As the 2019-20 flu season got underway, more than half of American adults had not yet been vaccinated, according to a survey from the research organization NORC at the University of Chicago.

Only 44% of the 1,020 adults surveyed said that they had already received the vaccine as of Nov. 7-11, when the poll was conducted. Another 18% were planning to get a flu shot, but 37% of respondents said that did not intend to get one this season, the NORC reported. About 1% of those surveyed said they didn’t know or skipped the question.

Age was a strong determinant of vaccination status: 35% of those aged 18-29 years had gotten their flu shot, along with 36% of respondents aged 30-44 years and 34% of those aged 45- 59 years, compared with 65% of those aged 60 years and older. Of the respondents with children under age 18 years, 43% said that they were not planning to have the children vaccinated, the NORC said.

Concern about side effects, mentioned by 37% of those who were not planning to get vaccinated, was the most common reason given to avoid a flu shot, followed by belief that the vaccine doesn’t work very well (36%) and “never get the flu” (26%), the survey results showed.

“Widespread misconceptions exist regarding the safety and efficacy of flu shots. Because of the way the flu spreads in a community, failing to get a vaccination not only puts you at risk but also others for whom the consequences of the flu can be severe. Policymakers should focus on changing erroneous beliefs about immunizing against the flu,” said Caitlin Oppenheimer, who is senior vice president of public health research for the NORC, which has conducted the National Immunization Survey for the Centers for Disease Control and Prevention since 2005.

rfranki@mdedge.com

As the 2019-20 flu season got underway, more than half of American adults had not yet been vaccinated, according to a survey from the research organization NORC at the University of Chicago.

Only 44% of the 1,020 adults surveyed said that they had already received the vaccine as of Nov. 7-11, when the poll was conducted. Another 18% were planning to get a flu shot, but 37% of respondents said that did not intend to get one this season, the NORC reported. About 1% of those surveyed said they didn’t know or skipped the question.

Age was a strong determinant of vaccination status: 35% of those aged 18-29 years had gotten their flu shot, along with 36% of respondents aged 30-44 years and 34% of those aged 45- 59 years, compared with 65% of those aged 60 years and older. Of the respondents with children under age 18 years, 43% said that they were not planning to have the children vaccinated, the NORC said.

Concern about side effects, mentioned by 37% of those who were not planning to get vaccinated, was the most common reason given to avoid a flu shot, followed by belief that the vaccine doesn’t work very well (36%) and “never get the flu” (26%), the survey results showed.

“Widespread misconceptions exist regarding the safety and efficacy of flu shots. Because of the way the flu spreads in a community, failing to get a vaccination not only puts you at risk but also others for whom the consequences of the flu can be severe. Policymakers should focus on changing erroneous beliefs about immunizing against the flu,” said Caitlin Oppenheimer, who is senior vice president of public health research for the NORC, which has conducted the National Immunization Survey for the Centers for Disease Control and Prevention since 2005.

rfranki@mdedge.com

As the 2019-20 flu season got underway, more than half of American adults had not yet been vaccinated, according to a survey from the research organization NORC at the University of Chicago.

Only 44% of the 1,020 adults surveyed said that they had already received the vaccine as of Nov. 7-11, when the poll was conducted. Another 18% were planning to get a flu shot, but 37% of respondents said that did not intend to get one this season, the NORC reported. About 1% of those surveyed said they didn’t know or skipped the question.

Age was a strong determinant of vaccination status: 35% of those aged 18-29 years had gotten their flu shot, along with 36% of respondents aged 30-44 years and 34% of those aged 45- 59 years, compared with 65% of those aged 60 years and older. Of the respondents with children under age 18 years, 43% said that they were not planning to have the children vaccinated, the NORC said.

Concern about side effects, mentioned by 37% of those who were not planning to get vaccinated, was the most common reason given to avoid a flu shot, followed by belief that the vaccine doesn’t work very well (36%) and “never get the flu” (26%), the survey results showed.

“Widespread misconceptions exist regarding the safety and efficacy of flu shots. Because of the way the flu spreads in a community, failing to get a vaccination not only puts you at risk but also others for whom the consequences of the flu can be severe. Policymakers should focus on changing erroneous beliefs about immunizing against the flu,” said Caitlin Oppenheimer, who is senior vice president of public health research for the NORC, which has conducted the National Immunization Survey for the Centers for Disease Control and Prevention since 2005.

rfranki@mdedge.com

SAN FRANCISCO – Among patients with severe aortic stenosis at low surgical risk, both transcatheter and surgical aortic valve replacement resulted in substantial health status benefits at 1 year despite most patients having New York Heart Association class I or II symptoms at baseline.

Doug Brunk/MDedge News

However, when compared with surgical replacement, transcatheter replacement was linked with significantly improved disease-specific health status not only at 1 month, but also at 6 months and 1 year.

The findings come from an analysis of patients enrolled in the randomized PARTNER 3 trial, which showed that transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve. At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with surgical aortic valve replacement (SAVR), for a highly significant 46% relative risk reduction (N Engl J Med 2019 May 2;380:1695-705).

“The PARTNER 3 and Evolut Low Risk trials have demonstrated that transfemoral TAVR is both safe and effective when compared with SAVR in patients with severe aortic stenosis at low surgical risk,” Suzanne J. Baron, MD, MSc, said at the Transcatheter Cardiovascular Therapeutics annual meeting. “While prior studies have demonstrated improved early health status with transfemoral TAVR, compared with SAVR in intermediate and high-risk patients, there is little evidence of any late health status benefit with TAVR.”

To address this gap in knowledge, Dr. Baron, director of interventional cardiology research at Lahey Hospital and Medical Center in Burlington, Mass., and associates performed a prospective study alongside the PARTNER 3 randomized trial to understand the impact of valve replacement strategy on early and late health status in aortic stenosis patients at low surgical risk. She reported results from 449 low-risk patients with severe aortic stenosis who were assigned to transfemoral TAVR using a balloon-expandable valve, and 449 who were assigned to surgery in PARTNER 3. At baseline, the mean age of patients was 73 years, 69% were male, and the average STS (Society of Thoracic Surgeons) Risk Score was 1.9%. Rates of other comorbidities were generally low.

Patients in both groups reported a mild baseline impairment in health status. The mean Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score was 70, “which corresponds to only New York Heart Association Class II symptoms,” Dr. Baron said. “The SF-36 [Short Form 36] physical summary score was 44 for both groups, which is approximately half of a standard deviation below the population mean.”

As expected, patients who underwent TAVR showed substantially improved health status at 1 month based on the KCCQ-OS (mean difference,16 points; P less than .001). However, in contrast to prior studies, the researchers observed a persistent, although attenuated, benefit of TAVR over SAVR in disease-specific health status at 6 and 12 months (mean difference in KCCQ-OS of 2.6 and 1.8 points respectively; P less than .04 for both).

Dr. Baron said that a sustained benefit of TAVR over SAVR at 6 months and 1 year was observed on several KCCQ subscales, but a similar benefit was not noted on the generic health status measures such as the SF-36 physical summary score. “That’s likely reflective of the fact that, as a disease-specific measure, the KCCQ is much more sensitive in detecting meaningful differences in this population,” she explained. When change in health status was analyzed as an ordinal variable, with death as the worst outcome and large clinical improvement, which was defined as a 20-point or greater increase in the KCCQ-OS score, TAVR showed a significant benefit, compared with surgery at all time points (P less than .05).

In an effort to better understand the mechanism underlying this persistent albeit small late benefit in disease-specific health status with TAVR, the researchers generated cumulative distribution curves to display the proportion of patients who achieved a given change on the KCCQ-OS. A clear separation of the curves emerged, with 5.2% more patients in the TAVR group experiencing a change of at least 20 points, compared with the surgery group. “This suggests that the difference in late health status between the two groups is driven by this 5.2% absolute risk difference in the proportion of patients who experienced a large clinical improvement,” Dr. Baron said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Next, the researchers performed subgroup analyses to examine the interaction between the 1-year health status benefit of TAVR over surgery and prespecified baseline characteristics including age, gender, STS risk score, ejection fraction, atrial fibrillation, and New York Heart Association (NYHA) class. They observed a significant interaction between NYHA class and treatment effect such that patients who had NYHA class III or IV symptoms at baseline derived greater benefit from TAVR, compared with those who had NYHA class I or II symptoms at baseline.

“This finding suggests that it’s the patients with worse functional impairment at baseline who may be that subset of patients on the cumulative responder curves who gained better health status outcomes with TAVR, compared with surgery in the low-risk population,” Dr. Baron said.

Suzanne V. Arnold, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who was an invited discussant, said that it was “remarkable” that patients in the substudy were not particularly symptomatic and yet they still experienced close to a 20-point improvement in the KCCQ-OS score following TAVR, and asked whether frailty may have played a role in the 1.8-point adjusted difference in the KCCQ-OS score between TAVR and surgery at 1 year. Dr. Baron responded that she and her colleagues performed a subgroup analysis of patients who had two or more markers of frailty versus those who had one or less. Noting that there were only 20 patients in that subgroup, she said there was a significant signal that patients who were considered have two or more frail measures were considered to do much better with TAVR.

Dr. Baron concluded that the study’s overall findings, taken together with the clinical outcomes of the PARTNER 3 trial, “further support the use of TAVR in patients with severe [aortic stenosis] at low surgical risk. Longer-term follow up is needed (and ongoing) to determine whether the health status benefits of TAVR at 1 year are durable.”
The content of the study was published online at the time of presentation (J Am Coll Cardiol 2019 Sep 29. doi: 10.1016/j.jacc.2019.09.007). The PARTNER 3 quality of life substudy was funded by Edwards Lifesciences. Dr. Baron disclosed research funding and advisory board compensation from Boston Scientific Corp and consulting fees from Edwards Lifesciences.

dbrunk@mdedge.com

SAN FRANCISCO – Among patients with severe aortic stenosis at low surgical risk, both transcatheter and surgical aortic valve replacement resulted in substantial health status benefits at 1 year despite most patients having New York Heart Association class I or II symptoms at baseline.

Doug Brunk/MDedge News

However, when compared with surgical replacement, transcatheter replacement was linked with significantly improved disease-specific health status not only at 1 month, but also at 6 months and 1 year.

The findings come from an analysis of patients enrolled in the randomized PARTNER 3 trial, which showed that transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve. At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with surgical aortic valve replacement (SAVR), for a highly significant 46% relative risk reduction (N Engl J Med 2019 May 2;380:1695-705).

“The PARTNER 3 and Evolut Low Risk trials have demonstrated that transfemoral TAVR is both safe and effective when compared with SAVR in patients with severe aortic stenosis at low surgical risk,” Suzanne J. Baron, MD, MSc, said at the Transcatheter Cardiovascular Therapeutics annual meeting. “While prior studies have demonstrated improved early health status with transfemoral TAVR, compared with SAVR in intermediate and high-risk patients, there is little evidence of any late health status benefit with TAVR.”

To address this gap in knowledge, Dr. Baron, director of interventional cardiology research at Lahey Hospital and Medical Center in Burlington, Mass., and associates performed a prospective study alongside the PARTNER 3 randomized trial to understand the impact of valve replacement strategy on early and late health status in aortic stenosis patients at low surgical risk. She reported results from 449 low-risk patients with severe aortic stenosis who were assigned to transfemoral TAVR using a balloon-expandable valve, and 449 who were assigned to surgery in PARTNER 3. At baseline, the mean age of patients was 73 years, 69% were male, and the average STS (Society of Thoracic Surgeons) Risk Score was 1.9%. Rates of other comorbidities were generally low.

