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NSAID continuation linked to less knee OA pain
in a randomized trial.
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.
Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).
“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.
They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.
“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.
The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.
The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.
The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.
“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.
Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).
“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.
“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.
Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.
“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.
He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.
“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”
Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.
It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”
Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.
SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.
in a randomized trial.
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.
Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).
“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.
They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.
“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.
The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.
The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.
The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.
“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.
Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).
“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.
“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.
Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.
“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.
He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.
“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”
Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.
It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”
Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.
SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.
in a randomized trial.
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.
Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).
“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.
They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.
“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.
The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.
The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.
The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.
“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.
Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).
“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.
“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.
Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.
“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.
He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.
“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”
Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.
It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”
Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.
SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.
FROM JAMA INTERNAL MEDICINE
Older adults often underestimate ability to prevent falls
but did identify important ways for clinicians to help, including screening all older patients for fall risk and deprescribing certain medications when possible.
The study was conducted by Shalender Bhasin, MD, MBBS, from Brigham and Women’s Hospital and Harvard Medical School in Boston and colleagues on behalf of the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial investigators and was published online July 8 in The New England Journal of Medicine.
Patients are often unaware of their increased risk until they have fallen for the first time, and they often underestimate how many of their risk factors can be improved, Dr. Bhasin said in an interview.
“Fall injuries are a very important cause of injury-related deaths among older adults, and these are preventable. Yet they are so difficult; for 30 years the rates of fall injuries have not declined,” he said.
Using a pragmatic, cluster-randomized trial, the researchers studied the clinical effectiveness of a “patient-centered intervention that combined elements of practice redesign (reconfiguration of workflow to improve quality of care) and an evidence-based, multifactorial, individually tailored intervention implemented by specially trained nurses in primary care settings,” the authors explained.
Participants in the intervention group worked with trained nurses (fall care managers) to identify their risk factors and determine which risks they wanted to modify. Participants in the control group received their typical care and a pamphlet with information on falls and were encouraged to talk with their primary care physicians (who received the results on risk factor screening) about fall prevention. Those in the intervention group also received the pamphlet.
Fall care managers evaluated patients’ home environments and in some cases visited the patient’s home, Dr. Bhasin said.
The researchers enrolled community-dwelling adults aged 70 years or older who were at higher risk for fall injuries from 86 primary care practices across 10 U.S. health care systems. Half of the practices were randomly assigned to provide the intervention to their patients; the other half of the practices provided enhanced usual care.
The researchers defined patients with increased risk for fall injuries as those who had suffered a fall-related injury at least twice during the previous year or those whose difficulties with balance or walking made them fearful of falling. Serious fall injuries were defined as falls that cause a fracture (other than a thoracic or lumbar vertebral fracture), joint dislocation, a cut needing closure, or falls that resulted in hospital admission for a “head injury, sprain or strain, bruising or swelling, or other serious injury,” they explained.
Demographic and baseline characteristics were similar for both groups of patients (mean age, 80 years; 62.0% women); 38.9% had experienced a fall-related injury during the previous year, and 35.1% had suffered at least two falls during the previous year.
The researchers hypothesized that serious fall injuries would be 20% lower in the intervention group, compared with the control group, but that was not the case.
The findings showed no significant difference between the intervention group (4.9 events per 100 person-years of follow-up) and the control group (5.3 events per 100 person-years of follow-up) for the rate of first adjudicated serious fall injury (hazard ratio, 0.92; P = .25). Results were similar in a practice-level analysis and a sensitivity analysis adjusted for participant-level covariates.
However, there was a difference in rates of first participant-reported fall injury, which was a secondary endpoint, at 25.6 events per 100 person-years of follow-up among participants in the intervention group versus 28.6 events among those in the control group (HR, 0.90; P = .004).
There were no significant differences between the groups for rates of all adjudicated serious fall injuries and all patient-reported fall injuries. Bone fractures and injuries resulting in hospitalization were the most frequent types of adjudicated serious fall injuries.
Rates of serious adverse events resulting in hospitalization were similar for the intervention group and the control group (32.8 and 33.3 hospitalizations per 100 person-years of follow-up, respectively), as well as rates of death (3.3 deaths per 100 person-years of follow-up in both groups).
Simple steps can help
“The most important thing clinicians can do is a quick screen for fall injury risk,” Dr. Bhasin said in an interview. The screening tool he uses consists of three questions and can be completed in less than a minute. Clinicians should share that information with patients, he continued.
“Just recognizing that they are at risk for falls, patients are much more motivated to take action,” Dr. Bhasin added.
The top three risk factors identified among trial participants were trouble with strength, gait, or balance; osteoporosis or vitamin D deficiency; and impaired vision. “The use of certain medications, postural hypotension, problems with feet or footwear, and home safety hazards were less commonly identified, and the use of certain medications was the least commonly prioritized,” the authors wrote.
It is vital that clinicians help patients implement changes, Dr. Bhasin said. He noted that many patients encounter barriers that prevent them from taking action, including transportation or insurance problems and lack of access to exercise programs in the community.
Deprescribing medications such as sleep medications and benzodiazepines is also a key piece of the puzzle, he added. “They’re pretty huge risks, and yet it is so hard to get people off these medications.”
Future research will focus on how to improve the intervention’s effectiveness and also will test the strategy among those with cognitive impairments who have even higher risk for fall injuries, Dr. Bhasin said.
Falls remain common
A report published online July 9 in Morbidity and Mortality Weekly Report underscores the prevalence of fall-related injuries: In 2018, more than one quarter (27.5%) of adults 65 years or older said they had fallen at least once during the previous year (35.6 million falls), and 10.2% said they had experienced a fall-related injury (8.4 million fall-related injuries). The percentage of adults who reported a fall increased during 2012-2016, then decreased during 2016-2018.
Briana Moreland, MPH, from Synergy America and the Division of Injury Prevention at National Center for Injury Prevention and Control of the Centers for Disease Control and Prevention and colleagues wrote that older adults and health care providers can work together to reduce fall risk.
“CDC created the Stopping Elderly Accidents, Deaths and Injuries (STEADI) initiative, which offers tools and resources for health care providers to screen their older patients for fall risk, assess modifiable fall risk factors, and to intervene with evidence-based fall prevention interventions (https://www.cdc.gov/steadi). These include medication management, vision screening, home modifications, referral to physical therapists who can address problems with gait, strength, and balance, and referral to effective community-based fall prevention programs,” Ms. Moreland and colleagues explain.
Dr. Bhasin has received grants from the National Institute on Aging (NIA) and Patient-Centered Outcomes Research Institute (PCORI) during the conduct of the study. He has received grants, personal fees, and nonfinancial support from AbbVie; grants from Transition Therapeutics, Alivegen, and Metro International Biotechnology; and personal fees from OPKO outside the submitted work. A coauthor received grants from the NIA and PCORI during the conduct of the study and is co-owner of Lynx Health, and another Peduzzi received grants and other compensation from NIA-PCORI during the conduct of the study. Two other authors have disclosed no relevant financial relationships. The remaining authors report a variety of relevant financial relationships; a complete list is available on the journal’s website. The authors of the article in Morbidity and Mortality Weekly Report have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
but did identify important ways for clinicians to help, including screening all older patients for fall risk and deprescribing certain medications when possible.
The study was conducted by Shalender Bhasin, MD, MBBS, from Brigham and Women’s Hospital and Harvard Medical School in Boston and colleagues on behalf of the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial investigators and was published online July 8 in The New England Journal of Medicine.
Patients are often unaware of their increased risk until they have fallen for the first time, and they often underestimate how many of their risk factors can be improved, Dr. Bhasin said in an interview.
“Fall injuries are a very important cause of injury-related deaths among older adults, and these are preventable. Yet they are so difficult; for 30 years the rates of fall injuries have not declined,” he said.
Using a pragmatic, cluster-randomized trial, the researchers studied the clinical effectiveness of a “patient-centered intervention that combined elements of practice redesign (reconfiguration of workflow to improve quality of care) and an evidence-based, multifactorial, individually tailored intervention implemented by specially trained nurses in primary care settings,” the authors explained.
Participants in the intervention group worked with trained nurses (fall care managers) to identify their risk factors and determine which risks they wanted to modify. Participants in the control group received their typical care and a pamphlet with information on falls and were encouraged to talk with their primary care physicians (who received the results on risk factor screening) about fall prevention. Those in the intervention group also received the pamphlet.
Fall care managers evaluated patients’ home environments and in some cases visited the patient’s home, Dr. Bhasin said.
The researchers enrolled community-dwelling adults aged 70 years or older who were at higher risk for fall injuries from 86 primary care practices across 10 U.S. health care systems. Half of the practices were randomly assigned to provide the intervention to their patients; the other half of the practices provided enhanced usual care.
