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Doug Brunk is a San Diego-based award-winning reporter who began covering health care in 1991. Before joining the company, he wrote for the health sciences division of Columbia University and was an associate editor at Contemporary Long Term Care magazine when it won a Jesse H. Neal Award. His work has been syndicated by the Los Angeles Times and he is the author of two books related to the University of Kentucky Wildcats men's basketball program. Doug has a master’s degree in magazine journalism from the S.I. Newhouse School of Public Communications at Syracuse University. Follow him on Twitter @dougbrunk.
Carboxytherapy caused small yet transient subcutaneous fat reduction
DALLAS – , a small randomized, controlled trial demonstrated.
“Carboxytherapy has been previously used therapeutically to reduce fat, and studies of carboxytherapy have been done in the past as well,” the study’s senior author, Murad Alam, MD, said in an interview in advance of a poster session at the annual conference of the American Society for Laser Medicine and Surgery Inc. “However, earlier studies have not been controlled trials.”
For the split-body study, he and his associates enrolled 16 adults and randomized one side of their body to receive infusions of 1,000 cc of CO2 every week for 5 weeks in the flank region, while the contralateral side received sham treatments. Outcomes of interest included fat layer thickness using a diagnostic ultrasound, total circumference, and body weight, said Dr. Alam, vice-chair of the department of dermatology and chief of the division of cutaneous and aesthetic surgery at Northwestern University, Chicago. He reported that a significant difference in fat thickness was observed in the carboxytherapy-treated side 1 week after the last treatment (P = .011), but this difference was not maintained at 28 weeks as measured by diagnostic ultrasound. Total circumference decreased nominally but not significantly. Body weights did not significantly change throughout the study.
Dr. Alam acknowledged that the study’s small sample size is a limitation. “We do think we did enough treatments, five per side, to obtain an effect if one were to be seen,” he said. The researchers reported having no financial disclosures.
DALLAS – , a small randomized, controlled trial demonstrated.
“Carboxytherapy has been previously used therapeutically to reduce fat, and studies of carboxytherapy have been done in the past as well,” the study’s senior author, Murad Alam, MD, said in an interview in advance of a poster session at the annual conference of the American Society for Laser Medicine and Surgery Inc. “However, earlier studies have not been controlled trials.”
For the split-body study, he and his associates enrolled 16 adults and randomized one side of their body to receive infusions of 1,000 cc of CO2 every week for 5 weeks in the flank region, while the contralateral side received sham treatments. Outcomes of interest included fat layer thickness using a diagnostic ultrasound, total circumference, and body weight, said Dr. Alam, vice-chair of the department of dermatology and chief of the division of cutaneous and aesthetic surgery at Northwestern University, Chicago. He reported that a significant difference in fat thickness was observed in the carboxytherapy-treated side 1 week after the last treatment (P = .011), but this difference was not maintained at 28 weeks as measured by diagnostic ultrasound. Total circumference decreased nominally but not significantly. Body weights did not significantly change throughout the study.
Dr. Alam acknowledged that the study’s small sample size is a limitation. “We do think we did enough treatments, five per side, to obtain an effect if one were to be seen,” he said. The researchers reported having no financial disclosures.
DALLAS – , a small randomized, controlled trial demonstrated.
“Carboxytherapy has been previously used therapeutically to reduce fat, and studies of carboxytherapy have been done in the past as well,” the study’s senior author, Murad Alam, MD, said in an interview in advance of a poster session at the annual conference of the American Society for Laser Medicine and Surgery Inc. “However, earlier studies have not been controlled trials.”
For the split-body study, he and his associates enrolled 16 adults and randomized one side of their body to receive infusions of 1,000 cc of CO2 every week for 5 weeks in the flank region, while the contralateral side received sham treatments. Outcomes of interest included fat layer thickness using a diagnostic ultrasound, total circumference, and body weight, said Dr. Alam, vice-chair of the department of dermatology and chief of the division of cutaneous and aesthetic surgery at Northwestern University, Chicago. He reported that a significant difference in fat thickness was observed in the carboxytherapy-treated side 1 week after the last treatment (P = .011), but this difference was not maintained at 28 weeks as measured by diagnostic ultrasound. Total circumference decreased nominally but not significantly. Body weights did not significantly change throughout the study.
Dr. Alam acknowledged that the study’s small sample size is a limitation. “We do think we did enough treatments, five per side, to obtain an effect if one were to be seen,” he said. The researchers reported having no financial disclosures.
REPORTING FROM ASLMS 2018
Key clinical point: Carboxytherapy yielded a modest reduction in fat that went away after a few months.
Major finding: A significant difference in fat thickness was observed in the carboxytherapy-treated flank region 1 week after the last treatment (P = .011).
Study details: A randomized, split-body study of 16 adults.
Disclosures: Dr. Alam reported having no financial disclosures.
The ‘holy grail’ of thrombosis prevention
SAN DIEGO – The “holy grail” of thrombosis prevention is the ability to determine the risk of recurrence with or without continuation of anticoagulant treatment, according to Philip S. Wells, MD.
“Very little data exists for the comparison of active treatment to placebo in the acute and long-term phases of treatment,” he said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “With low molecular weight heparin, vitamin K antagonists, and direct-acting oral anticoagulants, the relative risk reduction is about 90% in the acute phase and 80%-85% in the extended phase. After discontinuing anticoagulants, the absolute risk of recurrence varies depending on VTE category.”
Dr. Wells, chair and chief of the department of medicine at The Ottawa Hospital and the University of Ottawa, said that after 3 months of anticoagulation the chance of recurrence in postsurgical VTE patients is less than 1% per year. After 3 months of anticoagulant use in nonsurgical patients with provoked risk factors, it is around 4%. This includes medical patients, trauma victims, pregnant women, and patients wearing a plaster cast.
In patients who survive an unprovoked VTE, after 3-6 months of anticoagulant therapy their overall recurrence risk is 10% in the first year and 30% after 5 years. The risk of recurrence is 50% higher if a patient experiences a second unprovoked VTE, and the risk of fatality is 50% higher if the initial event was a pulmonary embolism (PE), he said.
According to the ongoing prospective Austrian Study on Recurrent Venous Thromboembolism, the risk of recurrent VTE is 20% in men and 6% in women (N Engl J Med. 2004 Jun 17;350[25]:2558-63). A multicenter prospective study in Canada yielded similar results. It found that the risk of recurrent VTE is 19% in men versus 9% in women (CMAJ 2008;179[5]:417-26).
That Canadian prospective study, led by Marc Rodger, MD, described the development of the HERDOO2 clinical decision rule for determining a patient’s risk for a recurrent VTE. This includes hyperpigmentation, edema, or redness in either leg (signs of postthrombotic syndrome), D-dimer level of 250 mcg/L or greater while on warfarin, body mass index of 30 kg/m2 or greater, and age of 65 years or older.
If patients have zero or one risk factor, the annual risk of VTE after 6 months of treatment is 1.6%, while two or more risk factors bumps the annual risk of VTE to 14.1%, according to the researchers.
In a subsequent study to validate the HERDOO2, researchers found that the risk of recurrent major VTE was 3.0% in low-risk women who discontinued oral anticoagulants (OACs), 8.1% in high-risk women and men who discontinued OACs, 1.6% in high-risk women and men who continued OACs, and 7.4% in high-risk women who discontinued OACs (BMJ 2017;356:j1065).
“I think the HERDOO2 rule is working pretty well to determine a low-risk group of women, and it’s not an unreasonable tool to be using,” Dr. Wells said.
Other variables that might help clinicians predict a patient’s VTE recurrence include the presence of recurrent venous obstruction (adjusted HR 1.32), and older age (HR 1.01 for every 1 year increase).
D-dimer levels can also be helpful. “If the serial D-dimers are positive, stay on anticoagulants,” Dr. Wells advised. “If they’re negative, discontinue anticoagulants and have the D-dimer levels repeated monthly for 3 months. If positive or positive conversions, return to OAC therapy.”
In one study, the annual risk of a VTE was 3% in the negative D-dimer patients, compared with 6.1% in those who had a history of an unprovoked VTE (Blood 2014;124:196-203).
In a separate study of 319 patients with two negative D-dimer results who did not restart anticoagulation therapy, the rate of recurrent VTE was 6.7% per patient-year (Ann Intern Med 2015;162:27-34). It was 9.7% per patient-year in men, compared with 5.4% per patient-year in women.
Dr. Wells emphasized the importance of shared decision-making with the patient when devising a strategy for long-term anticoagulation following a VTE. “We don’t have a lot of good tools, but [trying to elicit] patient preference is the right thing to try and do,” he said. “Physicians should present an unbiased perspective to patients regarding their treatment, including the benefits and harms, effect on quality of life, and cost.”
Dr. Wells also shared his current clinical approach. In women with an unprovoked VTE, he applies the HERDOO2 rule. If there’s a low recurrence risk, he discontinues the anticoagulant. If there’s a non-low recurrence risk he continues with the anticoagulant unless there’s a high risk for bleeding. Men with an unprovoked VTE receive indefinite anticoagulant therapy, but if the index event is a deep vein thrombosis (DVT), Dr. Wells applies a bleeding risk tool to help him determine management going forward. If the patient has a high risk of bleeding, he does not use an anticoagulant.
“If there is a high risk of bleeding it’s best of stay off anticoagulant therapy,” he said. “If there is an intermediate risk of bleeding and the index event was a DVT, the patient could stay off anticoagulants. I think we have a long way to go to developing tools that actually enable us to reach these points with each patient in discussions we have with them about continuing anticoagulants.”
Dr. Wells reported having received research support from BMS/Pfizer and honoraria from Bayer AG, Janssen, Pfizer, and Daiichi Sankyo. He is a member of the scientific advisory board for Bayer AG and Pfizer.
SAN DIEGO – The “holy grail” of thrombosis prevention is the ability to determine the risk of recurrence with or without continuation of anticoagulant treatment, according to Philip S. Wells, MD.
“Very little data exists for the comparison of active treatment to placebo in the acute and long-term phases of treatment,” he said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “With low molecular weight heparin, vitamin K antagonists, and direct-acting oral anticoagulants, the relative risk reduction is about 90% in the acute phase and 80%-85% in the extended phase. After discontinuing anticoagulants, the absolute risk of recurrence varies depending on VTE category.”
Dr. Wells, chair and chief of the department of medicine at The Ottawa Hospital and the University of Ottawa, said that after 3 months of anticoagulation the chance of recurrence in postsurgical VTE patients is less than 1% per year. After 3 months of anticoagulant use in nonsurgical patients with provoked risk factors, it is around 4%. This includes medical patients, trauma victims, pregnant women, and patients wearing a plaster cast.
In patients who survive an unprovoked VTE, after 3-6 months of anticoagulant therapy their overall recurrence risk is 10% in the first year and 30% after 5 years. The risk of recurrence is 50% higher if a patient experiences a second unprovoked VTE, and the risk of fatality is 50% higher if the initial event was a pulmonary embolism (PE), he said.
According to the ongoing prospective Austrian Study on Recurrent Venous Thromboembolism, the risk of recurrent VTE is 20% in men and 6% in women (N Engl J Med. 2004 Jun 17;350[25]:2558-63). A multicenter prospective study in Canada yielded similar results. It found that the risk of recurrent VTE is 19% in men versus 9% in women (CMAJ 2008;179[5]:417-26).
That Canadian prospective study, led by Marc Rodger, MD, described the development of the HERDOO2 clinical decision rule for determining a patient’s risk for a recurrent VTE. This includes hyperpigmentation, edema, or redness in either leg (signs of postthrombotic syndrome), D-dimer level of 250 mcg/L or greater while on warfarin, body mass index of 30 kg/m2 or greater, and age of 65 years or older.
If patients have zero or one risk factor, the annual risk of VTE after 6 months of treatment is 1.6%, while two or more risk factors bumps the annual risk of VTE to 14.1%, according to the researchers.
In a subsequent study to validate the HERDOO2, researchers found that the risk of recurrent major VTE was 3.0% in low-risk women who discontinued oral anticoagulants (OACs), 8.1% in high-risk women and men who discontinued OACs, 1.6% in high-risk women and men who continued OACs, and 7.4% in high-risk women who discontinued OACs (BMJ 2017;356:j1065).
“I think the HERDOO2 rule is working pretty well to determine a low-risk group of women, and it’s not an unreasonable tool to be using,” Dr. Wells said.
Other variables that might help clinicians predict a patient’s VTE recurrence include the presence of recurrent venous obstruction (adjusted HR 1.32), and older age (HR 1.01 for every 1 year increase).
D-dimer levels can also be helpful. “If the serial D-dimers are positive, stay on anticoagulants,” Dr. Wells advised. “If they’re negative, discontinue anticoagulants and have the D-dimer levels repeated monthly for 3 months. If positive or positive conversions, return to OAC therapy.”
In one study, the annual risk of a VTE was 3% in the negative D-dimer patients, compared with 6.1% in those who had a history of an unprovoked VTE (Blood 2014;124:196-203).
In a separate study of 319 patients with two negative D-dimer results who did not restart anticoagulation therapy, the rate of recurrent VTE was 6.7% per patient-year (Ann Intern Med 2015;162:27-34). It was 9.7% per patient-year in men, compared with 5.4% per patient-year in women.
Dr. Wells emphasized the importance of shared decision-making with the patient when devising a strategy for long-term anticoagulation following a VTE. “We don’t have a lot of good tools, but [trying to elicit] patient preference is the right thing to try and do,” he said. “Physicians should present an unbiased perspective to patients regarding their treatment, including the benefits and harms, effect on quality of life, and cost.”
Dr. Wells also shared his current clinical approach. In women with an unprovoked VTE, he applies the HERDOO2 rule. If there’s a low recurrence risk, he discontinues the anticoagulant. If there’s a non-low recurrence risk he continues with the anticoagulant unless there’s a high risk for bleeding. Men with an unprovoked VTE receive indefinite anticoagulant therapy, but if the index event is a deep vein thrombosis (DVT), Dr. Wells applies a bleeding risk tool to help him determine management going forward. If the patient has a high risk of bleeding, he does not use an anticoagulant.
“If there is a high risk of bleeding it’s best of stay off anticoagulant therapy,” he said. “If there is an intermediate risk of bleeding and the index event was a DVT, the patient could stay off anticoagulants. I think we have a long way to go to developing tools that actually enable us to reach these points with each patient in discussions we have with them about continuing anticoagulants.”
Dr. Wells reported having received research support from BMS/Pfizer and honoraria from Bayer AG, Janssen, Pfizer, and Daiichi Sankyo. He is a member of the scientific advisory board for Bayer AG and Pfizer.
SAN DIEGO – The “holy grail” of thrombosis prevention is the ability to determine the risk of recurrence with or without continuation of anticoagulant treatment, according to Philip S. Wells, MD.
