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Subcutaneous buprenorpine rivals sublingual for opioid use disorder
Long-acting subcutaneous doses of buprenorphine depot are an effective treatment option for opioid use disorder, results of a phase 3 study of 428 adults show.
Sublingual buprenorphine hydrochloride is a standard treatment for opioid use disorder (OUD), but challenges include poor medication adherence, potential for abuse, and accidental exposure to children, Michelle R. Lofwall, MD, of the University of Kentucky, Lexington, and her colleagues reported.
In a study published in JAMA Internal Medicine, Dr. Lofwall and her associates randomized treatment-seeking adults with moderate to severe opioid use disorder to subcutaneous buprenorphine depot weekly for 12 weeks followed by monthly for 12 weeks, or daily sublingual buprenorphine with naloxone for 24 weeks.
The proportion of opioid-negative urine samples was 35% in the subcutaneous buprenorphine depot group (1,347 of 3,834 samples) vs. 29% in the sublingual buprenorphine with naloxone group (1,099 of 3,870 samples) for a statistically significant difference of 6.7%. Urine samples were collected weekly for the first 12 weeks, and then at weeks 16, 20, and 24, reported Dr. Lofall, a psychiatrist and addiction medicine specialist, and her associates.
Patients in the sublingual buprenorphine with naloxone group received 4 mg of sublingual buprenorphine hydrochloride and naloxone hydrochloride at the start of the study, titrated to 16 mg/day. The average treatment dosage was 18-20 mg/day for sublingual buprenorphine with naloxone patients.
Patients in the subcutaneous buprenorphine depot group received 16 mg of subcutaneous buprenorphine in a weekly injection at the start of the study; monthly subcutaneous buprenorphine depot injections were 64, 96, 128, or 160 mg between weeks 12 and 24.
After initial titration, doses were flexible based on clinical judgment, the researchers noted, similar to the way in which patients would be managed in a clinical setting.
Adverse events were similar between the groups. The most common were injection-site pain, headache, constipation, nausea, and injection-site pruritus and erythema. Injection-site reactions were mild to moderate.
As a secondary outcome, the cumulative distribution function (CDF) in the subcutaneous buprenorphine depot group was statistically superior to the CDF found in the sublingual buprenorphine with naloxone in the percentage of opioid-negative results. “Cumulative distribution function values are an established endpoint used in early placebo-controlled, phase 3 clinical trials for OUD treatment,” Dr. Lofall and her associates wrote.
The study findings were limited by several factors, including an absence of assessment of patient adherence to sublingual medication and an inability to assess effectiveness vs. efficacy. However, the large size and diverse study population strengthen the results, which support the use of subcutaneous depot buprenorphine formulations for patients with OUD, the researchers noted.
“These formulations may also address potential limitations and concerns about daily dosing, including diversion, misuse, and accidental exposure of medication to children,” they said.
The study was supported in part by Braeburn Pharmaceuticals and the University of Kentucky, Lexington. Dr. Lofwall disclosed research funding and consulting fees from Braeburn Pharmaceuticals and Indivior.
SOURCE: Lofwall M et al. JAMA Intern Med. 2018 May 14. doi: 10.1001/jamainternmed.2018.1052.
Long-acting subcutaneous doses of buprenorphine depot are an effective treatment option for opioid use disorder, results of a phase 3 study of 428 adults show.
Sublingual buprenorphine hydrochloride is a standard treatment for opioid use disorder (OUD), but challenges include poor medication adherence, potential for abuse, and accidental exposure to children, Michelle R. Lofwall, MD, of the University of Kentucky, Lexington, and her colleagues reported.
In a study published in JAMA Internal Medicine, Dr. Lofwall and her associates randomized treatment-seeking adults with moderate to severe opioid use disorder to subcutaneous buprenorphine depot weekly for 12 weeks followed by monthly for 12 weeks, or daily sublingual buprenorphine with naloxone for 24 weeks.
The proportion of opioid-negative urine samples was 35% in the subcutaneous buprenorphine depot group (1,347 of 3,834 samples) vs. 29% in the sublingual buprenorphine with naloxone group (1,099 of 3,870 samples) for a statistically significant difference of 6.7%. Urine samples were collected weekly for the first 12 weeks, and then at weeks 16, 20, and 24, reported Dr. Lofall, a psychiatrist and addiction medicine specialist, and her associates.
Patients in the sublingual buprenorphine with naloxone group received 4 mg of sublingual buprenorphine hydrochloride and naloxone hydrochloride at the start of the study, titrated to 16 mg/day. The average treatment dosage was 18-20 mg/day for sublingual buprenorphine with naloxone patients.
Patients in the subcutaneous buprenorphine depot group received 16 mg of subcutaneous buprenorphine in a weekly injection at the start of the study; monthly subcutaneous buprenorphine depot injections were 64, 96, 128, or 160 mg between weeks 12 and 24.
After initial titration, doses were flexible based on clinical judgment, the researchers noted, similar to the way in which patients would be managed in a clinical setting.
Adverse events were similar between the groups. The most common were injection-site pain, headache, constipation, nausea, and injection-site pruritus and erythema. Injection-site reactions were mild to moderate.
As a secondary outcome, the cumulative distribution function (CDF) in the subcutaneous buprenorphine depot group was statistically superior to the CDF found in the sublingual buprenorphine with naloxone in the percentage of opioid-negative results. “Cumulative distribution function values are an established endpoint used in early placebo-controlled, phase 3 clinical trials for OUD treatment,” Dr. Lofall and her associates wrote.
The study findings were limited by several factors, including an absence of assessment of patient adherence to sublingual medication and an inability to assess effectiveness vs. efficacy. However, the large size and diverse study population strengthen the results, which support the use of subcutaneous depot buprenorphine formulations for patients with OUD, the researchers noted.
“These formulations may also address potential limitations and concerns about daily dosing, including diversion, misuse, and accidental exposure of medication to children,” they said.
The study was supported in part by Braeburn Pharmaceuticals and the University of Kentucky, Lexington. Dr. Lofwall disclosed research funding and consulting fees from Braeburn Pharmaceuticals and Indivior.
SOURCE: Lofwall M et al. JAMA Intern Med. 2018 May 14. doi: 10.1001/jamainternmed.2018.1052.
Long-acting subcutaneous doses of buprenorphine depot are an effective treatment option for opioid use disorder, results of a phase 3 study of 428 adults show.
Sublingual buprenorphine hydrochloride is a standard treatment for opioid use disorder (OUD), but challenges include poor medication adherence, potential for abuse, and accidental exposure to children, Michelle R. Lofwall, MD, of the University of Kentucky, Lexington, and her colleagues reported.
In a study published in JAMA Internal Medicine, Dr. Lofwall and her associates randomized treatment-seeking adults with moderate to severe opioid use disorder to subcutaneous buprenorphine depot weekly for 12 weeks followed by monthly for 12 weeks, or daily sublingual buprenorphine with naloxone for 24 weeks.
The proportion of opioid-negative urine samples was 35% in the subcutaneous buprenorphine depot group (1,347 of 3,834 samples) vs. 29% in the sublingual buprenorphine with naloxone group (1,099 of 3,870 samples) for a statistically significant difference of 6.7%. Urine samples were collected weekly for the first 12 weeks, and then at weeks 16, 20, and 24, reported Dr. Lofall, a psychiatrist and addiction medicine specialist, and her associates.
Patients in the sublingual buprenorphine with naloxone group received 4 mg of sublingual buprenorphine hydrochloride and naloxone hydrochloride at the start of the study, titrated to 16 mg/day. The average treatment dosage was 18-20 mg/day for sublingual buprenorphine with naloxone patients.
Patients in the subcutaneous buprenorphine depot group received 16 mg of subcutaneous buprenorphine in a weekly injection at the start of the study; monthly subcutaneous buprenorphine depot injections were 64, 96, 128, or 160 mg between weeks 12 and 24.
After initial titration, doses were flexible based on clinical judgment, the researchers noted, similar to the way in which patients would be managed in a clinical setting.
Adverse events were similar between the groups. The most common were injection-site pain, headache, constipation, nausea, and injection-site pruritus and erythema. Injection-site reactions were mild to moderate.
As a secondary outcome, the cumulative distribution function (CDF) in the subcutaneous buprenorphine depot group was statistically superior to the CDF found in the sublingual buprenorphine with naloxone in the percentage of opioid-negative results. “Cumulative distribution function values are an established endpoint used in early placebo-controlled, phase 3 clinical trials for OUD treatment,” Dr. Lofall and her associates wrote.
The study findings were limited by several factors, including an absence of assessment of patient adherence to sublingual medication and an inability to assess effectiveness vs. efficacy. However, the large size and diverse study population strengthen the results, which support the use of subcutaneous depot buprenorphine formulations for patients with OUD, the researchers noted.
“These formulations may also address potential limitations and concerns about daily dosing, including diversion, misuse, and accidental exposure of medication to children,” they said.
The study was supported in part by Braeburn Pharmaceuticals and the University of Kentucky, Lexington. Dr. Lofwall disclosed research funding and consulting fees from Braeburn Pharmaceuticals and Indivior.
SOURCE: Lofwall M et al. JAMA Intern Med. 2018 May 14. doi: 10.1001/jamainternmed.2018.1052.
FROM JAMA INTERNAL MEDICINE
Key clinical point: After 24 weeks, long-acting subcutaneous buprenorphine depot was noninferior to sublingual buprenorphine-naloxone for preventing opioid use.
Major finding: The proportion of opioid-negative urine samples was a statistically significant 6.7% higher in the subcutaneous group, compared with the sublingual group.
Study details: The data come from a randomized trial of 428 adults in treatment for opioid use disorder.
Disclosures: The study was supported in part by Braeburn Pharmaceuticals and the University of Kentucky, Lexington. Dr Lofwall disclosed research funding and consulting fees from Braeburn Pharmaceuticals and Indivior.
Source: Lofwall M et al. JAMA Intern Med. 2018 May 14; doi: 10.1001/jamainternmed.2018.1052.
Methotrexate-induced pulmonary fibrosis risk examined in 10-year study
LIVERPOOL, ENGLAND – A 10-year follow up of patients with inflammatory arthritis has shown that methotrexate does not appear to increase the risk of pulmonary fibrosis.
“As rheumatologists, it’s a really important message that methotrexate does not cause chronic pulmonary fibrosis and it should not be stopped because of pulmonary fibrosis,” Julie Dawson, MD, said in an interview at the British Society for Rheumatology annual conference. “It’s the rheumatoid arthritis. It’s not the methotrexate.”
Dr. Dawson, of St. Helens and Knowsley Teaching Hospitals NHS Trust, St. Helens, England, added that the current findings were consistent with her team’s prior research looking at earlier time periods. There was also no correlation between the duration or dose of methotrexate used and the development of the lung disease, she said.
“If anything, the suggestion is you’d be more symptomatic if you delay using methotrexate,” Dr. Dawson observed. If patients are not doing well on methotrexate, then perhaps adjusting therapy or changing to another drug would of course be the next step, but if patients are well controlled then “stopping it is the worst thing to do” for their arthritis, she said.
“This is of great clinical interest, and we can be reassured now about this, I think. This is really good, long-term data,” said Devesh Mewar, MD, of Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, England, who was not involved in the research.
“We know that methotrexate is associated with a pneumonitis reaction, but there is no high-quality evidence that methotrexate is associated with a chronic pulmonary fibrosis” Dr. Dawson said, explaining the rationale for the current study she presented during a poster session. Previous studies considered data for up to 5 years, she added, so the aim of the current study, therefore, was to look at the longer-term effect of methotrexate use on the incidence of pulmonary fibrosis.
Data on 129 patients who had started treatment with methotrexate from 2004 to 2007 were analyzed, of whom 63 (49%) had stayed on methotrexate for 10 or more years. Most (82%) had been given methotrexate to treat rheumatoid arthritis (RA), with other indications including inflammatory arthritis (5.4%) and psoriatic arthritis (4.7%).
“Practice was different 10 years ago, so just 56% of patients commenced methotrexate within the first year of the diagnosis of rheumatoid arthritis,” Dr. Dawson reported.
Only four cases of symptomatic pulmonary fibrosis were seen, all in the RA patients, and three of these were in patients who had started methotrexate over 1 year after their diagnosis. The incidence of 3.8% seen in the study matches the expected incidence of pulmonary fibrosis in RA and was actually “at the lower end of the expected incidence,” Dr. Dawson said. Previous studies have suggested an incidence rate of RA-associated interstitial lung disease of about 3%-7%.