The researchers defined patients with increased risk for fall injuries as those who had suffered a fall-related injury at least twice during the previous year or those whose difficulties with balance or walking made them fearful of falling. Serious fall injuries were defined as falls that cause a fracture (other than a thoracic or lumbar vertebral fracture), joint dislocation, a cut needing closure, or falls that resulted in hospital admission for a “head injury, sprain or strain, bruising or swelling, or other serious injury,” they explained.
Demographic and baseline characteristics were similar for both groups of patients (mean age, 80 years; 62.0% women); 38.9% had experienced a fall-related injury during the previous year, and 35.1% had suffered at least two falls during the previous year.
The researchers hypothesized that serious fall injuries would be 20% lower in the intervention group, compared with the control group, but that was not the case.
The findings showed no significant difference between the intervention group (4.9 events per 100 person-years of follow-up) and the control group (5.3 events per 100 person-years of follow-up) for the rate of first adjudicated serious fall injury (hazard ratio, 0.92; P = .25). Results were similar in a practice-level analysis and a sensitivity analysis adjusted for participant-level covariates.
However, there was a difference in rates of first participant-reported fall injury, which was a secondary endpoint, at 25.6 events per 100 person-years of follow-up among participants in the intervention group versus 28.6 events among those in the control group (HR, 0.90; P = .004).
There were no significant differences between the groups for rates of all adjudicated serious fall injuries and all patient-reported fall injuries. Bone fractures and injuries resulting in hospitalization were the most frequent types of adjudicated serious fall injuries.
Rates of serious adverse events resulting in hospitalization were similar for the intervention group and the control group (32.8 and 33.3 hospitalizations per 100 person-years of follow-up, respectively), as well as rates of death (3.3 deaths per 100 person-years of follow-up in both groups).
Simple steps can help
“The most important thing clinicians can do is a quick screen for fall injury risk,” Dr. Bhasin said in an interview. The screening tool he uses consists of three questions and can be completed in less than a minute. Clinicians should share that information with patients, he continued.
“Just recognizing that they are at risk for falls, patients are much more motivated to take action,” Dr. Bhasin added.
The top three risk factors identified among trial participants were trouble with strength, gait, or balance; osteoporosis or vitamin D deficiency; and impaired vision. “The use of certain medications, postural hypotension, problems with feet or footwear, and home safety hazards were less commonly identified, and the use of certain medications was the least commonly prioritized,” the authors wrote.
It is vital that clinicians help patients implement changes, Dr. Bhasin said. He noted that many patients encounter barriers that prevent them from taking action, including transportation or insurance problems and lack of access to exercise programs in the community.
Deprescribing medications such as sleep medications and benzodiazepines is also a key piece of the puzzle, he added. “They’re pretty huge risks, and yet it is so hard to get people off these medications.”
Future research will focus on how to improve the intervention’s effectiveness and also will test the strategy among those with cognitive impairments who have even higher risk for fall injuries, Dr. Bhasin said.
Falls remain common
A report published online July 9 in Morbidity and Mortality Weekly Report underscores the prevalence of fall-related injuries: In 2018, more than one quarter (27.5%) of adults 65 years or older said they had fallen at least once during the previous year (35.6 million falls), and 10.2% said they had experienced a fall-related injury (8.4 million fall-related injuries). The percentage of adults who reported a fall increased during 2012-2016, then decreased during 2016-2018.
Briana Moreland, MPH, from Synergy America and the Division of Injury Prevention at National Center for Injury Prevention and Control of the Centers for Disease Control and Prevention and colleagues wrote that older adults and health care providers can work together to reduce fall risk.
“CDC created the Stopping Elderly Accidents, Deaths and Injuries (STEADI) initiative, which offers tools and resources for health care providers to screen their older patients for fall risk, assess modifiable fall risk factors, and to intervene with evidence-based fall prevention interventions (https://www.cdc.gov/steadi). These include medication management, vision screening, home modifications, referral to physical therapists who can address problems with gait, strength, and balance, and referral to effective community-based fall prevention programs,” Ms. Moreland and colleagues explain.
Dr. Bhasin has received grants from the National Institute on Aging (NIA) and Patient-Centered Outcomes Research Institute (PCORI) during the conduct of the study. He has received grants, personal fees, and nonfinancial support from AbbVie; grants from Transition Therapeutics, Alivegen, and Metro International Biotechnology; and personal fees from OPKO outside the submitted work. A coauthor received grants from the NIA and PCORI during the conduct of the study and is co-owner of Lynx Health, and another Peduzzi received grants and other compensation from NIA-PCORI during the conduct of the study. Two other authors have disclosed no relevant financial relationships. The remaining authors report a variety of relevant financial relationships; a complete list is available on the journal’s website. The authors of the article in Morbidity and Mortality Weekly Report have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
but did identify important ways for clinicians to help, including screening all older patients for fall risk and deprescribing certain medications when possible.
The study was conducted by Shalender Bhasin, MD, MBBS, from Brigham and Women’s Hospital and Harvard Medical School in Boston and colleagues on behalf of the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial investigators and was published online July 8 in The New England Journal of Medicine.
Patients are often unaware of their increased risk until they have fallen for the first time, and they often underestimate how many of their risk factors can be improved, Dr. Bhasin said in an interview.
“Fall injuries are a very important cause of injury-related deaths among older adults, and these are preventable. Yet they are so difficult; for 30 years the rates of fall injuries have not declined,” he said.
Using a pragmatic, cluster-randomized trial, the researchers studied the clinical effectiveness of a “patient-centered intervention that combined elements of practice redesign (reconfiguration of workflow to improve quality of care) and an evidence-based, multifactorial, individually tailored intervention implemented by specially trained nurses in primary care settings,” the authors explained.
Participants in the intervention group worked with trained nurses (fall care managers) to identify their risk factors and determine which risks they wanted to modify. Participants in the control group received their typical care and a pamphlet with information on falls and were encouraged to talk with their primary care physicians (who received the results on risk factor screening) about fall prevention. Those in the intervention group also received the pamphlet.
Fall care managers evaluated patients’ home environments and in some cases visited the patient’s home, Dr. Bhasin said.
The researchers enrolled community-dwelling adults aged 70 years or older who were at higher risk for fall injuries from 86 primary care practices across 10 U.S. health care systems. Half of the practices were randomly assigned to provide the intervention to their patients; the other half of the practices provided enhanced usual care.
The researchers defined patients with increased risk for fall injuries as those who had suffered a fall-related injury at least twice during the previous year or those whose difficulties with balance or walking made them fearful of falling. Serious fall injuries were defined as falls that cause a fracture (other than a thoracic or lumbar vertebral fracture), joint dislocation, a cut needing closure, or falls that resulted in hospital admission for a “head injury, sprain or strain, bruising or swelling, or other serious injury,” they explained.
Demographic and baseline characteristics were similar for both groups of patients (mean age, 80 years; 62.0% women); 38.9% had experienced a fall-related injury during the previous year, and 35.1% had suffered at least two falls during the previous year.
The researchers hypothesized that serious fall injuries would be 20% lower in the intervention group, compared with the control group, but that was not the case.
The findings showed no significant difference between the intervention group (4.9 events per 100 person-years of follow-up) and the control group (5.3 events per 100 person-years of follow-up) for the rate of first adjudicated serious fall injury (hazard ratio, 0.92; P = .25). Results were similar in a practice-level analysis and a sensitivity analysis adjusted for participant-level covariates.
However, there was a difference in rates of first participant-reported fall injury, which was a secondary endpoint, at 25.6 events per 100 person-years of follow-up among participants in the intervention group versus 28.6 events among those in the control group (HR, 0.90; P = .004).
There were no significant differences between the groups for rates of all adjudicated serious fall injuries and all patient-reported fall injuries. Bone fractures and injuries resulting in hospitalization were the most frequent types of adjudicated serious fall injuries.
Rates of serious adverse events resulting in hospitalization were similar for the intervention group and the control group (32.8 and 33.3 hospitalizations per 100 person-years of follow-up, respectively), as well as rates of death (3.3 deaths per 100 person-years of follow-up in both groups).
Simple steps can help
“The most important thing clinicians can do is a quick screen for fall injury risk,” Dr. Bhasin said in an interview. The screening tool he uses consists of three questions and can be completed in less than a minute. Clinicians should share that information with patients, he continued.
“Just recognizing that they are at risk for falls, patients are much more motivated to take action,” Dr. Bhasin added.
The top three risk factors identified among trial participants were trouble with strength, gait, or balance; osteoporosis or vitamin D deficiency; and impaired vision. “The use of certain medications, postural hypotension, problems with feet or footwear, and home safety hazards were less commonly identified, and the use of certain medications was the least commonly prioritized,” the authors wrote.
It is vital that clinicians help patients implement changes, Dr. Bhasin said. He noted that many patients encounter barriers that prevent them from taking action, including transportation or insurance problems and lack of access to exercise programs in the community.
