Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

CHICAGO – Bempedoic acid, a novel oral lipid-lowering agent, reduced LDL cholesterol by 21% and high-sensitivity C-reactive protein by 24% with a side-effect profile similar to placebo in statin-intolerant hypercholesterolemic patients with or at high risk for atherosclerotic cardiovascular disease in the pivotal phase 3 CLEAR Serenity trial, Ulrich Laufs, MD, PhD, reported at the American Heart Association scientific sessions.

CLEAR Serenity is one of five pivotal phase 3 trials of bempedoic acid. The others evaluated bempedoic acid as add-on therapy to obtain additional lipid lowering in patients already on a maximum-dose statin, and in combination with ezetimibe (Zetia) as a single pill, also in patients on full-dose statin therapy. All of these trials met their efficacy and safety endpoints. The drug’s developer, Esperion Therapeutics, has announced plans to file for marketing approval of bempedoic acid and for the bempedoic acid/ezetimibe combo pill with the Food and Drug Administration and the European Medicines Agency in the first months of 2019.

CLEAR Serenity was a 24-week, double-blind, placebo-controlled trial conducted at 67 North American sites. The 345 statin-intolerant participants were randomized 2:1 to bempedoic acid at 180 mg once daily or placebo.

“I think the specific contribution of this study is, importantly, that myalgia and other muscle-related symptoms were not increased with bempedoic acid versus placebo in this population that’s statin intolerant, more than 90% of whom complained of statin-related muscle symptoms,” said Dr. Laufs, professor and chair of the department of cardiology at the University of Leipzig (Germany).

Rates of major adverse cardiovascular events were too low in this relatively short-term, modest-size trial to be informative, but the results of the previously presented CLEAR Harmony trial are reassuring in this regard, according to the cardiologist. CLEAR Harmony was a 52-week study that included 2,230 patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia whose LDL was inadequately controlled despite high-intensity statin therapy. They were randomized to add-on bempedoic acid or placebo. The adjudicated major adverse cardiovascular event rate was 4.6% in the bempedoic acid group and not significantly different at 5.7% in controls.

Definitive data on the effect of bempedoic acid on cardiovascular morbidity and mortality event rates will eventually be provided by an ongoing global randomized, double-blind, placebo-controlled trial expected to enroll more than 12,000 patients.

Rates of various types of adverse events were closely similar in the bempedoic acid and placebo groups in CLEAR Serenity, with a couple of intriguing exceptions, according to Dr. Laufs. For example, the rate of new-onset or worsening diabetes was 2.1% in the bempedoic acid group, compared with 4.5% in controls.

“This is consistent with results in the other studies in the overall bempedoic acid program. It will be something of great interest to follow up in the ongoing outcomes trial,” he said. “At this point I would feel comfortable in saying that there is no deterioration of glucose tolerance, unlike with statins. Whether there is an actual improvement or not needs to be characterized a little better.”

The other difference in the safety profile between the two study arms in CLEAR Serenity was a trend for higher uric acid levels and an increased risk of developing gout in the bempedoic acid group. Gout occurred in 1.7% of the bempedoic acid group and 0.9% of placebo-treated controls. A similar signal has been seen in the other pivotal trials, but a definitive answer as to gout risk must await the large ongoing outcomes trial, Dr. Laufs continued.

Bempedoic acid is a first-in-class oral inhibitor of ATP citrate lyase, an enzyme that is inactive in skeletal muscle – thus, the lack of myalgia complaints – and lies upstream of HMG-CoA reductase in cholesterol synthesis. When combined in a single pill with ezetimibe, which lowers LDL by stimulating the LDL receptor, the lipid-lowering impact is magnified over that of either drug alone. In the phase 3 program, the combination pill resulted in a further 35% reduction in LDL when added to a maximally tolerated statin and a 43% reduction in LDL when used as monotherapy.

Session cochair Robert H. Eckel, MD, commented that bempedoic acid appears to be poised to address a significant unmet need in preventive cardiology.

“We clearly need alternative therapies in patients with statin intolerance. We see a lot of these patients in referral centers. This drug looks safe and very effective at modifying LDL, about as much so as ezetimibe and maybe a little bit more,” said Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.

Dr. Laufs reported serving as a paid consultant to Esperion Therapeutics, the study sponsor, as well as to Amgen and Sanofi.

[email protected]

CHICAGO – Bempedoic acid, a novel oral lipid-lowering agent, reduced LDL cholesterol by 21% and high-sensitivity C-reactive protein by 24% with a side-effect profile similar to placebo in statin-intolerant hypercholesterolemic patients with or at high risk for atherosclerotic cardiovascular disease in the pivotal phase 3 CLEAR Serenity trial, Ulrich Laufs, MD, PhD, reported at the American Heart Association scientific sessions.

CLEAR Serenity is one of five pivotal phase 3 trials of bempedoic acid. The others evaluated bempedoic acid as add-on therapy to obtain additional lipid lowering in patients already on a maximum-dose statin, and in combination with ezetimibe (Zetia) as a single pill, also in patients on full-dose statin therapy. All of these trials met their efficacy and safety endpoints. The drug’s developer, Esperion Therapeutics, has announced plans to file for marketing approval of bempedoic acid and for the bempedoic acid/ezetimibe combo pill with the Food and Drug Administration and the European Medicines Agency in the first months of 2019.

CLEAR Serenity was a 24-week, double-blind, placebo-controlled trial conducted at 67 North American sites. The 345 statin-intolerant participants were randomized 2:1 to bempedoic acid at 180 mg once daily or placebo.

“I think the specific contribution of this study is, importantly, that myalgia and other muscle-related symptoms were not increased with bempedoic acid versus placebo in this population that’s statin intolerant, more than 90% of whom complained of statin-related muscle symptoms,” said Dr. Laufs, professor and chair of the department of cardiology at the University of Leipzig (Germany).

Rates of major adverse cardiovascular events were too low in this relatively short-term, modest-size trial to be informative, but the results of the previously presented CLEAR Harmony trial are reassuring in this regard, according to the cardiologist. CLEAR Harmony was a 52-week study that included 2,230 patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia whose LDL was inadequately controlled despite high-intensity statin therapy. They were randomized to add-on bempedoic acid or placebo. The adjudicated major adverse cardiovascular event rate was 4.6% in the bempedoic acid group and not significantly different at 5.7% in controls.

Definitive data on the effect of bempedoic acid on cardiovascular morbidity and mortality event rates will eventually be provided by an ongoing global randomized, double-blind, placebo-controlled trial expected to enroll more than 12,000 patients.

Rates of various types of adverse events were closely similar in the bempedoic acid and placebo groups in CLEAR Serenity, with a couple of intriguing exceptions, according to Dr. Laufs. For example, the rate of new-onset or worsening diabetes was 2.1% in the bempedoic acid group, compared with 4.5% in controls.

“This is consistent with results in the other studies in the overall bempedoic acid program. It will be something of great interest to follow up in the ongoing outcomes trial,” he said. “At this point I would feel comfortable in saying that there is no deterioration of glucose tolerance, unlike with statins. Whether there is an actual improvement or not needs to be characterized a little better.”

The other difference in the safety profile between the two study arms in CLEAR Serenity was a trend for higher uric acid levels and an increased risk of developing gout in the bempedoic acid group. Gout occurred in 1.7% of the bempedoic acid group and 0.9% of placebo-treated controls. A similar signal has been seen in the other pivotal trials, but a definitive answer as to gout risk must await the large ongoing outcomes trial, Dr. Laufs continued.

Bempedoic acid is a first-in-class oral inhibitor of ATP citrate lyase, an enzyme that is inactive in skeletal muscle – thus, the lack of myalgia complaints – and lies upstream of HMG-CoA reductase in cholesterol synthesis. When combined in a single pill with ezetimibe, which lowers LDL by stimulating the LDL receptor, the lipid-lowering impact is magnified over that of either drug alone. In the phase 3 program, the combination pill resulted in a further 35% reduction in LDL when added to a maximally tolerated statin and a 43% reduction in LDL when used as monotherapy.

Session cochair Robert H. Eckel, MD, commented that bempedoic acid appears to be poised to address a significant unmet need in preventive cardiology.

