The Trump administration bars federal funds for clinics that provide abortion counseling or referrals. Physician PAC dollars support candidates who don’t back gun regulation. Consider obesity as a cardiovascular disease risk factor in children. And the final ‘Vision’ report addresses maintenance of certification woes.

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The Trump administration bars federal funds for clinics that provide abortion counseling or referrals. Physician PAC dollars support candidates who don’t back gun regulation. Consider obesity as a cardiovascular disease risk factor in children. And the final ‘Vision’ report addresses maintenance of certification woes.

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Apple Podcasts
Google Podcasts
Spotify

The Trump administration bars federal funds for clinics that provide abortion counseling or referrals. Physician PAC dollars support candidates who don’t back gun regulation. Consider obesity as a cardiovascular disease risk factor in children. And the final ‘Vision’ report addresses maintenance of certification woes.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

SAN DIEGO – During resuscitation of patients with septic shock, a simple strategy of timing the refilling of peripheral capillaries trended toward better 28-day survival than using lactate level targeting, but missed statistical significance.

Jim Kling/MDedge News

Although the paper, published online in JAMA, concludes that normalization of capillary refill time cannot be recommended over targeting serum lactate levels, Glenn Hernández, MD, PhD, sounded more optimistic after presenting the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “I think it’s good news to develop techniques that, even though they have this integrated variability, they can provide a signal that is also very close to the [underlying] physiology,” Dr. Hernández, who is a professor of intensive medicine at Pontifical Catholic University in Santiago, Chile. The Peripheral perfusion was also associated with lower mean Sequential Organ Failure Assessment (SOFA) Score at 72 hours.

The technique involves pressing a glass microscope slide to the ventral surface of the right index finger distal phalanx, increasing pressure and maintaining pressure for 10 seconds. After release, a chronometer assessed return of normal skin color, with refill times over 3 seconds considered abnormal. Clinicians applied the technique every 30 minutes during until normalization (every hour after that), compared with every 2 hours for the lactate arm of the study.

The ANDROMEDA-SHOCK randomized clinical trial was conducted at 28 hospitals in five countries (Argentina, Chile, Colombia, Ecuador, Uruguay). The trial did not demonstrate superiority of capillary refill, and it was not designed for noninferiority. It nevertheless seems unlikely that assessment of capillary refill is inferior to lactate levels, according an accompanying editorial by JAMA-associated editor Derek Angus, MD, who also is a professor of critical care medicine at the University of Pittsburgh. The simplicity of using a capillary refill could be particularly useful in resource-limited settings, since it can be accomplished visually.

It also a natural marker for resuscitation. The body slows fluid flow to peripheral tissues until vital organs are well perfused. Normal capillary refill time “is an indirect signal of reperfusion,” said Dr. Hernández.

The researchers are not calling for this technique to replace lactate measurements, noting that in many ways the techniques can be complementary, since lactate levels are a good indicator of the patient’s overall improvement. In any case, it would take more research to prove superiority of the capillary refill, and that’s not something Dr. Hernández is planning to undertake. The current study had no external funding and required about half of his time over a 2-year period. Getting the work done at all “was sort of a miracle. We would not repeat this,” he said.

The researchers randomized 416 patients with septic shock (mean age, 63 years; 53% of whom were women) to be managed by peripheral perfusion or lactate measurement. By day 28, 43.4% in the lactate group had died, compared with 34.9% in the peripheral perfusion group (hazard ratio, 0.75; P = .06). At 72 hours, the peripheral perfusion group had less organ dysfunction as measured by SOFA (mean, 5.6 vs. 6.6; P = .045). Six other secondary outcomes revealed no between-group differences.

The peripheral perfusion group received an average of 408 fewer mL of resuscitation fluids during the first 8 hours (P = .01).

That result fits with the greater responsiveness of peripheral perfusion measurements, and it’s relevant because some septic shock patients who are unresponsive to fluids often receive fluids anyway. “The general knowledge, though not correct, is that you treat lactate or blood pressure with fluids,” said coauthor Jan Bakker, MD, PhD, who is a professor at New York-Presbyterian Hospital Columbia University, and Erasmus University Rotterdam, the Netherlands.

After a series of observational studies suggested that warm, well-perfused patients were doing well, the idea was tested in a small interventional trial in which physicians were forbidden from giving fluids once patients were warm and well perfused. Patients did better than did those on standard of care. “We have said, if the patient is warm and well perfused, even if they are hypotensive, don’t give fluids, it won’t benefit them anymore. Give vasopressors or whatever, but don’t give fluids,” said Dr. Bakker.

The latest research also reinforced a signal from the earlier, smaller trial. “You get less organ failure if you use [fewer] fluids,” Dr. Bakker added.

The study received no external funding. Dr. Hernández and Dr. Bakker had no relevant financial disclosures. Dr. Angus received consulting fees from Ferring Pharmaceutical, Bristol-Myers Squibb, Bayer AG, and others outside the submitted work; he also has patents pending for compounds, compositions, and methods for treating sepsis and for proteomic biomarkers.

SOURCE: Hernández G et al. JAMA 2019 Feb 17. doi: 10.1001/jama.2019.0071.

SAN DIEGO – During resuscitation of patients with septic shock, a simple strategy of timing the refilling of peripheral capillaries trended toward better 28-day survival than using lactate level targeting, but missed statistical significance.

Jim Kling/MDedge News

Although the paper, published online in JAMA, concludes that normalization of capillary refill time cannot be recommended over targeting serum lactate levels, Glenn Hernández, MD, PhD, sounded more optimistic after presenting the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “I think it’s good news to develop techniques that, even though they have this integrated variability, they can provide a signal that is also very close to the [underlying] physiology,” Dr. Hernández, who is a professor of intensive medicine at Pontifical Catholic University in Santiago, Chile. The Peripheral perfusion was also associated with lower mean Sequential Organ Failure Assessment (SOFA) Score at 72 hours.

The technique involves pressing a glass microscope slide to the ventral surface of the right index finger distal phalanx, increasing pressure and maintaining pressure for 10 seconds. After release, a chronometer assessed return of normal skin color, with refill times over 3 seconds considered abnormal. Clinicians applied the technique every 30 minutes during until normalization (every hour after that), compared with every 2 hours for the lactate arm of the study.

The ANDROMEDA-SHOCK randomized clinical trial was conducted at 28 hospitals in five countries (Argentina, Chile, Colombia, Ecuador, Uruguay). The trial did not demonstrate superiority of capillary refill, and it was not designed for noninferiority. It nevertheless seems unlikely that assessment of capillary refill is inferior to lactate levels, according an accompanying editorial by JAMA-associated editor Derek Angus, MD, who also is a professor of critical care medicine at the University of Pittsburgh. The simplicity of using a capillary refill could be particularly useful in resource-limited settings, since it can be accomplished visually.

It also a natural marker for resuscitation. The body slows fluid flow to peripheral tissues until vital organs are well perfused. Normal capillary refill time “is an indirect signal of reperfusion,” said Dr. Hernández.

The researchers are not calling for this technique to replace lactate measurements, noting that in many ways the techniques can be complementary, since lactate levels are a good indicator of the patient’s overall improvement. In any case, it would take more research to prove superiority of the capillary refill, and that’s not something Dr. Hernández is planning to undertake. The current study had no external funding and required about half of his time over a 2-year period. Getting the work done at all “was sort of a miracle. We would not repeat this,” he said.

The researchers randomized 416 patients with septic shock (mean age, 63 years; 53% of whom were women) to be managed by peripheral perfusion or lactate measurement. By day 28, 43.4% in the lactate group had died, compared with 34.9% in the peripheral perfusion group (hazard ratio, 0.75; P = .06). At 72 hours, the peripheral perfusion group had less organ dysfunction as measured by SOFA (mean, 5.6 vs. 6.6; P = .045). Six other secondary outcomes revealed no between-group differences.

The peripheral perfusion group received an average of 408 fewer mL of resuscitation fluids during the first 8 hours (P = .01).

That result fits with the greater responsiveness of peripheral perfusion measurements, and it’s relevant because some septic shock patients who are unresponsive to fluids often receive fluids anyway. “The general knowledge, though not correct, is that you treat lactate or blood pressure with fluids,” said coauthor Jan Bakker, MD, PhD, who is a professor at New York-Presbyterian Hospital Columbia University, and Erasmus University Rotterdam, the Netherlands.

