In a new analysis comparing only clinically similar outcomes in patients with acute coronary syndrome, the addition of rivaroxaban to standard antiplatelet therapy resulted in 115 fewer fatal or irreversible ischemic events per 10,000 patient-years than placebo, at the expense of only 10 additional fatal or seriously harmful events.

This new interpretation of the ATLAS ACS 2-TIMI 51 trial (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome–Thrombolysis in Myocardial Infarction-51) suggests that the factor Xa inhibitor may still carve out a place for itself in ACS therapy, despite Food and Drug Administration rejections for this indication.

Not only did the survival benefit of rivaroxaban appear early in postevent treatment, it continued to protect patients over time, C. Michael Gibson, MD, and colleagues reported in the Journal of the American College of Cardiology.

“Time-to-event analysis demonstrated that the risk of fatal or irreversible harm remained low and constant over time, whereas reduction in fatal or irreversible ischemic events expanded,” wrote Dr. Gibson, professor of medicine at Beth Israel Deaconess Medical Center, Boston, and his coinvestigators. “By 720 days, a net of 142 fatal or irreversible events would have been prevented by 2.5-mg oral doses twice per day of rivaroxaban. Additional time-to-event sensitivity analyses demonstrated similar results, even when TIMI major bleeding was included as a fatal or irreversible event.”

In conducting the new analysis, Dr. Gibson and his team argued that the original interpretation of the results of ATLAS ACS 2-TIMI 51 lumped both fatal and nonfatal events together in composite endpoints, resulting in an inaccurate real-life picture of rivaroxaban’s therapeutic potential. “All types of events [were] weighted equally; for example, reversible nonintracranial hemorrhage, nonfatal bleeds that can be managed with supportive care, are weighted equally with death and disabling stroke. Second, stroke can be either hemorrhagic or ischemic, and the relative contributions of hemorrhagic or ischemic stroke may not be appropriately assigned to risk-versus-benefit categories in many analyses.”

The net result was that, while rivaroxaban did reduce the risk of the composite endpoint (cardiovascular death, MI, or stroke), the 1.7% absolute difference in cardiovascular mortality was almost completely offset by a 1.3% increase in major bleeding. However, most of those bleeds were reversible and nonfatal, associated with a drop in hemoglobin and/or blood transfusion. The drug did not increase the risk of fatal bleeding.

Giving equal statistical weight to clinically equal events provides a clearer focus, the investigators said.

“In this form of analysis, only fatal or irreversible events were included so that benefit and seriously harmful events of similar clinical impact were compared,” they wrote. “This is particularly important when the endpoints and analyses do not include measurements of subjective clinical impact such as utility measurements or preference weights. This approach also uses risk differences rather than relative measurements such as hazard ratios, so the number of events prevented and caused are clearly distinguished.”

ATLAS comprised more than 15,000 patients with ST-segment elevation MI, non-STEMI, or unstable angina. They were randomized to either rivaroxaban 2.5 mg orally twice per day, 5 mg orally twice per day, or to placebo, in addition to standard of care, which included low-dose aspirin. Patients were stratified by the optional use of clopidogrel/ticlopidine.

Dr. Gibson and his team reanalyzed the data by comparing outcomes they judged as having a similar clinical impact: fatal and irreversible cardiovascular death, MI, and ischemic stroke. They also assessed all bleeding, TIMI life-threatening bleeding, and TIMI major bleeding.

In this analysis, the 2.5-mg dose was associated with 115 fewer fatal or irreversible ischemic deaths per 10,000 patient-years of exposure than placebo (548 vs. 663 nonbleeding cardiovascular deaths, MIs, or ischemic strokes).

However, the same dose was also associated with 10 more excessive, fatal, or irreversibly serious harmful events, compared with placebo per 10,000 patient years (33 fatal bleeds or intracranial hemorrhage vs. 23 for placebo).

“Considered together, there would be 105 fatal or irreversible events prevented per 10,000 patient-years of exposure to 2.5 mg of rivaroxaban taken orally twice a day, compared with placebo. An alternate interpretation of the data is that there would be 11 [10 of 115] fatal or irreversible ischemic events prevented for each fatal or irreversible harmful event caused,” Dr. Gibson and his colleagues wrote.

The benefit held when the outcomes were individually reckoned as well. If periprocedural MIs were excluded, rivaroxaban would still prevent 115 fatal or irreversible ischemic events. If only nonbleeding cardiovascular death or ischemic strokes were included, then 90 fatal or irreversible events would be prevented. And if only nonbleeding cardiovascular death was included, then 95 events would be prevented per 10,000 patient-years of exposure in the group taking rivaroxaban 2.5 mg twice daily.

“In all cases, the fatal or irreversible events prevented are 9-11 times the fatal or irreversible seriously harmful events caused,” the investigators said.

ATLAS ACS 2-TIMI 51 was supported by Johnson & Johnson and Bayer Healthcare. Dr. Gibson has received institutional funding, grants, and honoraria from those companies and from Portola Pharmaceuticals.
 

[email protected]

SOURCE: Gibson CM et al. J Am Coll Cardiol. 2018;72:129-36.

In a new analysis comparing only clinically similar outcomes in patients with acute coronary syndrome, the addition of rivaroxaban to standard antiplatelet therapy resulted in 115 fewer fatal or irreversible ischemic events per 10,000 patient-years than placebo, at the expense of only 10 additional fatal or seriously harmful events.

This new interpretation of the ATLAS ACS 2-TIMI 51 trial (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome–Thrombolysis in Myocardial Infarction-51) suggests that the factor Xa inhibitor may still carve out a place for itself in ACS therapy, despite Food and Drug Administration rejections for this indication.

Not only did the survival benefit of rivaroxaban appear early in postevent treatment, it continued to protect patients over time, C. Michael Gibson, MD, and colleagues reported in the Journal of the American College of Cardiology.

“Time-to-event analysis demonstrated that the risk of fatal or irreversible harm remained low and constant over time, whereas reduction in fatal or irreversible ischemic events expanded,” wrote Dr. Gibson, professor of medicine at Beth Israel Deaconess Medical Center, Boston, and his coinvestigators. “By 720 days, a net of 142 fatal or irreversible events would have been prevented by 2.5-mg oral doses twice per day of rivaroxaban. Additional time-to-event sensitivity analyses demonstrated similar results, even when TIMI major bleeding was included as a fatal or irreversible event.”

In conducting the new analysis, Dr. Gibson and his team argued that the original interpretation of the results of ATLAS ACS 2-TIMI 51 lumped both fatal and nonfatal events together in composite endpoints, resulting in an inaccurate real-life picture of rivaroxaban’s therapeutic potential. “All types of events [were] weighted equally; for example, reversible nonintracranial hemorrhage, nonfatal bleeds that can be managed with supportive care, are weighted equally with death and disabling stroke. Second, stroke can be either hemorrhagic or ischemic, and the relative contributions of hemorrhagic or ischemic stroke may not be appropriately assigned to risk-versus-benefit categories in many analyses.”

The net result was that, while rivaroxaban did reduce the risk of the composite endpoint (cardiovascular death, MI, or stroke), the 1.7% absolute difference in cardiovascular mortality was almost completely offset by a 1.3% increase in major bleeding. However, most of those bleeds were reversible and nonfatal, associated with a drop in hemoglobin and/or blood transfusion. The drug did not increase the risk of fatal bleeding.

Giving equal statistical weight to clinically equal events provides a clearer focus, the investigators said.

“In this form of analysis, only fatal or irreversible events were included so that benefit and seriously harmful events of similar clinical impact were compared,” they wrote. “This is particularly important when the endpoints and analyses do not include measurements of subjective clinical impact such as utility measurements or preference weights. This approach also uses risk differences rather than relative measurements such as hazard ratios, so the number of events prevented and caused are clearly distinguished.”

ATLAS comprised more than 15,000 patients with ST-segment elevation MI, non-STEMI, or unstable angina. They were randomized to either rivaroxaban 2.5 mg orally twice per day, 5 mg orally twice per day, or to placebo, in addition to standard of care, which included low-dose aspirin. Patients were stratified by the optional use of clopidogrel/ticlopidine.

Dr. Gibson and his team reanalyzed the data by comparing outcomes they judged as having a similar clinical impact: fatal and irreversible cardiovascular death, MI, and ischemic stroke. They also assessed all bleeding, TIMI life-threatening bleeding, and TIMI major bleeding.

In this analysis, the 2.5-mg dose was associated with 115 fewer fatal or irreversible ischemic deaths per 10,000 patient-years of exposure than placebo (548 vs. 663 nonbleeding cardiovascular deaths, MIs, or ischemic strokes).

However, the same dose was also associated with 10 more excessive, fatal, or irreversibly serious harmful events, compared with placebo per 10,000 patient years (33 fatal bleeds or intracranial hemorrhage vs. 23 for placebo).

“Considered together, there would be 105 fatal or irreversible events prevented per 10,000 patient-years of exposure to 2.5 mg of rivaroxaban taken orally twice a day, compared with placebo. An alternate interpretation of the data is that there would be 11 [10 of 115] fatal or irreversible ischemic events prevented for each fatal or irreversible harmful event caused,” Dr. Gibson and his colleagues wrote.