All of the pulmonary fibrosis cases had occurred in men and 75% were seropositive for rheumatoid factor. The mean duration of RA at the time of onset of pulmonary fibrosis was 7.8 years and the usual interstitial pattern of fibrosis was seen. The 125 patients without pulmonary fibrosis had taken methotrexate for a mean of 8 years at a mean final weekly dose of 16.3 mg, compared with a mean of 6 years at a mean dose of 18.1 mg per week in the 4 patients with pulmonary fibrosis.
One of the next steps is to look at cases where methotrexate has been stopped and the effects of that on pulmonary fibrosis and disease activity. In Dr. Dawson’s experience, stopping methotrexate just affects the management of the arthritis and had no difference to the progression of pulmonary fibrosis.
If patients start to experience any lung symptoms while continuing methotrexate, such as shortness of breath, then they would need to be assessed and undergo lung function tests to monitor their condition. Treating the fibrosis using an antifibrotic drug, such as pirfenidone, is something that might be possible in the future, but this needs investigation in inflammatory arthritis as the drug is currently only licensed for use in idiopathic cases.
This is something the British Rheumatoid Interstitial Lung network plans to investigate in a placebo-controlled study of RA patients with fibrotic lung disease. “We’re looking to see if antifibrotic agents are going to slow the disease as it does in idiopathic pulmonary fibrosis, which is obviously quite exciting when it’s such a hard condition to treat,” said Dr. Dawson, who will be one of the study’s investigators.
Dr. Dawson had no conflicts of interest to disclose. Dr. Mewar was not involved in the study and had nothing to disclose.
SOURCE: Dawson J et al. Rheumatology. 2018;57[Suppl. 3]:key075.470.
The subject of this retrospective study is of great interest. The authors point out that pulmonary fibrosis (as opposed to acute allergic reaction, which is extremely rare) is also extremely uncommon in patients using methotrexate over the long haul. Over 10 years, their data points to a 3.1% incidence of symptomatic pulmonary fibrosis.
The issue here is its generalizability. There were 63 patients who used methotrexate for 10 years or more and 88 who used it for 5 years or more, according to the poster. This must represent a highly selected population. For example, what percent of the total RA/psoriatic arthritis/”inflammatory arthritis” population do these patients represent, i.e., what is the denominator here? The authors stated that the 63 patients who stayed on methotrexate for 10 or more years represent 49% of the 129 patients on methotrexate overall in the study. This is a highly unusual datum, as most of the literature indicates that only 40% or less of patients stay on methotrexate for even 5 years. And this completely ignores the issue of adherence over this long a period; these patients must represent a truly minuscule percentage of the total if they actually stayed on methotrexate with even moderate adherence for 10 years.
Importantly, the authors point out that they had only four cases of symptomatic pulmonary fibrosis. Once more, this points to the highly selective group of patients seen, as this study does not examine patients with asymptomatic pulmonary fibrosis, including those with fibrosis on high-resolution CT of the lungs or chest film or evidence of abnormalities on pulmonary function tests, but who do not have sufficient symptoms ascribed to methotrexate to bring them to medical attention.
Daniel E. Furst, MD, is professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy. He was not involved with the study.
The subject of this retrospective study is of great interest. The authors point out that pulmonary fibrosis (as opposed to acute allergic reaction, which is extremely rare) is also extremely uncommon in patients using methotrexate over the long haul. Over 10 years, their data points to a 3.1% incidence of symptomatic pulmonary fibrosis.
The issue here is its generalizability. There were 63 patients who used methotrexate for 10 years or more and 88 who used it for 5 years or more, according to the poster. This must represent a highly selected population. For example, what percent of the total RA/psoriatic arthritis/”inflammatory arthritis” population do these patients represent, i.e., what is the denominator here? The authors stated that the 63 patients who stayed on methotrexate for 10 or more years represent 49% of the 129 patients on methotrexate overall in the study. This is a highly unusual datum, as most of the literature indicates that only 40% or less of patients stay on methotrexate for even 5 years. And this completely ignores the issue of adherence over this long a period; these patients must represent a truly minuscule percentage of the total if they actually stayed on methotrexate with even moderate adherence for 10 years.
Importantly, the authors point out that they had only four cases of symptomatic pulmonary fibrosis. Once more, this points to the highly selective group of patients seen, as this study does not examine patients with asymptomatic pulmonary fibrosis, including those with fibrosis on high-resolution CT of the lungs or chest film or evidence of abnormalities on pulmonary function tests, but who do not have sufficient symptoms ascribed to methotrexate to bring them to medical attention.
Daniel E. Furst, MD, is professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy. He was not involved with the study.
The subject of this retrospective study is of great interest. The authors point out that pulmonary fibrosis (as opposed to acute allergic reaction, which is extremely rare) is also extremely uncommon in patients using methotrexate over the long haul. Over 10 years, their data points to a 3.1% incidence of symptomatic pulmonary fibrosis.
The issue here is its generalizability. There were 63 patients who used methotrexate for 10 years or more and 88 who used it for 5 years or more, according to the poster. This must represent a highly selected population. For example, what percent of the total RA/psoriatic arthritis/”inflammatory arthritis” population do these patients represent, i.e., what is the denominator here? The authors stated that the 63 patients who stayed on methotrexate for 10 or more years represent 49% of the 129 patients on methotrexate overall in the study. This is a highly unusual datum, as most of the literature indicates that only 40% or less of patients stay on methotrexate for even 5 years. And this completely ignores the issue of adherence over this long a period; these patients must represent a truly minuscule percentage of the total if they actually stayed on methotrexate with even moderate adherence for 10 years.
Importantly, the authors point out that they had only four cases of symptomatic pulmonary fibrosis. Once more, this points to the highly selective group of patients seen, as this study does not examine patients with asymptomatic pulmonary fibrosis, including those with fibrosis on high-resolution CT of the lungs or chest film or evidence of abnormalities on pulmonary function tests, but who do not have sufficient symptoms ascribed to methotrexate to bring them to medical attention.
Daniel E. Furst, MD, is professor of rheumatology at the University of Washington, Seattle, who also is affiliated with the University of California, Los Angeles, and the University of Florence, Italy. He was not involved with the study.
LIVERPOOL, ENGLAND – A 10-year follow up of patients with inflammatory arthritis has shown that methotrexate does not appear to increase the risk of pulmonary fibrosis.
“As rheumatologists, it’s a really important message that methotrexate does not cause chronic pulmonary fibrosis and it should not be stopped because of pulmonary fibrosis,” Julie Dawson, MD, said in an interview at the British Society for Rheumatology annual conference. “It’s the rheumatoid arthritis. It’s not the methotrexate.”
Dr. Dawson, of St. Helens and Knowsley Teaching Hospitals NHS Trust, St. Helens, England, added that the current findings were consistent with her team’s prior research looking at earlier time periods. There was also no correlation between the duration or dose of methotrexate used and the development of the lung disease, she said.
“If anything, the suggestion is you’d be more symptomatic if you delay using methotrexate,” Dr. Dawson observed. If patients are not doing well on methotrexate, then perhaps adjusting therapy or changing to another drug would of course be the next step, but if patients are well controlled then “stopping it is the worst thing to do” for their arthritis, she said.
“This is of great clinical interest, and we can be reassured now about this, I think. This is really good, long-term data,” said Devesh Mewar, MD, of Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, England, who was not involved in the research.
“We know that methotrexate is associated with a pneumonitis reaction, but there is no high-quality evidence that methotrexate is associated with a chronic pulmonary fibrosis” Dr. Dawson said, explaining the rationale for the current study she presented during a poster session. Previous studies considered data for up to 5 years, she added, so the aim of the current study, therefore, was to look at the longer-term effect of methotrexate use on the incidence of pulmonary fibrosis.
Data on 129 patients who had started treatment with methotrexate from 2004 to 2007 were analyzed, of whom 63 (49%) had stayed on methotrexate for 10 or more years. Most (82%) had been given methotrexate to treat rheumatoid arthritis (RA), with other indications including inflammatory arthritis (5.4%) and psoriatic arthritis (4.7%).
“Practice was different 10 years ago, so just 56% of patients commenced methotrexate within the first year of the diagnosis of rheumatoid arthritis,” Dr. Dawson reported.
Only four cases of symptomatic pulmonary fibrosis were seen, all in the RA patients, and three of these were in patients who had started methotrexate over 1 year after their diagnosis. The incidence of 3.8% seen in the study matches the expected incidence of pulmonary fibrosis in RA and was actually “at the lower end of the expected incidence,” Dr. Dawson said. Previous studies have suggested an incidence rate of RA-associated interstitial lung disease of about 3%-7%.
All of the pulmonary fibrosis cases had occurred in men and 75% were seropositive for rheumatoid factor. The mean duration of RA at the time of onset of pulmonary fibrosis was 7.8 years and the usual interstitial pattern of fibrosis was seen. The 125 patients without pulmonary fibrosis had taken methotrexate for a mean of 8 years at a mean final weekly dose of 16.3 mg, compared with a mean of 6 years at a mean dose of 18.1 mg per week in the 4 patients with pulmonary fibrosis.
One of the next steps is to look at cases where methotrexate has been stopped and the effects of that on pulmonary fibrosis and disease activity. In Dr. Dawson’s experience, stopping methotrexate just affects the management of the arthritis and had no difference to the progression of pulmonary fibrosis.
If patients start to experience any lung symptoms while continuing methotrexate, such as shortness of breath, then they would need to be assessed and undergo lung function tests to monitor their condition. Treating the fibrosis using an antifibrotic drug, such as pirfenidone, is something that might be possible in the future, but this needs investigation in inflammatory arthritis as the drug is currently only licensed for use in idiopathic cases.
This is something the British Rheumatoid Interstitial Lung network plans to investigate in a placebo-controlled study of RA patients with fibrotic lung disease. “We’re looking to see if antifibrotic agents are going to slow the disease as it does in idiopathic pulmonary fibrosis, which is obviously quite exciting when it’s such a hard condition to treat,” said Dr. Dawson, who will be one of the study’s investigators.
Dr. Dawson had no conflicts of interest to disclose. Dr. Mewar was not involved in the study and had nothing to disclose.
SOURCE: Dawson J et al. Rheumatology. 2018;57[Suppl. 3]:key075.470.
LIVERPOOL, ENGLAND – A 10-year follow up of patients with inflammatory arthritis has shown that methotrexate does not appear to increase the risk of pulmonary fibrosis.
“As rheumatologists, it’s a really important message that methotrexate does not cause chronic pulmonary fibrosis and it should not be stopped because of pulmonary fibrosis,” Julie Dawson, MD, said in an interview at the British Society for Rheumatology annual conference. “It’s the rheumatoid arthritis. It’s not the methotrexate.”
Dr. Dawson, of St. Helens and Knowsley Teaching Hospitals NHS Trust, St. Helens, England, added that the current findings were consistent with her team’s prior research looking at earlier time periods. There was also no correlation between the duration or dose of methotrexate used and the development of the lung disease, she said.
“If anything, the suggestion is you’d be more symptomatic if you delay using methotrexate,” Dr. Dawson observed. If patients are not doing well on methotrexate, then perhaps adjusting therapy or changing to another drug would of course be the next step, but if patients are well controlled then “stopping it is the worst thing to do” for their arthritis, she said.
“This is of great clinical interest, and we can be reassured now about this, I think. This is really good, long-term data,” said Devesh Mewar, MD, of Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, England, who was not involved in the research.
“We know that methotrexate is associated with a pneumonitis reaction, but there is no high-quality evidence that methotrexate is associated with a chronic pulmonary fibrosis” Dr. Dawson said, explaining the rationale for the current study she presented during a poster session. Previous studies considered data for up to 5 years, she added, so the aim of the current study, therefore, was to look at the longer-term effect of methotrexate use on the incidence of pulmonary fibrosis.
Data on 129 patients who had started treatment with methotrexate from 2004 to 2007 were analyzed, of whom 63 (49%) had stayed on methotrexate for 10 or more years. Most (82%) had been given methotrexate to treat rheumatoid arthritis (RA), with other indications including inflammatory arthritis (5.4%) and psoriatic arthritis (4.7%).
“Practice was different 10 years ago, so just 56% of patients commenced methotrexate within the first year of the diagnosis of rheumatoid arthritis,” Dr. Dawson reported.
Only four cases of symptomatic pulmonary fibrosis were seen, all in the RA patients, and three of these were in patients who had started methotrexate over 1 year after their diagnosis. The incidence of 3.8% seen in the study matches the expected incidence of pulmonary fibrosis in RA and was actually “at the lower end of the expected incidence,” Dr. Dawson said. Previous studies have suggested an incidence rate of RA-associated interstitial lung disease of about 3%-7%.