After a series of observational studies suggested that warm, well-perfused patients were doing well, the idea was tested in a small interventional trial in which physicians were forbidden from giving fluids once patients were warm and well perfused. Patients did better than did those on standard of care. “We have said, if the patient is warm and well perfused, even if they are hypotensive, don’t give fluids, it won’t benefit them anymore. Give vasopressors or whatever, but don’t give fluids,” said Dr. Bakker.

The latest research also reinforced a signal from the earlier, smaller trial. “You get less organ failure if you use [fewer] fluids,” Dr. Bakker added.

The study received no external funding. Dr. Hernández and Dr. Bakker had no relevant financial disclosures. Dr. Angus received consulting fees from Ferring Pharmaceutical, Bristol-Myers Squibb, Bayer AG, and others outside the submitted work; he also has patents pending for compounds, compositions, and methods for treating sepsis and for proteomic biomarkers.

SOURCE: Hernández G et al. JAMA 2019 Feb 17. doi: 10.1001/jama.2019.0071.

SAN DIEGO – During resuscitation of patients with septic shock, a simple strategy of timing the refilling of peripheral capillaries trended toward better 28-day survival than using lactate level targeting, but missed statistical significance.

Jim Kling/MDedge News

Although the paper, published online in JAMA, concludes that normalization of capillary refill time cannot be recommended over targeting serum lactate levels, Glenn Hernández, MD, PhD, sounded more optimistic after presenting the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “I think it’s good news to develop techniques that, even though they have this integrated variability, they can provide a signal that is also very close to the [underlying] physiology,” Dr. Hernández, who is a professor of intensive medicine at Pontifical Catholic University in Santiago, Chile. The Peripheral perfusion was also associated with lower mean Sequential Organ Failure Assessment (SOFA) Score at 72 hours.

The technique involves pressing a glass microscope slide to the ventral surface of the right index finger distal phalanx, increasing pressure and maintaining pressure for 10 seconds. After release, a chronometer assessed return of normal skin color, with refill times over 3 seconds considered abnormal. Clinicians applied the technique every 30 minutes during until normalization (every hour after that), compared with every 2 hours for the lactate arm of the study.

The ANDROMEDA-SHOCK randomized clinical trial was conducted at 28 hospitals in five countries (Argentina, Chile, Colombia, Ecuador, Uruguay). The trial did not demonstrate superiority of capillary refill, and it was not designed for noninferiority. It nevertheless seems unlikely that assessment of capillary refill is inferior to lactate levels, according an accompanying editorial by JAMA-associated editor Derek Angus, MD, who also is a professor of critical care medicine at the University of Pittsburgh. The simplicity of using a capillary refill could be particularly useful in resource-limited settings, since it can be accomplished visually.

It also a natural marker for resuscitation. The body slows fluid flow to peripheral tissues until vital organs are well perfused. Normal capillary refill time “is an indirect signal of reperfusion,” said Dr. Hernández.

The researchers are not calling for this technique to replace lactate measurements, noting that in many ways the techniques can be complementary, since lactate levels are a good indicator of the patient’s overall improvement. In any case, it would take more research to prove superiority of the capillary refill, and that’s not something Dr. Hernández is planning to undertake. The current study had no external funding and required about half of his time over a 2-year period. Getting the work done at all “was sort of a miracle. We would not repeat this,” he said.

The researchers randomized 416 patients with septic shock (mean age, 63 years; 53% of whom were women) to be managed by peripheral perfusion or lactate measurement. By day 28, 43.4% in the lactate group had died, compared with 34.9% in the peripheral perfusion group (hazard ratio, 0.75; P = .06). At 72 hours, the peripheral perfusion group had less organ dysfunction as measured by SOFA (mean, 5.6 vs. 6.6; P = .045). Six other secondary outcomes revealed no between-group differences.

The peripheral perfusion group received an average of 408 fewer mL of resuscitation fluids during the first 8 hours (P = .01).

That result fits with the greater responsiveness of peripheral perfusion measurements, and it’s relevant because some septic shock patients who are unresponsive to fluids often receive fluids anyway. “The general knowledge, though not correct, is that you treat lactate or blood pressure with fluids,” said coauthor Jan Bakker, MD, PhD, who is a professor at New York-Presbyterian Hospital Columbia University, and Erasmus University Rotterdam, the Netherlands.

After a series of observational studies suggested that warm, well-perfused patients were doing well, the idea was tested in a small interventional trial in which physicians were forbidden from giving fluids once patients were warm and well perfused. Patients did better than did those on standard of care. “We have said, if the patient is warm and well perfused, even if they are hypotensive, don’t give fluids, it won’t benefit them anymore. Give vasopressors or whatever, but don’t give fluids,” said Dr. Bakker.

The latest research also reinforced a signal from the earlier, smaller trial. “You get less organ failure if you use [fewer] fluids,” Dr. Bakker added.

The study received no external funding. Dr. Hernández and Dr. Bakker had no relevant financial disclosures. Dr. Angus received consulting fees from Ferring Pharmaceutical, Bristol-Myers Squibb, Bayer AG, and others outside the submitted work; he also has patents pending for compounds, compositions, and methods for treating sepsis and for proteomic biomarkers.

SOURCE: Hernández G et al. JAMA 2019 Feb 17. doi: 10.1001/jama.2019.0071.

SAN FRANCISCO – The estimated U.S. prevalence of sesame allergy appears to be at least 0.23% among both adults and children, roughly about 750,000 people, according to a recent, representative survey of more than 78,000 Americans, which shows sesame allergy apparently is common enough to prompt the Food and Drug Administration to require food labels that identify sesame as an ingredient or possible contaminant.

The sesame-allergy data also showed that sesame reactions were rated as having been severe by about a third of respondents, they caused about two-thirds of people who responded to sesame to go to an emergency department at least once (the highest rate for this outcome among all food allergies), and reactions had led to use of an epinephrine automated injector by about a quarter of people who responded to it, Christopher M. Warren said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

These findings document the public health importance of sesame allergy, which seems widespread and often severe enough to warrant making sesame the ninth allergen to require specific food labeling, said Ruchi S. Gupta, MD, senior author of the study and a professor of pediatrics and medicine at Northwestern University in Chicago.

“It seems to rank up with other food allergens regarding reaction severity,” Dr. Gupta said in a video interview. In October 2018, the FDA requested information on sesame allergy so that its staff could consider adding sesame to its list of major food allergens. The eight current major food allergens that require specific labeling are: peanut, tree nuts, eggs, milk, fish, shellfish, wheat, and soy. The 0.23% prevalence of sesame among U.S. residents makes it more common than certain tree nuts, and so the prevalence numbers also seem to justify adding sesame to the FDA’s labeling list because 750,000 is “a lot of people,” she noted.

An established surveying group based at the University of Chicago ran the data collection, which received responses from 53,575 U.S. household including 40,443 adults and 38,408 children. Dr. Gupta and her associates recently published information on the methods of the survey and other findings it made about U.S. food allergy rates (JAMA Network Open. 2019 Jan 4. doi: 10.1001/jamanetworkopen.2018.5630). The descriptions people provided about their food allergy diagnoses, and the effects these allergies had, underwent detailed review by a panel of experts who decide whether or not the evidence for an allergy was “convincing.” The 0.23% prevalence rate reported for sesame represented people for whom this allergy was convincingly demonstrated, reflected a confirmed physician diagnosis, or both, and hence it was a conservative estimate, Dr. Gupta said.

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Chadha AS et al. AAAAI 2019, Abstract 615.

SAN FRANCISCO – The estimated U.S. prevalence of sesame allergy appears to be at least 0.23% among both adults and children, roughly about 750,000 people, according to a recent, representative survey of more than 78,000 Americans, which shows sesame allergy apparently is common enough to prompt the Food and Drug Administration to require food labels that identify sesame as an ingredient or possible contaminant.

The sesame-allergy data also showed that sesame reactions were rated as having been severe by about a third of respondents, they caused about two-thirds of people who responded to sesame to go to an emergency department at least once (the highest rate for this outcome among all food allergies), and reactions had led to use of an epinephrine automated injector by about a quarter of people who responded to it, Christopher M. Warren said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

These findings document the public health importance of sesame allergy, which seems widespread and often severe enough to warrant making sesame the ninth allergen to require specific food labeling, said Ruchi S. Gupta, MD, senior author of the study and a professor of pediatrics and medicine at Northwestern University in Chicago.