The benefit held when the outcomes were individually reckoned as well. If periprocedural MIs were excluded, rivaroxaban would still prevent 115 fatal or irreversible ischemic events. If only nonbleeding cardiovascular death or ischemic strokes were included, then 90 fatal or irreversible events would be prevented. And if only nonbleeding cardiovascular death was included, then 95 events would be prevented per 10,000 patient-years of exposure in the group taking rivaroxaban 2.5 mg twice daily.

“In all cases, the fatal or irreversible events prevented are 9-11 times the fatal or irreversible seriously harmful events caused,” the investigators said.

ATLAS ACS 2-TIMI 51 was supported by Johnson & Johnson and Bayer Healthcare. Dr. Gibson has received institutional funding, grants, and honoraria from those companies and from Portola Pharmaceuticals.
 

[email protected]

SOURCE: Gibson CM et al. J Am Coll Cardiol. 2018;72:129-36.

In a new analysis comparing only clinically similar outcomes in patients with acute coronary syndrome, the addition of rivaroxaban to standard antiplatelet therapy resulted in 115 fewer fatal or irreversible ischemic events per 10,000 patient-years than placebo, at the expense of only 10 additional fatal or seriously harmful events.

This new interpretation of the ATLAS ACS 2-TIMI 51 trial (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome–Thrombolysis in Myocardial Infarction-51) suggests that the factor Xa inhibitor may still carve out a place for itself in ACS therapy, despite Food and Drug Administration rejections for this indication.

Not only did the survival benefit of rivaroxaban appear early in postevent treatment, it continued to protect patients over time, C. Michael Gibson, MD, and colleagues reported in the Journal of the American College of Cardiology.

“Time-to-event analysis demonstrated that the risk of fatal or irreversible harm remained low and constant over time, whereas reduction in fatal or irreversible ischemic events expanded,” wrote Dr. Gibson, professor of medicine at Beth Israel Deaconess Medical Center, Boston, and his coinvestigators. “By 720 days, a net of 142 fatal or irreversible events would have been prevented by 2.5-mg oral doses twice per day of rivaroxaban. Additional time-to-event sensitivity analyses demonstrated similar results, even when TIMI major bleeding was included as a fatal or irreversible event.”

In conducting the new analysis, Dr. Gibson and his team argued that the original interpretation of the results of ATLAS ACS 2-TIMI 51 lumped both fatal and nonfatal events together in composite endpoints, resulting in an inaccurate real-life picture of rivaroxaban’s therapeutic potential. “All types of events [were] weighted equally; for example, reversible nonintracranial hemorrhage, nonfatal bleeds that can be managed with supportive care, are weighted equally with death and disabling stroke. Second, stroke can be either hemorrhagic or ischemic, and the relative contributions of hemorrhagic or ischemic stroke may not be appropriately assigned to risk-versus-benefit categories in many analyses.”

The net result was that, while rivaroxaban did reduce the risk of the composite endpoint (cardiovascular death, MI, or stroke), the 1.7% absolute difference in cardiovascular mortality was almost completely offset by a 1.3% increase in major bleeding. However, most of those bleeds were reversible and nonfatal, associated with a drop in hemoglobin and/or blood transfusion. The drug did not increase the risk of fatal bleeding.

Giving equal statistical weight to clinically equal events provides a clearer focus, the investigators said.

“In this form of analysis, only fatal or irreversible events were included so that benefit and seriously harmful events of similar clinical impact were compared,” they wrote. “This is particularly important when the endpoints and analyses do not include measurements of subjective clinical impact such as utility measurements or preference weights. This approach also uses risk differences rather than relative measurements such as hazard ratios, so the number of events prevented and caused are clearly distinguished.”

ATLAS comprised more than 15,000 patients with ST-segment elevation MI, non-STEMI, or unstable angina. They were randomized to either rivaroxaban 2.5 mg orally twice per day, 5 mg orally twice per day, or to placebo, in addition to standard of care, which included low-dose aspirin. Patients were stratified by the optional use of clopidogrel/ticlopidine.

Dr. Gibson and his team reanalyzed the data by comparing outcomes they judged as having a similar clinical impact: fatal and irreversible cardiovascular death, MI, and ischemic stroke. They also assessed all bleeding, TIMI life-threatening bleeding, and TIMI major bleeding.

In this analysis, the 2.5-mg dose was associated with 115 fewer fatal or irreversible ischemic deaths per 10,000 patient-years of exposure than placebo (548 vs. 663 nonbleeding cardiovascular deaths, MIs, or ischemic strokes).

However, the same dose was also associated with 10 more excessive, fatal, or irreversibly serious harmful events, compared with placebo per 10,000 patient years (33 fatal bleeds or intracranial hemorrhage vs. 23 for placebo).

“Considered together, there would be 105 fatal or irreversible events prevented per 10,000 patient-years of exposure to 2.5 mg of rivaroxaban taken orally twice a day, compared with placebo. An alternate interpretation of the data is that there would be 11 [10 of 115] fatal or irreversible ischemic events prevented for each fatal or irreversible harmful event caused,” Dr. Gibson and his colleagues wrote.

The benefit held when the outcomes were individually reckoned as well. If periprocedural MIs were excluded, rivaroxaban would still prevent 115 fatal or irreversible ischemic events. If only nonbleeding cardiovascular death or ischemic strokes were included, then 90 fatal or irreversible events would be prevented. And if only nonbleeding cardiovascular death was included, then 95 events would be prevented per 10,000 patient-years of exposure in the group taking rivaroxaban 2.5 mg twice daily.

“In all cases, the fatal or irreversible events prevented are 9-11 times the fatal or irreversible seriously harmful events caused,” the investigators said.

ATLAS ACS 2-TIMI 51 was supported by Johnson & Johnson and Bayer Healthcare. Dr. Gibson has received institutional funding, grants, and honoraria from those companies and from Portola Pharmaceuticals.
 

[email protected]

SOURCE: Gibson CM et al. J Am Coll Cardiol. 2018;72:129-36.

Clinical question: What are the risks for arterial and venous thrombosis in patients with myeloproliferative neoplasms (MPNs)?

Background: Myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Prior studies have investigated the incidence of arterial and venous thrombosis in patients with mye­loproliferative neoplasms, but the actual magnitude of thrombosis risk relative to the general population is unknown.

Study design: Retrospective matched-cohort study.

Setting: Sweden, using the Swedish Inpatient and Cancer Registers.

Synopsis: Using data from 1987 to 2009, 9,429 patients with MPNs were compared with 35,820 control participants to determine hazard ratios for arterial thrombosis, venous thrombosis, and any thrombosis. The highest hazard ratios were seen within 3 months of MPN diagnosis, with hazard ratios of 4.0 (95% confidence interval, 3.6-4.4) for any thrombosis, 3.0 (95% CI, 2.7-3.4) for arterial thrombosis, and 9.7 (95% CI, 7.8-12.0) for venous thrombosis. Risk decreased but remained significantly elevated through follow-up out to 20 years after diagnosis. This decrease was thought to be caused by effective thromboprophylactic and cytoreductive treatment of the MPN.

This study demonstrates significantly elevated risk for thrombosis in patients with MPNs, highest shortly after diagnosis. It suggests the importance of timely diagnosis and treatment of MPNs to decrease early thrombosis risk.

Bottom line: Patients with MPNs have increased rates of arterial and venous thrombosis, with the highest rates within 3 months of diagnosis.

Citation: Hultcrantz M et al. Risk for arterial and venous thrombosis in patients with myeloproliferative neoplasms. Ann Intern Med. 2018 Mar 6;168(5):317-25.

Dr. Komsoukaniants is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.

Clinical question: What are the risks for arterial and venous thrombosis in patients with myeloproliferative neoplasms (MPNs)?

Background: Myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Prior studies have investigated the incidence of arterial and venous thrombosis in patients with mye­loproliferative neoplasms, but the actual magnitude of thrombosis risk relative to the general population is unknown.

Study design: Retrospective matched-cohort study.

Setting: Sweden, using the Swedish Inpatient and Cancer Registers.

Synopsis: Using data from 1987 to 2009, 9,429 patients with MPNs were compared with 35,820 control participants to determine hazard ratios for arterial thrombosis, venous thrombosis, and any thrombosis. The highest hazard ratios were seen within 3 months of MPN diagnosis, with hazard ratios of 4.0 (95% confidence interval, 3.6-4.4) for any thrombosis, 3.0 (95% CI, 2.7-3.4) for arterial thrombosis, and 9.7 (95% CI, 7.8-12.0) for venous thrombosis. Risk decreased but remained significantly elevated through follow-up out to 20 years after diagnosis. This decrease was thought to be caused by effective thromboprophylactic and cytoreductive treatment of the MPN.

This study demonstrates significantly elevated risk for thrombosis in patients with MPNs, highest shortly after diagnosis. It suggests the importance of timely diagnosis and treatment of MPNs to decrease early thrombosis risk.

Bottom line: Patients with MPNs have increased rates of arterial and venous thrombosis, with the highest rates within 3 months of diagnosis.

Citation: Hultcrantz M et al. Risk for arterial and venous thrombosis in patients with myeloproliferative neoplasms. Ann Intern Med. 2018 Mar 6;168(5):317-25.

Dr. Komsoukaniants is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.

Clinical question: What are the risks for arterial and venous thrombosis in patients with myeloproliferative neoplasms (MPNs)?

