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Interventionalists eager for better bioresorbable stents
WASHINGTON – The published results with bioresorbable stents have been disappointing, but most interventionalists think such devices have the potential to prevail over drug-eluting stents by addressing unmet needs, judging from a debate on this topic that took place at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center..
“There is a clinical need for bioresorbable stents [BRS] unless drug-eluting stents [DES] are perfect, and I think we agree that they are not perfect,” argued Gregg Stone, MD, director of cardiovascular research and education at Columbia University Medical Center, New York.
“It does not matter what device you evaluate,” Dr. Stone said. Whether caused by late polymer sensitivity reactions, late strut fractures, or neoatherosclerosis formation, failure can occur suddenly after a decade or more in DES that were performing well up until that point, according to data cited by Dr. Stone. This is one of the key risks that BRS technology was designed to address.
“We now know that the bioresorbable scaffold is replaced by normal tissue at 3 years,” Dr. Stone said. He reported that he is encouraged by the absence of any scaffold thrombosis after 3 years in a recent series of 501 patients with a BRS that have been followed at least 4 years. “This is the first time that we have seen that,” he asserted, adding, “The concept is there.”
His debate opponent, Stephan Windecker, MD, director of invasive cardiology at the Swiss Cardiovascular Center in Bern, cited numerous studies to conclude that “there is clear inferiority” of BRS relative to DES for most important clinical outcomes, including TLF. Although he acknowledged late TLF does occur with DES devices, he contended that new design changes are at least as likely to mitigate risk in DES as improvements in BRS.
However, Dr. Stone suggested that reductions in strut thickness might be the answer for reduced TLF for both BRS and DES devices. If so, there are several reasons to believe that this would ultimately favor BRS as the dominant technology.
“We did not get there with the 150-mcm strut thickness scaffold, but now we have struts as thin as 80 mcm. I’m pretty confident that with smaller struts we will see great results,” countered Dr. Stone.
Returning to the theme that BRS devices address an unmet need, Dr. Stone contended that BRS is the preferred strategy if advances render BRS and drug-eluting stents equally safe and effective. Not least of the reasons is patient preference. “It is an undeniable fact that based on cultural, religious, or personal beliefs, many patients prefer not to live their lives with a permanently implanted device,” he said.
The audience agreed. Asked for a show of hands regarding whether bioresorbable stents technology has the potential to address an unmet need, the majority vote was overwhelmingly in favor of Dr. Stone’s position. Based on a visual vote count that seemed to clearly affirm that BRS addresses and unmet need, Dr. Stone contended that a statistical analysis would have had a P value “with about eight zeros after the decimal point.”
Dr. Stone reports a financial relationship with Reva Medical. Dr. Windecker reports financial relationships with Abbott, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, and St. Jude.
WASHINGTON – The published results with bioresorbable stents have been disappointing, but most interventionalists think such devices have the potential to prevail over drug-eluting stents by addressing unmet needs, judging from a debate on this topic that took place at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center..
“There is a clinical need for bioresorbable stents [BRS] unless drug-eluting stents [DES] are perfect, and I think we agree that they are not perfect,” argued Gregg Stone, MD, director of cardiovascular research and education at Columbia University Medical Center, New York.
“It does not matter what device you evaluate,” Dr. Stone said. Whether caused by late polymer sensitivity reactions, late strut fractures, or neoatherosclerosis formation, failure can occur suddenly after a decade or more in DES that were performing well up until that point, according to data cited by Dr. Stone. This is one of the key risks that BRS technology was designed to address.
“We now know that the bioresorbable scaffold is replaced by normal tissue at 3 years,” Dr. Stone said. He reported that he is encouraged by the absence of any scaffold thrombosis after 3 years in a recent series of 501 patients with a BRS that have been followed at least 4 years. “This is the first time that we have seen that,” he asserted, adding, “The concept is there.”
His debate opponent, Stephan Windecker, MD, director of invasive cardiology at the Swiss Cardiovascular Center in Bern, cited numerous studies to conclude that “there is clear inferiority” of BRS relative to DES for most important clinical outcomes, including TLF. Although he acknowledged late TLF does occur with DES devices, he contended that new design changes are at least as likely to mitigate risk in DES as improvements in BRS.
However, Dr. Stone suggested that reductions in strut thickness might be the answer for reduced TLF for both BRS and DES devices. If so, there are several reasons to believe that this would ultimately favor BRS as the dominant technology.
“We did not get there with the 150-mcm strut thickness scaffold, but now we have struts as thin as 80 mcm. I’m pretty confident that with smaller struts we will see great results,” countered Dr. Stone.
Returning to the theme that BRS devices address an unmet need, Dr. Stone contended that BRS is the preferred strategy if advances render BRS and drug-eluting stents equally safe and effective. Not least of the reasons is patient preference. “It is an undeniable fact that based on cultural, religious, or personal beliefs, many patients prefer not to live their lives with a permanently implanted device,” he said.
The audience agreed. Asked for a show of hands regarding whether bioresorbable stents technology has the potential to address an unmet need, the majority vote was overwhelmingly in favor of Dr. Stone’s position. Based on a visual vote count that seemed to clearly affirm that BRS addresses and unmet need, Dr. Stone contended that a statistical analysis would have had a P value “with about eight zeros after the decimal point.”
Dr. Stone reports a financial relationship with Reva Medical. Dr. Windecker reports financial relationships with Abbott, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, and St. Jude.
WASHINGTON – The published results with bioresorbable stents have been disappointing, but most interventionalists think such devices have the potential to prevail over drug-eluting stents by addressing unmet needs, judging from a debate on this topic that took place at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center..
“There is a clinical need for bioresorbable stents [BRS] unless drug-eluting stents [DES] are perfect, and I think we agree that they are not perfect,” argued Gregg Stone, MD, director of cardiovascular research and education at Columbia University Medical Center, New York.
“It does not matter what device you evaluate,” Dr. Stone said. Whether caused by late polymer sensitivity reactions, late strut fractures, or neoatherosclerosis formation, failure can occur suddenly after a decade or more in DES that were performing well up until that point, according to data cited by Dr. Stone. This is one of the key risks that BRS technology was designed to address.
“We now know that the bioresorbable scaffold is replaced by normal tissue at 3 years,” Dr. Stone said. He reported that he is encouraged by the absence of any scaffold thrombosis after 3 years in a recent series of 501 patients with a BRS that have been followed at least 4 years. “This is the first time that we have seen that,” he asserted, adding, “The concept is there.”
His debate opponent, Stephan Windecker, MD, director of invasive cardiology at the Swiss Cardiovascular Center in Bern, cited numerous studies to conclude that “there is clear inferiority” of BRS relative to DES for most important clinical outcomes, including TLF. Although he acknowledged late TLF does occur with DES devices, he contended that new design changes are at least as likely to mitigate risk in DES as improvements in BRS.
However, Dr. Stone suggested that reductions in strut thickness might be the answer for reduced TLF for both BRS and DES devices. If so, there are several reasons to believe that this would ultimately favor BRS as the dominant technology.
“We did not get there with the 150-mcm strut thickness scaffold, but now we have struts as thin as 80 mcm. I’m pretty confident that with smaller struts we will see great results,” countered Dr. Stone.
Returning to the theme that BRS devices address an unmet need, Dr. Stone contended that BRS is the preferred strategy if advances render BRS and drug-eluting stents equally safe and effective. Not least of the reasons is patient preference. “It is an undeniable fact that based on cultural, religious, or personal beliefs, many patients prefer not to live their lives with a permanently implanted device,” he said.
The audience agreed. Asked for a show of hands regarding whether bioresorbable stents technology has the potential to address an unmet need, the majority vote was overwhelmingly in favor of Dr. Stone’s position. Based on a visual vote count that seemed to clearly affirm that BRS addresses and unmet need, Dr. Stone contended that a statistical analysis would have had a P value “with about eight zeros after the decimal point.”
Dr. Stone reports a financial relationship with Reva Medical. Dr. Windecker reports financial relationships with Abbott, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, and St. Jude.
EXPERT ANALYSIS FROM CRT 2018
Most PsA patients discontinue initial biologic within 12 months
Most adult patients with psoriatic arthritis who newly initiate biologic therapy with a tumor necrosis factor (TNF) inhibitor or anti–interleukin-12/23 inhibitor discontinued the treatment before a year is up, according to a recent analysis of a U.S. claims database.
Over a 12-month follow-up period, 27% of psoriatic arthritis (PsA) patients discontinued the index biologic, 23% switched to a different biologic, and 6% discontinued the index biologic but later restarted it, according to the results, which were published in the Journal of Managed Care & Specialty Pharmacy.
“In this population of patients with PsA, additional options for concomitant therapies or alternatives to TNF inhibitors and anti–IL-12/23 inhibitors may be important,” the authors wrote.
The retrospective, observational study included administrative claims data from the Optum research database representing 1,235 adults with PsA who newly initiated a biologic therapy between Jan. 1, 2013, and Jan. 31, 2015. The patients (53% female; mean age, 50.3 years) had received biologic therapies approved for treatment of PsA at the time. These patients had commercial health coverage or Medicare Advantage, and nearly half were from the South. About half (48%) received etanercept, 24% received adalimumab, 10% received infliximab, and the rest received golimumab, ustekinumab, or certolizumab pegol.
The mean duration of persistence with a newly initiated biologic was just 246 days, the investigators reported. Infliximab had the highest 12-month persistence in this study, investigators said, with a mean of 293 days, while certolizumab pegol had the shortest, at a mean of 207 days.
Among patients who stayed on the index biologic for at least 90 days, nearly half started an adjunctive treatment, which was usually corticosteroids (22%), opioids (17%), or an NSAID (13%), Dr. Walsh and her coauthors said.
Dose escalation of the index biologic occurred in 9.6% of patients over the 12-month follow-up, they added.
“High rates of discontinuation and switching of biologic therapies, along with high rates of dose escalation, suggest a high frequency of suboptimal biologic experience in patients with PsA,” they wrote. Although the study did not address why patients discontinued or switched, previous studies suggest adverse effects and lack of efficacy are the most commonly reported reasons.
“Insufficient control of symptoms may lead patients to discontinue biologic therapy, which can contribute to disease progression,” the authors said in their conclusion.
Novartis sponsored the study. Some study authors reported disclosures related to Novartis, including consultancy and employment, and to Optum, which was commissioned to conduct the study.
SOURCE: Walsh JA et al. J Manag Care Spec Pharm. 2018 Mar 20. doi: 10.18553/jmcp.2018.17388.
Most adult patients with psoriatic arthritis who newly initiate biologic therapy with a tumor necrosis factor (TNF) inhibitor or anti–interleukin-12/23 inhibitor discontinued the treatment before a year is up, according to a recent analysis of a U.S. claims database.
Over a 12-month follow-up period, 27% of psoriatic arthritis (PsA) patients discontinued the index biologic, 23% switched to a different biologic, and 6% discontinued the index biologic but later restarted it, according to the results, which were published in the Journal of Managed Care & Specialty Pharmacy.
“In this population of patients with PsA, additional options for concomitant therapies or alternatives to TNF inhibitors and anti–IL-12/23 inhibitors may be important,” the authors wrote.
The retrospective, observational study included administrative claims data from the Optum research database representing 1,235 adults with PsA who newly initiated a biologic therapy between Jan. 1, 2013, and Jan. 31, 2015. The patients (53% female; mean age, 50.3 years) had received biologic therapies approved for treatment of PsA at the time. These patients had commercial health coverage or Medicare Advantage, and nearly half were from the South. About half (48%) received etanercept, 24% received adalimumab, 10% received infliximab, and the rest received golimumab, ustekinumab, or certolizumab pegol.