Patients in both groups reported a mild baseline impairment in health status. The mean Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score was 70, “which corresponds to only New York Heart Association Class II symptoms,” Dr. Baron said. “The SF-36 [Short Form 36] physical summary score was 44 for both groups, which is approximately half of a standard deviation below the population mean.”

As expected, patients who underwent TAVR showed substantially improved health status at 1 month based on the KCCQ-OS (mean difference,16 points; P less than .001). However, in contrast to prior studies, the researchers observed a persistent, although attenuated, benefit of TAVR over SAVR in disease-specific health status at 6 and 12 months (mean difference in KCCQ-OS of 2.6 and 1.8 points respectively; P less than .04 for both).

Dr. Baron said that a sustained benefit of TAVR over SAVR at 6 months and 1 year was observed on several KCCQ subscales, but a similar benefit was not noted on the generic health status measures such as the SF-36 physical summary score. “That’s likely reflective of the fact that, as a disease-specific measure, the KCCQ is much more sensitive in detecting meaningful differences in this population,” she explained. When change in health status was analyzed as an ordinal variable, with death as the worst outcome and large clinical improvement, which was defined as a 20-point or greater increase in the KCCQ-OS score, TAVR showed a significant benefit, compared with surgery at all time points (P less than .05).

In an effort to better understand the mechanism underlying this persistent albeit small late benefit in disease-specific health status with TAVR, the researchers generated cumulative distribution curves to display the proportion of patients who achieved a given change on the KCCQ-OS. A clear separation of the curves emerged, with 5.2% more patients in the TAVR group experiencing a change of at least 20 points, compared with the surgery group. “This suggests that the difference in late health status between the two groups is driven by this 5.2% absolute risk difference in the proportion of patients who experienced a large clinical improvement,” Dr. Baron said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Next, the researchers performed subgroup analyses to examine the interaction between the 1-year health status benefit of TAVR over surgery and prespecified baseline characteristics including age, gender, STS risk score, ejection fraction, atrial fibrillation, and New York Heart Association (NYHA) class. They observed a significant interaction between NYHA class and treatment effect such that patients who had NYHA class III or IV symptoms at baseline derived greater benefit from TAVR, compared with those who had NYHA class I or II symptoms at baseline.

“This finding suggests that it’s the patients with worse functional impairment at baseline who may be that subset of patients on the cumulative responder curves who gained better health status outcomes with TAVR, compared with surgery in the low-risk population,” Dr. Baron said.

Suzanne V. Arnold, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who was an invited discussant, said that it was “remarkable” that patients in the substudy were not particularly symptomatic and yet they still experienced close to a 20-point improvement in the KCCQ-OS score following TAVR, and asked whether frailty may have played a role in the 1.8-point adjusted difference in the KCCQ-OS score between TAVR and surgery at 1 year. Dr. Baron responded that she and her colleagues performed a subgroup analysis of patients who had two or more markers of frailty versus those who had one or less. Noting that there were only 20 patients in that subgroup, she said there was a significant signal that patients who were considered have two or more frail measures were considered to do much better with TAVR.

Dr. Baron concluded that the study’s overall findings, taken together with the clinical outcomes of the PARTNER 3 trial, “further support the use of TAVR in patients with severe [aortic stenosis] at low surgical risk. Longer-term follow up is needed (and ongoing) to determine whether the health status benefits of TAVR at 1 year are durable.”
The content of the study was published online at the time of presentation (J Am Coll Cardiol 2019 Sep 29. doi: 10.1016/j.jacc.2019.09.007). The PARTNER 3 quality of life substudy was funded by Edwards Lifesciences. Dr. Baron disclosed research funding and advisory board compensation from Boston Scientific Corp and consulting fees from Edwards Lifesciences.

dbrunk@mdedge.com

SAN FRANCISCO – Among patients with severe aortic stenosis at low surgical risk, both transcatheter and surgical aortic valve replacement resulted in substantial health status benefits at 1 year despite most patients having New York Heart Association class I or II symptoms at baseline.

Doug Brunk/MDedge News

However, when compared with surgical replacement, transcatheter replacement was linked with significantly improved disease-specific health status not only at 1 month, but also at 6 months and 1 year.

The findings come from an analysis of patients enrolled in the randomized PARTNER 3 trial, which showed that transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve. At 1 year post procedure, the rate of the primary composite endpoint comprising death, stroke, or cardiovascular rehospitalization was 8.5% in the TAVR group and 15.1% with surgical aortic valve replacement (SAVR), for a highly significant 46% relative risk reduction (N Engl J Med 2019 May 2;380:1695-705).

“The PARTNER 3 and Evolut Low Risk trials have demonstrated that transfemoral TAVR is both safe and effective when compared with SAVR in patients with severe aortic stenosis at low surgical risk,” Suzanne J. Baron, MD, MSc, said at the Transcatheter Cardiovascular Therapeutics annual meeting. “While prior studies have demonstrated improved early health status with transfemoral TAVR, compared with SAVR in intermediate and high-risk patients, there is little evidence of any late health status benefit with TAVR.”

To address this gap in knowledge, Dr. Baron, director of interventional cardiology research at Lahey Hospital and Medical Center in Burlington, Mass., and associates performed a prospective study alongside the PARTNER 3 randomized trial to understand the impact of valve replacement strategy on early and late health status in aortic stenosis patients at low surgical risk. She reported results from 449 low-risk patients with severe aortic stenosis who were assigned to transfemoral TAVR using a balloon-expandable valve, and 449 who were assigned to surgery in PARTNER 3. At baseline, the mean age of patients was 73 years, 69% were male, and the average STS (Society of Thoracic Surgeons) Risk Score was 1.9%. Rates of other comorbidities were generally low.

Patients in both groups reported a mild baseline impairment in health status. The mean Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score was 70, “which corresponds to only New York Heart Association Class II symptoms,” Dr. Baron said. “The SF-36 [Short Form 36] physical summary score was 44 for both groups, which is approximately half of a standard deviation below the population mean.”

As expected, patients who underwent TAVR showed substantially improved health status at 1 month based on the KCCQ-OS (mean difference,16 points; P less than .001). However, in contrast to prior studies, the researchers observed a persistent, although attenuated, benefit of TAVR over SAVR in disease-specific health status at 6 and 12 months (mean difference in KCCQ-OS of 2.6 and 1.8 points respectively; P less than .04 for both).

Dr. Baron said that a sustained benefit of TAVR over SAVR at 6 months and 1 year was observed on several KCCQ subscales, but a similar benefit was not noted on the generic health status measures such as the SF-36 physical summary score. “That’s likely reflective of the fact that, as a disease-specific measure, the KCCQ is much more sensitive in detecting meaningful differences in this population,” she explained. When change in health status was analyzed as an ordinal variable, with death as the worst outcome and large clinical improvement, which was defined as a 20-point or greater increase in the KCCQ-OS score, TAVR showed a significant benefit, compared with surgery at all time points (P less than .05).

In an effort to better understand the mechanism underlying this persistent albeit small late benefit in disease-specific health status with TAVR, the researchers generated cumulative distribution curves to display the proportion of patients who achieved a given change on the KCCQ-OS. A clear separation of the curves emerged, with 5.2% more patients in the TAVR group experiencing a change of at least 20 points, compared with the surgery group. “This suggests that the difference in late health status between the two groups is driven by this 5.2% absolute risk difference in the proportion of patients who experienced a large clinical improvement,” Dr. Baron said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Next, the researchers performed subgroup analyses to examine the interaction between the 1-year health status benefit of TAVR over surgery and prespecified baseline characteristics including age, gender, STS risk score, ejection fraction, atrial fibrillation, and New York Heart Association (NYHA) class. They observed a significant interaction between NYHA class and treatment effect such that patients who had NYHA class III or IV symptoms at baseline derived greater benefit from TAVR, compared with those who had NYHA class I or II symptoms at baseline.

“This finding suggests that it’s the patients with worse functional impairment at baseline who may be that subset of patients on the cumulative responder curves who gained better health status outcomes with TAVR, compared with surgery in the low-risk population,” Dr. Baron said.

Suzanne V. Arnold, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who was an invited discussant, said that it was “remarkable” that patients in the substudy were not particularly symptomatic and yet they still experienced close to a 20-point improvement in the KCCQ-OS score following TAVR, and asked whether frailty may have played a role in the 1.8-point adjusted difference in the KCCQ-OS score between TAVR and surgery at 1 year. Dr. Baron responded that she and her colleagues performed a subgroup analysis of patients who had two or more markers of frailty versus those who had one or less. Noting that there were only 20 patients in that subgroup, she said there was a significant signal that patients who were considered have two or more frail measures were considered to do much better with TAVR.

Dr. Baron concluded that the study’s overall findings, taken together with the clinical outcomes of the PARTNER 3 trial, “further support the use of TAVR in patients with severe [aortic stenosis] at low surgical risk. Longer-term follow up is needed (and ongoing) to determine whether the health status benefits of TAVR at 1 year are durable.”
The content of the study was published online at the time of presentation (J Am Coll Cardiol 2019 Sep 29. doi: 10.1016/j.jacc.2019.09.007). The PARTNER 3 quality of life substudy was funded by Edwards Lifesciences. Dr. Baron disclosed research funding and advisory board compensation from Boston Scientific Corp and consulting fees from Edwards Lifesciences.

dbrunk@mdedge.com

ORLANDO – Posttransplant cyclophosphamide may be superior to conventional immunosuppression as graft-versus-host disease prophylaxis, according to findings presented at the annual meeting of the American Society of Hematology.

Jennifer Smith/MDedge News

A phase 3 trial showed that posttransplant cyclophosphamide (PT-Cy) reduced graft-versus-host disease (GVHD) without affecting relapse. Rates of acute and chronic GVHD were significantly lower among patients who received PT-Cy than among those who received conventional immunosuppression (CIS). Rates of progression/relapse, progression-free survival, and overall survival were similar between the PT-Cy and CIS arms.

These results suggest PT-Cy provides a “long-term benefit and positive impact on quality of life” for patients undergoing allogeneic hematopoietic stem cell transplant, according to Annoek E.C. Broers, MD, PhD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands. Dr. Broers presented the results during the plenary session at ASH 2019.

The trial enrolled 160 patients with leukemias, lymphomas, myelomas, and other hematologic malignancies. All patients had a matched, related donor or an 8/8 or greater matched, unrelated donor.

The patients were randomized to receive CIS (n = 55) or PT-Cy (n = 105) as GVHD prophylaxis. The CIS regimen consisted of cyclosporine A (from day –3 to 180) and mycophenolic acid (from day 0 to 84). Patients in the PT-Cy arm received cyclophosphamide at 50 mg/kg (days 3 and 4) and cyclosporine A (from day 5 to 70).

Baseline characteristics were similar between the treatment arms. The median age was 58 years in the CIS arm and 57 years in the PT-Cy arm. A majority of patients were men – 63% and 67%, respectively.

Two patients in the CIS arm received myeloablative conditioning, but all other patients received reduced-intensity conditioning. Most patients in the CIS arm (67%) and the PT-Cy arm (70%) had a matched, unrelated donor. All patients in the CIS arm and 96% in the PT-Cy arm received peripheral blood cell grafts.