Background: Myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Prior studies have investigated the incidence of arterial and venous thrombosis in patients with mye­loproliferative neoplasms, but the actual magnitude of thrombosis risk relative to the general population is unknown.

Study design: Retrospective matched-cohort study.

Setting: Sweden, using the Swedish Inpatient and Cancer Registers.

Synopsis: Using data from 1987 to 2009, 9,429 patients with MPNs were compared with 35,820 control participants to determine hazard ratios for arterial thrombosis, venous thrombosis, and any thrombosis. The highest hazard ratios were seen within 3 months of MPN diagnosis, with hazard ratios of 4.0 (95% confidence interval, 3.6-4.4) for any thrombosis, 3.0 (95% CI, 2.7-3.4) for arterial thrombosis, and 9.7 (95% CI, 7.8-12.0) for venous thrombosis. Risk decreased but remained significantly elevated through follow-up out to 20 years after diagnosis. This decrease was thought to be caused by effective thromboprophylactic and cytoreductive treatment of the MPN.

This study demonstrates significantly elevated risk for thrombosis in patients with MPNs, highest shortly after diagnosis. It suggests the importance of timely diagnosis and treatment of MPNs to decrease early thrombosis risk.

Bottom line: Patients with MPNs have increased rates of arterial and venous thrombosis, with the highest rates within 3 months of diagnosis.

Citation: Hultcrantz M et al. Risk for arterial and venous thrombosis in patients with myeloproliferative neoplasms. Ann Intern Med. 2018 Mar 6;168(5):317-25.

Dr. Komsoukaniants is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.

SAN DIEGO – Many opioid users on the street are embracing homegrown “risk reduction” techniques to make sure they avoid the danger of fentanyl-laced heroin, while others seek out batches that have caused fatal overdoses because they figure these supplies must be extra-strong and desirable. “Anytime I hear that somebody OD’d off something,” said one user, “... I was like, ‘Oh, that stuff must be good. Where can I get it?’ ”

So say opioid users who are opening up to researchers about the deadly new American drug landscape.

There’s one common thread, said Daniel Ciccarone, MD, MPH, who presented findings from his team’s interviews at the annual meeting of the College on Problems of Drug Dependence. Attitudes about fentanyl are shifting, but not enough to turn the drug – which often is available instead of heroin – into a major crowd-pleaser.

• Some opioid users are shocked by the adulteration of heroin by fentanyl, and even dealers are surprised: “When we cut the dope, we don’t use fentanyl. The problem was that we were buying the dope already dirty with that, and we didn’t know it,” said a 42-year-old man from Lawrence, Mass.
• In the New Hampshire interviews, 84% of participants said fentanyl is the leading cause of overdose in the state. “Due to the fentanyl and the heroin, that’s how everyone that I know ended up passing away recently,” said one user.
• Also in New Hampshire, 84% of users interviewed said they’d used fentanyl before, accidentally in some cases. Also, study coauthor Andrea L. Meier said in an interview, “67% of users reported having a prescription for opioids in their lifetime due to some kind of illness or injury. Some were short-term prescriptions (injuries, C-sections, tooth extractions); others were prescribed long-term due to chronic pain or illness.”

Some say pursue fentanyl

In the New Hampshire interviews, 25% of the 84% who’d used fentanyl said they actively seek it out, with one expressing a preference for the “real dope” (heroin laced with fentanyl) versus the “maintenance dope” of heroin alone. Ms. Meier explained what that means: “We’ve heard that once you use fentanyl or fentanyl-laced heroin, heroin doesn’t adequately manage your withdrawal symptoms or give enough of a high. So they will use heroin to get by, but they really want fentanyl or fentanyl-laced heroin.”

She added: “We’ve learned that users are seeking fentanyl due to its potency (a stronger, better high with quicker onset than heroin), cost (cheaper than heroin, so more “bang for your buck”), and once they use fentanyl or fentanyl-laced heroin, heroin doesn’t have the same effect/high.”

As for the risk of overdose, “people want the best high they can get at the cheapest cost,” she said.” They presume it will be potent enough to produce an exceptional high but [they won’t] die from an overdose due to being sufficiently tolerant to handle it. Also, some just felt hopeless and weren’t afraid of an OD.”
 

Comments from users about fentanyl

• “The high is wonderful. It’s splendidly wonderful. It’s magnified heroin feeling by a great number,” said a 45-year-old man from Baltimore.
• “You spend the same amount of money or even less for it, and you’re getting 3 times as high as you did on heroin,” said one user in New Hampshire. “Who wouldn’t want that?”

Risk-reduction techniques embraced

• In Baltimore, a 39-year-old woman said: “I have a lot of associates that are letting me know, ‘Don’t go to that place because they selling fentanyl.’ ”
• Some users test their heroin. “Like when I get stuff I don’t know what it is, I do a little bit before I do something that I feel,” a Lawrence, Mass., female user in her 20s said. “Like, I want to kind of scale out how much I want to do. Because I don’t want to die. But these people are just doing a gram shot and just ... my friend just died 2 days ago.”

Dr. Ciccarone said some of the biggest proponents of harm-reduction among users were African Americans aged 60 and older who had used for many decades.

“They fear fentanyl and are using old-school harm reduction strategies for staying safer: “tooting” (snorting) and tester shots (small injections to test the quality),” he said. “These may seem like minor strategies, but if enough of the population applies them to their daily drug use, many deaths would be averted. In this crisis, we need all the wisdom we can get, so we should listen to these elders.”

Dr. Ciccarone’s research was funded by the National Institutes of Health and NIDA. Dr. Ciccarone reported no relevant disclosures. The Dartmouth College study was funded by NIDA, and those authors reported no relevant disclosures.

SAN DIEGO – Many opioid users on the street are embracing homegrown “risk reduction” techniques to make sure they avoid the danger of fentanyl-laced heroin, while others seek out batches that have caused fatal overdoses because they figure these supplies must be extra-strong and desirable. “Anytime I hear that somebody OD’d off something,” said one user, “... I was like, ‘Oh, that stuff must be good. Where can I get it?’ ”

So say opioid users who are opening up to researchers about the deadly new American drug landscape.

There’s one common thread, said Daniel Ciccarone, MD, MPH, who presented findings from his team’s interviews at the annual meeting of the College on Problems of Drug Dependence. Attitudes about fentanyl are shifting, but not enough to turn the drug – which often is available instead of heroin – into a major crowd-pleaser.

• Some opioid users are shocked by the adulteration of heroin by fentanyl, and even dealers are surprised: “When we cut the dope, we don’t use fentanyl. The problem was that we were buying the dope already dirty with that, and we didn’t know it,” said a 42-year-old man from Lawrence, Mass.
• In the New Hampshire interviews, 84% of participants said fentanyl is the leading cause of overdose in the state. “Due to the fentanyl and the heroin, that’s how everyone that I know ended up passing away recently,” said one user.
• Also in New Hampshire, 84% of users interviewed said they’d used fentanyl before, accidentally in some cases. Also, study coauthor Andrea L. Meier said in an interview, “67% of users reported having a prescription for opioids in their lifetime due to some kind of illness or injury. Some were short-term prescriptions (injuries, C-sections, tooth extractions); others were prescribed long-term due to chronic pain or illness.”

Some say pursue fentanyl

In the New Hampshire interviews, 25% of the 84% who’d used fentanyl said they actively seek it out, with one expressing a preference for the “real dope” (heroin laced with fentanyl) versus the “maintenance dope” of heroin alone. Ms. Meier explained what that means: “We’ve heard that once you use fentanyl or fentanyl-laced heroin, heroin doesn’t adequately manage your withdrawal symptoms or give enough of a high. So they will use heroin to get by, but they really want fentanyl or fentanyl-laced heroin.”

She added: “We’ve learned that users are seeking fentanyl due to its potency (a stronger, better high with quicker onset than heroin), cost (cheaper than heroin, so more “bang for your buck”), and once they use fentanyl or fentanyl-laced heroin, heroin doesn’t have the same effect/high.”

As for the risk of overdose, “people want the best high they can get at the cheapest cost,” she said.” They presume it will be potent enough to produce an exceptional high but [they won’t] die from an overdose due to being sufficiently tolerant to handle it. Also, some just felt hopeless and weren’t afraid of an OD.”
 

Comments from users about fentanyl

• “The high is wonderful. It’s splendidly wonderful. It’s magnified heroin feeling by a great number,” said a 45-year-old man from Baltimore.
• “You spend the same amount of money or even less for it, and you’re getting 3 times as high as you did on heroin,” said one user in New Hampshire. “Who wouldn’t want that?”

Risk-reduction techniques embraced

• In Baltimore, a 39-year-old woman said: “I have a lot of associates that are letting me know, ‘Don’t go to that place because they selling fentanyl.’ ”
• Some users test their heroin. “Like when I get stuff I don’t know what it is, I do a little bit before I do something that I feel,” a Lawrence, Mass., female user in her 20s said. “Like, I want to kind of scale out how much I want to do. Because I don’t want to die. But these people are just doing a gram shot and just ... my friend just died 2 days ago.”

Dr. Ciccarone said some of the biggest proponents of harm-reduction among users were African Americans aged 60 and older who had used for many decades.

“They fear fentanyl and are using old-school harm reduction strategies for staying safer: “tooting” (snorting) and tester shots (small injections to test the quality),” he said. “These may seem like minor strategies, but if enough of the population applies them to their daily drug use, many deaths would be averted. In this crisis, we need all the wisdom we can get, so we should listen to these elders.”