The mean duration of persistence with a newly initiated biologic was just 246 days, the investigators reported. Infliximab had the highest 12-month persistence in this study, investigators said, with a mean of 293 days, while certolizumab pegol had the shortest, at a mean of 207 days.
Among patients who stayed on the index biologic for at least 90 days, nearly half started an adjunctive treatment, which was usually corticosteroids (22%), opioids (17%), or an NSAID (13%), Dr. Walsh and her coauthors said.
Dose escalation of the index biologic occurred in 9.6% of patients over the 12-month follow-up, they added.
“High rates of discontinuation and switching of biologic therapies, along with high rates of dose escalation, suggest a high frequency of suboptimal biologic experience in patients with PsA,” they wrote. Although the study did not address why patients discontinued or switched, previous studies suggest adverse effects and lack of efficacy are the most commonly reported reasons.
“Insufficient control of symptoms may lead patients to discontinue biologic therapy, which can contribute to disease progression,” the authors said in their conclusion.
Novartis sponsored the study. Some study authors reported disclosures related to Novartis, including consultancy and employment, and to Optum, which was commissioned to conduct the study.
SOURCE: Walsh JA et al. J Manag Care Spec Pharm. 2018 Mar 20. doi: 10.18553/jmcp.2018.17388.
Most adult patients with psoriatic arthritis who newly initiate biologic therapy with a tumor necrosis factor (TNF) inhibitor or anti–interleukin-12/23 inhibitor discontinued the treatment before a year is up, according to a recent analysis of a U.S. claims database.
Over a 12-month follow-up period, 27% of psoriatic arthritis (PsA) patients discontinued the index biologic, 23% switched to a different biologic, and 6% discontinued the index biologic but later restarted it, according to the results, which were published in the Journal of Managed Care & Specialty Pharmacy.
“In this population of patients with PsA, additional options for concomitant therapies or alternatives to TNF inhibitors and anti–IL-12/23 inhibitors may be important,” the authors wrote.
The retrospective, observational study included administrative claims data from the Optum research database representing 1,235 adults with PsA who newly initiated a biologic therapy between Jan. 1, 2013, and Jan. 31, 2015. The patients (53% female; mean age, 50.3 years) had received biologic therapies approved for treatment of PsA at the time. These patients had commercial health coverage or Medicare Advantage, and nearly half were from the South. About half (48%) received etanercept, 24% received adalimumab, 10% received infliximab, and the rest received golimumab, ustekinumab, or certolizumab pegol.
The mean duration of persistence with a newly initiated biologic was just 246 days, the investigators reported. Infliximab had the highest 12-month persistence in this study, investigators said, with a mean of 293 days, while certolizumab pegol had the shortest, at a mean of 207 days.
Among patients who stayed on the index biologic for at least 90 days, nearly half started an adjunctive treatment, which was usually corticosteroids (22%), opioids (17%), or an NSAID (13%), Dr. Walsh and her coauthors said.
Dose escalation of the index biologic occurred in 9.6% of patients over the 12-month follow-up, they added.
“High rates of discontinuation and switching of biologic therapies, along with high rates of dose escalation, suggest a high frequency of suboptimal biologic experience in patients with PsA,” they wrote. Although the study did not address why patients discontinued or switched, previous studies suggest adverse effects and lack of efficacy are the most commonly reported reasons.
“Insufficient control of symptoms may lead patients to discontinue biologic therapy, which can contribute to disease progression,” the authors said in their conclusion.
Novartis sponsored the study. Some study authors reported disclosures related to Novartis, including consultancy and employment, and to Optum, which was commissioned to conduct the study.
SOURCE: Walsh JA et al. J Manag Care Spec Pharm. 2018 Mar 20. doi: 10.18553/jmcp.2018.17388.
FROM THE JOURNAL OF MANAGED CARE & SPECIALTY PHARMACY
Key clinical point: While treatment persistence is important to achieve optimal outcomes,
Major finding: Over a 12-month follow-up period, 27% of patients discontinued the index biologic, 23% switched to a different biologic, and 6% discontinued the index biologic but later restarted it.
Study details: A retrospective, observational study of U.S. administrative claims data representing 1,235 adults with PsA who newly initiated a biologic therapy between Jan. 1, 2013, and Jan. 31, 2015.
Disclosures: Novartis sponsored the study. Some study authors reported disclosures related to Novartis, including consultancy and employment, and to Optum, which was commissioned to conduct the study.
Source: Walsh JA et al. J Manag Care Spec Pharm. 2018 Mar 20. doi: 10.18553/jmcp.2018.17388.
Patients who hide. Patients who seek.
Some people are more likely to seek medical care, and some people are less likely, but which type is more common? The results of a survey of over 14,000 Medicare beneficiaries suggest that the avoid-care type may be a bit more prevalent.
In the survey, 40% of respondents said that they were more likely to keep it to themselves when they got sick, but 36% visit a physician as soon as they feel bad. Almost 29% reported that they avoid going to a physician, but 25% worry about their own health more than others, the Centers for Medicare & Medicaid Services reported based on the results of the 2015 Medicare Current Beneficiary Survey.
Race and ethnicity made a big difference for some questions: 59% of Hispanics said that they visit a doctor as soon as they feel bad, compared with 44% of non-Hispanic blacks and 31% of non-Hispanic whites. That same order was seen for “worry about your health more than others” – 54% Hispanic, 38% black, and 19% white – and for “avoid going to the doctor” – 44% Hispanic, 34% black, and 26% white, the CMS reported.
The three groups, which were the only race/ethnicities included in the report, were all around 40% for “when sick, keep it to yourself,” while two of the three were the same for “had a problem and did not seek a doctor” (blacks and Hispanics at 14% and whites at 10%) and for “ever had a prescription you did not fill” (whites and Hispanics at 7% and blacks at 10%), the report said.
The estimates on propensity to seek care did not include Medicare recipients who lived part or all of the year in a long-term care facility, which was about 4% of the Medicare population in 2015. The survey included a total of 14,068 respondents.
Some people are more likely to seek medical care, and some people are less likely, but which type is more common? The results of a survey of over 14,000 Medicare beneficiaries suggest that the avoid-care type may be a bit more prevalent.
In the survey, 40% of respondents said that they were more likely to keep it to themselves when they got sick, but 36% visit a physician as soon as they feel bad. Almost 29% reported that they avoid going to a physician, but 25% worry about their own health more than others, the Centers for Medicare & Medicaid Services reported based on the results of the 2015 Medicare Current Beneficiary Survey.
Race and ethnicity made a big difference for some questions: 59% of Hispanics said that they visit a doctor as soon as they feel bad, compared with 44% of non-Hispanic blacks and 31% of non-Hispanic whites. That same order was seen for “worry about your health more than others” – 54% Hispanic, 38% black, and 19% white – and for “avoid going to the doctor” – 44% Hispanic, 34% black, and 26% white, the CMS reported.
The three groups, which were the only race/ethnicities included in the report, were all around 40% for “when sick, keep it to yourself,” while two of the three were the same for “had a problem and did not seek a doctor” (blacks and Hispanics at 14% and whites at 10%) and for “ever had a prescription you did not fill” (whites and Hispanics at 7% and blacks at 10%), the report said.
The estimates on propensity to seek care did not include Medicare recipients who lived part or all of the year in a long-term care facility, which was about 4% of the Medicare population in 2015. The survey included a total of 14,068 respondents.
Some people are more likely to seek medical care, and some people are less likely, but which type is more common? The results of a survey of over 14,000 Medicare beneficiaries suggest that the avoid-care type may be a bit more prevalent.
In the survey, 40% of respondents said that they were more likely to keep it to themselves when they got sick, but 36% visit a physician as soon as they feel bad. Almost 29% reported that they avoid going to a physician, but 25% worry about their own health more than others, the Centers for Medicare & Medicaid Services reported based on the results of the 2015 Medicare Current Beneficiary Survey.
Race and ethnicity made a big difference for some questions: 59% of Hispanics said that they visit a doctor as soon as they feel bad, compared with 44% of non-Hispanic blacks and 31% of non-Hispanic whites. That same order was seen for “worry about your health more than others” – 54% Hispanic, 38% black, and 19% white – and for “avoid going to the doctor” – 44% Hispanic, 34% black, and 26% white, the CMS reported.
The three groups, which were the only race/ethnicities included in the report, were all around 40% for “when sick, keep it to yourself,” while two of the three were the same for “had a problem and did not seek a doctor” (blacks and Hispanics at 14% and whites at 10%) and for “ever had a prescription you did not fill” (whites and Hispanics at 7% and blacks at 10%), the report said.
The estimates on propensity to seek care did not include Medicare recipients who lived part or all of the year in a long-term care facility, which was about 4% of the Medicare population in 2015. The survey included a total of 14,068 respondents.
Certolizumab pegol: Has serious infection risk been overstated?
Contrary to prior reports, certolizumab pegol may not be associated with an increased risk of serious infections versus other biologics used in the treatment of rheumatoid arthritis, according to results of a recent U.K. registry study.
Certolizumab pegol (Cimzia) actually had a lower risk of serious infections, compared with etanercept in the primary analysis, according to a report on the study recently published in Annals of the Rheumatic Diseases.
In sensitivity analyses, though, the result in favor of certolizumab pegol was no longer significant, according to lead author Andrew I. Rutherford, MBBS, of King’s College London, and his coauthors.
“From these results, it would be wrong to conclude that certolizumab pegol has a lower rate of [serious infection] than other biologics,” Dr. Rutherford and his colleagues said in their report. “However, the risk does not appear to be significantly higher as has previously been suggested.”
The prospective, observational cohort study, based on data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), represented 19,282 patients with 46,771 years of follow-up, according to the authors.
For the entire cohort, the incidence of serious infections was 5.51 cases per 100 patient-years (95% confidence interval, 5.29-5.71), and the 30-day mortality after serious infection was 10.4% (95% CI, 9.2%-11.6%), the report said. Compared with etanercept, the risk of serious infections was lower for certolizumab pegol (adjusted hazard ratio, 0.75; 95% CI, 0.58-0.97). Etanercept was used as the reference arm for comparison since it was the most widely prescribed drug in the registry.
That finding is in “direct contradiction” to a 2011 Cochrane review finding that certolizumab pegol was associated with an infection rate three to four times higher than other anti–tumor necrosis factor (anti-TNF) drugs (Cochrane Database Syst Rev. 2011;2:Cd008794), the authors noted.
“It would seem unusual for drugs acting on the same pathway with similar efficacy to have such drastically different infection risks,” Dr. Rutherford and his coauthors observed in their report.
However, investigators noticed that in the certolizumab pegol cohort, a large number of patients had not previously been on a biologic. When those biologic-naive patients were excluded from analysis, there was no longer a difference in infection rate favoring certolizumab pegol. “This suggests that unmeasured confounders may be responsible for the difference that was observed in the primary analysis,” the investigators said in their discussion of the results.
The Cochrane review showing an increased risk of serious infections with certolizumab pegol was a large network meta-analysis, which they said relies on indirect comparisons between drugs and could be prone to error if there are differences in study design.
“In contrast, national registers use the same methodology for detecting and reporting of adverse events for each drug,” they added.
Dr. Rutherford reported no disclosures. Study coauthors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
SOURCE: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.
Contrary to prior reports, certolizumab pegol may not be associated with an increased risk of serious infections versus other biologics used in the treatment of rheumatoid arthritis, according to results of a recent U.K. registry study.
Certolizumab pegol (Cimzia) actually had a lower risk of serious infections, compared with etanercept in the primary analysis, according to a report on the study recently published in Annals of the Rheumatic Diseases.
In sensitivity analyses, though, the result in favor of certolizumab pegol was no longer significant, according to lead author Andrew I. Rutherford, MBBS, of King’s College London, and his coauthors.