“It seems to rank up with other food allergens regarding reaction severity,” Dr. Gupta said in a video interview. In October 2018, the FDA requested information on sesame allergy so that its staff could consider adding sesame to its list of major food allergens. The eight current major food allergens that require specific labeling are: peanut, tree nuts, eggs, milk, fish, shellfish, wheat, and soy. The 0.23% prevalence of sesame among U.S. residents makes it more common than certain tree nuts, and so the prevalence numbers also seem to justify adding sesame to the FDA’s labeling list because 750,000 is “a lot of people,” she noted.

An established surveying group based at the University of Chicago ran the data collection, which received responses from 53,575 U.S. household including 40,443 adults and 38,408 children. Dr. Gupta and her associates recently published information on the methods of the survey and other findings it made about U.S. food allergy rates (JAMA Network Open. 2019 Jan 4. doi: 10.1001/jamanetworkopen.2018.5630). The descriptions people provided about their food allergy diagnoses, and the effects these allergies had, underwent detailed review by a panel of experts who decide whether or not the evidence for an allergy was “convincing.” The 0.23% prevalence rate reported for sesame represented people for whom this allergy was convincingly demonstrated, reflected a confirmed physician diagnosis, or both, and hence it was a conservative estimate, Dr. Gupta said.

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Chadha AS et al. AAAAI 2019, Abstract 615.

SAN FRANCISCO – The estimated U.S. prevalence of sesame allergy appears to be at least 0.23% among both adults and children, roughly about 750,000 people, according to a recent, representative survey of more than 78,000 Americans, which shows sesame allergy apparently is common enough to prompt the Food and Drug Administration to require food labels that identify sesame as an ingredient or possible contaminant.

The sesame-allergy data also showed that sesame reactions were rated as having been severe by about a third of respondents, they caused about two-thirds of people who responded to sesame to go to an emergency department at least once (the highest rate for this outcome among all food allergies), and reactions had led to use of an epinephrine automated injector by about a quarter of people who responded to it, Christopher M. Warren said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

These findings document the public health importance of sesame allergy, which seems widespread and often severe enough to warrant making sesame the ninth allergen to require specific food labeling, said Ruchi S. Gupta, MD, senior author of the study and a professor of pediatrics and medicine at Northwestern University in Chicago.

“It seems to rank up with other food allergens regarding reaction severity,” Dr. Gupta said in a video interview. In October 2018, the FDA requested information on sesame allergy so that its staff could consider adding sesame to its list of major food allergens. The eight current major food allergens that require specific labeling are: peanut, tree nuts, eggs, milk, fish, shellfish, wheat, and soy. The 0.23% prevalence of sesame among U.S. residents makes it more common than certain tree nuts, and so the prevalence numbers also seem to justify adding sesame to the FDA’s labeling list because 750,000 is “a lot of people,” she noted.

An established surveying group based at the University of Chicago ran the data collection, which received responses from 53,575 U.S. household including 40,443 adults and 38,408 children. Dr. Gupta and her associates recently published information on the methods of the survey and other findings it made about U.S. food allergy rates (JAMA Network Open. 2019 Jan 4. doi: 10.1001/jamanetworkopen.2018.5630). The descriptions people provided about their food allergy diagnoses, and the effects these allergies had, underwent detailed review by a panel of experts who decide whether or not the evidence for an allergy was “convincing.” The 0.23% prevalence rate reported for sesame represented people for whom this allergy was convincingly demonstrated, reflected a confirmed physician diagnosis, or both, and hence it was a conservative estimate, Dr. Gupta said.

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Chadha AS et al. AAAAI 2019, Abstract 615.

Antidepressants could be the best adjunctive treatment for adult outpatients with schizophrenia who are taking a second-generation antipsychotic and need a change in medication, results of an observational study suggest. Patients who added antidepressants to their treatment had a lower risk of psychiatric hospitalization and emergency room visits than did those who tried an alternative antipsychotic, and those who took mood stabilizers and benzodiazepines were significantly more likely to die over 365 days.

Specifically, “the possibility that adjunctive use of gabapentin is associated with increased risk of death raises a serious concern,” wrote T. Scott Stroup, MD, MPH, of the department of psychiatry at Columbia University, New York, and his associates in JAMA Psychiatry.

Often, Dr. Stroup and his associates noted, second-generation antipsychotics often are insufficient to alleviate symptoms and leave patients with functional limitations. Still, there’s “little high-quality evidence” regarding the best treatments for schizophrenia, said Dr. Stroup, who is also affiliated with the New York State Psychiatric Institute, and his associates.

Using a Medicaid database, the researchers retrospectively tracked 81,921 outpatients with schizophrenia (aged 18-64 years; mean age, 41 years; 46% women) who were treated with a single antipsychotic from 2001-2010. Each patient added an antidepressant (31,117), a benzodiazepine (11,941), a mood stabilizer (12,849), or another second-generation antipsychotic (26,014).

The researchers examined treatment outcomes over a yearlong period after patients began their new treatment and compared the various groups to the reference group (those who began taking an additional antipsychotic medication).

Compared with the reference group, patients who took an antidepressant had a lower risk of psychiatric hospitalization (hazard ratio, 0.84; 95% confidence interval, 0.80-0.88), while the benzodiazepine group had a higher risk (HR, 1.08; 95% CI, 1.02-1.15), and the mood stabilizer group saw no major difference (HR, 0.98; 95% CI, 0.94-1.03). Similar results were found for the risk of psychiatric emergency department visits, compared with the reference group: The HR with the addition of an antidepressant was 0.92 (95% CI, 0.88-0.96), 1.12 with a benzodiazepine (95% CI, 1.07-1.19), and 0.99 with a mood stabilizer (95% CI, 0.94-1.04).

In regard to mortality, the researchers found that mood stabilizers and benzodiazepines stood apart on the risk front with HRs of 1.31 (95% CI, 1.04-1.66) and 1.22 (95% CI, 0.98-1.52), respectively. Among mood stabilizer use, Gabapentin accounted for 1,755 initiations (13.7%) and was associated with 45 deaths (28.0%), the researchers reported. “No other mood stabilizer appeared to be associated with a higher rate of death than the others.”

Dr. Stroup and his associates cited several limitations. One is that the results might not be generalizable because the investigators looked only at patients who were enrolled in the Medicaid program. Nevertheless, “improved pharmacologic treatment of schizophrenia and consequent reduced need for hospitalization and ED visits associated with more antidepressant and less benzodiazepine use would represent a significant benefit for individuals and for public health,” they wrote.

The study authors reported various relationships with drugmakers, including Auspex, Intra-Cellular Therapies, Eli Lilly, Bristol-Myers Squibb, and Merck. The study was funded by a Patient-Centered Outcomes Research Institute award.

SOURCE: Stroup TS et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4489.

Antidepressants could be the best adjunctive treatment for adult outpatients with schizophrenia who are taking a second-generation antipsychotic and need a change in medication, results of an observational study suggest. Patients who added antidepressants to their treatment had a lower risk of psychiatric hospitalization and emergency room visits than did those who tried an alternative antipsychotic, and those who took mood stabilizers and benzodiazepines were significantly more likely to die over 365 days.

Specifically, “the possibility that adjunctive use of gabapentin is associated with increased risk of death raises a serious concern,” wrote T. Scott Stroup, MD, MPH, of the department of psychiatry at Columbia University, New York, and his associates in JAMA Psychiatry.

Often, Dr. Stroup and his associates noted, second-generation antipsychotics often are insufficient to alleviate symptoms and leave patients with functional limitations. Still, there’s “little high-quality evidence” regarding the best treatments for schizophrenia, said Dr. Stroup, who is also affiliated with the New York State Psychiatric Institute, and his associates.

Using a Medicaid database, the researchers retrospectively tracked 81,921 outpatients with schizophrenia (aged 18-64 years; mean age, 41 years; 46% women) who were treated with a single antipsychotic from 2001-2010. Each patient added an antidepressant (31,117), a benzodiazepine (11,941), a mood stabilizer (12,849), or another second-generation antipsychotic (26,014).

The researchers examined treatment outcomes over a yearlong period after patients began their new treatment and compared the various groups to the reference group (those who began taking an additional antipsychotic medication).