“Very little data exists for the comparison of active treatment to placebo in the acute and long-term phases of treatment,” he said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “With low molecular weight heparin, vitamin K antagonists, and direct-acting oral anticoagulants, the relative risk reduction is about 90% in the acute phase and 80%-85% in the extended phase. After discontinuing anticoagulants, the absolute risk of recurrence varies depending on VTE category.”
Dr. Wells, chair and chief of the department of medicine at The Ottawa Hospital and the University of Ottawa, said that after 3 months of anticoagulation the chance of recurrence in postsurgical VTE patients is less than 1% per year. After 3 months of anticoagulant use in nonsurgical patients with provoked risk factors, it is around 4%. This includes medical patients, trauma victims, pregnant women, and patients wearing a plaster cast.
In patients who survive an unprovoked VTE, after 3-6 months of anticoagulant therapy their overall recurrence risk is 10% in the first year and 30% after 5 years. The risk of recurrence is 50% higher if a patient experiences a second unprovoked VTE, and the risk of fatality is 50% higher if the initial event was a pulmonary embolism (PE), he said.
According to the ongoing prospective Austrian Study on Recurrent Venous Thromboembolism, the risk of recurrent VTE is 20% in men and 6% in women (N Engl J Med. 2004 Jun 17;350[25]:2558-63). A multicenter prospective study in Canada yielded similar results. It found that the risk of recurrent VTE is 19% in men versus 9% in women (CMAJ 2008;179[5]:417-26).
That Canadian prospective study, led by Marc Rodger, MD, described the development of the HERDOO2 clinical decision rule for determining a patient’s risk for a recurrent VTE. This includes hyperpigmentation, edema, or redness in either leg (signs of postthrombotic syndrome), D-dimer level of 250 mcg/L or greater while on warfarin, body mass index of 30 kg/m2 or greater, and age of 65 years or older.
If patients have zero or one risk factor, the annual risk of VTE after 6 months of treatment is 1.6%, while two or more risk factors bumps the annual risk of VTE to 14.1%, according to the researchers.
In a subsequent study to validate the HERDOO2, researchers found that the risk of recurrent major VTE was 3.0% in low-risk women who discontinued oral anticoagulants (OACs), 8.1% in high-risk women and men who discontinued OACs, 1.6% in high-risk women and men who continued OACs, and 7.4% in high-risk women who discontinued OACs (BMJ 2017;356:j1065).
“I think the HERDOO2 rule is working pretty well to determine a low-risk group of women, and it’s not an unreasonable tool to be using,” Dr. Wells said.
Other variables that might help clinicians predict a patient’s VTE recurrence include the presence of recurrent venous obstruction (adjusted HR 1.32), and older age (HR 1.01 for every 1 year increase).
D-dimer levels can also be helpful. “If the serial D-dimers are positive, stay on anticoagulants,” Dr. Wells advised. “If they’re negative, discontinue anticoagulants and have the D-dimer levels repeated monthly for 3 months. If positive or positive conversions, return to OAC therapy.”
In one study, the annual risk of a VTE was 3% in the negative D-dimer patients, compared with 6.1% in those who had a history of an unprovoked VTE (Blood 2014;124:196-203).
In a separate study of 319 patients with two negative D-dimer results who did not restart anticoagulation therapy, the rate of recurrent VTE was 6.7% per patient-year (Ann Intern Med 2015;162:27-34). It was 9.7% per patient-year in men, compared with 5.4% per patient-year in women.
Dr. Wells emphasized the importance of shared decision-making with the patient when devising a strategy for long-term anticoagulation following a VTE. “We don’t have a lot of good tools, but [trying to elicit] patient preference is the right thing to try and do,” he said. “Physicians should present an unbiased perspective to patients regarding their treatment, including the benefits and harms, effect on quality of life, and cost.”
Dr. Wells also shared his current clinical approach. In women with an unprovoked VTE, he applies the HERDOO2 rule. If there’s a low recurrence risk, he discontinues the anticoagulant. If there’s a non-low recurrence risk he continues with the anticoagulant unless there’s a high risk for bleeding. Men with an unprovoked VTE receive indefinite anticoagulant therapy, but if the index event is a deep vein thrombosis (DVT), Dr. Wells applies a bleeding risk tool to help him determine management going forward. If the patient has a high risk of bleeding, he does not use an anticoagulant.
“If there is a high risk of bleeding it’s best of stay off anticoagulant therapy,” he said. “If there is an intermediate risk of bleeding and the index event was a DVT, the patient could stay off anticoagulants. I think we have a long way to go to developing tools that actually enable us to reach these points with each patient in discussions we have with them about continuing anticoagulants.”
Dr. Wells reported having received research support from BMS/Pfizer and honoraria from Bayer AG, Janssen, Pfizer, and Daiichi Sankyo. He is a member of the scientific advisory board for Bayer AG and Pfizer.
EXPERT ANALYSIS FROM THSNA 2018
Liability claims from cutaneous laser surgery continue to rise
DALLAS – , and the average indemnity claim is close to $320,000, results from an analysis of national data have shown.
“Physicians seeking to undertake laser surgery in their practice should ensure they have proper training in the physics, safety, and techniques of each procedure,” study author Saami Khalifian, MD, said in an interview in advance of the annual meeting of the American Society for Laser Medicine and Surgery. “Legal precedent has demonstrated that nonphysicians performing laser surgery will likely be held to a standard of care and training corresponding to a physician with appropriate training. Therefore, physicians who delegate laser operations to their nonphysician agents are ultimately responsible for the actions of their agents.”
For the period between June 2012 and December 2017, Dr. Khalifian and his colleagues identified 32 cases with public decision related to injury secondary to cutaneous laser surgery. The incidence of litigation related to laser surgery demonstrates an increasing trend since 1985, with peak occurrence in 2010 (total of 22 cases, which represents 10.7% of 206 cases reported in the entire data set since 1985). Laser hair removal was the most common litigated procedure prior to 2012, but since then has been surpassed by laser rejuvenation, which includes ablative and nonablative resurfacing, fractionated lasers, and intense pulsed light (47% of cases since mid-2012). Nonphysician operators accounted for a substantial subset of these cases (66% of all cases since mid-2012), with their physician supervisors named as defendants, despite not performing the procedure.
Dr. Khalifian noted that medical spas in the study “uniformly had unsupervised nonphysician operators in nonmedical office settings,” and therefore “had one of the highest litigation rates and number of cases. What is interesting about this, however, is that medical spas that are run by nonphysicians are also less likely to have medical liability insurance to satisfy a potential malpractice claim and therefore would be less likely to be pursued by a plaintiff’s attorney. Despite this, they had one of the highest patient injury rates, which is likely underrepresented based on the lack of malpractice insurance to be pursued in a legal claim.”
The researchers also found that delegated procedures were most frequently litigated against regardless of subspecialty of supervising physician (66%). Of the preventable causes of action, the most common was failure to obtain an informed consent (34%) and negligence (50%). Of the 32 cases with public decisions, 17 (53.1%) resulted in decisions in favor of the plaintiff. The mean indemnity payment was $318,832.
“Our current work evaluating data from 2012-2017 is consistent with our prior work dating back to 1985 and demonstrates again that nonphysician operators account for the majority of cases of legal action,” Dr. Khalifian said. “In fact, there is an increasing trend since about 2008 for a higher proportion of cases being performed by physician extenders and nonphysician operators. Despite physicians acting as supervisors and not the actual laser operator they are nonetheless named as defendants in legal claims,” he added.
The data on allegations and causes of legal action “should serve as a guide to help improve patient safety and decrease professional liability,” he pointed out. “It is critical that physicians take steps to mitigate risk to patients by ensuring robust and adequate training for their agents and by directly supervising procedures. However, the data clearly show that the safest treatments are performed directly by physicians who have had such dedicated training in laser and light sources.”
Dr. Khalifian acknowledged certain limitations of the study, including the fact that the data were extracted from only one legal database and did not include cases settled outside of the justice system through third-party arbitration or other means. “It is also limited by search terms in our query,” he said. “It is possible that some cases did not include the terms we used. Finally, only incomplete information was available for some cases even when supplemented through other resources and additional research.”
He reported having no financial disclosures. Study coauthor Mathew M. Avram, MD, JD, serves on the medical advisory board of Sciton and on the scientific advisory boards of Sienna Biopharmaceuticals, Cytrellis, and Allergan. He is also consultant for Merz Aesthetics, Allergan, Soliton, Invasix, and Revance, and has intellectual property with Cytrellis. He also holds stock options with Cytrellis, Invasix, and Zalea.
SOURCE: Khalifian et al. ASLMS 2018.
DALLAS – , and the average indemnity claim is close to $320,000, results from an analysis of national data have shown.
“Physicians seeking to undertake laser surgery in their practice should ensure they have proper training in the physics, safety, and techniques of each procedure,” study author Saami Khalifian, MD, said in an interview in advance of the annual meeting of the American Society for Laser Medicine and Surgery. “Legal precedent has demonstrated that nonphysicians performing laser surgery will likely be held to a standard of care and training corresponding to a physician with appropriate training. Therefore, physicians who delegate laser operations to their nonphysician agents are ultimately responsible for the actions of their agents.”
For the period between June 2012 and December 2017, Dr. Khalifian and his colleagues identified 32 cases with public decision related to injury secondary to cutaneous laser surgery. The incidence of litigation related to laser surgery demonstrates an increasing trend since 1985, with peak occurrence in 2010 (total of 22 cases, which represents 10.7% of 206 cases reported in the entire data set since 1985). Laser hair removal was the most common litigated procedure prior to 2012, but since then has been surpassed by laser rejuvenation, which includes ablative and nonablative resurfacing, fractionated lasers, and intense pulsed light (47% of cases since mid-2012). Nonphysician operators accounted for a substantial subset of these cases (66% of all cases since mid-2012), with their physician supervisors named as defendants, despite not performing the procedure.
Dr. Khalifian noted that medical spas in the study “uniformly had unsupervised nonphysician operators in nonmedical office settings,” and therefore “had one of the highest litigation rates and number of cases. What is interesting about this, however, is that medical spas that are run by nonphysicians are also less likely to have medical liability insurance to satisfy a potential malpractice claim and therefore would be less likely to be pursued by a plaintiff’s attorney. Despite this, they had one of the highest patient injury rates, which is likely underrepresented based on the lack of malpractice insurance to be pursued in a legal claim.”
The researchers also found that delegated procedures were most frequently litigated against regardless of subspecialty of supervising physician (66%). Of the preventable causes of action, the most common was failure to obtain an informed consent (34%) and negligence (50%). Of the 32 cases with public decisions, 17 (53.1%) resulted in decisions in favor of the plaintiff. The mean indemnity payment was $318,832.
“Our current work evaluating data from 2012-2017 is consistent with our prior work dating back to 1985 and demonstrates again that nonphysician operators account for the majority of cases of legal action,” Dr. Khalifian said. “In fact, there is an increasing trend since about 2008 for a higher proportion of cases being performed by physician extenders and nonphysician operators. Despite physicians acting as supervisors and not the actual laser operator they are nonetheless named as defendants in legal claims,” he added.
The data on allegations and causes of legal action “should serve as a guide to help improve patient safety and decrease professional liability,” he pointed out. “It is critical that physicians take steps to mitigate risk to patients by ensuring robust and adequate training for their agents and by directly supervising procedures. However, the data clearly show that the safest treatments are performed directly by physicians who have had such dedicated training in laser and light sources.”
Dr. Khalifian acknowledged certain limitations of the study, including the fact that the data were extracted from only one legal database and did not include cases settled outside of the justice system through third-party arbitration or other means. “It is also limited by search terms in our query,” he said. “It is possible that some cases did not include the terms we used. Finally, only incomplete information was available for some cases even when supplemented through other resources and additional research.”
He reported having no financial disclosures. Study coauthor Mathew M. Avram, MD, JD, serves on the medical advisory board of Sciton and on the scientific advisory boards of Sienna Biopharmaceuticals, Cytrellis, and Allergan. He is also consultant for Merz Aesthetics, Allergan, Soliton, Invasix, and Revance, and has intellectual property with Cytrellis. He also holds stock options with Cytrellis, Invasix, and Zalea.
SOURCE: Khalifian et al. ASLMS 2018.
DALLAS – , and the average indemnity claim is close to $320,000, results from an analysis of national data have shown.
“Physicians seeking to undertake laser surgery in their practice should ensure they have proper training in the physics, safety, and techniques of each procedure,” study author Saami Khalifian, MD, said in an interview in advance of the annual meeting of the American Society for Laser Medicine and Surgery. “Legal precedent has demonstrated that nonphysicians performing laser surgery will likely be held to a standard of care and training corresponding to a physician with appropriate training. Therefore, physicians who delegate laser operations to their nonphysician agents are ultimately responsible for the actions of their agents.”
For the period between June 2012 and December 2017, Dr. Khalifian and his colleagues identified 32 cases with public decision related to injury secondary to cutaneous laser surgery. The incidence of litigation related to laser surgery demonstrates an increasing trend since 1985, with peak occurrence in 2010 (total of 22 cases, which represents 10.7% of 206 cases reported in the entire data set since 1985). Laser hair removal was the most common litigated procedure prior to 2012, but since then has been surpassed by laser rejuvenation, which includes ablative and nonablative resurfacing, fractionated lasers, and intense pulsed light (47% of cases since mid-2012). Nonphysician operators accounted for a substantial subset of these cases (66% of all cases since mid-2012), with their physician supervisors named as defendants, despite not performing the procedure.
Dr. Khalifian noted that medical spas in the study “uniformly had unsupervised nonphysician operators in nonmedical office settings,” and therefore “had one of the highest litigation rates and number of cases. What is interesting about this, however, is that medical spas that are run by nonphysicians are also less likely to have medical liability insurance to satisfy a potential malpractice claim and therefore would be less likely to be pursued by a plaintiff’s attorney. Despite this, they had one of the highest patient injury rates, which is likely underrepresented based on the lack of malpractice insurance to be pursued in a legal claim.”
The researchers also found that delegated procedures were most frequently litigated against regardless of subspecialty of supervising physician (66%). Of the preventable causes of action, the most common was failure to obtain an informed consent (34%) and negligence (50%). Of the 32 cases with public decisions, 17 (53.1%) resulted in decisions in favor of the plaintiff. The mean indemnity payment was $318,832.
“Our current work evaluating data from 2012-2017 is consistent with our prior work dating back to 1985 and demonstrates again that nonphysician operators account for the majority of cases of legal action,” Dr. Khalifian said. “In fact, there is an increasing trend since about 2008 for a higher proportion of cases being performed by physician extenders and nonphysician operators. Despite physicians acting as supervisors and not the actual laser operator they are nonetheless named as defendants in legal claims,” he added.