“From these results, it would be wrong to conclude that certolizumab pegol has a lower rate of [serious infection] than other biologics,” Dr. Rutherford and his colleagues said in their report. “However, the risk does not appear to be significantly higher as has previously been suggested.”
The prospective, observational cohort study, based on data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), represented 19,282 patients with 46,771 years of follow-up, according to the authors.
For the entire cohort, the incidence of serious infections was 5.51 cases per 100 patient-years (95% confidence interval, 5.29-5.71), and the 30-day mortality after serious infection was 10.4% (95% CI, 9.2%-11.6%), the report said. Compared with etanercept, the risk of serious infections was lower for certolizumab pegol (adjusted hazard ratio, 0.75; 95% CI, 0.58-0.97). Etanercept was used as the reference arm for comparison since it was the most widely prescribed drug in the registry.
That finding is in “direct contradiction” to a 2011 Cochrane review finding that certolizumab pegol was associated with an infection rate three to four times higher than other anti–tumor necrosis factor (anti-TNF) drugs (Cochrane Database Syst Rev. 2011;2:Cd008794), the authors noted.
“It would seem unusual for drugs acting on the same pathway with similar efficacy to have such drastically different infection risks,” Dr. Rutherford and his coauthors observed in their report.
However, investigators noticed that in the certolizumab pegol cohort, a large number of patients had not previously been on a biologic. When those biologic-naive patients were excluded from analysis, there was no longer a difference in infection rate favoring certolizumab pegol. “This suggests that unmeasured confounders may be responsible for the difference that was observed in the primary analysis,” the investigators said in their discussion of the results.
The Cochrane review showing an increased risk of serious infections with certolizumab pegol was a large network meta-analysis, which they said relies on indirect comparisons between drugs and could be prone to error if there are differences in study design.
“In contrast, national registers use the same methodology for detecting and reporting of adverse events for each drug,” they added.
Dr. Rutherford reported no disclosures. Study coauthors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
SOURCE: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.
Contrary to prior reports, certolizumab pegol may not be associated with an increased risk of serious infections versus other biologics used in the treatment of rheumatoid arthritis, according to results of a recent U.K. registry study.
Certolizumab pegol (Cimzia) actually had a lower risk of serious infections, compared with etanercept in the primary analysis, according to a report on the study recently published in Annals of the Rheumatic Diseases.
In sensitivity analyses, though, the result in favor of certolizumab pegol was no longer significant, according to lead author Andrew I. Rutherford, MBBS, of King’s College London, and his coauthors.
“From these results, it would be wrong to conclude that certolizumab pegol has a lower rate of [serious infection] than other biologics,” Dr. Rutherford and his colleagues said in their report. “However, the risk does not appear to be significantly higher as has previously been suggested.”
The prospective, observational cohort study, based on data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), represented 19,282 patients with 46,771 years of follow-up, according to the authors.
For the entire cohort, the incidence of serious infections was 5.51 cases per 100 patient-years (95% confidence interval, 5.29-5.71), and the 30-day mortality after serious infection was 10.4% (95% CI, 9.2%-11.6%), the report said. Compared with etanercept, the risk of serious infections was lower for certolizumab pegol (adjusted hazard ratio, 0.75; 95% CI, 0.58-0.97). Etanercept was used as the reference arm for comparison since it was the most widely prescribed drug in the registry.
That finding is in “direct contradiction” to a 2011 Cochrane review finding that certolizumab pegol was associated with an infection rate three to four times higher than other anti–tumor necrosis factor (anti-TNF) drugs (Cochrane Database Syst Rev. 2011;2:Cd008794), the authors noted.
“It would seem unusual for drugs acting on the same pathway with similar efficacy to have such drastically different infection risks,” Dr. Rutherford and his coauthors observed in their report.
However, investigators noticed that in the certolizumab pegol cohort, a large number of patients had not previously been on a biologic. When those biologic-naive patients were excluded from analysis, there was no longer a difference in infection rate favoring certolizumab pegol. “This suggests that unmeasured confounders may be responsible for the difference that was observed in the primary analysis,” the investigators said in their discussion of the results.
The Cochrane review showing an increased risk of serious infections with certolizumab pegol was a large network meta-analysis, which they said relies on indirect comparisons between drugs and could be prone to error if there are differences in study design.
“In contrast, national registers use the same methodology for detecting and reporting of adverse events for each drug,” they added.
Dr. Rutherford reported no disclosures. Study coauthors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
SOURCE: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: Certolizumab pegol had a lower risk of serious infections compared to etanercept (HR, 0.75; 95% CI, 0.58-0.97), though in sensitivity analyses, the difference was no longer significant.
Study details: A prospective observational cohort study of data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) representing 19,282 patients with 46,771 years of follow-up.
Disclosures: Study authors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
Source: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.
Wound protectors lower risk of surgical site infections
particularly dual-ring devices, new research suggests.
A meta-analysis of 12 randomized, controlled trials with 3,029 participants found that the use of wound protectors during surgery was associated with 34% lower odds of surgical site infection (95% confidence interval, 0.45–0.90; P less than .01).
The study, published in the March edition of Surgical Endoscopy, also showed that dual-ring wound protectors were associated with a highly significant 69% reduction in the odds of surgical site infections (95% CI, 0.18-0.52; P less than .0001), while the benefits of single-ring wound protectors did not reach statistical significance (OR, 0.84; 95% CI, 0.67–1.04; P = .11).
Wound protectors – also known as wound guards or wound retractors – are intended to prevent the edges of a surgical wound from coming into contact with the contaminated surgical field.
The single-ring model consists of a plastic ring that sits within the wound and a protective drape that extends out from it. In the dual-ring model, one ring sits inside the wound and the other outside the wound, with the two rings joined by the protective plastic.
Of the 12 studies included in the meta-analysis, 5 involved colorectal surgery only, 5 included both colorectal and other gastrointestinal surgery, and 2 studies focused on appendectomies. All but one study involved open surgery.
“Our study is more specific in the interventions included in that we included lower gastrointestinal surgery only, which is a population that would likely benefit the most from the intervention due to the high incidence of SSIs in bowel surgery, compared to other abdominal surgeries,” wrote Lisa Zhang, MD, a general surgery resident at the department of surgery at Kingston (Ont.) General Hospital and her coauthors.
There was no difference in the effect of wound protectors based on the target organ for surgery, even with a high number of patients in one of the appendectomy trials, which the authors were concerned may have skewed the results.
Overall, the authors rated the evidence to be of moderate quality, but several studies had a high risk of bias.
The authors said that one barrier to routine use of these devices was cost. However, given that surgical site infections are estimated to cost around $3.5 billion to $10 billion annually in health care expenditures, they argued that “the use of dual-ring wound edge protectors should be considered in open lower gastrointestinal surgery, including open appendectomies.”
No funding sources or conflicts of interest were declared.
SOURCE: Zhang L et al. Surg Endosc. 2018;32:1111–22.
particularly dual-ring devices, new research suggests.
A meta-analysis of 12 randomized, controlled trials with 3,029 participants found that the use of wound protectors during surgery was associated with 34% lower odds of surgical site infection (95% confidence interval, 0.45–0.90; P less than .01).
The study, published in the March edition of Surgical Endoscopy, also showed that dual-ring wound protectors were associated with a highly significant 69% reduction in the odds of surgical site infections (95% CI, 0.18-0.52; P less than .0001), while the benefits of single-ring wound protectors did not reach statistical significance (OR, 0.84; 95% CI, 0.67–1.04; P = .11).
Wound protectors – also known as wound guards or wound retractors – are intended to prevent the edges of a surgical wound from coming into contact with the contaminated surgical field.
The single-ring model consists of a plastic ring that sits within the wound and a protective drape that extends out from it. In the dual-ring model, one ring sits inside the wound and the other outside the wound, with the two rings joined by the protective plastic.
Of the 12 studies included in the meta-analysis, 5 involved colorectal surgery only, 5 included both colorectal and other gastrointestinal surgery, and 2 studies focused on appendectomies. All but one study involved open surgery.
“Our study is more specific in the interventions included in that we included lower gastrointestinal surgery only, which is a population that would likely benefit the most from the intervention due to the high incidence of SSIs in bowel surgery, compared to other abdominal surgeries,” wrote Lisa Zhang, MD, a general surgery resident at the department of surgery at Kingston (Ont.) General Hospital and her coauthors.
There was no difference in the effect of wound protectors based on the target organ for surgery, even with a high number of patients in one of the appendectomy trials, which the authors were concerned may have skewed the results.
Overall, the authors rated the evidence to be of moderate quality, but several studies had a high risk of bias.
The authors said that one barrier to routine use of these devices was cost. However, given that surgical site infections are estimated to cost around $3.5 billion to $10 billion annually in health care expenditures, they argued that “the use of dual-ring wound edge protectors should be considered in open lower gastrointestinal surgery, including open appendectomies.”
No funding sources or conflicts of interest were declared.
SOURCE: Zhang L et al. Surg Endosc. 2018;32:1111–22.
particularly dual-ring devices, new research suggests.
A meta-analysis of 12 randomized, controlled trials with 3,029 participants found that the use of wound protectors during surgery was associated with 34% lower odds of surgical site infection (95% confidence interval, 0.45–0.90; P less than .01).
The study, published in the March edition of Surgical Endoscopy, also showed that dual-ring wound protectors were associated with a highly significant 69% reduction in the odds of surgical site infections (95% CI, 0.18-0.52; P less than .0001), while the benefits of single-ring wound protectors did not reach statistical significance (OR, 0.84; 95% CI, 0.67–1.04; P = .11).
Wound protectors – also known as wound guards or wound retractors – are intended to prevent the edges of a surgical wound from coming into contact with the contaminated surgical field.
The single-ring model consists of a plastic ring that sits within the wound and a protective drape that extends out from it. In the dual-ring model, one ring sits inside the wound and the other outside the wound, with the two rings joined by the protective plastic.
Of the 12 studies included in the meta-analysis, 5 involved colorectal surgery only, 5 included both colorectal and other gastrointestinal surgery, and 2 studies focused on appendectomies. All but one study involved open surgery.
“Our study is more specific in the interventions included in that we included lower gastrointestinal surgery only, which is a population that would likely benefit the most from the intervention due to the high incidence of SSIs in bowel surgery, compared to other abdominal surgeries,” wrote Lisa Zhang, MD, a general surgery resident at the department of surgery at Kingston (Ont.) General Hospital and her coauthors.
There was no difference in the effect of wound protectors based on the target organ for surgery, even with a high number of patients in one of the appendectomy trials, which the authors were concerned may have skewed the results.
Overall, the authors rated the evidence to be of moderate quality, but several studies had a high risk of bias.
The authors said that one barrier to routine use of these devices was cost. However, given that surgical site infections are estimated to cost around $3.5 billion to $10 billion annually in health care expenditures, they argued that “the use of dual-ring wound edge protectors should be considered in open lower gastrointestinal surgery, including open appendectomies.”
No funding sources or conflicts of interest were declared.
SOURCE: Zhang L et al. Surg Endosc. 2018;32:1111–22.
FROM SURGICAL ENDOSCOPY
Key clinical point: Dual-ring wound protectors significantly decrease the risk of gastrointestinal surgical site infections.
Major finding: Dual-ring wound protectors were associated with a 69% reduction in the odds of surgical site infections.
Study details: A meta-analysis of 12 randomized, controlled trials.
Disclosures: No funding source or conflicts of interest were declared.
Source: Zhang L et al. Surg Endosc. 2018;32:1111–22.
Clean-Surfaced Nanocrystalline Gold May Promote Remyelination
SAN DIEGO—A novel therapy designed to promote the maturation and activation of myelin-producing oligodendrocytes is moving to phase II clinical trials based on evidence of safety and efficacy in animal models and humans. The therapy, a suspension of clean-surfaced gold nanocrystals, may remyelinate multiple sclerosis (MS) lesions, according to research presented at the ACTRIMS 2018 Forum.