“We clearly need alternative therapies in patients with statin intolerance. We see a lot of these patients in referral centers. This drug looks safe and very effective at modifying LDL, about as much so as ezetimibe and maybe a little bit more,” said Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.

Dr. Laufs reported serving as a paid consultant to Esperion Therapeutics, the study sponsor, as well as to Amgen and Sanofi.

[email protected]

CHICAGO – Bempedoic acid, a novel oral lipid-lowering agent, reduced LDL cholesterol by 21% and high-sensitivity C-reactive protein by 24% with a side-effect profile similar to placebo in statin-intolerant hypercholesterolemic patients with or at high risk for atherosclerotic cardiovascular disease in the pivotal phase 3 CLEAR Serenity trial, Ulrich Laufs, MD, PhD, reported at the American Heart Association scientific sessions.

CLEAR Serenity is one of five pivotal phase 3 trials of bempedoic acid. The others evaluated bempedoic acid as add-on therapy to obtain additional lipid lowering in patients already on a maximum-dose statin, and in combination with ezetimibe (Zetia) as a single pill, also in patients on full-dose statin therapy. All of these trials met their efficacy and safety endpoints. The drug’s developer, Esperion Therapeutics, has announced plans to file for marketing approval of bempedoic acid and for the bempedoic acid/ezetimibe combo pill with the Food and Drug Administration and the European Medicines Agency in the first months of 2019.

CLEAR Serenity was a 24-week, double-blind, placebo-controlled trial conducted at 67 North American sites. The 345 statin-intolerant participants were randomized 2:1 to bempedoic acid at 180 mg once daily or placebo.

“I think the specific contribution of this study is, importantly, that myalgia and other muscle-related symptoms were not increased with bempedoic acid versus placebo in this population that’s statin intolerant, more than 90% of whom complained of statin-related muscle symptoms,” said Dr. Laufs, professor and chair of the department of cardiology at the University of Leipzig (Germany).

Rates of major adverse cardiovascular events were too low in this relatively short-term, modest-size trial to be informative, but the results of the previously presented CLEAR Harmony trial are reassuring in this regard, according to the cardiologist. CLEAR Harmony was a 52-week study that included 2,230 patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia whose LDL was inadequately controlled despite high-intensity statin therapy. They were randomized to add-on bempedoic acid or placebo. The adjudicated major adverse cardiovascular event rate was 4.6% in the bempedoic acid group and not significantly different at 5.7% in controls.

Definitive data on the effect of bempedoic acid on cardiovascular morbidity and mortality event rates will eventually be provided by an ongoing global randomized, double-blind, placebo-controlled trial expected to enroll more than 12,000 patients.

Rates of various types of adverse events were closely similar in the bempedoic acid and placebo groups in CLEAR Serenity, with a couple of intriguing exceptions, according to Dr. Laufs. For example, the rate of new-onset or worsening diabetes was 2.1% in the bempedoic acid group, compared with 4.5% in controls.

“This is consistent with results in the other studies in the overall bempedoic acid program. It will be something of great interest to follow up in the ongoing outcomes trial,” he said. “At this point I would feel comfortable in saying that there is no deterioration of glucose tolerance, unlike with statins. Whether there is an actual improvement or not needs to be characterized a little better.”

The other difference in the safety profile between the two study arms in CLEAR Serenity was a trend for higher uric acid levels and an increased risk of developing gout in the bempedoic acid group. Gout occurred in 1.7% of the bempedoic acid group and 0.9% of placebo-treated controls. A similar signal has been seen in the other pivotal trials, but a definitive answer as to gout risk must await the large ongoing outcomes trial, Dr. Laufs continued.

Bempedoic acid is a first-in-class oral inhibitor of ATP citrate lyase, an enzyme that is inactive in skeletal muscle – thus, the lack of myalgia complaints – and lies upstream of HMG-CoA reductase in cholesterol synthesis. When combined in a single pill with ezetimibe, which lowers LDL by stimulating the LDL receptor, the lipid-lowering impact is magnified over that of either drug alone. In the phase 3 program, the combination pill resulted in a further 35% reduction in LDL when added to a maximally tolerated statin and a 43% reduction in LDL when used as monotherapy.

Session cochair Robert H. Eckel, MD, commented that bempedoic acid appears to be poised to address a significant unmet need in preventive cardiology.

“We clearly need alternative therapies in patients with statin intolerance. We see a lot of these patients in referral centers. This drug looks safe and very effective at modifying LDL, about as much so as ezetimibe and maybe a little bit more,” said Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.

Dr. Laufs reported serving as a paid consultant to Esperion Therapeutics, the study sponsor, as well as to Amgen and Sanofi.

[email protected]

A new smartphone app under development seeks to detect the first moments of an overdose-related respiratory crisis and summon help before it’s too late.

“We’re hoping a device that most people carry around could be transformed into technology that could save your life in an overdose,” said anesthesiologist Jacob (Jake) E. Sunshine, MD, an assistant professor with the University of Washington, Seattle, and coauthor of a study about the app’s development.

The ultimate goal is “to provide a harm reduction system that can automatically connect naloxone-equipped friends and family or emergency medical services to help prevent fatal overdose events,” Rajalakshmi Nandakumar, and her associates wrote in the study, published in Science Translational Medicine.

An estimated 70,000 people in the United States died from drug overdoses in 2017, according to a 2018 data brief from the Centers for Disease Control and Prevention. On an age-adjusted basis, the overdose death rate in 2017 was more than three times higher than in 1999.

The app, which builds on previous work aimed at detecting disordered breathing in sleep apnea, uses a “short-range active sonar system” to detect respiration in a person within the distance of about 3 feet. The approach is similar to the echolocation strategy used by a dolphin or bat, Dr. Sunshine said, and relies on sending out an audio tone that humans cannot hear.

The app’s microphone detects an “audio reflection” of the tone after it bounces off a nearby person’s body and then analyzes it to calculate the distance to the person’s chest. “We’re able to use those distances to measure when someone is taking a breath, and when they’re not taking a breath,” said Dr. Sunshine, who conceptualized the study.

If a disordered breathing pattern is detected, the app is designed to send a text message with a GPS-pinpointed location to a prespecified contact, Dr. Sunshine said. Or the app could be set to call 911.

In the study, the investigators tested the app’s algorithm at a supervised injection facility – a space designed to allow users to inject illicit drugs safely – in Vancouver. They tested the app on 94 drug users as they injected themselves; half of the users “experienced clinically important respiratory depression,” and two needed to be treated by clinic staff for overdose. Both users survived, reported Ms. Nandakumar, a PhD candidate at the University of Washington, Seattle; Shyamnath Gollakota, PhD, an associate professor at the university; and Dr. Sunshine.

The new study found that the app detected cessation of breathing for 10 seconds or longer 95.9% of the time (95% confidence interval, 86.0%-99.5%) with 97.7% specificity (95% confidence interval, 88.2%-99.9%). However, the app was less adept at identifying respiratory depression (respiratory rate equal to or less than 7 breaths per minute): The investigators reported 87.2% sensitivity (95% CI, 74.2%-95.1%) and 89.3% specificity (95% CI, 76.9%-96.4%).

Ms. Nandakumar and her associates also tested the app’s algorithm on patients undergoing anesthesia. It correctly detected disordered breathing in 19 of 20 patients.

It’s not clear how the app would work in environments full of breathing people and, potentially, breathing animals such as pets. And the app has clear limitations. Since it needs to be able to bounce audio signals off a user’s chest, it will not work if a phone is in a pocket or if a user is face down, turns around, or wanders off.

However, the app can detect sudden changes in motion, Dr. Sunshine said, and investigators are developing a way to require users to check in with the app in certain situations that might signal trouble.

“For harm reduction interventions to be efficacious, further studies with participant feedback and human factor testing are needed to ensure that the system meets the needs, values, and preferences of people who use opioids, in addition to establishing the system’s safety vis-à-vis its potential to encourage moral hazard,” the investigators wrote in the article.

The next steps are to refine the app’s user interface and figure out how to connect it to the 911 emergency-response system, Dr. Sunshine said. Meanwhile, researchers have created a company to develop the product. “We’re going to do additional development through that entity and seek [Food and Drug Administration] approval,” Dr. Sunshine said. The investigators do not plan to charge users for the product, which can be used on iPhones and Androids, he said.

