algorithm in patients suspected for choledocholithiasis, whenever appropriate, given its reasonable safety profile,” the researchers said. “This might specially apply to the patients who need an esophagogastroduodenoscopy for investigating other alternative causes of abdominal pain,” they added. The researchers had no financial conflicts to disclose.
Endoscopic ultrasound (EUS) beat magnetic resonance cholangiopancreatography (MRCP) on diagnostic accuracy for choledocholithiasis, but both provided similar specificity, according to data from a meta-analysis of head-to-head comparisons. The findings were published in Gastrointestinal Endoscopy.
EUS and MRCP can provide accurate diagnosis of choledocholithiasis with lower adverse event rates than the clinical standards of endoscopic retrograde cholangiopancreatography and intraoperative cholangiography, but a meta-analysis of the diagnostic test accuracy (DTA) of the two methods was lacking, wrote Mohammad Yaghoobi, MD, of McMaster University, Hamilton, Ont., and his colleagues (Gastrointest Endosc. 2017. doi: 10.1016/j.gie.2017.06.009).
“The methodology of a meta-analysis of DTA is different from a conventional meta-analysis in several aspects, including statistical analysis and quality assessment of the included trials,” the researchers wrote.
They reviewed data from studies conducted between 1980 and January 2017 and identified five studies of head-to-head comparisons of EUS and MRCP. Studies involving children, and those with insufficient data, no reference standards, and a gap of more than 48 hours between two index tests were excluded.
Overall, the diagnostic odds ratio was significantly higher for EUS than MRCP (P = .008). This difference was mainly a factor of the significantly higher sensitivity of EUS vs. MRCP (P = .006). Specificity was not significantly different between the two tests.
The results were limited by several factors, including inadequate data for a subgroup analysis based on stone size and the relatively small number of studies included in the analysis, but the strict inclusion criteria add to the strength of the findings, the researchers noted.
“EUS should be incorporated in the diagnostic algorithm in patients suspected for choledocholithiasis, whenever appropriate, given its reasonable safety profile,” the researchers said. “This might specially apply to the patients who need an esophagogastroduodenoscopy for investigating other alternative causes of abdominal pain,” they added. The researchers had no financial conflicts to disclose.
Endoscopic ultrasound (EUS) beat magnetic resonance cholangiopancreatography (MRCP) on diagnostic accuracy for choledocholithiasis, but both provided similar specificity, according to data from a meta-analysis of head-to-head comparisons. The findings were published in Gastrointestinal Endoscopy.
EUS and MRCP can provide accurate diagnosis of choledocholithiasis with lower adverse event rates than the clinical standards of endoscopic retrograde cholangiopancreatography and intraoperative cholangiography, but a meta-analysis of the diagnostic test accuracy (DTA) of the two methods was lacking, wrote Mohammad Yaghoobi, MD, of McMaster University, Hamilton, Ont., and his colleagues (Gastrointest Endosc. 2017. doi: 10.1016/j.gie.2017.06.009).
“The methodology of a meta-analysis of DTA is different from a conventional meta-analysis in several aspects, including statistical analysis and quality assessment of the included trials,” the researchers wrote.
They reviewed data from studies conducted between 1980 and January 2017 and identified five studies of head-to-head comparisons of EUS and MRCP. Studies involving children, and those with insufficient data, no reference standards, and a gap of more than 48 hours between two index tests were excluded.
Overall, the diagnostic odds ratio was significantly higher for EUS than MRCP (P = .008). This difference was mainly a factor of the significantly higher sensitivity of EUS vs. MRCP (P = .006). Specificity was not significantly different between the two tests.
The results were limited by several factors, including inadequate data for a subgroup analysis based on stone size and the relatively small number of studies included in the analysis, but the strict inclusion criteria add to the strength of the findings, the researchers noted.
“EUS should be incorporated in the diagnostic algorithm in patients suspected for choledocholithiasis, whenever appropriate, given its reasonable safety profile,” the researchers said. “This might specially apply to the patients who need an esophagogastroduodenoscopy for investigating other alternative causes of abdominal pain,” they added. The researchers had no financial conflicts to disclose.
FROM GASTROINTESTINAL ENDOSCOPY
Key clinical point: EUS offers greater sensitivity and similar specificity compared with MRCP in detecting choledocholithiasis.
Major finding: The diagnostic odds ratio was significantly higher for EUS than MRCP (P = .008).
Data source: A meta-analysis of diagnostic test accuracy including five head-to-head studies.
Disclosures: The researchers had no financial conflicts to disclose.
Study finds family history, chocolate intake increases acne risk
Having two parents with a history of acne was associated with an eightfold higher risk of acne during adolescence and young adulthood, in a European study that surveyed people aged 15-24 years in seven European countries.
Researchers conducted an online population-based survey of 10,521 individuals aged 15-24 years in Belgium, Czech and Slovak republics, France, Italy, Poland, and Spain, with questions about the presence or absence of acne, sociodemographic characteristics, and lifestyle factors (such as diet, tobacco, cannabis or alcohol use, and family history). The results were published online on July 14.
The overall prevalence of self-reported acne was 57.8%, with the highest prevalence – 65.8% – found in the 15- to 17-years age group, and the lowest being 52.6% in the 21- to 24-years age group. Individuals who reported having one parent with a history of acne had a threefold greater incidence of acne compared to those without a history of paternal or maternal acne (P less than .0001 for both). Individuals whose parents both had acne had a nearly eightfold higher risk, which the authors noted was consistent with other studies showing a strong hereditary component of acne (J Eur Acad Dermatol Venereol. 2017 Jul 14. doi: 10.1111/jdv.14475).
“Previous studies have demonstrated an association between high glycemic index foods and acne, although in our study, only chocolate, and not pasta or sweets, was independently associated in multivariate analysis,” wrote Pierre Wolkenstein, MD, of the department of dermatology, Hôpital Henri Mondor, Créteil, France, and his coauthors.
“The relationship between smoking and acne is not clear. Some observational studies have found that smoking increases the prevalence of acne, others have found a negative association, and some have found no relationship,” they added.
The study also showed significant variation in the incidence of acne across different countries. Using Spain, which had a median prevalence of acne, as a reference point, the researchers found that respondents in the Czech and Slovak republics had a 96% higher incidence of acne, while those in Poland had a 55% lower incidence.