This agent, known as CNM-Au8, has been associated with improved behavioral function in animal models of MS, according to Michael Hotchkin, Head of Strategic Operations at Clene Nanomedicine in Salt Lake City. Clene Nanomedicine is developing CNM-Au8. Although the mechanism of action is “multifactorial,” the benefit has been linked to bioenergetic support for the differentiation and maturation of oligodendrocyte precursor cells, said Mr. Hotchkin.
In one behavioral study of fine motor kinetics in an experimental model of MS, mice treated with CNM-Au8 “were effectively indistinguishable” from animals with no demyelination, he said.
Treatment Improved Two Models of Demyelination
Following in vitro studies that suggested that CNM-Au8 can promote the differentiation of oligodendrocyte precursor cells into mature myelin-producing oligodendrocytes, a series of studies was conducted in lysolecithin and cuprizone animal models of MS demyelination.
The studies using the lysolecithin model included vehicle controls and compared CNM-Au8’s effect on remyelinated axons after inducing spinal demyelination with lysolecithin. In the cuprizone studies, the treatments were delivered before injury to test prophylactic efficacy and after injury to test treatment efficacy. Markers of remyelination, such as oligodendrocyte maturation, myelin basic protein expression, and axonal staining, were evaluated by immunohistochemistry and transmission electron microscopy in animals sacrificed at various times after injury.
CNM-Au8 produced “striking visible evidence of progressive increase in myelin,” according to Mr. Hotchkin. The treatment was associated with reductions in myelin sheath degeneration and demyelinated areas, relative to vehicle. In one analysis of the lysolecithin model, CNM-Au8 was associated with a 43% increase in myelinated axon count. Moreover, an increase in mature oligodendrocytes localized at the site of focal demyelination injury in the CNM-Au8-treated animals was consistent with stimulation of oligodendrocyte maturation, according to Mr. Hotchkin.
In both models, investigators found evidence of increased oligodendrocyte maturation and remyelination when CNM-Au8 was administered after injury, as well as when it was administered before injury. The results suggest that CNM-Au8 has important activity in the remyelination of demyelinated axons.
Researchers also conducted behavioral studies in the cuprizone model of MS. They tracked the animals’ movement with lasers and used computer software to analyze the movement. These studies included relevant controls and compared animals with no demyelination, vehicle-treated animals dosed with cuprizone, and CNM-Au8-treated animals similarly dosed with cuprizone, to determine whether delayed treatment following initial damage from the toxin would result in functional recovery in the animals.
The investigators observed protective effects of CNM-Au8 when the drug was administered in this treatment paradigm. Improvements in several behavioral end points when the drug was administered after the demyelinating insult “demonstrated that CNM-Au8 restored behavioral function following demyelination,” said Mr. Hotchkin.
Furthermore, in a behavioral study of fine motor kinetics, function improved by 78% at week 6, compared with week 3 (ie, immediately following the start of treatment) in the group treated with CMN-Au8 that was receiving cuprizone. The animals treated with vehicle and cuprizone had a 39% functional improvement at week 6, compared with week 3. Notably, there was not a statistically significant difference in function at week 6 between CNM-Au8-treated animals and the normal healthy control animals without demyelination, indicating that the functional recovery made the former and latter animals indistinguishable.
Therapy Promotes Bioenergetics Catalysis
CNM-Au8 may generate remyelination by more than one mechanism, said Mr. Hotchkin, and evidence indicates that the drug promotes bioenergetic catalysis that is important to the maturation of oligodendrocyte precursors. Published literature suggests an association between altered oligodendrocyte energy utilization and remyelination failure in the human brain. Other evidence suggests that CNM-Au8 may trigger oligodendrocytes’ remyelinating activity by improving energy sources such as adenosine triphosphate, lactate, and oxidized nicotinamide adenine dinucleotide (NAD+), said Mr. Hotchkin. For example, CNM-Au8 increased NAD+ levels in mouse hippocampal cultures by about 40%, relative to vehicle.
In response to questions about the catalytic mechanism, Mr. Hotchkin responded, “You can fill a car’s tank with gas, but if the electrical system is fouled, the car goes nowhere. CNM-Au8 is the catalytic engine driving bioenergetic improvements in the oligodendrocytes driving them to remyelinate.” Data suggest that CNM-Au8 may have applications in other neurodegenerative diseases, based on the bioenergetic failure hypothesis of neurodegeneration and aging, said Mr. Hotchkin.
Oligodendrocyte precursor cells are known to be present in the human brain in and around MS lesions even years after an MS attack. Thus, the animal studies may be relevant to clinical MS. As an oral agent, CNM-Au8 has the potential to be a major clinical advance if human trials show activity comparable to that in animal studies, said Mr. Hotchkin.
Initial phase I human clinical work and extensive animal toxicology has supported the safety of this agent. Trials in patients with MS that examine clinical end points are planned. “A phase II study in chronic optic neuropathy in relapsing-remitting MS patients will commence in 2018,” Glen Frick, MD, PhD, Chief Medical Officer of Clene Nanomedicine, told Neurology Reviews.
—Ted Bosworth
Suggested Reading
Rone
SAN DIEGO—A novel therapy designed to promote the maturation and activation of myelin-producing oligodendrocytes is moving to phase II clinical trials based on evidence of safety and efficacy in animal models and humans. The therapy, a suspension of clean-surfaced gold nanocrystals, may remyelinate multiple sclerosis (MS) lesions, according to research presented at the ACTRIMS 2018 Forum.
This agent, known as CNM-Au8, has been associated with improved behavioral function in animal models of MS, according to Michael Hotchkin, Head of Strategic Operations at Clene Nanomedicine in Salt Lake City. Clene Nanomedicine is developing CNM-Au8. Although the mechanism of action is “multifactorial,” the benefit has been linked to bioenergetic support for the differentiation and maturation of oligodendrocyte precursor cells, said Mr. Hotchkin.
In one behavioral study of fine motor kinetics in an experimental model of MS, mice treated with CNM-Au8 “were effectively indistinguishable” from animals with no demyelination, he said.
Treatment Improved Two Models of Demyelination
Following in vitro studies that suggested that CNM-Au8 can promote the differentiation of oligodendrocyte precursor cells into mature myelin-producing oligodendrocytes, a series of studies was conducted in lysolecithin and cuprizone animal models of MS demyelination.
The studies using the lysolecithin model included vehicle controls and compared CNM-Au8’s effect on remyelinated axons after inducing spinal demyelination with lysolecithin. In the cuprizone studies, the treatments were delivered before injury to test prophylactic efficacy and after injury to test treatment efficacy. Markers of remyelination, such as oligodendrocyte maturation, myelin basic protein expression, and axonal staining, were evaluated by immunohistochemistry and transmission electron microscopy in animals sacrificed at various times after injury.
CNM-Au8 produced “striking visible evidence of progressive increase in myelin,” according to Mr. Hotchkin. The treatment was associated with reductions in myelin sheath degeneration and demyelinated areas, relative to vehicle. In one analysis of the lysolecithin model, CNM-Au8 was associated with a 43% increase in myelinated axon count. Moreover, an increase in mature oligodendrocytes localized at the site of focal demyelination injury in the CNM-Au8-treated animals was consistent with stimulation of oligodendrocyte maturation, according to Mr. Hotchkin.
In both models, investigators found evidence of increased oligodendrocyte maturation and remyelination when CNM-Au8 was administered after injury, as well as when it was administered before injury. The results suggest that CNM-Au8 has important activity in the remyelination of demyelinated axons.
Researchers also conducted behavioral studies in the cuprizone model of MS. They tracked the animals’ movement with lasers and used computer software to analyze the movement. These studies included relevant controls and compared animals with no demyelination, vehicle-treated animals dosed with cuprizone, and CNM-Au8-treated animals similarly dosed with cuprizone, to determine whether delayed treatment following initial damage from the toxin would result in functional recovery in the animals.
The investigators observed protective effects of CNM-Au8 when the drug was administered in this treatment paradigm. Improvements in several behavioral end points when the drug was administered after the demyelinating insult “demonstrated that CNM-Au8 restored behavioral function following demyelination,” said Mr. Hotchkin.
Furthermore, in a behavioral study of fine motor kinetics, function improved by 78% at week 6, compared with week 3 (ie, immediately following the start of treatment) in the group treated with CMN-Au8 that was receiving cuprizone. The animals treated with vehicle and cuprizone had a 39% functional improvement at week 6, compared with week 3. Notably, there was not a statistically significant difference in function at week 6 between CNM-Au8-treated animals and the normal healthy control animals without demyelination, indicating that the functional recovery made the former and latter animals indistinguishable.
Therapy Promotes Bioenergetics Catalysis
CNM-Au8 may generate remyelination by more than one mechanism, said Mr. Hotchkin, and evidence indicates that the drug promotes bioenergetic catalysis that is important to the maturation of oligodendrocyte precursors. Published literature suggests an association between altered oligodendrocyte energy utilization and remyelination failure in the human brain. Other evidence suggests that CNM-Au8 may trigger oligodendrocytes’ remyelinating activity by improving energy sources such as adenosine triphosphate, lactate, and oxidized nicotinamide adenine dinucleotide (NAD+), said Mr. Hotchkin. For example, CNM-Au8 increased NAD+ levels in mouse hippocampal cultures by about 40%, relative to vehicle.
In response to questions about the catalytic mechanism, Mr. Hotchkin responded, “You can fill a car’s tank with gas, but if the electrical system is fouled, the car goes nowhere. CNM-Au8 is the catalytic engine driving bioenergetic improvements in the oligodendrocytes driving them to remyelinate.” Data suggest that CNM-Au8 may have applications in other neurodegenerative diseases, based on the bioenergetic failure hypothesis of neurodegeneration and aging, said Mr. Hotchkin.
Oligodendrocyte precursor cells are known to be present in the human brain in and around MS lesions even years after an MS attack. Thus, the animal studies may be relevant to clinical MS. As an oral agent, CNM-Au8 has the potential to be a major clinical advance if human trials show activity comparable to that in animal studies, said Mr. Hotchkin.
Initial phase I human clinical work and extensive animal toxicology has supported the safety of this agent. Trials in patients with MS that examine clinical end points are planned. “A phase II study in chronic optic neuropathy in relapsing-remitting MS patients will commence in 2018,” Glen Frick, MD, PhD, Chief Medical Officer of Clene Nanomedicine, told Neurology Reviews.
—Ted Bosworth
Suggested Reading
Rone
SAN DIEGO—A novel therapy designed to promote the maturation and activation of myelin-producing oligodendrocytes is moving to phase II clinical trials based on evidence of safety and efficacy in animal models and humans. The therapy, a suspension of clean-surfaced gold nanocrystals, may remyelinate multiple sclerosis (MS) lesions, according to research presented at the ACTRIMS 2018 Forum.
This agent, known as CNM-Au8, has been associated with improved behavioral function in animal models of MS, according to Michael Hotchkin, Head of Strategic Operations at Clene Nanomedicine in Salt Lake City. Clene Nanomedicine is developing CNM-Au8. Although the mechanism of action is “multifactorial,” the benefit has been linked to bioenergetic support for the differentiation and maturation of oligodendrocyte precursor cells, said Mr. Hotchkin.
In one behavioral study of fine motor kinetics in an experimental model of MS, mice treated with CNM-Au8 “were effectively indistinguishable” from animals with no demyelination, he said.
Treatment Improved Two Models of Demyelination
Following in vitro studies that suggested that CNM-Au8 can promote the differentiation of oligodendrocyte precursor cells into mature myelin-producing oligodendrocytes, a series of studies was conducted in lysolecithin and cuprizone animal models of MS demyelination.