All of the pulmonary fibrosis cases had occurred in men and 75% were seropositive for rheumatoid factor. The mean duration of RA at the time of onset of pulmonary fibrosis was 7.8 years and the usual interstitial pattern of fibrosis was seen. The 125 patients without pulmonary fibrosis had taken methotrexate for a mean of 8 years at a mean final weekly dose of 16.3 mg, compared with a mean of 6 years at a mean dose of 18.1 mg per week in the 4 patients with pulmonary fibrosis.
One of the next steps is to look at cases where methotrexate has been stopped and the effects of that on pulmonary fibrosis and disease activity. In Dr. Dawson’s experience, stopping methotrexate just affects the management of the arthritis and had no difference to the progression of pulmonary fibrosis.
If patients start to experience any lung symptoms while continuing methotrexate, such as shortness of breath, then they would need to be assessed and undergo lung function tests to monitor their condition. Treating the fibrosis using an antifibrotic drug, such as pirfenidone, is something that might be possible in the future, but this needs investigation in inflammatory arthritis as the drug is currently only licensed for use in idiopathic cases.
This is something the British Rheumatoid Interstitial Lung network plans to investigate in a placebo-controlled study of RA patients with fibrotic lung disease. “We’re looking to see if antifibrotic agents are going to slow the disease as it does in idiopathic pulmonary fibrosis, which is obviously quite exciting when it’s such a hard condition to treat,” said Dr. Dawson, who will be one of the study’s investigators.
Dr. Dawson had no conflicts of interest to disclose. Dr. Mewar was not involved in the study and had nothing to disclose.
SOURCE: Dawson J et al. Rheumatology. 2018;57[Suppl. 3]:key075.470.
REPORTING FROM RHEUMATOLOGY 2018
Key clinical point:
Major finding: At 10 years’ follow-up, four patients (3.1%) developed pulmonary fibrosis.
Study details: Retrospective analysis of 129 patients with inflammatory arthritis treated with methotrexate for up to 10 years.
Disclosures: Dr. Dawson had no conflicts of interest to disclose. Dr. Mewar was not involved in the study and had nothing to disclose.
Source: Dawson J et al. Rheumatology. 2018;57[Suppl. 3]:key075.470.
First, marijuana. Are magic mushrooms next?
In Oregon and Denver, where marijuana is legal for recreational use, activists are now pushing toward a psychedelic frontier: “magic mushrooms.”
“We don’t want individuals to lose their freedom over something that’s natural and has health benefits,” said Kevin Matthews, the campaign director of Denver for Psilocybin, the group working to decriminalize magic mushrooms in Colorado’s capital.
The recent failure of a nationally publicized campaign to decriminalize hallucinogenic mushrooms in California may not portend well for the psilocybin advocates in Oregon and Denver – though their initiatives are more limited than California’s.
The proposal in the Golden State would have decriminalized sales and transportation of magic mushrooms, not just possession. The proposed Denver measure would apply only to that city, while in Oregon mushroom use would be allowed only with the approval of a physician and under the supervision of a registered therapist.
None of the proposed initiatives envisions fully legalizing psilocybin mushrooms, which would allow the government to regulate and tax sales in a similar fashion to medical and recreational marijuana.
In Oregon, advocates face a steep climb to qualify their measure for the ballot, because such statewide initiatives typically require hiring paid signature gatherers, said William Lunch, a political analyst for Oregon Public Broadcasting and a former political science professor at Oregon State University.
Still, familiarity with recreational marijuana may have “softened up” voters and opponents of drug decriminalization, he said. Oregon legalized marijuana for recreational use in 2015, Colorado in 2012.
The Oregon and Denver activists, echoing Lunch, say they hope voters who already accepted pot would now feel comfortable decriminalizing personal use of magic mushrooms as well.
Taking mushrooms can lead to nausea, panic attacks and, rarely, paranoia and psychosis. But they generally are considered safer and less addictive than other illegal street drugs.
Even so, Paul Hutson, professor of pharmacy at the University of Wisconsin who has conducted psilocybin research, says he is wary of the drive for decriminalization. Psilocybin isn’t safe for some people – particularly those with paranoia or psychosis, he said.
“I reject the idea that that this is a natural progression from medical marijuana,” Hutson said, noting that the safety of pot is much better established. Mushrooms, he added, “are very, very potent medicines that are affecting your mind. In the proper setting, they’re safe, but in an uncontrolled fashion, I have grave concerns.”
Even psilocybin advocates share Hutson’s concerns. “It is such a powerful compound. People should take it very seriously when experimenting,” Matthews said.
These efforts to legitimize hallucinogenic mushrooms come at a time of renewed interest in the potential mental health benefits of psychedelics, including mushrooms, LSD and MDMA (known as ecstasy). Two small studies published in 2016 by researchers from Johns Hopkins University and New York University found that a single large dose of psilocybin, combined with psychotherapy, helped relieve depression and anxiety in cancer patients.
A British company backed by Silicon Valley investor Peter Thiel plans clinical studies in eight European countries to test the use of psilocybin for depression. Other research has examined the effectiveness of psilocybin in treating alcohol and tobacco addiction.
In California, the campaign to decriminalize psilocybin was always a long shot – even though the famously liberal state legalized possession of recreational marijuana in November 2016 and sales starting this year.
California ballot measures typically require nearly 366,000 signatures to qualify, and supporters usually have to spend between $1 million and $2 million to pay signature gatherers. A Monterey County couple leading the decriminalization campaign managed to collect more than 90,000 signatures for their proposal with the help of volunteers, but they halted their efforts late last month.
The initiative would have exempted Californians 21 and over from criminal penalties for possessing, selling, transporting or cultivating psilocybin mushrooms.
Possessing them is generally a misdemeanor under California law, but selling them is a felony. State statistics on psilocybin offenses are scarce, but few people are jailed for such crimes, according to an analysis by the California attorney general’s office.
“It’s not a reckless community,” said Kitty Merchant of Marina, Calif., who spearheaded the California psilocybin campaign alongside her husband, Kevin Saunders. “It’s experimentation with your mind and your thoughts. There’s a safeness to it. And there’s an intelligence to it.”
Merchant said she and Saunders, both medical marijuana advocates, spent about $20,000 of their own money on the campaign.
In Denver, Matthews and his pro-psilocybin colleagues want voters to pass a city ordinance eliminating criminal penalties for possessing, using or growing magic mushrooms. City officials have cleared the measure for signature gathering. Supporters need 5,000 signatures to get it on the ballot in November. Matthews said he has already lined up dozens of volunteer signature gatherers.
He said he has used mushrooms to help alleviate depression and other mental health problems. A big part of the decriminalization campaign, he said, is promoting responsible use.
Denver, a progressive city in a state that was the first to legalize recreational marijuana, “is a good testing place for this initiative nationwide,” Matthews said. Just getting it on the ballot, whether or not it passes, would be “a huge victory,” he added.
In Oregon, activists are proposing a measure for the 2020 ballot that would decriminalize psilocybin statewide for adults 21 and over who get approval from their doctors and agree to participate in a “psilocybin service.” The service would include a preparatory meeting with a therapist, one session of supervised mushroom use and a follow-up visit. Patients would be under the care of state-certified “Psilocybin Service Facilitators.”
Tom Eckert, a Portland, Ore.-based therapist who leads the psilocybin decriminalization campaign with his wife, Sheri, said the proposed limitations on psilocybin use are important.
“Psilocybin is generally safe, but it puts you in a vulnerable state of mind,” he said. “If you do it in the wrong setting, things can go sideways.”
This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
In Oregon and Denver, where marijuana is legal for recreational use, activists are now pushing toward a psychedelic frontier: “magic mushrooms.”
“We don’t want individuals to lose their freedom over something that’s natural and has health benefits,” said Kevin Matthews, the campaign director of Denver for Psilocybin, the group working to decriminalize magic mushrooms in Colorado’s capital.
The recent failure of a nationally publicized campaign to decriminalize hallucinogenic mushrooms in California may not portend well for the psilocybin advocates in Oregon and Denver – though their initiatives are more limited than California’s.
The proposal in the Golden State would have decriminalized sales and transportation of magic mushrooms, not just possession. The proposed Denver measure would apply only to that city, while in Oregon mushroom use would be allowed only with the approval of a physician and under the supervision of a registered therapist.
None of the proposed initiatives envisions fully legalizing psilocybin mushrooms, which would allow the government to regulate and tax sales in a similar fashion to medical and recreational marijuana.
In Oregon, advocates face a steep climb to qualify their measure for the ballot, because such statewide initiatives typically require hiring paid signature gatherers, said William Lunch, a political analyst for Oregon Public Broadcasting and a former political science professor at Oregon State University.
Still, familiarity with recreational marijuana may have “softened up” voters and opponents of drug decriminalization, he said. Oregon legalized marijuana for recreational use in 2015, Colorado in 2012.
The Oregon and Denver activists, echoing Lunch, say they hope voters who already accepted pot would now feel comfortable decriminalizing personal use of magic mushrooms as well.
Taking mushrooms can lead to nausea, panic attacks and, rarely, paranoia and psychosis. But they generally are considered safer and less addictive than other illegal street drugs.
Even so, Paul Hutson, professor of pharmacy at the University of Wisconsin who has conducted psilocybin research, says he is wary of the drive for decriminalization. Psilocybin isn’t safe for some people – particularly those with paranoia or psychosis, he said.
“I reject the idea that that this is a natural progression from medical marijuana,” Hutson said, noting that the safety of pot is much better established. Mushrooms, he added, “are very, very potent medicines that are affecting your mind. In the proper setting, they’re safe, but in an uncontrolled fashion, I have grave concerns.”
Even psilocybin advocates share Hutson’s concerns. “It is such a powerful compound. People should take it very seriously when experimenting,” Matthews said.
These efforts to legitimize hallucinogenic mushrooms come at a time of renewed interest in the potential mental health benefits of psychedelics, including mushrooms, LSD and MDMA (known as ecstasy). Two small studies published in 2016 by researchers from Johns Hopkins University and New York University found that a single large dose of psilocybin, combined with psychotherapy, helped relieve depression and anxiety in cancer patients.
A British company backed by Silicon Valley investor Peter Thiel plans clinical studies in eight European countries to test the use of psilocybin for depression. Other research has examined the effectiveness of psilocybin in treating alcohol and tobacco addiction.
In California, the campaign to decriminalize psilocybin was always a long shot – even though the famously liberal state legalized possession of recreational marijuana in November 2016 and sales starting this year.
California ballot measures typically require nearly 366,000 signatures to qualify, and supporters usually have to spend between $1 million and $2 million to pay signature gatherers. A Monterey County couple leading the decriminalization campaign managed to collect more than 90,000 signatures for their proposal with the help of volunteers, but they halted their efforts late last month.
The initiative would have exempted Californians 21 and over from criminal penalties for possessing, selling, transporting or cultivating psilocybin mushrooms.
Possessing them is generally a misdemeanor under California law, but selling them is a felony. State statistics on psilocybin offenses are scarce, but few people are jailed for such crimes, according to an analysis by the California attorney general’s office.
“It’s not a reckless community,” said Kitty Merchant of Marina, Calif., who spearheaded the California psilocybin campaign alongside her husband, Kevin Saunders. “It’s experimentation with your mind and your thoughts. There’s a safeness to it. And there’s an intelligence to it.”
Merchant said she and Saunders, both medical marijuana advocates, spent about $20,000 of their own money on the campaign.
In Denver, Matthews and his pro-psilocybin colleagues want voters to pass a city ordinance eliminating criminal penalties for possessing, using or growing magic mushrooms. City officials have cleared the measure for signature gathering. Supporters need 5,000 signatures to get it on the ballot in November. Matthews said he has already lined up dozens of volunteer signature gatherers.
He said he has used mushrooms to help alleviate depression and other mental health problems. A big part of the decriminalization campaign, he said, is promoting responsible use.
Denver, a progressive city in a state that was the first to legalize recreational marijuana, “is a good testing place for this initiative nationwide,” Matthews said. Just getting it on the ballot, whether or not it passes, would be “a huge victory,” he added.
In Oregon, activists are proposing a measure for the 2020 ballot that would decriminalize psilocybin statewide for adults 21 and over who get approval from their doctors and agree to participate in a “psilocybin service.” The service would include a preparatory meeting with a therapist, one session of supervised mushroom use and a follow-up visit. Patients would be under the care of state-certified “Psilocybin Service Facilitators.”