The data on allegations and causes of legal action “should serve as a guide to help improve patient safety and decrease professional liability,” he pointed out. “It is critical that physicians take steps to mitigate risk to patients by ensuring robust and adequate training for their agents and by directly supervising procedures. However, the data clearly show that the safest treatments are performed directly by physicians who have had such dedicated training in laser and light sources.”
Dr. Khalifian acknowledged certain limitations of the study, including the fact that the data were extracted from only one legal database and did not include cases settled outside of the justice system through third-party arbitration or other means. “It is also limited by search terms in our query,” he said. “It is possible that some cases did not include the terms we used. Finally, only incomplete information was available for some cases even when supplemented through other resources and additional research.”
He reported having no financial disclosures. Study coauthor Mathew M. Avram, MD, JD, serves on the medical advisory board of Sciton and on the scientific advisory boards of Sienna Biopharmaceuticals, Cytrellis, and Allergan. He is also consultant for Merz Aesthetics, Allergan, Soliton, Invasix, and Revance, and has intellectual property with Cytrellis. He also holds stock options with Cytrellis, Invasix, and Zalea.
SOURCE: Khalifian et al. ASLMS 2018.
REPORTING FROM ASLMS 2018
Key clinical point: Claims related to cutaneous laser surgery are steadily increasing, as are the average indemnity payments.
Major finding: Among cases with public decision related to injury secondary to cutaneous laser surgery, nearly half since mid-2012 (47%) have been due to laser rejuvenation.
Study details: An analysis of 32 medical professional liability claims related to cutaneous laser surgery June 2012 through December 2017.
Disclosures: Dr. Khalifian reported having no financial disclosures. Study coauthor Mathew Avram, MD, serves on the medical advisory board of Sciton and on the scientific advisory boards of Sienna Biopharmaceuticals, Cytrellis, and Allergan. He is also consultant for Merz Aesthetics, Allergan, Soliton, Invasix, and Revance, and has intellectual property with Cytrellis. He also holds stock options with Cytrellis, Invasix, and Zalea.
Source: Khalifian et al. ASLMS 2018.
The outcomes of “GOLD 2017”
After the Global Initiative for Chronic Obstructive Lung Disease released updated recommendations for grading COPD patients’ level of disease in November of 2016, Imran Iftikhar, MD, tried to incorporate them into his practice, but he encountered problems.
For one thing, the new classification system, which became known as GOLD 2017, uncoupled spirometry results from the ABCD treatment algorithm. “I found it wasn’t really helping me in terms of prognostication or COPD management,” said Dr. Iftikhar, section chief of pulmonary and critical care at Emory Saint Joseph’s Hospital, Atlanta. “Although the purpose of the GOLD classification was not really meant for prognostication, most practicing physicians are frequently asked about prognosis by patients, and I am not sure if the 2017 reclassification really helps with that.”
The GOLD 2017 classification simplified the chronic obstructive pulmonary disease staging that was available from 2011 to 2015 from three variables (spirometry thresholds, exacerbation risk, and dyspnea scale) to two variables (exacerbation risk and dyspnea scale). In the 2017 report, authors of the new guidelines characterized forced expiratory volume in 1 second (FEV1) as “a poor predictor of disease status” and proposed that clinicians derive ABCD groups exclusively from patient symptoms and their exacerbations. FEV1 is an “important parameter at the population level” in predicting hospitalization and mortality, the authors wrote, but keeping results separate “acknowledges the limitations of FEV1 in making treatment decisions for individualized patient care and highlights the importance of patient symptoms and exacerbation risks in guiding therapies in COPD.”
According to Meilan Han, MD, MS, a member of the GOLD Science Committee, since release of the 2017 guidelines, “clinicians have indicated that they like the flexibility the system provides in separating spirometry, symptoms, and exacerbation risk as this more accurately reflects the heterogeneity we see in the COPD patient population.” Nevertheless, how this approach influences long-term outcomes remains unclear.
Daniel Ouellette, MD, FCCP, a pulmonologist with the Henry Ford Health System in Detroit, described the GOLD 2017 criteria as “a good step forward” but said he wasn’t sure if the optimal or perfect tool exists for categorizing COPD patients’ level of disease.
“I think what we see is an effort to use all of these criteria to help us better treat our patients. I think ,” he said in an interview.
“All guidelines need to be modified as further research becomes available. I think that the frontiers of this area are going to be to incorporate new elements such as tobacco history, more emphasis on clinical signs and symptoms, and use of markers other than spirometry, such as eosinophil count, to categorize patients with COPD,” Dr. Ouellette added.
In an analysis of the GOLD 2017 criteria applied to 819 COPD patients in Spain and the United States, published online Nov. 3, 2017, in the American Journal of Respiratory and Critical Care Medicine, Carlos Cabrera López, MD, and his colleagues concluded that the mortality risk was better predicted by the 2015 GOLD classification system than by the 2017 iteration (Am J Respir Crit Care Med. 2018 Feb. doi: 10.101164/rccm.201707-1363OC).
The distribution of Charlson index scores also changed. Whereas group D was higher than B in 2015, they became similar in the 2017 system. For her part, Dr. Han emphasized that the primary goal of the GOLD ABCD classification system is to categorize patients with respect to treatment groups. “Current therapy targets symptoms and exacerbations, which are the key current elements of the classification schema,” she said in an interview. “The results of the Cabrera Lopez analysis are not necessarily unexpected, as FEV1 is associated with mortality.”
In a prospective, multicenter analysis, Portuguese researchers compared the performance of GOLD 2011 and 2017 in terms of how 200 COPD patients were reclassified, the level of agreement between the two iterations, and the performance of each to predict future exacerbations (COPD. 2018 Feb;15[1]; 21-6). They found that about half of patients classified as GOLD D under the 2011 guidelines became classified as GOLD B when the 2017 version was used, and the extent of agreement between the two iterations was moderate (P less than .001). They also found that the two versions of the guidelines were equivalently effective at predicting exacerbations (69.7% vs. 67.6% in the 2011 and 2017 iterations, respectively). In addition, patients who met the criteria for a GOLD B grouping in the 2017 iteration exacerbated 17% more often and had a lower percent predicted post bronchodilator FEV1 than did those who met the criteria for a GOLD B classification under the 2011 guidelines.
Dr. Han, who is also an associate professor of medicine at the University of Michigan Hospital, acknowledged that GOLD 2017 has resulted in the reclassification of some previously group D patients as group B patients. “Our primary goal is to aid clinicians with the diagnosis and management of patients with COPD,” she said. “We look forward to additional data coming in from ongoing clinical trials that will provide longer term data to further refine treatment algorithms.”
In a recent study of more than 33,000 Danish patients older than age 30 with COPD, researchers led by Anne Gedebjerg, MD, found that the GOLD 2017 ABCD classification did not predict all-cause and respiratory mortality more accurately than previous GOLD iterations from 2007 and 2011. Area under the curve for all-cause mortality was 0.61 for GOLD 2007, 0.61 for GOLD 2011, and 0.63 for GOLD 2017, while the area under the curve for respiratory mortality was 0.64 for GOLD 2007, 0.63 for GOLD 2011, and 0.65 for GOLD 2017 (Lancet Respir Med. 2018 Jan;6[3]:204-12).
However, when the spirometric stages 1-4 were combined with the A to D groupings based on symptoms and exacerbations, the 2017 classification predicted mortality with greater accuracy, compared with previous iterations (P less than .0001). “My practice is very much like this paper,” Dr. Iftikhar said. “I use both the spirometric grade and the ABCD grouping to specify which ‘group’ and ‘grade’ my patient belongs to. I think future investigators need to combine ABCD with spirometry classification to see how we can improve the classification system.”
In a commentary published in the same issue of the Lancet Respiratory Medicine as the large Danish study, Joan B. Soriano, MD, PhD, wrote that the 2011 GOLD guideline’s collapse of four spirometric thresholds (greater than 80%, 50%-80%, 30%-50%, and less than 30%) into just two (greater than 50% or 50% or less) “reduced the system’s ability to inform and predict mortality from the short term up to 10 years” (Lancet Respir Med. 2018 Jan;6[3]:165-6).
Lung function remains the best available biomarker for life expectancy in both patients with COPD and the general population,” wrote Dr. Soriano, a respiratory medicine researcher based in Madrid, Spain.
Additional important outcomes
Dr. Ouellette noted that while mortality is an important outcome for COPD patients, it’s not the only outcome of interest. “In addition to [trying to] help people live longer, which is certainly a desirable goal, we also want to make people be able to be more functional during their life, have fewer hospitalizations, and have less of a need of other types of supportive medical care for worsening of their disease,” he said. “The fact that the current guidelines don’t improve mortality more than the previous ones may not be a negative thing. It may tell us that the previous guidelines already did a pretty good job of helping us to improve mortality.”
Dr. Ouellette was quick to add that none of inhaled drugs currently available to treat COPD have been conclusively shown to improve mortality. “The only things we know that improve mortality for COPD patients are quitting smoking and using oxygen if a patient meets predefined goals for oxygen,” he said. “So the fact that GOLD criteria doesn’t improve mortality shouldn’t make us think that it’s not a useful tool. We already know that the medicines may not help people live longer.”
Dr. Han pointed out that spirometry “is still used to further clarify the choice of therapy recommended based on the nature and degree of airflow obstruction in light of severity of patient symptoms. The data are still designed to be used in conjunction to personalize therapy for patients.”
She added that the GOLD Science Committee “welcomes additional data analyses so that future recommendations can be further refined.”
Dr. Han disclosed that she has consulted for Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline. She has also received in-kind research support from Novartis and Sunovion.
Dr. Iftikhar reported having no financial disclosures. Dr. Ouellette is a member of CHEST® Physician’s editorial advisory board. He disclosed being part of a federally funded study being carried out by the Patient-Centered Outcomes Research Institute.
There was no industry involvement in the GOLD 2017 report, but many of its authors and board members had pharmaceutical company ties, and GOLD’s treatment advice relies on data from industry-sponsored studies.
After the Global Initiative for Chronic Obstructive Lung Disease released updated recommendations for grading COPD patients’ level of disease in November of 2016, Imran Iftikhar, MD, tried to incorporate them into his practice, but he encountered problems.
For one thing, the new classification system, which became known as GOLD 2017, uncoupled spirometry results from the ABCD treatment algorithm. “I found it wasn’t really helping me in terms of prognostication or COPD management,” said Dr. Iftikhar, section chief of pulmonary and critical care at Emory Saint Joseph’s Hospital, Atlanta. “Although the purpose of the GOLD classification was not really meant for prognostication, most practicing physicians are frequently asked about prognosis by patients, and I am not sure if the 2017 reclassification really helps with that.”
The GOLD 2017 classification simplified the chronic obstructive pulmonary disease staging that was available from 2011 to 2015 from three variables (spirometry thresholds, exacerbation risk, and dyspnea scale) to two variables (exacerbation risk and dyspnea scale). In the 2017 report, authors of the new guidelines characterized forced expiratory volume in 1 second (FEV1) as “a poor predictor of disease status” and proposed that clinicians derive ABCD groups exclusively from patient symptoms and their exacerbations. FEV1 is an “important parameter at the population level” in predicting hospitalization and mortality, the authors wrote, but keeping results separate “acknowledges the limitations of FEV1 in making treatment decisions for individualized patient care and highlights the importance of patient symptoms and exacerbation risks in guiding therapies in COPD.”
According to Meilan Han, MD, MS, a member of the GOLD Science Committee, since release of the 2017 guidelines, “clinicians have indicated that they like the flexibility the system provides in separating spirometry, symptoms, and exacerbation risk as this more accurately reflects the heterogeneity we see in the COPD patient population.” Nevertheless, how this approach influences long-term outcomes remains unclear.
Daniel Ouellette, MD, FCCP, a pulmonologist with the Henry Ford Health System in Detroit, described the GOLD 2017 criteria as “a good step forward” but said he wasn’t sure if the optimal or perfect tool exists for categorizing COPD patients’ level of disease.
“I think what we see is an effort to use all of these criteria to help us better treat our patients. I think ,” he said in an interview.
“All guidelines need to be modified as further research becomes available. I think that the frontiers of this area are going to be to incorporate new elements such as tobacco history, more emphasis on clinical signs and symptoms, and use of markers other than spirometry, such as eosinophil count, to categorize patients with COPD,” Dr. Ouellette added.
In an analysis of the GOLD 2017 criteria applied to 819 COPD patients in Spain and the United States, published online Nov. 3, 2017, in the American Journal of Respiratory and Critical Care Medicine, Carlos Cabrera López, MD, and his colleagues concluded that the mortality risk was better predicted by the 2015 GOLD classification system than by the 2017 iteration (Am J Respir Crit Care Med. 2018 Feb. doi: 10.101164/rccm.201707-1363OC).
The distribution of Charlson index scores also changed. Whereas group D was higher than B in 2015, they became similar in the 2017 system. For her part, Dr. Han emphasized that the primary goal of the GOLD ABCD classification system is to categorize patients with respect to treatment groups. “Current therapy targets symptoms and exacerbations, which are the key current elements of the classification schema,” she said in an interview. “The results of the Cabrera Lopez analysis are not necessarily unexpected, as FEV1 is associated with mortality.”
In a prospective, multicenter analysis, Portuguese researchers compared the performance of GOLD 2011 and 2017 in terms of how 200 COPD patients were reclassified, the level of agreement between the two iterations, and the performance of each to predict future exacerbations (COPD. 2018 Feb;15[1]; 21-6). They found that about half of patients classified as GOLD D under the 2011 guidelines became classified as GOLD B when the 2017 version was used, and the extent of agreement between the two iterations was moderate (P less than .001). They also found that the two versions of the guidelines were equivalently effective at predicting exacerbations (69.7% vs. 67.6% in the 2011 and 2017 iterations, respectively). In addition, patients who met the criteria for a GOLD B grouping in the 2017 iteration exacerbated 17% more often and had a lower percent predicted post bronchodilator FEV1 than did those who met the criteria for a GOLD B classification under the 2011 guidelines.
Dr. Han, who is also an associate professor of medicine at the University of Michigan Hospital, acknowledged that GOLD 2017 has resulted in the reclassification of some previously group D patients as group B patients. “Our primary goal is to aid clinicians with the diagnosis and management of patients with COPD,” she said. “We look forward to additional data coming in from ongoing clinical trials that will provide longer term data to further refine treatment algorithms.”
In a recent study of more than 33,000 Danish patients older than age 30 with COPD, researchers led by Anne Gedebjerg, MD, found that the GOLD 2017 ABCD classification did not predict all-cause and respiratory mortality more accurately than previous GOLD iterations from 2007 and 2011. Area under the curve for all-cause mortality was 0.61 for GOLD 2007, 0.61 for GOLD 2011, and 0.63 for GOLD 2017, while the area under the curve for respiratory mortality was 0.64 for GOLD 2007, 0.63 for GOLD 2011, and 0.65 for GOLD 2017 (Lancet Respir Med. 2018 Jan;6[3]:204-12).