The studies using the lysolecithin model included vehicle controls and compared CNM-Au8’s effect on remyelinated axons after inducing spinal demyelination with lysolecithin. In the cuprizone studies, the treatments were delivered before injury to test prophylactic efficacy and after injury to test treatment efficacy. Markers of remyelination, such as oligodendrocyte maturation, myelin basic protein expression, and axonal staining, were evaluated by immunohistochemistry and transmission electron microscopy in animals sacrificed at various times after injury.
CNM-Au8 produced “striking visible evidence of progressive increase in myelin,” according to Mr. Hotchkin. The treatment was associated with reductions in myelin sheath degeneration and demyelinated areas, relative to vehicle. In one analysis of the lysolecithin model, CNM-Au8 was associated with a 43% increase in myelinated axon count. Moreover, an increase in mature oligodendrocytes localized at the site of focal demyelination injury in the CNM-Au8-treated animals was consistent with stimulation of oligodendrocyte maturation, according to Mr. Hotchkin.
In both models, investigators found evidence of increased oligodendrocyte maturation and remyelination when CNM-Au8 was administered after injury, as well as when it was administered before injury. The results suggest that CNM-Au8 has important activity in the remyelination of demyelinated axons.
Researchers also conducted behavioral studies in the cuprizone model of MS. They tracked the animals’ movement with lasers and used computer software to analyze the movement. These studies included relevant controls and compared animals with no demyelination, vehicle-treated animals dosed with cuprizone, and CNM-Au8-treated animals similarly dosed with cuprizone, to determine whether delayed treatment following initial damage from the toxin would result in functional recovery in the animals.
The investigators observed protective effects of CNM-Au8 when the drug was administered in this treatment paradigm. Improvements in several behavioral end points when the drug was administered after the demyelinating insult “demonstrated that CNM-Au8 restored behavioral function following demyelination,” said Mr. Hotchkin.
Furthermore, in a behavioral study of fine motor kinetics, function improved by 78% at week 6, compared with week 3 (ie, immediately following the start of treatment) in the group treated with CMN-Au8 that was receiving cuprizone. The animals treated with vehicle and cuprizone had a 39% functional improvement at week 6, compared with week 3. Notably, there was not a statistically significant difference in function at week 6 between CNM-Au8-treated animals and the normal healthy control animals without demyelination, indicating that the functional recovery made the former and latter animals indistinguishable.
Therapy Promotes Bioenergetics Catalysis
CNM-Au8 may generate remyelination by more than one mechanism, said Mr. Hotchkin, and evidence indicates that the drug promotes bioenergetic catalysis that is important to the maturation of oligodendrocyte precursors. Published literature suggests an association between altered oligodendrocyte energy utilization and remyelination failure in the human brain. Other evidence suggests that CNM-Au8 may trigger oligodendrocytes’ remyelinating activity by improving energy sources such as adenosine triphosphate, lactate, and oxidized nicotinamide adenine dinucleotide (NAD+), said Mr. Hotchkin. For example, CNM-Au8 increased NAD+ levels in mouse hippocampal cultures by about 40%, relative to vehicle.
In response to questions about the catalytic mechanism, Mr. Hotchkin responded, “You can fill a car’s tank with gas, but if the electrical system is fouled, the car goes nowhere. CNM-Au8 is the catalytic engine driving bioenergetic improvements in the oligodendrocytes driving them to remyelinate.” Data suggest that CNM-Au8 may have applications in other neurodegenerative diseases, based on the bioenergetic failure hypothesis of neurodegeneration and aging, said Mr. Hotchkin.
Oligodendrocyte precursor cells are known to be present in the human brain in and around MS lesions even years after an MS attack. Thus, the animal studies may be relevant to clinical MS. As an oral agent, CNM-Au8 has the potential to be a major clinical advance if human trials show activity comparable to that in animal studies, said Mr. Hotchkin.
Initial phase I human clinical work and extensive animal toxicology has supported the safety of this agent. Trials in patients with MS that examine clinical end points are planned. “A phase II study in chronic optic neuropathy in relapsing-remitting MS patients will commence in 2018,” Glen Frick, MD, PhD, Chief Medical Officer of Clene Nanomedicine, told Neurology Reviews.
—Ted Bosworth
Suggested Reading
Rone
PPIs, H2RAs in infants raise later allergy risk
Children prescribed histamine2-receptor antagonists (H2RAs), proton pump inhibitors (PPIs), or antibiotics during the first 6 months of life may be at greater risk of developing allergic disease, research suggests.
A retrospective cohort study looked at the incidence of subsequent allergic disease in 792,130 children, 7.6% of whom were prescribed an H2RA, 1.7% were prescribed a PPI, and 16.6% were prescribed an antibiotic during the first 6 months of life.
Children who were prescribed a H2RA or a PPI had a greater than twofold higher incidence of food allergy (adjusted hazard ratios 2.18 and 2.59, respectively), reported Edward Mitre, MD, of the Uniformed Services University of the Health Sciences, Bethesda, Md., and his coauthors, reported in the April 2 online edition of JAMA Pediatrics.
In particular, the use of acid-suppressing medications was associated with a 2.4-fold increase in the risk of being diagnosed with cow’s milk allergy, while the risk of egg allergy was 74% higher in children prescribed an H2RA and 35% higher in children prescribed a PPI. In children prescribed an H2RA, the risk of peanut allergy was 21% higher, and in children prescribed a PPI, it was 27% higher.
There also was a dose-dependent interaction between the duration of medication and risk of food allergy. Children who were prescribed more than 60 days of PPIs had a 52% higher risk than did those who were prescribed 1-60 days, and a similar but slightly lower increased risk was seen in those prescribed more than 60 days of H2RAs (hazard ratio, 1.32).
Acid-suppressing medication use also was associated with an increased risk of nonfood allergies, in particular medication allergy (adjusted HR, 1.70 for H2RAs and 1.84 for PPIs), allergic rhinitis (aHR, 1.50 for H2RAs and 1.44 for PPIs), anaphylaxis (aHR, 1.51 for H2RAs and 1.45 for PPIs).
Infants prescribed acid-suppressing medication also showed higher rates of asthma, allergic conjunctivitis, and urticaria during childhood.
The use of antibiotics in the first 6 months of life was associated with a 14% higher incidence of food allergy but with a 24% higher risk of cow’s milk allergy and egg allergy. Children prescribed antibiotics also had a twofold greater risk of asthma, a 51% higher risk of anaphylaxis, 42% higher risk of allergic conjunctivitis, and a 34% higher risk of medication allergy.
“This study adds to the mounting evidence that agents that disrupt the normal intestinal microbiome during infancy may increase the development of allergic disease,” said Dr. Mitre and his coauthors. “Thus, this study provides further impetus that antibiotics and acid-suppressive medications should be used during infancy only in situations of clear clinical benefit.”
No funding source or conflicts of interest were declared.
SOURCE: Mitre E et al. JAMA Pediatrics. 2018 Apr 2. doi: 10.1001/jamapediatrics.2018.0315.
Children prescribed histamine2-receptor antagonists (H2RAs), proton pump inhibitors (PPIs), or antibiotics during the first 6 months of life may be at greater risk of developing allergic disease, research suggests.
A retrospective cohort study looked at the incidence of subsequent allergic disease in 792,130 children, 7.6% of whom were prescribed an H2RA, 1.7% were prescribed a PPI, and 16.6% were prescribed an antibiotic during the first 6 months of life.
Children who were prescribed a H2RA or a PPI had a greater than twofold higher incidence of food allergy (adjusted hazard ratios 2.18 and 2.59, respectively), reported Edward Mitre, MD, of the Uniformed Services University of the Health Sciences, Bethesda, Md., and his coauthors, reported in the April 2 online edition of JAMA Pediatrics.
In particular, the use of acid-suppressing medications was associated with a 2.4-fold increase in the risk of being diagnosed with cow’s milk allergy, while the risk of egg allergy was 74% higher in children prescribed an H2RA and 35% higher in children prescribed a PPI. In children prescribed an H2RA, the risk of peanut allergy was 21% higher, and in children prescribed a PPI, it was 27% higher.
There also was a dose-dependent interaction between the duration of medication and risk of food allergy. Children who were prescribed more than 60 days of PPIs had a 52% higher risk than did those who were prescribed 1-60 days, and a similar but slightly lower increased risk was seen in those prescribed more than 60 days of H2RAs (hazard ratio, 1.32).
Acid-suppressing medication use also was associated with an increased risk of nonfood allergies, in particular medication allergy (adjusted HR, 1.70 for H2RAs and 1.84 for PPIs), allergic rhinitis (aHR, 1.50 for H2RAs and 1.44 for PPIs), anaphylaxis (aHR, 1.51 for H2RAs and 1.45 for PPIs).
Infants prescribed acid-suppressing medication also showed higher rates of asthma, allergic conjunctivitis, and urticaria during childhood.
The use of antibiotics in the first 6 months of life was associated with a 14% higher incidence of food allergy but with a 24% higher risk of cow’s milk allergy and egg allergy. Children prescribed antibiotics also had a twofold greater risk of asthma, a 51% higher risk of anaphylaxis, 42% higher risk of allergic conjunctivitis, and a 34% higher risk of medication allergy.
“This study adds to the mounting evidence that agents that disrupt the normal intestinal microbiome during infancy may increase the development of allergic disease,” said Dr. Mitre and his coauthors. “Thus, this study provides further impetus that antibiotics and acid-suppressive medications should be used during infancy only in situations of clear clinical benefit.”
No funding source or conflicts of interest were declared.
SOURCE: Mitre E et al. JAMA Pediatrics. 2018 Apr 2. doi: 10.1001/jamapediatrics.2018.0315.
Children prescribed histamine2-receptor antagonists (H2RAs), proton pump inhibitors (PPIs), or antibiotics during the first 6 months of life may be at greater risk of developing allergic disease, research suggests.
A retrospective cohort study looked at the incidence of subsequent allergic disease in 792,130 children, 7.6% of whom were prescribed an H2RA, 1.7% were prescribed a PPI, and 16.6% were prescribed an antibiotic during the first 6 months of life.
Children who were prescribed a H2RA or a PPI had a greater than twofold higher incidence of food allergy (adjusted hazard ratios 2.18 and 2.59, respectively), reported Edward Mitre, MD, of the Uniformed Services University of the Health Sciences, Bethesda, Md., and his coauthors, reported in the April 2 online edition of JAMA Pediatrics.
In particular, the use of acid-suppressing medications was associated with a 2.4-fold increase in the risk of being diagnosed with cow’s milk allergy, while the risk of egg allergy was 74% higher in children prescribed an H2RA and 35% higher in children prescribed a PPI. In children prescribed an H2RA, the risk of peanut allergy was 21% higher, and in children prescribed a PPI, it was 27% higher.
There also was a dose-dependent interaction between the duration of medication and risk of food allergy. Children who were prescribed more than 60 days of PPIs had a 52% higher risk than did those who were prescribed 1-60 days, and a similar but slightly lower increased risk was seen in those prescribed more than 60 days of H2RAs (hazard ratio, 1.32).
Acid-suppressing medication use also was associated with an increased risk of nonfood allergies, in particular medication allergy (adjusted HR, 1.70 for H2RAs and 1.84 for PPIs), allergic rhinitis (aHR, 1.50 for H2RAs and 1.44 for PPIs), anaphylaxis (aHR, 1.51 for H2RAs and 1.45 for PPIs).
Infants prescribed acid-suppressing medication also showed higher rates of asthma, allergic conjunctivitis, and urticaria during childhood.