The authors cautioned that their results were based on self-report, rather than a physician diagnosis, but they noted that since acne is so common, false positive or false negative reports were unlikely. “An association between self-reported acne and chocolate consumption, and an apparent inverse relationship with smoking, need to be confirmed by additional studies,” they noted.
The survey was funded and supported by Pierre Fabre Dermatologie. Five authors declared fees as members of the European Severe Acne Board, supported by Pierre Fabre Dermatologie, and one author is an employee of the company.
Having two parents with a history of acne was associated with an eightfold higher risk of acne during adolescence and young adulthood, in a European study that surveyed people aged 15-24 years in seven European countries.
Researchers conducted an online population-based survey of 10,521 individuals aged 15-24 years in Belgium, Czech and Slovak republics, France, Italy, Poland, and Spain, with questions about the presence or absence of acne, sociodemographic characteristics, and lifestyle factors (such as diet, tobacco, cannabis or alcohol use, and family history). The results were published online on July 14.
The overall prevalence of self-reported acne was 57.8%, with the highest prevalence – 65.8% – found in the 15- to 17-years age group, and the lowest being 52.6% in the 21- to 24-years age group. Individuals who reported having one parent with a history of acne had a threefold greater incidence of acne compared to those without a history of paternal or maternal acne (P less than .0001 for both). Individuals whose parents both had acne had a nearly eightfold higher risk, which the authors noted was consistent with other studies showing a strong hereditary component of acne (J Eur Acad Dermatol Venereol. 2017 Jul 14. doi: 10.1111/jdv.14475).
“Previous studies have demonstrated an association between high glycemic index foods and acne, although in our study, only chocolate, and not pasta or sweets, was independently associated in multivariate analysis,” wrote Pierre Wolkenstein, MD, of the department of dermatology, Hôpital Henri Mondor, Créteil, France, and his coauthors.
“The relationship between smoking and acne is not clear. Some observational studies have found that smoking increases the prevalence of acne, others have found a negative association, and some have found no relationship,” they added.
The study also showed significant variation in the incidence of acne across different countries. Using Spain, which had a median prevalence of acne, as a reference point, the researchers found that respondents in the Czech and Slovak republics had a 96% higher incidence of acne, while those in Poland had a 55% lower incidence.
The authors cautioned that their results were based on self-report, rather than a physician diagnosis, but they noted that since acne is so common, false positive or false negative reports were unlikely. “An association between self-reported acne and chocolate consumption, and an apparent inverse relationship with smoking, need to be confirmed by additional studies,” they noted.
The survey was funded and supported by Pierre Fabre Dermatologie. Five authors declared fees as members of the European Severe Acne Board, supported by Pierre Fabre Dermatologie, and one author is an employee of the company.
Having two parents with a history of acne was associated with an eightfold higher risk of acne during adolescence and young adulthood, in a European study that surveyed people aged 15-24 years in seven European countries.
Researchers conducted an online population-based survey of 10,521 individuals aged 15-24 years in Belgium, Czech and Slovak republics, France, Italy, Poland, and Spain, with questions about the presence or absence of acne, sociodemographic characteristics, and lifestyle factors (such as diet, tobacco, cannabis or alcohol use, and family history). The results were published online on July 14.
The overall prevalence of self-reported acne was 57.8%, with the highest prevalence – 65.8% – found in the 15- to 17-years age group, and the lowest being 52.6% in the 21- to 24-years age group. Individuals who reported having one parent with a history of acne had a threefold greater incidence of acne compared to those without a history of paternal or maternal acne (P less than .0001 for both). Individuals whose parents both had acne had a nearly eightfold higher risk, which the authors noted was consistent with other studies showing a strong hereditary component of acne (J Eur Acad Dermatol Venereol. 2017 Jul 14. doi: 10.1111/jdv.14475).
“Previous studies have demonstrated an association between high glycemic index foods and acne, although in our study, only chocolate, and not pasta or sweets, was independently associated in multivariate analysis,” wrote Pierre Wolkenstein, MD, of the department of dermatology, Hôpital Henri Mondor, Créteil, France, and his coauthors.
“The relationship between smoking and acne is not clear. Some observational studies have found that smoking increases the prevalence of acne, others have found a negative association, and some have found no relationship,” they added.
The study also showed significant variation in the incidence of acne across different countries. Using Spain, which had a median prevalence of acne, as a reference point, the researchers found that respondents in the Czech and Slovak republics had a 96% higher incidence of acne, while those in Poland had a 55% lower incidence.
The authors cautioned that their results were based on self-report, rather than a physician diagnosis, but they noted that since acne is so common, false positive or false negative reports were unlikely. “An association between self-reported acne and chocolate consumption, and an apparent inverse relationship with smoking, need to be confirmed by additional studies,” they noted.
The survey was funded and supported by Pierre Fabre Dermatologie. Five authors declared fees as members of the European Severe Acne Board, supported by Pierre Fabre Dermatologie, and one author is an employee of the company.
FROM THE JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Key clinical point: A parental history of acne, higher levels of personal chocolate consumption, and younger age were significantly associated with an increased risk of acne.
Major finding: Adolescents and young adults with two parents with a history of acne have a nearly eightfold higher risk of the condition.
Data source: A population-based survey of 10,521 individuals aged 15-24 years in seven European countries.
Disclosures: Five authors declared fees as members of the European Severe Acne Board – supported by Pierre Fabre Dermatologie, which funded the survey – and one author is an employee of the company.
Get involved with AGA
We’re soliciting members to serve in AGA leadership positions – as committee and center members, as well as on the AGA Institute Governing Board. This is an opportunity to network with other physicians and scientists, pursue a special interest, and make an impact in an area that is important to you.
Join a committee or center
AGA and AGA Institute are seeking members to serve on several committees and centers that recommend and oversee new and existing policies and programs. Terms will start in June 2018; nominations must be received by Nov. 1, 2017. Members can either nominate themselves or other members. For more information on the positions available, take a look at the AGA Committee page, http://www.gastro.org/about/people/committees.
Serve in a leadership position
The AGA Nominating Committee is in the midst of identifying candidates to join the governing board – in the offices of vice president, clinical research councillor, and practice councillor – as well as 10 nominees for the 2018-2019 AGA Nominating Committee. To learn more, or to nominate yourself or a colleague, email [email protected]. Nominations are due by Oct. 1, 2017; earlier submissions are encouraged.