Compared with the reference group, patients who took an antidepressant had a lower risk of psychiatric hospitalization (hazard ratio, 0.84; 95% confidence interval, 0.80-0.88), while the benzodiazepine group had a higher risk (HR, 1.08; 95% CI, 1.02-1.15), and the mood stabilizer group saw no major difference (HR, 0.98; 95% CI, 0.94-1.03). Similar results were found for the risk of psychiatric emergency department visits, compared with the reference group: The HR with the addition of an antidepressant was 0.92 (95% CI, 0.88-0.96), 1.12 with a benzodiazepine (95% CI, 1.07-1.19), and 0.99 with a mood stabilizer (95% CI, 0.94-1.04).

In regard to mortality, the researchers found that mood stabilizers and benzodiazepines stood apart on the risk front with HRs of 1.31 (95% CI, 1.04-1.66) and 1.22 (95% CI, 0.98-1.52), respectively. Among mood stabilizer use, Gabapentin accounted for 1,755 initiations (13.7%) and was associated with 45 deaths (28.0%), the researchers reported. “No other mood stabilizer appeared to be associated with a higher rate of death than the others.”

Dr. Stroup and his associates cited several limitations. One is that the results might not be generalizable because the investigators looked only at patients who were enrolled in the Medicaid program. Nevertheless, “improved pharmacologic treatment of schizophrenia and consequent reduced need for hospitalization and ED visits associated with more antidepressant and less benzodiazepine use would represent a significant benefit for individuals and for public health,” they wrote.

The study authors reported various relationships with drugmakers, including Auspex, Intra-Cellular Therapies, Eli Lilly, Bristol-Myers Squibb, and Merck. The study was funded by a Patient-Centered Outcomes Research Institute award.

SOURCE: Stroup TS et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4489.

Antidepressants could be the best adjunctive treatment for adult outpatients with schizophrenia who are taking a second-generation antipsychotic and need a change in medication, results of an observational study suggest. Patients who added antidepressants to their treatment had a lower risk of psychiatric hospitalization and emergency room visits than did those who tried an alternative antipsychotic, and those who took mood stabilizers and benzodiazepines were significantly more likely to die over 365 days.

Specifically, “the possibility that adjunctive use of gabapentin is associated with increased risk of death raises a serious concern,” wrote T. Scott Stroup, MD, MPH, of the department of psychiatry at Columbia University, New York, and his associates in JAMA Psychiatry.

Often, Dr. Stroup and his associates noted, second-generation antipsychotics often are insufficient to alleviate symptoms and leave patients with functional limitations. Still, there’s “little high-quality evidence” regarding the best treatments for schizophrenia, said Dr. Stroup, who is also affiliated with the New York State Psychiatric Institute, and his associates.

Using a Medicaid database, the researchers retrospectively tracked 81,921 outpatients with schizophrenia (aged 18-64 years; mean age, 41 years; 46% women) who were treated with a single antipsychotic from 2001-2010. Each patient added an antidepressant (31,117), a benzodiazepine (11,941), a mood stabilizer (12,849), or another second-generation antipsychotic (26,014).

The researchers examined treatment outcomes over a yearlong period after patients began their new treatment and compared the various groups to the reference group (those who began taking an additional antipsychotic medication).

Compared with the reference group, patients who took an antidepressant had a lower risk of psychiatric hospitalization (hazard ratio, 0.84; 95% confidence interval, 0.80-0.88), while the benzodiazepine group had a higher risk (HR, 1.08; 95% CI, 1.02-1.15), and the mood stabilizer group saw no major difference (HR, 0.98; 95% CI, 0.94-1.03). Similar results were found for the risk of psychiatric emergency department visits, compared with the reference group: The HR with the addition of an antidepressant was 0.92 (95% CI, 0.88-0.96), 1.12 with a benzodiazepine (95% CI, 1.07-1.19), and 0.99 with a mood stabilizer (95% CI, 0.94-1.04).

In regard to mortality, the researchers found that mood stabilizers and benzodiazepines stood apart on the risk front with HRs of 1.31 (95% CI, 1.04-1.66) and 1.22 (95% CI, 0.98-1.52), respectively. Among mood stabilizer use, Gabapentin accounted for 1,755 initiations (13.7%) and was associated with 45 deaths (28.0%), the researchers reported. “No other mood stabilizer appeared to be associated with a higher rate of death than the others.”

Dr. Stroup and his associates cited several limitations. One is that the results might not be generalizable because the investigators looked only at patients who were enrolled in the Medicaid program. Nevertheless, “improved pharmacologic treatment of schizophrenia and consequent reduced need for hospitalization and ED visits associated with more antidepressant and less benzodiazepine use would represent a significant benefit for individuals and for public health,” they wrote.

The study authors reported various relationships with drugmakers, including Auspex, Intra-Cellular Therapies, Eli Lilly, Bristol-Myers Squibb, and Merck. The study was funded by a Patient-Centered Outcomes Research Institute award.

SOURCE: Stroup TS et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4489.

The correlation between parental nonmedical prescription opioid use and offspring use should be considered in targeted efforts to reduce adolescent use, reported Pamela C. Griesler, PhD, of Columbia University, New York, and her associates.

BackyardProduction/Thinkstock

Given the significant link between parental and adolescent smoking and adolescent nonmedical prescription opioid (NMPO) use, smoking also should be included in targeted interventions, they wrote in Pediatrics.

Dr. Griesler and her colleagues noted that there actually are three classes of factors influencing the association between parent and adolescent NMPO use: phenotypic heritability, parental role modeling, and parental socialization and other environmental influences.

In the first known study to explore the relationship of parent-adolescent NMPO use within a nationally representative sampling of parent-child dyads taken from the National Surveys on Drug Use and Health, Dr. Griesler and her colleagues examined the intergenerational association of lifetime NMPO use among 35,000 parent-adolescent dyads (21,200 mothers, 13,800 fathers). Of the 35,000 children aged 12-17 years included in the sample, 90% were biological, 8% were stepchildren, and 2% were adopted.

Given the absence of previous studies exploring the relationship between parent-adolescent NMPO use, Dr. Griesler and her associates used established findings for smoking and substance use to hypothesize that there would be stronger associations for mothers than fathers, daughters than sons, and for whites than African Americans.

The investigators posed three questions that formed the basis of their research: 1) What is the association between lifetime parental and child NMPO use? 2) What is the unique association between parental and child NMPO use, controlling for other factors? 3) Do parental/adolescent NMPO use associations differ by parent/child gender and race and/or ethnicity?

About 14% of parents reported ever using an NMPO; fathers (14%) had slightly higher rates of usage than mothers (13%), and white parents had higher rates of use (16%) than African American (10%) or Hispanic (9%) parents. Among adolescents, 9% reported ever having used an NMPO; this included similar rates for boys (9%) and girls (9%), as well as whites (9%), Hispanics (9%), and African Americans (8%). Use increased with age over time, from 4% among 12-year-olds to 15% among 17-year-olds.

SOURCE: Griesler PC et al. Pediatrics. 2019;143(3):e20182354.

The correlation between parental nonmedical prescription opioid use and offspring use should be considered in targeted efforts to reduce adolescent use, reported Pamela C. Griesler, PhD, of Columbia University, New York, and her associates.

BackyardProduction/Thinkstock

Given the significant link between parental and adolescent smoking and adolescent nonmedical prescription opioid (NMPO) use, smoking also should be included in targeted interventions, they wrote in Pediatrics.

Dr. Griesler and her colleagues noted that there actually are three classes of factors influencing the association between parent and adolescent NMPO use: phenotypic heritability, parental role modeling, and parental socialization and other environmental influences.

In the first known study to explore the relationship of parent-adolescent NMPO use within a nationally representative sampling of parent-child dyads taken from the National Surveys on Drug Use and Health, Dr. Griesler and her colleagues examined the intergenerational association of lifetime NMPO use among 35,000 parent-adolescent dyads (21,200 mothers, 13,800 fathers). Of the 35,000 children aged 12-17 years included in the sample, 90% were biological, 8% were stepchildren, and 2% were adopted.

Given the absence of previous studies exploring the relationship between parent-adolescent NMPO use, Dr. Griesler and her associates used established findings for smoking and substance use to hypothesize that there would be stronger associations for mothers than fathers, daughters than sons, and for whites than African Americans.

The investigators posed three questions that formed the basis of their research: 1) What is the association between lifetime parental and child NMPO use? 2) What is the unique association between parental and child NMPO use, controlling for other factors? 3) Do parental/adolescent NMPO use associations differ by parent/child gender and race and/or ethnicity?