The use of antibiotics in the first 6 months of life was associated with a 14% higher incidence of food allergy but with a 24% higher risk of cow’s milk allergy and egg allergy. Children prescribed antibiotics also had a twofold greater risk of asthma, a 51% higher risk of anaphylaxis, 42% higher risk of allergic conjunctivitis, and a 34% higher risk of medication allergy.
“This study adds to the mounting evidence that agents that disrupt the normal intestinal microbiome during infancy may increase the development of allergic disease,” said Dr. Mitre and his coauthors. “Thus, this study provides further impetus that antibiotics and acid-suppressive medications should be used during infancy only in situations of clear clinical benefit.”
No funding source or conflicts of interest were declared.
SOURCE: Mitre E et al. JAMA Pediatrics. 2018 Apr 2. doi: 10.1001/jamapediatrics.2018.0315.
FROM JAMA PEDIATRICS
Key clinical point:
Major finding: Children prescribed acid-suppressing medications before 6 months had a greater than twofold higher incidence of food allergy.
Study details: A retrospective cohort study in 792,130 children between Oct. 1, 2001, and Sept. 30, 2013.
Disclosures: No funding source or conflicts of interest were declared.
Source: Mitre E et al. JAMA Pediatrics. 2018 Apr 2. doi: 10.1001/jamapediatrics.2018.0315.
Neurology faculty gender gap confirmed, but explanations remain scant
Despite a wide gap between male and female neurologists, both in terms of academic faculty rank and number of publications, there may be some good news for women in this medical field.
A recent study of the 1,712 academic neurologists across 29 top-ranked neurology programs revealed that 1,184 (69%) were men and 528 (31%) were women, and men outnumbered women in all academic faculty ranks with a gap that increased as the rank advanced. For example, at the rank of instructor/lecturer, the male-to-female ratio was 59% to 41%. The gap only widens from there: assistant professor (57% male), associate professor (70%), and professor (86%).
Additionally, unadjusted analyses showed that men had significantly more publications listed in PubMed than women at the positions of assistant professor, associate professor, and full professor.
The investigators compiled their list of programs and faculty members by combining the top 20 programs listed on either the 2016 or 2017 Doximity Residency Navigator tool with the top 20 programs listed in the U.S. News and World Report ranking of Best Graduate Schools and a search of the programs’ departmental websites between December 1, 2015, and April 30, 2016.
The study was not able to account for many potential explanations for the gender gap, suggesting that the findings may not necessarily be indicative of bad news.
The results “can be viewed as either disappointing or encouraging, depending on whether they reflect persistent barriers to women trying to achieve similar goals as men, or whether they reflect a system that supports women with different goals altogether,” Dr. McDermott and her colleagues wrote.
For example, the authors note that there are a variety of explanations for the gender gap in both rank and publication, including asymmetric home or childcare responsibilities, cultural stereotypes, professional isolation, and different career motivations, though the study was not able to account for those variables.
“Compared with men, women may be more likely to be recruited for employment positions that emphasize teaching and mentoring rather than research, or women may be more inclined to choose such positions,” the authors noted, adding that academic institutions are moving beyond traditional measures of academic productivity (publication rate, publication impact, and grant support) to recognize other factors, such as the quality and quantity of teaching, the development of educational resources, and administrative effectiveness.
If the numbers reflect persistent barriers to women, “it will be important to develop programs to heighten awareness of diversity in academic neurology,” the authors stated. On the flip side, if the numbers reflect a system that is supporting different goals, “academic neurology departments should be encouraged to foster a variety of career paths and expectations for all faculty.”
The authors reported no conflicts of interest. The study was funded by the Jerry Isler Neuromuscular Fund.
SOURCE: McDermott M et al. JAMA Neurol. 2018 Apr 2. doi: 10.1001/jamaneurol.2018.0275.
While there may be positive ways to interpret the data, challenges remain for women who want to pursue a career path that features more traditional ways of being recognized. These include ensuring that career paths that require protected time for research and depend on publication and grant support are carefully monitored; and determining that barriers do not hinder women from advancing.
Training programs also must be revisited to ensure that parity across the wider spectrum of careers in neurology is maintained and opportunities continue to exist for both men and women as the specialty continues to grow.
Frances Jensen, MD , is with the University of Pennsylvania, Philadelphia. Her remarks are derived from an editorial accompanying the report by Dr. McDermott and colleagues (JAMA Neurol. 2018 Apr 2. doi: 10.1001/jamaneurol.2018.0300). She reported no disclosures.
While there may be positive ways to interpret the data, challenges remain for women who want to pursue a career path that features more traditional ways of being recognized. These include ensuring that career paths that require protected time for research and depend on publication and grant support are carefully monitored; and determining that barriers do not hinder women from advancing.
Training programs also must be revisited to ensure that parity across the wider spectrum of careers in neurology is maintained and opportunities continue to exist for both men and women as the specialty continues to grow.
Frances Jensen, MD , is with the University of Pennsylvania, Philadelphia. Her remarks are derived from an editorial accompanying the report by Dr. McDermott and colleagues (JAMA Neurol. 2018 Apr 2. doi: 10.1001/jamaneurol.2018.0300). She reported no disclosures.
While there may be positive ways to interpret the data, challenges remain for women who want to pursue a career path that features more traditional ways of being recognized. These include ensuring that career paths that require protected time for research and depend on publication and grant support are carefully monitored; and determining that barriers do not hinder women from advancing.
Training programs also must be revisited to ensure that parity across the wider spectrum of careers in neurology is maintained and opportunities continue to exist for both men and women as the specialty continues to grow.
Frances Jensen, MD , is with the University of Pennsylvania, Philadelphia. Her remarks are derived from an editorial accompanying the report by Dr. McDermott and colleagues (JAMA Neurol. 2018 Apr 2. doi: 10.1001/jamaneurol.2018.0300). She reported no disclosures.
Despite a wide gap between male and female neurologists, both in terms of academic faculty rank and number of publications, there may be some good news for women in this medical field.
A recent study of the 1,712 academic neurologists across 29 top-ranked neurology programs revealed that 1,184 (69%) were men and 528 (31%) were women, and men outnumbered women in all academic faculty ranks with a gap that increased as the rank advanced. For example, at the rank of instructor/lecturer, the male-to-female ratio was 59% to 41%. The gap only widens from there: assistant professor (57% male), associate professor (70%), and professor (86%).
Additionally, unadjusted analyses showed that men had significantly more publications listed in PubMed than women at the positions of assistant professor, associate professor, and full professor.
The investigators compiled their list of programs and faculty members by combining the top 20 programs listed on either the 2016 or 2017 Doximity Residency Navigator tool with the top 20 programs listed in the U.S. News and World Report ranking of Best Graduate Schools and a search of the programs’ departmental websites between December 1, 2015, and April 30, 2016.
The study was not able to account for many potential explanations for the gender gap, suggesting that the findings may not necessarily be indicative of bad news.
The results “can be viewed as either disappointing or encouraging, depending on whether they reflect persistent barriers to women trying to achieve similar goals as men, or whether they reflect a system that supports women with different goals altogether,” Dr. McDermott and her colleagues wrote.
For example, the authors note that there are a variety of explanations for the gender gap in both rank and publication, including asymmetric home or childcare responsibilities, cultural stereotypes, professional isolation, and different career motivations, though the study was not able to account for those variables.
“Compared with men, women may be more likely to be recruited for employment positions that emphasize teaching and mentoring rather than research, or women may be more inclined to choose such positions,” the authors noted, adding that academic institutions are moving beyond traditional measures of academic productivity (publication rate, publication impact, and grant support) to recognize other factors, such as the quality and quantity of teaching, the development of educational resources, and administrative effectiveness.
If the numbers reflect persistent barriers to women, “it will be important to develop programs to heighten awareness of diversity in academic neurology,” the authors stated. On the flip side, if the numbers reflect a system that is supporting different goals, “academic neurology departments should be encouraged to foster a variety of career paths and expectations for all faculty.”
The authors reported no conflicts of interest. The study was funded by the Jerry Isler Neuromuscular Fund.
SOURCE: McDermott M et al. JAMA Neurol. 2018 Apr 2. doi: 10.1001/jamaneurol.2018.0275.
Despite a wide gap between male and female neurologists, both in terms of academic faculty rank and number of publications, there may be some good news for women in this medical field.
A recent study of the 1,712 academic neurologists across 29 top-ranked neurology programs revealed that 1,184 (69%) were men and 528 (31%) were women, and men outnumbered women in all academic faculty ranks with a gap that increased as the rank advanced. For example, at the rank of instructor/lecturer, the male-to-female ratio was 59% to 41%. The gap only widens from there: assistant professor (57% male), associate professor (70%), and professor (86%).
Additionally, unadjusted analyses showed that men had significantly more publications listed in PubMed than women at the positions of assistant professor, associate professor, and full professor.
The investigators compiled their list of programs and faculty members by combining the top 20 programs listed on either the 2016 or 2017 Doximity Residency Navigator tool with the top 20 programs listed in the U.S. News and World Report ranking of Best Graduate Schools and a search of the programs’ departmental websites between December 1, 2015, and April 30, 2016.
The study was not able to account for many potential explanations for the gender gap, suggesting that the findings may not necessarily be indicative of bad news.
The results “can be viewed as either disappointing or encouraging, depending on whether they reflect persistent barriers to women trying to achieve similar goals as men, or whether they reflect a system that supports women with different goals altogether,” Dr. McDermott and her colleagues wrote.
For example, the authors note that there are a variety of explanations for the gender gap in both rank and publication, including asymmetric home or childcare responsibilities, cultural stereotypes, professional isolation, and different career motivations, though the study was not able to account for those variables.
“Compared with men, women may be more likely to be recruited for employment positions that emphasize teaching and mentoring rather than research, or women may be more inclined to choose such positions,” the authors noted, adding that academic institutions are moving beyond traditional measures of academic productivity (publication rate, publication impact, and grant support) to recognize other factors, such as the quality and quantity of teaching, the development of educational resources, and administrative effectiveness.
If the numbers reflect persistent barriers to women, “it will be important to develop programs to heighten awareness of diversity in academic neurology,” the authors stated. On the flip side, if the numbers reflect a system that is supporting different goals, “academic neurology departments should be encouraged to foster a variety of career paths and expectations for all faculty.”
The authors reported no conflicts of interest. The study was funded by the Jerry Isler Neuromuscular Fund.
SOURCE: McDermott M et al. JAMA Neurol. 2018 Apr 2. doi: 10.1001/jamaneurol.2018.0275.
FROM JAMA NEUROLOGY
Major finding: Male-to-female ratio widens as rank advances, from 59% male at instructor/lecturer to 86% male at full professor.
Study details: An examination of 1,712 academic neurologists across 29 top-ranked academic institutions.
Disclosures: The study authors reported no conflicts of interest. The study was funded by the Jerry Isler Neuromuscular Fund.
Source: McDermott M et al. JAMA Neurol. 2018 Apr 2. doi: 10.1001/jamaneurol.2018.0275.
Pot legalization tied to drop in opioid prescribing rates
Laws covering medical or recreational use of marijuana are associated with reduced rates of opioid prescribing among federal health care program enrollees, results of two recently published investigations show.
In one study, researchers investigated whether medical cannabis access affected opioid prescribing in Medicare Part D, the federal program that subsidizes cost of prescription drugs and drug insurance premiums.
“Medical cannabis policies may be one mechanism that can encourage lower prescription opioid use and serve as a harm abatement tool in the opioid crisis,” Ms. Bradford and her coauthors wrote in JAMA Internal Medicine.
Medical marijuana laws were associated with a decrease of 2.11 million daily opioid doses yearly from an average of 23.08 million doses yearly in the Medicare Part D population, according to results of the longitudinal analysis daily opioids doses filled in Medicare Part D from 2010 through 2015.