We’re soliciting members to serve in AGA leadership positions – as committee and center members, as well as on the AGA Institute Governing Board. This is an opportunity to network with other physicians and scientists, pursue a special interest, and make an impact in an area that is important to you.
Join a committee or center
AGA and AGA Institute are seeking members to serve on several committees and centers that recommend and oversee new and existing policies and programs. Terms will start in June 2018; nominations must be received by Nov. 1, 2017. Members can either nominate themselves or other members. For more information on the positions available, take a look at the AGA Committee page, http://www.gastro.org/about/people/committees.
Serve in a leadership position
The AGA Nominating Committee is in the midst of identifying candidates to join the governing board – in the offices of vice president, clinical research councillor, and practice councillor – as well as 10 nominees for the 2018-2019 AGA Nominating Committee. To learn more, or to nominate yourself or a colleague, email [email protected]. Nominations are due by Oct. 1, 2017; earlier submissions are encouraged.
We’re soliciting members to serve in AGA leadership positions – as committee and center members, as well as on the AGA Institute Governing Board. This is an opportunity to network with other physicians and scientists, pursue a special interest, and make an impact in an area that is important to you.
Join a committee or center
AGA and AGA Institute are seeking members to serve on several committees and centers that recommend and oversee new and existing policies and programs. Terms will start in June 2018; nominations must be received by Nov. 1, 2017. Members can either nominate themselves or other members. For more information on the positions available, take a look at the AGA Committee page, http://www.gastro.org/about/people/committees.
Serve in a leadership position
The AGA Nominating Committee is in the midst of identifying candidates to join the governing board – in the offices of vice president, clinical research councillor, and practice councillor – as well as 10 nominees for the 2018-2019 AGA Nominating Committee. To learn more, or to nominate yourself or a colleague, email [email protected]. Nominations are due by Oct. 1, 2017; earlier submissions are encouraged.
Mark your calendar: 2018 AGA grants cycle announced
The AGA Research Foundation is excited to announce the start of its 2018 Research Grants cycle. This year the foundation will be awarding over $2 million in funding to support researchers within gastroenterology and hepatology. Now is your chance to view upcoming opportunities and plan your applications. Learn more below about the first application due in August, and visit the AGA Research Funding website (www.gastro.org/research-funding) for the full list. Contact [email protected] with any questions.
Applications due: Aug. 4, 2017
AGA-R. Robert & Sally Funderburg Research Award in Gastric Cancer
This award provides $50,000 per year for 2 years to an established investigator working on novel approaches in gastric cancer research. For the past 25 years, this $100,000 award has enhanced the fundamental understanding of gastric cancer pathobiology toward ultimately developing a cure for the disease.
The AGA Research Foundation is excited to announce the start of its 2018 Research Grants cycle. This year the foundation will be awarding over $2 million in funding to support researchers within gastroenterology and hepatology. Now is your chance to view upcoming opportunities and plan your applications. Learn more below about the first application due in August, and visit the AGA Research Funding website (www.gastro.org/research-funding) for the full list. Contact [email protected] with any questions.
Applications due: Aug. 4, 2017
AGA-R. Robert & Sally Funderburg Research Award in Gastric Cancer
This award provides $50,000 per year for 2 years to an established investigator working on novel approaches in gastric cancer research. For the past 25 years, this $100,000 award has enhanced the fundamental understanding of gastric cancer pathobiology toward ultimately developing a cure for the disease.
The AGA Research Foundation is excited to announce the start of its 2018 Research Grants cycle. This year the foundation will be awarding over $2 million in funding to support researchers within gastroenterology and hepatology. Now is your chance to view upcoming opportunities and plan your applications. Learn more below about the first application due in August, and visit the AGA Research Funding website (www.gastro.org/research-funding) for the full list. Contact [email protected] with any questions.
Applications due: Aug. 4, 2017
AGA-R. Robert & Sally Funderburg Research Award in Gastric Cancer
This award provides $50,000 per year for 2 years to an established investigator working on novel approaches in gastric cancer research. For the past 25 years, this $100,000 award has enhanced the fundamental understanding of gastric cancer pathobiology toward ultimately developing a cure for the disease.
Physician compensation growing but at a slightly slower pace
Physicians working in large multispecialty groups saw their compensation increase in 2016, albeit at a slower pace than in 2015, according to survey results reported by AMGA.
The 2017 Medical Group Compensation and Productivity Survey shows that the overall weighted average increase in physician compensation for the calendar year 2016 was 2.9%, slightly lower than the 3.1% increase seen in 2015. Doctors in more than three-quarters (77%) of specialties saw increases in 2016.
Opthalmologic surgery saw the largest compensation increase at 7.7%, followed by cardiothoracic surgery (7.0%), hematology and medical oncology (6.7%), allergy/immunology (5.9%) and pulmonary disease (5.6%). Emergency medicine saw a decrease in compensation of 2.0% in 2016 after experiencing a 9.6% increase in 2015.
Value-based payment is beginning to factor into the growth in payment by specialty. Overall, about 8% of compensation is being linked to value-based pay, and that number is expected to rise, with some medical practice groups linking 15% or more of compensation to value-based metrics.
“In almost all of the groups that I have worked with in the last few years on [compensation] design, that has been one of the drivers of decision to do the compensation redesign is to allocate to the value-based metrics,” Wayne Hartley, vice president of AMGA Consulting, said in an interview. 
AMGA said that the data covers responses from 269 medical groups covering more than 102,000 providers and is representative of large multispecialty groups and integrated health systems that average 380 providers per group.
Physicians working in large multispecialty groups saw their compensation increase in 2016, albeit at a slower pace than in 2015, according to survey results reported by AMGA.
The 2017 Medical Group Compensation and Productivity Survey shows that the overall weighted average increase in physician compensation for the calendar year 2016 was 2.9%, slightly lower than the 3.1% increase seen in 2015. Doctors in more than three-quarters (77%) of specialties saw increases in 2016.