Tom Eckert, a Portland, Ore.-based therapist who leads the psilocybin decriminalization campaign with his wife, Sheri, said the proposed limitations on psilocybin use are important.
“Psilocybin is generally safe, but it puts you in a vulnerable state of mind,” he said. “If you do it in the wrong setting, things can go sideways.”
This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
In Oregon and Denver, where marijuana is legal for recreational use, activists are now pushing toward a psychedelic frontier: “magic mushrooms.”
“We don’t want individuals to lose their freedom over something that’s natural and has health benefits,” said Kevin Matthews, the campaign director of Denver for Psilocybin, the group working to decriminalize magic mushrooms in Colorado’s capital.
The recent failure of a nationally publicized campaign to decriminalize hallucinogenic mushrooms in California may not portend well for the psilocybin advocates in Oregon and Denver – though their initiatives are more limited than California’s.
The proposal in the Golden State would have decriminalized sales and transportation of magic mushrooms, not just possession. The proposed Denver measure would apply only to that city, while in Oregon mushroom use would be allowed only with the approval of a physician and under the supervision of a registered therapist.
None of the proposed initiatives envisions fully legalizing psilocybin mushrooms, which would allow the government to regulate and tax sales in a similar fashion to medical and recreational marijuana.
In Oregon, advocates face a steep climb to qualify their measure for the ballot, because such statewide initiatives typically require hiring paid signature gatherers, said William Lunch, a political analyst for Oregon Public Broadcasting and a former political science professor at Oregon State University.
Still, familiarity with recreational marijuana may have “softened up” voters and opponents of drug decriminalization, he said. Oregon legalized marijuana for recreational use in 2015, Colorado in 2012.
The Oregon and Denver activists, echoing Lunch, say they hope voters who already accepted pot would now feel comfortable decriminalizing personal use of magic mushrooms as well.
Taking mushrooms can lead to nausea, panic attacks and, rarely, paranoia and psychosis. But they generally are considered safer and less addictive than other illegal street drugs.
Even so, Paul Hutson, professor of pharmacy at the University of Wisconsin who has conducted psilocybin research, says he is wary of the drive for decriminalization. Psilocybin isn’t safe for some people – particularly those with paranoia or psychosis, he said.
“I reject the idea that that this is a natural progression from medical marijuana,” Hutson said, noting that the safety of pot is much better established. Mushrooms, he added, “are very, very potent medicines that are affecting your mind. In the proper setting, they’re safe, but in an uncontrolled fashion, I have grave concerns.”
Even psilocybin advocates share Hutson’s concerns. “It is such a powerful compound. People should take it very seriously when experimenting,” Matthews said.
These efforts to legitimize hallucinogenic mushrooms come at a time of renewed interest in the potential mental health benefits of psychedelics, including mushrooms, LSD and MDMA (known as ecstasy). Two small studies published in 2016 by researchers from Johns Hopkins University and New York University found that a single large dose of psilocybin, combined with psychotherapy, helped relieve depression and anxiety in cancer patients.
A British company backed by Silicon Valley investor Peter Thiel plans clinical studies in eight European countries to test the use of psilocybin for depression. Other research has examined the effectiveness of psilocybin in treating alcohol and tobacco addiction.
In California, the campaign to decriminalize psilocybin was always a long shot – even though the famously liberal state legalized possession of recreational marijuana in November 2016 and sales starting this year.
California ballot measures typically require nearly 366,000 signatures to qualify, and supporters usually have to spend between $1 million and $2 million to pay signature gatherers. A Monterey County couple leading the decriminalization campaign managed to collect more than 90,000 signatures for their proposal with the help of volunteers, but they halted their efforts late last month.
The initiative would have exempted Californians 21 and over from criminal penalties for possessing, selling, transporting or cultivating psilocybin mushrooms.
Possessing them is generally a misdemeanor under California law, but selling them is a felony. State statistics on psilocybin offenses are scarce, but few people are jailed for such crimes, according to an analysis by the California attorney general’s office.
“It’s not a reckless community,” said Kitty Merchant of Marina, Calif., who spearheaded the California psilocybin campaign alongside her husband, Kevin Saunders. “It’s experimentation with your mind and your thoughts. There’s a safeness to it. And there’s an intelligence to it.”
Merchant said she and Saunders, both medical marijuana advocates, spent about $20,000 of their own money on the campaign.
In Denver, Matthews and his pro-psilocybin colleagues want voters to pass a city ordinance eliminating criminal penalties for possessing, using or growing magic mushrooms. City officials have cleared the measure for signature gathering. Supporters need 5,000 signatures to get it on the ballot in November. Matthews said he has already lined up dozens of volunteer signature gatherers.
He said he has used mushrooms to help alleviate depression and other mental health problems. A big part of the decriminalization campaign, he said, is promoting responsible use.
Denver, a progressive city in a state that was the first to legalize recreational marijuana, “is a good testing place for this initiative nationwide,” Matthews said. Just getting it on the ballot, whether or not it passes, would be “a huge victory,” he added.
In Oregon, activists are proposing a measure for the 2020 ballot that would decriminalize psilocybin statewide for adults 21 and over who get approval from their doctors and agree to participate in a “psilocybin service.” The service would include a preparatory meeting with a therapist, one session of supervised mushroom use and a follow-up visit. Patients would be under the care of state-certified “Psilocybin Service Facilitators.”
Tom Eckert, a Portland, Ore.-based therapist who leads the psilocybin decriminalization campaign with his wife, Sheri, said the proposed limitations on psilocybin use are important.
“Psilocybin is generally safe, but it puts you in a vulnerable state of mind,” he said. “If you do it in the wrong setting, things can go sideways.”
This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
Parkinson’s disease patients have impaired insulin secretion
LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.
The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).
In short, “PD patients had higher blood glucose following oral glucose intake without … the expected concomitant rise in insulin levels, suggesting an under-active insulin response. PD patients with advanced disease” – all the patients had had PD for more than 5 years – “have impaired blood glucose levels in response to oral glucose intake,” said lead investigator Ana Marques, MD, of the Université Clermont Auvergne in Clermont-Ferrand, France.
“Blood glucose dysregulation should be screened in PD patients with moderate to advanced disease. Insulin releasing drugs should possibly be preferred [over] insulin sensitizer drugs in PD patients with diabetes,” she said at the annual meeting of the American Academy of Neurology.
Higher blood glucose levels were also associated with longer PD duration, lower dopaminergic therapy doses, and higher degrees of dysautonomia. Mean PD duration in the study was about 8 years, and mean levodopa-equivalent dose 884 mg/d.
The findings add weight to the proposed and still somewhat controversial link between PD and diabetes. “Dysglycemia appears to be another nonmotor consequence of PD,” Dr. Marques said. Because insulin production “is modulated by the autonomic nervous system, the severity of dysautonomia in PD could be linked with blood glucose dysregulation. Sympathetic denervation might lead to beta-cell dysfunction.”
Subjects were 61 years old, on average; two-thirds were men. The mean BMI was about 25 kg/m2. Patients were excluded if they had a change in dopaminergic therapy in the previous month, previous deep brain stimulation, medications that would interfere with glucose metabolism, or diabetes, among other things.
PD patients had slightly higher fasting urine glucose (P = .02). They also had lower fasting plasma insulin, but the difference wasn’t statistically significant (P = .5). Dysglycemia was also associated with higher BMI. Male gender and higher levodopa-equivalent doses were protective.
“The association between dysglycemia and PD is bilateral. In many studies, PD enhances the risk, but dysglycemia and particularly diabetes have been reported to increase the risk of PD. It goes both ways. There’s a lot that remains to be understood,” Dr. Marques said.
There was no external funding, and the investigators had nothing to disclose.
SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008
LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.
The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).
In short, “PD patients had higher blood glucose following oral glucose intake without … the expected concomitant rise in insulin levels, suggesting an under-active insulin response. PD patients with advanced disease” – all the patients had had PD for more than 5 years – “have impaired blood glucose levels in response to oral glucose intake,” said lead investigator Ana Marques, MD, of the Université Clermont Auvergne in Clermont-Ferrand, France.
“Blood glucose dysregulation should be screened in PD patients with moderate to advanced disease. Insulin releasing drugs should possibly be preferred [over] insulin sensitizer drugs in PD patients with diabetes,” she said at the annual meeting of the American Academy of Neurology.
Higher blood glucose levels were also associated with longer PD duration, lower dopaminergic therapy doses, and higher degrees of dysautonomia. Mean PD duration in the study was about 8 years, and mean levodopa-equivalent dose 884 mg/d.
The findings add weight to the proposed and still somewhat controversial link between PD and diabetes. “Dysglycemia appears to be another nonmotor consequence of PD,” Dr. Marques said. Because insulin production “is modulated by the autonomic nervous system, the severity of dysautonomia in PD could be linked with blood glucose dysregulation. Sympathetic denervation might lead to beta-cell dysfunction.”
Subjects were 61 years old, on average; two-thirds were men. The mean BMI was about 25 kg/m2. Patients were excluded if they had a change in dopaminergic therapy in the previous month, previous deep brain stimulation, medications that would interfere with glucose metabolism, or diabetes, among other things.
PD patients had slightly higher fasting urine glucose (P = .02). They also had lower fasting plasma insulin, but the difference wasn’t statistically significant (P = .5). Dysglycemia was also associated with higher BMI. Male gender and higher levodopa-equivalent doses were protective.
“The association between dysglycemia and PD is bilateral. In many studies, PD enhances the risk, but dysglycemia and particularly diabetes have been reported to increase the risk of PD. It goes both ways. There’s a lot that remains to be understood,” Dr. Marques said.
There was no external funding, and the investigators had nothing to disclose.
SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008
LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.
The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).
In short, “PD patients had higher blood glucose following oral glucose intake without … the expected concomitant rise in insulin levels, suggesting an under-active insulin response. PD patients with advanced disease” – all the patients had had PD for more than 5 years – “have impaired blood glucose levels in response to oral glucose intake,” said lead investigator Ana Marques, MD, of the Université Clermont Auvergne in Clermont-Ferrand, France.
“Blood glucose dysregulation should be screened in PD patients with moderate to advanced disease. Insulin releasing drugs should possibly be preferred [over] insulin sensitizer drugs in PD patients with diabetes,” she said at the annual meeting of the American Academy of Neurology.
Higher blood glucose levels were also associated with longer PD duration, lower dopaminergic therapy doses, and higher degrees of dysautonomia. Mean PD duration in the study was about 8 years, and mean levodopa-equivalent dose 884 mg/d.
The findings add weight to the proposed and still somewhat controversial link between PD and diabetes. “Dysglycemia appears to be another nonmotor consequence of PD,” Dr. Marques said. Because insulin production “is modulated by the autonomic nervous system, the severity of dysautonomia in PD could be linked with blood glucose dysregulation. Sympathetic denervation might lead to beta-cell dysfunction.”
Subjects were 61 years old, on average; two-thirds were men. The mean BMI was about 25 kg/m2. Patients were excluded if they had a change in dopaminergic therapy in the previous month, previous deep brain stimulation, medications that would interfere with glucose metabolism, or diabetes, among other things.
PD patients had slightly higher fasting urine glucose (P = .02). They also had lower fasting plasma insulin, but the difference wasn’t statistically significant (P = .5). Dysglycemia was also associated with higher BMI. Male gender and higher levodopa-equivalent doses were protective.
“The association between dysglycemia and PD is bilateral. In many studies, PD enhances the risk, but dysglycemia and particularly diabetes have been reported to increase the risk of PD. It goes both ways. There’s a lot that remains to be understood,” Dr. Marques said.
There was no external funding, and the investigators had nothing to disclose.
SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008
REPORTING FROM AAN 2018
Key clinical point: instead of insulin sensitizers, when necessary.
Major finding: The total blood glucose area under the time curve was significantly higher in the PD group after oral glucose challenge.
Study details: A study of 50 PD patients and 50 controls.
Disclosures: There was no external funding, and the investigators had nothing to disclose.
Source: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008
Mohammed Sanjak, PhD
Is adjuvant chemo warranted in stage I ovarian clear cell carcinoma?
In patients with stage I ovarian clear cell carcinoma, the use of adjuvant chemotherapy was associated with superior overall survival (OS), according to results of a large, retrospective cohort study.
The finding, published in Gynecologic Oncology, provides further evidence that adjuvant chemotherapy may provide a survival advantage for patients with this relatively common epithelial ovarian cancer subtype.