The study was funded by the Foundation for Anesthesia Education and Research, the National Science Foundation, and the University of Washington’s Alcohol and Drug Abuse Institute. Dr. Sunshine, Ms. Nandakumar, and Dr. Gollakota are inventors on a provisional patient application related to the project, and all have equity stakes in a company that is developing the technology. Dr. Gollakota is a paid consultant to Jeeva Wireless and Edus Health.

SOURCE: Nandakumar R et al. Sci Transl Med. 2019 Jan 9;11(474). doi: 10.1126/scitranslmed.aau8914.

A new smartphone app under development seeks to detect the first moments of an overdose-related respiratory crisis and summon help before it’s too late.

“We’re hoping a device that most people carry around could be transformed into technology that could save your life in an overdose,” said anesthesiologist Jacob (Jake) E. Sunshine, MD, an assistant professor with the University of Washington, Seattle, and coauthor of a study about the app’s development.

The ultimate goal is “to provide a harm reduction system that can automatically connect naloxone-equipped friends and family or emergency medical services to help prevent fatal overdose events,” Rajalakshmi Nandakumar, and her associates wrote in the study, published in Science Translational Medicine.

An estimated 70,000 people in the United States died from drug overdoses in 2017, according to a 2018 data brief from the Centers for Disease Control and Prevention. On an age-adjusted basis, the overdose death rate in 2017 was more than three times higher than in 1999.

The app, which builds on previous work aimed at detecting disordered breathing in sleep apnea, uses a “short-range active sonar system” to detect respiration in a person within the distance of about 3 feet. The approach is similar to the echolocation strategy used by a dolphin or bat, Dr. Sunshine said, and relies on sending out an audio tone that humans cannot hear.

The app’s microphone detects an “audio reflection” of the tone after it bounces off a nearby person’s body and then analyzes it to calculate the distance to the person’s chest. “We’re able to use those distances to measure when someone is taking a breath, and when they’re not taking a breath,” said Dr. Sunshine, who conceptualized the study.

If a disordered breathing pattern is detected, the app is designed to send a text message with a GPS-pinpointed location to a prespecified contact, Dr. Sunshine said. Or the app could be set to call 911.

In the study, the investigators tested the app’s algorithm at a supervised injection facility – a space designed to allow users to inject illicit drugs safely – in Vancouver. They tested the app on 94 drug users as they injected themselves; half of the users “experienced clinically important respiratory depression,” and two needed to be treated by clinic staff for overdose. Both users survived, reported Ms. Nandakumar, a PhD candidate at the University of Washington, Seattle; Shyamnath Gollakota, PhD, an associate professor at the university; and Dr. Sunshine.

The new study found that the app detected cessation of breathing for 10 seconds or longer 95.9% of the time (95% confidence interval, 86.0%-99.5%) with 97.7% specificity (95% confidence interval, 88.2%-99.9%). However, the app was less adept at identifying respiratory depression (respiratory rate equal to or less than 7 breaths per minute): The investigators reported 87.2% sensitivity (95% CI, 74.2%-95.1%) and 89.3% specificity (95% CI, 76.9%-96.4%).

Ms. Nandakumar and her associates also tested the app’s algorithm on patients undergoing anesthesia. It correctly detected disordered breathing in 19 of 20 patients.

It’s not clear how the app would work in environments full of breathing people and, potentially, breathing animals such as pets. And the app has clear limitations. Since it needs to be able to bounce audio signals off a user’s chest, it will not work if a phone is in a pocket or if a user is face down, turns around, or wanders off.

However, the app can detect sudden changes in motion, Dr. Sunshine said, and investigators are developing a way to require users to check in with the app in certain situations that might signal trouble.

“For harm reduction interventions to be efficacious, further studies with participant feedback and human factor testing are needed to ensure that the system meets the needs, values, and preferences of people who use opioids, in addition to establishing the system’s safety vis-à-vis its potential to encourage moral hazard,” the investigators wrote in the article.

The next steps are to refine the app’s user interface and figure out how to connect it to the 911 emergency-response system, Dr. Sunshine said. Meanwhile, researchers have created a company to develop the product. “We’re going to do additional development through that entity and seek [Food and Drug Administration] approval,” Dr. Sunshine said. The investigators do not plan to charge users for the product, which can be used on iPhones and Androids, he said.

The study was funded by the Foundation for Anesthesia Education and Research, the National Science Foundation, and the University of Washington’s Alcohol and Drug Abuse Institute. Dr. Sunshine, Ms. Nandakumar, and Dr. Gollakota are inventors on a provisional patient application related to the project, and all have equity stakes in a company that is developing the technology. Dr. Gollakota is a paid consultant to Jeeva Wireless and Edus Health.

SOURCE: Nandakumar R et al. Sci Transl Med. 2019 Jan 9;11(474). doi: 10.1126/scitranslmed.aau8914.

A new smartphone app under development seeks to detect the first moments of an overdose-related respiratory crisis and summon help before it’s too late.

“We’re hoping a device that most people carry around could be transformed into technology that could save your life in an overdose,” said anesthesiologist Jacob (Jake) E. Sunshine, MD, an assistant professor with the University of Washington, Seattle, and coauthor of a study about the app’s development.

The ultimate goal is “to provide a harm reduction system that can automatically connect naloxone-equipped friends and family or emergency medical services to help prevent fatal overdose events,” Rajalakshmi Nandakumar, and her associates wrote in the study, published in Science Translational Medicine.

An estimated 70,000 people in the United States died from drug overdoses in 2017, according to a 2018 data brief from the Centers for Disease Control and Prevention. On an age-adjusted basis, the overdose death rate in 2017 was more than three times higher than in 1999.

The app, which builds on previous work aimed at detecting disordered breathing in sleep apnea, uses a “short-range active sonar system” to detect respiration in a person within the distance of about 3 feet. The approach is similar to the echolocation strategy used by a dolphin or bat, Dr. Sunshine said, and relies on sending out an audio tone that humans cannot hear.

The app’s microphone detects an “audio reflection” of the tone after it bounces off a nearby person’s body and then analyzes it to calculate the distance to the person’s chest. “We’re able to use those distances to measure when someone is taking a breath, and when they’re not taking a breath,” said Dr. Sunshine, who conceptualized the study.

If a disordered breathing pattern is detected, the app is designed to send a text message with a GPS-pinpointed location to a prespecified contact, Dr. Sunshine said. Or the app could be set to call 911.

In the study, the investigators tested the app’s algorithm at a supervised injection facility – a space designed to allow users to inject illicit drugs safely – in Vancouver. They tested the app on 94 drug users as they injected themselves; half of the users “experienced clinically important respiratory depression,” and two needed to be treated by clinic staff for overdose. Both users survived, reported Ms. Nandakumar, a PhD candidate at the University of Washington, Seattle; Shyamnath Gollakota, PhD, an associate professor at the university; and Dr. Sunshine.

The new study found that the app detected cessation of breathing for 10 seconds or longer 95.9% of the time (95% confidence interval, 86.0%-99.5%) with 97.7% specificity (95% confidence interval, 88.2%-99.9%). However, the app was less adept at identifying respiratory depression (respiratory rate equal to or less than 7 breaths per minute): The investigators reported 87.2% sensitivity (95% CI, 74.2%-95.1%) and 89.3% specificity (95% CI, 76.9%-96.4%).

Ms. Nandakumar and her associates also tested the app’s algorithm on patients undergoing anesthesia. It correctly detected disordered breathing in 19 of 20 patients.

It’s not clear how the app would work in environments full of breathing people and, potentially, breathing animals such as pets. And the app has clear limitations. Since it needs to be able to bounce audio signals off a user’s chest, it will not work if a phone is in a pocket or if a user is face down, turns around, or wanders off.

However, the app can detect sudden changes in motion, Dr. Sunshine said, and investigators are developing a way to require users to check in with the app in certain situations that might signal trouble.

“For harm reduction interventions to be efficacious, further studies with participant feedback and human factor testing are needed to ensure that the system meets the needs, values, and preferences of people who use opioids, in addition to establishing the system’s safety vis-à-vis its potential to encourage moral hazard,” the investigators wrote in the article.

The next steps are to refine the app’s user interface and figure out how to connect it to the 911 emergency-response system, Dr. Sunshine said. Meanwhile, researchers have created a company to develop the product. “We’re going to do additional development through that entity and seek [Food and Drug Administration] approval,” Dr. Sunshine said. The investigators do not plan to charge users for the product, which can be used on iPhones and Androids, he said.