Deprescribing medications such as sleep medications and benzodiazepines is also a key piece of the puzzle, he added. “They’re pretty huge risks, and yet it is so hard to get people off these medications.”
Future research will focus on how to improve the intervention’s effectiveness and also will test the strategy among those with cognitive impairments who have even higher risk for fall injuries, Dr. Bhasin said.
Falls remain common
A report published online July 9 in Morbidity and Mortality Weekly Report underscores the prevalence of fall-related injuries: In 2018, more than one quarter (27.5%) of adults 65 years or older said they had fallen at least once during the previous year (35.6 million falls), and 10.2% said they had experienced a fall-related injury (8.4 million fall-related injuries). The percentage of adults who reported a fall increased during 2012-2016, then decreased during 2016-2018.
Briana Moreland, MPH, from Synergy America and the Division of Injury Prevention at National Center for Injury Prevention and Control of the Centers for Disease Control and Prevention and colleagues wrote that older adults and health care providers can work together to reduce fall risk.
“CDC created the Stopping Elderly Accidents, Deaths and Injuries (STEADI) initiative, which offers tools and resources for health care providers to screen their older patients for fall risk, assess modifiable fall risk factors, and to intervene with evidence-based fall prevention interventions (https://www.cdc.gov/steadi). These include medication management, vision screening, home modifications, referral to physical therapists who can address problems with gait, strength, and balance, and referral to effective community-based fall prevention programs,” Ms. Moreland and colleagues explain.
Dr. Bhasin has received grants from the National Institute on Aging (NIA) and Patient-Centered Outcomes Research Institute (PCORI) during the conduct of the study. He has received grants, personal fees, and nonfinancial support from AbbVie; grants from Transition Therapeutics, Alivegen, and Metro International Biotechnology; and personal fees from OPKO outside the submitted work. A coauthor received grants from the NIA and PCORI during the conduct of the study and is co-owner of Lynx Health, and another Peduzzi received grants and other compensation from NIA-PCORI during the conduct of the study. Two other authors have disclosed no relevant financial relationships. The remaining authors report a variety of relevant financial relationships; a complete list is available on the journal’s website. The authors of the article in Morbidity and Mortality Weekly Report have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
ACR issues guidances for MIS-C and pediatric rheumatic disease during pandemic
Two new clinical guidance documents from the American College of Rheumatology provide evidence-based recommendations for managing pediatric rheumatic disease during the COVID-19 pandemic as well as diagnostic and treatment recommendations for multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection.
Although several children’s hospitals have published their treatment protocols for MIS-C since the condition’s initial discovery, the ACR appears to be the first medical organization to review all the most current evidence to issue interim guidance with the expectations that it will change as more data become available.
“It is challenging having to make recommendations not having a lot of scientific evidence, but we still felt we had to use whatever’s out there to the best of our ability and use our experience to put together these recommendations,” Dawn M. Wahezi, MD, chief of pediatric rheumatology at Children’s Hospital at Montefiore and an associate professor of pediatrics at Albert Einstein College of Medicine, New York, said in an interview.
“We wanted to be mindful of the fact that there are things we know and things we don’t know, and we have to be careful about what we’re recommending,” said Dr. Wahezi, a member of the ACR working group that assembled the recommendations for pediatric rheumatic disease management during the pandemic. “We’re recommending the best we can at this moment, but if there are new studies that come out and suggest otherwise, we will definitely have to go back and amend the document.”
The foremost priority of the pediatric rheumatic disease guidance focuses on maintaining control of the disease and avoiding flares that may put children at greater risk of infection. Dr. Wahezi said the ACR has received many calls from patients and clinicians asking whether patients should continue their immunosuppressant medications. Fear of the coronavirus infection, medication shortages, difficulty getting to the pharmacy, uneasiness about going to the clinic or hospital for infusions, and other barriers may have led to gaps in medication.
“We didn’t want people to be too quick to hold patients’ medications just because they were scared of COVID,” Dr. Wahezi said. “If they did have medication stopped for one reason or another and their disease flared, having active disease, regardless of which disease it is, actually puts you at higher risk for infection. By controlling their disease, that would be the way to protect them the most.”
A key takeaway in the guidance on MIS-C, meanwhile, is an emphasis on its rarity lest physicians be too quick to diagnose it and miss another serious condition with overlapping symptoms, explained Lauren Henderson, MD, an attending rheumatologist at Boston Children’s Hospital and assistant professor of pediatrics at Harvard Medical School, Boston. Dr. Henderson participated in the ACR group that wrote the MIS-C guidance.
“The first thing we want to be thoughtful about clinically is to recognize that children in general with the acute infectious phase of SARS-CoV-2 have mild symptoms and generally do well,” Dr. Henderson said. “From what we can tell from all the data, MIS-C is rare. That really needs to be considered when clinicians on the ground are doing the diagnostic evaluation” because of concerns that clinicians “could rush to diagnose and treat patients with MIS-C and miss important diagnoses like malignancies and infections.”
Management of pediatric rheumatic disease during the pandemic
The COVID-19 clinical guidance for managing pediatric rheumatic disease grew from the work of the North American Pediatric Rheumatology Clinical Guidance Task Force, which included seven pediatric rheumatologists, two pediatric infectious disease physicians, one adult rheumatologist, and one pediatric nurse practitioner. The general guidance covers usual preventive measures for reducing risk for COVID-19 infection, the recommendation that children continue to receive recommended vaccines unless contraindicated by medication, and routine in-person visits for ophthalmologic surveillance of those with a history of uveitis or at high risk for chronic uveitis. The guidance also notes the risk of mental health concerns, such as depression and anxiety, related to quarantine and the pandemic.
The top recommendation is initiation or continuation of all medications necessary to control underlying disease, including NSAIDs, hydroxychloroquine, ACE inhibitors/angiotensin II receptor blockers, colchicine, conventional disease-modifying antirheumatic drugs (cDMARDs), biologic DMARDs, and targeted synthetic DMARDs. Even patients who may have had exposure to COVID-19 or who have an asymptomatic COVID-19 infection should continue to take these medications with the exception of ACEi/ARBs.
In those with pediatric rheumatic disease who have a symptomatic COVID-19 infection, “NSAIDs, HCQ, and colchicine may be continued, if necessary, to control underlying disease,” as can interleukin (IL)-1 and IL-6 inhibitors, but “cDMARDs, bDMARDs [except IL-1 and IL-6 inhibitors] and tsDMARDs should be temporarily delayed or withheld,” according to the guidance. Glucocorticoids can be continued at the lowest possible dose to control disease.
“There’s nothing in the literature that suggests people who have rheumatic disease, especially children, and people who are on these medications, really are at increased risk for COVID-19,” Dr. Wahezi said. “That’s why we didn’t want people to be overcautious in stopping medications when the main priority is to control their disease.”
She noted some experts’ speculations that these medications may actually benefit patients with rheumatic disease who develop a COVID-19 infection because the medications keep the immune response in check. “If you allow them to have this dysregulated immune response and have active disease, you’re potentially putting them at greater risk,” Dr. Wahezi said, although she stressed that inadequate evidence exists to support these speculations right now.
Lack of evidence has been the biggest challenge all around with developing this guidance, she said.
“Because this is such an unprecedented situation and because people are so desperate to find treatments both for the illness and to protect those at risk for it, there are lots of people trying to put evidence out there, but it may not be the best-quality evidence,” Dr. Wahezi said.
Insufficient evidence also drove the group’s determination that “SARS-CoV-2 antibody testing is not useful in informing on the history of infection or risk of reinfection,” as the guidance states. Too much variability in the assays exist, Dr. Wahezi said, and, further, it’s unclear what the clinical significance of a positive test would be.
“We didn’t want anyone to feel they had to make clinical decisions based on the results of that antibody testing,” she said. “Even if the test is accurate, we don’t know how to interpret it because it’s so new.”
The guidance also notes that patients with stable disease and previously stable lab markers on stable doses of their medication may be able to extend the interval for medication toxicity lab testing a few months if there is concern about exposure to COVID-19 to get the blood work.
“If you’re just starting a medicine or there’s someone who’s had abnormalities with the medicine in the past or you’re making medication adjustments, you wouldn’t do it in those scenarios, but if there’s someone who’s been on the drug for a long time and are nervous to get [blood] drawn, it’s probably okay to delay it,” Dr. Wahezi said. Lab work for disease activity measures, on the other hand, remain particularly important, especially since telemedicine visits may require clinicians to rely on lab results more than previously.
Management of MIS-C associated with COVID-19
The task force that developed guidance for the new inflammatory condition recently linked to SARS-CoV-2 infections in children included nine pediatric rheumatologists, two adult rheumatologists, two pediatric cardiologists, two pediatric infectious disease specialists, and one pediatric critical care physician.