PT-Cy significantly reduced the cumulative incidence of acute and chronic GVHD. The incidence of grade 2-4 acute GVHD at 6 months was 48% in the CIS arm and 32% in the PT-Cy arm (P = .014). The incidence of chronic extensive GVHD at 24 months was 50% and 19%, respectively (P = .001).

There were no significant between-arm differences for any other individual endpoint assessed.

“With a median follow-up of 3.2 years, so far, there’s no difference in the cumulative incidence of progression or relapse, nor is there a difference in progression-free or overall survival,” Dr. Broers said.

At 60 months, the rate of relapse/progression was 32% in the PT-Cy arm and 26% in the CIS arm (P = .36). The rate of nonrelapse mortality was 11% and 14%, respectively (P = .53).

At 60 months, the progression-free survival was 60% in the CIS arm and 58% in the PT-Cy arm (P = .67). The overall survival was 69% and 63%, respectively (P = .63).

In addition to assessing endpoints that “determine the success of our transplant strategy,” Dr. Broers said she and her colleagues also looked at a combined endpoint to account for “the effect GVHD has on morbidity and quality of life.” That endpoint is GVHD- and relapse-free survival.

The researchers found that PT-Cy improved GVHD- and relapse-free survival at 12 months. It was 22% in the CIS arm and 45% in the PT-Cy arm (P = .001). PT-Cy conferred this benefit irrespective of donor type, Dr. Broers noted.

Overall, the incidence of adverse events was somewhat higher in the PT-Cy arm (60%) than in the CIS arm (42%). The incidence of infections also was higher in the PT-Cy arm (41%) than in the CIS arm (21%), and this was largely caused by a greater incidence of neutropenic fever with PT-Cy (25% vs. 15%).

The study was funded by the Dutch Cancer Society, and Novartis provided the mycophenolic acid used in the study. Dr. Broers reported having no conflicts of interest.

jensmith@mdedge.com

SOURCE: Broers AEC et al. ASH 2019, Abstract 1.
 

ORLANDO – Posttransplant cyclophosphamide may be superior to conventional immunosuppression as graft-versus-host disease prophylaxis, according to findings presented at the annual meeting of the American Society of Hematology.

Jennifer Smith/MDedge News

A phase 3 trial showed that posttransplant cyclophosphamide (PT-Cy) reduced graft-versus-host disease (GVHD) without affecting relapse. Rates of acute and chronic GVHD were significantly lower among patients who received PT-Cy than among those who received conventional immunosuppression (CIS). Rates of progression/relapse, progression-free survival, and overall survival were similar between the PT-Cy and CIS arms.

These results suggest PT-Cy provides a “long-term benefit and positive impact on quality of life” for patients undergoing allogeneic hematopoietic stem cell transplant, according to Annoek E.C. Broers, MD, PhD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands. Dr. Broers presented the results during the plenary session at ASH 2019.

The trial enrolled 160 patients with leukemias, lymphomas, myelomas, and other hematologic malignancies. All patients had a matched, related donor or an 8/8 or greater matched, unrelated donor.

The patients were randomized to receive CIS (n = 55) or PT-Cy (n = 105) as GVHD prophylaxis. The CIS regimen consisted of cyclosporine A (from day –3 to 180) and mycophenolic acid (from day 0 to 84). Patients in the PT-Cy arm received cyclophosphamide at 50 mg/kg (days 3 and 4) and cyclosporine A (from day 5 to 70).

Baseline characteristics were similar between the treatment arms. The median age was 58 years in the CIS arm and 57 years in the PT-Cy arm. A majority of patients were men – 63% and 67%, respectively.

Two patients in the CIS arm received myeloablative conditioning, but all other patients received reduced-intensity conditioning. Most patients in the CIS arm (67%) and the PT-Cy arm (70%) had a matched, unrelated donor. All patients in the CIS arm and 96% in the PT-Cy arm received peripheral blood cell grafts.

PT-Cy significantly reduced the cumulative incidence of acute and chronic GVHD. The incidence of grade 2-4 acute GVHD at 6 months was 48% in the CIS arm and 32% in the PT-Cy arm (P = .014). The incidence of chronic extensive GVHD at 24 months was 50% and 19%, respectively (P = .001).

There were no significant between-arm differences for any other individual endpoint assessed.

“With a median follow-up of 3.2 years, so far, there’s no difference in the cumulative incidence of progression or relapse, nor is there a difference in progression-free or overall survival,” Dr. Broers said.

At 60 months, the rate of relapse/progression was 32% in the PT-Cy arm and 26% in the CIS arm (P = .36). The rate of nonrelapse mortality was 11% and 14%, respectively (P = .53).

At 60 months, the progression-free survival was 60% in the CIS arm and 58% in the PT-Cy arm (P = .67). The overall survival was 69% and 63%, respectively (P = .63).

In addition to assessing endpoints that “determine the success of our transplant strategy,” Dr. Broers said she and her colleagues also looked at a combined endpoint to account for “the effect GVHD has on morbidity and quality of life.” That endpoint is GVHD- and relapse-free survival.

The researchers found that PT-Cy improved GVHD- and relapse-free survival at 12 months. It was 22% in the CIS arm and 45% in the PT-Cy arm (P = .001). PT-Cy conferred this benefit irrespective of donor type, Dr. Broers noted.

Overall, the incidence of adverse events was somewhat higher in the PT-Cy arm (60%) than in the CIS arm (42%). The incidence of infections also was higher in the PT-Cy arm (41%) than in the CIS arm (21%), and this was largely caused by a greater incidence of neutropenic fever with PT-Cy (25% vs. 15%).

The study was funded by the Dutch Cancer Society, and Novartis provided the mycophenolic acid used in the study. Dr. Broers reported having no conflicts of interest.

jensmith@mdedge.com

SOURCE: Broers AEC et al. ASH 2019, Abstract 1.
 

ORLANDO – Posttransplant cyclophosphamide may be superior to conventional immunosuppression as graft-versus-host disease prophylaxis, according to findings presented at the annual meeting of the American Society of Hematology.

Jennifer Smith/MDedge News

A phase 3 trial showed that posttransplant cyclophosphamide (PT-Cy) reduced graft-versus-host disease (GVHD) without affecting relapse. Rates of acute and chronic GVHD were significantly lower among patients who received PT-Cy than among those who received conventional immunosuppression (CIS). Rates of progression/relapse, progression-free survival, and overall survival were similar between the PT-Cy and CIS arms.

These results suggest PT-Cy provides a “long-term benefit and positive impact on quality of life” for patients undergoing allogeneic hematopoietic stem cell transplant, according to Annoek E.C. Broers, MD, PhD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands. Dr. Broers presented the results during the plenary session at ASH 2019.

The trial enrolled 160 patients with leukemias, lymphomas, myelomas, and other hematologic malignancies. All patients had a matched, related donor or an 8/8 or greater matched, unrelated donor.

The patients were randomized to receive CIS (n = 55) or PT-Cy (n = 105) as GVHD prophylaxis. The CIS regimen consisted of cyclosporine A (from day –3 to 180) and mycophenolic acid (from day 0 to 84). Patients in the PT-Cy arm received cyclophosphamide at 50 mg/kg (days 3 and 4) and cyclosporine A (from day 5 to 70).

Baseline characteristics were similar between the treatment arms. The median age was 58 years in the CIS arm and 57 years in the PT-Cy arm. A majority of patients were men – 63% and 67%, respectively.

Two patients in the CIS arm received myeloablative conditioning, but all other patients received reduced-intensity conditioning. Most patients in the CIS arm (67%) and the PT-Cy arm (70%) had a matched, unrelated donor. All patients in the CIS arm and 96% in the PT-Cy arm received peripheral blood cell grafts.

PT-Cy significantly reduced the cumulative incidence of acute and chronic GVHD. The incidence of grade 2-4 acute GVHD at 6 months was 48% in the CIS arm and 32% in the PT-Cy arm (P = .014). The incidence of chronic extensive GVHD at 24 months was 50% and 19%, respectively (P = .001).

There were no significant between-arm differences for any other individual endpoint assessed.

“With a median follow-up of 3.2 years, so far, there’s no difference in the cumulative incidence of progression or relapse, nor is there a difference in progression-free or overall survival,” Dr. Broers said.

At 60 months, the rate of relapse/progression was 32% in the PT-Cy arm and 26% in the CIS arm (P = .36). The rate of nonrelapse mortality was 11% and 14%, respectively (P = .53).

At 60 months, the progression-free survival was 60% in the CIS arm and 58% in the PT-Cy arm (P = .67). The overall survival was 69% and 63%, respectively (P = .63).

In addition to assessing endpoints that “determine the success of our transplant strategy,” Dr. Broers said she and her colleagues also looked at a combined endpoint to account for “the effect GVHD has on morbidity and quality of life.” That endpoint is GVHD- and relapse-free survival.

The researchers found that PT-Cy improved GVHD- and relapse-free survival at 12 months. It was 22% in the CIS arm and 45% in the PT-Cy arm (P = .001). PT-Cy conferred this benefit irrespective of donor type, Dr. Broers noted.

Overall, the incidence of adverse events was somewhat higher in the PT-Cy arm (60%) than in the CIS arm (42%). The incidence of infections also was higher in the PT-Cy arm (41%) than in the CIS arm (21%), and this was largely caused by a greater incidence of neutropenic fever with PT-Cy (25% vs. 15%).

The study was funded by the Dutch Cancer Society, and Novartis provided the mycophenolic acid used in the study. Dr. Broers reported having no conflicts of interest.

jensmith@mdedge.com

SOURCE: Broers AEC et al. ASH 2019, Abstract 1.
 

BALTIMORE – Initial presentations of Dravet syndrome often differ from the prototypical phenotype, researchers said at the annual meeting of the American Epilepsy Society. About half of patients have an afebrile seizure as their first seizure, and it is common for patients to present with seizures before age 5 months. Patients also may have seizure onset after age 18 months, said Wenhui Li, a researcher affiliated with Children’s Hospital of Fudan University in Shanghai and University of Melbourne, and colleagues.

“Subtle differences in Dravet syndrome phenotypes lead to delayed diagnosis,” the researchers said. “Understanding key features within the phenotypic spectrum will assist clinicians in evaluating whether a child has Dravet syndrome, facilitating early diagnosis for precision therapies.”

Typically, Dravet syndrome is thought to begin with prolonged febrile hemiclonic or generalized tonic-clonic seizures at about age 6 months in normally developing infants. Multiple seizure types occur during subsequent years, including focal impaired awareness, bilateral tonic-clonic, absence, and myoclonic seizures.

Patients often do not receive a diagnosis of Dravet syndrome until they are older than 3 years, after “developmental plateau or regression occurs in the second year,” the investigators said. “Earlier diagnosis is critical for optimal management.”

To outline the range of phenotypes, researchers analyzed the clinical histories of 188 patients with Dravet syndrome and pathogenic SCN1A variants. They excluded from their analysis patients with SCN1A-positive genetic epilepsy with febrile seizures plus (GEFS+).

In all, 53% of the patients were female, and 2% had developmental delay prior to the onset of seizures. Age at seizure onset ranged from 1.5 months to 21 months (median, 5.75 months). Three patients had seizure onset after age 12 months, the authors noted.

In cases where the first seizure type could be classified, 52% had generalized tonic-clonic seizures at onset, 37% had hemiclonic seizures, 4% myoclonic seizures, 4% focal impaired awareness seizures, and 0.5% absence seizures. In addition, 1% had hemiclonic and myoclonic seizures, and 2% had tonic-clonic and myoclonic seizures.