Dr. Ciccarone’s research was funded by the National Institutes of Health and NIDA. Dr. Ciccarone reported no relevant disclosures. The Dartmouth College study was funded by NIDA, and those authors reported no relevant disclosures.

SAN DIEGO – Many opioid users on the street are embracing homegrown “risk reduction” techniques to make sure they avoid the danger of fentanyl-laced heroin, while others seek out batches that have caused fatal overdoses because they figure these supplies must be extra-strong and desirable. “Anytime I hear that somebody OD’d off something,” said one user, “... I was like, ‘Oh, that stuff must be good. Where can I get it?’ ”

So say opioid users who are opening up to researchers about the deadly new American drug landscape.

There’s one common thread, said Daniel Ciccarone, MD, MPH, who presented findings from his team’s interviews at the annual meeting of the College on Problems of Drug Dependence. Attitudes about fentanyl are shifting, but not enough to turn the drug – which often is available instead of heroin – into a major crowd-pleaser.

• Some opioid users are shocked by the adulteration of heroin by fentanyl, and even dealers are surprised: “When we cut the dope, we don’t use fentanyl. The problem was that we were buying the dope already dirty with that, and we didn’t know it,” said a 42-year-old man from Lawrence, Mass.
• In the New Hampshire interviews, 84% of participants said fentanyl is the leading cause of overdose in the state. “Due to the fentanyl and the heroin, that’s how everyone that I know ended up passing away recently,” said one user.
• Also in New Hampshire, 84% of users interviewed said they’d used fentanyl before, accidentally in some cases. Also, study coauthor Andrea L. Meier said in an interview, “67% of users reported having a prescription for opioids in their lifetime due to some kind of illness or injury. Some were short-term prescriptions (injuries, C-sections, tooth extractions); others were prescribed long-term due to chronic pain or illness.”

Some say pursue fentanyl

In the New Hampshire interviews, 25% of the 84% who’d used fentanyl said they actively seek it out, with one expressing a preference for the “real dope” (heroin laced with fentanyl) versus the “maintenance dope” of heroin alone. Ms. Meier explained what that means: “We’ve heard that once you use fentanyl or fentanyl-laced heroin, heroin doesn’t adequately manage your withdrawal symptoms or give enough of a high. So they will use heroin to get by, but they really want fentanyl or fentanyl-laced heroin.”

She added: “We’ve learned that users are seeking fentanyl due to its potency (a stronger, better high with quicker onset than heroin), cost (cheaper than heroin, so more “bang for your buck”), and once they use fentanyl or fentanyl-laced heroin, heroin doesn’t have the same effect/high.”

As for the risk of overdose, “people want the best high they can get at the cheapest cost,” she said.” They presume it will be potent enough to produce an exceptional high but [they won’t] die from an overdose due to being sufficiently tolerant to handle it. Also, some just felt hopeless and weren’t afraid of an OD.”
 

Comments from users about fentanyl

• “The high is wonderful. It’s splendidly wonderful. It’s magnified heroin feeling by a great number,” said a 45-year-old man from Baltimore.
• “You spend the same amount of money or even less for it, and you’re getting 3 times as high as you did on heroin,” said one user in New Hampshire. “Who wouldn’t want that?”

Risk-reduction techniques embraced

• In Baltimore, a 39-year-old woman said: “I have a lot of associates that are letting me know, ‘Don’t go to that place because they selling fentanyl.’ ”
• Some users test their heroin. “Like when I get stuff I don’t know what it is, I do a little bit before I do something that I feel,” a Lawrence, Mass., female user in her 20s said. “Like, I want to kind of scale out how much I want to do. Because I don’t want to die. But these people are just doing a gram shot and just ... my friend just died 2 days ago.”

Dr. Ciccarone said some of the biggest proponents of harm-reduction among users were African Americans aged 60 and older who had used for many decades.

“They fear fentanyl and are using old-school harm reduction strategies for staying safer: “tooting” (snorting) and tester shots (small injections to test the quality),” he said. “These may seem like minor strategies, but if enough of the population applies them to their daily drug use, many deaths would be averted. In this crisis, we need all the wisdom we can get, so we should listen to these elders.”

Dr. Ciccarone’s research was funded by the National Institutes of Health and NIDA. Dr. Ciccarone reported no relevant disclosures. The Dartmouth College study was funded by NIDA, and those authors reported no relevant disclosures.

CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.

The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.

The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.

Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”

The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.

Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.

Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.

Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.

With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.

Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.

Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.

Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.

Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.

SOURCE: Chari A et al. ASCO 2018, Abstract 8002.

CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.

The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.

The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.

Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”

The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.

Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.

Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.

Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.

With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.

Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.

Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.

Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.

Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.

SOURCE: Chari A et al. ASCO 2018, Abstract 8002.

CHICAGO – Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.

The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.

The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.

Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”

The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.

Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.

Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.

Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.

With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.

Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.

Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.

Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.

Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.

SOURCE: Chari A et al. ASCO 2018, Abstract 8002.

Researchers have highlighted the need for contraception counseling for transgender men, after a study found around half of transgender men had not been asked by their health care providers about their fertility desires.

Writing in Contraception, researchers reported the results of an anonymous, online survey of 197 female-to-male transgender men, 86% of whom were taking masculinizing hormones.

Overall, 17% of respondents had experienced a pregnancy, with 60 pregnancies reported in total. While participants who had never taken hormones had a nearly 200% higher incidence of pregnancy, compared with those who had taken testosterone, one pregnancy occurred while the subject was taking testosterone, and five of seven reported abortions were in participants who had used testosterone prior to conception.

A total of 30 participants (16.4%) believed testosterone was a contraceptive method, and 10 said that a health care provider had advised them to use testosterone for contraception. However, nearly half of all participants did report using condoms for contraception, making it the most common method. IUDs were the second most common method of contraception currently used.

Nearly one-third of participants said they had used some type of contraceptive pill at some point, 17 said they had tried more than one type of pill, and 36 had used combination pills. However, of those who had used combination pills, nearly half stopped using them because of side effects or because of concern about extra feminine hormones.

The authors noted that most study participants expressed a desire to become a parent. Around one-quarter wanted to bear a child while the majority said they would consider adoption.

One-quarter of respondents had fears about not achieving a desired pregnancy, and for some, those fears began after initiating hormone treatments. Just over half the respondents said their health care provider had not asked about their fertility desires.

“Transgender men have unintended pregnancy as well as future fertility desires, and yet, there is a paucity of reproductive health care best practices research for this unique population,” wrote Alexis Light, MD, MPH, of MedStar Washington Hospital Center, and her coauthors. “This survey confirms earlier studies: Transgender men do become pregnant, both intentionally and unintentionally, and some transgender men engage in behaviors that can lead to unintended pregnancy.”

The study authors called for doctors to be more equipped and prepared to counsel transgender men on contraception and discuss other reproductive health concerns.

The study was supported by MedStar Washington Hospital Center. No conflicts of interest were declared.

SOURCE: Light A et al. Contraception. 2018 Jun 23. doi: 10.1016/j.contraception.2018.06.006.

Researchers have highlighted the need for contraception counseling for transgender men, after a study found around half of transgender men had not been asked by their health care providers about their fertility desires.

Writing in Contraception, researchers reported the results of an anonymous, online survey of 197 female-to-male transgender men, 86% of whom were taking masculinizing hormones.

Overall, 17% of respondents had experienced a pregnancy, with 60 pregnancies reported in total. While participants who had never taken hormones had a nearly 200% higher incidence of pregnancy, compared with those who had taken testosterone, one pregnancy occurred while the subject was taking testosterone, and five of seven reported abortions were in participants who had used testosterone prior to conception.

A total of 30 participants (16.4%) believed testosterone was a contraceptive method, and 10 said that a health care provider had advised them to use testosterone for contraception. However, nearly half of all participants did report using condoms for contraception, making it the most common method. IUDs were the second most common method of contraception currently used.

Nearly one-third of participants said they had used some type of contraceptive pill at some point, 17 said they had tried more than one type of pill, and 36 had used combination pills. However, of those who had used combination pills, nearly half stopped using them because of side effects or because of concern about extra feminine hormones.

The authors noted that most study participants expressed a desire to become a parent. Around one-quarter wanted to bear a child while the majority said they would consider adoption.

One-quarter of respondents had fears about not achieving a desired pregnancy, and for some, those fears began after initiating hormone treatments. Just over half the respondents said their health care provider had not asked about their fertility desires.

“Transgender men have unintended pregnancy as well as future fertility desires, and yet, there is a paucity of reproductive health care best practices research for this unique population,” wrote Alexis Light, MD, MPH, of MedStar Washington Hospital Center, and her coauthors. “This survey confirms earlier studies: Transgender men do become pregnant, both intentionally and unintentionally, and some transgender men engage in behaviors that can lead to unintended pregnancy.”

The study authors called for doctors to be more equipped and prepared to counsel transgender men on contraception and discuss other reproductive health concerns.

The study was supported by MedStar Washington Hospital Center. No conflicts of interest were declared.

SOURCE: Light A et al. Contraception. 2018 Jun 23. doi: 10.1016/j.contraception.2018.06.006.

Researchers have highlighted the need for contraception counseling for transgender men, after a study found around half of transgender men had not been asked by their health care providers about their fertility desires.