Opthalmologic surgery saw the largest compensation increase at 7.7%, followed by cardiothoracic surgery (7.0%), hematology and medical oncology (6.7%), allergy/immunology (5.9%) and pulmonary disease (5.6%). Emergency medicine saw a decrease in compensation of 2.0% in 2016 after experiencing a 9.6% increase in 2015.
Value-based payment is beginning to factor into the growth in payment by specialty. Overall, about 8% of compensation is being linked to value-based pay, and that number is expected to rise, with some medical practice groups linking 15% or more of compensation to value-based metrics.
“In almost all of the groups that I have worked with in the last few years on [compensation] design, that has been one of the drivers of decision to do the compensation redesign is to allocate to the value-based metrics,” Wayne Hartley, vice president of AMGA Consulting, said in an interview.
AMGA said that the data covers responses from 269 medical groups covering more than 102,000 providers and is representative of large multispecialty groups and integrated health systems that average 380 providers per group.
Physicians working in large multispecialty groups saw their compensation increase in 2016, albeit at a slower pace than in 2015, according to survey results reported by AMGA.
The 2017 Medical Group Compensation and Productivity Survey shows that the overall weighted average increase in physician compensation for the calendar year 2016 was 2.9%, slightly lower than the 3.1% increase seen in 2015. Doctors in more than three-quarters (77%) of specialties saw increases in 2016.
Opthalmologic surgery saw the largest compensation increase at 7.7%, followed by cardiothoracic surgery (7.0%), hematology and medical oncology (6.7%), allergy/immunology (5.9%) and pulmonary disease (5.6%). Emergency medicine saw a decrease in compensation of 2.0% in 2016 after experiencing a 9.6% increase in 2015.
Value-based payment is beginning to factor into the growth in payment by specialty. Overall, about 8% of compensation is being linked to value-based pay, and that number is expected to rise, with some medical practice groups linking 15% or more of compensation to value-based metrics.
“In almost all of the groups that I have worked with in the last few years on [compensation] design, that has been one of the drivers of decision to do the compensation redesign is to allocate to the value-based metrics,” Wayne Hartley, vice president of AMGA Consulting, said in an interview.
AMGA said that the data covers responses from 269 medical groups covering more than 102,000 providers and is representative of large multispecialty groups and integrated health systems that average 380 providers per group.
HHS eliminates funding for teen pregnancy prevention programs
The Trump administration’s sudden funding cut to the Teen Pregnancy Prevention Program will not only halt research and programming efforts at more than 80 institutions across the country, but also will likely unravel recent progress made in reducing teen pregnancies, physicians and program advocates say.
In early July, officials at the U.S. Department of Health & Human Services notified program grantees that the administration would be eliminating funding for the Teen Pregnancy Prevention Program (TPP Program) and that 5-year grants awarded under the Obama administration would be ending in June 2018, 2 years earlier than planned.
The TPP Program is a national, evidence-based initiative established in 2010 to fund medically accurate and age-appropriate programs that work to prevent teen pregnancy in the United States.
“Those programs serve many youth across the country, so of course the individuals in the programs are going to be impacted,” Dr. Oelschlager said in an interview. “It’s demoralizing for the educators, [and] the researchers, who are looking at innovative methods, to have their funding cut in the middle of evaluating whether their programs are effective.”
An HHS spokeswoman confirmed that on July 1, the agency informed TPP Program grantees that funding for the program would be eliminated as detailed in President Trump’s fiscal 2018 budget proposal. The HHS awarded 81 continuations for TPP Program Tier 1 and Tier 2 grant awards for a total of $89 million through June 30, 2018, according to the spokeswoman. The HHS informed the grantees of their June 30, 2018, end date “to give them an opportunity to adjust their programs and plan for an orderly closeout,” she said.
The University of Southern California, Los Angeles, is one of many institutions impacted by the funding cut. The primary objectives of the Keeping it Real Together project are to implement evidence-based sexual health education programs for youth in middle and alternative high schools and provide an education program for parents of middle school–aged youth, said Luanne Rohrbach, PhD, associate professor of clinical preventive medicine at the university’s Institute for Health Promotion & Disease Prevention and principal investigator for the program.
Dr. Rohrbach said she anticipated pushback from the new administration as far as receiving the full 5-year funding, but the sudden program elimination was unexpected.
In March, when President Trump announced his budget priorities for fiscal 2016 and 2017, it was clear that the TPP Program was on the chopping block, Dr. Rohrbach said. However, when Congress passed a continuing resolution for the remainder of fiscal 2016 and 2017, the program remained intact. In his budget recommendations for fiscal 2017 and 2018, the President proposed that the TPP Program be eliminated.
“Despite this recommendation, it was our understanding that the program would be debated in Congress as they developed their recommendations for FY 2017-18 funding,” she said. “That is, we expected there would at least be discussion about it in Congressional budget committees. We did not expect that the program would be eliminated by the Office of the Secretary of HHS.”
Haywood L. Brown, MD, president of the American Congress of Obstetricians and Gynecologists (ACOG) called the administration’s decision “highly unusual” and said it is a step backward for ensuring healthy moms and healthy babies.
“This program and others provide vital research and programming that successfully brought our nation to an all-time low rate of teen pregnancies – progress we cannot afford to jeopardize,” Dr. Brown said in a statement.
Federal data show that the teen pregnancy rate has steadily declined over the last decade. In 2015, the birth rate for girls and young women aged 15-19 years fell by nearly 8% from 2014, according to data from the National Center for Health Statistics. Since 1991, the rate has fallen by 64%. The rate for the younger half of the age group, girls aged 15-17 years, was down 9% from 2014.
Researchers attribute the decline to a combination of economic, cultural, and social factors, as well as a lower prevalence of sexual activity among youth, the use of more effective contraception, and the provision of more information about pregnancy prevention, Dr. Rohrbach said.
“The [TPP Program] has been focused on implementation of evidence-based, comprehensive sexual health education,” she said. “Elimination of these efforts endangers the progress that has been made in reducing teen pregnancies.”
Dr. Oelschlager noted that between 2008 and 2015, the teen birth rate in King County, Washington, declined by 55%. She attributed the reduction to multiple drivers, including a program called Flash, that incorporates a sexual health education curriculum in Seattle-area public schools. Some TPP programs in Northwest Seattle are using the FLASH curriculum, she said.