The study was funded by the Foundation for Anesthesia Education and Research, the National Science Foundation, and the University of Washington’s Alcohol and Drug Abuse Institute. Dr. Sunshine, Ms. Nandakumar, and Dr. Gollakota are inventors on a provisional patient application related to the project, and all have equity stakes in a company that is developing the technology. Dr. Gollakota is a paid consultant to Jeeva Wireless and Edus Health.

SOURCE: Nandakumar R et al. Sci Transl Med. 2019 Jan 9;11(474). doi: 10.1126/scitranslmed.aau8914.

The patient was diagnosed with lichen spinulosus (LS) based on the physical appearance of the lesions (hyperkeratotic spiny papules forming plaques), the lack of pruritus, and negative personal history of atopic dermatitis.

Lichen spinulosus is an underreported entity, first described in 1908 by Adamson as superficial circumscribed chronic dermatitis in children and adolescents. The median age of presentation is age 16 years. There are several reports of possible associations with systemic infections such as HIV, fungi, and syphilis, as well as chronic diseases such as Crohn’s disease, Hodgkin disease, seborrhea, and secondary to certain medications such as omeprazole. There are no prior reports of infliximab being associated with LS, but it has been reported to cause other lichenoid reactions such as lichen planus and lichen planopilaris.

Clinically the lesions are characterized by asymptomatic, small (1 cm), skin color, hyperkeratotic, follicular papules that coalesce into plaques. The lesions usually occur on the extensor surfaces of the arms, neck, torso, and buttocks. Mild pruritus can occur in some patients.

The lesions in keratosis pilaris can be very similar to lichen spinulosus, but usually they don’t coalesce into plaques and are commonly present on the extensor surfaces of the arms, thighs, and cheeks. Histopathology of both conditions is very similar.

Another condition to consider includes papular eczema. The lesions in papular eczema tend to be pruritic and are not as circumscribed as LS lesions. Papular eczema responds well to the use of topical corticosteroids, while LS lesions usually do not. Lichen nitidus (LN) is characterized by monomorphic, skin color, 1-mm, flat-topped papules. Lesions tend to occur in crops rather than circumscribed papules forming plaques. LN most commonly presents on the extensor surface of the arms, trunk, dorsal hands, and genitalia. Koebner phenomenon is usually seen. Although uncommon in children, a more generalized type of follicular mucinosis can present very similar to lichen spinulosus. A recent study found LS-like lesions with associated hypopigmentation and hair loss should be suspicious for folliculotropic mycosis fungoides.

Keratolytics such as lactic acid, urea, and salicylic acid can help improve LS, although they do not cure it. Other reported treatments include the use of topical adapalene, tacalcitol cream, and tretinoin gel with hydroactive adhesive.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at [email protected].

The patient was diagnosed with lichen spinulosus (LS) based on the physical appearance of the lesions (hyperkeratotic spiny papules forming plaques), the lack of pruritus, and negative personal history of atopic dermatitis.

Lichen spinulosus is an underreported entity, first described in 1908 by Adamson as superficial circumscribed chronic dermatitis in children and adolescents. The median age of presentation is age 16 years. There are several reports of possible associations with systemic infections such as HIV, fungi, and syphilis, as well as chronic diseases such as Crohn’s disease, Hodgkin disease, seborrhea, and secondary to certain medications such as omeprazole. There are no prior reports of infliximab being associated with LS, but it has been reported to cause other lichenoid reactions such as lichen planus and lichen planopilaris.

Clinically the lesions are characterized by asymptomatic, small (1 cm), skin color, hyperkeratotic, follicular papules that coalesce into plaques. The lesions usually occur on the extensor surfaces of the arms, neck, torso, and buttocks. Mild pruritus can occur in some patients.

The lesions in keratosis pilaris can be very similar to lichen spinulosus, but usually they don’t coalesce into plaques and are commonly present on the extensor surfaces of the arms, thighs, and cheeks. Histopathology of both conditions is very similar.

Another condition to consider includes papular eczema. The lesions in papular eczema tend to be pruritic and are not as circumscribed as LS lesions. Papular eczema responds well to the use of topical corticosteroids, while LS lesions usually do not. Lichen nitidus (LN) is characterized by monomorphic, skin color, 1-mm, flat-topped papules. Lesions tend to occur in crops rather than circumscribed papules forming plaques. LN most commonly presents on the extensor surface of the arms, trunk, dorsal hands, and genitalia. Koebner phenomenon is usually seen. Although uncommon in children, a more generalized type of follicular mucinosis can present very similar to lichen spinulosus. A recent study found LS-like lesions with associated hypopigmentation and hair loss should be suspicious for folliculotropic mycosis fungoides.

Keratolytics such as lactic acid, urea, and salicylic acid can help improve LS, although they do not cure it. Other reported treatments include the use of topical adapalene, tacalcitol cream, and tretinoin gel with hydroactive adhesive.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at [email protected].

The patient was diagnosed with lichen spinulosus (LS) based on the physical appearance of the lesions (hyperkeratotic spiny papules forming plaques), the lack of pruritus, and negative personal history of atopic dermatitis.

Lichen spinulosus is an underreported entity, first described in 1908 by Adamson as superficial circumscribed chronic dermatitis in children and adolescents. The median age of presentation is age 16 years. There are several reports of possible associations with systemic infections such as HIV, fungi, and syphilis, as well as chronic diseases such as Crohn’s disease, Hodgkin disease, seborrhea, and secondary to certain medications such as omeprazole. There are no prior reports of infliximab being associated with LS, but it has been reported to cause other lichenoid reactions such as lichen planus and lichen planopilaris.

Clinically the lesions are characterized by asymptomatic, small (1 cm), skin color, hyperkeratotic, follicular papules that coalesce into plaques. The lesions usually occur on the extensor surfaces of the arms, neck, torso, and buttocks. Mild pruritus can occur in some patients.

The lesions in keratosis pilaris can be very similar to lichen spinulosus, but usually they don’t coalesce into plaques and are commonly present on the extensor surfaces of the arms, thighs, and cheeks. Histopathology of both conditions is very similar.

Another condition to consider includes papular eczema. The lesions in papular eczema tend to be pruritic and are not as circumscribed as LS lesions. Papular eczema responds well to the use of topical corticosteroids, while LS lesions usually do not. Lichen nitidus (LN) is characterized by monomorphic, skin color, 1-mm, flat-topped papules. Lesions tend to occur in crops rather than circumscribed papules forming plaques. LN most commonly presents on the extensor surface of the arms, trunk, dorsal hands, and genitalia. Koebner phenomenon is usually seen. Although uncommon in children, a more generalized type of follicular mucinosis can present very similar to lichen spinulosus. A recent study found LS-like lesions with associated hypopigmentation and hair loss should be suspicious for folliculotropic mycosis fungoides.

Keratolytics such as lactic acid, urea, and salicylic acid can help improve LS, although they do not cure it. Other reported treatments include the use of topical adapalene, tacalcitol cream, and tretinoin gel with hydroactive adhesive.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at [email protected].

The Food and Drug Administration has approved the expanded use of Adacel (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine Adsorbed) to include repeat vaccinations 8 years or more after the first vaccination in people aged 10-64 years.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The expanded indication was based on results of a randomized, controlled trial, published in the Journal of the Pediatric Infectious Diseases Society, in which more than 1,300 adults aged 18-64 years received either Adacel or a Td (tetanus-diphtheria) vaccine 8-12 years after receiving a previous dose of Adacel.

Over the course of the study, no significant difference in adverse event incidence was observed between groups. Injection-site reaction was the most common adverse event during the study, occurring in 87.7% of those who received Adacel and 88.0% of those who received the Td vaccine. Other common adverse events associated with Adacel include headache, body ache or muscle weakness, tiredness, muscle aches, and general discomfort.

“While strong vaccination programs are in place for young adolescents, a single Tdap immunization does not offer lifetime protection against pertussis due to waning immunity. The licensure of Adacel as the first Tdap vaccine in the U.S. for repeat vaccination is an important step for eligible patients and offers flexibility for health care providers to help manage their immunization schedules,” said David P. Greenberg, MD, regional medical head North America at Sanofi Pasteur, in the press release.