Writing in Contraception, researchers reported the results of an anonymous, online survey of 197 female-to-male transgender men, 86% of whom were taking masculinizing hormones.

Overall, 17% of respondents had experienced a pregnancy, with 60 pregnancies reported in total. While participants who had never taken hormones had a nearly 200% higher incidence of pregnancy, compared with those who had taken testosterone, one pregnancy occurred while the subject was taking testosterone, and five of seven reported abortions were in participants who had used testosterone prior to conception.

A total of 30 participants (16.4%) believed testosterone was a contraceptive method, and 10 said that a health care provider had advised them to use testosterone for contraception. However, nearly half of all participants did report using condoms for contraception, making it the most common method. IUDs were the second most common method of contraception currently used.

Nearly one-third of participants said they had used some type of contraceptive pill at some point, 17 said they had tried more than one type of pill, and 36 had used combination pills. However, of those who had used combination pills, nearly half stopped using them because of side effects or because of concern about extra feminine hormones.

The authors noted that most study participants expressed a desire to become a parent. Around one-quarter wanted to bear a child while the majority said they would consider adoption.

One-quarter of respondents had fears about not achieving a desired pregnancy, and for some, those fears began after initiating hormone treatments. Just over half the respondents said their health care provider had not asked about their fertility desires.

“Transgender men have unintended pregnancy as well as future fertility desires, and yet, there is a paucity of reproductive health care best practices research for this unique population,” wrote Alexis Light, MD, MPH, of MedStar Washington Hospital Center, and her coauthors. “This survey confirms earlier studies: Transgender men do become pregnant, both intentionally and unintentionally, and some transgender men engage in behaviors that can lead to unintended pregnancy.”

The study authors called for doctors to be more equipped and prepared to counsel transgender men on contraception and discuss other reproductive health concerns.

The study was supported by MedStar Washington Hospital Center. No conflicts of interest were declared.

SOURCE: Light A et al. Contraception. 2018 Jun 23. doi: 10.1016/j.contraception.2018.06.006.

PARIS – The most appropriate stroke prevention strategy in patients undergoing transcatheter aortic valve replacement is routine use of a cerebroembolic protection device for all, because no identifiable high-risk anatomic subsets exist, Hasan Jilaihawi, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Bruce Jancin/MDedge News

A wealth of evidence shows that the average stroke rate associated with contemporary TAVR is 4.4%, although this figure is probably on the low side because most of the data come from nonrandomized registries, which typically underreport neurologic outcomes. The stroke rate is independent of operator experience and volume, surgical risk score, and institutional TAVR volume. Moreover, in the SENTINEL trial, embolic debris was captured in 99% of patients fitted with the cerebroembolic protection device.

“A huge variety of material was captured, including thrombus, valve tissue, calcified material, and – alarmingly – foreign material in 35% of cases,” Dr. Jilaihawi noted.

Nonetheless, the issue of routine versus selective use of cardioembolic protection remains controversial at a time when interventionalists are trying to make TAVR a simpler, briefer procedure, even though the approved Sentinel device is successfully deployed in a median of only 4 minutes. This was the impetus for Dr. Jilaihawi to examine baseline anatomy as a potential predictor of stroke.

He looked at four key anatomic features: aortic arch type, aortic root angulation, aortic arch calcium, and aortic valve calcification. The bottom line: The benefit of cerebroembolic protection with the Sentinel device was consistent across all anatomic subgroups. For example, in patients with an aortic root angulation angle of less than 50 degrees, the incidence of stroke within 3 days post TAVR was 3.2% with and 5.9% without cerebroembolic protection, while in those with an angle of 50 degrees or more the stroke rate was 2.6% with and 9.1% without the Sentinel device. With a total of only 16 strokes by day 3 in the study, those stroke rates in the absence of cerebroembolic protection aren’t significantly different.

[email protected]

SOURCE: Jilaihawi H. EuroPCR 2018.

PARIS – The most appropriate stroke prevention strategy in patients undergoing transcatheter aortic valve replacement is routine use of a cerebroembolic protection device for all, because no identifiable high-risk anatomic subsets exist, Hasan Jilaihawi, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Bruce Jancin/MDedge News

A wealth of evidence shows that the average stroke rate associated with contemporary TAVR is 4.4%, although this figure is probably on the low side because most of the data come from nonrandomized registries, which typically underreport neurologic outcomes. The stroke rate is independent of operator experience and volume, surgical risk score, and institutional TAVR volume. Moreover, in the SENTINEL trial, embolic debris was captured in 99% of patients fitted with the cerebroembolic protection device.

“A huge variety of material was captured, including thrombus, valve tissue, calcified material, and – alarmingly – foreign material in 35% of cases,” Dr. Jilaihawi noted.

Nonetheless, the issue of routine versus selective use of cardioembolic protection remains controversial at a time when interventionalists are trying to make TAVR a simpler, briefer procedure, even though the approved Sentinel device is successfully deployed in a median of only 4 minutes. This was the impetus for Dr. Jilaihawi to examine baseline anatomy as a potential predictor of stroke.

He looked at four key anatomic features: aortic arch type, aortic root angulation, aortic arch calcium, and aortic valve calcification. The bottom line: The benefit of cerebroembolic protection with the Sentinel device was consistent across all anatomic subgroups. For example, in patients with an aortic root angulation angle of less than 50 degrees, the incidence of stroke within 3 days post TAVR was 3.2% with and 5.9% without cerebroembolic protection, while in those with an angle of 50 degrees or more the stroke rate was 2.6% with and 9.1% without the Sentinel device. With a total of only 16 strokes by day 3 in the study, those stroke rates in the absence of cerebroembolic protection aren’t significantly different.

[email protected]

SOURCE: Jilaihawi H. EuroPCR 2018.

PARIS – The most appropriate stroke prevention strategy in patients undergoing transcatheter aortic valve replacement is routine use of a cerebroembolic protection device for all, because no identifiable high-risk anatomic subsets exist, Hasan Jilaihawi, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Bruce Jancin/MDedge News

A wealth of evidence shows that the average stroke rate associated with contemporary TAVR is 4.4%, although this figure is probably on the low side because most of the data come from nonrandomized registries, which typically underreport neurologic outcomes. The stroke rate is independent of operator experience and volume, surgical risk score, and institutional TAVR volume. Moreover, in the SENTINEL trial, embolic debris was captured in 99% of patients fitted with the cerebroembolic protection device.

“A huge variety of material was captured, including thrombus, valve tissue, calcified material, and – alarmingly – foreign material in 35% of cases,” Dr. Jilaihawi noted.

Nonetheless, the issue of routine versus selective use of cardioembolic protection remains controversial at a time when interventionalists are trying to make TAVR a simpler, briefer procedure, even though the approved Sentinel device is successfully deployed in a median of only 4 minutes. This was the impetus for Dr. Jilaihawi to examine baseline anatomy as a potential predictor of stroke.

He looked at four key anatomic features: aortic arch type, aortic root angulation, aortic arch calcium, and aortic valve calcification. The bottom line: The benefit of cerebroembolic protection with the Sentinel device was consistent across all anatomic subgroups. For example, in patients with an aortic root angulation angle of less than 50 degrees, the incidence of stroke within 3 days post TAVR was 3.2% with and 5.9% without cerebroembolic protection, while in those with an angle of 50 degrees or more the stroke rate was 2.6% with and 9.1% without the Sentinel device. With a total of only 16 strokes by day 3 in the study, those stroke rates in the absence of cerebroembolic protection aren’t significantly different.

[email protected]

SOURCE: Jilaihawi H. EuroPCR 2018.

The number of Medicaid enrollees receiving medication treatment with methadone and buprenorphine rose from 2002 to 2009 because of the availability of buprenorphine. A cause for concern, however, is that medication treatment increased at a much higher rate in counties with lower poverty rates – and lower concentrations of black and Hispanic residents.

“Concerted efforts are needed to ensure that [medication treatment] benefits are equitably distributed across society and reach disadvantaged individuals who may be at higher risk of experiencing opioid use disorders,” wrote Bradley D. Stein, MD, PhD, and his colleagues. The report was published in Substance Abuse.

Dr. Stein, of Rand Corporation, and his colleagues set out to assess the changes in medication treatment use over time and how medication treatment was being used at the county level – in addition to the associations between poverty, race/ethnicity, and urbanicity. The research team analyzed Medicaid claims from 2002 to 2009 from 14 states, representing 53% of the U.S. population and 47% of 2009 Medicaid enrollees. The states selected in the analysis, chosen to represent regional and population diversity, were California, Connecticut, Florida, Georgia, Illinois, Louisiana, Massachusetts, Maryland, New York, Pennsylvania, Rhode Island, Texas, Vermont, and Wisconsin. The researchers looked at medication treatment use among 18- to 64-year-old Medicaid enrollees, excluding people who were eligible for both Medicare and Medicaid.

The variables for who received medication treatment and data on county characteristics were well defined. Individuals who had received either methadone or buprenorphine were identified as receiving medication treatment. Some patients (3% or less) used both methadone or buprenorphine but were categorized as methadone users in the analysis to better elucidate the role of buprenorphine in medication treatment. Counties were classified as low poverty if the percentage of the county population was below the median (less than 13.5%) of the counties in the 14 states in the analysis and the federal poverty line.