The guidance includes a figure for the diagnostic pathway in evaluating children suspected of having MIS-C and extensive detail on diagnostic work-up, but the task force intentionally avoided providing a case definition for the condition. Existing case definitions from the Centers for Disease Control and Prevention, World Health Organization, and the United Kingdom’s Royal College of Paediatrics and Child Health differ from one another and are based on unclear evidence, Dr. Henderson noted. “We really don’t have enough data to know the sensitivity and specificity of each parameter, and until that’s available, we didn’t want to add to the confusion,” she said.
The guidance also stresses that MIS-C is a rare complication, so patients suspected of having the condition who do not have “life-threatening manifestations should undergo diagnostic evaluation for MIS-C as well as other possible infectious and noninfectious etiologies before immunomodulatory treatment is initiated,” the guidance states.
Unless a child is in shock or otherwise requires urgent care, physicians should take the time to complete the diagnostic work-up while monitoring the child, Dr. Henderson said. If the child does have MIS-C, the guidance currently recommends intravenous immunoglobulin (IVIG) and/or glucocorticoids to prevent coronary artery aneurysms, the same treatment other institutions have been recommending.
“We don’t have rigorous comparative studies looking at different types of treatments,” Dr. Henderson said, noting that the vast majority of children in the literature received IVIG and/or glucocorticoid treatment. “Often children really responded quite forcefully to those treatments, but we don’t have high-quality data yet to know that this treatment is better than supportive care or another medication.”
Dr. Henderson also stressed the importance of children receiving care at a facility with the necessary expertise to manage MIS-C and receiving long-term follow-up care from a multidisciplinary clinical team that includes a rheumatologist, an infectious disease doctor, a cardiologist, and possibly a hematologist.
“Making sure children are admitted to a hospital that has the resources and are followed by physicians with expertise or understanding of the intricacies of MIS-C is really important,” she said, particularly for children with cardiac involvement. “We don’t know if all the kids presenting with left ventricular dysfunction and shock are at risk for having myocardial fibrosis down the line,” she noted. “There is so much we do not understand and very little data to guide us on what to do, so these children really need to be under the care of a cardiologist and rheumatologist to make sure that their care is tailored to them.”
Although MIS-C shares overlapping symptoms with Kawasaki disease, it’s still unclear how similar or different the two conditions are, Dr. Henderson said.
“We can definitely say that when we look at MIS-C and compare it to historical groups of Kawasaki disease before the pandemic, there are definitely different features in the MIS-C group,” she said. Kawasaki disease generally only affects children under age 5, whereas MIS-C patients run the gamut from age 1-17. Racial demographics are also different, with a higher proportion of black children affected by MIS-C.
It’s possible that the pathophysiology of both conditions will turn out to be similar, particularly given the hypothesis that Kawasaki disease is triggered by infections in genetically predisposed people. However, the severity of symptoms and risk of aneurysms appear greater with MIS-C so far.
“The degree to which these patients are presenting with left ventricular dysfunction and shock is much higher than what we’ve seen previously,” Dr. Henderson said. “Children can have aneurysms even if they don’t meet all the Kawasaki disease features, which makes it feel that this is somehow clinically different from what we’ve seen before. It’s not just the kids who have the rash and the conjunctivitis and the extremity changes and oral changes who have the aneurysms.”
The reason for including both IVIG and glucocorticoids as possible first-line drugs to prevent aneurysms is that some evidence suggests children with MIS-C may have higher levels of IVIG resistance, she said.
Like Dr. Wahezi, Dr. Henderson emphasized the necessarily transient nature of these recommendations.
“These recommendations will almost certainly change based on evolving understanding of MIS-C and the data,” Dr. Henderson said, adding that this new, unique condition highlights the importance of including children in allocating funding for research and in clinical trials.
“Children are not always identical to adults, and it’s really important that we have high-quality data to inform our decisions about how to care for them,” she said.
Dr. Wahezi had no disclosures. Dr. Henderson has consulted for Sobi and Adaptive Technologies. The guidelines did not note other disclosures for members of the ACR groups.
SOURCES: COVID-19 Clinical Guidance for Pediatric Patients with Rheumatic Disease and Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19
Two new clinical guidance documents from the American College of Rheumatology provide evidence-based recommendations for managing pediatric rheumatic disease during the COVID-19 pandemic as well as diagnostic and treatment recommendations for multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection.
Although several children’s hospitals have published their treatment protocols for MIS-C since the condition’s initial discovery, the ACR appears to be the first medical organization to review all the most current evidence to issue interim guidance with the expectations that it will change as more data become available.
“It is challenging having to make recommendations not having a lot of scientific evidence, but we still felt we had to use whatever’s out there to the best of our ability and use our experience to put together these recommendations,” Dawn M. Wahezi, MD, chief of pediatric rheumatology at Children’s Hospital at Montefiore and an associate professor of pediatrics at Albert Einstein College of Medicine, New York, said in an interview.
“We wanted to be mindful of the fact that there are things we know and things we don’t know, and we have to be careful about what we’re recommending,” said Dr. Wahezi, a member of the ACR working group that assembled the recommendations for pediatric rheumatic disease management during the pandemic. “We’re recommending the best we can at this moment, but if there are new studies that come out and suggest otherwise, we will definitely have to go back and amend the document.”
The foremost priority of the pediatric rheumatic disease guidance focuses on maintaining control of the disease and avoiding flares that may put children at greater risk of infection. Dr. Wahezi said the ACR has received many calls from patients and clinicians asking whether patients should continue their immunosuppressant medications. Fear of the coronavirus infection, medication shortages, difficulty getting to the pharmacy, uneasiness about going to the clinic or hospital for infusions, and other barriers may have led to gaps in medication.
“We didn’t want people to be too quick to hold patients’ medications just because they were scared of COVID,” Dr. Wahezi said. “If they did have medication stopped for one reason or another and their disease flared, having active disease, regardless of which disease it is, actually puts you at higher risk for infection. By controlling their disease, that would be the way to protect them the most.”
A key takeaway in the guidance on MIS-C, meanwhile, is an emphasis on its rarity lest physicians be too quick to diagnose it and miss another serious condition with overlapping symptoms, explained Lauren Henderson, MD, an attending rheumatologist at Boston Children’s Hospital and assistant professor of pediatrics at Harvard Medical School, Boston. Dr. Henderson participated in the ACR group that wrote the MIS-C guidance.
“The first thing we want to be thoughtful about clinically is to recognize that children in general with the acute infectious phase of SARS-CoV-2 have mild symptoms and generally do well,” Dr. Henderson said. “From what we can tell from all the data, MIS-C is rare. That really needs to be considered when clinicians on the ground are doing the diagnostic evaluation” because of concerns that clinicians “could rush to diagnose and treat patients with MIS-C and miss important diagnoses like malignancies and infections.”
Management of pediatric rheumatic disease during the pandemic
The COVID-19 clinical guidance for managing pediatric rheumatic disease grew from the work of the North American Pediatric Rheumatology Clinical Guidance Task Force, which included seven pediatric rheumatologists, two pediatric infectious disease physicians, one adult rheumatologist, and one pediatric nurse practitioner. The general guidance covers usual preventive measures for reducing risk for COVID-19 infection, the recommendation that children continue to receive recommended vaccines unless contraindicated by medication, and routine in-person visits for ophthalmologic surveillance of those with a history of uveitis or at high risk for chronic uveitis. The guidance also notes the risk of mental health concerns, such as depression and anxiety, related to quarantine and the pandemic.
The top recommendation is initiation or continuation of all medications necessary to control underlying disease, including NSAIDs, hydroxychloroquine, ACE inhibitors/angiotensin II receptor blockers, colchicine, conventional disease-modifying antirheumatic drugs (cDMARDs), biologic DMARDs, and targeted synthetic DMARDs. Even patients who may have had exposure to COVID-19 or who have an asymptomatic COVID-19 infection should continue to take these medications with the exception of ACEi/ARBs.
In those with pediatric rheumatic disease who have a symptomatic COVID-19 infection, “NSAIDs, HCQ, and colchicine may be continued, if necessary, to control underlying disease,” as can interleukin (IL)-1 and IL-6 inhibitors, but “cDMARDs, bDMARDs [except IL-1 and IL-6 inhibitors] and tsDMARDs should be temporarily delayed or withheld,” according to the guidance. Glucocorticoids can be continued at the lowest possible dose to control disease.
“There’s nothing in the literature that suggests people who have rheumatic disease, especially children, and people who are on these medications, really are at increased risk for COVID-19,” Dr. Wahezi said. “That’s why we didn’t want people to be overcautious in stopping medications when the main priority is to control their disease.”
She noted some experts’ speculations that these medications may actually benefit patients with rheumatic disease who develop a COVID-19 infection because the medications keep the immune response in check. “If you allow them to have this dysregulated immune response and have active disease, you’re potentially putting them at greater risk,” Dr. Wahezi said, although she stressed that inadequate evidence exists to support these speculations right now.