“This is a very comprehensive program, which includes discussion about reproductive health, sexual violence, prevention of teen pregnancy, sexually transmitted infections, [and] harm reduction,” she said. “That’s been a very effective method of educating our teens about these issues.”
[email protected]
On Twitter @legal_med
The Trump administration’s sudden funding cut to the Teen Pregnancy Prevention Program will not only halt research and programming efforts at more than 80 institutions across the country, but also will likely unravel recent progress made in reducing teen pregnancies, physicians and program advocates say.
In early July, officials at the U.S. Department of Health & Human Services notified program grantees that the administration would be eliminating funding for the Teen Pregnancy Prevention Program (TPP Program) and that 5-year grants awarded under the Obama administration would be ending in June 2018, 2 years earlier than planned.
The TPP Program is a national, evidence-based initiative established in 2010 to fund medically accurate and age-appropriate programs that work to prevent teen pregnancy in the United States.
“Those programs serve many youth across the country, so of course the individuals in the programs are going to be impacted,” Dr. Oelschlager said in an interview. “It’s demoralizing for the educators, [and] the researchers, who are looking at innovative methods, to have their funding cut in the middle of evaluating whether their programs are effective.”
An HHS spokeswoman confirmed that on July 1, the agency informed TPP Program grantees that funding for the program would be eliminated as detailed in President Trump’s fiscal 2018 budget proposal. The HHS awarded 81 continuations for TPP Program Tier 1 and Tier 2 grant awards for a total of $89 million through June 30, 2018, according to the spokeswoman. The HHS informed the grantees of their June 30, 2018, end date “to give them an opportunity to adjust their programs and plan for an orderly closeout,” she said.
The University of Southern California, Los Angeles, is one of many institutions impacted by the funding cut. The primary objectives of the Keeping it Real Together project are to implement evidence-based sexual health education programs for youth in middle and alternative high schools and provide an education program for parents of middle school–aged youth, said Luanne Rohrbach, PhD, associate professor of clinical preventive medicine at the university’s Institute for Health Promotion & Disease Prevention and principal investigator for the program.
Dr. Rohrbach said she anticipated pushback from the new administration as far as receiving the full 5-year funding, but the sudden program elimination was unexpected.
In March, when President Trump announced his budget priorities for fiscal 2016 and 2017, it was clear that the TPP Program was on the chopping block, Dr. Rohrbach said. However, when Congress passed a continuing resolution for the remainder of fiscal 2016 and 2017, the program remained intact. In his budget recommendations for fiscal 2017 and 2018, the President proposed that the TPP Program be eliminated.
“Despite this recommendation, it was our understanding that the program would be debated in Congress as they developed their recommendations for FY 2017-18 funding,” she said. “That is, we expected there would at least be discussion about it in Congressional budget committees. We did not expect that the program would be eliminated by the Office of the Secretary of HHS.”
Haywood L. Brown, MD, president of the American Congress of Obstetricians and Gynecologists (ACOG) called the administration’s decision “highly unusual” and said it is a step backward for ensuring healthy moms and healthy babies.
“This program and others provide vital research and programming that successfully brought our nation to an all-time low rate of teen pregnancies – progress we cannot afford to jeopardize,” Dr. Brown said in a statement.
Federal data show that the teen pregnancy rate has steadily declined over the last decade. In 2015, the birth rate for girls and young women aged 15-19 years fell by nearly 8% from 2014, according to data from the National Center for Health Statistics. Since 1991, the rate has fallen by 64%. The rate for the younger half of the age group, girls aged 15-17 years, was down 9% from 2014.
Researchers attribute the decline to a combination of economic, cultural, and social factors, as well as a lower prevalence of sexual activity among youth, the use of more effective contraception, and the provision of more information about pregnancy prevention, Dr. Rohrbach said.
“The [TPP Program] has been focused on implementation of evidence-based, comprehensive sexual health education,” she said. “Elimination of these efforts endangers the progress that has been made in reducing teen pregnancies.”
Dr. Oelschlager noted that between 2008 and 2015, the teen birth rate in King County, Washington, declined by 55%. She attributed the reduction to multiple drivers, including a program called Flash, that incorporates a sexual health education curriculum in Seattle-area public schools. Some TPP programs in Northwest Seattle are using the FLASH curriculum, she said.
“This is a very comprehensive program, which includes discussion about reproductive health, sexual violence, prevention of teen pregnancy, sexually transmitted infections, [and] harm reduction,” she said. “That’s been a very effective method of educating our teens about these issues.”
[email protected]
On Twitter @legal_med
The Trump administration’s sudden funding cut to the Teen Pregnancy Prevention Program will not only halt research and programming efforts at more than 80 institutions across the country, but also will likely unravel recent progress made in reducing teen pregnancies, physicians and program advocates say.
In early July, officials at the U.S. Department of Health & Human Services notified program grantees that the administration would be eliminating funding for the Teen Pregnancy Prevention Program (TPP Program) and that 5-year grants awarded under the Obama administration would be ending in June 2018, 2 years earlier than planned.
The TPP Program is a national, evidence-based initiative established in 2010 to fund medically accurate and age-appropriate programs that work to prevent teen pregnancy in the United States.
“Those programs serve many youth across the country, so of course the individuals in the programs are going to be impacted,” Dr. Oelschlager said in an interview. “It’s demoralizing for the educators, [and] the researchers, who are looking at innovative methods, to have their funding cut in the middle of evaluating whether their programs are effective.”
An HHS spokeswoman confirmed that on July 1, the agency informed TPP Program grantees that funding for the program would be eliminated as detailed in President Trump’s fiscal 2018 budget proposal. The HHS awarded 81 continuations for TPP Program Tier 1 and Tier 2 grant awards for a total of $89 million through June 30, 2018, according to the spokeswoman. The HHS informed the grantees of their June 30, 2018, end date “to give them an opportunity to adjust their programs and plan for an orderly closeout,” she said.
The University of Southern California, Los Angeles, is one of many institutions impacted by the funding cut. The primary objectives of the Keeping it Real Together project are to implement evidence-based sexual health education programs for youth in middle and alternative high schools and provide an education program for parents of middle school–aged youth, said Luanne Rohrbach, PhD, associate professor of clinical preventive medicine at the university’s Institute for Health Promotion & Disease Prevention and principal investigator for the program.