However, when the spirometric stages 1-4 were combined with the A to D groupings based on symptoms and exacerbations, the 2017 classification predicted mortality with greater accuracy, compared with previous iterations (P less than .0001). “My practice is very much like this paper,” Dr. Iftikhar said. “I use both the spirometric grade and the ABCD grouping to specify which ‘group’ and ‘grade’ my patient belongs to. I think future investigators need to combine ABCD with spirometry classification to see how we can improve the classification system.”
In a commentary published in the same issue of the Lancet Respiratory Medicine as the large Danish study, Joan B. Soriano, MD, PhD, wrote that the 2011 GOLD guideline’s collapse of four spirometric thresholds (greater than 80%, 50%-80%, 30%-50%, and less than 30%) into just two (greater than 50% or 50% or less) “reduced the system’s ability to inform and predict mortality from the short term up to 10 years” (Lancet Respir Med. 2018 Jan;6[3]:165-6).
Lung function remains the best available biomarker for life expectancy in both patients with COPD and the general population,” wrote Dr. Soriano, a respiratory medicine researcher based in Madrid, Spain.
Additional important outcomes
Dr. Ouellette noted that while mortality is an important outcome for COPD patients, it’s not the only outcome of interest. “In addition to [trying to] help people live longer, which is certainly a desirable goal, we also want to make people be able to be more functional during their life, have fewer hospitalizations, and have less of a need of other types of supportive medical care for worsening of their disease,” he said. “The fact that the current guidelines don’t improve mortality more than the previous ones may not be a negative thing. It may tell us that the previous guidelines already did a pretty good job of helping us to improve mortality.”
Dr. Ouellette was quick to add that none of inhaled drugs currently available to treat COPD have been conclusively shown to improve mortality. “The only things we know that improve mortality for COPD patients are quitting smoking and using oxygen if a patient meets predefined goals for oxygen,” he said. “So the fact that GOLD criteria doesn’t improve mortality shouldn’t make us think that it’s not a useful tool. We already know that the medicines may not help people live longer.”
Dr. Han pointed out that spirometry “is still used to further clarify the choice of therapy recommended based on the nature and degree of airflow obstruction in light of severity of patient symptoms. The data are still designed to be used in conjunction to personalize therapy for patients.”
She added that the GOLD Science Committee “welcomes additional data analyses so that future recommendations can be further refined.”
Dr. Han disclosed that she has consulted for Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline. She has also received in-kind research support from Novartis and Sunovion.
Dr. Iftikhar reported having no financial disclosures. Dr. Ouellette is a member of CHEST® Physician’s editorial advisory board. He disclosed being part of a federally funded study being carried out by the Patient-Centered Outcomes Research Institute.
There was no industry involvement in the GOLD 2017 report, but many of its authors and board members had pharmaceutical company ties, and GOLD’s treatment advice relies on data from industry-sponsored studies.
After the Global Initiative for Chronic Obstructive Lung Disease released updated recommendations for grading COPD patients’ level of disease in November of 2016, Imran Iftikhar, MD, tried to incorporate them into his practice, but he encountered problems.
For one thing, the new classification system, which became known as GOLD 2017, uncoupled spirometry results from the ABCD treatment algorithm. “I found it wasn’t really helping me in terms of prognostication or COPD management,” said Dr. Iftikhar, section chief of pulmonary and critical care at Emory Saint Joseph’s Hospital, Atlanta. “Although the purpose of the GOLD classification was not really meant for prognostication, most practicing physicians are frequently asked about prognosis by patients, and I am not sure if the 2017 reclassification really helps with that.”
The GOLD 2017 classification simplified the chronic obstructive pulmonary disease staging that was available from 2011 to 2015 from three variables (spirometry thresholds, exacerbation risk, and dyspnea scale) to two variables (exacerbation risk and dyspnea scale). In the 2017 report, authors of the new guidelines characterized forced expiratory volume in 1 second (FEV1) as “a poor predictor of disease status” and proposed that clinicians derive ABCD groups exclusively from patient symptoms and their exacerbations. FEV1 is an “important parameter at the population level” in predicting hospitalization and mortality, the authors wrote, but keeping results separate “acknowledges the limitations of FEV1 in making treatment decisions for individualized patient care and highlights the importance of patient symptoms and exacerbation risks in guiding therapies in COPD.”
According to Meilan Han, MD, MS, a member of the GOLD Science Committee, since release of the 2017 guidelines, “clinicians have indicated that they like the flexibility the system provides in separating spirometry, symptoms, and exacerbation risk as this more accurately reflects the heterogeneity we see in the COPD patient population.” Nevertheless, how this approach influences long-term outcomes remains unclear.
Daniel Ouellette, MD, FCCP, a pulmonologist with the Henry Ford Health System in Detroit, described the GOLD 2017 criteria as “a good step forward” but said he wasn’t sure if the optimal or perfect tool exists for categorizing COPD patients’ level of disease.
“I think what we see is an effort to use all of these criteria to help us better treat our patients. I think ,” he said in an interview.
“All guidelines need to be modified as further research becomes available. I think that the frontiers of this area are going to be to incorporate new elements such as tobacco history, more emphasis on clinical signs and symptoms, and use of markers other than spirometry, such as eosinophil count, to categorize patients with COPD,” Dr. Ouellette added.
In an analysis of the GOLD 2017 criteria applied to 819 COPD patients in Spain and the United States, published online Nov. 3, 2017, in the American Journal of Respiratory and Critical Care Medicine, Carlos Cabrera López, MD, and his colleagues concluded that the mortality risk was better predicted by the 2015 GOLD classification system than by the 2017 iteration (Am J Respir Crit Care Med. 2018 Feb. doi: 10.101164/rccm.201707-1363OC).
The distribution of Charlson index scores also changed. Whereas group D was higher than B in 2015, they became similar in the 2017 system. For her part, Dr. Han emphasized that the primary goal of the GOLD ABCD classification system is to categorize patients with respect to treatment groups. “Current therapy targets symptoms and exacerbations, which are the key current elements of the classification schema,” she said in an interview. “The results of the Cabrera Lopez analysis are not necessarily unexpected, as FEV1 is associated with mortality.”
In a prospective, multicenter analysis, Portuguese researchers compared the performance of GOLD 2011 and 2017 in terms of how 200 COPD patients were reclassified, the level of agreement between the two iterations, and the performance of each to predict future exacerbations (COPD. 2018 Feb;15[1]; 21-6). They found that about half of patients classified as GOLD D under the 2011 guidelines became classified as GOLD B when the 2017 version was used, and the extent of agreement between the two iterations was moderate (P less than .001). They also found that the two versions of the guidelines were equivalently effective at predicting exacerbations (69.7% vs. 67.6% in the 2011 and 2017 iterations, respectively). In addition, patients who met the criteria for a GOLD B grouping in the 2017 iteration exacerbated 17% more often and had a lower percent predicted post bronchodilator FEV1 than did those who met the criteria for a GOLD B classification under the 2011 guidelines.
Dr. Han, who is also an associate professor of medicine at the University of Michigan Hospital, acknowledged that GOLD 2017 has resulted in the reclassification of some previously group D patients as group B patients. “Our primary goal is to aid clinicians with the diagnosis and management of patients with COPD,” she said. “We look forward to additional data coming in from ongoing clinical trials that will provide longer term data to further refine treatment algorithms.”
In a recent study of more than 33,000 Danish patients older than age 30 with COPD, researchers led by Anne Gedebjerg, MD, found that the GOLD 2017 ABCD classification did not predict all-cause and respiratory mortality more accurately than previous GOLD iterations from 2007 and 2011. Area under the curve for all-cause mortality was 0.61 for GOLD 2007, 0.61 for GOLD 2011, and 0.63 for GOLD 2017, while the area under the curve for respiratory mortality was 0.64 for GOLD 2007, 0.63 for GOLD 2011, and 0.65 for GOLD 2017 (Lancet Respir Med. 2018 Jan;6[3]:204-12).
However, when the spirometric stages 1-4 were combined with the A to D groupings based on symptoms and exacerbations, the 2017 classification predicted mortality with greater accuracy, compared with previous iterations (P less than .0001). “My practice is very much like this paper,” Dr. Iftikhar said. “I use both the spirometric grade and the ABCD grouping to specify which ‘group’ and ‘grade’ my patient belongs to. I think future investigators need to combine ABCD with spirometry classification to see how we can improve the classification system.”
In a commentary published in the same issue of the Lancet Respiratory Medicine as the large Danish study, Joan B. Soriano, MD, PhD, wrote that the 2011 GOLD guideline’s collapse of four spirometric thresholds (greater than 80%, 50%-80%, 30%-50%, and less than 30%) into just two (greater than 50% or 50% or less) “reduced the system’s ability to inform and predict mortality from the short term up to 10 years” (Lancet Respir Med. 2018 Jan;6[3]:165-6).
Lung function remains the best available biomarker for life expectancy in both patients with COPD and the general population,” wrote Dr. Soriano, a respiratory medicine researcher based in Madrid, Spain.
Additional important outcomes
Dr. Ouellette noted that while mortality is an important outcome for COPD patients, it’s not the only outcome of interest. “In addition to [trying to] help people live longer, which is certainly a desirable goal, we also want to make people be able to be more functional during their life, have fewer hospitalizations, and have less of a need of other types of supportive medical care for worsening of their disease,” he said. “The fact that the current guidelines don’t improve mortality more than the previous ones may not be a negative thing. It may tell us that the previous guidelines already did a pretty good job of helping us to improve mortality.”
Dr. Ouellette was quick to add that none of inhaled drugs currently available to treat COPD have been conclusively shown to improve mortality. “The only things we know that improve mortality for COPD patients are quitting smoking and using oxygen if a patient meets predefined goals for oxygen,” he said. “So the fact that GOLD criteria doesn’t improve mortality shouldn’t make us think that it’s not a useful tool. We already know that the medicines may not help people live longer.”
Dr. Han pointed out that spirometry “is still used to further clarify the choice of therapy recommended based on the nature and degree of airflow obstruction in light of severity of patient symptoms. The data are still designed to be used in conjunction to personalize therapy for patients.”
She added that the GOLD Science Committee “welcomes additional data analyses so that future recommendations can be further refined.”
Dr. Han disclosed that she has consulted for Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline. She has also received in-kind research support from Novartis and Sunovion.
Dr. Iftikhar reported having no financial disclosures. Dr. Ouellette is a member of CHEST® Physician’s editorial advisory board. He disclosed being part of a federally funded study being carried out by the Patient-Centered Outcomes Research Institute.
There was no industry involvement in the GOLD 2017 report, but many of its authors and board members had pharmaceutical company ties, and GOLD’s treatment advice relies on data from industry-sponsored studies.
Two scoring systems helpful in diagnosing heparin-induced thrombocytopenia
SAN DIEGO – Both the 4Ts Score and the HIT Expert Probability (HEP) Score are useful in clinical practice for the diagnosis of heparin-induced thrombocytopenia, but the HEP score may have better operative characteristics in ICU patients, results from a “real world” analysis showed.
“The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging,” Allyson M. Pishko, MD, one of the study authors, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The 4Ts Score is commonly used, but limitations include its low positive predictive value and significant interobserver variability.”
One external prospective study showed operating characteristics similar to those of 4Ts scores (Thromb Haemost 2015;113[3]:633-40).
The aim of the current study was to validate the HEP Score in a “real world” setting and to compare the performance of the HEP Score versus the 4Ts Score. The researchers enrolled 292 adults with suspected acute HIT who were hospitalized at the University of Pennsylvania or affiliated community hospitals, and who had HIT laboratory testing ordered.
The HEP Score and the 4Ts Score were calculated by a member of the clinical team and were completed prior to return of the HIT lab test result. The majority of scorers (62%) were hematology fellows, followed by attendings (35%), and residents/students (3%). All patients underwent testing with an HIT ELISA and serotonin-release assay (SRA). Patients in whom the optical density of the ELISA was less than 0.4 units were classified as not having HIT. The researchers used the Wilcoxon rank-sum test to compare HEP and 4Ts Scores in patients with and without HIT.
Of the 292 patients, 209 were HIT negative and 83 had their data reviewed by an expert panel. Of these 83 patients, 40 were found to be HIT negative and 43 were HIT positive, and their mean ages were 65 years and 63 years, respectively. Among the cases found to be positive for HIT, 93% had HIT ELISA optical density of 1 or greater and 69.7% were SRA positive. The median HEP Score in patients with and without HIT was 8 versus 5 (P less than .0001).
At the prespecified screening cut-off of 2 or more points, the HEP Score was 97.7% sensitive and 21.9% specific, with a positive predictive value of 17.7% and a negative predictive value of 98.2%. A cut-off of 5 or greater provided 90.7% sensitivity and 47.8% specificity with a positive predictive value of 23.1% and a negative predictive value of 96.8%. The mean time to calculate the HEP Score was 4.1 minutes.
The median 4Ts Score in patients with and without HIT was 5 versus 4 (P less than .0001), Dr. Pishko reported. A 4Ts Score of 4 or greater had a sensitivity of 97.7% and specificity of 32.9%, with a positive predictive value of 20.1% and a negative predictive value of 98.8%.
The area under the ROC curves for the HEP Score and 4Ts Score were similar (0.81 vs. 0.76; P = .121). Subset analysis revealed that compared with the 4Ts Score, the HEP Score had better operating characteristics in ICU patients (AUC 0.87 vs. 0.79; P= .029) and with trainee scorers (AUC 0.79 vs. 0.73; P = .032).
“Our data suggest that either the HEP Score or the 4Ts Score could be used in clinical practice,” Dr. Pishko said.
The National Institutes of Health funded the study. Dr. Pishko reported having no financial disclosures.
SOURCE: Pishko A et al. THSNA 2018.
SAN DIEGO – Both the 4Ts Score and the HIT Expert Probability (HEP) Score are useful in clinical practice for the diagnosis of heparin-induced thrombocytopenia, but the HEP score may have better operative characteristics in ICU patients, results from a “real world” analysis showed.
“The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging,” Allyson M. Pishko, MD, one of the study authors, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The 4Ts Score is commonly used, but limitations include its low positive predictive value and significant interobserver variability.”
One external prospective study showed operating characteristics similar to those of 4Ts scores (Thromb Haemost 2015;113[3]:633-40).
The aim of the current study was to validate the HEP Score in a “real world” setting and to compare the performance of the HEP Score versus the 4Ts Score. The researchers enrolled 292 adults with suspected acute HIT who were hospitalized at the University of Pennsylvania or affiliated community hospitals, and who had HIT laboratory testing ordered.