About 14% of parents reported ever using an NMPO; fathers (14%) had slightly higher rates of usage than mothers (13%), and white parents had higher rates of use (16%) than African American (10%) or Hispanic (9%) parents. Among adolescents, 9% reported ever having used an NMPO; this included similar rates for boys (9%) and girls (9%), as well as whites (9%), Hispanics (9%), and African Americans (8%). Use increased with age over time, from 4% among 12-year-olds to 15% among 17-year-olds.

SOURCE: Griesler PC et al. Pediatrics. 2019;143(3):e20182354.

The correlation between parental nonmedical prescription opioid use and offspring use should be considered in targeted efforts to reduce adolescent use, reported Pamela C. Griesler, PhD, of Columbia University, New York, and her associates.

BackyardProduction/Thinkstock

Given the significant link between parental and adolescent smoking and adolescent nonmedical prescription opioid (NMPO) use, smoking also should be included in targeted interventions, they wrote in Pediatrics.

Dr. Griesler and her colleagues noted that there actually are three classes of factors influencing the association between parent and adolescent NMPO use: phenotypic heritability, parental role modeling, and parental socialization and other environmental influences.

In the first known study to explore the relationship of parent-adolescent NMPO use within a nationally representative sampling of parent-child dyads taken from the National Surveys on Drug Use and Health, Dr. Griesler and her colleagues examined the intergenerational association of lifetime NMPO use among 35,000 parent-adolescent dyads (21,200 mothers, 13,800 fathers). Of the 35,000 children aged 12-17 years included in the sample, 90% were biological, 8% were stepchildren, and 2% were adopted.

Given the absence of previous studies exploring the relationship between parent-adolescent NMPO use, Dr. Griesler and her associates used established findings for smoking and substance use to hypothesize that there would be stronger associations for mothers than fathers, daughters than sons, and for whites than African Americans.

The investigators posed three questions that formed the basis of their research: 1) What is the association between lifetime parental and child NMPO use? 2) What is the unique association between parental and child NMPO use, controlling for other factors? 3) Do parental/adolescent NMPO use associations differ by parent/child gender and race and/or ethnicity?

About 14% of parents reported ever using an NMPO; fathers (14%) had slightly higher rates of usage than mothers (13%), and white parents had higher rates of use (16%) than African American (10%) or Hispanic (9%) parents. Among adolescents, 9% reported ever having used an NMPO; this included similar rates for boys (9%) and girls (9%), as well as whites (9%), Hispanics (9%), and African Americans (8%). Use increased with age over time, from 4% among 12-year-olds to 15% among 17-year-olds.

SOURCE: Griesler PC et al. Pediatrics. 2019;143(3):e20182354.

The Food and Drug Administration has approved Orsiro, an ultrathin drug-eluting stent (DES), for the treatment of coronary artery disease.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval was based on 2-year results from BIOFLOW-V, an international, randomized trial in 1,344 patients with coronary artery disease who received either Orsiro or Xience, the current clinical standard. At 2 years, patients who received Orsiro had a 37% lower target lesion failure rate, a 47% lower ischemia-driven target lesion revascularization rate, and a 70% lower spontaneous MI rate. These results were published in the Journal of the American College of Cardiology and presented at the Transcatheter Cardiovascular Therapeutics annual meeting in November  2018.

Orsiro previously received CE marking in Europe in 2011 and has been used to treat more than 1 million patients. The device elutes sirolimus and is available in 52 sizes ranging from 2.25 to 4.0 mm in diameter and lengths up to 40 mm, according to Biotronik’s press release.

“Orsiro has set a new standard for safety and efficacy clinical endpoints, including statistically lower target lesion revascularization and target vessel MI rates. BIOFLOW-V data are the best clinical outcomes witnessed with modern DES. It was largely thought that efficacy findings were unsurpassable, but Orsiro proves we can further reduce event rates with meaningful innovation,” David Kandzari, MD, a cardiologist at Piedmont Heart Institute in Atlanta and principal U.S. investigator for BIOFLOW-V, said in the press release.

[email protected]

The Food and Drug Administration has approved Orsiro, an ultrathin drug-eluting stent (DES), for the treatment of coronary artery disease.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval was based on 2-year results from BIOFLOW-V, an international, randomized trial in 1,344 patients with coronary artery disease who received either Orsiro or Xience, the current clinical standard. At 2 years, patients who received Orsiro had a 37% lower target lesion failure rate, a 47% lower ischemia-driven target lesion revascularization rate, and a 70% lower spontaneous MI rate. These results were published in the Journal of the American College of Cardiology and presented at the Transcatheter Cardiovascular Therapeutics annual meeting in November  2018.

Orsiro previously received CE marking in Europe in 2011 and has been used to treat more than 1 million patients. The device elutes sirolimus and is available in 52 sizes ranging from 2.25 to 4.0 mm in diameter and lengths up to 40 mm, according to Biotronik’s press release.

“Orsiro has set a new standard for safety and efficacy clinical endpoints, including statistically lower target lesion revascularization and target vessel MI rates. BIOFLOW-V data are the best clinical outcomes witnessed with modern DES. It was largely thought that efficacy findings were unsurpassable, but Orsiro proves we can further reduce event rates with meaningful innovation,” David Kandzari, MD, a cardiologist at Piedmont Heart Institute in Atlanta and principal U.S. investigator for BIOFLOW-V, said in the press release.

[email protected]

The Food and Drug Administration has approved Orsiro, an ultrathin drug-eluting stent (DES), for the treatment of coronary artery disease.

Wikimedia Commons/FitzColinGerald/Creative Commons License

FDA approval was based on 2-year results from BIOFLOW-V, an international, randomized trial in 1,344 patients with coronary artery disease who received either Orsiro or Xience, the current clinical standard. At 2 years, patients who received Orsiro had a 37% lower target lesion failure rate, a 47% lower ischemia-driven target lesion revascularization rate, and a 70% lower spontaneous MI rate. These results were published in the Journal of the American College of Cardiology and presented at the Transcatheter Cardiovascular Therapeutics annual meeting in November  2018.

Orsiro previously received CE marking in Europe in 2011 and has been used to treat more than 1 million patients. The device elutes sirolimus and is available in 52 sizes ranging from 2.25 to 4.0 mm in diameter and lengths up to 40 mm, according to Biotronik’s press release.

“Orsiro has set a new standard for safety and efficacy clinical endpoints, including statistically lower target lesion revascularization and target vessel MI rates. BIOFLOW-V data are the best clinical outcomes witnessed with modern DES. It was largely thought that efficacy findings were unsurpassable, but Orsiro proves we can further reduce event rates with meaningful innovation,” David Kandzari, MD, a cardiologist at Piedmont Heart Institute in Atlanta and principal U.S. investigator for BIOFLOW-V, said in the press release.

[email protected]

The Food and Drug Administration has approved Taiho’s trifluridine/tipiracil combination Lonsurf for adult patients with either gastric or gastroesophageal junction adenocarcinomas. Specifically, these patients will have been previously treated with at least two lines of chemotherapy that included fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy, according to a statement from the company.

The approval was based on the TAGS trial (NCT02500043), which was a global, randomized, phase 3 study that evaluated Lonsurf plus best supportive care versus placebo plus best supportive care. The trial demonstrated prolonged overall survival with the drug combo, compared with that seen with placebo, and thereby met its primary and secondary endpoint. The safety profile seen in the trial was consistent with what’s previously been seen with the drug. Results from this trial were published in The Lancet Oncology.

Warnings and precautions for the drug combination include severe myelosuppression and embryo-fetal toxicity, as well as fatigue, nausea, diarrhea, infections, pyrexia, alopecia, and others. The full prescribing information can be found on the Taiho website.

[email protected]

The Food and Drug Administration has approved Taiho’s trifluridine/tipiracil combination Lonsurf for adult patients with either gastric or gastroesophageal junction adenocarcinomas. Specifically, these patients will have been previously treated with at least two lines of chemotherapy that included fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy, according to a statement from the company.

The approval was based on the TAGS trial (NCT02500043), which was a global, randomized, phase 3 study that evaluated Lonsurf plus best supportive care versus placebo plus best supportive care. The trial demonstrated prolonged overall survival with the drug combo, compared with that seen with placebo, and thereby met its primary and secondary endpoint. The safety profile seen in the trial was consistent with what’s previously been seen with the drug. Results from this trial were published in The Lancet Oncology.