Find the full press release on the Sanofi website.

[email protected]

The Food and Drug Administration has approved the expanded use of Adacel (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine Adsorbed) to include repeat vaccinations 8 years or more after the first vaccination in people aged 10-64 years.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The expanded indication was based on results of a randomized, controlled trial, published in the Journal of the Pediatric Infectious Diseases Society, in which more than 1,300 adults aged 18-64 years received either Adacel or a Td (tetanus-diphtheria) vaccine 8-12 years after receiving a previous dose of Adacel.

Over the course of the study, no significant difference in adverse event incidence was observed between groups. Injection-site reaction was the most common adverse event during the study, occurring in 87.7% of those who received Adacel and 88.0% of those who received the Td vaccine. Other common adverse events associated with Adacel include headache, body ache or muscle weakness, tiredness, muscle aches, and general discomfort.

“While strong vaccination programs are in place for young adolescents, a single Tdap immunization does not offer lifetime protection against pertussis due to waning immunity. The licensure of Adacel as the first Tdap vaccine in the U.S. for repeat vaccination is an important step for eligible patients and offers flexibility for health care providers to help manage their immunization schedules,” said David P. Greenberg, MD, regional medical head North America at Sanofi Pasteur, in the press release.

Find the full press release on the Sanofi website.

[email protected]

The Food and Drug Administration has approved the expanded use of Adacel (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine Adsorbed) to include repeat vaccinations 8 years or more after the first vaccination in people aged 10-64 years.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The expanded indication was based on results of a randomized, controlled trial, published in the Journal of the Pediatric Infectious Diseases Society, in which more than 1,300 adults aged 18-64 years received either Adacel or a Td (tetanus-diphtheria) vaccine 8-12 years after receiving a previous dose of Adacel.

Over the course of the study, no significant difference in adverse event incidence was observed between groups. Injection-site reaction was the most common adverse event during the study, occurring in 87.7% of those who received Adacel and 88.0% of those who received the Td vaccine. Other common adverse events associated with Adacel include headache, body ache or muscle weakness, tiredness, muscle aches, and general discomfort.

“While strong vaccination programs are in place for young adolescents, a single Tdap immunization does not offer lifetime protection against pertussis due to waning immunity. The licensure of Adacel as the first Tdap vaccine in the U.S. for repeat vaccination is an important step for eligible patients and offers flexibility for health care providers to help manage their immunization schedules,” said David P. Greenberg, MD, regional medical head North America at Sanofi Pasteur, in the press release.

Find the full press release on the Sanofi website.

[email protected]

Background: Previous studies have shown that lower muscle function is associated with increased mortality; however, studies have not been able to fully examine associations with age and disease-specific mortality.

Dr. Marr is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

Background: Previous studies have shown that lower muscle function is associated with increased mortality; however, studies have not been able to fully examine associations with age and disease-specific mortality.

Dr. Marr is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

Background: Previous studies have shown that lower muscle function is associated with increased mortality; however, studies have not been able to fully examine associations with age and disease-specific mortality.

Dr. Marr is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

Checkpoint inhibitors can cause rare, but serious, hematological immune-related adverse events (hem-irAEs), which require early detection and intervention, according to a recent French study.

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs in the population, reported lead author, Nicolas Delanoy, MD, of Gustave Roussy, Université Paris-Saclay, Villejuif, France, and his colleagues.

“About 71% of patients treated have any-grade irAEs and 10% have grade 3-4 irAEs after anti-PD-1 immunotherapy,” the investigators wrote. The report is in The Lancet Haematology. “In most cases, they involve the skin, gastrointestinal tract, thyroid or endocrine glands, liver, lungs, or joints. However, all organs can potentially be affected, including the hemopoietic system.”

Despite this possibility, few reports detail the frequency or character of hematological toxicities from immunotherapy.

The present study involved 948 patients who entered into three French registries between 2014 and 2018. The first registry, consisting of 745 patients, was observed prospectively during checkpoint inhibitor therapy. The other two registries provided retrospective data on confirmed irAEs or hem-irAEs.

Among 745 patients followed during checkpoint inhibitor therapy, four developed hem-irAEs, providing an incidence rate of 0.5%. The other two databases added 31 patients with confirmed hem-irAEs, allowing for characterization of 35 total cases.

The group of 35 patients had a median age of 65 years, with more men (n = 21) than women (n = 14). Melanoma was the most common type of malignancy (43%), followed by non–small-cell lung cancer (34%), lymphoma (11%), and others. The majority of patients received nivolumab (57%), slightly fewer received pembrolizumab (40%), and a small minority received atezolizumab (3%).

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs, each occurring in nine patients (26%). Five patients (14%) had aplastic anemia or pancytopenia, two patients had bicytopenia (6%; neutropenia and anemia or thrombocytopenia and anemia), and one patient had pure red cell aplasia (3%).

Hem-irAEs resolved in 60% of patients, but two patients (6%) died due to febrile neutropenia. Overall, 71% of hem-irAEs were grade 4.

These findings suggest that hem-irAEs are rare, but they are often serious, and potentially life-threatening, the researchers noted.

In 7 of 35 patients (20%) who were rechallenged with checkpoint inhibitor therapy, 3 (43%) had recurrence of hem-irAEs. This finding should elicit caution and close monitoring if rechallenge is elected.

“This observational study encourages further, in-depth investigations of hematological immune toxicities, to search for biomarkers that can be helpful for earlier detection,” the investigators concluded.

This study was funded by Gustave Roussy and the Gustave Roussy Immunotherapy Program. Dr. Delanoy reported nonfinancial support from Sanofi and other authors reported financial relationships with pharmaceutical companies.

SOURCE: Delanoy N et al. Lancet Haematol. 2018 Dec 4. doi: 10.1016/S2352-3026(18)30175-3.

Checkpoint inhibitors can cause rare, but serious, hematological immune-related adverse events (hem-irAEs), which require early detection and intervention, according to a recent French study.

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs in the population, reported lead author, Nicolas Delanoy, MD, of Gustave Roussy, Université Paris-Saclay, Villejuif, France, and his colleagues.

“About 71% of patients treated have any-grade irAEs and 10% have grade 3-4 irAEs after anti-PD-1 immunotherapy,” the investigators wrote. The report is in The Lancet Haematology. “In most cases, they involve the skin, gastrointestinal tract, thyroid or endocrine glands, liver, lungs, or joints. However, all organs can potentially be affected, including the hemopoietic system.”

Despite this possibility, few reports detail the frequency or character of hematological toxicities from immunotherapy.

The present study involved 948 patients who entered into three French registries between 2014 and 2018. The first registry, consisting of 745 patients, was observed prospectively during checkpoint inhibitor therapy. The other two registries provided retrospective data on confirmed irAEs or hem-irAEs.

Among 745 patients followed during checkpoint inhibitor therapy, four developed hem-irAEs, providing an incidence rate of 0.5%. The other two databases added 31 patients with confirmed hem-irAEs, allowing for characterization of 35 total cases.

The group of 35 patients had a median age of 65 years, with more men (n = 21) than women (n = 14). Melanoma was the most common type of malignancy (43%), followed by non–small-cell lung cancer (34%), lymphoma (11%), and others. The majority of patients received nivolumab (57%), slightly fewer received pembrolizumab (40%), and a small minority received atezolizumab (3%).

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs, each occurring in nine patients (26%). Five patients (14%) had aplastic anemia or pancytopenia, two patients had bicytopenia (6%; neutropenia and anemia or thrombocytopenia and anemia), and one patient had pure red cell aplasia (3%).

Hem-irAEs resolved in 60% of patients, but two patients (6%) died due to febrile neutropenia. Overall, 71% of hem-irAEs were grade 4.

These findings suggest that hem-irAEs are rare, but they are often serious, and potentially life-threatening, the researchers noted.

In 7 of 35 patients (20%) who were rechallenged with checkpoint inhibitor therapy, 3 (43%) had recurrence of hem-irAEs. This finding should elicit caution and close monitoring if rechallenge is elected.

“This observational study encourages further, in-depth investigations of hematological immune toxicities, to search for biomarkers that can be helpful for earlier detection,” the investigators concluded.