Lack of evidence has been the biggest challenge all around with developing this guidance, she said.
“Because this is such an unprecedented situation and because people are so desperate to find treatments both for the illness and to protect those at risk for it, there are lots of people trying to put evidence out there, but it may not be the best-quality evidence,” Dr. Wahezi said.
Insufficient evidence also drove the group’s determination that “SARS-CoV-2 antibody testing is not useful in informing on the history of infection or risk of reinfection,” as the guidance states. Too much variability in the assays exist, Dr. Wahezi said, and, further, it’s unclear what the clinical significance of a positive test would be.
“We didn’t want anyone to feel they had to make clinical decisions based on the results of that antibody testing,” she said. “Even if the test is accurate, we don’t know how to interpret it because it’s so new.”
The guidance also notes that patients with stable disease and previously stable lab markers on stable doses of their medication may be able to extend the interval for medication toxicity lab testing a few months if there is concern about exposure to COVID-19 to get the blood work.
“If you’re just starting a medicine or there’s someone who’s had abnormalities with the medicine in the past or you’re making medication adjustments, you wouldn’t do it in those scenarios, but if there’s someone who’s been on the drug for a long time and are nervous to get [blood] drawn, it’s probably okay to delay it,” Dr. Wahezi said. Lab work for disease activity measures, on the other hand, remain particularly important, especially since telemedicine visits may require clinicians to rely on lab results more than previously.
Management of MIS-C associated with COVID-19
The task force that developed guidance for the new inflammatory condition recently linked to SARS-CoV-2 infections in children included nine pediatric rheumatologists, two adult rheumatologists, two pediatric cardiologists, two pediatric infectious disease specialists, and one pediatric critical care physician.
The guidance includes a figure for the diagnostic pathway in evaluating children suspected of having MIS-C and extensive detail on diagnostic work-up, but the task force intentionally avoided providing a case definition for the condition. Existing case definitions from the Centers for Disease Control and Prevention, World Health Organization, and the United Kingdom’s Royal College of Paediatrics and Child Health differ from one another and are based on unclear evidence, Dr. Henderson noted. “We really don’t have enough data to know the sensitivity and specificity of each parameter, and until that’s available, we didn’t want to add to the confusion,” she said.
The guidance also stresses that MIS-C is a rare complication, so patients suspected of having the condition who do not have “life-threatening manifestations should undergo diagnostic evaluation for MIS-C as well as other possible infectious and noninfectious etiologies before immunomodulatory treatment is initiated,” the guidance states.
Unless a child is in shock or otherwise requires urgent care, physicians should take the time to complete the diagnostic work-up while monitoring the child, Dr. Henderson said. If the child does have MIS-C, the guidance currently recommends intravenous immunoglobulin (IVIG) and/or glucocorticoids to prevent coronary artery aneurysms, the same treatment other institutions have been recommending.
“We don’t have rigorous comparative studies looking at different types of treatments,” Dr. Henderson said, noting that the vast majority of children in the literature received IVIG and/or glucocorticoid treatment. “Often children really responded quite forcefully to those treatments, but we don’t have high-quality data yet to know that this treatment is better than supportive care or another medication.”
Dr. Henderson also stressed the importance of children receiving care at a facility with the necessary expertise to manage MIS-C and receiving long-term follow-up care from a multidisciplinary clinical team that includes a rheumatologist, an infectious disease doctor, a cardiologist, and possibly a hematologist.
“Making sure children are admitted to a hospital that has the resources and are followed by physicians with expertise or understanding of the intricacies of MIS-C is really important,” she said, particularly for children with cardiac involvement. “We don’t know if all the kids presenting with left ventricular dysfunction and shock are at risk for having myocardial fibrosis down the line,” she noted. “There is so much we do not understand and very little data to guide us on what to do, so these children really need to be under the care of a cardiologist and rheumatologist to make sure that their care is tailored to them.”
Although MIS-C shares overlapping symptoms with Kawasaki disease, it’s still unclear how similar or different the two conditions are, Dr. Henderson said.
“We can definitely say that when we look at MIS-C and compare it to historical groups of Kawasaki disease before the pandemic, there are definitely different features in the MIS-C group,” she said. Kawasaki disease generally only affects children under age 5, whereas MIS-C patients run the gamut from age 1-17. Racial demographics are also different, with a higher proportion of black children affected by MIS-C.
It’s possible that the pathophysiology of both conditions will turn out to be similar, particularly given the hypothesis that Kawasaki disease is triggered by infections in genetically predisposed people. However, the severity of symptoms and risk of aneurysms appear greater with MIS-C so far.
“The degree to which these patients are presenting with left ventricular dysfunction and shock is much higher than what we’ve seen previously,” Dr. Henderson said. “Children can have aneurysms even if they don’t meet all the Kawasaki disease features, which makes it feel that this is somehow clinically different from what we’ve seen before. It’s not just the kids who have the rash and the conjunctivitis and the extremity changes and oral changes who have the aneurysms.”
The reason for including both IVIG and glucocorticoids as possible first-line drugs to prevent aneurysms is that some evidence suggests children with MIS-C may have higher levels of IVIG resistance, she said.
Like Dr. Wahezi, Dr. Henderson emphasized the necessarily transient nature of these recommendations.
“These recommendations will almost certainly change based on evolving understanding of MIS-C and the data,” Dr. Henderson said, adding that this new, unique condition highlights the importance of including children in allocating funding for research and in clinical trials.
“Children are not always identical to adults, and it’s really important that we have high-quality data to inform our decisions about how to care for them,” she said.
Dr. Wahezi had no disclosures. Dr. Henderson has consulted for Sobi and Adaptive Technologies. The guidelines did not note other disclosures for members of the ACR groups.
SOURCES: COVID-19 Clinical Guidance for Pediatric Patients with Rheumatic Disease and Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19
Two new clinical guidance documents from the American College of Rheumatology provide evidence-based recommendations for managing pediatric rheumatic disease during the COVID-19 pandemic as well as diagnostic and treatment recommendations for multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection.
Although several children’s hospitals have published their treatment protocols for MIS-C since the condition’s initial discovery, the ACR appears to be the first medical organization to review all the most current evidence to issue interim guidance with the expectations that it will change as more data become available.
“It is challenging having to make recommendations not having a lot of scientific evidence, but we still felt we had to use whatever’s out there to the best of our ability and use our experience to put together these recommendations,” Dawn M. Wahezi, MD, chief of pediatric rheumatology at Children’s Hospital at Montefiore and an associate professor of pediatrics at Albert Einstein College of Medicine, New York, said in an interview.
“We wanted to be mindful of the fact that there are things we know and things we don’t know, and we have to be careful about what we’re recommending,” said Dr. Wahezi, a member of the ACR working group that assembled the recommendations for pediatric rheumatic disease management during the pandemic. “We’re recommending the best we can at this moment, but if there are new studies that come out and suggest otherwise, we will definitely have to go back and amend the document.”
The foremost priority of the pediatric rheumatic disease guidance focuses on maintaining control of the disease and avoiding flares that may put children at greater risk of infection. Dr. Wahezi said the ACR has received many calls from patients and clinicians asking whether patients should continue their immunosuppressant medications. Fear of the coronavirus infection, medication shortages, difficulty getting to the pharmacy, uneasiness about going to the clinic or hospital for infusions, and other barriers may have led to gaps in medication.
“We didn’t want people to be too quick to hold patients’ medications just because they were scared of COVID,” Dr. Wahezi said. “If they did have medication stopped for one reason or another and their disease flared, having active disease, regardless of which disease it is, actually puts you at higher risk for infection. By controlling their disease, that would be the way to protect them the most.”
A key takeaway in the guidance on MIS-C, meanwhile, is an emphasis on its rarity lest physicians be too quick to diagnose it and miss another serious condition with overlapping symptoms, explained Lauren Henderson, MD, an attending rheumatologist at Boston Children’s Hospital and assistant professor of pediatrics at Harvard Medical School, Boston. Dr. Henderson participated in the ACR group that wrote the MIS-C guidance.
“The first thing we want to be thoughtful about clinically is to recognize that children in general with the acute infectious phase of SARS-CoV-2 have mild symptoms and generally do well,” Dr. Henderson said. “From what we can tell from all the data, MIS-C is rare. That really needs to be considered when clinicians on the ground are doing the diagnostic evaluation” because of concerns that clinicians “could rush to diagnose and treat patients with MIS-C and miss important diagnoses like malignancies and infections.”
Management of pediatric rheumatic disease during the pandemic
The COVID-19 clinical guidance for managing pediatric rheumatic disease grew from the work of the North American Pediatric Rheumatology Clinical Guidance Task Force, which included seven pediatric rheumatologists, two pediatric infectious disease physicians, one adult rheumatologist, and one pediatric nurse practitioner. The general guidance covers usual preventive measures for reducing risk for COVID-19 infection, the recommendation that children continue to receive recommended vaccines unless contraindicated by medication, and routine in-person visits for ophthalmologic surveillance of those with a history of uveitis or at high risk for chronic uveitis. The guidance also notes the risk of mental health concerns, such as depression and anxiety, related to quarantine and the pandemic.