Warnings and precautions for the drug combination include severe myelosuppression and embryo-fetal toxicity, as well as fatigue, nausea, diarrhea, infections, pyrexia, alopecia, and others. The full prescribing information can be found on the Taiho website.

[email protected]

The Food and Drug Administration has approved Taiho’s trifluridine/tipiracil combination Lonsurf for adult patients with either gastric or gastroesophageal junction adenocarcinomas. Specifically, these patients will have been previously treated with at least two lines of chemotherapy that included fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy, according to a statement from the company.

The approval was based on the TAGS trial (NCT02500043), which was a global, randomized, phase 3 study that evaluated Lonsurf plus best supportive care versus placebo plus best supportive care. The trial demonstrated prolonged overall survival with the drug combo, compared with that seen with placebo, and thereby met its primary and secondary endpoint. The safety profile seen in the trial was consistent with what’s previously been seen with the drug. Results from this trial were published in The Lancet Oncology.

Warnings and precautions for the drug combination include severe myelosuppression and embryo-fetal toxicity, as well as fatigue, nausea, diarrhea, infections, pyrexia, alopecia, and others. The full prescribing information can be found on the Taiho website.

[email protected]

First-line treatment with nivolumab plus ipilimumab may be cost effective when compared with sunitinib for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC), according to a cost-effectiveness analysis.

“A Markov model was developed to estimate the costs and effectiveness of treatment of mRCC,” XiaoMin Wan, PhD, of the Capital Medical University in Beijing and his colleagues wrote in JAMA Oncology.

The researchers used data from an economic model that extrapolated findings from a phase 3 randomized study of 1,096 patients with intermediate- and poor-risk mRCC treated with first-line sunitinib or nivolumab plus ipilimumab.

“We assumed that the first-line treatments continued until disease progression or unacceptable toxic effects,” the team wrote.

Several measures were estimated using the model, including quality-adjusted life-years (QALYs), lifetime costs, and life-years. The team set a willingness-to-pay threshold of $100,000-$150,000 per QALY. In addition, Dr. Wan and his colleagues completed a sensitivity analysis to investigate how the results changed across different ranges of drug cost.

After analysis, the researchers found that first-line therapy with nivolumab plus ipilimumab was estimated to cost $108,363 per QALY gained. The incremental QALYs added using the combination was 0.96 years versus sunitinib, at the same cost per QALY.

With respect to the sensitivity analysis, the likelihood of the combination being cost effective, compared with sunitinib, was calculated to be 42.5% and 80.2% at the minimum and maximum of the willingness-to-pay threshold, respectively.

“The results of subgroup analyses showed that nivolumab plus ipilimumab was most cost effective for patients with 1% or greater programmed cell death 1 ligand 1 (PD-L1) expression,” they added.

The researchers acknowledged a key limitation of the study was that the analysis used data from only a single randomized trial. Consequently, Dr. Wan and his colleagues reported that any bias contained within that trial will also be present in this analysis.

The study was supported by funding from the National Natural Science Foundation of China and the Health and Family Planning Commission of Hunan province. The authors reported no conflicts of interest.

SOURCE: Wan X et al. JAMA Oncol. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.7086.

First-line treatment with nivolumab plus ipilimumab may be cost effective when compared with sunitinib for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC), according to a cost-effectiveness analysis.

“A Markov model was developed to estimate the costs and effectiveness of treatment of mRCC,” XiaoMin Wan, PhD, of the Capital Medical University in Beijing and his colleagues wrote in JAMA Oncology.

The researchers used data from an economic model that extrapolated findings from a phase 3 randomized study of 1,096 patients with intermediate- and poor-risk mRCC treated with first-line sunitinib or nivolumab plus ipilimumab.

“We assumed that the first-line treatments continued until disease progression or unacceptable toxic effects,” the team wrote.

Several measures were estimated using the model, including quality-adjusted life-years (QALYs), lifetime costs, and life-years. The team set a willingness-to-pay threshold of $100,000-$150,000 per QALY. In addition, Dr. Wan and his colleagues completed a sensitivity analysis to investigate how the results changed across different ranges of drug cost.

After analysis, the researchers found that first-line therapy with nivolumab plus ipilimumab was estimated to cost $108,363 per QALY gained. The incremental QALYs added using the combination was 0.96 years versus sunitinib, at the same cost per QALY.

With respect to the sensitivity analysis, the likelihood of the combination being cost effective, compared with sunitinib, was calculated to be 42.5% and 80.2% at the minimum and maximum of the willingness-to-pay threshold, respectively.

“The results of subgroup analyses showed that nivolumab plus ipilimumab was most cost effective for patients with 1% or greater programmed cell death 1 ligand 1 (PD-L1) expression,” they added.

The researchers acknowledged a key limitation of the study was that the analysis used data from only a single randomized trial. Consequently, Dr. Wan and his colleagues reported that any bias contained within that trial will also be present in this analysis.

The study was supported by funding from the National Natural Science Foundation of China and the Health and Family Planning Commission of Hunan province. The authors reported no conflicts of interest.

SOURCE: Wan X et al. JAMA Oncol. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.7086.

First-line treatment with nivolumab plus ipilimumab may be cost effective when compared with sunitinib for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC), according to a cost-effectiveness analysis.

“A Markov model was developed to estimate the costs and effectiveness of treatment of mRCC,” XiaoMin Wan, PhD, of the Capital Medical University in Beijing and his colleagues wrote in JAMA Oncology.

The researchers used data from an economic model that extrapolated findings from a phase 3 randomized study of 1,096 patients with intermediate- and poor-risk mRCC treated with first-line sunitinib or nivolumab plus ipilimumab.

“We assumed that the first-line treatments continued until disease progression or unacceptable toxic effects,” the team wrote.

Several measures were estimated using the model, including quality-adjusted life-years (QALYs), lifetime costs, and life-years. The team set a willingness-to-pay threshold of $100,000-$150,000 per QALY. In addition, Dr. Wan and his colleagues completed a sensitivity analysis to investigate how the results changed across different ranges of drug cost.

After analysis, the researchers found that first-line therapy with nivolumab plus ipilimumab was estimated to cost $108,363 per QALY gained. The incremental QALYs added using the combination was 0.96 years versus sunitinib, at the same cost per QALY.

With respect to the sensitivity analysis, the likelihood of the combination being cost effective, compared with sunitinib, was calculated to be 42.5% and 80.2% at the minimum and maximum of the willingness-to-pay threshold, respectively.

“The results of subgroup analyses showed that nivolumab plus ipilimumab was most cost effective for patients with 1% or greater programmed cell death 1 ligand 1 (PD-L1) expression,” they added.

The researchers acknowledged a key limitation of the study was that the analysis used data from only a single randomized trial. Consequently, Dr. Wan and his colleagues reported that any bias contained within that trial will also be present in this analysis.

The study was supported by funding from the National Natural Science Foundation of China and the Health and Family Planning Commission of Hunan province. The authors reported no conflicts of interest.

SOURCE: Wan X et al. JAMA Oncol. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.7086.

PRAGUE – Emicizumab appears safe and effective for patients with hemophilia A undergoing surgical procedures, based on experience with a subpopulation of HAVEN 3 trial participants.

Out of 28 minor procedures performed without preventive factor VIII (FVIII), only 2 were associated with postoperative bleeds requiring treatment, reported lead author Elena Santagostino, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, and her colleagues.

All events requiring bleeding treatment were associated with dental procedures, highlighting an area where clinicians and dentists may need to exercise caution. Still, overall results supported emicizumab in a surgical setting.

“There were no thrombotic complications or other unexpected events, including inhibitor development,” Dr. Santagostino said at the annual congress of the European Association for Haemophilia and Allied Disorders.

The findings were drawn from 30 patients who underwent 50 surgeries (46 minor, 4 major) during HAVEN 3, a previously reported phase 3 trial investigating the use of emicizumab, a humanized bispecific monoclonal antibody for patients with hemophilia A without inhibitors.

The minor surgeries included dental or orthopedic procedures, esophagogastroduodenoscopy, or colonoscopy. The four major procedures were all orthopedic (knee arthroscopic synovectomy, biceps femoris tear repair, total ankle arthroplasty, and total hip replacement). The investigators analyzed surgery-related bleeds and the nature of FVIII usage.

Preventive FVIII was used in 18 procedures; infusion duration was 24 hours or less in 14 procedures, between 25 hours and 48 hours in 2 procedures, and more than 72 hours in 2 procedures. The median cumulative preventive FVIII dose per procedure was 30 IU/kg.