This study was funded by Gustave Roussy and the Gustave Roussy Immunotherapy Program. Dr. Delanoy reported nonfinancial support from Sanofi and other authors reported financial relationships with pharmaceutical companies.

SOURCE: Delanoy N et al. Lancet Haematol. 2018 Dec 4. doi: 10.1016/S2352-3026(18)30175-3.

Checkpoint inhibitors can cause rare, but serious, hematological immune-related adverse events (hem-irAEs), which require early detection and intervention, according to a recent French study.

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs in the population, reported lead author, Nicolas Delanoy, MD, of Gustave Roussy, Université Paris-Saclay, Villejuif, France, and his colleagues.

“About 71% of patients treated have any-grade irAEs and 10% have grade 3-4 irAEs after anti-PD-1 immunotherapy,” the investigators wrote. The report is in The Lancet Haematology. “In most cases, they involve the skin, gastrointestinal tract, thyroid or endocrine glands, liver, lungs, or joints. However, all organs can potentially be affected, including the hemopoietic system.”

Despite this possibility, few reports detail the frequency or character of hematological toxicities from immunotherapy.

The present study involved 948 patients who entered into three French registries between 2014 and 2018. The first registry, consisting of 745 patients, was observed prospectively during checkpoint inhibitor therapy. The other two registries provided retrospective data on confirmed irAEs or hem-irAEs.

Among 745 patients followed during checkpoint inhibitor therapy, four developed hem-irAEs, providing an incidence rate of 0.5%. The other two databases added 31 patients with confirmed hem-irAEs, allowing for characterization of 35 total cases.

The group of 35 patients had a median age of 65 years, with more men (n = 21) than women (n = 14). Melanoma was the most common type of malignancy (43%), followed by non–small-cell lung cancer (34%), lymphoma (11%), and others. The majority of patients received nivolumab (57%), slightly fewer received pembrolizumab (40%), and a small minority received atezolizumab (3%).

Immune thrombocytopenia, hemolytic anemia, and neutropenia were the most common hem-irAEs, each occurring in nine patients (26%). Five patients (14%) had aplastic anemia or pancytopenia, two patients had bicytopenia (6%; neutropenia and anemia or thrombocytopenia and anemia), and one patient had pure red cell aplasia (3%).

Hem-irAEs resolved in 60% of patients, but two patients (6%) died due to febrile neutropenia. Overall, 71% of hem-irAEs were grade 4.

These findings suggest that hem-irAEs are rare, but they are often serious, and potentially life-threatening, the researchers noted.

In 7 of 35 patients (20%) who were rechallenged with checkpoint inhibitor therapy, 3 (43%) had recurrence of hem-irAEs. This finding should elicit caution and close monitoring if rechallenge is elected.

“This observational study encourages further, in-depth investigations of hematological immune toxicities, to search for biomarkers that can be helpful for earlier detection,” the investigators concluded.

This study was funded by Gustave Roussy and the Gustave Roussy Immunotherapy Program. Dr. Delanoy reported nonfinancial support from Sanofi and other authors reported financial relationships with pharmaceutical companies.

SOURCE: Delanoy N et al. Lancet Haematol. 2018 Dec 4. doi: 10.1016/S2352-3026(18)30175-3.

BARCELONA – Consider the possibility of an autoantibody-related etiology in all cases of first-onset psychosis, Josep Dalmau, MD, PhD, urged at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“There are patients in our clinics all of us – neurologists and psychiatrists – are missing. These patients are believed to have psychiatric presentations, but they do not. They are autoimmune,” said Dr. Dalmau, professor of neurology at the University of Barcelona.

Dr. Dalmau urged psychiatrists to become familiar with the red flags suggestive of synaptic autoimmunity as the underlying cause of first-episode, out-of-the-blue psychosis.

“If you have a patient with a classical presentation of schizophrenia or bipolar disorder, you probably won’t find antibodies,” according to the neurologist.

It’s important to have a high index of suspicion, because anti–NMDA receptor encephalitis is treatable with immunotherapy. And firm evidence shows that earlier recognition and treatment lead to improved outcomes. Also, the disorder is refractory to antipsychotics; indeed, antipsychotic agents make affected patients much worse, even to the point of developing something akin to neuroleptic malignant syndrome.

Manifestations of anti–NMDA receptor encephalitis follow a characteristic pattern, beginning with a prodromal flulike phase lasting several days to a week. This is followed by acute-onset bizarre behavioral changes, irritability, and psychosis with delusions and/or hallucinations, often progressing to catatonia. After 1-4 weeks of this, florid neurologic symptoms usually appear, including seizures, abnormal movements, autonomic dysregulation, and hypoventilation requiring prolonged ICU support for weeks to months. This is followed by a prolonged recovery phase lasting 5-24 months, and a period marked by deficits in executive function and working memory, impulsivity, and disinhibition. Impressively, the patient has no memory of the illness.

In one large series of patients with confirmed anti–NMDA receptor encephalitis reported by Dr. Dalmau and coinvestigators, psychiatric symptoms occurred in isolation without subsequent neurologic involvement in just 4% of cases (JAMA Neurol. 2013 Sep 1;70[9]:1133-9).

Dr. Dalmau was senior author of an international cohort study including 577 patients with anti-NMDA receptor encephalitis with serial follow-up for 24 months. The study provided an unprecedented picture of the epidemiology and clinical features of the disorder.

“It’s a disease predominantly of women and young people,” he observed.

Indeed, the median age of the study population was 21 years, and 37% of subjects were less than 18 years of age. Roughly 80% of patients were female and most of them had a benign ovarian teratoma, which played a key role in their neuropsychiatric disease (Lancet Neurol. 2013 Feb;12[2]:157-65). These benign tumors express the NMDA receptor in ectopic nerve tissue, triggering a systemic immune response.

One or more relapses – again treatable via immunotherapy – occurred in 12% of patients during 24 months of follow-up.

When a red flag suggestive of synaptic autoimmunity is present, it’s important to obtain a cerebrospinal fluid (CSF) sample for analysis, along with an EEG and/or brain MRI.

“I don’t know if you as psychiatrists are set up to do spinal taps in all persons with first presentation of psychosis, but this would be my suggestion. It’s extremely useful in this situation,” Dr. Dalmau said.

The vast majority of patients with anti–NMDA receptor encephalitis have CSF pleocytosis with a mild lymphocytic predominance. The MRI is abnormal in about 35% of cases. EEG abnormalities are common but nonspecific. The diagnosis is confirmed by identification of anti–NMDA receptor antibodies in the CSF.

First-line therapy is corticosteroids, intravenous immunoglobulin, and/or plasma exchange to remove the pathogenic antibodies, along with resection of the tumor if present. These treatments are effective in almost half of affected patients. When they’re not, the second-line options are rituximab (Rituxan) and cyclophosphamide, alone or combined.

Antibodies to the NMDA receptor are far and away the most common cause of synaptic autoimmunity-induced psychosis, but other targets of autoimmunity have been documented as well, including the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, contactin-associated protein-like 2 (CASPR2), and neurexin-3-alpha.

Dr. Dalmau and various collaborators continue to advance the understanding of this novel category of neuropsychiatric disease. They have developed a simple 5-point score, known as the NEOS score, that predicts 1-year functional status in patients with anti–NMDA receptor encephalitis (Neurology. 2018 Dec 21. doi: 10.1212/WNL.0000000000006783). He and his colleagues have also recently shown in a prospective study that herpes simplex encephalitis can result in an autoimmune encephalitis, with NMDA receptor antibodies present in most cases (Lancet Neurol. 2018 Sep;17[9]:760-72).

Dr. Dalmau’s research is supported by the U.S. National Institute of Neurological Disorders and Stroke, the Spanish Ministry of Health, and Spanish research foundations. He reported receiving royalties from the use of several neuronal antibody tests.

[email protected]

BARCELONA – Consider the possibility of an autoantibody-related etiology in all cases of first-onset psychosis, Josep Dalmau, MD, PhD, urged at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“There are patients in our clinics all of us – neurologists and psychiatrists – are missing. These patients are believed to have psychiatric presentations, but they do not. They are autoimmune,” said Dr. Dalmau, professor of neurology at the University of Barcelona.

Dr. Dalmau urged psychiatrists to become familiar with the red flags suggestive of synaptic autoimmunity as the underlying cause of first-episode, out-of-the-blue psychosis.