Fifty-four percent of patients were febrile during their first seizure, and 46% were afebrile.

Status epilepticus as the first seizure occurred in about 44% of cases, while 35% of patients had a first seizure duration of 5 minutes or less.

The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Li W et al. AES 2019. Abstract 2.116.

BALTIMORE – Initial presentations of Dravet syndrome often differ from the prototypical phenotype, researchers said at the annual meeting of the American Epilepsy Society. About half of patients have an afebrile seizure as their first seizure, and it is common for patients to present with seizures before age 5 months. Patients also may have seizure onset after age 18 months, said Wenhui Li, a researcher affiliated with Children’s Hospital of Fudan University in Shanghai and University of Melbourne, and colleagues.

“Subtle differences in Dravet syndrome phenotypes lead to delayed diagnosis,” the researchers said. “Understanding key features within the phenotypic spectrum will assist clinicians in evaluating whether a child has Dravet syndrome, facilitating early diagnosis for precision therapies.”

Typically, Dravet syndrome is thought to begin with prolonged febrile hemiclonic or generalized tonic-clonic seizures at about age 6 months in normally developing infants. Multiple seizure types occur during subsequent years, including focal impaired awareness, bilateral tonic-clonic, absence, and myoclonic seizures.

Patients often do not receive a diagnosis of Dravet syndrome until they are older than 3 years, after “developmental plateau or regression occurs in the second year,” the investigators said. “Earlier diagnosis is critical for optimal management.”

To outline the range of phenotypes, researchers analyzed the clinical histories of 188 patients with Dravet syndrome and pathogenic SCN1A variants. They excluded from their analysis patients with SCN1A-positive genetic epilepsy with febrile seizures plus (GEFS+).

In all, 53% of the patients were female, and 2% had developmental delay prior to the onset of seizures. Age at seizure onset ranged from 1.5 months to 21 months (median, 5.75 months). Three patients had seizure onset after age 12 months, the authors noted.

In cases where the first seizure type could be classified, 52% had generalized tonic-clonic seizures at onset, 37% had hemiclonic seizures, 4% myoclonic seizures, 4% focal impaired awareness seizures, and 0.5% absence seizures. In addition, 1% had hemiclonic and myoclonic seizures, and 2% had tonic-clonic and myoclonic seizures.

Fifty-four percent of patients were febrile during their first seizure, and 46% were afebrile.

Status epilepticus as the first seizure occurred in about 44% of cases, while 35% of patients had a first seizure duration of 5 minutes or less.

The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Li W et al. AES 2019. Abstract 2.116.

BALTIMORE – Initial presentations of Dravet syndrome often differ from the prototypical phenotype, researchers said at the annual meeting of the American Epilepsy Society. About half of patients have an afebrile seizure as their first seizure, and it is common for patients to present with seizures before age 5 months. Patients also may have seizure onset after age 18 months, said Wenhui Li, a researcher affiliated with Children’s Hospital of Fudan University in Shanghai and University of Melbourne, and colleagues.

“Subtle differences in Dravet syndrome phenotypes lead to delayed diagnosis,” the researchers said. “Understanding key features within the phenotypic spectrum will assist clinicians in evaluating whether a child has Dravet syndrome, facilitating early diagnosis for precision therapies.”

Typically, Dravet syndrome is thought to begin with prolonged febrile hemiclonic or generalized tonic-clonic seizures at about age 6 months in normally developing infants. Multiple seizure types occur during subsequent years, including focal impaired awareness, bilateral tonic-clonic, absence, and myoclonic seizures.

Patients often do not receive a diagnosis of Dravet syndrome until they are older than 3 years, after “developmental plateau or regression occurs in the second year,” the investigators said. “Earlier diagnosis is critical for optimal management.”

To outline the range of phenotypes, researchers analyzed the clinical histories of 188 patients with Dravet syndrome and pathogenic SCN1A variants. They excluded from their analysis patients with SCN1A-positive genetic epilepsy with febrile seizures plus (GEFS+).

In all, 53% of the patients were female, and 2% had developmental delay prior to the onset of seizures. Age at seizure onset ranged from 1.5 months to 21 months (median, 5.75 months). Three patients had seizure onset after age 12 months, the authors noted.

In cases where the first seizure type could be classified, 52% had generalized tonic-clonic seizures at onset, 37% had hemiclonic seizures, 4% myoclonic seizures, 4% focal impaired awareness seizures, and 0.5% absence seizures. In addition, 1% had hemiclonic and myoclonic seizures, and 2% had tonic-clonic and myoclonic seizures.

Fifty-four percent of patients were febrile during their first seizure, and 46% were afebrile.

Status epilepticus as the first seizure occurred in about 44% of cases, while 35% of patients had a first seizure duration of 5 minutes or less.

The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Li W et al. AES 2019. Abstract 2.116.

PHILADELPHIA – Obese people living in the United Kingdom who underwent bariatric surgery had a two-thirds lower rate of major cerebrovascular events than that of a matched group of obese residents who did not undergo bariatric surgery, in a retrospective study of 8,424 people followed for a mean of just over 11 years.

Mitchel L. Zoler/MDedge News

Although the cut in cerebrovascular events that linked with bariatric surgery shown by the analysis was mostly driven by a reduced rate of transient ischemic attacks, a potentially unreliable diagnosis, the results showed consistent reductions in the rates of acute ischemic strokes as well as in acute, nontraumatic intracranial hemorrhages, two other components of the combined primary endpoint, Maddalena Ardissino, MBBS, said at the American Heart Association scientific sessions.

This finding of an apparent benefit from bariatric surgery in obese patients in a large U.K. database confirms other findings from a “fast-growing” evidence base showing benefits from bariatric surgery for reducing other types of cardiovascular disease events, said Dr. Ardissino, a researcher at Imperial College, London. However, the impact of bariatric surgery specifically on cerebrovascular events had not received much attention in published studies, she noted.

Her study used data collected by the Clinical Practice Research Datalink, which has primary and secondary care health records for about 42 million U.K. residents. The researchers focused on more than 251,000 obese U.K. adults (body mass index of 30 kg/m² or greater) without a history of a cerebrovascular event who had at least 1 year of follow-up, a data file that included 4,212 adults who had undergone bariatric surgery. Their analysis matched these surgical patients with an equal number of obese adults who did not have surgery, pairing the cases and controls based on age, sex, and BMI. The resulting matched cohorts each averaged 50 years old, with a mean BMI of 40.5 kg/m².

During just over 11 years of average follow-up, the incidence of acute ischemic stroke, acute intracranial hemorrhage, subarachnoid hemorrhage, or transient ischemic attack was about 1.3% in those without bariatric surgery and about 0.4% in those who had surgery, an absolute risk reduction of 0.9 linked with surgery and a relative risk reduction of 65% that was statistically significant, Dr. Ardissino reported. All-cause mortality was about 70% lower in the group that underwent bariatric surgery compared with those who did not have surgery, a finding that confirmed prior reports. She cautioned that the analysis was limited by a relatively low number of total events, and by the small number of criteria used for cohort matching that might have left unadjusted certain potential confounders such as the level of engagement people had with their medical care.

mzoler@mdedge.com

SOURCE: Ardissino M. AHA 2019, Abstract 335.

PHILADELPHIA – Obese people living in the United Kingdom who underwent bariatric surgery had a two-thirds lower rate of major cerebrovascular events than that of a matched group of obese residents who did not undergo bariatric surgery, in a retrospective study of 8,424 people followed for a mean of just over 11 years.

Mitchel L. Zoler/MDedge News

Although the cut in cerebrovascular events that linked with bariatric surgery shown by the analysis was mostly driven by a reduced rate of transient ischemic attacks, a potentially unreliable diagnosis, the results showed consistent reductions in the rates of acute ischemic strokes as well as in acute, nontraumatic intracranial hemorrhages, two other components of the combined primary endpoint, Maddalena Ardissino, MBBS, said at the American Heart Association scientific sessions.

This finding of an apparent benefit from bariatric surgery in obese patients in a large U.K. database confirms other findings from a “fast-growing” evidence base showing benefits from bariatric surgery for reducing other types of cardiovascular disease events, said Dr. Ardissino, a researcher at Imperial College, London. However, the impact of bariatric surgery specifically on cerebrovascular events had not received much attention in published studies, she noted.

Her study used data collected by the Clinical Practice Research Datalink, which has primary and secondary care health records for about 42 million U.K. residents. The researchers focused on more than 251,000 obese U.K. adults (body mass index of 30 kg/m² or greater) without a history of a cerebrovascular event who had at least 1 year of follow-up, a data file that included 4,212 adults who had undergone bariatric surgery. Their analysis matched these surgical patients with an equal number of obese adults who did not have surgery, pairing the cases and controls based on age, sex, and BMI. The resulting matched cohorts each averaged 50 years old, with a mean BMI of 40.5 kg/m².

During just over 11 years of average follow-up, the incidence of acute ischemic stroke, acute intracranial hemorrhage, subarachnoid hemorrhage, or transient ischemic attack was about 1.3% in those without bariatric surgery and about 0.4% in those who had surgery, an absolute risk reduction of 0.9 linked with surgery and a relative risk reduction of 65% that was statistically significant, Dr. Ardissino reported. All-cause mortality was about 70% lower in the group that underwent bariatric surgery compared with those who did not have surgery, a finding that confirmed prior reports. She cautioned that the analysis was limited by a relatively low number of total events, and by the small number of criteria used for cohort matching that might have left unadjusted certain potential confounders such as the level of engagement people had with their medical care.

mzoler@mdedge.com

SOURCE: Ardissino M. AHA 2019, Abstract 335.

PHILADELPHIA – Obese people living in the United Kingdom who underwent bariatric surgery had a two-thirds lower rate of major cerebrovascular events than that of a matched group of obese residents who did not undergo bariatric surgery, in a retrospective study of 8,424 people followed for a mean of just over 11 years.

Mitchel L. Zoler/MDedge News

Although the cut in cerebrovascular events that linked with bariatric surgery shown by the analysis was mostly driven by a reduced rate of transient ischemic attacks, a potentially unreliable diagnosis, the results showed consistent reductions in the rates of acute ischemic strokes as well as in acute, nontraumatic intracranial hemorrhages, two other components of the combined primary endpoint, Maddalena Ardissino, MBBS, said at the American Heart Association scientific sessions.

This finding of an apparent benefit from bariatric surgery in obese patients in a large U.K. database confirms other findings from a “fast-growing” evidence base showing benefits from bariatric surgery for reducing other types of cardiovascular disease events, said Dr. Ardissino, a researcher at Imperial College, London. However, the impact of bariatric surgery specifically on cerebrovascular events had not received much attention in published studies, she noted.

Her study used data collected by the Clinical Practice Research Datalink, which has primary and secondary care health records for about 42 million U.K. residents. The researchers focused on more than 251,000 obese U.K. adults (body mass index of 30 kg/m² or greater) without a history of a cerebrovascular event who had at least 1 year of follow-up, a data file that included 4,212 adults who had undergone bariatric surgery. Their analysis matched these surgical patients with an equal number of obese adults who did not have surgery, pairing the cases and controls based on age, sex, and BMI. The resulting matched cohorts each averaged 50 years old, with a mean BMI of 40.5 kg/m².