The top recommendation is initiation or continuation of all medications necessary to control underlying disease, including NSAIDs, hydroxychloroquine, ACE inhibitors/angiotensin II receptor blockers, colchicine, conventional disease-modifying antirheumatic drugs (cDMARDs), biologic DMARDs, and targeted synthetic DMARDs. Even patients who may have had exposure to COVID-19 or who have an asymptomatic COVID-19 infection should continue to take these medications with the exception of ACEi/ARBs.
In those with pediatric rheumatic disease who have a symptomatic COVID-19 infection, “NSAIDs, HCQ, and colchicine may be continued, if necessary, to control underlying disease,” as can interleukin (IL)-1 and IL-6 inhibitors, but “cDMARDs, bDMARDs [except IL-1 and IL-6 inhibitors] and tsDMARDs should be temporarily delayed or withheld,” according to the guidance. Glucocorticoids can be continued at the lowest possible dose to control disease.
“There’s nothing in the literature that suggests people who have rheumatic disease, especially children, and people who are on these medications, really are at increased risk for COVID-19,” Dr. Wahezi said. “That’s why we didn’t want people to be overcautious in stopping medications when the main priority is to control their disease.”
She noted some experts’ speculations that these medications may actually benefit patients with rheumatic disease who develop a COVID-19 infection because the medications keep the immune response in check. “If you allow them to have this dysregulated immune response and have active disease, you’re potentially putting them at greater risk,” Dr. Wahezi said, although she stressed that inadequate evidence exists to support these speculations right now.
Lack of evidence has been the biggest challenge all around with developing this guidance, she said.
“Because this is such an unprecedented situation and because people are so desperate to find treatments both for the illness and to protect those at risk for it, there are lots of people trying to put evidence out there, but it may not be the best-quality evidence,” Dr. Wahezi said.
Insufficient evidence also drove the group’s determination that “SARS-CoV-2 antibody testing is not useful in informing on the history of infection or risk of reinfection,” as the guidance states. Too much variability in the assays exist, Dr. Wahezi said, and, further, it’s unclear what the clinical significance of a positive test would be.
“We didn’t want anyone to feel they had to make clinical decisions based on the results of that antibody testing,” she said. “Even if the test is accurate, we don’t know how to interpret it because it’s so new.”
The guidance also notes that patients with stable disease and previously stable lab markers on stable doses of their medication may be able to extend the interval for medication toxicity lab testing a few months if there is concern about exposure to COVID-19 to get the blood work.
“If you’re just starting a medicine or there’s someone who’s had abnormalities with the medicine in the past or you’re making medication adjustments, you wouldn’t do it in those scenarios, but if there’s someone who’s been on the drug for a long time and are nervous to get [blood] drawn, it’s probably okay to delay it,” Dr. Wahezi said. Lab work for disease activity measures, on the other hand, remain particularly important, especially since telemedicine visits may require clinicians to rely on lab results more than previously.
Management of MIS-C associated with COVID-19
The task force that developed guidance for the new inflammatory condition recently linked to SARS-CoV-2 infections in children included nine pediatric rheumatologists, two adult rheumatologists, two pediatric cardiologists, two pediatric infectious disease specialists, and one pediatric critical care physician.
The guidance includes a figure for the diagnostic pathway in evaluating children suspected of having MIS-C and extensive detail on diagnostic work-up, but the task force intentionally avoided providing a case definition for the condition. Existing case definitions from the Centers for Disease Control and Prevention, World Health Organization, and the United Kingdom’s Royal College of Paediatrics and Child Health differ from one another and are based on unclear evidence, Dr. Henderson noted. “We really don’t have enough data to know the sensitivity and specificity of each parameter, and until that’s available, we didn’t want to add to the confusion,” she said.
The guidance also stresses that MIS-C is a rare complication, so patients suspected of having the condition who do not have “life-threatening manifestations should undergo diagnostic evaluation for MIS-C as well as other possible infectious and noninfectious etiologies before immunomodulatory treatment is initiated,” the guidance states.
Unless a child is in shock or otherwise requires urgent care, physicians should take the time to complete the diagnostic work-up while monitoring the child, Dr. Henderson said. If the child does have MIS-C, the guidance currently recommends intravenous immunoglobulin (IVIG) and/or glucocorticoids to prevent coronary artery aneurysms, the same treatment other institutions have been recommending.
“We don’t have rigorous comparative studies looking at different types of treatments,” Dr. Henderson said, noting that the vast majority of children in the literature received IVIG and/or glucocorticoid treatment. “Often children really responded quite forcefully to those treatments, but we don’t have high-quality data yet to know that this treatment is better than supportive care or another medication.”
Dr. Henderson also stressed the importance of children receiving care at a facility with the necessary expertise to manage MIS-C and receiving long-term follow-up care from a multidisciplinary clinical team that includes a rheumatologist, an infectious disease doctor, a cardiologist, and possibly a hematologist.
“Making sure children are admitted to a hospital that has the resources and are followed by physicians with expertise or understanding of the intricacies of MIS-C is really important,” she said, particularly for children with cardiac involvement. “We don’t know if all the kids presenting with left ventricular dysfunction and shock are at risk for having myocardial fibrosis down the line,” she noted. “There is so much we do not understand and very little data to guide us on what to do, so these children really need to be under the care of a cardiologist and rheumatologist to make sure that their care is tailored to them.”
Although MIS-C shares overlapping symptoms with Kawasaki disease, it’s still unclear how similar or different the two conditions are, Dr. Henderson said.
“We can definitely say that when we look at MIS-C and compare it to historical groups of Kawasaki disease before the pandemic, there are definitely different features in the MIS-C group,” she said. Kawasaki disease generally only affects children under age 5, whereas MIS-C patients run the gamut from age 1-17. Racial demographics are also different, with a higher proportion of black children affected by MIS-C.
It’s possible that the pathophysiology of both conditions will turn out to be similar, particularly given the hypothesis that Kawasaki disease is triggered by infections in genetically predisposed people. However, the severity of symptoms and risk of aneurysms appear greater with MIS-C so far.
“The degree to which these patients are presenting with left ventricular dysfunction and shock is much higher than what we’ve seen previously,” Dr. Henderson said. “Children can have aneurysms even if they don’t meet all the Kawasaki disease features, which makes it feel that this is somehow clinically different from what we’ve seen before. It’s not just the kids who have the rash and the conjunctivitis and the extremity changes and oral changes who have the aneurysms.”
The reason for including both IVIG and glucocorticoids as possible first-line drugs to prevent aneurysms is that some evidence suggests children with MIS-C may have higher levels of IVIG resistance, she said.
Like Dr. Wahezi, Dr. Henderson emphasized the necessarily transient nature of these recommendations.
“These recommendations will almost certainly change based on evolving understanding of MIS-C and the data,” Dr. Henderson said, adding that this new, unique condition highlights the importance of including children in allocating funding for research and in clinical trials.
“Children are not always identical to adults, and it’s really important that we have high-quality data to inform our decisions about how to care for them,” she said.
Dr. Wahezi had no disclosures. Dr. Henderson has consulted for Sobi and Adaptive Technologies. The guidelines did not note other disclosures for members of the ACR groups.
SOURCES: COVID-19 Clinical Guidance for Pediatric Patients with Rheumatic Disease and Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19
Newer anticoagulants linked to lower fracture risk in AFib
The direct oral anticoagulant (DOAC) drugs apixaban, dabigatran, and rivaroxaban are associated with a lower risk of osteoporotic fracture than is warfarin in patients with atrial fibrillation (AFib), according to a new retrospective analysis.
There was no difference in risk between individual DOAC medications.
The study drew from an EHR database of the Hong Kong Hospital Authority. It was led by Wallis C.Y. Lau, PhD, of the University of Hong Kong and appeared online May 19 in Annals of Internal Medicine.
Warfarin is suspected to contribute to osteoporotic fracturing in AFib patients, but previous studies returned mixed results. The more recently introduced DOACs were not tested for fracture risks, and it hasn’t been determined if individual DOACs have different risks. The question is even more important in AFib, in which patients are older and often have comorbidities that could predispose them to fractures.
The study included 23,515 patients with AFib who used anticoagulants. 3,241 used apixaban, 6,867 dabigatran, 3,866 rivaroxaban, and 9,541 used warfarin. The median follow-up was 423 days.
According to Cox proportional hazards model analyses, DOAC use was associated with fewer fractures than was warfarin (hazard ratio for apixaban vs. warfarin, 0.62; 95% confidence interval, 0.41-0.94; HR for dabigatran, 0.65; 95% CI, 0.49-0.86; HR for rivaroxaban, 0.52; 95% CI, 0.37-0.73). Subanalyses in men and women showed similar results (P for interaction >.05).