The HEP Score and the 4Ts Score were calculated by a member of the clinical team and were completed prior to return of the HIT lab test result. The majority of scorers (62%) were hematology fellows, followed by attendings (35%), and residents/students (3%). All patients underwent testing with an HIT ELISA and serotonin-release assay (SRA). Patients in whom the optical density of the ELISA was less than 0.4 units were classified as not having HIT. The researchers used the Wilcoxon rank-sum test to compare HEP and 4Ts Scores in patients with and without HIT.
Of the 292 patients, 209 were HIT negative and 83 had their data reviewed by an expert panel. Of these 83 patients, 40 were found to be HIT negative and 43 were HIT positive, and their mean ages were 65 years and 63 years, respectively. Among the cases found to be positive for HIT, 93% had HIT ELISA optical density of 1 or greater and 69.7% were SRA positive. The median HEP Score in patients with and without HIT was 8 versus 5 (P less than .0001).
At the prespecified screening cut-off of 2 or more points, the HEP Score was 97.7% sensitive and 21.9% specific, with a positive predictive value of 17.7% and a negative predictive value of 98.2%. A cut-off of 5 or greater provided 90.7% sensitivity and 47.8% specificity with a positive predictive value of 23.1% and a negative predictive value of 96.8%. The mean time to calculate the HEP Score was 4.1 minutes.
The median 4Ts Score in patients with and without HIT was 5 versus 4 (P less than .0001), Dr. Pishko reported. A 4Ts Score of 4 or greater had a sensitivity of 97.7% and specificity of 32.9%, with a positive predictive value of 20.1% and a negative predictive value of 98.8%.
The area under the ROC curves for the HEP Score and 4Ts Score were similar (0.81 vs. 0.76; P = .121). Subset analysis revealed that compared with the 4Ts Score, the HEP Score had better operating characteristics in ICU patients (AUC 0.87 vs. 0.79; P= .029) and with trainee scorers (AUC 0.79 vs. 0.73; P = .032).
“Our data suggest that either the HEP Score or the 4Ts Score could be used in clinical practice,” Dr. Pishko said.
The National Institutes of Health funded the study. Dr. Pishko reported having no financial disclosures.
SOURCE: Pishko A et al. THSNA 2018.
SAN DIEGO – Both the 4Ts Score and the HIT Expert Probability (HEP) Score are useful in clinical practice for the diagnosis of heparin-induced thrombocytopenia, but the HEP score may have better operative characteristics in ICU patients, results from a “real world” analysis showed.
“The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging,” Allyson M. Pishko, MD, one of the study authors, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The 4Ts Score is commonly used, but limitations include its low positive predictive value and significant interobserver variability.”
One external prospective study showed operating characteristics similar to those of 4Ts scores (Thromb Haemost 2015;113[3]:633-40).
The aim of the current study was to validate the HEP Score in a “real world” setting and to compare the performance of the HEP Score versus the 4Ts Score. The researchers enrolled 292 adults with suspected acute HIT who were hospitalized at the University of Pennsylvania or affiliated community hospitals, and who had HIT laboratory testing ordered.
The HEP Score and the 4Ts Score were calculated by a member of the clinical team and were completed prior to return of the HIT lab test result. The majority of scorers (62%) were hematology fellows, followed by attendings (35%), and residents/students (3%). All patients underwent testing with an HIT ELISA and serotonin-release assay (SRA). Patients in whom the optical density of the ELISA was less than 0.4 units were classified as not having HIT. The researchers used the Wilcoxon rank-sum test to compare HEP and 4Ts Scores in patients with and without HIT.
Of the 292 patients, 209 were HIT negative and 83 had their data reviewed by an expert panel. Of these 83 patients, 40 were found to be HIT negative and 43 were HIT positive, and their mean ages were 65 years and 63 years, respectively. Among the cases found to be positive for HIT, 93% had HIT ELISA optical density of 1 or greater and 69.7% were SRA positive. The median HEP Score in patients with and without HIT was 8 versus 5 (P less than .0001).
At the prespecified screening cut-off of 2 or more points, the HEP Score was 97.7% sensitive and 21.9% specific, with a positive predictive value of 17.7% and a negative predictive value of 98.2%. A cut-off of 5 or greater provided 90.7% sensitivity and 47.8% specificity with a positive predictive value of 23.1% and a negative predictive value of 96.8%. The mean time to calculate the HEP Score was 4.1 minutes.
The median 4Ts Score in patients with and without HIT was 5 versus 4 (P less than .0001), Dr. Pishko reported. A 4Ts Score of 4 or greater had a sensitivity of 97.7% and specificity of 32.9%, with a positive predictive value of 20.1% and a negative predictive value of 98.8%.
The area under the ROC curves for the HEP Score and 4Ts Score were similar (0.81 vs. 0.76; P = .121). Subset analysis revealed that compared with the 4Ts Score, the HEP Score had better operating characteristics in ICU patients (AUC 0.87 vs. 0.79; P= .029) and with trainee scorers (AUC 0.79 vs. 0.73; P = .032).
“Our data suggest that either the HEP Score or the 4Ts Score could be used in clinical practice,” Dr. Pishko said.
The National Institutes of Health funded the study. Dr. Pishko reported having no financial disclosures.
SOURCE: Pishko A et al. THSNA 2018.
REPORTING FROM THSNA 2018
Key clinical point:
Major finding: The area under the ROC curves for the HEP Score and 4Ts Score were similar (0.81 vs. 0.76; P = .121).
Study details: A prospective study of 292 adults with suspected acute HIT who were hospitalized at the University of Pennsylvania or affiliated community hospitals.
Disclosures: The National Institutes of Health funded the study. Dr. Pishko reported having no financial disclosures.
Source: Pishko A et al. THSNA 2018.
Researchers seek better understanding of von Willebrand disease
SAN DIEGO – Several groups of researchers are examining cohorts of von Willebrand disease (VWD), looking at its pathogenesis and molecular causes, as well as ways to improve treatment strategies.
At the biennial summit of the Thrombosis & Hemostasis Societies of North America, Robert F. Sidonio Jr., MD, MSc, highlighted the efforts underway, including the Zimmerman Program for the Molecular and Clinical Biology of VWD study (ZPMCB-VWD), a large grant project funded by the National Institutes of Health.
At the time of publication, there were more than 700 index cases and more than 2,200 families in the study. It includes data from 8 primary centers and 23 secondary centers. The goals are to characterize the molecular causes of VWD and the examine the fidelity of diagnosis, “which is a critical component of the study,” said Dr. Sidonio, clinical director of the hemostasis/thrombosis program at Children’s Healthcare of Atlanta.
When the ZPMCB-VWD investigators examined the correlation of bleeding phenotype and the genotype, the found that as the level of VW factor goes down, the bleeding score generally goes up, but it becomes a little bit flat in the 20-30 IU/dL range.
“Where we spend a lot of our time is with patients who have levels of 30%-50%, which can be quite heterogeneous,” Dr. Sidonio said.
Another finding made out of the ZPMCB-VWD project was the discovery of the single nucleotide polymorphism p.D1472H, which was noted to be more common in African American patients and leads to low Von Willebrand Ristocetin Cofactor (VWF:RCo) and VWF:RCo/VWF:Ag ratio, but does not increase the bleeding score.
The fidelity of diagnosis was another key finding to come out of ZPMCB-VWD. Most type 1 VWD cases were identified by low VWF:RCo. There was poor correlation between historical and current assays (r2 = 0.22), and diagnostic labs improved after central lab testing.
Next, Dr. Sidonio discussed findings from RENAWI 1 and 2, which are Italian registries of about 1,000 VWF patients that were organized by 12 centers in 2002. The goals are to evaluate the natural history of VWD in Italy and to characterize treatment strategies. According to preliminary findings from the researchers, the biological response to desmopressin (DDAVP) was 69% in those with VWD1, 26% in those with VWD2A, 20% in those with VWD2B, 33% in those with VWD2M, 71% in those with VWD2N, and 0% in those with VWD3 (Blood 2014;123:4037-44).
These researchers also found that a mean bleeding score of 3.5 corresponds to a VWF:RCo score of 30 U/dL or greater. “This indicates that there is something slightly different about patients that are above and below that threshold,” Dr. Sidonio said. “I think that’s something we’ve all been struggling with: trying to understand where the differences are and how aggressively we should be treating our patients with mild VWD.”
Another effort, The Willebrand in the Netherlands’ study (WiN), is a prospective cohort trial of about 700 patients with types 1, 2, and 3 VWD from 12 centers in that country (Blood 2008;112:4510). It was the first large study to use VWF propeptide (pp) to discriminate between severe type 1 and type 3 VWD. It also found that type 2 VWD is more characterized by increased clearance in VWF in contrast to type 1 VWD, leading to higher VWFpp/VWF:Ag ratio. In addition, in type 1 VWD, antigen rates increased about 3.5 U/dL per decade, RCo increased about 9.5 U/dL per decade, and Factor VIII: C increased about 7.1 U/dL per decade (J Thromb Haemost. 2014; 12[7]:1066-75).
“I don’t think we have a study to be able to follow patients for 20 years or so, knowing that we rely on the assays that we were using 20 years ago,” Dr. Sidonio said. “That’s a challenge at a lot of our centers, but we know that VWF generally rises with age in mild VWD patients.”
In patients with definitively diagnosed type 2 VWD, no age-related VWF or FVIII changes were observed. The researchers also observed an increase in surgical bleeding and GI bleeding in elderly VWD patients.
In the meantime, the Canadian Type 1 VWD study was one of the first to elucidate the complexity of the pathogenesis of type 1 VWD. It identified CLEC4M as playing a role in VWF clearance, with polymorphisms contributing to the variability of VWF.
More data collection is underway through a partnership between the Centers for Disease Control and Prevention and the American Thrombosis and Hemostasis Network (ATHN).
The CDC Universal Data Collection Project gathered surveillance data on bleeding disorders on patients from 1998-2011. The goals were to characterize bleeding complications, monitor safety of blood-based products to manage bleeding, identify health issues in need of additional research, evaluate bleeding disorders over the lifespan, and evaluate quality of life. In 2006, the ATHN was formed to provide stewardship of the secured national database housed at the CDC. To date, at least 34,000 patients have opted in to the data set, which includes demographic and clinical data used for research.
In a separate, phase 4 study of about 130 patients funded by Shire and led by Dr. Sidonio and Angela C. Weyand, MD, researchers will conduct a “real-world” safety and efficacy study of prophylaxis for severe VWD. Known as ATHN 9, the study includes patients currently enrolled in the ATHN data set. Treatment regimen is at the discretion of patients’ providers, and patients will be followed for up to 2 years from the start of enrollment. The study’s primary aim is to collect data on effectiveness and safety, including adverse events of various VWF regimens in adult and pediatric patients with severe congenital VWD.
Another effort is the Medical and Scientific Advisory Council (MASAC) Working Group, of which Dr. Sidonio is a member. The first meeting took place in July of 2016. The goals include making improvements to diagnostic testing and laboratory standards, assessing existing standards of care and clinical practice guidelines, developing educational programming, conducting research to better understand and develop effective treatments for VWD, and collaborating with partner organizations.
Dr. Sidonio reported that he has participated in advisory boards for Shire, CSL Behring, Biogen/Bioverativ, Pfizer, Emergent Solutions, Roche/Genentech, Aptevo, Novo Nordisk, Hema Biologics, and Octapharma. He also has received investigator-initiated grant funding from Bioverativ, Grifols, Kedrion, and Shire.
SAN DIEGO – Several groups of researchers are examining cohorts of von Willebrand disease (VWD), looking at its pathogenesis and molecular causes, as well as ways to improve treatment strategies.
At the biennial summit of the Thrombosis & Hemostasis Societies of North America, Robert F. Sidonio Jr., MD, MSc, highlighted the efforts underway, including the Zimmerman Program for the Molecular and Clinical Biology of VWD study (ZPMCB-VWD), a large grant project funded by the National Institutes of Health.
At the time of publication, there were more than 700 index cases and more than 2,200 families in the study. It includes data from 8 primary centers and 23 secondary centers. The goals are to characterize the molecular causes of VWD and the examine the fidelity of diagnosis, “which is a critical component of the study,” said Dr. Sidonio, clinical director of the hemostasis/thrombosis program at Children’s Healthcare of Atlanta.
When the ZPMCB-VWD investigators examined the correlation of bleeding phenotype and the genotype, the found that as the level of VW factor goes down, the bleeding score generally goes up, but it becomes a little bit flat in the 20-30 IU/dL range.
“Where we spend a lot of our time is with patients who have levels of 30%-50%, which can be quite heterogeneous,” Dr. Sidonio said.
Another finding made out of the ZPMCB-VWD project was the discovery of the single nucleotide polymorphism p.D1472H, which was noted to be more common in African American patients and leads to low Von Willebrand Ristocetin Cofactor (VWF:RCo) and VWF:RCo/VWF:Ag ratio, but does not increase the bleeding score.
The fidelity of diagnosis was another key finding to come out of ZPMCB-VWD. Most type 1 VWD cases were identified by low VWF:RCo. There was poor correlation between historical and current assays (r2 = 0.22), and diagnostic labs improved after central lab testing.
Next, Dr. Sidonio discussed findings from RENAWI 1 and 2, which are Italian registries of about 1,000 VWF patients that were organized by 12 centers in 2002. The goals are to evaluate the natural history of VWD in Italy and to characterize treatment strategies. According to preliminary findings from the researchers, the biological response to desmopressin (DDAVP) was 69% in those with VWD1, 26% in those with VWD2A, 20% in those with VWD2B, 33% in those with VWD2M, 71% in those with VWD2N, and 0% in those with VWD3 (Blood 2014;123:4037-44).
These researchers also found that a mean bleeding score of 3.5 corresponds to a VWF:RCo score of 30 U/dL or greater. “This indicates that there is something slightly different about patients that are above and below that threshold,” Dr. Sidonio said. “I think that’s something we’ve all been struggling with: trying to understand where the differences are and how aggressively we should be treating our patients with mild VWD.”
Another effort, The Willebrand in the Netherlands’ study (WiN), is a prospective cohort trial of about 700 patients with types 1, 2, and 3 VWD from 12 centers in that country (Blood 2008;112:4510). It was the first large study to use VWF propeptide (pp) to discriminate between severe type 1 and type 3 VWD. It also found that type 2 VWD is more characterized by increased clearance in VWF in contrast to type 1 VWD, leading to higher VWFpp/VWF:Ag ratio. In addition, in type 1 VWD, antigen rates increased about 3.5 U/dL per decade, RCo increased about 9.5 U/dL per decade, and Factor VIII: C increased about 7.1 U/dL per decade (J Thromb Haemost. 2014; 12[7]:1066-75).
“I don’t think we have a study to be able to follow patients for 20 years or so, knowing that we rely on the assays that we were using 20 years ago,” Dr. Sidonio said. “That’s a challenge at a lot of our centers, but we know that VWF generally rises with age in mild VWD patients.”