During just over 11 years of average follow-up, the incidence of acute ischemic stroke, acute intracranial hemorrhage, subarachnoid hemorrhage, or transient ischemic attack was about 1.3% in those without bariatric surgery and about 0.4% in those who had surgery, an absolute risk reduction of 0.9 linked with surgery and a relative risk reduction of 65% that was statistically significant, Dr. Ardissino reported. All-cause mortality was about 70% lower in the group that underwent bariatric surgery compared with those who did not have surgery, a finding that confirmed prior reports. She cautioned that the analysis was limited by a relatively low number of total events, and by the small number of criteria used for cohort matching that might have left unadjusted certain potential confounders such as the level of engagement people had with their medical care.

mzoler@mdedge.com

SOURCE: Ardissino M. AHA 2019, Abstract 335.

Currently available fibrosis scoring systems appear to have only a modest predictive ability for development of severe liver disease in the general population, according to authors of a large, retrospective cohort study.

Of five noninvasive scoring systems evaluated, all did have high negative predictive value in the general population, according to authors of the study, which included data on more than 800,000 individuals in Sweden. However, their sensitivities were low, with most of the individuals who developed severe liver disease over a 10-year follow-up period initially classified as being at low risk for advanced fibrosis, according to the study authors, led by Hannes Hagström, MD, PhD, of the division of hepatology, Karolinska University Hospital, Stockholm.

The scoring systems tended to perform better in patients at higher risk for nonalcoholic fatty liver disease (NAFLD) at baseline, suggesting the best use of the tools is in patients at increased risk or who have liver disease indications, Dr. Hagström and coauthors wrote in a report on the study.

“Although useful in populations with a high prevalence of advanced fibrosis, current scores lack precision for usage in the general population for which the prevalence of advanced fibrosis is much lower,” Dr. Hagström and colleagues said.

The scoring systems were derived from high-risk cohorts with liver diseases, the authors noted, stating that the disease prevalence in any given population will affect the performance of a test that’s intended to diagnose that specific disease.

“New and improved” scoring systems should be developed to more effectively pinpoint patients with NAFLD who are at higher risk of a severe liver event, they added in the report, which appears in Gastroenterology.

The population-based cohort study by Dr. Hagström and colleagues was based on data from 812,073 patients enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort between 1985 and 1996. Investigators said they excluded patients under 35 and over 79 years of age, patients with severe liver disease at baseline, and those with a prior diagnosis of alcohol or drug abuse.

Investigators used available data to calculate five scores, including the AST to Platelet Ratio Index (APRI); the body mass index, AST/ALT ratio, and diabetes (BARD) score; the Fibrosis-4 (FIB-4) score; Forns Index; and NAFLD Fibrosis Score (NFS).

At baseline, 0.5%-8.0% of patients were considered to be at high risk for advanced fibrosis, depending on the test used, investigators said. With up to 10 years of follow-up, the proportion of individuals who developed severe liver diseases (cirrhosis, liver failure, hepatocellular carcinoma, liver transplantation, or decompensated liver disease) was 0.3%-0.6%, and with the maximum 27 years of follow-up, the incidence ranged from 1.0% to 1.4%.

There was a “strong association” between baseline risk of fibrosis and development of severe liver diseases; however, the majority of cases occurred in patients deemed low risk at baseline, Dr. Hagström and colleagues noted in their report.

For example, 12.4% of individuals classified as high risk by APRI developed severe liver diseases over 10 years, compared to just 0.4% of the low-risk group, yet out of 723 cases, 502 (69%) occurred in the low-risk patients, the data show.

Hazard ratios did increase with risk level, and at the high-risk level, adjusted hazard ratios ranged from 1.7 (95% confidence interval [CI], 1.1-2.5) for the high-risk BARD patients to 45.9 (95% CI, 36.1-58.3) for the high-risk APRI patients, investigators reported.

Taken together, results of this study demonstrate that the performance of all scores was low in an unselected population, according to investigators.

Of all tests, APRI was least likely to falsely classify patients who never developed severe liver diseases and had an intermediate-risk group of 4%, the lowest of any test, which are findings that may have implications for routine primary care, according to investigators.

“APRI could be the currently best score to exclude a high risk of liver-related events in the near future, and thereby reduce unnecessary testing in a general population,” they said in a discussion of their results.

The study was supported by an independent grant from AstraZeneca. Dr. Hagström reported disclosures related to that company, as well as Novo Nordisk, Gilead Sciences, IQVIA, Intercept, and Bristol Myers-Squibb.

SOURCE: Hagström H et al. Gastroenterology. 2019 Sep 26. doi: 10.1053/j.gastro.2019.09.008.

Currently available fibrosis scoring systems appear to have only a modest predictive ability for development of severe liver disease in the general population, according to authors of a large, retrospective cohort study.

Of five noninvasive scoring systems evaluated, all did have high negative predictive value in the general population, according to authors of the study, which included data on more than 800,000 individuals in Sweden. However, their sensitivities were low, with most of the individuals who developed severe liver disease over a 10-year follow-up period initially classified as being at low risk for advanced fibrosis, according to the study authors, led by Hannes Hagström, MD, PhD, of the division of hepatology, Karolinska University Hospital, Stockholm.

The scoring systems tended to perform better in patients at higher risk for nonalcoholic fatty liver disease (NAFLD) at baseline, suggesting the best use of the tools is in patients at increased risk or who have liver disease indications, Dr. Hagström and coauthors wrote in a report on the study.

“Although useful in populations with a high prevalence of advanced fibrosis, current scores lack precision for usage in the general population for which the prevalence of advanced fibrosis is much lower,” Dr. Hagström and colleagues said.

The scoring systems were derived from high-risk cohorts with liver diseases, the authors noted, stating that the disease prevalence in any given population will affect the performance of a test that’s intended to diagnose that specific disease.

“New and improved” scoring systems should be developed to more effectively pinpoint patients with NAFLD who are at higher risk of a severe liver event, they added in the report, which appears in Gastroenterology.

The population-based cohort study by Dr. Hagström and colleagues was based on data from 812,073 patients enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort between 1985 and 1996. Investigators said they excluded patients under 35 and over 79 years of age, patients with severe liver disease at baseline, and those with a prior diagnosis of alcohol or drug abuse.

Investigators used available data to calculate five scores, including the AST to Platelet Ratio Index (APRI); the body mass index, AST/ALT ratio, and diabetes (BARD) score; the Fibrosis-4 (FIB-4) score; Forns Index; and NAFLD Fibrosis Score (NFS).

At baseline, 0.5%-8.0% of patients were considered to be at high risk for advanced fibrosis, depending on the test used, investigators said. With up to 10 years of follow-up, the proportion of individuals who developed severe liver diseases (cirrhosis, liver failure, hepatocellular carcinoma, liver transplantation, or decompensated liver disease) was 0.3%-0.6%, and with the maximum 27 years of follow-up, the incidence ranged from 1.0% to 1.4%.

There was a “strong association” between baseline risk of fibrosis and development of severe liver diseases; however, the majority of cases occurred in patients deemed low risk at baseline, Dr. Hagström and colleagues noted in their report.

For example, 12.4% of individuals classified as high risk by APRI developed severe liver diseases over 10 years, compared to just 0.4% of the low-risk group, yet out of 723 cases, 502 (69%) occurred in the low-risk patients, the data show.

Hazard ratios did increase with risk level, and at the high-risk level, adjusted hazard ratios ranged from 1.7 (95% confidence interval [CI], 1.1-2.5) for the high-risk BARD patients to 45.9 (95% CI, 36.1-58.3) for the high-risk APRI patients, investigators reported.

Taken together, results of this study demonstrate that the performance of all scores was low in an unselected population, according to investigators.

Of all tests, APRI was least likely to falsely classify patients who never developed severe liver diseases and had an intermediate-risk group of 4%, the lowest of any test, which are findings that may have implications for routine primary care, according to investigators.

“APRI could be the currently best score to exclude a high risk of liver-related events in the near future, and thereby reduce unnecessary testing in a general population,” they said in a discussion of their results.

The study was supported by an independent grant from AstraZeneca. Dr. Hagström reported disclosures related to that company, as well as Novo Nordisk, Gilead Sciences, IQVIA, Intercept, and Bristol Myers-Squibb.

SOURCE: Hagström H et al. Gastroenterology. 2019 Sep 26. doi: 10.1053/j.gastro.2019.09.008.

Currently available fibrosis scoring systems appear to have only a modest predictive ability for development of severe liver disease in the general population, according to authors of a large, retrospective cohort study.

Of five noninvasive scoring systems evaluated, all did have high negative predictive value in the general population, according to authors of the study, which included data on more than 800,000 individuals in Sweden. However, their sensitivities were low, with most of the individuals who developed severe liver disease over a 10-year follow-up period initially classified as being at low risk for advanced fibrosis, according to the study authors, led by Hannes Hagström, MD, PhD, of the division of hepatology, Karolinska University Hospital, Stockholm.

The scoring systems tended to perform better in patients at higher risk for nonalcoholic fatty liver disease (NAFLD) at baseline, suggesting the best use of the tools is in patients at increased risk or who have liver disease indications, Dr. Hagström and coauthors wrote in a report on the study.

“Although useful in populations with a high prevalence of advanced fibrosis, current scores lack precision for usage in the general population for which the prevalence of advanced fibrosis is much lower,” Dr. Hagström and colleagues said.

The scoring systems were derived from high-risk cohorts with liver diseases, the authors noted, stating that the disease prevalence in any given population will affect the performance of a test that’s intended to diagnose that specific disease.

“New and improved” scoring systems should be developed to more effectively pinpoint patients with NAFLD who are at higher risk of a severe liver event, they added in the report, which appears in Gastroenterology.

The population-based cohort study by Dr. Hagström and colleagues was based on data from 812,073 patients enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort between 1985 and 1996. Investigators said they excluded patients under 35 and over 79 years of age, patients with severe liver disease at baseline, and those with a prior diagnosis of alcohol or drug abuse.

Investigators used available data to calculate five scores, including the AST to Platelet Ratio Index (APRI); the body mass index, AST/ALT ratio, and diabetes (BARD) score; the Fibrosis-4 (FIB-4) score; Forns Index; and NAFLD Fibrosis Score (NFS).

At baseline, 0.5%-8.0% of patients were considered to be at high risk for advanced fibrosis, depending on the test used, investigators said. With up to 10 years of follow-up, the proportion of individuals who developed severe liver diseases (cirrhosis, liver failure, hepatocellular carcinoma, liver transplantation, or decompensated liver disease) was 0.3%-0.6%, and with the maximum 27 years of follow-up, the incidence ranged from 1.0% to 1.4%.

There was a “strong association” between baseline risk of fibrosis and development of severe liver diseases; however, the majority of cases occurred in patients deemed low risk at baseline, Dr. Hagström and colleagues noted in their report.

For example, 12.4% of individuals classified as high risk by APRI developed severe liver diseases over 10 years, compared to just 0.4% of the low-risk group, yet out of 723 cases, 502 (69%) occurred in the low-risk patients, the data show.

Hazard ratios did increase with risk level, and at the high-risk level, adjusted hazard ratios ranged from 1.7 (95% confidence interval [CI], 1.1-2.5) for the high-risk BARD patients to 45.9 (95% CI, 36.1-58.3) for the high-risk APRI patients, investigators reported.

Taken together, results of this study demonstrate that the performance of all scores was low in an unselected population, according to investigators.