Dr. Rohrbach said she anticipated pushback from the new administration as far as receiving the full 5-year funding, but the sudden program elimination was unexpected.
In March, when President Trump announced his budget priorities for fiscal 2016 and 2017, it was clear that the TPP Program was on the chopping block, Dr. Rohrbach said. However, when Congress passed a continuing resolution for the remainder of fiscal 2016 and 2017, the program remained intact. In his budget recommendations for fiscal 2017 and 2018, the President proposed that the TPP Program be eliminated.
“Despite this recommendation, it was our understanding that the program would be debated in Congress as they developed their recommendations for FY 2017-18 funding,” she said. “That is, we expected there would at least be discussion about it in Congressional budget committees. We did not expect that the program would be eliminated by the Office of the Secretary of HHS.”
Haywood L. Brown, MD, president of the American Congress of Obstetricians and Gynecologists (ACOG) called the administration’s decision “highly unusual” and said it is a step backward for ensuring healthy moms and healthy babies.
“This program and others provide vital research and programming that successfully brought our nation to an all-time low rate of teen pregnancies – progress we cannot afford to jeopardize,” Dr. Brown said in a statement.
Federal data show that the teen pregnancy rate has steadily declined over the last decade. In 2015, the birth rate for girls and young women aged 15-19 years fell by nearly 8% from 2014, according to data from the National Center for Health Statistics. Since 1991, the rate has fallen by 64%. The rate for the younger half of the age group, girls aged 15-17 years, was down 9% from 2014.
Researchers attribute the decline to a combination of economic, cultural, and social factors, as well as a lower prevalence of sexual activity among youth, the use of more effective contraception, and the provision of more information about pregnancy prevention, Dr. Rohrbach said.
“The [TPP Program] has been focused on implementation of evidence-based, comprehensive sexual health education,” she said. “Elimination of these efforts endangers the progress that has been made in reducing teen pregnancies.”
Dr. Oelschlager noted that between 2008 and 2015, the teen birth rate in King County, Washington, declined by 55%. She attributed the reduction to multiple drivers, including a program called Flash, that incorporates a sexual health education curriculum in Seattle-area public schools. Some TPP programs in Northwest Seattle are using the FLASH curriculum, she said.
“This is a very comprehensive program, which includes discussion about reproductive health, sexual violence, prevention of teen pregnancy, sexually transmitted infections, [and] harm reduction,” she said. “That’s been a very effective method of educating our teens about these issues.”
[email protected]
On Twitter @legal_med
Blocking a lipoprotein lipase inhibitor improves lipid profiles
Two different approaches to shutting down the function of a human liver protein that inhibits lipoprotein lipase showed preliminary evidence of safely producing favorable lipid changes in healthy volunteers in two separate, phase 1 studies.
These findings, coupled with promising observational data from people who carry loss-of-function mutations in the gene for this protein, angiopoietin-like 3 (ANGPTL3), have raised hopes that interventions that interfere with the function of the ANGPTL3 protein may provide new and effective ways to improve lipid levels and cut the incidence of cardiovascular disease events.
“There is now a growing body of epidemiologic, genetic, and genomewide association studies supporting the hypothesis that lowering levels of ANGPTL3 in plasma by inhibiting hepatic ANGPTL3 synthesis will be beneficial in terms of reducing plasma levels of atherogenic apolipoprotein B and in improving metabolic measures associated with dyslipidemia,” wrote Mark J. Graham and his associates in a recently published article (N Engl J Med. 2017 Jul 20;377[3]:222-32).
The phase 1 study results reported by this group came from 44 healthy adults aged 18-65 years who received varying doses of a commercially developed antisense drug, ANGPTL3-LRX, as either single or serial subcutaneous injections. ANGPTL3-LRX is an oligonucleotide designed to inhibit production of messenger RNA for the ANGPTL3 protein.
Six people received the highest ANGPTL3-LRX dosage administered, 60 mg given as a weekly injection for 6 weeks, and after this regimen they showed an average 50% cut in triglycerides levels, compared with baseline, and an average 33% drop in their low LDL cholesterol levels from baseline. None of the 33 people treated with ANGPTL3-LRX in the trial had a documented serious adverse event, and the only treatment dropout was a patient who was lost to follow-up during the treatment phase, reported Mr. Graham, a researcher at Ionis Pharmaceuticals, the sponsor of the study and the company developing the antisense drug, and his associates.
The second phase 1 study examined a different way to block ANGPTL3 activity, with a human monoclonal antibody to this protein. The study involved 83 healthy adults aged 18-65 years with fasting triglyceride levels of 150-450 mg/dL and fasting LDL cholesterol levels of at least 100 mg/dL. Each participant received a single subcutaneous injection or intravenous dose of the antibody, evinacumab, at varying amounts or placebo. The maximum observed lipid changes seen was a drop in triglycerides of 76% and a fall in LDL cholesterol by 23%. Treatment also produced a maximum drop in HDL cholesterol of 18%. No person left the study because of an adverse event. The most common adverse event was headache, in seven people (11% of evinacumab recipients), reported Frederick E. Dewey, MD, a researcher at Regeneron Pharmaceuticals, the company developing evinacumab, and his associates (N Engl J Med. 2017 Jul 20;377[3]:211-21).
The Regeneron report also included results from population studies they ran. They reported performing genome sequencing on specimens from 58,335 adults enrolled in the DiscovEHR study, and identified 13 distinct loss-of-function variants in the ANGPTL3 genes that occurred individually in a small number of these people.
They then ran analyses of lipid levels and coronary artery disease prevalence rates in people who carry one of these 13 loss-of-function genetic signatures in one of their ANGTPL3 genes. Among 45,226 of the people in DiscovEHR those with a variant had on average a 27% lower triglyceride level, a 9% lower LDL cholesterol level, and a 4% lower HDL cholesterol level than noncarriers, after adjustment for covariates. Analysis of coronary artery disease prevalence showed that, after adjusting for age, sex, and ancestry, carrying a loss-of-function variant was linked with a statistically significant 41% lower prevalence of all coronary artery disease, and a 34% lower prevalence of myocardial infarction that fell short of statistical significance.