In patients with definitively diagnosed type 2 VWD, no age-related VWF or FVIII changes were observed. The researchers also observed an increase in surgical bleeding and GI bleeding in elderly VWD patients.
In the meantime, the Canadian Type 1 VWD study was one of the first to elucidate the complexity of the pathogenesis of type 1 VWD. It identified CLEC4M as playing a role in VWF clearance, with polymorphisms contributing to the variability of VWF.
More data collection is underway through a partnership between the Centers for Disease Control and Prevention and the American Thrombosis and Hemostasis Network (ATHN).
The CDC Universal Data Collection Project gathered surveillance data on bleeding disorders on patients from 1998-2011. The goals were to characterize bleeding complications, monitor safety of blood-based products to manage bleeding, identify health issues in need of additional research, evaluate bleeding disorders over the lifespan, and evaluate quality of life. In 2006, the ATHN was formed to provide stewardship of the secured national database housed at the CDC. To date, at least 34,000 patients have opted in to the data set, which includes demographic and clinical data used for research.
In a separate, phase 4 study of about 130 patients funded by Shire and led by Dr. Sidonio and Angela C. Weyand, MD, researchers will conduct a “real-world” safety and efficacy study of prophylaxis for severe VWD. Known as ATHN 9, the study includes patients currently enrolled in the ATHN data set. Treatment regimen is at the discretion of patients’ providers, and patients will be followed for up to 2 years from the start of enrollment. The study’s primary aim is to collect data on effectiveness and safety, including adverse events of various VWF regimens in adult and pediatric patients with severe congenital VWD.
Another effort is the Medical and Scientific Advisory Council (MASAC) Working Group, of which Dr. Sidonio is a member. The first meeting took place in July of 2016. The goals include making improvements to diagnostic testing and laboratory standards, assessing existing standards of care and clinical practice guidelines, developing educational programming, conducting research to better understand and develop effective treatments for VWD, and collaborating with partner organizations.
Dr. Sidonio reported that he has participated in advisory boards for Shire, CSL Behring, Biogen/Bioverativ, Pfizer, Emergent Solutions, Roche/Genentech, Aptevo, Novo Nordisk, Hema Biologics, and Octapharma. He also has received investigator-initiated grant funding from Bioverativ, Grifols, Kedrion, and Shire.
SAN DIEGO – Several groups of researchers are examining cohorts of von Willebrand disease (VWD), looking at its pathogenesis and molecular causes, as well as ways to improve treatment strategies.
At the biennial summit of the Thrombosis & Hemostasis Societies of North America, Robert F. Sidonio Jr., MD, MSc, highlighted the efforts underway, including the Zimmerman Program for the Molecular and Clinical Biology of VWD study (ZPMCB-VWD), a large grant project funded by the National Institutes of Health.
At the time of publication, there were more than 700 index cases and more than 2,200 families in the study. It includes data from 8 primary centers and 23 secondary centers. The goals are to characterize the molecular causes of VWD and the examine the fidelity of diagnosis, “which is a critical component of the study,” said Dr. Sidonio, clinical director of the hemostasis/thrombosis program at Children’s Healthcare of Atlanta.
When the ZPMCB-VWD investigators examined the correlation of bleeding phenotype and the genotype, the found that as the level of VW factor goes down, the bleeding score generally goes up, but it becomes a little bit flat in the 20-30 IU/dL range.
“Where we spend a lot of our time is with patients who have levels of 30%-50%, which can be quite heterogeneous,” Dr. Sidonio said.
Another finding made out of the ZPMCB-VWD project was the discovery of the single nucleotide polymorphism p.D1472H, which was noted to be more common in African American patients and leads to low Von Willebrand Ristocetin Cofactor (VWF:RCo) and VWF:RCo/VWF:Ag ratio, but does not increase the bleeding score.
The fidelity of diagnosis was another key finding to come out of ZPMCB-VWD. Most type 1 VWD cases were identified by low VWF:RCo. There was poor correlation between historical and current assays (r2 = 0.22), and diagnostic labs improved after central lab testing.
Next, Dr. Sidonio discussed findings from RENAWI 1 and 2, which are Italian registries of about 1,000 VWF patients that were organized by 12 centers in 2002. The goals are to evaluate the natural history of VWD in Italy and to characterize treatment strategies. According to preliminary findings from the researchers, the biological response to desmopressin (DDAVP) was 69% in those with VWD1, 26% in those with VWD2A, 20% in those with VWD2B, 33% in those with VWD2M, 71% in those with VWD2N, and 0% in those with VWD3 (Blood 2014;123:4037-44).
These researchers also found that a mean bleeding score of 3.5 corresponds to a VWF:RCo score of 30 U/dL or greater. “This indicates that there is something slightly different about patients that are above and below that threshold,” Dr. Sidonio said. “I think that’s something we’ve all been struggling with: trying to understand where the differences are and how aggressively we should be treating our patients with mild VWD.”
Another effort, The Willebrand in the Netherlands’ study (WiN), is a prospective cohort trial of about 700 patients with types 1, 2, and 3 VWD from 12 centers in that country (Blood 2008;112:4510). It was the first large study to use VWF propeptide (pp) to discriminate between severe type 1 and type 3 VWD. It also found that type 2 VWD is more characterized by increased clearance in VWF in contrast to type 1 VWD, leading to higher VWFpp/VWF:Ag ratio. In addition, in type 1 VWD, antigen rates increased about 3.5 U/dL per decade, RCo increased about 9.5 U/dL per decade, and Factor VIII: C increased about 7.1 U/dL per decade (J Thromb Haemost. 2014; 12[7]:1066-75).
“I don’t think we have a study to be able to follow patients for 20 years or so, knowing that we rely on the assays that we were using 20 years ago,” Dr. Sidonio said. “That’s a challenge at a lot of our centers, but we know that VWF generally rises with age in mild VWD patients.”
In patients with definitively diagnosed type 2 VWD, no age-related VWF or FVIII changes were observed. The researchers also observed an increase in surgical bleeding and GI bleeding in elderly VWD patients.
In the meantime, the Canadian Type 1 VWD study was one of the first to elucidate the complexity of the pathogenesis of type 1 VWD. It identified CLEC4M as playing a role in VWF clearance, with polymorphisms contributing to the variability of VWF.
More data collection is underway through a partnership between the Centers for Disease Control and Prevention and the American Thrombosis and Hemostasis Network (ATHN).
The CDC Universal Data Collection Project gathered surveillance data on bleeding disorders on patients from 1998-2011. The goals were to characterize bleeding complications, monitor safety of blood-based products to manage bleeding, identify health issues in need of additional research, evaluate bleeding disorders over the lifespan, and evaluate quality of life. In 2006, the ATHN was formed to provide stewardship of the secured national database housed at the CDC. To date, at least 34,000 patients have opted in to the data set, which includes demographic and clinical data used for research.
In a separate, phase 4 study of about 130 patients funded by Shire and led by Dr. Sidonio and Angela C. Weyand, MD, researchers will conduct a “real-world” safety and efficacy study of prophylaxis for severe VWD. Known as ATHN 9, the study includes patients currently enrolled in the ATHN data set. Treatment regimen is at the discretion of patients’ providers, and patients will be followed for up to 2 years from the start of enrollment. The study’s primary aim is to collect data on effectiveness and safety, including adverse events of various VWF regimens in adult and pediatric patients with severe congenital VWD.
Another effort is the Medical and Scientific Advisory Council (MASAC) Working Group, of which Dr. Sidonio is a member. The first meeting took place in July of 2016. The goals include making improvements to diagnostic testing and laboratory standards, assessing existing standards of care and clinical practice guidelines, developing educational programming, conducting research to better understand and develop effective treatments for VWD, and collaborating with partner organizations.
Dr. Sidonio reported that he has participated in advisory boards for Shire, CSL Behring, Biogen/Bioverativ, Pfizer, Emergent Solutions, Roche/Genentech, Aptevo, Novo Nordisk, Hema Biologics, and Octapharma. He also has received investigator-initiated grant funding from Bioverativ, Grifols, Kedrion, and Shire.
EXPERT ANALYSIS FROM THSNA 2018
Why is gene therapy for hemophilia taking so long?
SAN DIEGO – The goal of gene therapy for hemophilia and other genetic diseases is to achieve long-term expression and levels adequate to improve the phenotype of disease, according to Katherine A. High, MD.
“Sometimes people ask me, ‘Why is it taking so long to develop these therapeutics?’ ” Dr. High said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The answer is that gene therapy vectors are arguably one of the most complex therapeutics yet developed.”
Spark Therapeutics is currently developing gene therapies for hemophilia A (SPK-8011) and hemophilia B (SPK-9001).
Hemostasis and thrombosis targets in gene therapy trials include hemophilia, as well as peripheral artery disease/claudication and congestive heart failure. In the latter, a prior phase 2b trial of adeno-associated virus (AAV) expressing SERCA2a did not support efficacy (Lancet 2016;387:1178-86), while a current trial of adenovirus 5–vector expressing adenylyl cyclase–type 6 is entering phase 3 study (NCT03360448).
To get a sense of how long it may take for a new class of therapeutics to become established, Dr. High noted that the first monoclonal antibody to be licensed was OKT3 (muromonab-CD3) in 1986, followed by abciximab in 1994, rituximab and daclizumab in 1997, and four additional products in 1998. By 2007, 8 of the top 20 biotech drugs were monoclonal antibodies.
Hemophilia has long been a favored gene therapy target because biology is in its favor. “It has a wide therapeutic window, it does not require tissue-specific expression of transgene, small and large animal models exist, and endpoints are well validated and easy to measure,” she said. “Thus, early gene-therapy clinical investigation since 1998 explored many strategies.”
There are several current investigational efforts in AAV-mediated gene transfer in hemophilia, including:
- A single-arm study to evaluate the efficacy and safety of valoctocogene roxaparvovec in hemophilia A patients at a dose of 4×1013 vector genome per kilogram (NCT03392974).
- A dose-ranging study of recombinant AAV2/6 human factor 8 gene therapy SB-525 in subjects with severe hemophilia A (NCT03061201).
- A safety and dose-escalation study of an adeno-associated viral vector for gene transfer in hemophilia A subjects (NCT03370172).
Other approaches in preclinical investigation include lentiviral transduction of hematopoietic stem cells with megakaryocyte-restricted expression, lentiviral transduction of liver cells and endothelial cells, and genome editing using zinc finger nucleases.
“AAV vectors are one of the smallest of all naturally occurring viruses,” said Dr. High, who is also emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia. “The recombinant AAV consists of a highly ordered set of proteins [vector capsid] containing DNA [the active agent].”
Overall goals for a hemophilia gene therapy include long-term expression and levels adequate to prevent bleeds in someone with a normal active lifestyle. “We’d like to see consistency of results from one person to the next, and we’d like to use the lowest possible dose,” she said. “In the setting of gene transfer, the lower the dose, the lower the likelihood of immune responses that need to be managed. Theoretically, the lower the dose, the lower the risk of insertional mutagenesis, and the shorter-term duration of vector shedding in body fluids, including in semen.”
Going forward, a key question for researchers relates to the long-term effect of gene therapy. “How long is long enough?” Dr. High asked. “The longest reported durability is 8 years, with observation ongoing, from studies initially reported in men with severe hemophilia B. The durability in large animal models exceeds 10 years.”
Another unanswered question is what level of factor VIII to aim for in treatment. “Some data suggest that FVIII levels greater than 100 IU/dL are associated with a greater level of thrombosis,” Dr. High said. “So I think somewhere between 12% and 100% is probably the ideal level.”
SAN DIEGO – The goal of gene therapy for hemophilia and other genetic diseases is to achieve long-term expression and levels adequate to improve the phenotype of disease, according to Katherine A. High, MD.
“Sometimes people ask me, ‘Why is it taking so long to develop these therapeutics?’ ” Dr. High said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The answer is that gene therapy vectors are arguably one of the most complex therapeutics yet developed.”
Spark Therapeutics is currently developing gene therapies for hemophilia A (SPK-8011) and hemophilia B (SPK-9001).
Hemostasis and thrombosis targets in gene therapy trials include hemophilia, as well as peripheral artery disease/claudication and congestive heart failure. In the latter, a prior phase 2b trial of adeno-associated virus (AAV) expressing SERCA2a did not support efficacy (Lancet 2016;387:1178-86), while a current trial of adenovirus 5–vector expressing adenylyl cyclase–type 6 is entering phase 3 study (NCT03360448).
To get a sense of how long it may take for a new class of therapeutics to become established, Dr. High noted that the first monoclonal antibody to be licensed was OKT3 (muromonab-CD3) in 1986, followed by abciximab in 1994, rituximab and daclizumab in 1997, and four additional products in 1998. By 2007, 8 of the top 20 biotech drugs were monoclonal antibodies.
Hemophilia has long been a favored gene therapy target because biology is in its favor. “It has a wide therapeutic window, it does not require tissue-specific expression of transgene, small and large animal models exist, and endpoints are well validated and easy to measure,” she said. “Thus, early gene-therapy clinical investigation since 1998 explored many strategies.”
There are several current investigational efforts in AAV-mediated gene transfer in hemophilia, including:
- A single-arm study to evaluate the efficacy and safety of valoctocogene roxaparvovec in hemophilia A patients at a dose of 4×1013 vector genome per kilogram (NCT03392974).
- A dose-ranging study of recombinant AAV2/6 human factor 8 gene therapy SB-525 in subjects with severe hemophilia A (NCT03061201).
- A safety and dose-escalation study of an adeno-associated viral vector for gene transfer in hemophilia A subjects (NCT03370172).
Other approaches in preclinical investigation include lentiviral transduction of hematopoietic stem cells with megakaryocyte-restricted expression, lentiviral transduction of liver cells and endothelial cells, and genome editing using zinc finger nucleases.
“AAV vectors are one of the smallest of all naturally occurring viruses,” said Dr. High, who is also emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia. “The recombinant AAV consists of a highly ordered set of proteins [vector capsid] containing DNA [the active agent].”
Overall goals for a hemophilia gene therapy include long-term expression and levels adequate to prevent bleeds in someone with a normal active lifestyle. “We’d like to see consistency of results from one person to the next, and we’d like to use the lowest possible dose,” she said. “In the setting of gene transfer, the lower the dose, the lower the likelihood of immune responses that need to be managed. Theoretically, the lower the dose, the lower the risk of insertional mutagenesis, and the shorter-term duration of vector shedding in body fluids, including in semen.”
Going forward, a key question for researchers relates to the long-term effect of gene therapy. “How long is long enough?” Dr. High asked. “The longest reported durability is 8 years, with observation ongoing, from studies initially reported in men with severe hemophilia B. The durability in large animal models exceeds 10 years.”