The racial/ethnic makeup of a county was determined to be low percentage of black people if the percentage of the black population was below the median (less than 5.6%) in all counties. Similarly, a county was considered low percentage of Hispanic residents if the proportion of the Hispanic population was below the median of less than 4.2%, reported Dr. Stein, who also is affiliated with the University of Pittsburgh.

The analysis showed that from 2002 to 2009, the proportion of Medicaid users receiving methadone increased by 20% (42,235 to 50,587), accounting for a fraction of the 62% increase in Medicaid enrollment (42,263 to 68,278). The real driver in increased medication treatment rates was the adoption of buprenorphine, which soared from 75 in 2002 to 19,691 in 2009. In 2009, 29% of Medicaid enrollees received medication treatment with buprenorphine. The growth of medication treatment varied by the characteristics of a county’s population. In 2002, urban counties had substantially higher rates of primarily methadone therapy than did rural counties (P less than.001). But no significant differences were found across the county based the concentration of black residents or poverty. Communities that did not have low concentrations of Hispanic residents experienced higher rates of medication treatment, regardless of poverty (P less than .01 for low poverty and not low poverty)

The study was supported by a grant from the National Institute on Drug Abuse. The authors disclosed no relevant conflicts of interest.

SOURCE: Stein BD et al. Subst Abuse. 2018 Jun 22. doi: 10.1080/08897077.2018.1449166.

The number of Medicaid enrollees receiving medication treatment with methadone and buprenorphine rose from 2002 to 2009 because of the availability of buprenorphine. A cause for concern, however, is that medication treatment increased at a much higher rate in counties with lower poverty rates – and lower concentrations of black and Hispanic residents.

“Concerted efforts are needed to ensure that [medication treatment] benefits are equitably distributed across society and reach disadvantaged individuals who may be at higher risk of experiencing opioid use disorders,” wrote Bradley D. Stein, MD, PhD, and his colleagues. The report was published in Substance Abuse.

Dr. Stein, of Rand Corporation, and his colleagues set out to assess the changes in medication treatment use over time and how medication treatment was being used at the county level – in addition to the associations between poverty, race/ethnicity, and urbanicity. The research team analyzed Medicaid claims from 2002 to 2009 from 14 states, representing 53% of the U.S. population and 47% of 2009 Medicaid enrollees. The states selected in the analysis, chosen to represent regional and population diversity, were California, Connecticut, Florida, Georgia, Illinois, Louisiana, Massachusetts, Maryland, New York, Pennsylvania, Rhode Island, Texas, Vermont, and Wisconsin. The researchers looked at medication treatment use among 18- to 64-year-old Medicaid enrollees, excluding people who were eligible for both Medicare and Medicaid.

The variables for who received medication treatment and data on county characteristics were well defined. Individuals who had received either methadone or buprenorphine were identified as receiving medication treatment. Some patients (3% or less) used both methadone or buprenorphine but were categorized as methadone users in the analysis to better elucidate the role of buprenorphine in medication treatment. Counties were classified as low poverty if the percentage of the county population was below the median (less than 13.5%) of the counties in the 14 states in the analysis and the federal poverty line.

The racial/ethnic makeup of a county was determined to be low percentage of black people if the percentage of the black population was below the median (less than 5.6%) in all counties. Similarly, a county was considered low percentage of Hispanic residents if the proportion of the Hispanic population was below the median of less than 4.2%, reported Dr. Stein, who also is affiliated with the University of Pittsburgh.

The analysis showed that from 2002 to 2009, the proportion of Medicaid users receiving methadone increased by 20% (42,235 to 50,587), accounting for a fraction of the 62% increase in Medicaid enrollment (42,263 to 68,278). The real driver in increased medication treatment rates was the adoption of buprenorphine, which soared from 75 in 2002 to 19,691 in 2009. In 2009, 29% of Medicaid enrollees received medication treatment with buprenorphine. The growth of medication treatment varied by the characteristics of a county’s population. In 2002, urban counties had substantially higher rates of primarily methadone therapy than did rural counties (P less than.001). But no significant differences were found across the county based the concentration of black residents or poverty. Communities that did not have low concentrations of Hispanic residents experienced higher rates of medication treatment, regardless of poverty (P less than .01 for low poverty and not low poverty)

The study was supported by a grant from the National Institute on Drug Abuse. The authors disclosed no relevant conflicts of interest.

SOURCE: Stein BD et al. Subst Abuse. 2018 Jun 22. doi: 10.1080/08897077.2018.1449166.

The number of Medicaid enrollees receiving medication treatment with methadone and buprenorphine rose from 2002 to 2009 because of the availability of buprenorphine. A cause for concern, however, is that medication treatment increased at a much higher rate in counties with lower poverty rates – and lower concentrations of black and Hispanic residents.

“Concerted efforts are needed to ensure that [medication treatment] benefits are equitably distributed across society and reach disadvantaged individuals who may be at higher risk of experiencing opioid use disorders,” wrote Bradley D. Stein, MD, PhD, and his colleagues. The report was published in Substance Abuse.

Dr. Stein, of Rand Corporation, and his colleagues set out to assess the changes in medication treatment use over time and how medication treatment was being used at the county level – in addition to the associations between poverty, race/ethnicity, and urbanicity. The research team analyzed Medicaid claims from 2002 to 2009 from 14 states, representing 53% of the U.S. population and 47% of 2009 Medicaid enrollees. The states selected in the analysis, chosen to represent regional and population diversity, were California, Connecticut, Florida, Georgia, Illinois, Louisiana, Massachusetts, Maryland, New York, Pennsylvania, Rhode Island, Texas, Vermont, and Wisconsin. The researchers looked at medication treatment use among 18- to 64-year-old Medicaid enrollees, excluding people who were eligible for both Medicare and Medicaid.

The variables for who received medication treatment and data on county characteristics were well defined. Individuals who had received either methadone or buprenorphine were identified as receiving medication treatment. Some patients (3% or less) used both methadone or buprenorphine but were categorized as methadone users in the analysis to better elucidate the role of buprenorphine in medication treatment. Counties were classified as low poverty if the percentage of the county population was below the median (less than 13.5%) of the counties in the 14 states in the analysis and the federal poverty line.

The racial/ethnic makeup of a county was determined to be low percentage of black people if the percentage of the black population was below the median (less than 5.6%) in all counties. Similarly, a county was considered low percentage of Hispanic residents if the proportion of the Hispanic population was below the median of less than 4.2%, reported Dr. Stein, who also is affiliated with the University of Pittsburgh.

The analysis showed that from 2002 to 2009, the proportion of Medicaid users receiving methadone increased by 20% (42,235 to 50,587), accounting for a fraction of the 62% increase in Medicaid enrollment (42,263 to 68,278). The real driver in increased medication treatment rates was the adoption of buprenorphine, which soared from 75 in 2002 to 19,691 in 2009. In 2009, 29% of Medicaid enrollees received medication treatment with buprenorphine. The growth of medication treatment varied by the characteristics of a county’s population. In 2002, urban counties had substantially higher rates of primarily methadone therapy than did rural counties (P less than.001). But no significant differences were found across the county based the concentration of black residents or poverty. Communities that did not have low concentrations of Hispanic residents experienced higher rates of medication treatment, regardless of poverty (P less than .01 for low poverty and not low poverty)

The study was supported by a grant from the National Institute on Drug Abuse. The authors disclosed no relevant conflicts of interest.

SOURCE: Stein BD et al. Subst Abuse. 2018 Jun 22. doi: 10.1080/08897077.2018.1449166.

The combination a long-acting beta agonist (LABA) and an inhaled glucocorticoid decreases the risk of an asthma exacerbation by 17%, without increasing the risk of asthma-related intubation or death.

MattZ90/thinkstockphotos

An independent analysis of four large, drug company–sponsored trials supports the Food and Drug Administration’s recent decision to remove the black box warning on LABA/inhaled glucocorticoid products, wrote William W. Busse, MD, and his colleagues. The report was published in the New England Journal of Medicine.

“Our analysis confirmed a lower relative risk of asthma exacerbations of 17% with combination therapy than with an inhaled glucocorticoid alone. This finding corresponds to the lower relative rates of asthma exacerbations that were reported in the sponsored individual trials: by 21% in the GlaxoSmithKline trial [hazard ratio 0.79], by 16% in the AstraZeneca trial [HR. 0.84], and by 11% in the Merck trial [HR 0.89],” wrote Dr. Busse of the University of Wisconsin, Madison, and his coauthors.

The FDA based its December 2017 reversal on an initial review of the studies, which were reviewed by an independent committee and are now public. Dr. Busse led the expert analysis of the studies, which the FDA required after it put the black box warning on the combination products.

In 2010, the FDA advised that LABAs shouldn’t be used as first-line therapy for asthma and required a black box warning on all LABA-containing products. Despite an FDA-conducted meta-analysis that found no increase in serious asthma-related incidents, the agency said there wasn’t enough subgroup evidence to support the safety of LABAs when combined with an inhaled glucocorticoid.

“FDA stated that the small numbers of patients who were enrolled in these studies prevented a definitive conclusion regarding mitigation of serious asthma-related events with the addition of inhaled glucocorticoids,” the investigators stated.