In a second study, medical marijuana laws were associated with lower opioid prescribing rates among Medicaid enrollees.
That finding was consistent with earlier studies looking more broadly at pain prescriptions covered by Medicaid that also showed a reduction, researchers Hefei Wen, PhD, and Jason M. Hockenberry, PhD, wrote in their JAMA Internal Medicine article.
However, adult-use marijuana laws were associated with “even-lower” opioid prescribing rates, something that had not been investigated previously, according to Dr. Wen, who is with the University of Kentucky, Lexington, and Dr. Hockenberry of Emory University, Atlanta.
“Medical and adult-use marijuana laws have the potential to lower opioid prescribing for Medicaid enrollees, a high-risk population for chronic pain, opioid use disorder, and opioid overdose,” Dr. Wen and Dr. Hockenberry wrote in their report on the study, a cross-sectional analysis including all Medicaid fee-for-service and managed care enrollees during 2011-2016.
The rate of opioid prescribing in the study was –5.88% lower (95% confidence interval, –11.55% to approximately –0.21%) in association with medical marijuana laws, and –6.38% lower (95% CI, –12.20% to approximately –0.56%) for adult-use laws, they reported.
Based on those findings, policy discussions about the opioid epidemic should include the potential for liberalization of marijuana policies to reduce prescription opioid use and consequences in Medicaid enrollees, Dr. Wen and Dr. Hockenberry concluded.
However, legal marijuana alone won’t solve the opioid epidemic, they cautioned.
“As with other policies evaluated in the previous literature, marijuana liberalization is but one potential aspect of a comprehensive package to tackle the epidemic,” they said in the article.
None of the study authors reported conflicts of interest.
SOURCES: Bradford AC et al. JAMA Intern Med. 2018 Apr 2. doi: 10.1001/jamainternmed.2018.0266; Wen H, Hockenberry JM. JAMA Intern Med. 2018 Apr 2. doi: 10.1001/jamainternmed.2018.1007.
Results of these two investigations suggest that the legalization of marijuana may help combat the opioid crisis, but more rigorous investigations are needed, according to Kevin P. Hill, MD, and Andrew J. Saxon, MD.
The new studies show an association between state marijuana laws and fewer opioid prescriptions in Medicare and Medicaid populations.
Those findings do support previous investigations of administrative data sets suggesting that cannabis legalization policies are associated with reductions in opioid use and mortality, Dr. Hill and Dr. Saxon said in an editorial.
However, not all studies suggest that cannabis replaces opioid use, according to the authors, who cited a study suggesting an association between illicit cannabis use and subsequent cannabis use.
“The association between illicit cannabis use and opioid use may be different than the association of legalized cannabis use and opioids,” the editorial authors wrote. “Nevertheless, the findings demonstrating that cannabis use is associated with initiation of or increase in opioid use underscores the fact that rigorous scientific studies are needed.”
Those studies should focus not only analysis of policies on legal medical and recreational cannabis but also on clinical trials of cannabis and cannabinoids for chronic pain and other conditions where opioids are used, they added.
One limitation of the studies is that , according to the authors.
Nevertheless, the authors wrote, a decrease tied to legal marijuana availability would “dovetail” with preclinical evidence that cannabinoid and opioid receptor systems mediate signaling pathways involved in tolerance, dependence, and addiction.
“These concepts support anecdotal evidence from patients who describe a decreased need for opioids to treat chronic pain after initiation of medical cannabis pharmacotherapy,” the authors wrote.
Kevin P. Hill, MD, is with the division of addiction psychiatry at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston. Andrew J. Saxon, MD, is with the Center of Excellence in Substance Abuse Treatment and Education at the VA Puget Sound Healthcare System, and the department of psychiatry and behavioral sciences at University of Washington, both in Seattle. These comments are derived from their editorial (JAMA Intern Med. 2018 Apr 2. doi: 10.1001/jamainternmed.2018.0254). The authors reported no conflicts of interest.
Results of these two investigations suggest that the legalization of marijuana may help combat the opioid crisis, but more rigorous investigations are needed, according to Kevin P. Hill, MD, and Andrew J. Saxon, MD.
The new studies show an association between state marijuana laws and fewer opioid prescriptions in Medicare and Medicaid populations.
Those findings do support previous investigations of administrative data sets suggesting that cannabis legalization policies are associated with reductions in opioid use and mortality, Dr. Hill and Dr. Saxon said in an editorial.
However, not all studies suggest that cannabis replaces opioid use, according to the authors, who cited a study suggesting an association between illicit cannabis use and subsequent cannabis use.
“The association between illicit cannabis use and opioid use may be different than the association of legalized cannabis use and opioids,” the editorial authors wrote. “Nevertheless, the findings demonstrating that cannabis use is associated with initiation of or increase in opioid use underscores the fact that rigorous scientific studies are needed.”
Those studies should focus not only analysis of policies on legal medical and recreational cannabis but also on clinical trials of cannabis and cannabinoids for chronic pain and other conditions where opioids are used, they added.
One limitation of the studies is that , according to the authors.
Nevertheless, the authors wrote, a decrease tied to legal marijuana availability would “dovetail” with preclinical evidence that cannabinoid and opioid receptor systems mediate signaling pathways involved in tolerance, dependence, and addiction.
“These concepts support anecdotal evidence from patients who describe a decreased need for opioids to treat chronic pain after initiation of medical cannabis pharmacotherapy,” the authors wrote.
Kevin P. Hill, MD, is with the division of addiction psychiatry at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston. Andrew J. Saxon, MD, is with the Center of Excellence in Substance Abuse Treatment and Education at the VA Puget Sound Healthcare System, and the department of psychiatry and behavioral sciences at University of Washington, both in Seattle. These comments are derived from their editorial (JAMA Intern Med. 2018 Apr 2. doi: 10.1001/jamainternmed.2018.0254). The authors reported no conflicts of interest.
Results of these two investigations suggest that the legalization of marijuana may help combat the opioid crisis, but more rigorous investigations are needed, according to Kevin P. Hill, MD, and Andrew J. Saxon, MD.
The new studies show an association between state marijuana laws and fewer opioid prescriptions in Medicare and Medicaid populations.
Those findings do support previous investigations of administrative data sets suggesting that cannabis legalization policies are associated with reductions in opioid use and mortality, Dr. Hill and Dr. Saxon said in an editorial.
However, not all studies suggest that cannabis replaces opioid use, according to the authors, who cited a study suggesting an association between illicit cannabis use and subsequent cannabis use.
“The association between illicit cannabis use and opioid use may be different than the association of legalized cannabis use and opioids,” the editorial authors wrote. “Nevertheless, the findings demonstrating that cannabis use is associated with initiation of or increase in opioid use underscores the fact that rigorous scientific studies are needed.”
Those studies should focus not only analysis of policies on legal medical and recreational cannabis but also on clinical trials of cannabis and cannabinoids for chronic pain and other conditions where opioids are used, they added.
One limitation of the studies is that , according to the authors.
Nevertheless, the authors wrote, a decrease tied to legal marijuana availability would “dovetail” with preclinical evidence that cannabinoid and opioid receptor systems mediate signaling pathways involved in tolerance, dependence, and addiction.
“These concepts support anecdotal evidence from patients who describe a decreased need for opioids to treat chronic pain after initiation of medical cannabis pharmacotherapy,” the authors wrote.
Kevin P. Hill, MD, is with the division of addiction psychiatry at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston. Andrew J. Saxon, MD, is with the Center of Excellence in Substance Abuse Treatment and Education at the VA Puget Sound Healthcare System, and the department of psychiatry and behavioral sciences at University of Washington, both in Seattle. These comments are derived from their editorial (JAMA Intern Med. 2018 Apr 2. doi: 10.1001/jamainternmed.2018.0254). The authors reported no conflicts of interest.
Laws covering medical or recreational use of marijuana are associated with reduced rates of opioid prescribing among federal health care program enrollees, results of two recently published investigations show.
In one study, researchers investigated whether medical cannabis access affected opioid prescribing in Medicare Part D, the federal program that subsidizes cost of prescription drugs and drug insurance premiums.
“Medical cannabis policies may be one mechanism that can encourage lower prescription opioid use and serve as a harm abatement tool in the opioid crisis,” Ms. Bradford and her coauthors wrote in JAMA Internal Medicine.
Medical marijuana laws were associated with a decrease of 2.11 million daily opioid doses yearly from an average of 23.08 million doses yearly in the Medicare Part D population, according to results of the longitudinal analysis daily opioids doses filled in Medicare Part D from 2010 through 2015.
In a second study, medical marijuana laws were associated with lower opioid prescribing rates among Medicaid enrollees.
That finding was consistent with earlier studies looking more broadly at pain prescriptions covered by Medicaid that also showed a reduction, researchers Hefei Wen, PhD, and Jason M. Hockenberry, PhD, wrote in their JAMA Internal Medicine article.
However, adult-use marijuana laws were associated with “even-lower” opioid prescribing rates, something that had not been investigated previously, according to Dr. Wen, who is with the University of Kentucky, Lexington, and Dr. Hockenberry of Emory University, Atlanta.
“Medical and adult-use marijuana laws have the potential to lower opioid prescribing for Medicaid enrollees, a high-risk population for chronic pain, opioid use disorder, and opioid overdose,” Dr. Wen and Dr. Hockenberry wrote in their report on the study, a cross-sectional analysis including all Medicaid fee-for-service and managed care enrollees during 2011-2016.
The rate of opioid prescribing in the study was –5.88% lower (95% confidence interval, –11.55% to approximately –0.21%) in association with medical marijuana laws, and –6.38% lower (95% CI, –12.20% to approximately –0.56%) for adult-use laws, they reported.
Based on those findings, policy discussions about the opioid epidemic should include the potential for liberalization of marijuana policies to reduce prescription opioid use and consequences in Medicaid enrollees, Dr. Wen and Dr. Hockenberry concluded.
However, legal marijuana alone won’t solve the opioid epidemic, they cautioned.
“As with other policies evaluated in the previous literature, marijuana liberalization is but one potential aspect of a comprehensive package to tackle the epidemic,” they said in the article.
None of the study authors reported conflicts of interest.
SOURCES: Bradford AC et al. JAMA Intern Med. 2018 Apr 2. doi: 10.1001/jamainternmed.2018.0266; Wen H, Hockenberry JM. JAMA Intern Med. 2018 Apr 2. doi: 10.1001/jamainternmed.2018.1007.
Laws covering medical or recreational use of marijuana are associated with reduced rates of opioid prescribing among federal health care program enrollees, results of two recently published investigations show.
In one study, researchers investigated whether medical cannabis access affected opioid prescribing in Medicare Part D, the federal program that subsidizes cost of prescription drugs and drug insurance premiums.
“Medical cannabis policies may be one mechanism that can encourage lower prescription opioid use and serve as a harm abatement tool in the opioid crisis,” Ms. Bradford and her coauthors wrote in JAMA Internal Medicine.
Medical marijuana laws were associated with a decrease of 2.11 million daily opioid doses yearly from an average of 23.08 million doses yearly in the Medicare Part D population, according to results of the longitudinal analysis daily opioids doses filled in Medicare Part D from 2010 through 2015.
In a second study, medical marijuana laws were associated with lower opioid prescribing rates among Medicaid enrollees.
That finding was consistent with earlier studies looking more broadly at pain prescriptions covered by Medicaid that also showed a reduction, researchers Hefei Wen, PhD, and Jason M. Hockenberry, PhD, wrote in their JAMA Internal Medicine article.
However, adult-use marijuana laws were associated with “even-lower” opioid prescribing rates, something that had not been investigated previously, according to Dr. Wen, who is with the University of Kentucky, Lexington, and Dr. Hockenberry of Emory University, Atlanta.