Of all tests, APRI was least likely to falsely classify patients who never developed severe liver diseases and had an intermediate-risk group of 4%, the lowest of any test, which are findings that may have implications for routine primary care, according to investigators.

“APRI could be the currently best score to exclude a high risk of liver-related events in the near future, and thereby reduce unnecessary testing in a general population,” they said in a discussion of their results.

The study was supported by an independent grant from AstraZeneca. Dr. Hagström reported disclosures related to that company, as well as Novo Nordisk, Gilead Sciences, IQVIA, Intercept, and Bristol Myers-Squibb.

SOURCE: Hagström H et al. Gastroenterology. 2019 Sep 26. doi: 10.1053/j.gastro.2019.09.008.

ORLANDO – For a patient with chronic lymphocytic leukemia (CLL) who has discontinued venetoclax, choosing the best next therapy may depend on what novel agents the patient was exposed to and why they discontinued them, according to Anthony R. Mato, MD, with the Center for CLL at Memorial Sloan Kettering Cancer Center in New York.

Andrew D. Bowser/MDedge News

If the patient is Bruton tyrosine kinase (BTK) inhibitor naive, then use of a BTK inhibitor after venetoclax would be supported, Dr. Mato said, by the high overall response rates and durable remissions that he and his coinvestigators documented in a retrospective, multicenter study designed specifically to address the gap in knowledge regarding what to use after venetoclax.

If the patient is BTK inhibitor exposed, then the reason for discontinuation needs to be considered before going with that venetoclax-to-BTK inhibitor sequence, Dr. Mato said during an oral presentation at the annual meeting of the American Society of Hematology.

“In patients with resistance to a BTK inhibitor, the sequence was not supported – it did not appear to be effective,” he said. “However, in the setting of intolerance, an alternate BTK inhibitor could be considered.”

The study did not support a venetoclax-to-PI3K inhibitor sequence in PI3K-naive patients, he added, noting that remissions did not appear to be durable, suggesting a potential overlap in resistance mechanisms between agents.

All told, the most effective therapies for in the postvenetoclax setting included the use of a BTK inhibitor in BTK inhibitor–naive or previously responsive patients, and allogeneic transplant following double novel-agent exposure.

“These data may provide support for venetoclax’s earlier use in the course of CLL, and may guide clinical practice and aid in the design of future clinical trials to address sequencing of novel agents,” Dr. Mato told attendees.

While prospective and real-world data clearly show that venetoclax is active in ibrutinib- or idelalisib-exposed patients, data are conversely “variable and limited” with regard to outcomes for next therapies following venetoclax.

“Current data addressing this key sequencing question, I feel, is a major limitation in supporting the sequence of venetoclax to a BTK inhibitor,” Dr. Mato said.

Accordingly, Dr. Mato and colleagues at 31 centers internationally planned and conducted this study, which included data on 326 patients treated with venetoclax who then discontinued for any reason.

“I wanted to highlight that 50% of the sites for this trial were recruited by a single tweet,” said Dr. Mato, adding that he and his coauthors received no funding to conduct this study and volunteered their time to complete it.

They found that, in BTK inhibitor–naive patients who discontinued venetoclax, subsequent BTK inhibitor treatment was associated with a high overall response rate and durable remissions, with a median progression-free survival (PFS) of 32 months.

In BTK inhibitor–exposed patients, response to postvenetoclax BTK inhibitor treatment depended on the reason for discontinuation, with a favorable result (PFS not reached with a mean follow-up of 7.7 months) in patients who were intolerant of the prior BTK inhibitor. By contrast, median PFS was only about 4 months for patients who were resistant to the prior BTK inhibitor.

PI3K inhibitors did not produce durable remissions after venetoclax, with a median PFS also of just 4 months, Dr. Mato reported.

However, cellular therapies appeared to be effective after venetoclax. Allogeneic hematopoietic stem cell transplantation was particularly effective, with the median PFS not reached, while chimeric antigen receptor T-cell therapy produced a PFS of 9 months.

Dr. Mato emphasized that the results of the retrospective trial were “hypothesis generating” and noted that patients in the study had received a median of 3, and up to 11, prior therapies. “This population are probably not our patients receiving venetoclax in clinical practice. They’re more heavily pretreated.”

Dr. Mato reported disclosures related to Gilead, AstraZeneca, AbbVie, Sunesis, Johnson & Johnson, TG Therapeutics, Loxo Oncology, DTRM Biopharma, Genentech, Janssen, Acerta Pharma, Pharmacyclics, and Celgene.

SOURCE: Mato AR et al. ASH 2019, Abstract 502.

ORLANDO – For a patient with chronic lymphocytic leukemia (CLL) who has discontinued venetoclax, choosing the best next therapy may depend on what novel agents the patient was exposed to and why they discontinued them, according to Anthony R. Mato, MD, with the Center for CLL at Memorial Sloan Kettering Cancer Center in New York.

Andrew D. Bowser/MDedge News

If the patient is Bruton tyrosine kinase (BTK) inhibitor naive, then use of a BTK inhibitor after venetoclax would be supported, Dr. Mato said, by the high overall response rates and durable remissions that he and his coinvestigators documented in a retrospective, multicenter study designed specifically to address the gap in knowledge regarding what to use after venetoclax.

If the patient is BTK inhibitor exposed, then the reason for discontinuation needs to be considered before going with that venetoclax-to-BTK inhibitor sequence, Dr. Mato said during an oral presentation at the annual meeting of the American Society of Hematology.

“In patients with resistance to a BTK inhibitor, the sequence was not supported – it did not appear to be effective,” he said. “However, in the setting of intolerance, an alternate BTK inhibitor could be considered.”

The study did not support a venetoclax-to-PI3K inhibitor sequence in PI3K-naive patients, he added, noting that remissions did not appear to be durable, suggesting a potential overlap in resistance mechanisms between agents.

All told, the most effective therapies for in the postvenetoclax setting included the use of a BTK inhibitor in BTK inhibitor–naive or previously responsive patients, and allogeneic transplant following double novel-agent exposure.

“These data may provide support for venetoclax’s earlier use in the course of CLL, and may guide clinical practice and aid in the design of future clinical trials to address sequencing of novel agents,” Dr. Mato told attendees.

While prospective and real-world data clearly show that venetoclax is active in ibrutinib- or idelalisib-exposed patients, data are conversely “variable and limited” with regard to outcomes for next therapies following venetoclax.

“Current data addressing this key sequencing question, I feel, is a major limitation in supporting the sequence of venetoclax to a BTK inhibitor,” Dr. Mato said.

Accordingly, Dr. Mato and colleagues at 31 centers internationally planned and conducted this study, which included data on 326 patients treated with venetoclax who then discontinued for any reason.

“I wanted to highlight that 50% of the sites for this trial were recruited by a single tweet,” said Dr. Mato, adding that he and his coauthors received no funding to conduct this study and volunteered their time to complete it.

They found that, in BTK inhibitor–naive patients who discontinued venetoclax, subsequent BTK inhibitor treatment was associated with a high overall response rate and durable remissions, with a median progression-free survival (PFS) of 32 months.

In BTK inhibitor–exposed patients, response to postvenetoclax BTK inhibitor treatment depended on the reason for discontinuation, with a favorable result (PFS not reached with a mean follow-up of 7.7 months) in patients who were intolerant of the prior BTK inhibitor. By contrast, median PFS was only about 4 months for patients who were resistant to the prior BTK inhibitor.

PI3K inhibitors did not produce durable remissions after venetoclax, with a median PFS also of just 4 months, Dr. Mato reported.

However, cellular therapies appeared to be effective after venetoclax. Allogeneic hematopoietic stem cell transplantation was particularly effective, with the median PFS not reached, while chimeric antigen receptor T-cell therapy produced a PFS of 9 months.

Dr. Mato emphasized that the results of the retrospective trial were “hypothesis generating” and noted that patients in the study had received a median of 3, and up to 11, prior therapies. “This population are probably not our patients receiving venetoclax in clinical practice. They’re more heavily pretreated.”

Dr. Mato reported disclosures related to Gilead, AstraZeneca, AbbVie, Sunesis, Johnson & Johnson, TG Therapeutics, Loxo Oncology, DTRM Biopharma, Genentech, Janssen, Acerta Pharma, Pharmacyclics, and Celgene.

SOURCE: Mato AR et al. ASH 2019, Abstract 502.

ORLANDO – For a patient with chronic lymphocytic leukemia (CLL) who has discontinued venetoclax, choosing the best next therapy may depend on what novel agents the patient was exposed to and why they discontinued them, according to Anthony R. Mato, MD, with the Center for CLL at Memorial Sloan Kettering Cancer Center in New York.

Andrew D. Bowser/MDedge News

If the patient is Bruton tyrosine kinase (BTK) inhibitor naive, then use of a BTK inhibitor after venetoclax would be supported, Dr. Mato said, by the high overall response rates and durable remissions that he and his coinvestigators documented in a retrospective, multicenter study designed specifically to address the gap in knowledge regarding what to use after venetoclax.

If the patient is BTK inhibitor exposed, then the reason for discontinuation needs to be considered before going with that venetoclax-to-BTK inhibitor sequence, Dr. Mato said during an oral presentation at the annual meeting of the American Society of Hematology.

“In patients with resistance to a BTK inhibitor, the sequence was not supported – it did not appear to be effective,” he said. “However, in the setting of intolerance, an alternate BTK inhibitor could be considered.”

The study did not support a venetoclax-to-PI3K inhibitor sequence in PI3K-naive patients, he added, noting that remissions did not appear to be durable, suggesting a potential overlap in resistance mechanisms between agents.

All told, the most effective therapies for in the postvenetoclax setting included the use of a BTK inhibitor in BTK inhibitor–naive or previously responsive patients, and allogeneic transplant following double novel-agent exposure.

“These data may provide support for venetoclax’s earlier use in the course of CLL, and may guide clinical practice and aid in the design of future clinical trials to address sequencing of novel agents,” Dr. Mato told attendees.

While prospective and real-world data clearly show that venetoclax is active in ibrutinib- or idelalisib-exposed patients, data are conversely “variable and limited” with regard to outcomes for next therapies following venetoclax.

“Current data addressing this key sequencing question, I feel, is a major limitation in supporting the sequence of venetoclax to a BTK inhibitor,” Dr. Mato said.

Accordingly, Dr. Mato and colleagues at 31 centers internationally planned and conducted this study, which included data on 326 patients treated with venetoclax who then discontinued for any reason.

“I wanted to highlight that 50% of the sites for this trial were recruited by a single tweet,” said Dr. Mato, adding that he and his coauthors received no funding to conduct this study and volunteered their time to complete it.

They found that, in BTK inhibitor–naive patients who discontinued venetoclax, subsequent BTK inhibitor treatment was associated with a high overall response rate and durable remissions, with a median progression-free survival (PFS) of 32 months.

In BTK inhibitor–exposed patients, response to postvenetoclax BTK inhibitor treatment depended on the reason for discontinuation, with a favorable result (PFS not reached with a mean follow-up of 7.7 months) in patients who were intolerant of the prior BTK inhibitor. By contrast, median PFS was only about 4 months for patients who were resistant to the prior BTK inhibitor.

PI3K inhibitors did not produce durable remissions after venetoclax, with a median PFS also of just 4 months, Dr. Mato reported.

However, cellular therapies appeared to be effective after venetoclax. Allogeneic hematopoietic stem cell transplantation was particularly effective, with the median PFS not reached, while chimeric antigen receptor T-cell therapy produced a PFS of 9 months.