A second population study looked at links between loss-of-function variants and coronary artery disease in more than 130,000 Danish people. This showed a nonsignificant 37% lower prevalence of coronary artery disease in people with a variant. Two different types of meta-analyses of the data from both the DiscovEHR and Danish studies showed coronary disease rates reduced by either 31% or 39% in variant carriers depending on which meta-analysis approach the researchers used, both statistically significant reductions.
[email protected]
On Twitter @mitchelzoler
The findings from these two studies together with other recent study results open a new therapeutic window for reducing elevated levels of triglyceride-rich lipoproteins by activating lipoprotein lipase.
The findings also suggest that inhibition of the ANGPTL3 gene or protein is potentially an effective way to treat patients with familial hypercholesterolemia because of a deficiency in the receptor for low density lipoprotein. It is likely that lowering triglyceride levels with an agent that boosts the activity of lipoprotein lipase will result in a different spectrum of benefits and adverse effects, compared with agents that boost the number of LDL receptors.
New approaches to boost lipoprotein lipase activity, such as inhibiting ANGPTL3 function as was done in these two reports, represents a fresh frontier for treatment of hypertriglyceridemia and coronary artery disease.
Alan R. Tall, MD , professor of medicine at Columbia University, New York, made these comments in an editorial ( N Engl J Med. 2017 Jul 20;377[3]:280-3 ).
The findings from these two studies together with other recent study results open a new therapeutic window for reducing elevated levels of triglyceride-rich lipoproteins by activating lipoprotein lipase.
The findings also suggest that inhibition of the ANGPTL3 gene or protein is potentially an effective way to treat patients with familial hypercholesterolemia because of a deficiency in the receptor for low density lipoprotein. It is likely that lowering triglyceride levels with an agent that boosts the activity of lipoprotein lipase will result in a different spectrum of benefits and adverse effects, compared with agents that boost the number of LDL receptors.
New approaches to boost lipoprotein lipase activity, such as inhibiting ANGPTL3 function as was done in these two reports, represents a fresh frontier for treatment of hypertriglyceridemia and coronary artery disease.
Alan R. Tall, MD , professor of medicine at Columbia University, New York, made these comments in an editorial ( N Engl J Med. 2017 Jul 20;377[3]:280-3 ).
The findings from these two studies together with other recent study results open a new therapeutic window for reducing elevated levels of triglyceride-rich lipoproteins by activating lipoprotein lipase.
The findings also suggest that inhibition of the ANGPTL3 gene or protein is potentially an effective way to treat patients with familial hypercholesterolemia because of a deficiency in the receptor for low density lipoprotein. It is likely that lowering triglyceride levels with an agent that boosts the activity of lipoprotein lipase will result in a different spectrum of benefits and adverse effects, compared with agents that boost the number of LDL receptors.
New approaches to boost lipoprotein lipase activity, such as inhibiting ANGPTL3 function as was done in these two reports, represents a fresh frontier for treatment of hypertriglyceridemia and coronary artery disease.
Alan R. Tall, MD , professor of medicine at Columbia University, New York, made these comments in an editorial ( N Engl J Med. 2017 Jul 20;377[3]:280-3 ).
Two different approaches to shutting down the function of a human liver protein that inhibits lipoprotein lipase showed preliminary evidence of safely producing favorable lipid changes in healthy volunteers in two separate, phase 1 studies.
These findings, coupled with promising observational data from people who carry loss-of-function mutations in the gene for this protein, angiopoietin-like 3 (ANGPTL3), have raised hopes that interventions that interfere with the function of the ANGPTL3 protein may provide new and effective ways to improve lipid levels and cut the incidence of cardiovascular disease events.
“There is now a growing body of epidemiologic, genetic, and genomewide association studies supporting the hypothesis that lowering levels of ANGPTL3 in plasma by inhibiting hepatic ANGPTL3 synthesis will be beneficial in terms of reducing plasma levels of atherogenic apolipoprotein B and in improving metabolic measures associated with dyslipidemia,” wrote Mark J. Graham and his associates in a recently published article (N Engl J Med. 2017 Jul 20;377[3]:222-32).
The phase 1 study results reported by this group came from 44 healthy adults aged 18-65 years who received varying doses of a commercially developed antisense drug, ANGPTL3-LRX, as either single or serial subcutaneous injections. ANGPTL3-LRX is an oligonucleotide designed to inhibit production of messenger RNA for the ANGPTL3 protein.
Six people received the highest ANGPTL3-LRX dosage administered, 60 mg given as a weekly injection for 6 weeks, and after this regimen they showed an average 50% cut in triglycerides levels, compared with baseline, and an average 33% drop in their low LDL cholesterol levels from baseline. None of the 33 people treated with ANGPTL3-LRX in the trial had a documented serious adverse event, and the only treatment dropout was a patient who was lost to follow-up during the treatment phase, reported Mr. Graham, a researcher at Ionis Pharmaceuticals, the sponsor of the study and the company developing the antisense drug, and his associates.
The second phase 1 study examined a different way to block ANGPTL3 activity, with a human monoclonal antibody to this protein. The study involved 83 healthy adults aged 18-65 years with fasting triglyceride levels of 150-450 mg/dL and fasting LDL cholesterol levels of at least 100 mg/dL. Each participant received a single subcutaneous injection or intravenous dose of the antibody, evinacumab, at varying amounts or placebo. The maximum observed lipid changes seen was a drop in triglycerides of 76% and a fall in LDL cholesterol by 23%. Treatment also produced a maximum drop in HDL cholesterol of 18%. No person left the study because of an adverse event. The most common adverse event was headache, in seven people (11% of evinacumab recipients), reported Frederick E. Dewey, MD, a researcher at Regeneron Pharmaceuticals, the company developing evinacumab, and his associates (N Engl J Med. 2017 Jul 20;377[3]:211-21).
The Regeneron report also included results from population studies they ran. They reported performing genome sequencing on specimens from 58,335 adults enrolled in the DiscovEHR study, and identified 13 distinct loss-of-function variants in the ANGPTL3 genes that occurred individually in a small number of these people.
They then ran analyses of lipid levels and coronary artery disease prevalence rates in people who carry one of these 13 loss-of-function genetic signatures in one of their ANGTPL3 genes. Among 45,226 of the people in DiscovEHR those with a variant had on average a 27% lower triglyceride level, a 9% lower LDL cholesterol level, and a 4% lower HDL cholesterol level than noncarriers, after adjustment for covariates. Analysis of coronary artery disease prevalence showed that, after adjusting for age, sex, and ancestry, carrying a loss-of-function variant was linked with a statistically significant 41% lower prevalence of all coronary artery disease, and a 34% lower prevalence of myocardial infarction that fell short of statistical significance.