However, not all data to date point toward a benefit of adjuvant chemotherapy. “Its utility has yet to be established, especially for patients with stage IA disease,” wrote Dimitrios Nasioudis, MD, and his coauthors in the department of obstetrics and gynecology, Hospital of the University of Pennsylvania, Philadelphia.
In one recent large population-based study, chemotherapy was not associated with superior OS in patients with stage I disease, whereas two smaller retrospective studies suggested that chemotherapy may improve progression-free survival in that setting, noted Dr. Nasioudis and his colleagues.
Their study included data on 2,325 patients in the National Cancer Data Base diagnosed with stage I ovarian clear cell carcinoma between 2004 and 2014. That is the largest cohort of patients with stage I ovarian clear cell carcinoma with adequate staging reported to date in the medical literature, the investigators noted.
The rate of OS at 5 years was 89.2% for patients receiving adjuvant chemotherapy, versus 82.6% for those who did not (P less than .001). Furthermore, adjuvant chemotherapy was associated with improved OS after the researchers controlled for medical comorbidities, age, race, disease substage, and hospital type (hazard ratio, 0.59; 95% confidence interval, 0.45-0.78).
When the researchers looked at disease substage, women with stage IA or IB disease had superior OS with chemotherapy versus no chemotherapy, while in women with stage IC disease, there was a trend toward better OS with chemotherapy that did not reach statistical significance.
“The administration of adjuvant chemotherapy was associated with a survival benefit, even for those with stage IA disease,” the researchers wrote.
Ovarian clear cell carcinoma is the third most common subtype of epithelial ovarian carcinoma, accounting for up to 25% of new diagnoses, they said. Current U.S. and European clinical practice guidelines recommend adjuvant chemotherapy for all women with stage I disease because of a high risk of relapse associated with this subtype.
Observation could be acceptable for patients with surgical stage IA disease, in light of excellent survival rates, the Gynecologic Cancer Intergroup has suggested.
While the present study suggests a survival benefit associated with chemotherapy in stage I ovarian clear cell carcinoma, the investigators had no information on morbidity, cost, or quality-of-life impacts associated with treatment, which limit the findings.
“International collaboration, such as the creation of ovarian clear cell carcinoma registry, is greatly needed to further elucidate the optimal management of those patients,” they wrote.
Dr. Nasioudis and his coauthors had no conflicts of interest to report.
SOURCE: Nasioudis D et al. Gynecol Oncol. 2018 May 8. doi: 10.1016/j.ygyno.2018.04.567.
In patients with stage I ovarian clear cell carcinoma, the use of adjuvant chemotherapy was associated with superior overall survival (OS), according to results of a large, retrospective cohort study.
The finding, published in Gynecologic Oncology, provides further evidence that adjuvant chemotherapy may provide a survival advantage for patients with this relatively common epithelial ovarian cancer subtype.
However, not all data to date point toward a benefit of adjuvant chemotherapy. “Its utility has yet to be established, especially for patients with stage IA disease,” wrote Dimitrios Nasioudis, MD, and his coauthors in the department of obstetrics and gynecology, Hospital of the University of Pennsylvania, Philadelphia.
In one recent large population-based study, chemotherapy was not associated with superior OS in patients with stage I disease, whereas two smaller retrospective studies suggested that chemotherapy may improve progression-free survival in that setting, noted Dr. Nasioudis and his colleagues.
Their study included data on 2,325 patients in the National Cancer Data Base diagnosed with stage I ovarian clear cell carcinoma between 2004 and 2014. That is the largest cohort of patients with stage I ovarian clear cell carcinoma with adequate staging reported to date in the medical literature, the investigators noted.
The rate of OS at 5 years was 89.2% for patients receiving adjuvant chemotherapy, versus 82.6% for those who did not (P less than .001). Furthermore, adjuvant chemotherapy was associated with improved OS after the researchers controlled for medical comorbidities, age, race, disease substage, and hospital type (hazard ratio, 0.59; 95% confidence interval, 0.45-0.78).
When the researchers looked at disease substage, women with stage IA or IB disease had superior OS with chemotherapy versus no chemotherapy, while in women with stage IC disease, there was a trend toward better OS with chemotherapy that did not reach statistical significance.
“The administration of adjuvant chemotherapy was associated with a survival benefit, even for those with stage IA disease,” the researchers wrote.
Ovarian clear cell carcinoma is the third most common subtype of epithelial ovarian carcinoma, accounting for up to 25% of new diagnoses, they said. Current U.S. and European clinical practice guidelines recommend adjuvant chemotherapy for all women with stage I disease because of a high risk of relapse associated with this subtype.
Observation could be acceptable for patients with surgical stage IA disease, in light of excellent survival rates, the Gynecologic Cancer Intergroup has suggested.
While the present study suggests a survival benefit associated with chemotherapy in stage I ovarian clear cell carcinoma, the investigators had no information on morbidity, cost, or quality-of-life impacts associated with treatment, which limit the findings.
“International collaboration, such as the creation of ovarian clear cell carcinoma registry, is greatly needed to further elucidate the optimal management of those patients,” they wrote.
Dr. Nasioudis and his coauthors had no conflicts of interest to report.
SOURCE: Nasioudis D et al. Gynecol Oncol. 2018 May 8. doi: 10.1016/j.ygyno.2018.04.567.
In patients with stage I ovarian clear cell carcinoma, the use of adjuvant chemotherapy was associated with superior overall survival (OS), according to results of a large, retrospective cohort study.
The finding, published in Gynecologic Oncology, provides further evidence that adjuvant chemotherapy may provide a survival advantage for patients with this relatively common epithelial ovarian cancer subtype.
However, not all data to date point toward a benefit of adjuvant chemotherapy. “Its utility has yet to be established, especially for patients with stage IA disease,” wrote Dimitrios Nasioudis, MD, and his coauthors in the department of obstetrics and gynecology, Hospital of the University of Pennsylvania, Philadelphia.
In one recent large population-based study, chemotherapy was not associated with superior OS in patients with stage I disease, whereas two smaller retrospective studies suggested that chemotherapy may improve progression-free survival in that setting, noted Dr. Nasioudis and his colleagues.
Their study included data on 2,325 patients in the National Cancer Data Base diagnosed with stage I ovarian clear cell carcinoma between 2004 and 2014. That is the largest cohort of patients with stage I ovarian clear cell carcinoma with adequate staging reported to date in the medical literature, the investigators noted.
The rate of OS at 5 years was 89.2% for patients receiving adjuvant chemotherapy, versus 82.6% for those who did not (P less than .001). Furthermore, adjuvant chemotherapy was associated with improved OS after the researchers controlled for medical comorbidities, age, race, disease substage, and hospital type (hazard ratio, 0.59; 95% confidence interval, 0.45-0.78).
When the researchers looked at disease substage, women with stage IA or IB disease had superior OS with chemotherapy versus no chemotherapy, while in women with stage IC disease, there was a trend toward better OS with chemotherapy that did not reach statistical significance.
“The administration of adjuvant chemotherapy was associated with a survival benefit, even for those with stage IA disease,” the researchers wrote.
Ovarian clear cell carcinoma is the third most common subtype of epithelial ovarian carcinoma, accounting for up to 25% of new diagnoses, they said. Current U.S. and European clinical practice guidelines recommend adjuvant chemotherapy for all women with stage I disease because of a high risk of relapse associated with this subtype.
Observation could be acceptable for patients with surgical stage IA disease, in light of excellent survival rates, the Gynecologic Cancer Intergroup has suggested.
While the present study suggests a survival benefit associated with chemotherapy in stage I ovarian clear cell carcinoma, the investigators had no information on morbidity, cost, or quality-of-life impacts associated with treatment, which limit the findings.
“International collaboration, such as the creation of ovarian clear cell carcinoma registry, is greatly needed to further elucidate the optimal management of those patients,” they wrote.
Dr. Nasioudis and his coauthors had no conflicts of interest to report.
SOURCE: Nasioudis D et al. Gynecol Oncol. 2018 May 8. doi: 10.1016/j.ygyno.2018.04.567.
FROM GYNECOLOGIC ONCOLOGY
Key clinical point: Adjuvant chemotherapy was associated with improved survival in patients with stage I OCCC.
Major finding: Five-year overall survival was 89.2% for patients receiving adjuvant chemotherapy versus 82.6% for those who did not (P less than .001).
Study details: A retrospective cohort study of 2,325 patients with stage I ovarian clear cell carcinoma diagnosed between 2004 and 2014.
Disclosures: The authors had no conflicts of interest to report.
Source: Nasioudis D et al. Gynecol Oncol. 2018 May 8. doi: 10.1016/j.ygyno.2018.04.567.
ESBL-resistant bacteria spread in hospital despite strict contact precautions
MADRID – even when staff employed an active surveillance screening protocol to identify every carrier at admission.
The failure of precautions may have root in two thorny issues, said Friederike Maechler, MD, who presented the data at the the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“Adherence to strict contact isolation and hand hygiene is never 100% in a real-life scenario,” said Dr. Maechler, of Charite University Hospital, Berlin. Also, she said, contact isolation can only be effective in a ward if all, or at least most, of the ESBL-E carriers are identified. “Even with an extensive surveillance screening program established, many carriers remained unknown to the health care staff.”
The 25-month study, dubbed R-Gnosis, was conducted in 20 Western European hospitals in Madrid, Berlin, Utrecht, and Geneva. It compared 12 months of contact precaution with standard precaution infection control strategies in medical and surgical non-ICUs.
The entire study hinged on a strict protocol to identify as many ESBL-E carriers as possible. This was done by screening upon admission to the unit, screening once per week during the hospital stay, and screening on discharge. Each patient underwent deep rectal swabs that were cultured on agar and screened for resistance.
The crossover design trial randomized each unit to either contact precautions or standard precautions for 12 months, followed by a 1-month washout period, after which they began the other protocol.
In all, 50,870 patients were entered into the study. By the end, Dr. Maechler had data on 11,367 patients with full screening and follow-up.
Standard precautions did not require a private bedroom, with gloves, gowns, and apron needed for direct contact to body fluids or wounds only, and consistent hand hygiene. Contact precautions required a private bedroom and strict hand hygiene, with gloves, gowns, and aprons used for any patient contact. Study staff monitored compliance with these procedures monthly.
The primary outcome was the ESBL-E acquisition rate per 1,000 patient days. This was defined as a new ESBL-E detection after the patient had a prior negative screen. Dr. Maechler noted that by epidemiological definition, acquisition does not necessarily imply cross-transmission from other patients.
Adherence to the study protocols was good, she said. Adherence to both contact and standard precautions was about 85%, while adherence to hand hygiene was less at around 62%.
Admission ESBL-E screenings revealed that about 12% of the study population was colonized with the strain at admission. The proportion was nearly identical in the contact and standard precaution groups (11.6%, 12.2%).
The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6 in both intervention periods, regardless of the type of precaution taken. Contact precautions appeared to be slightly less effective for Escherichia coli (3.6 per 1,000 patient-days in contact precautions vs. 3.5 in standard), compared with Klebsiella pneumoniae (1.8 vs. 2.2).
A multivariate analysis controlled for screening compliance, colonization pressure, and length of stay, study site, and season of year. It showed that strict contact precautions did not reduce the risk of ward-acquired ESBL-E carriage.
Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
SOURCE: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
MADRID – even when staff employed an active surveillance screening protocol to identify every carrier at admission.
The failure of precautions may have root in two thorny issues, said Friederike Maechler, MD, who presented the data at the the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“Adherence to strict contact isolation and hand hygiene is never 100% in a real-life scenario,” said Dr. Maechler, of Charite University Hospital, Berlin. Also, she said, contact isolation can only be effective in a ward if all, or at least most, of the ESBL-E carriers are identified. “Even with an extensive surveillance screening program established, many carriers remained unknown to the health care staff.”
The 25-month study, dubbed R-Gnosis, was conducted in 20 Western European hospitals in Madrid, Berlin, Utrecht, and Geneva. It compared 12 months of contact precaution with standard precaution infection control strategies in medical and surgical non-ICUs.
The entire study hinged on a strict protocol to identify as many ESBL-E carriers as possible. This was done by screening upon admission to the unit, screening once per week during the hospital stay, and screening on discharge. Each patient underwent deep rectal swabs that were cultured on agar and screened for resistance.
The crossover design trial randomized each unit to either contact precautions or standard precautions for 12 months, followed by a 1-month washout period, after which they began the other protocol.
In all, 50,870 patients were entered into the study. By the end, Dr. Maechler had data on 11,367 patients with full screening and follow-up.