Dr. Mato emphasized that the results of the retrospective trial were “hypothesis generating” and noted that patients in the study had received a median of 3, and up to 11, prior therapies. “This population are probably not our patients receiving venetoclax in clinical practice. They’re more heavily pretreated.”

Dr. Mato reported disclosures related to Gilead, AstraZeneca, AbbVie, Sunesis, Johnson & Johnson, TG Therapeutics, Loxo Oncology, DTRM Biopharma, Genentech, Janssen, Acerta Pharma, Pharmacyclics, and Celgene.

SOURCE: Mato AR et al. ASH 2019, Abstract 502.

Adults aged 18-64 years were more likely to see or talk to a health care professional in 2017-2018 than they were in 2012-2013, according to the Centers for Disease Control and Prevention.

The percentage of American adults who had seen or talked to a health care professional in the past 12 months rose from 79.3% in 2012-2013 to 82.1% in 2017-2018, Michael E. Martinez, MPH, and Tainya C. Clarke, PhD, reported in the Morbidity and Mortality Weekly Report.

Analysis by race/ethnicity showed that Hispanic adults were still the least likely to have seen or talked to a health care professional in 2017-2018, even though they had the largest increase – more than six percentage points – between the two time periods, the CDC investigators reported.

White adults were the most likely to have seen or talked to a health care provider in both 2012-2013 and 2017-2018 but their 2.1-percentage-point increase over the course of the analysis was the smallest of the four groups included, based on data from the National Health Interview Survey.

rfranki@mdedge.com

SOURCE: Martinez ME, Clarke TC. MMWR. 2019 Dec 6;68(48):1124.

Adults aged 18-64 years were more likely to see or talk to a health care professional in 2017-2018 than they were in 2012-2013, according to the Centers for Disease Control and Prevention.

The percentage of American adults who had seen or talked to a health care professional in the past 12 months rose from 79.3% in 2012-2013 to 82.1% in 2017-2018, Michael E. Martinez, MPH, and Tainya C. Clarke, PhD, reported in the Morbidity and Mortality Weekly Report.

Analysis by race/ethnicity showed that Hispanic adults were still the least likely to have seen or talked to a health care professional in 2017-2018, even though they had the largest increase – more than six percentage points – between the two time periods, the CDC investigators reported.

White adults were the most likely to have seen or talked to a health care provider in both 2012-2013 and 2017-2018 but their 2.1-percentage-point increase over the course of the analysis was the smallest of the four groups included, based on data from the National Health Interview Survey.

rfranki@mdedge.com

SOURCE: Martinez ME, Clarke TC. MMWR. 2019 Dec 6;68(48):1124.

Adults aged 18-64 years were more likely to see or talk to a health care professional in 2017-2018 than they were in 2012-2013, according to the Centers for Disease Control and Prevention.

The percentage of American adults who had seen or talked to a health care professional in the past 12 months rose from 79.3% in 2012-2013 to 82.1% in 2017-2018, Michael E. Martinez, MPH, and Tainya C. Clarke, PhD, reported in the Morbidity and Mortality Weekly Report.

Analysis by race/ethnicity showed that Hispanic adults were still the least likely to have seen or talked to a health care professional in 2017-2018, even though they had the largest increase – more than six percentage points – between the two time periods, the CDC investigators reported.

White adults were the most likely to have seen or talked to a health care provider in both 2012-2013 and 2017-2018 but their 2.1-percentage-point increase over the course of the analysis was the smallest of the four groups included, based on data from the National Health Interview Survey.

rfranki@mdedge.com

SOURCE: Martinez ME, Clarke TC. MMWR. 2019 Dec 6;68(48):1124.

Men aged 65-75 years with a history of smoking should undergo one-time screening for abdominal aortic aneurysms (AAA), but clinicians can selectively screen men in this age group who don’t smoke, according to updated recommendations from the U.S. Preventive Services Task Force published in JAMA.

The task force issued a B recommendation for screening men aged 65-75 years with a smoking history and a C recommendation for selectively screening male never smokers in this age group in an update to the previous recommendations issued in 2014.

The task force also recommended against screening for AAA in women with no history of smoking (D recommendation) and cited insufficient evidence to make recommendations about AAA screening for women with a history of smoking or a family history of AAA (I statement).

The current prevalence of AAA in the United States is unclear because of the low rate of screening, but data from countries including the United Kingdom, Sweden, Denmark, and New Zealand have shown a decline in AAA among screened men aged 65 years and older, according to the USPSTF report.

Risk factors for AAA include smoking, male gender, older age, and having a first-degree relative with AAA, the task force noted.

In an evidence review accompanying the recommendations, Janelle M. Guirguis-Blake, MD, of the University of Washington, Tacoma, and colleagues analyzed data from 33 studies. They found a significant reduction in AAA-related mortality over 12-15 years’ follow-up among men aged 65 years and older who underwent AAA screening, compared with unscreened controls (odds ratio, 0.65). In addition, the risk of ruptures related to AAA was significantly lower over 12-15 years among men who underwent screening, compared with unscreened controls (OR, 0.62). However, no significant difference was noted in all-cause mortality over 12-15 years between screened and unscreened groups (relative risk, 0.99; 95% confidence interval, 0.98-1.00).

Data from four studies of early surgery to treat small aneurysms showed no significant difference in AAA-related mortality or all-cause mortality.

“Screening for AAA entails a simple, noninvasive, and focused ultrasonography examination that costs roughly $50. The only potential harms are the psychologic burden of knowing of the presence of an aneurysm and the risk of elective surgery,” wrote Marc Schermerhorn, MD, of Beth Israel Deaconess Medical Center, Boston, in an accompanying editorial published in JAMA Surgery (doi: 10.1001/jamasurg.2019.5234).

“The latter can be calculated for each patient, weighed against the risk of rupture, and together with the estimated life expectancy, should be factored into the decision to screen and the decision to operate. We as a country can do better to detect and treat this disease cost effectively for all appropriate patients including women and elderly individuals,” he said.

Dr. Schermerhorn noted that overall the recommendations are reasonable, but he expressed concern for three populations excluded from the guidelines that warrant additional consideration: nonsmokers with equivalent risk factors, patients older than 75 years, and women. “In the meantime, we should work to ensure that patients determined appropriate by the USPSTF are actually screened,” he said.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose. Dr. Schermerhorn disclosed relationships with Abbott, Cook Medical, Endologix, Medtronic, and Philips.

SOURCE: Guirguis-Blake JM et al. JAMA. 2019. doi: 10.1001/jama.2019.17021.
 

Men aged 65-75 years with a history of smoking should undergo one-time screening for abdominal aortic aneurysms (AAA), but clinicians can selectively screen men in this age group who don’t smoke, according to updated recommendations from the U.S. Preventive Services Task Force published in JAMA.

The task force issued a B recommendation for screening men aged 65-75 years with a smoking history and a C recommendation for selectively screening male never smokers in this age group in an update to the previous recommendations issued in 2014.

The task force also recommended against screening for AAA in women with no history of smoking (D recommendation) and cited insufficient evidence to make recommendations about AAA screening for women with a history of smoking or a family history of AAA (I statement).

The current prevalence of AAA in the United States is unclear because of the low rate of screening, but data from countries including the United Kingdom, Sweden, Denmark, and New Zealand have shown a decline in AAA among screened men aged 65 years and older, according to the USPSTF report.

Risk factors for AAA include smoking, male gender, older age, and having a first-degree relative with AAA, the task force noted.

In an evidence review accompanying the recommendations, Janelle M. Guirguis-Blake, MD, of the University of Washington, Tacoma, and colleagues analyzed data from 33 studies. They found a significant reduction in AAA-related mortality over 12-15 years’ follow-up among men aged 65 years and older who underwent AAA screening, compared with unscreened controls (odds ratio, 0.65). In addition, the risk of ruptures related to AAA was significantly lower over 12-15 years among men who underwent screening, compared with unscreened controls (OR, 0.62). However, no significant difference was noted in all-cause mortality over 12-15 years between screened and unscreened groups (relative risk, 0.99; 95% confidence interval, 0.98-1.00).

Data from four studies of early surgery to treat small aneurysms showed no significant difference in AAA-related mortality or all-cause mortality.

“Screening for AAA entails a simple, noninvasive, and focused ultrasonography examination that costs roughly $50. The only potential harms are the psychologic burden of knowing of the presence of an aneurysm and the risk of elective surgery,” wrote Marc Schermerhorn, MD, of Beth Israel Deaconess Medical Center, Boston, in an accompanying editorial published in JAMA Surgery (doi: 10.1001/jamasurg.2019.5234).

“The latter can be calculated for each patient, weighed against the risk of rupture, and together with the estimated life expectancy, should be factored into the decision to screen and the decision to operate. We as a country can do better to detect and treat this disease cost effectively for all appropriate patients including women and elderly individuals,” he said.

Dr. Schermerhorn noted that overall the recommendations are reasonable, but he expressed concern for three populations excluded from the guidelines that warrant additional consideration: nonsmokers with equivalent risk factors, patients older than 75 years, and women. “In the meantime, we should work to ensure that patients determined appropriate by the USPSTF are actually screened,” he said.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose. Dr. Schermerhorn disclosed relationships with Abbott, Cook Medical, Endologix, Medtronic, and Philips.

SOURCE: Guirguis-Blake JM et al. JAMA. 2019. doi: 10.1001/jama.2019.17021.
 

Men aged 65-75 years with a history of smoking should undergo one-time screening for abdominal aortic aneurysms (AAA), but clinicians can selectively screen men in this age group who don’t smoke, according to updated recommendations from the U.S. Preventive Services Task Force published in JAMA.

The task force issued a B recommendation for screening men aged 65-75 years with a smoking history and a C recommendation for selectively screening male never smokers in this age group in an update to the previous recommendations issued in 2014.

The task force also recommended against screening for AAA in women with no history of smoking (D recommendation) and cited insufficient evidence to make recommendations about AAA screening for women with a history of smoking or a family history of AAA (I statement).

The current prevalence of AAA in the United States is unclear because of the low rate of screening, but data from countries including the United Kingdom, Sweden, Denmark, and New Zealand have shown a decline in AAA among screened men aged 65 years and older, according to the USPSTF report.

Risk factors for AAA include smoking, male gender, older age, and having a first-degree relative with AAA, the task force noted.

In an evidence review accompanying the recommendations, Janelle M. Guirguis-Blake, MD, of the University of Washington, Tacoma, and colleagues analyzed data from 33 studies. They found a significant reduction in AAA-related mortality over 12-15 years’ follow-up among men aged 65 years and older who underwent AAA screening, compared with unscreened controls (odds ratio, 0.65). In addition, the risk of ruptures related to AAA was significantly lower over 12-15 years among men who underwent screening, compared with unscreened controls (OR, 0.62). However, no significant difference was noted in all-cause mortality over 12-15 years between screened and unscreened groups (relative risk, 0.99; 95% confidence interval, 0.98-1.00).

Data from four studies of early surgery to treat small aneurysms showed no significant difference in AAA-related mortality or all-cause mortality.

“Screening for AAA entails a simple, noninvasive, and focused ultrasonography examination that costs roughly $50. The only potential harms are the psychologic burden of knowing of the presence of an aneurysm and the risk of elective surgery,” wrote Marc Schermerhorn, MD, of Beth Israel Deaconess Medical Center, Boston, in an accompanying editorial published in JAMA Surgery (doi: 10.1001/jamasurg.2019.5234).