A second population study looked at links between loss-of-function variants and coronary artery disease in more than 130,000 Danish people. This showed a nonsignificant 37% lower prevalence of coronary artery disease in people with a variant. Two different types of meta-analyses of the data from both the DiscovEHR and Danish studies showed coronary disease rates reduced by either 31% or 39% in variant carriers depending on which meta-analysis approach the researchers used, both statistically significant reductions.
[email protected]
On Twitter @mitchelzoler
Two different approaches to shutting down the function of a human liver protein that inhibits lipoprotein lipase showed preliminary evidence of safely producing favorable lipid changes in healthy volunteers in two separate, phase 1 studies.
These findings, coupled with promising observational data from people who carry loss-of-function mutations in the gene for this protein, angiopoietin-like 3 (ANGPTL3), have raised hopes that interventions that interfere with the function of the ANGPTL3 protein may provide new and effective ways to improve lipid levels and cut the incidence of cardiovascular disease events.
“There is now a growing body of epidemiologic, genetic, and genomewide association studies supporting the hypothesis that lowering levels of ANGPTL3 in plasma by inhibiting hepatic ANGPTL3 synthesis will be beneficial in terms of reducing plasma levels of atherogenic apolipoprotein B and in improving metabolic measures associated with dyslipidemia,” wrote Mark J. Graham and his associates in a recently published article (N Engl J Med. 2017 Jul 20;377[3]:222-32).
The phase 1 study results reported by this group came from 44 healthy adults aged 18-65 years who received varying doses of a commercially developed antisense drug, ANGPTL3-LRX, as either single or serial subcutaneous injections. ANGPTL3-LRX is an oligonucleotide designed to inhibit production of messenger RNA for the ANGPTL3 protein.
Six people received the highest ANGPTL3-LRX dosage administered, 60 mg given as a weekly injection for 6 weeks, and after this regimen they showed an average 50% cut in triglycerides levels, compared with baseline, and an average 33% drop in their low LDL cholesterol levels from baseline. None of the 33 people treated with ANGPTL3-LRX in the trial had a documented serious adverse event, and the only treatment dropout was a patient who was lost to follow-up during the treatment phase, reported Mr. Graham, a researcher at Ionis Pharmaceuticals, the sponsor of the study and the company developing the antisense drug, and his associates.
The second phase 1 study examined a different way to block ANGPTL3 activity, with a human monoclonal antibody to this protein. The study involved 83 healthy adults aged 18-65 years with fasting triglyceride levels of 150-450 mg/dL and fasting LDL cholesterol levels of at least 100 mg/dL. Each participant received a single subcutaneous injection or intravenous dose of the antibody, evinacumab, at varying amounts or placebo. The maximum observed lipid changes seen was a drop in triglycerides of 76% and a fall in LDL cholesterol by 23%. Treatment also produced a maximum drop in HDL cholesterol of 18%. No person left the study because of an adverse event. The most common adverse event was headache, in seven people (11% of evinacumab recipients), reported Frederick E. Dewey, MD, a researcher at Regeneron Pharmaceuticals, the company developing evinacumab, and his associates (N Engl J Med. 2017 Jul 20;377[3]:211-21).
The Regeneron report also included results from population studies they ran. They reported performing genome sequencing on specimens from 58,335 adults enrolled in the DiscovEHR study, and identified 13 distinct loss-of-function variants in the ANGPTL3 genes that occurred individually in a small number of these people.
They then ran analyses of lipid levels and coronary artery disease prevalence rates in people who carry one of these 13 loss-of-function genetic signatures in one of their ANGTPL3 genes. Among 45,226 of the people in DiscovEHR those with a variant had on average a 27% lower triglyceride level, a 9% lower LDL cholesterol level, and a 4% lower HDL cholesterol level than noncarriers, after adjustment for covariates. Analysis of coronary artery disease prevalence showed that, after adjusting for age, sex, and ancestry, carrying a loss-of-function variant was linked with a statistically significant 41% lower prevalence of all coronary artery disease, and a 34% lower prevalence of myocardial infarction that fell short of statistical significance.
A second population study looked at links between loss-of-function variants and coronary artery disease in more than 130,000 Danish people. This showed a nonsignificant 37% lower prevalence of coronary artery disease in people with a variant. Two different types of meta-analyses of the data from both the DiscovEHR and Danish studies showed coronary disease rates reduced by either 31% or 39% in variant carriers depending on which meta-analysis approach the researchers used, both statistically significant reductions.
[email protected]
On Twitter @mitchelzoler
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Serial doses of the antisense oligonucleotide ANGPTL3-LRX produced an average 50% cut in triglycerides and 33% cut in LDL cholesterol.
Data source: The ANGPTL3-LRX phase 1 trial enrolled 44 healthy adults. The evinacumab phase 1 trial enrolled 83 healthy adults.
Disclosures: The ANGPTL3-LRX study was funded by Ionis. Mr. Graham is an employee of Ionis. The evinacumab study was funded by Regeneron. Dr. Dewey is an employee of Regeneron.
Cord Blood and Cord Tissue Preservation Information for Your Patients
Your patients may be overwhelmed with so many decisions as they prepare for their newborn to arrive. We want to help make one decision easier. The Cord Blood and Cord Tissue Preservation Patient Handout provides simple and clear education about their cord blood and cord tissue preservation options.
Access and print the handout now and give it to your patients so they can review the information at their own pace.
Your patients may be overwhelmed with so many decisions as they prepare for their newborn to arrive. We want to help make one decision easier. The Cord Blood and Cord Tissue Preservation Patient Handout provides simple and clear education about their cord blood and cord tissue preservation options.
Access and print the handout now and give it to your patients so they can review the information at their own pace.
Your patients may be overwhelmed with so many decisions as they prepare for their newborn to arrive. We want to help make one decision easier. The Cord Blood and Cord Tissue Preservation Patient Handout provides simple and clear education about their cord blood and cord tissue preservation options.
Access and print the handout now and give it to your patients so they can review the information at their own pace.