Another unanswered question is what level of factor VIII to aim for in treatment. “Some data suggest that FVIII levels greater than 100 IU/dL are associated with a greater level of thrombosis,” Dr. High said. “So I think somewhere between 12% and 100% is probably the ideal level.”
SAN DIEGO – The goal of gene therapy for hemophilia and other genetic diseases is to achieve long-term expression and levels adequate to improve the phenotype of disease, according to Katherine A. High, MD.
“Sometimes people ask me, ‘Why is it taking so long to develop these therapeutics?’ ” Dr. High said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The answer is that gene therapy vectors are arguably one of the most complex therapeutics yet developed.”
Spark Therapeutics is currently developing gene therapies for hemophilia A (SPK-8011) and hemophilia B (SPK-9001).
Hemostasis and thrombosis targets in gene therapy trials include hemophilia, as well as peripheral artery disease/claudication and congestive heart failure. In the latter, a prior phase 2b trial of adeno-associated virus (AAV) expressing SERCA2a did not support efficacy (Lancet 2016;387:1178-86), while a current trial of adenovirus 5–vector expressing adenylyl cyclase–type 6 is entering phase 3 study (NCT03360448).
To get a sense of how long it may take for a new class of therapeutics to become established, Dr. High noted that the first monoclonal antibody to be licensed was OKT3 (muromonab-CD3) in 1986, followed by abciximab in 1994, rituximab and daclizumab in 1997, and four additional products in 1998. By 2007, 8 of the top 20 biotech drugs were monoclonal antibodies.
Hemophilia has long been a favored gene therapy target because biology is in its favor. “It has a wide therapeutic window, it does not require tissue-specific expression of transgene, small and large animal models exist, and endpoints are well validated and easy to measure,” she said. “Thus, early gene-therapy clinical investigation since 1998 explored many strategies.”
There are several current investigational efforts in AAV-mediated gene transfer in hemophilia, including:
- A single-arm study to evaluate the efficacy and safety of valoctocogene roxaparvovec in hemophilia A patients at a dose of 4×1013 vector genome per kilogram (NCT03392974).
- A dose-ranging study of recombinant AAV2/6 human factor 8 gene therapy SB-525 in subjects with severe hemophilia A (NCT03061201).
- A safety and dose-escalation study of an adeno-associated viral vector for gene transfer in hemophilia A subjects (NCT03370172).
Other approaches in preclinical investigation include lentiviral transduction of hematopoietic stem cells with megakaryocyte-restricted expression, lentiviral transduction of liver cells and endothelial cells, and genome editing using zinc finger nucleases.
“AAV vectors are one of the smallest of all naturally occurring viruses,” said Dr. High, who is also emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia. “The recombinant AAV consists of a highly ordered set of proteins [vector capsid] containing DNA [the active agent].”
Overall goals for a hemophilia gene therapy include long-term expression and levels adequate to prevent bleeds in someone with a normal active lifestyle. “We’d like to see consistency of results from one person to the next, and we’d like to use the lowest possible dose,” she said. “In the setting of gene transfer, the lower the dose, the lower the likelihood of immune responses that need to be managed. Theoretically, the lower the dose, the lower the risk of insertional mutagenesis, and the shorter-term duration of vector shedding in body fluids, including in semen.”
Going forward, a key question for researchers relates to the long-term effect of gene therapy. “How long is long enough?” Dr. High asked. “The longest reported durability is 8 years, with observation ongoing, from studies initially reported in men with severe hemophilia B. The durability in large animal models exceeds 10 years.”
Another unanswered question is what level of factor VIII to aim for in treatment. “Some data suggest that FVIII levels greater than 100 IU/dL are associated with a greater level of thrombosis,” Dr. High said. “So I think somewhere between 12% and 100% is probably the ideal level.”
EXPERT ANALYSIS FROM THSNA 2018
Clearer picture emerging of renal impact of SGLT2s
LOS ANGELES – Results from recent trials suggest that
“Despite optimal care around blood pressure control, glycemic control, and control of other risk factors, our patients still have a significant risk of both cardiovascular disease progression and renal disease progression,” David Cherney, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “In fact, when we have a narrow focus on glycemia, there is a lot of additional residual risk, and that A1c lowering by itself does not negate that risk and in fact has very little effect on clinical outcomes. That brings us to the newer hyperglycemic therapies, including the SGLT2 inhibitors. While these agents do indeed block the reabsorption of glucose in the kidney, they also have an effect on other nonglycemic risk factors.”
“Inside the kidney, there are direct effects on reducing intraglomerular hypertension, leading to reductions in proteinuria,” he said. “These agents are interesting because of the way that they influence how the kidney handles sodium. As a consequence, they impact on glomerular hypertension.”
Under normal physiological conditions, humans who become volume depleted or hypotensive experience a reduction in sodium delivery to the kidney by the afferent arteriole, he explained. If less sodium is delivered to the afferent arteriole, less is filtered and delivered to the macula densa, which is the sodium-sensing area of the kidney.
“If less sodium is delivered to the macula densa, less sodium will be reabsorbed, which is an energy-requiring process that leads to the breakdown of ATP [adenosine triphosphate],” Dr. Cherney said. “If less ATP is broken down to adenosine, then less adenosine is produced. Adenosine is a vasoconstrictor in this area. So, under conditions of hypervolemia or hypotension, that’s great, because we want to maintain blood flow to the kidney; that’s a protective autoregulatory response that all of us have called tubular glomerular feedback. It’s through sodium delivery to the macula densa.”
He went on to note that hyperglycemic patients who are not taking an SGLT2 inhibitor experience an increase in sodium absorption proximally, which decreases sodium delivery to the macula densa. As a result, this causes afferent dilation, which leads to a rise in glomerular pressure, glomerular hypertension, hyperfiltration, and an increased risk of renal disease progression.
“This leads to all the effects that we see clinically, including the GFR [glomerular filtration rate] dip and the reduction in proteinuria that these agents cause either when used alone or with an ACE or ARB [angiotensin II receptor blocker],” Dr. Cherney said. “SGLT2s constrict the afferent arterial and reduce glomerular hypertension and proteinuria, whereas ACE inhibitors dilate the efferent arterial, which also reduces glomerular hypertension and proteinuria.”
An analysis of renal data from the multicenter EMPA-REG OUTCOME trial (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) found that the use of empagliflozin was associated with slower progression of kidney disease than was placebo when added to standard care. Empagliflozin was also associated with a significantly lower risk of clinically relevant renal events, including a 40%-50% reduction in microalbuminuria in patients with micro- or macroalbuminuria (N Engl J Med. 2016 Jul 28;375:323-34).
In a recent study of EMPA-REG OUTCOME patients, Dr. Cherney and his associates examined the effects of empagliflozin on the urinary albumin to creatinine ratio in patients with type 2 diabetes and established cardiovascular disease (Lancet Diabetes Endocrinol. 2017 Aug;5[8]:610-21). They found that even in patients with normal albuminuria at baseline, by the end of the trial at about 3 years there was a modest but statistically significant 15% reduction in urinary albumin secretion. “That reduction was greater in patients with microalbuminuria at baseline,” Dr. Cherney said. “There was a more than 40% reduction in microalbuminuric patients, and almost a 50% in patients who had macroalbuminuria at baseline, suggesting that the effect is greater in patients with higher levels of albuminuria.”
Meanwhile, results from the CANVAS program, which integrated data from two trials of more than 10,000 patients with type 2 diabetes and high cardiovascular disease risk, showed that those who received canagliflozin had a 14% reduced risk of 3-point major adverse cardiovascular events (3P-MACE), compared with those who received placebo. (N Engl J Med. 2017 Aug;377:644-57). “There was a curious increased risk of amputation and fracture in the canagliflozin group, which has not been seen in other trials,” Dr. Cherney said. “That certainly merits further thought and investigation, to better understand how significant this risk is.”
Upcoming trials of renal endpoints to look out for, he said, include the CREDENCE study (results expected in 2019), DAPA-CKD, which is in the recruitment stage, and a new outcome study to evaluate the effect of empagliflozin for the treatment of people with chronic kidney disease. “This is an expanding area in the renal and cardiovascular world that we will hear a lot more about in the next 3-5 years,” he said.
Dr. Cherney reported consulting fees and/or honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck, Mitsubishi Tanabe, and Sanofi.
LOS ANGELES – Results from recent trials suggest that
“Despite optimal care around blood pressure control, glycemic control, and control of other risk factors, our patients still have a significant risk of both cardiovascular disease progression and renal disease progression,” David Cherney, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “In fact, when we have a narrow focus on glycemia, there is a lot of additional residual risk, and that A1c lowering by itself does not negate that risk and in fact has very little effect on clinical outcomes. That brings us to the newer hyperglycemic therapies, including the SGLT2 inhibitors. While these agents do indeed block the reabsorption of glucose in the kidney, they also have an effect on other nonglycemic risk factors.”
“Inside the kidney, there are direct effects on reducing intraglomerular hypertension, leading to reductions in proteinuria,” he said. “These agents are interesting because of the way that they influence how the kidney handles sodium. As a consequence, they impact on glomerular hypertension.”
Under normal physiological conditions, humans who become volume depleted or hypotensive experience a reduction in sodium delivery to the kidney by the afferent arteriole, he explained. If less sodium is delivered to the afferent arteriole, less is filtered and delivered to the macula densa, which is the sodium-sensing area of the kidney.
“If less sodium is delivered to the macula densa, less sodium will be reabsorbed, which is an energy-requiring process that leads to the breakdown of ATP [adenosine triphosphate],” Dr. Cherney said. “If less ATP is broken down to adenosine, then less adenosine is produced. Adenosine is a vasoconstrictor in this area. So, under conditions of hypervolemia or hypotension, that’s great, because we want to maintain blood flow to the kidney; that’s a protective autoregulatory response that all of us have called tubular glomerular feedback. It’s through sodium delivery to the macula densa.”
He went on to note that hyperglycemic patients who are not taking an SGLT2 inhibitor experience an increase in sodium absorption proximally, which decreases sodium delivery to the macula densa. As a result, this causes afferent dilation, which leads to a rise in glomerular pressure, glomerular hypertension, hyperfiltration, and an increased risk of renal disease progression.
“This leads to all the effects that we see clinically, including the GFR [glomerular filtration rate] dip and the reduction in proteinuria that these agents cause either when used alone or with an ACE or ARB [angiotensin II receptor blocker],” Dr. Cherney said. “SGLT2s constrict the afferent arterial and reduce glomerular hypertension and proteinuria, whereas ACE inhibitors dilate the efferent arterial, which also reduces glomerular hypertension and proteinuria.”
An analysis of renal data from the multicenter EMPA-REG OUTCOME trial (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) found that the use of empagliflozin was associated with slower progression of kidney disease than was placebo when added to standard care. Empagliflozin was also associated with a significantly lower risk of clinically relevant renal events, including a 40%-50% reduction in microalbuminuria in patients with micro- or macroalbuminuria (N Engl J Med. 2016 Jul 28;375:323-34).
In a recent study of EMPA-REG OUTCOME patients, Dr. Cherney and his associates examined the effects of empagliflozin on the urinary albumin to creatinine ratio in patients with type 2 diabetes and established cardiovascular disease (Lancet Diabetes Endocrinol. 2017 Aug;5[8]:610-21). They found that even in patients with normal albuminuria at baseline, by the end of the trial at about 3 years there was a modest but statistically significant 15% reduction in urinary albumin secretion. “That reduction was greater in patients with microalbuminuria at baseline,” Dr. Cherney said. “There was a more than 40% reduction in microalbuminuric patients, and almost a 50% in patients who had macroalbuminuria at baseline, suggesting that the effect is greater in patients with higher levels of albuminuria.”
Meanwhile, results from the CANVAS program, which integrated data from two trials of more than 10,000 patients with type 2 diabetes and high cardiovascular disease risk, showed that those who received canagliflozin had a 14% reduced risk of 3-point major adverse cardiovascular events (3P-MACE), compared with those who received placebo. (N Engl J Med. 2017 Aug;377:644-57). “There was a curious increased risk of amputation and fracture in the canagliflozin group, which has not been seen in other trials,” Dr. Cherney said. “That certainly merits further thought and investigation, to better understand how significant this risk is.”
Upcoming trials of renal endpoints to look out for, he said, include the CREDENCE study (results expected in 2019), DAPA-CKD, which is in the recruitment stage, and a new outcome study to evaluate the effect of empagliflozin for the treatment of people with chronic kidney disease. “This is an expanding area in the renal and cardiovascular world that we will hear a lot more about in the next 3-5 years,” he said.
Dr. Cherney reported consulting fees and/or honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck, Mitsubishi Tanabe, and Sanofi.
LOS ANGELES – Results from recent trials suggest that
“Despite optimal care around blood pressure control, glycemic control, and control of other risk factors, our patients still have a significant risk of both cardiovascular disease progression and renal disease progression,” David Cherney, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “In fact, when we have a narrow focus on glycemia, there is a lot of additional residual risk, and that A1c lowering by itself does not negate that risk and in fact has very little effect on clinical outcomes. That brings us to the newer hyperglycemic therapies, including the SGLT2 inhibitors. While these agents do indeed block the reabsorption of glucose in the kidney, they also have an effect on other nonglycemic risk factors.”
“Inside the kidney, there are direct effects on reducing intraglomerular hypertension, leading to reductions in proteinuria,” he said. “These agents are interesting because of the way that they influence how the kidney handles sodium. As a consequence, they impact on glomerular hypertension.”
Under normal physiological conditions, humans who become volume depleted or hypotensive experience a reduction in sodium delivery to the kidney by the afferent arteriole, he explained. If less sodium is delivered to the afferent arteriole, less is filtered and delivered to the macula densa, which is the sodium-sensing area of the kidney.
“If less sodium is delivered to the macula densa, less sodium will be reabsorbed, which is an energy-requiring process that leads to the breakdown of ATP [adenosine triphosphate],” Dr. Cherney said. “If less ATP is broken down to adenosine, then less adenosine is produced. Adenosine is a vasoconstrictor in this area. So, under conditions of hypervolemia or hypotension, that’s great, because we want to maintain blood flow to the kidney; that’s a protective autoregulatory response that all of us have called tubular glomerular feedback. It’s through sodium delivery to the macula densa.”
He went on to note that hyperglycemic patients who are not taking an SGLT2 inhibitor experience an increase in sodium absorption proximally, which decreases sodium delivery to the macula densa. As a result, this causes afferent dilation, which leads to a rise in glomerular pressure, glomerular hypertension, hyperfiltration, and an increased risk of renal disease progression.
“This leads to all the effects that we see clinically, including the GFR [glomerular filtration rate] dip and the reduction in proteinuria that these agents cause either when used alone or with an ACE or ARB [angiotensin II receptor blocker],” Dr. Cherney said. “SGLT2s constrict the afferent arterial and reduce glomerular hypertension and proteinuria, whereas ACE inhibitors dilate the efferent arterial, which also reduces glomerular hypertension and proteinuria.”