The agency required the four companies marketing a LABA for asthma to conduct prospective randomized trials comparing the safety of LABA/inhaled glucocorticoid to inhaled glucocorticoid alone. The trials by AstraZeneca, GlaxoSmithKline, Merck, and Novartis were identical. Three had complete, 26-week data; Novartis submitted partial data, as it withdrew its product from the American market in 2015. The committee reviewed all of the studies, which comprised a total of 36,010 teens and adults (aged 12-91 years). The primary endpoint was a composite of asthma-related intubation or death; secondary endpoints were a composite of hospitalization, intubation, or death, and individual assessments of each of those events.

Among the four studies, there were three asthma-related intubations: two in the inhaled-glucocorticoid group and one in the combination-therapy group. There were also two asthma-related deaths, both in the combination group.

Serious asthma-related events occurred in 108 of the inhaled glucocorticoid group (0.60%) and in 119 of the combination-therapy group (0.66%), a nonsignificant difference.

However, the combination therapy did confer a significant 17% reduction in asthma exacerbations. Exacerbations occurred in 11.7% of the inhaled glucocorticoid group and in 9.8% of the combination therapy group (relative risk 0.83; P less than 0.001). All four trials showed a similarly decreased risk of exacerbation.

The committee looked at several subgroups, dividing the cohort by age, race/ethnicity/ obesity, and smoking history. The advantage associated with combination therapy remained significant in all these analyses.

[email protected]

SOURCE: Busse WW et al. N Engl J Med. 2018;78:2497-505.

The combination a long-acting beta agonist (LABA) and an inhaled glucocorticoid decreases the risk of an asthma exacerbation by 17%, without increasing the risk of asthma-related intubation or death.

MattZ90/thinkstockphotos

An independent analysis of four large, drug company–sponsored trials supports the Food and Drug Administration’s recent decision to remove the black box warning on LABA/inhaled glucocorticoid products, wrote William W. Busse, MD, and his colleagues. The report was published in the New England Journal of Medicine.

“Our analysis confirmed a lower relative risk of asthma exacerbations of 17% with combination therapy than with an inhaled glucocorticoid alone. This finding corresponds to the lower relative rates of asthma exacerbations that were reported in the sponsored individual trials: by 21% in the GlaxoSmithKline trial [hazard ratio 0.79], by 16% in the AstraZeneca trial [HR. 0.84], and by 11% in the Merck trial [HR 0.89],” wrote Dr. Busse of the University of Wisconsin, Madison, and his coauthors.

The FDA based its December 2017 reversal on an initial review of the studies, which were reviewed by an independent committee and are now public. Dr. Busse led the expert analysis of the studies, which the FDA required after it put the black box warning on the combination products.

In 2010, the FDA advised that LABAs shouldn’t be used as first-line therapy for asthma and required a black box warning on all LABA-containing products. Despite an FDA-conducted meta-analysis that found no increase in serious asthma-related incidents, the agency said there wasn’t enough subgroup evidence to support the safety of LABAs when combined with an inhaled glucocorticoid.

“FDA stated that the small numbers of patients who were enrolled in these studies prevented a definitive conclusion regarding mitigation of serious asthma-related events with the addition of inhaled glucocorticoids,” the investigators stated.

The agency required the four companies marketing a LABA for asthma to conduct prospective randomized trials comparing the safety of LABA/inhaled glucocorticoid to inhaled glucocorticoid alone. The trials by AstraZeneca, GlaxoSmithKline, Merck, and Novartis were identical. Three had complete, 26-week data; Novartis submitted partial data, as it withdrew its product from the American market in 2015. The committee reviewed all of the studies, which comprised a total of 36,010 teens and adults (aged 12-91 years). The primary endpoint was a composite of asthma-related intubation or death; secondary endpoints were a composite of hospitalization, intubation, or death, and individual assessments of each of those events.

Among the four studies, there were three asthma-related intubations: two in the inhaled-glucocorticoid group and one in the combination-therapy group. There were also two asthma-related deaths, both in the combination group.

Serious asthma-related events occurred in 108 of the inhaled glucocorticoid group (0.60%) and in 119 of the combination-therapy group (0.66%), a nonsignificant difference.

However, the combination therapy did confer a significant 17% reduction in asthma exacerbations. Exacerbations occurred in 11.7% of the inhaled glucocorticoid group and in 9.8% of the combination therapy group (relative risk 0.83; P less than 0.001). All four trials showed a similarly decreased risk of exacerbation.

The committee looked at several subgroups, dividing the cohort by age, race/ethnicity/ obesity, and smoking history. The advantage associated with combination therapy remained significant in all these analyses.

[email protected]

SOURCE: Busse WW et al. N Engl J Med. 2018;78:2497-505.

The combination a long-acting beta agonist (LABA) and an inhaled glucocorticoid decreases the risk of an asthma exacerbation by 17%, without increasing the risk of asthma-related intubation or death.

MattZ90/thinkstockphotos

An independent analysis of four large, drug company–sponsored trials supports the Food and Drug Administration’s recent decision to remove the black box warning on LABA/inhaled glucocorticoid products, wrote William W. Busse, MD, and his colleagues. The report was published in the New England Journal of Medicine.

“Our analysis confirmed a lower relative risk of asthma exacerbations of 17% with combination therapy than with an inhaled glucocorticoid alone. This finding corresponds to the lower relative rates of asthma exacerbations that were reported in the sponsored individual trials: by 21% in the GlaxoSmithKline trial [hazard ratio 0.79], by 16% in the AstraZeneca trial [HR. 0.84], and by 11% in the Merck trial [HR 0.89],” wrote Dr. Busse of the University of Wisconsin, Madison, and his coauthors.

The FDA based its December 2017 reversal on an initial review of the studies, which were reviewed by an independent committee and are now public. Dr. Busse led the expert analysis of the studies, which the FDA required after it put the black box warning on the combination products.

In 2010, the FDA advised that LABAs shouldn’t be used as first-line therapy for asthma and required a black box warning on all LABA-containing products. Despite an FDA-conducted meta-analysis that found no increase in serious asthma-related incidents, the agency said there wasn’t enough subgroup evidence to support the safety of LABAs when combined with an inhaled glucocorticoid.

“FDA stated that the small numbers of patients who were enrolled in these studies prevented a definitive conclusion regarding mitigation of serious asthma-related events with the addition of inhaled glucocorticoids,” the investigators stated.

The agency required the four companies marketing a LABA for asthma to conduct prospective randomized trials comparing the safety of LABA/inhaled glucocorticoid to inhaled glucocorticoid alone. The trials by AstraZeneca, GlaxoSmithKline, Merck, and Novartis were identical. Three had complete, 26-week data; Novartis submitted partial data, as it withdrew its product from the American market in 2015. The committee reviewed all of the studies, which comprised a total of 36,010 teens and adults (aged 12-91 years). The primary endpoint was a composite of asthma-related intubation or death; secondary endpoints were a composite of hospitalization, intubation, or death, and individual assessments of each of those events.

Among the four studies, there were three asthma-related intubations: two in the inhaled-glucocorticoid group and one in the combination-therapy group. There were also two asthma-related deaths, both in the combination group.

Serious asthma-related events occurred in 108 of the inhaled glucocorticoid group (0.60%) and in 119 of the combination-therapy group (0.66%), a nonsignificant difference.

However, the combination therapy did confer a significant 17% reduction in asthma exacerbations. Exacerbations occurred in 11.7% of the inhaled glucocorticoid group and in 9.8% of the combination therapy group (relative risk 0.83; P less than 0.001). All four trials showed a similarly decreased risk of exacerbation.

The committee looked at several subgroups, dividing the cohort by age, race/ethnicity/ obesity, and smoking history. The advantage associated with combination therapy remained significant in all these analyses.

[email protected]

SOURCE: Busse WW et al. N Engl J Med. 2018;78:2497-505.

After years of decline, the overall death rate has risen 12% over the last 3 years among children and adolescents aged 10-19 years, driven by an increase in deaths caused by injury, according to the National Center for Health Statistics.

Mortality in this age group, which had dropped nearly 33% from 1999 to 2013, climbed from 29.6 per 100,000 population aged 10-19 years in 2013 to 33.1 per 100,000 in 2016, the last year for which data are available. Meanwhile, deaths from injuries – unintentional injuries, suicides, homicides, and legal intervention – went from 19.8 per 100,000 to 23.3, an increase of almost 18%, from 2013 to 2016, and the noninjury death rate “was relatively stable,” Sally C. Curtin and her associates at the NCHS Division of Vital Statistics said in a National Vital Statistics Report.

The recent surge in injury deaths was more substantial in the older half of the age group. The mortality rate for children aged 10-14 years went from a low of 6.4 per 100,000 in 2012 to 7.1 in 2016, an increase of 11%, while the rate for those aged 15-19 rose 19% as it jumped from 32.8 per 100,000 in 2013 to 39.0 in 2016, the investigators wrote in the report.

The rate of unintentional injury deaths in 10- to 19-year-olds shows the same pattern as all deaths and injury deaths: Decline from 1999 to 2013 and then a rise for the last 3 years. That recent rise also can be seen in the most common form of unintentional injury deaths, motor vehicle traffic accidents, and in poisoning deaths, although that uptick began a year later. Homicide deaths declined by one-third from 2007 to 2014 and then increased, while suicide rates have been rising since 2007, the investigators said. Legal intervention deaths, defined as those caused by law enforcement actions, were not included because of relatively small annual numbers.