Standard precautions did not require a private bedroom, with gloves, gowns, and apron needed for direct contact to body fluids or wounds only, and consistent hand hygiene. Contact precautions required a private bedroom and strict hand hygiene, with gloves, gowns, and aprons used for any patient contact. Study staff monitored compliance with these procedures monthly.
The primary outcome was the ESBL-E acquisition rate per 1,000 patient days. This was defined as a new ESBL-E detection after the patient had a prior negative screen. Dr. Maechler noted that by epidemiological definition, acquisition does not necessarily imply cross-transmission from other patients.
Adherence to the study protocols was good, she said. Adherence to both contact and standard precautions was about 85%, while adherence to hand hygiene was less at around 62%.
Admission ESBL-E screenings revealed that about 12% of the study population was colonized with the strain at admission. The proportion was nearly identical in the contact and standard precaution groups (11.6%, 12.2%).
The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6 in both intervention periods, regardless of the type of precaution taken. Contact precautions appeared to be slightly less effective for Escherichia coli (3.6 per 1,000 patient-days in contact precautions vs. 3.5 in standard), compared with Klebsiella pneumoniae (1.8 vs. 2.2).
A multivariate analysis controlled for screening compliance, colonization pressure, and length of stay, study site, and season of year. It showed that strict contact precautions did not reduce the risk of ward-acquired ESBL-E carriage.
Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
SOURCE: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
MADRID – even when staff employed an active surveillance screening protocol to identify every carrier at admission.
The failure of precautions may have root in two thorny issues, said Friederike Maechler, MD, who presented the data at the the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“Adherence to strict contact isolation and hand hygiene is never 100% in a real-life scenario,” said Dr. Maechler, of Charite University Hospital, Berlin. Also, she said, contact isolation can only be effective in a ward if all, or at least most, of the ESBL-E carriers are identified. “Even with an extensive surveillance screening program established, many carriers remained unknown to the health care staff.”
The 25-month study, dubbed R-Gnosis, was conducted in 20 Western European hospitals in Madrid, Berlin, Utrecht, and Geneva. It compared 12 months of contact precaution with standard precaution infection control strategies in medical and surgical non-ICUs.
The entire study hinged on a strict protocol to identify as many ESBL-E carriers as possible. This was done by screening upon admission to the unit, screening once per week during the hospital stay, and screening on discharge. Each patient underwent deep rectal swabs that were cultured on agar and screened for resistance.
The crossover design trial randomized each unit to either contact precautions or standard precautions for 12 months, followed by a 1-month washout period, after which they began the other protocol.
In all, 50,870 patients were entered into the study. By the end, Dr. Maechler had data on 11,367 patients with full screening and follow-up.
Standard precautions did not require a private bedroom, with gloves, gowns, and apron needed for direct contact to body fluids or wounds only, and consistent hand hygiene. Contact precautions required a private bedroom and strict hand hygiene, with gloves, gowns, and aprons used for any patient contact. Study staff monitored compliance with these procedures monthly.
The primary outcome was the ESBL-E acquisition rate per 1,000 patient days. This was defined as a new ESBL-E detection after the patient had a prior negative screen. Dr. Maechler noted that by epidemiological definition, acquisition does not necessarily imply cross-transmission from other patients.
Adherence to the study protocols was good, she said. Adherence to both contact and standard precautions was about 85%, while adherence to hand hygiene was less at around 62%.
Admission ESBL-E screenings revealed that about 12% of the study population was colonized with the strain at admission. The proportion was nearly identical in the contact and standard precaution groups (11.6%, 12.2%).
The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6 in both intervention periods, regardless of the type of precaution taken. Contact precautions appeared to be slightly less effective for Escherichia coli (3.6 per 1,000 patient-days in contact precautions vs. 3.5 in standard), compared with Klebsiella pneumoniae (1.8 vs. 2.2).
A multivariate analysis controlled for screening compliance, colonization pressure, and length of stay, study site, and season of year. It showed that strict contact precautions did not reduce the risk of ward-acquired ESBL-E carriage.
Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
SOURCE: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
REPORTING FROM ECCMID 2018
Key clinical point: A protocol of strict contact precautions and hand hygiene was no better than standard contact precautions at preventing the spread of extended-spectrum, beta-lactamase–resistant Enterobacteriaceae.
Major finding: The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6, regardless of precaution.
Study details: The 25-month crossover trial comprised more than 11,000 patients.
Disclosures: Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
Source: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
Multiple analgesia options for kids with acute pain
TORONTO – according to Naveen Poonai, MD, FRCPC.
“Too many times, nonpharmacologic therapies are relegated to the very last paragraph of recommendations or to the very bottom of a URL,” he said at the Pediatric Academic Societies meeting. “Nonpharmacologic therapies are things that our grandparents told us to do: common sense things that can be done at triage. They don’t require memorization of dosing, and most importantly, they don’t have side effects.”
When analgesia is indicated, clinicians can choose from a variety of agents in the postcodeine era. Dr. Poonai said that musculoskeletal injuries constitute 10-20% of pediatric emergency department visits, yet fewer than 60% of children receive adequate analgesia. “That’s what’s really important for patient and caregiver satisfaction,” he said.
Mounting evidence supports the use of ibuprofen as a go-to agent for mild to moderate pain in patients with musculoskeletal injuries, including results from a randomized, controlled multicenter trial of 500 youth (Canadian J Emerg Med. 2016:18:S29). “We know that ibuprofen is superior to acetaminophen or codeine and that it’s as good or better than oral opioids and with fewer side effects,” Dr. Poonai said, adding that it provides a 25 mm visual analog score (VAS) reduction in pain at 60 minutes. Another study that compared ibuprofen with codeine for acute pediatric arm fracture pain found that ibuprofen was associated with improved functioning and was at least as effective as acetaminophen plus codeine (Ann Emerg Med. 2009 Oct;54[4]:553-60).
A number of oral opioids have gained favor for use in children who present with acute pain. However, in a randomized trial, Dr. Poonai and his associates found no significant difference in analgesic efficacy between orally administered morphine and ibuprofen for the management of postfracture pain in 134 children (CMAJ. 2014 Dec 9;186[18]:1358-63). Oral morphine was also associated with more side effects. At the same time, tramadol and hydromorphone have not been well studied in children with musculoskeletal pain. “Currently, the use of hydromorphone is limited to children with sickle cell disease, but the use is branching out,” he said. “Oxycodone and oral morphine pose the greatest risk of side effects. The bottom line here is that opioids should be added to ibuprofen and acetaminophen rather than replacing them for mild to moderate pain.”
In 2014, a study from the Cochrane Database of Systematic Reviews concluded that intranasal fentanyl can be effective for the management of moderate to severe pain in children. A dose of 1.0-1.5 mcg/kg is associated with a 40-mm pain reduction in VAS at 10 minutes. “The benefits are that it is not an invasive approach, it’s been rigorously studied, and it is equivalent to IV morphine for moderate to severe pain,” said Dr. Poonai, who was not part of the Cochrane review. “It lasts about 60 minutes, with minimal side effects.”
A separate analysis found that intranasal fentanyl and ketamine were associated with similar pain reduction in children with moderate to severe pain from limb injury (Ann Emerg Med. 2015 Mar;65[3]:248-54.e1). Ketamine was associated with more minor adverse events. An intranasal dose of 1 mg/kg can cause a 40- to 45-mm reduction in VAS at 30 minutes.
Dr. Poonai went on to discuss treatment options for abdominal pain, noting that fewer than two-thirds of children with suspected appendicitis receive analgesia. “If they are receiving it, it’s often not until after the ultrasound is performed,” he said. “There is a still a reluctance toward providing opioid analgesia for a child with suspected appendicitis for fear of masking a diagnosis or leading to complications.” A systematic review led by Dr. Poonai found that the use of opioids in undifferentiated acute abdominal pain in children is associated with no difference in pain scores and an increased risk of mild side effects (Acad Emerg Med. 2014 21[11]:1183-92). However, there was no increased risk of perforation or abscess. “We found that single-dose IV opioids were actually beneficial,” he said.
Dr. Poonai characterized most of the current evidence on IV morphine for suspected appendicitis as being of low to moderate quality, “but they are generally favorable for the indication,” he said. “It is titratable to effect, and triage-initiated protocols improve timing and consistency of analgesia.” He reported having no financial disclosures.
TORONTO – according to Naveen Poonai, MD, FRCPC.
“Too many times, nonpharmacologic therapies are relegated to the very last paragraph of recommendations or to the very bottom of a URL,” he said at the Pediatric Academic Societies meeting. “Nonpharmacologic therapies are things that our grandparents told us to do: common sense things that can be done at triage. They don’t require memorization of dosing, and most importantly, they don’t have side effects.”
When analgesia is indicated, clinicians can choose from a variety of agents in the postcodeine era. Dr. Poonai said that musculoskeletal injuries constitute 10-20% of pediatric emergency department visits, yet fewer than 60% of children receive adequate analgesia. “That’s what’s really important for patient and caregiver satisfaction,” he said.
Mounting evidence supports the use of ibuprofen as a go-to agent for mild to moderate pain in patients with musculoskeletal injuries, including results from a randomized, controlled multicenter trial of 500 youth (Canadian J Emerg Med. 2016:18:S29). “We know that ibuprofen is superior to acetaminophen or codeine and that it’s as good or better than oral opioids and with fewer side effects,” Dr. Poonai said, adding that it provides a 25 mm visual analog score (VAS) reduction in pain at 60 minutes. Another study that compared ibuprofen with codeine for acute pediatric arm fracture pain found that ibuprofen was associated with improved functioning and was at least as effective as acetaminophen plus codeine (Ann Emerg Med. 2009 Oct;54[4]:553-60).
A number of oral opioids have gained favor for use in children who present with acute pain. However, in a randomized trial, Dr. Poonai and his associates found no significant difference in analgesic efficacy between orally administered morphine and ibuprofen for the management of postfracture pain in 134 children (CMAJ. 2014 Dec 9;186[18]:1358-63). Oral morphine was also associated with more side effects. At the same time, tramadol and hydromorphone have not been well studied in children with musculoskeletal pain. “Currently, the use of hydromorphone is limited to children with sickle cell disease, but the use is branching out,” he said. “Oxycodone and oral morphine pose the greatest risk of side effects. The bottom line here is that opioids should be added to ibuprofen and acetaminophen rather than replacing them for mild to moderate pain.”
In 2014, a study from the Cochrane Database of Systematic Reviews concluded that intranasal fentanyl can be effective for the management of moderate to severe pain in children. A dose of 1.0-1.5 mcg/kg is associated with a 40-mm pain reduction in VAS at 10 minutes. “The benefits are that it is not an invasive approach, it’s been rigorously studied, and it is equivalent to IV morphine for moderate to severe pain,” said Dr. Poonai, who was not part of the Cochrane review. “It lasts about 60 minutes, with minimal side effects.”
A separate analysis found that intranasal fentanyl and ketamine were associated with similar pain reduction in children with moderate to severe pain from limb injury (Ann Emerg Med. 2015 Mar;65[3]:248-54.e1). Ketamine was associated with more minor adverse events. An intranasal dose of 1 mg/kg can cause a 40- to 45-mm reduction in VAS at 30 minutes.
Dr. Poonai went on to discuss treatment options for abdominal pain, noting that fewer than two-thirds of children with suspected appendicitis receive analgesia. “If they are receiving it, it’s often not until after the ultrasound is performed,” he said. “There is a still a reluctance toward providing opioid analgesia for a child with suspected appendicitis for fear of masking a diagnosis or leading to complications.” A systematic review led by Dr. Poonai found that the use of opioids in undifferentiated acute abdominal pain in children is associated with no difference in pain scores and an increased risk of mild side effects (Acad Emerg Med. 2014 21[11]:1183-92). However, there was no increased risk of perforation or abscess. “We found that single-dose IV opioids were actually beneficial,” he said.
Dr. Poonai characterized most of the current evidence on IV morphine for suspected appendicitis as being of low to moderate quality, “but they are generally favorable for the indication,” he said. “It is titratable to effect, and triage-initiated protocols improve timing and consistency of analgesia.” He reported having no financial disclosures.
TORONTO – according to Naveen Poonai, MD, FRCPC.
“Too many times, nonpharmacologic therapies are relegated to the very last paragraph of recommendations or to the very bottom of a URL,” he said at the Pediatric Academic Societies meeting. “Nonpharmacologic therapies are things that our grandparents told us to do: common sense things that can be done at triage. They don’t require memorization of dosing, and most importantly, they don’t have side effects.”