An analysis of renal data from the multicenter EMPA-REG OUTCOME trial (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) found that the use of empagliflozin was associated with slower progression of kidney disease than was placebo when added to standard care. Empagliflozin was also associated with a significantly lower risk of clinically relevant renal events, including a 40%-50% reduction in microalbuminuria in patients with micro- or macroalbuminuria (N Engl J Med. 2016 Jul 28;375:323-34).
In a recent study of EMPA-REG OUTCOME patients, Dr. Cherney and his associates examined the effects of empagliflozin on the urinary albumin to creatinine ratio in patients with type 2 diabetes and established cardiovascular disease (Lancet Diabetes Endocrinol. 2017 Aug;5[8]:610-21). They found that even in patients with normal albuminuria at baseline, by the end of the trial at about 3 years there was a modest but statistically significant 15% reduction in urinary albumin secretion. “That reduction was greater in patients with microalbuminuria at baseline,” Dr. Cherney said. “There was a more than 40% reduction in microalbuminuric patients, and almost a 50% in patients who had macroalbuminuria at baseline, suggesting that the effect is greater in patients with higher levels of albuminuria.”
Meanwhile, results from the CANVAS program, which integrated data from two trials of more than 10,000 patients with type 2 diabetes and high cardiovascular disease risk, showed that those who received canagliflozin had a 14% reduced risk of 3-point major adverse cardiovascular events (3P-MACE), compared with those who received placebo. (N Engl J Med. 2017 Aug;377:644-57). “There was a curious increased risk of amputation and fracture in the canagliflozin group, which has not been seen in other trials,” Dr. Cherney said. “That certainly merits further thought and investigation, to better understand how significant this risk is.”
Upcoming trials of renal endpoints to look out for, he said, include the CREDENCE study (results expected in 2019), DAPA-CKD, which is in the recruitment stage, and a new outcome study to evaluate the effect of empagliflozin for the treatment of people with chronic kidney disease. “This is an expanding area in the renal and cardiovascular world that we will hear a lot more about in the next 3-5 years,” he said.
Dr. Cherney reported consulting fees and/or honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck, Mitsubishi Tanabe, and Sanofi.
EXPERT ANALYSIS FROM WCIRDC 2017
Few acutely ill hospitalized patients receive VTE prophylaxis
SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.
Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.
“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.
The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.
Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.
SOURCE: Amin A et al. THSNA 2018, Poster 51.
SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.
Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.
“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.
The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.
Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.
SOURCE: Amin A et al. THSNA 2018, Poster 51.
SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.
Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.
“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.
The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.
Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.
SOURCE: Amin A et al. THSNA 2018, Poster 51.
REPORTING FROM THSNA 2018
Key clinical point: There is a significant unmet medical need for VTE prophylaxis in the continuum of care of patients hospitalized for acute medical illnesses.
Major finding: Of the overall study population, only 7% received both inpatient and outpatient VTE prophylaxis.
Study details: An analysis of national data from 17,895 acutely ill hospitalized patients.
Disclosures: The study was funded by Portola Pharmaceuticals. The presenter reported having no financial conflicts.
Source: Amin A et al. THSNA 2018, Poster 51.
Protocol helped identify hospitalized children at risk for VTE
SAN DIEGO – Following simple institutional care guidelines helped clinicians identify pediatric patients at moderate-to-severe risk of venous thromboembolism (VTE), results from a single-center study showed.
“Hospital-acquired VTE is on the rise in the pediatric population,” lead study author Emily Southard, MD, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “This consists of a DVT or [pulmonary embolism] 48 hours or more after admission, or any time at the site of a central venous catheter.”
One published study found a 70% increased incidence in the pediatric population from 2001-2007 (Pediatrics 2009;124[4]:1001-8). More than half of the children in that study (63%) had at least one coexisting complex medical condition, with malignancy being the most common.
Hospital-acquired VTE cases tend to harbor a number of complications, said Dr. Southard, who is a pediatric hematology/oncology fellow at Children’s Hospital Colorado, Aurora. For example, 15%-20% of patients with a DVT will have a pulmonary embolism (PE) as well, 26% of patients with upper or lower extremity DVT develop post-thrombotic syndrome, and 3% of patients with PE develop chronic pulmonary hypertension.
“Medical costs are also impacted,” she said. “The cost for a hospital-acquired VTE in pediatrics increased the length of stay by about 8 days and increased the cost of hospital admission by more than $27,000.”
Known risk factors for VTE in this patient population include ICU admission (Odds Ratio, 2.14), presence of a central venous catheter (OR, 2.12), mechanical ventilation (OR, 1.56), and prolonged admission (OR, 1.03 for each day).
Risk factors in pediatric trauma patients include ICU admission (OR, 6.25), transfusion of blood products (OR, 2.1), lower extremity fracture (OR, 1.8), and neurosurgery (OR, 2.13). She and her associates hypothesized that understanding the relative contributions of clinical, biological, and genetic risk factors for pediatric VTE would help appropriately risk-stratify patients and allow better prophylactic approaches.
In 2012, Children’s Hospital Colorado implemented a VTE risk assessment tool as part of a hospital-wide patient safety initiative. The assessment is triggered via an Epic Best Practice Advisory to complete in certain higher-risk patients, including ICU patients, hematology/oncology floor patients, any patients with a central line catheter, and those who are over age 12 and obese.
Clinicians also assess for risk factors such as significant infection, recent surgery, and personal or family history of thrombophilia. Next, they classify each patient’s risk of hospital-acquired VTE as high, moderate, or low risk.
In a pilot study, Dr. Southard and her associates set out to validate the accuracy of the institution’s VTE risk assessment tool since it was implemented in 2012. She presented findings from 215 hospital-acquired VTE cases in patients younger than age 18, compared with age-matched inpatient controls. Data from patients under 6 months of age is available after October 2016, coinciding with a change in definition of pediatric hospital-acquired VTE.
Most hospital-acquired VTE patients (77.2%) ranged in age from 1-17 years. The number of patients admitted for a trauma diagnosis was similar between VTE cases and controls (7.4% vs. 7.9%, respectively). However, compared with controls, a significantly greater number of VTE cases were immobile (41.8% vs. 10.3%, respectively), required ICU admission (86.4% vs. 26.5%), had a central venous catheter (80.4% vs. 10.9%), had a positive blood culture (16.7% vs. 1.9%), required surgery or a medical procedure (57.7% vs. 36.7%), and had a longer procedure time (a mean of 151 vs. 133 minutes).
The researchers also found that upon initial admission, 7.9% of VTE cases were identified as high risk and another 21.9% were identified as moderate risk, compared with 1.2% and 3.7% in the controls, respectively.
“Patients identified as moderate or high risk for VTE were generally more medically complex patients,” Dr. Southard said.
Future directions of this project include expanding the patient population that has a risk assessment performed.
Dr. Southard reported having no financial disclosures.
SOURCE: Southard E et al. THSNA 2018.
SAN DIEGO – Following simple institutional care guidelines helped clinicians identify pediatric patients at moderate-to-severe risk of venous thromboembolism (VTE), results from a single-center study showed.
“Hospital-acquired VTE is on the rise in the pediatric population,” lead study author Emily Southard, MD, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “This consists of a DVT or [pulmonary embolism] 48 hours or more after admission, or any time at the site of a central venous catheter.”
One published study found a 70% increased incidence in the pediatric population from 2001-2007 (Pediatrics 2009;124[4]:1001-8). More than half of the children in that study (63%) had at least one coexisting complex medical condition, with malignancy being the most common.
Hospital-acquired VTE cases tend to harbor a number of complications, said Dr. Southard, who is a pediatric hematology/oncology fellow at Children’s Hospital Colorado, Aurora. For example, 15%-20% of patients with a DVT will have a pulmonary embolism (PE) as well, 26% of patients with upper or lower extremity DVT develop post-thrombotic syndrome, and 3% of patients with PE develop chronic pulmonary hypertension.
“Medical costs are also impacted,” she said. “The cost for a hospital-acquired VTE in pediatrics increased the length of stay by about 8 days and increased the cost of hospital admission by more than $27,000.”
Known risk factors for VTE in this patient population include ICU admission (Odds Ratio, 2.14), presence of a central venous catheter (OR, 2.12), mechanical ventilation (OR, 1.56), and prolonged admission (OR, 1.03 for each day).
Risk factors in pediatric trauma patients include ICU admission (OR, 6.25), transfusion of blood products (OR, 2.1), lower extremity fracture (OR, 1.8), and neurosurgery (OR, 2.13). She and her associates hypothesized that understanding the relative contributions of clinical, biological, and genetic risk factors for pediatric VTE would help appropriately risk-stratify patients and allow better prophylactic approaches.
In 2012, Children’s Hospital Colorado implemented a VTE risk assessment tool as part of a hospital-wide patient safety initiative. The assessment is triggered via an Epic Best Practice Advisory to complete in certain higher-risk patients, including ICU patients, hematology/oncology floor patients, any patients with a central line catheter, and those who are over age 12 and obese.
Clinicians also assess for risk factors such as significant infection, recent surgery, and personal or family history of thrombophilia. Next, they classify each patient’s risk of hospital-acquired VTE as high, moderate, or low risk.
In a pilot study, Dr. Southard and her associates set out to validate the accuracy of the institution’s VTE risk assessment tool since it was implemented in 2012. She presented findings from 215 hospital-acquired VTE cases in patients younger than age 18, compared with age-matched inpatient controls. Data from patients under 6 months of age is available after October 2016, coinciding with a change in definition of pediatric hospital-acquired VTE.
Most hospital-acquired VTE patients (77.2%) ranged in age from 1-17 years. The number of patients admitted for a trauma diagnosis was similar between VTE cases and controls (7.4% vs. 7.9%, respectively). However, compared with controls, a significantly greater number of VTE cases were immobile (41.8% vs. 10.3%, respectively), required ICU admission (86.4% vs. 26.5%), had a central venous catheter (80.4% vs. 10.9%), had a positive blood culture (16.7% vs. 1.9%), required surgery or a medical procedure (57.7% vs. 36.7%), and had a longer procedure time (a mean of 151 vs. 133 minutes).
The researchers also found that upon initial admission, 7.9% of VTE cases were identified as high risk and another 21.9% were identified as moderate risk, compared with 1.2% and 3.7% in the controls, respectively.
“Patients identified as moderate or high risk for VTE were generally more medically complex patients,” Dr. Southard said.
Future directions of this project include expanding the patient population that has a risk assessment performed.
Dr. Southard reported having no financial disclosures.
SOURCE: Southard E et al. THSNA 2018.
SAN DIEGO – Following simple institutional care guidelines helped clinicians identify pediatric patients at moderate-to-severe risk of venous thromboembolism (VTE), results from a single-center study showed.
“Hospital-acquired VTE is on the rise in the pediatric population,” lead study author Emily Southard, MD, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “This consists of a DVT or [pulmonary embolism] 48 hours or more after admission, or any time at the site of a central venous catheter.”
One published study found a 70% increased incidence in the pediatric population from 2001-2007 (Pediatrics 2009;124[4]:1001-8). More than half of the children in that study (63%) had at least one coexisting complex medical condition, with malignancy being the most common.
Hospital-acquired VTE cases tend to harbor a number of complications, said Dr. Southard, who is a pediatric hematology/oncology fellow at Children’s Hospital Colorado, Aurora. For example, 15%-20% of patients with a DVT will have a pulmonary embolism (PE) as well, 26% of patients with upper or lower extremity DVT develop post-thrombotic syndrome, and 3% of patients with PE develop chronic pulmonary hypertension.
“Medical costs are also impacted,” she said. “The cost for a hospital-acquired VTE in pediatrics increased the length of stay by about 8 days and increased the cost of hospital admission by more than $27,000.”
Known risk factors for VTE in this patient population include ICU admission (Odds Ratio, 2.14), presence of a central venous catheter (OR, 2.12), mechanical ventilation (OR, 1.56), and prolonged admission (OR, 1.03 for each day).
Risk factors in pediatric trauma patients include ICU admission (OR, 6.25), transfusion of blood products (OR, 2.1), lower extremity fracture (OR, 1.8), and neurosurgery (OR, 2.13). She and her associates hypothesized that understanding the relative contributions of clinical, biological, and genetic risk factors for pediatric VTE would help appropriately risk-stratify patients and allow better prophylactic approaches.
In 2012, Children’s Hospital Colorado implemented a VTE risk assessment tool as part of a hospital-wide patient safety initiative. The assessment is triggered via an Epic Best Practice Advisory to complete in certain higher-risk patients, including ICU patients, hematology/oncology floor patients, any patients with a central line catheter, and those who are over age 12 and obese.
Clinicians also assess for risk factors such as significant infection, recent surgery, and personal or family history of thrombophilia. Next, they classify each patient’s risk of hospital-acquired VTE as high, moderate, or low risk.
In a pilot study, Dr. Southard and her associates set out to validate the accuracy of the institution’s VTE risk assessment tool since it was implemented in 2012. She presented findings from 215 hospital-acquired VTE cases in patients younger than age 18, compared with age-matched inpatient controls. Data from patients under 6 months of age is available after October 2016, coinciding with a change in definition of pediatric hospital-acquired VTE.
Most hospital-acquired VTE patients (77.2%) ranged in age from 1-17 years. The number of patients admitted for a trauma diagnosis was similar between VTE cases and controls (7.4% vs. 7.9%, respectively). However, compared with controls, a significantly greater number of VTE cases were immobile (41.8% vs. 10.3%, respectively), required ICU admission (86.4% vs. 26.5%), had a central venous catheter (80.4% vs. 10.9%), had a positive blood culture (16.7% vs. 1.9%), required surgery or a medical procedure (57.7% vs. 36.7%), and had a longer procedure time (a mean of 151 vs. 133 minutes).
The researchers also found that upon initial admission, 7.9% of VTE cases were identified as high risk and another 21.9% were identified as moderate risk, compared with 1.2% and 3.7% in the controls, respectively.
“Patients identified as moderate or high risk for VTE were generally more medically complex patients,” Dr. Southard said.
Future directions of this project include expanding the patient population that has a risk assessment performed.
Dr. Southard reported having no financial disclosures.
SOURCE: Southard E et al. THSNA 2018.
REPORTING FROM THSNA 2018
Key clinical point:
Major finding: A significantly greater number of VTE patients were immobile (41.8% vs. 10.3%, respectively), required ICU admission (86.4% vs. 26.5%), and had a central venous catheter (80.4% vs. 10.9%), compared with controls.
Study details: A retrospective analysis of 215 hospital-acquired VTE cases in patients younger than age 18.
Disclosures: Dr. Southard reported having no financial disclosures.
Source: Southard E et al. THSNA 2018.