“If you have a patient with a classical presentation of schizophrenia or bipolar disorder, you probably won’t find antibodies,” according to the neurologist.

It’s important to have a high index of suspicion, because anti–NMDA receptor encephalitis is treatable with immunotherapy. And firm evidence shows that earlier recognition and treatment lead to improved outcomes. Also, the disorder is refractory to antipsychotics; indeed, antipsychotic agents make affected patients much worse, even to the point of developing something akin to neuroleptic malignant syndrome.

Manifestations of anti–NMDA receptor encephalitis follow a characteristic pattern, beginning with a prodromal flulike phase lasting several days to a week. This is followed by acute-onset bizarre behavioral changes, irritability, and psychosis with delusions and/or hallucinations, often progressing to catatonia. After 1-4 weeks of this, florid neurologic symptoms usually appear, including seizures, abnormal movements, autonomic dysregulation, and hypoventilation requiring prolonged ICU support for weeks to months. This is followed by a prolonged recovery phase lasting 5-24 months, and a period marked by deficits in executive function and working memory, impulsivity, and disinhibition. Impressively, the patient has no memory of the illness.

In one large series of patients with confirmed anti–NMDA receptor encephalitis reported by Dr. Dalmau and coinvestigators, psychiatric symptoms occurred in isolation without subsequent neurologic involvement in just 4% of cases (JAMA Neurol. 2013 Sep 1;70[9]:1133-9).

Dr. Dalmau was senior author of an international cohort study including 577 patients with anti-NMDA receptor encephalitis with serial follow-up for 24 months. The study provided an unprecedented picture of the epidemiology and clinical features of the disorder.

“It’s a disease predominantly of women and young people,” he observed.

Indeed, the median age of the study population was 21 years, and 37% of subjects were less than 18 years of age. Roughly 80% of patients were female and most of them had a benign ovarian teratoma, which played a key role in their neuropsychiatric disease (Lancet Neurol. 2013 Feb;12[2]:157-65). These benign tumors express the NMDA receptor in ectopic nerve tissue, triggering a systemic immune response.

One or more relapses – again treatable via immunotherapy – occurred in 12% of patients during 24 months of follow-up.

When a red flag suggestive of synaptic autoimmunity is present, it’s important to obtain a cerebrospinal fluid (CSF) sample for analysis, along with an EEG and/or brain MRI.

“I don’t know if you as psychiatrists are set up to do spinal taps in all persons with first presentation of psychosis, but this would be my suggestion. It’s extremely useful in this situation,” Dr. Dalmau said.

The vast majority of patients with anti–NMDA receptor encephalitis have CSF pleocytosis with a mild lymphocytic predominance. The MRI is abnormal in about 35% of cases. EEG abnormalities are common but nonspecific. The diagnosis is confirmed by identification of anti–NMDA receptor antibodies in the CSF.

First-line therapy is corticosteroids, intravenous immunoglobulin, and/or plasma exchange to remove the pathogenic antibodies, along with resection of the tumor if present. These treatments are effective in almost half of affected patients. When they’re not, the second-line options are rituximab (Rituxan) and cyclophosphamide, alone or combined.

Antibodies to the NMDA receptor are far and away the most common cause of synaptic autoimmunity-induced psychosis, but other targets of autoimmunity have been documented as well, including the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, contactin-associated protein-like 2 (CASPR2), and neurexin-3-alpha.

Dr. Dalmau and various collaborators continue to advance the understanding of this novel category of neuropsychiatric disease. They have developed a simple 5-point score, known as the NEOS score, that predicts 1-year functional status in patients with anti–NMDA receptor encephalitis (Neurology. 2018 Dec 21. doi: 10.1212/WNL.0000000000006783). He and his colleagues have also recently shown in a prospective study that herpes simplex encephalitis can result in an autoimmune encephalitis, with NMDA receptor antibodies present in most cases (Lancet Neurol. 2018 Sep;17[9]:760-72).

Dr. Dalmau’s research is supported by the U.S. National Institute of Neurological Disorders and Stroke, the Spanish Ministry of Health, and Spanish research foundations. He reported receiving royalties from the use of several neuronal antibody tests.

[email protected]

BARCELONA – Consider the possibility of an autoantibody-related etiology in all cases of first-onset psychosis, Josep Dalmau, MD, PhD, urged at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“There are patients in our clinics all of us – neurologists and psychiatrists – are missing. These patients are believed to have psychiatric presentations, but they do not. They are autoimmune,” said Dr. Dalmau, professor of neurology at the University of Barcelona.

Dr. Dalmau urged psychiatrists to become familiar with the red flags suggestive of synaptic autoimmunity as the underlying cause of first-episode, out-of-the-blue psychosis.

“If you have a patient with a classical presentation of schizophrenia or bipolar disorder, you probably won’t find antibodies,” according to the neurologist.

It’s important to have a high index of suspicion, because anti–NMDA receptor encephalitis is treatable with immunotherapy. And firm evidence shows that earlier recognition and treatment lead to improved outcomes. Also, the disorder is refractory to antipsychotics; indeed, antipsychotic agents make affected patients much worse, even to the point of developing something akin to neuroleptic malignant syndrome.

Manifestations of anti–NMDA receptor encephalitis follow a characteristic pattern, beginning with a prodromal flulike phase lasting several days to a week. This is followed by acute-onset bizarre behavioral changes, irritability, and psychosis with delusions and/or hallucinations, often progressing to catatonia. After 1-4 weeks of this, florid neurologic symptoms usually appear, including seizures, abnormal movements, autonomic dysregulation, and hypoventilation requiring prolonged ICU support for weeks to months. This is followed by a prolonged recovery phase lasting 5-24 months, and a period marked by deficits in executive function and working memory, impulsivity, and disinhibition. Impressively, the patient has no memory of the illness.

In one large series of patients with confirmed anti–NMDA receptor encephalitis reported by Dr. Dalmau and coinvestigators, psychiatric symptoms occurred in isolation without subsequent neurologic involvement in just 4% of cases (JAMA Neurol. 2013 Sep 1;70[9]:1133-9).

Dr. Dalmau was senior author of an international cohort study including 577 patients with anti-NMDA receptor encephalitis with serial follow-up for 24 months. The study provided an unprecedented picture of the epidemiology and clinical features of the disorder.

“It’s a disease predominantly of women and young people,” he observed.

Indeed, the median age of the study population was 21 years, and 37% of subjects were less than 18 years of age. Roughly 80% of patients were female and most of them had a benign ovarian teratoma, which played a key role in their neuropsychiatric disease (Lancet Neurol. 2013 Feb;12[2]:157-65). These benign tumors express the NMDA receptor in ectopic nerve tissue, triggering a systemic immune response.

One or more relapses – again treatable via immunotherapy – occurred in 12% of patients during 24 months of follow-up.

When a red flag suggestive of synaptic autoimmunity is present, it’s important to obtain a cerebrospinal fluid (CSF) sample for analysis, along with an EEG and/or brain MRI.

“I don’t know if you as psychiatrists are set up to do spinal taps in all persons with first presentation of psychosis, but this would be my suggestion. It’s extremely useful in this situation,” Dr. Dalmau said.

The vast majority of patients with anti–NMDA receptor encephalitis have CSF pleocytosis with a mild lymphocytic predominance. The MRI is abnormal in about 35% of cases. EEG abnormalities are common but nonspecific. The diagnosis is confirmed by identification of anti–NMDA receptor antibodies in the CSF.

First-line therapy is corticosteroids, intravenous immunoglobulin, and/or plasma exchange to remove the pathogenic antibodies, along with resection of the tumor if present. These treatments are effective in almost half of affected patients. When they’re not, the second-line options are rituximab (Rituxan) and cyclophosphamide, alone or combined.

Antibodies to the NMDA receptor are far and away the most common cause of synaptic autoimmunity-induced psychosis, but other targets of autoimmunity have been documented as well, including the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, contactin-associated protein-like 2 (CASPR2), and neurexin-3-alpha.

Dr. Dalmau and various collaborators continue to advance the understanding of this novel category of neuropsychiatric disease. They have developed a simple 5-point score, known as the NEOS score, that predicts 1-year functional status in patients with anti–NMDA receptor encephalitis (Neurology. 2018 Dec 21. doi: 10.1212/WNL.0000000000006783). He and his colleagues have also recently shown in a prospective study that herpes simplex encephalitis can result in an autoimmune encephalitis, with NMDA receptor antibodies present in most cases (Lancet Neurol. 2018 Sep;17[9]:760-72).