When analgesia is indicated, clinicians can choose from a variety of agents in the postcodeine era. Dr. Poonai said that musculoskeletal injuries constitute 10-20% of pediatric emergency department visits, yet fewer than 60% of children receive adequate analgesia. “That’s what’s really important for patient and caregiver satisfaction,” he said.
Mounting evidence supports the use of ibuprofen as a go-to agent for mild to moderate pain in patients with musculoskeletal injuries, including results from a randomized, controlled multicenter trial of 500 youth (Canadian J Emerg Med. 2016:18:S29). “We know that ibuprofen is superior to acetaminophen or codeine and that it’s as good or better than oral opioids and with fewer side effects,” Dr. Poonai said, adding that it provides a 25 mm visual analog score (VAS) reduction in pain at 60 minutes. Another study that compared ibuprofen with codeine for acute pediatric arm fracture pain found that ibuprofen was associated with improved functioning and was at least as effective as acetaminophen plus codeine (Ann Emerg Med. 2009 Oct;54[4]:553-60).
A number of oral opioids have gained favor for use in children who present with acute pain. However, in a randomized trial, Dr. Poonai and his associates found no significant difference in analgesic efficacy between orally administered morphine and ibuprofen for the management of postfracture pain in 134 children (CMAJ. 2014 Dec 9;186[18]:1358-63). Oral morphine was also associated with more side effects. At the same time, tramadol and hydromorphone have not been well studied in children with musculoskeletal pain. “Currently, the use of hydromorphone is limited to children with sickle cell disease, but the use is branching out,” he said. “Oxycodone and oral morphine pose the greatest risk of side effects. The bottom line here is that opioids should be added to ibuprofen and acetaminophen rather than replacing them for mild to moderate pain.”
In 2014, a study from the Cochrane Database of Systematic Reviews concluded that intranasal fentanyl can be effective for the management of moderate to severe pain in children. A dose of 1.0-1.5 mcg/kg is associated with a 40-mm pain reduction in VAS at 10 minutes. “The benefits are that it is not an invasive approach, it’s been rigorously studied, and it is equivalent to IV morphine for moderate to severe pain,” said Dr. Poonai, who was not part of the Cochrane review. “It lasts about 60 minutes, with minimal side effects.”
A separate analysis found that intranasal fentanyl and ketamine were associated with similar pain reduction in children with moderate to severe pain from limb injury (Ann Emerg Med. 2015 Mar;65[3]:248-54.e1). Ketamine was associated with more minor adverse events. An intranasal dose of 1 mg/kg can cause a 40- to 45-mm reduction in VAS at 30 minutes.
Dr. Poonai went on to discuss treatment options for abdominal pain, noting that fewer than two-thirds of children with suspected appendicitis receive analgesia. “If they are receiving it, it’s often not until after the ultrasound is performed,” he said. “There is a still a reluctance toward providing opioid analgesia for a child with suspected appendicitis for fear of masking a diagnosis or leading to complications.” A systematic review led by Dr. Poonai found that the use of opioids in undifferentiated acute abdominal pain in children is associated with no difference in pain scores and an increased risk of mild side effects (Acad Emerg Med. 2014 21[11]:1183-92). However, there was no increased risk of perforation or abscess. “We found that single-dose IV opioids were actually beneficial,” he said.
Dr. Poonai characterized most of the current evidence on IV morphine for suspected appendicitis as being of low to moderate quality, “but they are generally favorable for the indication,” he said. “It is titratable to effect, and triage-initiated protocols improve timing and consistency of analgesia.” He reported having no financial disclosures.
EXPERT ANALYSIS FROM PAS 2018
TissueGene-C effects on knee OA seen at 3 years
LIVERPOOL, ENGLAND – TissueGene-C continues to show promise as a potential disease-modifying osteoarthritis drug, according to the long-term follow-up data of a phase 3 trial.
Within 2-3 years of receiving a single injection of the novel cell-gene therapy, patients with moderate knee OA were still experiencing significant improvement in the coprimary endpoints of knee symptoms, function, sports activity, and knee pain versus baseline values.
Differences in International Knee Documentation Committee (IKDC) scores from baseline to 2 and 3 years were a respective 15.3 and 14.8 points (both P less than .05 vs. baseline). Pain, assessed on a visual analog scale, was also significantly improved from baseline to 2 and 3 years (score changes –23.5 and –23.3; P less than .05 vs. baseline).
There were also significant improvements in the secondary endpoint of pain, stiffness, and physical function measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), with changes in scores of –19.8 and –17.4 versus baseline at 2 and 3 years, respectively (both P less than .05 vs. baseline).
“INVOISSA-K [TissueGene-C] is the first-in-class cell and gene therapy for the treatment of knee OA,” Dr. Lee reminded delegates at the congress, which is sponsored by the Osteoarthritis Research Society International. The novel treatment was made by collecting chondrocytes from a subject with polydactyl hands and then culturing these to create two subpopulations of cells, one with allogenic chondrocytes and the other with genetically modified chondrocytes that overexpress transforming growth factor-beta1. These subpopulations are then mixed in the ratio of 3:1 and delivered in a single intra-articular injection.
Dr. Lee, who is the president and chief executive officer of Kolon TissueGene, Rockville, Md., reported new findings of a phase 3 trial conducted exclusively in Korea at 12 study centers, the results of which were first presented at OARSI 2016.
At that time only the 12-month primary endpoint data were available, which showed that TissueGene-C improved IKDC scores from baseline by a significantly greater amount than a saline placebo, with changes in scores of 15.1 and 5 points, respectively, versus baseline values. Improvements in IKDC scores were seen as early as 3 months but only became significantly better than placebo at 6 months.
Similarly, visual analog scale pain scores had improved from baseline as early as 3 months but were only significantly different from placebo at 6 months (–23.4 change from baseline for TissueGene-C vs. –14.6 for placebo) and out to 12 months (–24.5 vs. –10.3). WOMAC scores with TissueGene-C were only significantly different from placebo at 12 months (–13.5 vs. –6.2 from baseline, respectively).
The 12-month OMERACT-OARSI responder rate was 84% for TissueGene-C and 45% for placebo. The most common adverse events seen with TissueGene-C were related to the injection site, with peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection-site pain (5%) reported.
A total of 163 patients were recruited into the study, all had Kellgren-Lawrence grade 3 knee OA, which was also graded as 3 or 4 on the International Cartilage Regeneration & Joint Preservation Society scale. Major lesions had be 6 cm2 or smaller. Active treatment was given to 78 patients, and 81 received placebo. The primary assessment period was at 12 months, but patients continued to be followed out to 5 years.
At OARSI 2018, Dr. Lee presented the findings of 12-month structural modification analyses for the first time. These showed that while the osteophyte score on MRI was not significantly different from baseline in the active-treatment arm, there was a significantly increased osteophyte score and total cartilage defect in the placebo-treated patients versus baseline values.
Subchondral bone changes at 12 months showed a trend for less bone area change with TissueGene-C than placebo and a trend for increased cartilage thickness. Greater reductions in serum CTX-1 and urine CTX-II were seen with active treatment than placebo, relative to screening values.
X-ray evaluation of joint-space narrowing showed that nonprogression was more likely in patients treated with TissueGene-C than with placebo (77% vs. 57%), although this was not significant. In addition, fewer patients treated with TissueGene-C than placebo who needed a total knee replacement at 2 years (0% and 7.5%) and at 3 years (2% and 14%).
TissueGene-C “has great potential” for being the first disease-modifying osteoarthritis drug to get to market, Dr. Lee suggested.
The clinical development program for TissueGene-C is further advanced in Korea than in the United States, where a phase 3 trial is about to start recruitment soon.
“We started our clinical trials in 2005 in Korea and in the U.S. simultaneously,” Dr. Lee said, noting that a biologics license application submitted in Korea in 2016 had been accepted by the Ministry of Food and Drug Safety on July 12, 2017, while only phase 1 and 2 trials have been completed in the United States
The study was funded by Kolon Life Science and TissueGene. Dr. Lee is an employee of TissueGene.
SOURCE: Lee B et al. Osteoarthritis Cartilage. 2018 Apr;26(1):S43-4.
LIVERPOOL, ENGLAND – TissueGene-C continues to show promise as a potential disease-modifying osteoarthritis drug, according to the long-term follow-up data of a phase 3 trial.
Within 2-3 years of receiving a single injection of the novel cell-gene therapy, patients with moderate knee OA were still experiencing significant improvement in the coprimary endpoints of knee symptoms, function, sports activity, and knee pain versus baseline values.
Differences in International Knee Documentation Committee (IKDC) scores from baseline to 2 and 3 years were a respective 15.3 and 14.8 points (both P less than .05 vs. baseline). Pain, assessed on a visual analog scale, was also significantly improved from baseline to 2 and 3 years (score changes –23.5 and –23.3; P less than .05 vs. baseline).
There were also significant improvements in the secondary endpoint of pain, stiffness, and physical function measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), with changes in scores of –19.8 and –17.4 versus baseline at 2 and 3 years, respectively (both P less than .05 vs. baseline).
“INVOISSA-K [TissueGene-C] is the first-in-class cell and gene therapy for the treatment of knee OA,” Dr. Lee reminded delegates at the congress, which is sponsored by the Osteoarthritis Research Society International. The novel treatment was made by collecting chondrocytes from a subject with polydactyl hands and then culturing these to create two subpopulations of cells, one with allogenic chondrocytes and the other with genetically modified chondrocytes that overexpress transforming growth factor-beta1. These subpopulations are then mixed in the ratio of 3:1 and delivered in a single intra-articular injection.
Dr. Lee, who is the president and chief executive officer of Kolon TissueGene, Rockville, Md., reported new findings of a phase 3 trial conducted exclusively in Korea at 12 study centers, the results of which were first presented at OARSI 2016.
At that time only the 12-month primary endpoint data were available, which showed that TissueGene-C improved IKDC scores from baseline by a significantly greater amount than a saline placebo, with changes in scores of 15.1 and 5 points, respectively, versus baseline values. Improvements in IKDC scores were seen as early as 3 months but only became significantly better than placebo at 6 months.
Similarly, visual analog scale pain scores had improved from baseline as early as 3 months but were only significantly different from placebo at 6 months (–23.4 change from baseline for TissueGene-C vs. –14.6 for placebo) and out to 12 months (–24.5 vs. –10.3). WOMAC scores with TissueGene-C were only significantly different from placebo at 12 months (–13.5 vs. –6.2 from baseline, respectively).
The 12-month OMERACT-OARSI responder rate was 84% for TissueGene-C and 45% for placebo. The most common adverse events seen with TissueGene-C were related to the injection site, with peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection-site pain (5%) reported.
A total of 163 patients were recruited into the study, all had Kellgren-Lawrence grade 3 knee OA, which was also graded as 3 or 4 on the International Cartilage Regeneration & Joint Preservation Society scale. Major lesions had be 6 cm2 or smaller. Active treatment was given to 78 patients, and 81 received placebo. The primary assessment period was at 12 months, but patients continued to be followed out to 5 years.
At OARSI 2018, Dr. Lee presented the findings of 12-month structural modification analyses for the first time. These showed that while the osteophyte score on MRI was not significantly different from baseline in the active-treatment arm, there was a significantly increased osteophyte score and total cartilage defect in the placebo-treated patients versus baseline values.
Subchondral bone changes at 12 months showed a trend for less bone area change with TissueGene-C than placebo and a trend for increased cartilage thickness. Greater reductions in serum CTX-1 and urine CTX-II were seen with active treatment than placebo, relative to screening values.
X-ray evaluation of joint-space narrowing showed that nonprogression was more likely in patients treated with TissueGene-C than with placebo (77% vs. 57%), although this was not significant. In addition, fewer patients treated with TissueGene-C than placebo who needed a total knee replacement at 2 years (0% and 7.5%) and at 3 years (2% and 14%).
TissueGene-C “has great potential” for being the first disease-modifying osteoarthritis drug to get to market, Dr. Lee suggested.
The clinical development program for TissueGene-C is further advanced in Korea than in the United States, where a phase 3 trial is about to start recruitment soon.
“We started our clinical trials in 2005 in Korea and in the U.S. simultaneously,” Dr. Lee said, noting that a biologics license application submitted in Korea in 2016 had been accepted by the Ministry of Food and Drug Safety on July 12, 2017, while only phase 1 and 2 trials have been completed in the United States
The study was funded by Kolon Life Science and TissueGene. Dr. Lee is an employee of TissueGene.
SOURCE: Lee B et al. Osteoarthritis Cartilage. 2018 Apr;26(1):S43-4.