“The latter can be calculated for each patient, weighed against the risk of rupture, and together with the estimated life expectancy, should be factored into the decision to screen and the decision to operate. We as a country can do better to detect and treat this disease cost effectively for all appropriate patients including women and elderly individuals,” he said.

Dr. Schermerhorn noted that overall the recommendations are reasonable, but he expressed concern for three populations excluded from the guidelines that warrant additional consideration: nonsmokers with equivalent risk factors, patients older than 75 years, and women. “In the meantime, we should work to ensure that patients determined appropriate by the USPSTF are actually screened,” he said.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose. Dr. Schermerhorn disclosed relationships with Abbott, Cook Medical, Endologix, Medtronic, and Philips.

SOURCE: Guirguis-Blake JM et al. JAMA. 2019. doi: 10.1001/jama.2019.17021.
 

BALTIMORE – Decrease in the frequency of convulsive seizures is significantly associated with improvement in executive function among patients with Dravet syndrome, according to data presented at the annual meeting of the American Epilepsy Society. Large reductions in convulsive seizure frequency for prolonged periods may improve everyday deficits in executive function in these patients, according to the investigators.

Dravet syndrome often entails cognitive impairment, including deficits in executive function. The frequency and severity of convulsive seizures are believed to worsen cognitive impairment over time, but few researchers have conducted long-term studies to test this hypothesis. Adjunctive fenfluramine significantly reduced the frequency of convulsive seizures and improved executive function after 14 weeks in a phase 3 study of patients with Dravet syndrome.
 

An open-label extension of a phase 3 study

In an open-label extension of this study, Joseph Sullivan, MD, director of the pediatric epilepsy center at the University of California, San Francisco, Benioff Children’s Hospital, and colleagues analyzed the relationship between changes in convulsive seizure frequency and executive function. The investigators also examined the effect of reducing convulsive seizure frequency by comparing patients with profound reductions (greater than 75%) versus patients with minimal reductions (less than 25%).

Patients aged 2-18 years entered the open-label study and received adjunctive fenfluramine for 1 year. At the beginning of the open-label phase, the dose was titrated to effect. The dose ranged from 0.2 mg/kg per day to 0.7 mg/kg per day and was administered as 2.5 mg/mL of fenfluramine. The maximum dose was 17 mg with stiripentol or 26 mg without.

The investigators calculated the percent difference in convulsive seizure frequency per 28 days from baseline to the end of the open-label study. They evaluated executive function using the Behavior Rating Inventory of Executive Function (BRIEF), which caregivers completed at baseline and year 1 for patients aged 5-18 years. Scores on the BRIEF were updated to the newer version: BRIEF2. Dr. Sullivan and colleagues calculated Spearman’s rho correlation coefficients to evaluate the association between BRIEF2 Behavior Regulation Index, Emotion Regulation Index, Cognitive Regulation Index, and Global Executive Composite scores. Lower scores on the BRIEF2 indexes and composite indicate better executive functioning. In addition, the researchers compared clinically meaningful change in BRIEF2 indexes and composite scores from baseline to year 1 between patients with minimal and profound reductions in convulsive seizure frequency using Fisher’s exact test. They defined a clinically meaningful change as an improvement in the Reliable Change Index of greater than 95%.
 

Profound reduction in seizure frequency was common

At the time of analysis, 53 patients had completed at least 1 year of open-label fenfluramine and had baseline and year 1 BRIEF2 data. Patients’ median age was 10 years, and 57% of patients were male. The median reduction from prerandomization baseline in convulsive seizure frequency was 71%. The reduction ranged from 99.7% to 55.0%.

Twenty-four (45%) patients had a reduction in convulsive seizure frequency of greater than 75%, and 11 (21%) had a reduction of less than 25%. Change in convulsive seizure frequency correlated significantly with Emotion Regulation Index and Global Executive Composite. Change in seizure frequency tended to correlate with Cognitive Regulation Index, but the result was not statistically significant. Change in convulsive seizure frequency was not significantly associated with Behavior Regulation Index. A significantly higher percentage of patients in the profound responder group had significant, clinically meaningful improvements on Emotion Regulation Index and Global Executive Composite, compared with minimal responders.

Zogenix, the company that is developing fenfluramine as a treatment for Dravet syndrome, funded the study. Several investigators are employees of Zogenix.

egreb@mdedge.com

SOURCE: Bishop KI et al. AES 2019, Abstract 2.438.

BALTIMORE – Decrease in the frequency of convulsive seizures is significantly associated with improvement in executive function among patients with Dravet syndrome, according to data presented at the annual meeting of the American Epilepsy Society. Large reductions in convulsive seizure frequency for prolonged periods may improve everyday deficits in executive function in these patients, according to the investigators.

Dravet syndrome often entails cognitive impairment, including deficits in executive function. The frequency and severity of convulsive seizures are believed to worsen cognitive impairment over time, but few researchers have conducted long-term studies to test this hypothesis. Adjunctive fenfluramine significantly reduced the frequency of convulsive seizures and improved executive function after 14 weeks in a phase 3 study of patients with Dravet syndrome.
 

An open-label extension of a phase 3 study

In an open-label extension of this study, Joseph Sullivan, MD, director of the pediatric epilepsy center at the University of California, San Francisco, Benioff Children’s Hospital, and colleagues analyzed the relationship between changes in convulsive seizure frequency and executive function. The investigators also examined the effect of reducing convulsive seizure frequency by comparing patients with profound reductions (greater than 75%) versus patients with minimal reductions (less than 25%).

Patients aged 2-18 years entered the open-label study and received adjunctive fenfluramine for 1 year. At the beginning of the open-label phase, the dose was titrated to effect. The dose ranged from 0.2 mg/kg per day to 0.7 mg/kg per day and was administered as 2.5 mg/mL of fenfluramine. The maximum dose was 17 mg with stiripentol or 26 mg without.

The investigators calculated the percent difference in convulsive seizure frequency per 28 days from baseline to the end of the open-label study. They evaluated executive function using the Behavior Rating Inventory of Executive Function (BRIEF), which caregivers completed at baseline and year 1 for patients aged 5-18 years. Scores on the BRIEF were updated to the newer version: BRIEF2. Dr. Sullivan and colleagues calculated Spearman’s rho correlation coefficients to evaluate the association between BRIEF2 Behavior Regulation Index, Emotion Regulation Index, Cognitive Regulation Index, and Global Executive Composite scores. Lower scores on the BRIEF2 indexes and composite indicate better executive functioning. In addition, the researchers compared clinically meaningful change in BRIEF2 indexes and composite scores from baseline to year 1 between patients with minimal and profound reductions in convulsive seizure frequency using Fisher’s exact test. They defined a clinically meaningful change as an improvement in the Reliable Change Index of greater than 95%.
 

Profound reduction in seizure frequency was common

At the time of analysis, 53 patients had completed at least 1 year of open-label fenfluramine and had baseline and year 1 BRIEF2 data. Patients’ median age was 10 years, and 57% of patients were male. The median reduction from prerandomization baseline in convulsive seizure frequency was 71%. The reduction ranged from 99.7% to 55.0%.

Twenty-four (45%) patients had a reduction in convulsive seizure frequency of greater than 75%, and 11 (21%) had a reduction of less than 25%. Change in convulsive seizure frequency correlated significantly with Emotion Regulation Index and Global Executive Composite. Change in seizure frequency tended to correlate with Cognitive Regulation Index, but the result was not statistically significant. Change in convulsive seizure frequency was not significantly associated with Behavior Regulation Index. A significantly higher percentage of patients in the profound responder group had significant, clinically meaningful improvements on Emotion Regulation Index and Global Executive Composite, compared with minimal responders.

Zogenix, the company that is developing fenfluramine as a treatment for Dravet syndrome, funded the study. Several investigators are employees of Zogenix.

egreb@mdedge.com

SOURCE: Bishop KI et al. AES 2019, Abstract 2.438.

BALTIMORE – Decrease in the frequency of convulsive seizures is significantly associated with improvement in executive function among patients with Dravet syndrome, according to data presented at the annual meeting of the American Epilepsy Society. Large reductions in convulsive seizure frequency for prolonged periods may improve everyday deficits in executive function in these patients, according to the investigators.

Dravet syndrome often entails cognitive impairment, including deficits in executive function. The frequency and severity of convulsive seizures are believed to worsen cognitive impairment over time, but few researchers have conducted long-term studies to test this hypothesis. Adjunctive fenfluramine significantly reduced the frequency of convulsive seizures and improved executive function after 14 weeks in a phase 3 study of patients with Dravet syndrome.
 

An open-label extension of a phase 3 study

In an open-label extension of this study, Joseph Sullivan, MD, director of the pediatric epilepsy center at the University of California, San Francisco, Benioff Children’s Hospital, and colleagues analyzed the relationship between changes in convulsive seizure frequency and executive function. The investigators also examined the effect of reducing convulsive seizure frequency by comparing patients with profound reductions (greater than 75%) versus patients with minimal reductions (less than 25%).

Patients aged 2-18 years entered the open-label study and received adjunctive fenfluramine for 1 year. At the beginning of the open-label phase, the dose was titrated to effect. The dose ranged from 0.2 mg/kg per day to 0.7 mg/kg per day and was administered as 2.5 mg/mL of fenfluramine. The maximum dose was 17 mg with stiripentol or 26 mg without.

The investigators calculated the percent difference in convulsive seizure frequency per 28 days from baseline to the end of the open-label study. They evaluated executive function using the Behavior Rating Inventory of Executive Function (BRIEF), which caregivers completed at baseline and year 1 for patients aged 5-18 years. Scores on the BRIEF were updated to the newer version: BRIEF2. Dr. Sullivan and colleagues calculated Spearman’s rho correlation coefficients to evaluate the association between BRIEF2 Behavior Regulation Index, Emotion Regulation Index, Cognitive Regulation Index, and Global Executive Composite scores. Lower scores on the BRIEF2 indexes and composite indicate better executive functioning. In addition, the researchers compared clinically meaningful change in BRIEF2 indexes and composite scores from baseline to year 1 between patients with minimal and profound reductions in convulsive seizure frequency using Fisher’s exact test. They defined a clinically meaningful change as an improvement in the Reliable Change Index of greater than 95%.
 

Profound reduction in seizure frequency was common

At the time of analysis, 53 patients had completed at least 1 year of open-label fenfluramine and had baseline and year 1 BRIEF2 data. Patients’ median age was 10 years, and 57% of patients were male. The median reduction from prerandomization baseline in convulsive seizure frequency was 71%. The reduction ranged from 99.7% to 55.0%.

Twenty-four (45%) patients had a reduction in convulsive seizure frequency of greater than 75%, and 11 (21%) had a reduction of less than 25%. Change in convulsive seizure frequency correlated significantly with Emotion Regulation Index and Global Executive Composite. Change in seizure frequency tended to correlate with Cognitive Regulation Index, but the result was not statistically significant. Change in convulsive seizure frequency was not significantly associated with Behavior Regulation Index. A significantly higher percentage of patients in the profound responder group had significant, clinically meaningful improvements on Emotion Regulation Index and Global Executive Composite, compared with minimal responders.

Zogenix, the company that is developing fenfluramine as a treatment for Dravet syndrome, funded the study. Several investigators are employees of Zogenix.

egreb@mdedge.com

SOURCE: Bishop KI et al. AES 2019, Abstract 2.438.