Dr. Dalmau’s research is supported by the U.S. National Institute of Neurological Disorders and Stroke, the Spanish Ministry of Health, and Spanish research foundations. He reported receiving royalties from the use of several neuronal antibody tests.

[email protected]

NEW YORK – Conflicts of interest, whether reported or unreported, are just one component of a broken system that has misaligned incentives with meaningful advances in breast cancer research, agreed a panel of experts who participated in an evening program sponsored by SHARE, a breast cancer patient advocacy group.

Ted Bosworth/MDedge News

“The issue of disclosures, while it is important, is not really the key issue. The key issue for me is about the amazing amount of money that is changing hands,” said Fran Visco, president of the National Breast Cancer Coalition, Washington. She contended not enough money in breast cancer research is being applied to save women’s lives rather than driving profits for institutions, physicians, and the pharmaceutical industry.

The other two participants in this panel, called Conflicts of Interest in Research and Treatment: What Breast Cancer Patients Should Know, largely agreed. In turn, they each explained that major sums of money in play for physicians and institutions collaborating with industry are earmarked for generating income much more than improving outcomes.

“Most of where this money is going is for these little tiny improvements and there is no association between the outcome increment that you get and what you pay for that outcome increment,” said Robert Cook-Deegan, MD, a bioethicist and a professor at the School for Innovation in Society, Arizona State University, Tempe.

Ted Bosworth/MDedge News

Ted Bosworth/MDEdge News

Ted Bosworth/MDEdge News

NEW YORK – Conflicts of interest, whether reported or unreported, are just one component of a broken system that has misaligned incentives with meaningful advances in breast cancer research, agreed a panel of experts who participated in an evening program sponsored by SHARE, a breast cancer patient advocacy group.

Ted Bosworth/MDedge News

“The issue of disclosures, while it is important, is not really the key issue. The key issue for me is about the amazing amount of money that is changing hands,” said Fran Visco, president of the National Breast Cancer Coalition, Washington. She contended not enough money in breast cancer research is being applied to save women’s lives rather than driving profits for institutions, physicians, and the pharmaceutical industry.

The other two participants in this panel, called Conflicts of Interest in Research and Treatment: What Breast Cancer Patients Should Know, largely agreed. In turn, they each explained that major sums of money in play for physicians and institutions collaborating with industry are earmarked for generating income much more than improving outcomes.

“Most of where this money is going is for these little tiny improvements and there is no association between the outcome increment that you get and what you pay for that outcome increment,” said Robert Cook-Deegan, MD, a bioethicist and a professor at the School for Innovation in Society, Arizona State University, Tempe.

Ted Bosworth/MDedge News

Ted Bosworth/MDEdge News

Ted Bosworth/MDEdge News

NEW YORK – Conflicts of interest, whether reported or unreported, are just one component of a broken system that has misaligned incentives with meaningful advances in breast cancer research, agreed a panel of experts who participated in an evening program sponsored by SHARE, a breast cancer patient advocacy group.

Ted Bosworth/MDedge News

“The issue of disclosures, while it is important, is not really the key issue. The key issue for me is about the amazing amount of money that is changing hands,” said Fran Visco, president of the National Breast Cancer Coalition, Washington. She contended not enough money in breast cancer research is being applied to save women’s lives rather than driving profits for institutions, physicians, and the pharmaceutical industry.

The other two participants in this panel, called Conflicts of Interest in Research and Treatment: What Breast Cancer Patients Should Know, largely agreed. In turn, they each explained that major sums of money in play for physicians and institutions collaborating with industry are earmarked for generating income much more than improving outcomes.

“Most of where this money is going is for these little tiny improvements and there is no association between the outcome increment that you get and what you pay for that outcome increment,” said Robert Cook-Deegan, MD, a bioethicist and a professor at the School for Innovation in Society, Arizona State University, Tempe.

Ted Bosworth/MDedge News

Ted Bosworth/MDEdge News

Ted Bosworth/MDEdge News

A clinical trial has begun which will examine whether fecal microbiota transplantation (FMT) by enema is safe and can prevent recurrent Clostridium difficile–associated disease (CDAD), according to a press release from the National Institutes of Health.

CDC/D. Holdeman

CDAD is normally treated with antibiotics such as vancomycin or fidaxomicin; however, it recurs in about 20% of people who receive this treatment. FMT is effective at curing patients with recurring C. diff infections, but long-term safety and a standardized process have yet to be established.

An estimated 162 people aged 18 years or older who have had two or more episodes of CDAD within the previous 6 months will be included in the clinical trial. These patients will be split into two groups: The first will receive an antidiarrheal medication and an FMT delivered by retention enema; the second will receive an antidiarrheal and a placebo colored to look like an active stool sample.

All patients will provide stool and blood samples at designated time points for 1 year after they undergo treatment for CDAD. Stool samples will be examined for gut microbial diversity changes and infectious pathogens; blood samples will be examined for metabolic syndrome markers.

“Clostridium difficile–associated disease, a significant problem in health care facilities, causes an estimated 15,000 deaths in the United States each year. This randomized, controlled trial aims to provide critical data on the efficacy and long-term safety of using fecal microbiota transplants by enema to cure C. diff infections,” NIAID director Anthony S. Fauci, MD, said in the press release.

The full trial page can be found at Clinicaltrials.gov.

[email protected]

A clinical trial has begun which will examine whether fecal microbiota transplantation (FMT) by enema is safe and can prevent recurrent Clostridium difficile–associated disease (CDAD), according to a press release from the National Institutes of Health.

CDC/D. Holdeman

CDAD is normally treated with antibiotics such as vancomycin or fidaxomicin; however, it recurs in about 20% of people who receive this treatment. FMT is effective at curing patients with recurring C. diff infections, but long-term safety and a standardized process have yet to be established.

An estimated 162 people aged 18 years or older who have had two or more episodes of CDAD within the previous 6 months will be included in the clinical trial. These patients will be split into two groups: The first will receive an antidiarrheal medication and an FMT delivered by retention enema; the second will receive an antidiarrheal and a placebo colored to look like an active stool sample.

All patients will provide stool and blood samples at designated time points for 1 year after they undergo treatment for CDAD. Stool samples will be examined for gut microbial diversity changes and infectious pathogens; blood samples will be examined for metabolic syndrome markers.

“Clostridium difficile–associated disease, a significant problem in health care facilities, causes an estimated 15,000 deaths in the United States each year. This randomized, controlled trial aims to provide critical data on the efficacy and long-term safety of using fecal microbiota transplants by enema to cure C. diff infections,” NIAID director Anthony S. Fauci, MD, said in the press release.

The full trial page can be found at Clinicaltrials.gov.

[email protected]

A clinical trial has begun which will examine whether fecal microbiota transplantation (FMT) by enema is safe and can prevent recurrent Clostridium difficile–associated disease (CDAD), according to a press release from the National Institutes of Health.

CDC/D. Holdeman

CDAD is normally treated with antibiotics such as vancomycin or fidaxomicin; however, it recurs in about 20% of people who receive this treatment. FMT is effective at curing patients with recurring C. diff infections, but long-term safety and a standardized process have yet to be established.

An estimated 162 people aged 18 years or older who have had two or more episodes of CDAD within the previous 6 months will be included in the clinical trial. These patients will be split into two groups: The first will receive an antidiarrheal medication and an FMT delivered by retention enema; the second will receive an antidiarrheal and a placebo colored to look like an active stool sample.

All patients will provide stool and blood samples at designated time points for 1 year after they undergo treatment for CDAD. Stool samples will be examined for gut microbial diversity changes and infectious pathogens; blood samples will be examined for metabolic syndrome markers.

“Clostridium difficile–associated disease, a significant problem in health care facilities, causes an estimated 15,000 deaths in the United States each year. This randomized, controlled trial aims to provide critical data on the efficacy and long-term safety of using fecal microbiota transplants by enema to cure C. diff infections,” NIAID director Anthony S. Fauci, MD, said in the press release.

The full trial page can be found at Clinicaltrials.gov.

[email protected]