Of the 46 minor procedures, 28 (61%) were performed without preventive FVIII, and 2 (7.1%) were associated with bleeding requiring treatment, both after dental procedures. Two other participants who received preventive FVIII also needed postoperative bleeding treatment. Of note, these events were also after dental procedures, meaning all four instances of bleeding requiring treatment during the trial were associated with dentistry.

“[I]n this experience, dental procedures were somewhat tricky because the bleeding complications were mainly there,” Dr. Santagostino said.

When asked by an audience member if this trend was unique to mucosal bleeding, Dr. Santagostino said it was too early to draw such a conclusion but offered some insight. “To control and prevent bleeding during a dental procedure is not trivial, because … sometimes if you stop factor VIII treatment quite early, you may have late bleeding, mainly due to local reasons, because … dental procedures are very heterogenous.”

Among three other participants who had postoperative bleeding but did not require treatment, two underwent dental procedures, further supporting this association. Although the study numbers are relatively small, the findings may at least support caution, if not preventive FVIII in the dental setting, Dr. Santagostino said.

The four major procedures – all orthopedic – were knee arthroscopic synovectomy, biceps femoris tear repair, total ankle arthroplasty, and total hip replacement. Along with preoperative preventive FVIII, three of four patients undergoing major surgery received preventive FVIII for 14-18 days postoperatively. Doses ranged from 99-522 IU/kg. No postoperative bleeds occurred in this subgroup.

Study funding was provided by F. Hoffmann–La Roche and Chugai Pharmaceutical. The investigators reported financial relationships with Bayer, Shire, Pfizer, Novo Nordisk, and others.

SOURCE: Santagostino E et al. EAHAD 2019, Abstract OR15.

PRAGUE – Emicizumab appears safe and effective for patients with hemophilia A undergoing surgical procedures, based on experience with a subpopulation of HAVEN 3 trial participants.

Out of 28 minor procedures performed without preventive factor VIII (FVIII), only 2 were associated with postoperative bleeds requiring treatment, reported lead author Elena Santagostino, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, and her colleagues.

All events requiring bleeding treatment were associated with dental procedures, highlighting an area where clinicians and dentists may need to exercise caution. Still, overall results supported emicizumab in a surgical setting.

“There were no thrombotic complications or other unexpected events, including inhibitor development,” Dr. Santagostino said at the annual congress of the European Association for Haemophilia and Allied Disorders.

The findings were drawn from 30 patients who underwent 50 surgeries (46 minor, 4 major) during HAVEN 3, a previously reported phase 3 trial investigating the use of emicizumab, a humanized bispecific monoclonal antibody for patients with hemophilia A without inhibitors.

The minor surgeries included dental or orthopedic procedures, esophagogastroduodenoscopy, or colonoscopy. The four major procedures were all orthopedic (knee arthroscopic synovectomy, biceps femoris tear repair, total ankle arthroplasty, and total hip replacement). The investigators analyzed surgery-related bleeds and the nature of FVIII usage.

Preventive FVIII was used in 18 procedures; infusion duration was 24 hours or less in 14 procedures, between 25 hours and 48 hours in 2 procedures, and more than 72 hours in 2 procedures. The median cumulative preventive FVIII dose per procedure was 30 IU/kg.

Of the 46 minor procedures, 28 (61%) were performed without preventive FVIII, and 2 (7.1%) were associated with bleeding requiring treatment, both after dental procedures. Two other participants who received preventive FVIII also needed postoperative bleeding treatment. Of note, these events were also after dental procedures, meaning all four instances of bleeding requiring treatment during the trial were associated with dentistry.

“[I]n this experience, dental procedures were somewhat tricky because the bleeding complications were mainly there,” Dr. Santagostino said.

When asked by an audience member if this trend was unique to mucosal bleeding, Dr. Santagostino said it was too early to draw such a conclusion but offered some insight. “To control and prevent bleeding during a dental procedure is not trivial, because … sometimes if you stop factor VIII treatment quite early, you may have late bleeding, mainly due to local reasons, because … dental procedures are very heterogenous.”

Among three other participants who had postoperative bleeding but did not require treatment, two underwent dental procedures, further supporting this association. Although the study numbers are relatively small, the findings may at least support caution, if not preventive FVIII in the dental setting, Dr. Santagostino said.

The four major procedures – all orthopedic – were knee arthroscopic synovectomy, biceps femoris tear repair, total ankle arthroplasty, and total hip replacement. Along with preoperative preventive FVIII, three of four patients undergoing major surgery received preventive FVIII for 14-18 days postoperatively. Doses ranged from 99-522 IU/kg. No postoperative bleeds occurred in this subgroup.

Study funding was provided by F. Hoffmann–La Roche and Chugai Pharmaceutical. The investigators reported financial relationships with Bayer, Shire, Pfizer, Novo Nordisk, and others.

SOURCE: Santagostino E et al. EAHAD 2019, Abstract OR15.

PRAGUE – Emicizumab appears safe and effective for patients with hemophilia A undergoing surgical procedures, based on experience with a subpopulation of HAVEN 3 trial participants.

Out of 28 minor procedures performed without preventive factor VIII (FVIII), only 2 were associated with postoperative bleeds requiring treatment, reported lead author Elena Santagostino, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, and her colleagues.

All events requiring bleeding treatment were associated with dental procedures, highlighting an area where clinicians and dentists may need to exercise caution. Still, overall results supported emicizumab in a surgical setting.

“There were no thrombotic complications or other unexpected events, including inhibitor development,” Dr. Santagostino said at the annual congress of the European Association for Haemophilia and Allied Disorders.

The findings were drawn from 30 patients who underwent 50 surgeries (46 minor, 4 major) during HAVEN 3, a previously reported phase 3 trial investigating the use of emicizumab, a humanized bispecific monoclonal antibody for patients with hemophilia A without inhibitors.

The minor surgeries included dental or orthopedic procedures, esophagogastroduodenoscopy, or colonoscopy. The four major procedures were all orthopedic (knee arthroscopic synovectomy, biceps femoris tear repair, total ankle arthroplasty, and total hip replacement). The investigators analyzed surgery-related bleeds and the nature of FVIII usage.

Preventive FVIII was used in 18 procedures; infusion duration was 24 hours or less in 14 procedures, between 25 hours and 48 hours in 2 procedures, and more than 72 hours in 2 procedures. The median cumulative preventive FVIII dose per procedure was 30 IU/kg.

Of the 46 minor procedures, 28 (61%) were performed without preventive FVIII, and 2 (7.1%) were associated with bleeding requiring treatment, both after dental procedures. Two other participants who received preventive FVIII also needed postoperative bleeding treatment. Of note, these events were also after dental procedures, meaning all four instances of bleeding requiring treatment during the trial were associated with dentistry.

“[I]n this experience, dental procedures were somewhat tricky because the bleeding complications were mainly there,” Dr. Santagostino said.

When asked by an audience member if this trend was unique to mucosal bleeding, Dr. Santagostino said it was too early to draw such a conclusion but offered some insight. “To control and prevent bleeding during a dental procedure is not trivial, because … sometimes if you stop factor VIII treatment quite early, you may have late bleeding, mainly due to local reasons, because … dental procedures are very heterogenous.”

Among three other participants who had postoperative bleeding but did not require treatment, two underwent dental procedures, further supporting this association. Although the study numbers are relatively small, the findings may at least support caution, if not preventive FVIII in the dental setting, Dr. Santagostino said.

The four major procedures – all orthopedic – were knee arthroscopic synovectomy, biceps femoris tear repair, total ankle arthroplasty, and total hip replacement. Along with preoperative preventive FVIII, three of four patients undergoing major surgery received preventive FVIII for 14-18 days postoperatively. Doses ranged from 99-522 IU/kg. No postoperative bleeds occurred in this subgroup.

Study funding was provided by F. Hoffmann–La Roche and Chugai Pharmaceutical. The investigators reported financial relationships with Bayer, Shire, Pfizer, Novo Nordisk, and others.

SOURCE: Santagostino E et al. EAHAD 2019, Abstract OR15.

Kenneth Frazier, CEO of pharma giant Merck, is set to face senators Feb. 26 who say drug costs are “sky-high” and “out of control.”

But Frazier doesn’t need new talking points. Sixty years ago, a different panel of senators grilled a different Merck boss about the same problem.