“Although progress was made in reducing injury deaths among children and adolescents aged 10-19 years during 1999-2013, the recent upturn shows that persistent as well as emerging challenges remain. … Further reductions will require renewed focus and effort,” Ms. Curtin and her associates wrote.

[email protected]

SOURCE: Curtin SC et al. Natl Vital Stat Rep. 2018 Jun;67(4):1-16.


 

After years of decline, the overall death rate has risen 12% over the last 3 years among children and adolescents aged 10-19 years, driven by an increase in deaths caused by injury, according to the National Center for Health Statistics.

Mortality in this age group, which had dropped nearly 33% from 1999 to 2013, climbed from 29.6 per 100,000 population aged 10-19 years in 2013 to 33.1 per 100,000 in 2016, the last year for which data are available. Meanwhile, deaths from injuries – unintentional injuries, suicides, homicides, and legal intervention – went from 19.8 per 100,000 to 23.3, an increase of almost 18%, from 2013 to 2016, and the noninjury death rate “was relatively stable,” Sally C. Curtin and her associates at the NCHS Division of Vital Statistics said in a National Vital Statistics Report.

The recent surge in injury deaths was more substantial in the older half of the age group. The mortality rate for children aged 10-14 years went from a low of 6.4 per 100,000 in 2012 to 7.1 in 2016, an increase of 11%, while the rate for those aged 15-19 rose 19% as it jumped from 32.8 per 100,000 in 2013 to 39.0 in 2016, the investigators wrote in the report.

The rate of unintentional injury deaths in 10- to 19-year-olds shows the same pattern as all deaths and injury deaths: Decline from 1999 to 2013 and then a rise for the last 3 years. That recent rise also can be seen in the most common form of unintentional injury deaths, motor vehicle traffic accidents, and in poisoning deaths, although that uptick began a year later. Homicide deaths declined by one-third from 2007 to 2014 and then increased, while suicide rates have been rising since 2007, the investigators said. Legal intervention deaths, defined as those caused by law enforcement actions, were not included because of relatively small annual numbers.

“Although progress was made in reducing injury deaths among children and adolescents aged 10-19 years during 1999-2013, the recent upturn shows that persistent as well as emerging challenges remain. … Further reductions will require renewed focus and effort,” Ms. Curtin and her associates wrote.

[email protected]

SOURCE: Curtin SC et al. Natl Vital Stat Rep. 2018 Jun;67(4):1-16.


 

After years of decline, the overall death rate has risen 12% over the last 3 years among children and adolescents aged 10-19 years, driven by an increase in deaths caused by injury, according to the National Center for Health Statistics.

Mortality in this age group, which had dropped nearly 33% from 1999 to 2013, climbed from 29.6 per 100,000 population aged 10-19 years in 2013 to 33.1 per 100,000 in 2016, the last year for which data are available. Meanwhile, deaths from injuries – unintentional injuries, suicides, homicides, and legal intervention – went from 19.8 per 100,000 to 23.3, an increase of almost 18%, from 2013 to 2016, and the noninjury death rate “was relatively stable,” Sally C. Curtin and her associates at the NCHS Division of Vital Statistics said in a National Vital Statistics Report.

The recent surge in injury deaths was more substantial in the older half of the age group. The mortality rate for children aged 10-14 years went from a low of 6.4 per 100,000 in 2012 to 7.1 in 2016, an increase of 11%, while the rate for those aged 15-19 rose 19% as it jumped from 32.8 per 100,000 in 2013 to 39.0 in 2016, the investigators wrote in the report.

The rate of unintentional injury deaths in 10- to 19-year-olds shows the same pattern as all deaths and injury deaths: Decline from 1999 to 2013 and then a rise for the last 3 years. That recent rise also can be seen in the most common form of unintentional injury deaths, motor vehicle traffic accidents, and in poisoning deaths, although that uptick began a year later. Homicide deaths declined by one-third from 2007 to 2014 and then increased, while suicide rates have been rising since 2007, the investigators said. Legal intervention deaths, defined as those caused by law enforcement actions, were not included because of relatively small annual numbers.

“Although progress was made in reducing injury deaths among children and adolescents aged 10-19 years during 1999-2013, the recent upturn shows that persistent as well as emerging challenges remain. … Further reductions will require renewed focus and effort,” Ms. Curtin and her associates wrote.

[email protected]

SOURCE: Curtin SC et al. Natl Vital Stat Rep. 2018 Jun;67(4):1-16.


 

Q2. Correct Answer: A

Rationale
Anti-TNF therapy is relatively safe and well-tolerated. However, there are a few important issues to consider prior to initiation of therapy. There is a risk of reactivation of both Mycobacterium tuberculosis and hepatitis B. In this patient’s case, her PPD positivity is likely a false positive from remote BCG vaccination. An interferon gamma release assay (e.g. QuantiFERON®) can be checked to confirm this; even if that is positive, in the absence of active tuberculosis (TB), she can be treated for latent TB for several weeks prior to initiation of anti-TNF therapy. Her hepatitis B serologies do not suggest chronic infection but rather prior infection with resolution. In this case, anti-TNF therapy is not precluded; rather, the AGA recommends considering concurrent antiviral prophylaxis while on anti-TNF therapy. Anti-TNF agents are not known to significantly increase the risk of progressive multifocal leukoencephalopathy like the nonselective anti-integrin natalizumab, so JC virus antibody positivity does not preclude their use. There is a slight increased risk of melanoma in those on anti-TNF therapy; non-melanoma skin cancers are of greater concern in those on thiopurine therapy. Finally, anti-TNF therapy should be avoided in those with demyelinating diseases or those at high risk for such diseases.

References
1. Reddy K.R., Beavers K.L., Hammond S.P., et al. American Gastroenterological Association Institute Guideline on the prevention and treatment of Hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2014;148[1]:215-9.
2. Long M.D., Martin C.F., Pipkin C.A., et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143[2]:390-9.
3. Ariyaratnam J., Subramanian V. Association between thiopurine use and nonmelanoma skin cancers in patients with inflammatory bowel disease: A meta-analysis. Am J Gastroenterol. 2014;109:163-9.

Q2. Correct Answer: A

Rationale
Anti-TNF therapy is relatively safe and well-tolerated. However, there are a few important issues to consider prior to initiation of therapy. There is a risk of reactivation of both Mycobacterium tuberculosis and hepatitis B. In this patient’s case, her PPD positivity is likely a false positive from remote BCG vaccination. An interferon gamma release assay (e.g. QuantiFERON®) can be checked to confirm this; even if that is positive, in the absence of active tuberculosis (TB), she can be treated for latent TB for several weeks prior to initiation of anti-TNF therapy. Her hepatitis B serologies do not suggest chronic infection but rather prior infection with resolution. In this case, anti-TNF therapy is not precluded; rather, the AGA recommends considering concurrent antiviral prophylaxis while on anti-TNF therapy. Anti-TNF agents are not known to significantly increase the risk of progressive multifocal leukoencephalopathy like the nonselective anti-integrin natalizumab, so JC virus antibody positivity does not preclude their use. There is a slight increased risk of melanoma in those on anti-TNF therapy; non-melanoma skin cancers are of greater concern in those on thiopurine therapy. Finally, anti-TNF therapy should be avoided in those with demyelinating diseases or those at high risk for such diseases.

References
1. Reddy K.R., Beavers K.L., Hammond S.P., et al. American Gastroenterological Association Institute Guideline on the prevention and treatment of Hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2014;148[1]:215-9.
2. Long M.D., Martin C.F., Pipkin C.A., et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143[2]:390-9.
3. Ariyaratnam J., Subramanian V. Association between thiopurine use and nonmelanoma skin cancers in patients with inflammatory bowel disease: A meta-analysis. Am J Gastroenterol. 2014;109:163-9.

Q2. Correct Answer: A

Rationale
Anti-TNF therapy is relatively safe and well-tolerated. However, there are a few important issues to consider prior to initiation of therapy. There is a risk of reactivation of both Mycobacterium tuberculosis and hepatitis B. In this patient’s case, her PPD positivity is likely a false positive from remote BCG vaccination. An interferon gamma release assay (e.g. QuantiFERON®) can be checked to confirm this; even if that is positive, in the absence of active tuberculosis (TB), she can be treated for latent TB for several weeks prior to initiation of anti-TNF therapy. Her hepatitis B serologies do not suggest chronic infection but rather prior infection with resolution. In this case, anti-TNF therapy is not precluded; rather, the AGA recommends considering concurrent antiviral prophylaxis while on anti-TNF therapy. Anti-TNF agents are not known to significantly increase the risk of progressive multifocal leukoencephalopathy like the nonselective anti-integrin natalizumab, so JC virus antibody positivity does not preclude their use. There is a slight increased risk of melanoma in those on anti-TNF therapy; non-melanoma skin cancers are of greater concern in those on thiopurine therapy. Finally, anti-TNF therapy should be avoided in those with demyelinating diseases or those at high risk for such diseases.

References
1. Reddy K.R., Beavers K.L., Hammond S.P., et al. American Gastroenterological Association Institute Guideline on the prevention and treatment of Hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2014;148[1]:215-9.
2. Long M.D., Martin C.F., Pipkin C.A., et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143[2]:390-9.
3. Ariyaratnam J., Subramanian V. Association between thiopurine use and nonmelanoma skin cancers in patients with inflammatory bowel disease: A meta-analysis. Am J Gastroenterol. 2014;109:163-9.