Head-to-head comparisons between individual DOACs yielded no statistically significant differences in osteoporotic fracture risk.
Although the findings couldn’t absolutely rule out a difference in osteoporotic fracture risk between different DOACs, the authors argue that any clinical significance would likely be small.
“Given the supportive evidence from experimental settings, findings from our study using clinical data, and the indirect evidence provided by the previous meta-analysis of randomized, controlled trials, there exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” the authors wrote.
The study is limited by the potential for residual confounding, the investigators noted.
The study was funded by the University of Hong Kong and University College London Strategic Partnership Fund.
SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 19. doi: 10.7326/M19-3671.
The direct oral anticoagulant (DOAC) drugs apixaban, dabigatran, and rivaroxaban are associated with a lower risk of osteoporotic fracture than is warfarin in patients with atrial fibrillation (AFib), according to a new retrospective analysis.
There was no difference in risk between individual DOAC medications.
The study drew from an EHR database of the Hong Kong Hospital Authority. It was led by Wallis C.Y. Lau, PhD, of the University of Hong Kong and appeared online May 19 in Annals of Internal Medicine.
Warfarin is suspected to contribute to osteoporotic fracturing in AFib patients, but previous studies returned mixed results. The more recently introduced DOACs were not tested for fracture risks, and it hasn’t been determined if individual DOACs have different risks. The question is even more important in AFib, in which patients are older and often have comorbidities that could predispose them to fractures.
The study included 23,515 patients with AFib who used anticoagulants. 3,241 used apixaban, 6,867 dabigatran, 3,866 rivaroxaban, and 9,541 used warfarin. The median follow-up was 423 days.
According to Cox proportional hazards model analyses, DOAC use was associated with fewer fractures than was warfarin (hazard ratio for apixaban vs. warfarin, 0.62; 95% confidence interval, 0.41-0.94; HR for dabigatran, 0.65; 95% CI, 0.49-0.86; HR for rivaroxaban, 0.52; 95% CI, 0.37-0.73). Subanalyses in men and women showed similar results (P for interaction >.05).
Head-to-head comparisons between individual DOACs yielded no statistically significant differences in osteoporotic fracture risk.
Although the findings couldn’t absolutely rule out a difference in osteoporotic fracture risk between different DOACs, the authors argue that any clinical significance would likely be small.
“Given the supportive evidence from experimental settings, findings from our study using clinical data, and the indirect evidence provided by the previous meta-analysis of randomized, controlled trials, there exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” the authors wrote.
The study is limited by the potential for residual confounding, the investigators noted.
The study was funded by the University of Hong Kong and University College London Strategic Partnership Fund.
SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 19. doi: 10.7326/M19-3671.
The direct oral anticoagulant (DOAC) drugs apixaban, dabigatran, and rivaroxaban are associated with a lower risk of osteoporotic fracture than is warfarin in patients with atrial fibrillation (AFib), according to a new retrospective analysis.
There was no difference in risk between individual DOAC medications.
The study drew from an EHR database of the Hong Kong Hospital Authority. It was led by Wallis C.Y. Lau, PhD, of the University of Hong Kong and appeared online May 19 in Annals of Internal Medicine.
Warfarin is suspected to contribute to osteoporotic fracturing in AFib patients, but previous studies returned mixed results. The more recently introduced DOACs were not tested for fracture risks, and it hasn’t been determined if individual DOACs have different risks. The question is even more important in AFib, in which patients are older and often have comorbidities that could predispose them to fractures.
The study included 23,515 patients with AFib who used anticoagulants. 3,241 used apixaban, 6,867 dabigatran, 3,866 rivaroxaban, and 9,541 used warfarin. The median follow-up was 423 days.
According to Cox proportional hazards model analyses, DOAC use was associated with fewer fractures than was warfarin (hazard ratio for apixaban vs. warfarin, 0.62; 95% confidence interval, 0.41-0.94; HR for dabigatran, 0.65; 95% CI, 0.49-0.86; HR for rivaroxaban, 0.52; 95% CI, 0.37-0.73). Subanalyses in men and women showed similar results (P for interaction >.05).
Head-to-head comparisons between individual DOACs yielded no statistically significant differences in osteoporotic fracture risk.
Although the findings couldn’t absolutely rule out a difference in osteoporotic fracture risk between different DOACs, the authors argue that any clinical significance would likely be small.
“Given the supportive evidence from experimental settings, findings from our study using clinical data, and the indirect evidence provided by the previous meta-analysis of randomized, controlled trials, there exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” the authors wrote.
The study is limited by the potential for residual confounding, the investigators noted.
The study was funded by the University of Hong Kong and University College London Strategic Partnership Fund.
SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 19. doi: 10.7326/M19-3671.
FROM ANNALS OF INTERNAL MEDICINE
Protective levels of vitamin D achievable in SCD with oral supplementation
Sickle cell disease is associated with worse long-term bone health than that of the general population, and SCD patients are more likely to experience vitamin D [25(OH)D] deficiency. Oral vitamin D3 supplementation can achieve protective levels in children with sickle cell disease, and a daily dose was able to achieved optimal blood levels, according to a report published online in Bone.
The researchers performed a prospective, longitudinal, single-center study of 80 children with SCD. They collected demographic, clinical, and management data, as well as 25(OH)D levels. Bone densitometries (DXA) were also collected.
Among the 80 patients were included in the analysis, there were significant differences between the means of 25(OH)D levels based on whether the patient started prophylactic treatment as an infant or not (35.7 vs. 27.9 ng/mL, respectively [P = .014]), according to the researchers.
They also found that, in multivariate analysis, an oral 800 IU daily dose of vitamin D3 was shown to be a protective factor (P = .044) in reaching optimal 25(OH)D blood levels (≥ 30 ng/mL).
Kaplan-Meier analysis showed that those patients younger than 10 years of age reached optimal levels significantly earlier than older patients when on supplementation (P = .002), as did those patients who were not being treated with hydroxyurea (P = .039), the researchers wrote.
Significant differences were seen between the mean bone mineral density in both DXAs performed when comparing suboptimal vs. optimal blood levels of 25(OH)D (0.54 g/cm2 vs. 0.64 g/cm2, respectively, P = .001), for the initial DXA, and for the most recent DXA (0.59 g/cm2 vs. 0.77 g/cm2, respectively, P = .044). “VitD3 prophylaxis is a safe practice in SCD. It is important to start this prophylactic treatment when the child is an infant. The daily regimen with 800 IU could be more effective for reaching levels ≥ 30 ng/mL, and, especially in preadolescent and adolescent patients, we should raise awareness about the importance of good bone health,” the authors concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Garrido C et al. Bone. 2020;133: doi.org/10.1016/j.bone.2020.115228.
Sickle cell disease is associated with worse long-term bone health than that of the general population, and SCD patients are more likely to experience vitamin D [25(OH)D] deficiency. Oral vitamin D3 supplementation can achieve protective levels in children with sickle cell disease, and a daily dose was able to achieved optimal blood levels, according to a report published online in Bone.
The researchers performed a prospective, longitudinal, single-center study of 80 children with SCD. They collected demographic, clinical, and management data, as well as 25(OH)D levels. Bone densitometries (DXA) were also collected.
Among the 80 patients were included in the analysis, there were significant differences between the means of 25(OH)D levels based on whether the patient started prophylactic treatment as an infant or not (35.7 vs. 27.9 ng/mL, respectively [P = .014]), according to the researchers.
They also found that, in multivariate analysis, an oral 800 IU daily dose of vitamin D3 was shown to be a protective factor (P = .044) in reaching optimal 25(OH)D blood levels (≥ 30 ng/mL).
Kaplan-Meier analysis showed that those patients younger than 10 years of age reached optimal levels significantly earlier than older patients when on supplementation (P = .002), as did those patients who were not being treated with hydroxyurea (P = .039), the researchers wrote.
Significant differences were seen between the mean bone mineral density in both DXAs performed when comparing suboptimal vs. optimal blood levels of 25(OH)D (0.54 g/cm2 vs. 0.64 g/cm2, respectively, P = .001), for the initial DXA, and for the most recent DXA (0.59 g/cm2 vs. 0.77 g/cm2, respectively, P = .044). “VitD3 prophylaxis is a safe practice in SCD. It is important to start this prophylactic treatment when the child is an infant. The daily regimen with 800 IU could be more effective for reaching levels ≥ 30 ng/mL, and, especially in preadolescent and adolescent patients, we should raise awareness about the importance of good bone health,” the authors concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Garrido C et al. Bone. 2020;133: doi.org/10.1016/j.bone.2020.115228.