To a striking degree, the subjects likely to surface during the hearing – high drug prices and profits, limited price transparency, aggressive marketing, alleged patent abuse and mediocre, “me-too” drugs – are identical to the issues senators investigated decades ago, historical transcripts show.

Frazier is scheduled to testify before the Senate Finance Committee, led by Sen. Chuck Grassley (R-Iowa), along with the CEOs of AbbVie, AstraZeneca, Bristol-Myers Squibb, Pfizer, and Sanofi and a top executive for Johnson & Johnson.

Hearings led by Sen. Estes Kefauver (D-Tenn.) in 1959 and 1960 were the first significant congressional inquiry into rising drug costs and drug-company profits. While that showdown led to new legal standards for drug safety and effectiveness, cost-control measures never made it to the final bill.

Health policy scholars say the similar hearings show just how much unfinished business remains and how well pharma companies have protected profits and limited regulation over the years.

“Every decade since the Kefauver hearings has seen at least one set of congressional hearings into the increasing prices of prescription drugs,” said Jeremy Greene, MD, PhD, a drug-industry historian at Johns Hopkins University, Baltimore.

“Drug prices, especially at the high end, are only ever higher” since the 1960s, said Scott Podolsky, MD, a health care historian at Harvard Medical School, Boston. “The issues of transparency and profitability certainly have been there from the very first day of Kefauver.”

A Tennessee Democrat known for investigating the Mafia, Sen. Kefauver launched a series of hearings on business in the late 1950s. His Senate antitrust subcommittee began taking testimony on high pharmaceutical prices in late 1959.

“While this country has the best drugs in the world, it would appear from the great number of letters which the subcommittee has received that many of our citizens are experiencing difficulty in being able to purchase them,” Sen. Kefauver said in opening remarks.

The sessions, which lasted off and on until Sept. 1960, were “among the most sensational” hearings of that Congress, a syndicated columnist wrote at the time. Appearing were the bosses of Merck, Pfizer, Schering, Bristol-Myers, Upjohn, Smith Kline, and American Home Products. Senators dug into the prices of antibiotics, corticosteroids and tranquilizers, the wonder drugs of the time.

There was no need to limit drug prices, Austin Smith, president of the Pharmaceutical Manufacturers Association, told the Kefauver committee. Attempts to prove excessive pharma profits were “doomed to failure,” he said. Drug prices were rising more slowly than consumer prices generally, Smith said.

Smith’s counterpart today is Stephen Ubl, who runs what is now known as the Pharmaceutical Research and Manufacturers of America. He takes a similar line, one that is likely to be repeated on Feb. 26. “Drug prices are rapidly decelerating,” Ubl tweeted last month.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Kenneth Frazier, CEO of pharma giant Merck, is set to face senators Feb. 26 who say drug costs are “sky-high” and “out of control.”

But Frazier doesn’t need new talking points. Sixty years ago, a different panel of senators grilled a different Merck boss about the same problem.

To a striking degree, the subjects likely to surface during the hearing – high drug prices and profits, limited price transparency, aggressive marketing, alleged patent abuse and mediocre, “me-too” drugs – are identical to the issues senators investigated decades ago, historical transcripts show.

Frazier is scheduled to testify before the Senate Finance Committee, led by Sen. Chuck Grassley (R-Iowa), along with the CEOs of AbbVie, AstraZeneca, Bristol-Myers Squibb, Pfizer, and Sanofi and a top executive for Johnson & Johnson.

Hearings led by Sen. Estes Kefauver (D-Tenn.) in 1959 and 1960 were the first significant congressional inquiry into rising drug costs and drug-company profits. While that showdown led to new legal standards for drug safety and effectiveness, cost-control measures never made it to the final bill.

Health policy scholars say the similar hearings show just how much unfinished business remains and how well pharma companies have protected profits and limited regulation over the years.

“Every decade since the Kefauver hearings has seen at least one set of congressional hearings into the increasing prices of prescription drugs,” said Jeremy Greene, MD, PhD, a drug-industry historian at Johns Hopkins University, Baltimore.

“Drug prices, especially at the high end, are only ever higher” since the 1960s, said Scott Podolsky, MD, a health care historian at Harvard Medical School, Boston. “The issues of transparency and profitability certainly have been there from the very first day of Kefauver.”

A Tennessee Democrat known for investigating the Mafia, Sen. Kefauver launched a series of hearings on business in the late 1950s. His Senate antitrust subcommittee began taking testimony on high pharmaceutical prices in late 1959.

“While this country has the best drugs in the world, it would appear from the great number of letters which the subcommittee has received that many of our citizens are experiencing difficulty in being able to purchase them,” Sen. Kefauver said in opening remarks.

The sessions, which lasted off and on until Sept. 1960, were “among the most sensational” hearings of that Congress, a syndicated columnist wrote at the time. Appearing were the bosses of Merck, Pfizer, Schering, Bristol-Myers, Upjohn, Smith Kline, and American Home Products. Senators dug into the prices of antibiotics, corticosteroids and tranquilizers, the wonder drugs of the time.

There was no need to limit drug prices, Austin Smith, president of the Pharmaceutical Manufacturers Association, told the Kefauver committee. Attempts to prove excessive pharma profits were “doomed to failure,” he said. Drug prices were rising more slowly than consumer prices generally, Smith said.

Smith’s counterpart today is Stephen Ubl, who runs what is now known as the Pharmaceutical Research and Manufacturers of America. He takes a similar line, one that is likely to be repeated on Feb. 26. “Drug prices are rapidly decelerating,” Ubl tweeted last month.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Kenneth Frazier, CEO of pharma giant Merck, is set to face senators Feb. 26 who say drug costs are “sky-high” and “out of control.”

But Frazier doesn’t need new talking points. Sixty years ago, a different panel of senators grilled a different Merck boss about the same problem.

To a striking degree, the subjects likely to surface during the hearing – high drug prices and profits, limited price transparency, aggressive marketing, alleged patent abuse and mediocre, “me-too” drugs – are identical to the issues senators investigated decades ago, historical transcripts show.

Frazier is scheduled to testify before the Senate Finance Committee, led by Sen. Chuck Grassley (R-Iowa), along with the CEOs of AbbVie, AstraZeneca, Bristol-Myers Squibb, Pfizer, and Sanofi and a top executive for Johnson & Johnson.

Hearings led by Sen. Estes Kefauver (D-Tenn.) in 1959 and 1960 were the first significant congressional inquiry into rising drug costs and drug-company profits. While that showdown led to new legal standards for drug safety and effectiveness, cost-control measures never made it to the final bill.

Health policy scholars say the similar hearings show just how much unfinished business remains and how well pharma companies have protected profits and limited regulation over the years.

“Every decade since the Kefauver hearings has seen at least one set of congressional hearings into the increasing prices of prescription drugs,” said Jeremy Greene, MD, PhD, a drug-industry historian at Johns Hopkins University, Baltimore.

“Drug prices, especially at the high end, are only ever higher” since the 1960s, said Scott Podolsky, MD, a health care historian at Harvard Medical School, Boston. “The issues of transparency and profitability certainly have been there from the very first day of Kefauver.”

A Tennessee Democrat known for investigating the Mafia, Sen. Kefauver launched a series of hearings on business in the late 1950s. His Senate antitrust subcommittee began taking testimony on high pharmaceutical prices in late 1959.

“While this country has the best drugs in the world, it would appear from the great number of letters which the subcommittee has received that many of our citizens are experiencing difficulty in being able to purchase them,” Sen. Kefauver said in opening remarks.

The sessions, which lasted off and on until Sept. 1960, were “among the most sensational” hearings of that Congress, a syndicated columnist wrote at the time. Appearing were the bosses of Merck, Pfizer, Schering, Bristol-Myers, Upjohn, Smith Kline, and American Home Products. Senators dug into the prices of antibiotics, corticosteroids and tranquilizers, the wonder drugs of the time.

There was no need to limit drug prices, Austin Smith, president of the Pharmaceutical Manufacturers Association, told the Kefauver committee. Attempts to prove excessive pharma profits were “doomed to failure,” he said. Drug prices were rising more slowly than consumer prices generally, Smith said.

Smith’s counterpart today is Stephen Ubl, who runs what is now known as the Pharmaceutical Research and Manufacturers of America. He takes a similar line, one that is likely to be repeated on Feb. 26. “Drug prices are rapidly decelerating,” Ubl tweeted last month.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.