LIVERPOOL, ENGLAND – TissueGene-C continues to show promise as a potential disease-modifying osteoarthritis drug, according to the long-term follow-up data of a phase 3 trial.
Within 2-3 years of receiving a single injection of the novel cell-gene therapy, patients with moderate knee OA were still experiencing significant improvement in the coprimary endpoints of knee symptoms, function, sports activity, and knee pain versus baseline values.
Differences in International Knee Documentation Committee (IKDC) scores from baseline to 2 and 3 years were a respective 15.3 and 14.8 points (both P less than .05 vs. baseline). Pain, assessed on a visual analog scale, was also significantly improved from baseline to 2 and 3 years (score changes –23.5 and –23.3; P less than .05 vs. baseline).
There were also significant improvements in the secondary endpoint of pain, stiffness, and physical function measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), with changes in scores of –19.8 and –17.4 versus baseline at 2 and 3 years, respectively (both P less than .05 vs. baseline).
“INVOISSA-K [TissueGene-C] is the first-in-class cell and gene therapy for the treatment of knee OA,” Dr. Lee reminded delegates at the congress, which is sponsored by the Osteoarthritis Research Society International. The novel treatment was made by collecting chondrocytes from a subject with polydactyl hands and then culturing these to create two subpopulations of cells, one with allogenic chondrocytes and the other with genetically modified chondrocytes that overexpress transforming growth factor-beta1. These subpopulations are then mixed in the ratio of 3:1 and delivered in a single intra-articular injection.
Dr. Lee, who is the president and chief executive officer of Kolon TissueGene, Rockville, Md., reported new findings of a phase 3 trial conducted exclusively in Korea at 12 study centers, the results of which were first presented at OARSI 2016.
At that time only the 12-month primary endpoint data were available, which showed that TissueGene-C improved IKDC scores from baseline by a significantly greater amount than a saline placebo, with changes in scores of 15.1 and 5 points, respectively, versus baseline values. Improvements in IKDC scores were seen as early as 3 months but only became significantly better than placebo at 6 months.
Similarly, visual analog scale pain scores had improved from baseline as early as 3 months but were only significantly different from placebo at 6 months (–23.4 change from baseline for TissueGene-C vs. –14.6 for placebo) and out to 12 months (–24.5 vs. –10.3). WOMAC scores with TissueGene-C were only significantly different from placebo at 12 months (–13.5 vs. –6.2 from baseline, respectively).
The 12-month OMERACT-OARSI responder rate was 84% for TissueGene-C and 45% for placebo. The most common adverse events seen with TissueGene-C were related to the injection site, with peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection-site pain (5%) reported.
A total of 163 patients were recruited into the study, all had Kellgren-Lawrence grade 3 knee OA, which was also graded as 3 or 4 on the International Cartilage Regeneration & Joint Preservation Society scale. Major lesions had be 6 cm2 or smaller. Active treatment was given to 78 patients, and 81 received placebo. The primary assessment period was at 12 months, but patients continued to be followed out to 5 years.
At OARSI 2018, Dr. Lee presented the findings of 12-month structural modification analyses for the first time. These showed that while the osteophyte score on MRI was not significantly different from baseline in the active-treatment arm, there was a significantly increased osteophyte score and total cartilage defect in the placebo-treated patients versus baseline values.
Subchondral bone changes at 12 months showed a trend for less bone area change with TissueGene-C than placebo and a trend for increased cartilage thickness. Greater reductions in serum CTX-1 and urine CTX-II were seen with active treatment than placebo, relative to screening values.
X-ray evaluation of joint-space narrowing showed that nonprogression was more likely in patients treated with TissueGene-C than with placebo (77% vs. 57%), although this was not significant. In addition, fewer patients treated with TissueGene-C than placebo who needed a total knee replacement at 2 years (0% and 7.5%) and at 3 years (2% and 14%).
TissueGene-C “has great potential” for being the first disease-modifying osteoarthritis drug to get to market, Dr. Lee suggested.
The clinical development program for TissueGene-C is further advanced in Korea than in the United States, where a phase 3 trial is about to start recruitment soon.
“We started our clinical trials in 2005 in Korea and in the U.S. simultaneously,” Dr. Lee said, noting that a biologics license application submitted in Korea in 2016 had been accepted by the Ministry of Food and Drug Safety on July 12, 2017, while only phase 1 and 2 trials have been completed in the United States
The study was funded by Kolon Life Science and TissueGene. Dr. Lee is an employee of TissueGene.
SOURCE: Lee B et al. Osteoarthritis Cartilage. 2018 Apr;26(1):S43-4.
REPORTING FROM OARSI 2018
Key clinical point: A single intra-articular injection of TissueGene C produced significant and long-term relief of knee osteoarthritis.
Major finding: Changes in baseline International Knee Documentation Committee and visual analog scale pain scores from baseline to 2 and 3 years were 15.3 and 14.8 points (P less than .05), and –23.5 and –23.3 (P less than .05), respectively.
Study details: A multicenter, phase 3, randomized, double-blind, placebo-controlled trial of 163 patients with knee osteoarthritis.
Disclosures: The study was funded by Kolon Life Science and TissueGene. Dr. Lee is an employee of TissueGene.
Source: Lee B et al. Osteoarthritis Cartilage. 2018 Apr;26(1):S43-4.
Fewer preterm deliveries, and perinatal mortality down
Fewer infants are being delivered early, and there has been a decline in neonatal mortality, according to a retrospective cohort study of more than 34 million singleton live births.
Researchers presented the results of a study in the May 14 online edition of JAMA Pediatrics that attempted to quantify changes in gestational age distribution and gestational age–specific perinatal mortality in the United States between 2007 and 2015.
However the proportion of births at a gestational age of 39-40 weeks increased from 54.5% to 60.2% in that same time period.
“The decreasing proportion of births at gestational ages of 34-36 and 37-38 weeks may be associated with changes in the timing of elective delivery, with hospital policies and quality initiatives effectively reducing unindicated deliveries before 39 completed weeks of gestation,” wrote Cande V. Ananth, PhD, of Columbia University, New York, and coauthors.
“Increased use of low-dose aspirin in women with ischemic placental disease may additionally have resulted in decreased need for indicated delivery before 39 weeks.”
At the same time, perinatal mortality rates decreased overall, from 9 per 1,000 births in 2007 to 8.6 per 1,000 births in 2015, but increased significantly in gestational ages 32-33 weeks (7%), 34-36 weeks (15%), and 37-38 weeks (23%) over that period. There was also a significant 31% increase in perinatal mortality at gestational age 42-44 weeks, but decreases at 20-27 weeks and 39-40 weeks.
Stillbirth rates also increased for gestational ages of 20-27 weeks, 28-31 weeks, 32-33 weeks, 34-36 weeks, 37-38 weeks, and 42-44 weeks.
Commenting on the changes in perinatal and neonatal mortality rates at gestational ages of 34-36 weeks and 37-38 weeks, the authors suggested this may have been the result of recommendations to postpone elective deliveries until 39 weeks.
“A possible reason for the increased mortality at a gestational age of 37-38 weeks could be that physicians may be more likely to defer to 39 weeks for delivery for women at moderately increased risk for adverse perinatal outcomes,” they wrote.
“We found that the decrease in neonatal mortality rates from 2007 to 2015 in the United States was largely associated with changes in the underlying gestational age distribution and less associated with changes in gestational age–specific mortality.”
The researchers reported that they had no conflicts of interest.
SOURCE: Ananth C et al. JAMA Pediatrics. 2018 May 14. doi: 10.1001/jamapediatrics.2018.0249.
Fewer infants are being delivered early, and there has been a decline in neonatal mortality, according to a retrospective cohort study of more than 34 million singleton live births.
Researchers presented the results of a study in the May 14 online edition of JAMA Pediatrics that attempted to quantify changes in gestational age distribution and gestational age–specific perinatal mortality in the United States between 2007 and 2015.
However the proportion of births at a gestational age of 39-40 weeks increased from 54.5% to 60.2% in that same time period.
“The decreasing proportion of births at gestational ages of 34-36 and 37-38 weeks may be associated with changes in the timing of elective delivery, with hospital policies and quality initiatives effectively reducing unindicated deliveries before 39 completed weeks of gestation,” wrote Cande V. Ananth, PhD, of Columbia University, New York, and coauthors.
“Increased use of low-dose aspirin in women with ischemic placental disease may additionally have resulted in decreased need for indicated delivery before 39 weeks.”
At the same time, perinatal mortality rates decreased overall, from 9 per 1,000 births in 2007 to 8.6 per 1,000 births in 2015, but increased significantly in gestational ages 32-33 weeks (7%), 34-36 weeks (15%), and 37-38 weeks (23%) over that period. There was also a significant 31% increase in perinatal mortality at gestational age 42-44 weeks, but decreases at 20-27 weeks and 39-40 weeks.
Stillbirth rates also increased for gestational ages of 20-27 weeks, 28-31 weeks, 32-33 weeks, 34-36 weeks, 37-38 weeks, and 42-44 weeks.
Commenting on the changes in perinatal and neonatal mortality rates at gestational ages of 34-36 weeks and 37-38 weeks, the authors suggested this may have been the result of recommendations to postpone elective deliveries until 39 weeks.
“A possible reason for the increased mortality at a gestational age of 37-38 weeks could be that physicians may be more likely to defer to 39 weeks for delivery for women at moderately increased risk for adverse perinatal outcomes,” they wrote.
“We found that the decrease in neonatal mortality rates from 2007 to 2015 in the United States was largely associated with changes in the underlying gestational age distribution and less associated with changes in gestational age–specific mortality.”
The researchers reported that they had no conflicts of interest.
SOURCE: Ananth C et al. JAMA Pediatrics. 2018 May 14. doi: 10.1001/jamapediatrics.2018.0249.
Fewer infants are being delivered early, and there has been a decline in neonatal mortality, according to a retrospective cohort study of more than 34 million singleton live births.
Researchers presented the results of a study in the May 14 online edition of JAMA Pediatrics that attempted to quantify changes in gestational age distribution and gestational age–specific perinatal mortality in the United States between 2007 and 2015.
However the proportion of births at a gestational age of 39-40 weeks increased from 54.5% to 60.2% in that same time period.
“The decreasing proportion of births at gestational ages of 34-36 and 37-38 weeks may be associated with changes in the timing of elective delivery, with hospital policies and quality initiatives effectively reducing unindicated deliveries before 39 completed weeks of gestation,” wrote Cande V. Ananth, PhD, of Columbia University, New York, and coauthors.
“Increased use of low-dose aspirin in women with ischemic placental disease may additionally have resulted in decreased need for indicated delivery before 39 weeks.”
At the same time, perinatal mortality rates decreased overall, from 9 per 1,000 births in 2007 to 8.6 per 1,000 births in 2015, but increased significantly in gestational ages 32-33 weeks (7%), 34-36 weeks (15%), and 37-38 weeks (23%) over that period. There was also a significant 31% increase in perinatal mortality at gestational age 42-44 weeks, but decreases at 20-27 weeks and 39-40 weeks.
Stillbirth rates also increased for gestational ages of 20-27 weeks, 28-31 weeks, 32-33 weeks, 34-36 weeks, 37-38 weeks, and 42-44 weeks.
Commenting on the changes in perinatal and neonatal mortality rates at gestational ages of 34-36 weeks and 37-38 weeks, the authors suggested this may have been the result of recommendations to postpone elective deliveries until 39 weeks.
“A possible reason for the increased mortality at a gestational age of 37-38 weeks could be that physicians may be more likely to defer to 39 weeks for delivery for women at moderately increased risk for adverse perinatal outcomes,” they wrote.
“We found that the decrease in neonatal mortality rates from 2007 to 2015 in the United States was largely associated with changes in the underlying gestational age distribution and less associated with changes in gestational age–specific mortality.”
The researchers reported that they had no conflicts of interest.
SOURCE: Ananth C et al. JAMA Pediatrics. 2018 May 14. doi: 10.1001/jamapediatrics.2018.0249.
FROM JAMA PEDIATRICS
Key clinical point: Preterm births and perinatal mortality decreased from 2007 to 2015.
Major finding: The proportion of births at 39-40 weeks increased from 54.5% to 60.2% between 2007 and 2015.
Study details: A retrospective cohort study of nearly 35 million singleton births.
Disclosures: The researchers reported that they had no conflicts of interest.
Source: Ananth C et al. JAMA Pediatrics. 2018 May 14. doi: 10.1001/jamapediatrics.2018.0249.