“Medical and adult-use marijuana laws have the potential to lower opioid prescribing for Medicaid enrollees, a high-risk population for chronic pain, opioid use disorder, and opioid overdose,” Dr. Wen and Dr. Hockenberry wrote in their report on the study, a cross-sectional analysis including all Medicaid fee-for-service and managed care enrollees during 2011-2016.
The rate of opioid prescribing in the study was –5.88% lower (95% confidence interval, –11.55% to approximately –0.21%) in association with medical marijuana laws, and –6.38% lower (95% CI, –12.20% to approximately –0.56%) for adult-use laws, they reported.
Based on those findings, policy discussions about the opioid epidemic should include the potential for liberalization of marijuana policies to reduce prescription opioid use and consequences in Medicaid enrollees, Dr. Wen and Dr. Hockenberry concluded.
However, legal marijuana alone won’t solve the opioid epidemic, they cautioned.
“As with other policies evaluated in the previous literature, marijuana liberalization is but one potential aspect of a comprehensive package to tackle the epidemic,” they said in the article.
None of the study authors reported conflicts of interest.
SOURCES: Bradford AC et al. JAMA Intern Med. 2018 Apr 2. doi: 10.1001/jamainternmed.2018.0266; Wen H, Hockenberry JM. JAMA Intern Med. 2018 Apr 2. doi: 10.1001/jamainternmed.2018.1007.
FROM JAMA INTERNAL MEDICINE
Key clinical point: State laws governing medical and adult use of marijuana may lower prescription opioid use in Medicaid enrollees – a population at high risk for chronic pain and opioid overdose – and in the Medicare Part D population.
Major finding: Medical and adult-use marijuana laws were associated with lower opioid prescribing rates in Medicaid prescription data (–5.88% and –6.38%, respectively). Medical marijuana laws were associated with a decrease of 2.11 million daily doses yearly from an average of 23.08 million doses yearly in the Medicare Part D population.
Study details: A cross-sectional, quasiexperimental study of opioid prescribing trends between 2011 and 2016 for all Medicaid fee-for-service and managed care enrollees, and a longitudinal analysis daily opioids doses filled in Medicare Part D from 2010 through 2015.
Disclosures: None of the study authors reported conflicts of interest.
Sources: Bradford AC et al. JAMA Intern Med. 2018 Apr 2. doi:10.1001/jamainternmed.2018.0266; Wen H, Hockenberry JM. JAMA Intern Med. 2018 Apr 2. doi:10.1001/jamainternmed.2018.1007.
Alopecia areata has female predominance, more severe types common in boys
reported Iris Wohlmuth-Wieser, MD, of the department of dermatology, MD Anderson Cancer Center, Houston, and her associates, who conducted a large review of U.S. registry data.
Although it is the third most common dermatosis in children, there are not much data on AA in children, so the researchers used information from the National Alopecia Areata Registry, which was established in 2000. First, interested patients and parents were contacted and asked to fill out a web-based screening questionnaire. In the second phase, they were asked to fill out a more extensive survey and visit one of five U.S. sites for a clinical exam by a dermatologist.
Of the 2,218 children and teens who completed the initial questionnaire, the mean age at the time of the survey was 10 years, and their mean age of onset of AA was 6 years. The female to male ratio was 1.5:1; boys were significantly more likely to have severe types of AA (P = .009). Most patients (70%) were white, followed by mixed ethnicity (11%), Hispanic (3%), and then other ethnicities. About 3% of patients said they had a sibling with AA, 14% said that another first-degree relative had AA, and 8% said that at least three first-degree relatives had AA.
In terms of the degree of hair loss, 45% lost all scalp hair, 31% lost all body hair, and 14% lost all nails.
Concomitant diseases were reported by 47% of the responders, with atopic dermatitis, asthma, hay fever, and allergies the most common.
Of the 643 children and teens who completed a more detailed questionnaire and underwent clinical examination, 63% were female; 26% had at least one relative with AA and 8% had at least three first-degree relatives with AA. Almost 4% had congenital AA.
At the physical exam, there were data on the amount of hair loss in 617 children: Of these children, 37% had lost all scalp hair and 19% had lost up to three-quarters of their scalp hair. In 618 children (in whom information on body hair loss was obtained at the physical exam), 72% lost all or some of their body hair. Information on nails was available in 609 children; in this group, 44% had some nail involvement. More detailed information was available in 290 children; in this group, findings included pitting in 86%, dystrophy in 10%, onycholysis in 2%, ridging in 1%, and onychomycosis in 1%.
Commenting on the 25 children who presented with congenital AA, the authors wrote that this is “an extremely rare and infrequently reported form of AA.
“This is an interesting and important finding, because AA has traditionally been described as an acquired disease,” they added.
In their cohort overall, 25% had a family history of AA, with 8% having more than three first-degree relatives with AA. The researchers said that the percentage of children with AA and a positive family history ranges from 8% to 52% in the literature.
“The predominant presentation of AA types in our cohort (61.4%) was severe hair loss (76%-100% of scalp hair loss). This is comparable with a European study reporting a prevalence of 65%. Other studies on childhood AA conducted in Asian and Arab populations observed mainly mild cases,” they wrote.
Nail involvement, often reported with AA, was evident in 39% of patients who completed the questionnaire online and in 44% on physical exam. This agreed with the 26%-40% involvement reported in the literature.
There were no conflicts of interest or funding information reported.
SOURCE: Wohlmuth-Wieser I et al. Pediatr Dermatol. 2018 Jan 15. doi: 10.1111/pde.13387.
reported Iris Wohlmuth-Wieser, MD, of the department of dermatology, MD Anderson Cancer Center, Houston, and her associates, who conducted a large review of U.S. registry data.
Although it is the third most common dermatosis in children, there are not much data on AA in children, so the researchers used information from the National Alopecia Areata Registry, which was established in 2000. First, interested patients and parents were contacted and asked to fill out a web-based screening questionnaire. In the second phase, they were asked to fill out a more extensive survey and visit one of five U.S. sites for a clinical exam by a dermatologist.
Of the 2,218 children and teens who completed the initial questionnaire, the mean age at the time of the survey was 10 years, and their mean age of onset of AA was 6 years. The female to male ratio was 1.5:1; boys were significantly more likely to have severe types of AA (P = .009). Most patients (70%) were white, followed by mixed ethnicity (11%), Hispanic (3%), and then other ethnicities. About 3% of patients said they had a sibling with AA, 14% said that another first-degree relative had AA, and 8% said that at least three first-degree relatives had AA.
In terms of the degree of hair loss, 45% lost all scalp hair, 31% lost all body hair, and 14% lost all nails.
Concomitant diseases were reported by 47% of the responders, with atopic dermatitis, asthma, hay fever, and allergies the most common.
Of the 643 children and teens who completed a more detailed questionnaire and underwent clinical examination, 63% were female; 26% had at least one relative with AA and 8% had at least three first-degree relatives with AA. Almost 4% had congenital AA.
At the physical exam, there were data on the amount of hair loss in 617 children: Of these children, 37% had lost all scalp hair and 19% had lost up to three-quarters of their scalp hair. In 618 children (in whom information on body hair loss was obtained at the physical exam), 72% lost all or some of their body hair. Information on nails was available in 609 children; in this group, 44% had some nail involvement. More detailed information was available in 290 children; in this group, findings included pitting in 86%, dystrophy in 10%, onycholysis in 2%, ridging in 1%, and onychomycosis in 1%.
Commenting on the 25 children who presented with congenital AA, the authors wrote that this is “an extremely rare and infrequently reported form of AA.
“This is an interesting and important finding, because AA has traditionally been described as an acquired disease,” they added.
In their cohort overall, 25% had a family history of AA, with 8% having more than three first-degree relatives with AA. The researchers said that the percentage of children with AA and a positive family history ranges from 8% to 52% in the literature.
“The predominant presentation of AA types in our cohort (61.4%) was severe hair loss (76%-100% of scalp hair loss). This is comparable with a European study reporting a prevalence of 65%. Other studies on childhood AA conducted in Asian and Arab populations observed mainly mild cases,” they wrote.
Nail involvement, often reported with AA, was evident in 39% of patients who completed the questionnaire online and in 44% on physical exam. This agreed with the 26%-40% involvement reported in the literature.
There were no conflicts of interest or funding information reported.
SOURCE: Wohlmuth-Wieser I et al. Pediatr Dermatol. 2018 Jan 15. doi: 10.1111/pde.13387.
reported Iris Wohlmuth-Wieser, MD, of the department of dermatology, MD Anderson Cancer Center, Houston, and her associates, who conducted a large review of U.S. registry data.
Although it is the third most common dermatosis in children, there are not much data on AA in children, so the researchers used information from the National Alopecia Areata Registry, which was established in 2000. First, interested patients and parents were contacted and asked to fill out a web-based screening questionnaire. In the second phase, they were asked to fill out a more extensive survey and visit one of five U.S. sites for a clinical exam by a dermatologist.
Of the 2,218 children and teens who completed the initial questionnaire, the mean age at the time of the survey was 10 years, and their mean age of onset of AA was 6 years. The female to male ratio was 1.5:1; boys were significantly more likely to have severe types of AA (P = .009). Most patients (70%) were white, followed by mixed ethnicity (11%), Hispanic (3%), and then other ethnicities. About 3% of patients said they had a sibling with AA, 14% said that another first-degree relative had AA, and 8% said that at least three first-degree relatives had AA.
In terms of the degree of hair loss, 45% lost all scalp hair, 31% lost all body hair, and 14% lost all nails.
Concomitant diseases were reported by 47% of the responders, with atopic dermatitis, asthma, hay fever, and allergies the most common.
Of the 643 children and teens who completed a more detailed questionnaire and underwent clinical examination, 63% were female; 26% had at least one relative with AA and 8% had at least three first-degree relatives with AA. Almost 4% had congenital AA.
At the physical exam, there were data on the amount of hair loss in 617 children: Of these children, 37% had lost all scalp hair and 19% had lost up to three-quarters of their scalp hair. In 618 children (in whom information on body hair loss was obtained at the physical exam), 72% lost all or some of their body hair. Information on nails was available in 609 children; in this group, 44% had some nail involvement. More detailed information was available in 290 children; in this group, findings included pitting in 86%, dystrophy in 10%, onycholysis in 2%, ridging in 1%, and onychomycosis in 1%.
Commenting on the 25 children who presented with congenital AA, the authors wrote that this is “an extremely rare and infrequently reported form of AA.
“This is an interesting and important finding, because AA has traditionally been described as an acquired disease,” they added.
In their cohort overall, 25% had a family history of AA, with 8% having more than three first-degree relatives with AA. The researchers said that the percentage of children with AA and a positive family history ranges from 8% to 52% in the literature.
“The predominant presentation of AA types in our cohort (61.4%) was severe hair loss (76%-100% of scalp hair loss). This is comparable with a European study reporting a prevalence of 65%. Other studies on childhood AA conducted in Asian and Arab populations observed mainly mild cases,” they wrote.
Nail involvement, often reported with AA, was evident in 39% of patients who completed the questionnaire online and in 44% on physical exam. This agreed with the 26%-40% involvement reported in the literature.
There were no conflicts of interest or funding information reported.
SOURCE: Wohlmuth-Wieser I et al. Pediatr Dermatol. 2018 Jan 15. doi: 10.1111/pde.13387.
FROM PEDIATRIC DERMATOLOGY
Key clinical point: The predominant presentation is total hair loss and nail involvement is common.
Major finding: The female to male ratio was 1.5:1; the boys were significantly more likely to have severe types of AA (P = .009).
Study details: National Alopecia Areata Registry registrants under age 18 years were asked to complete a survey.
Disclosures: There were no conflicts of interest or funding information reported.
Source: Wohlmuth-Wieser I et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13387.