Sickle cell disease is associated with worse long-term bone health than that of the general population, and SCD patients are more likely to experience vitamin D [25(OH)D] deficiency. Oral vitamin D3 supplementation can achieve protective levels in children with sickle cell disease, and a daily dose was able to achieved optimal blood levels, according to a report published online in Bone.
The researchers performed a prospective, longitudinal, single-center study of 80 children with SCD. They collected demographic, clinical, and management data, as well as 25(OH)D levels. Bone densitometries (DXA) were also collected.
Among the 80 patients were included in the analysis, there were significant differences between the means of 25(OH)D levels based on whether the patient started prophylactic treatment as an infant or not (35.7 vs. 27.9 ng/mL, respectively [P = .014]), according to the researchers.
They also found that, in multivariate analysis, an oral 800 IU daily dose of vitamin D3 was shown to be a protective factor (P = .044) in reaching optimal 25(OH)D blood levels (≥ 30 ng/mL).
Kaplan-Meier analysis showed that those patients younger than 10 years of age reached optimal levels significantly earlier than older patients when on supplementation (P = .002), as did those patients who were not being treated with hydroxyurea (P = .039), the researchers wrote.
Significant differences were seen between the mean bone mineral density in both DXAs performed when comparing suboptimal vs. optimal blood levels of 25(OH)D (0.54 g/cm2 vs. 0.64 g/cm2, respectively, P = .001), for the initial DXA, and for the most recent DXA (0.59 g/cm2 vs. 0.77 g/cm2, respectively, P = .044). “VitD3 prophylaxis is a safe practice in SCD. It is important to start this prophylactic treatment when the child is an infant. The daily regimen with 800 IU could be more effective for reaching levels ≥ 30 ng/mL, and, especially in preadolescent and adolescent patients, we should raise awareness about the importance of good bone health,” the authors concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Garrido C et al. Bone. 2020;133: doi.org/10.1016/j.bone.2020.115228.
FROM BONE
Expert discusses red flags for interstitial lung disease in pediatric rheumatology
MAUI, HAWAII – Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.
In addition to detailing the autoantibody red flags for ILD in juvenile dermatomyositis (JDM), she called for “hypervigilance” in patients with systemic juvenile idiopathic arthritis (SJIA) who exhibit any of a series of risk factors for ILD.
“Most of the lung disease in kids with systemic JIA is asymptomatic until very late, but it can be reversible if we treat it. So it’s worth finding and monitoring and giving everyone PCP [pneumocystis pneumonia] prophylaxis, because they have a high incidence of PCP if they have any of those risk factors,” observed Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
Autoantibodies predict ILD in JDM
Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 12% of 25 patients with juvenile polymyositis and in 18% of 44 youths with an overlap of juvenile connective tissue disease and myositis. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: Namely, 9% of the cohort were positive for antimelanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl tRNA synthestase (anti-Jo-1) autoantibodies were present in 4%.
A total of 33 of the 371 juvenile myositis patients had ILD based upon CT imaging, chest X-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo-1. After controlling for the presence of these other myositis-specific autoantibodies, auto-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.
Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52- and anti-Jo-1 positive.
Patients with anti-Ro52 autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
Novel potential treatment for ILD in JDM: JAK inhibitors
Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, intravenous immunoglobulin (IVIG), and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody-positive disease, according to Dr. Stevens.
For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody-positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near-resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.
Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals.
Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than did the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms.
The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.
Risk factors for ILD in SJIA
In the past half-dozen years or so, pediatric rheumatologists have become increasingly aware of and concerned about a new development in SJIA: the occurrence of comorbid ILD. This is a poor-prognosis disease: In a cohort from the United Kingdom, 5-year mortality from the time of diagnosis was 41%, fully 40-fold higher than in patients with SJIA only.
Patient cohorts with SJIA and ILD have unusual clinical and laboratory features that aren’t part of the typical picture in SJIA. These include acute clubbing, lymphopenia, a fixed pruritic rash, unexplained abdominal pain, peripheral eosinophilia, facial swelling, and an increased ferritin level, a hallmark of acute macrophage activation syndrome. Onset of SJIA before 2 years of age is another red flag associated with increased risk for ILD. So is trisomy 21, which is up to 50 times more prevalent in patients with SJIA and ILD than in the general population or in patients with SJIA only. Another clue is an adverse reaction to tocilizumab (Actemra).
Any of these findings warrant hypervigilance: “Be on high alert and monitor these patients for ILD much more closely,” Dr. Stevens advised.
This means ordering a CT scan, prescribing PCP prophylaxis, and regularly measuring pulmonary function, admittedly a challenge in children under 7 years old. In these younger kids, practical solutions include measuring their oxygen saturation before and after running around the room to see if it drops. A 6-minute walk test and sleep oximetry are other options.
The explanation for the abrupt arrival of ILD as part of the picture in SJIA during the past decade remains unclear. The timing coincides with a major advance in the treatment of SJIA: the arrival of biologic agents blocking interleukin-1 and -6. Could this be a serious treatment side effect?
“It’s all association so far, and we’re not really sure why we’re seeing this association. Is it because we’re using a lot [fewer] corticosteroids now, and maybe those were preventing lung disease in the past?” Dr. Stevens speculated.
At this point, she and her fellow pediatric rheumatologists are awaiting further evidence before discussing a curb in their use of IL-1 or -6 inhibitors in patients with SJIA.
“These drugs have turned around the lives of kids with SJIA. They used to suffer through all our ineffective treatments for years, with terrible joint destruction and a pretty high mortality rate. These are great drugs for this disease, and we certainly don’t want to limit them,” she said.
Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.
MAUI, HAWAII – Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.
In addition to detailing the autoantibody red flags for ILD in juvenile dermatomyositis (JDM), she called for “hypervigilance” in patients with systemic juvenile idiopathic arthritis (SJIA) who exhibit any of a series of risk factors for ILD.
“Most of the lung disease in kids with systemic JIA is asymptomatic until very late, but it can be reversible if we treat it. So it’s worth finding and monitoring and giving everyone PCP [pneumocystis pneumonia] prophylaxis, because they have a high incidence of PCP if they have any of those risk factors,” observed Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
Autoantibodies predict ILD in JDM
Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 12% of 25 patients with juvenile polymyositis and in 18% of 44 youths with an overlap of juvenile connective tissue disease and myositis. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: Namely, 9% of the cohort were positive for antimelanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl tRNA synthestase (anti-Jo-1) autoantibodies were present in 4%.
A total of 33 of the 371 juvenile myositis patients had ILD based upon CT imaging, chest X-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo-1. After controlling for the presence of these other myositis-specific autoantibodies, auto-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.
Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52- and anti-Jo-1 positive.
Patients with anti-Ro52 autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
Novel potential treatment for ILD in JDM: JAK inhibitors
Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, intravenous immunoglobulin (IVIG), and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody-positive disease, according to Dr. Stevens.
For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody-positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near-resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.
Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals.
Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than did the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms.
The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.
Risk factors for ILD in SJIA
In the past half-dozen years or so, pediatric rheumatologists have become increasingly aware of and concerned about a new development in SJIA: the occurrence of comorbid ILD. This is a poor-prognosis disease: In a cohort from the United Kingdom, 5-year mortality from the time of diagnosis was 41%, fully 40-fold higher than in patients with SJIA only.
Patient cohorts with SJIA and ILD have unusual clinical and laboratory features that aren’t part of the typical picture in SJIA. These include acute clubbing, lymphopenia, a fixed pruritic rash, unexplained abdominal pain, peripheral eosinophilia, facial swelling, and an increased ferritin level, a hallmark of acute macrophage activation syndrome. Onset of SJIA before 2 years of age is another red flag associated with increased risk for ILD. So is trisomy 21, which is up to 50 times more prevalent in patients with SJIA and ILD than in the general population or in patients with SJIA only. Another clue is an adverse reaction to tocilizumab (Actemra).
Any of these findings warrant hypervigilance: “Be on high alert and monitor these patients for ILD much more closely,” Dr. Stevens advised.
This means ordering a CT scan, prescribing PCP prophylaxis, and regularly measuring pulmonary function, admittedly a challenge in children under 7 years old. In these younger kids, practical solutions include measuring their oxygen saturation before and after running around the room to see if it drops. A 6-minute walk test and sleep oximetry are other options.
The explanation for the abrupt arrival of ILD as part of the picture in SJIA during the past decade remains unclear. The timing coincides with a major advance in the treatment of SJIA: the arrival of biologic agents blocking interleukin-1 and -6. Could this be a serious treatment side effect?
“It’s all association so far, and we’re not really sure why we’re seeing this association. Is it because we’re using a lot [fewer] corticosteroids now, and maybe those were preventing lung disease in the past?” Dr. Stevens speculated.
At this point, she and her fellow pediatric rheumatologists are awaiting further evidence before discussing a curb in their use of IL-1 or -6 inhibitors in patients with SJIA.
“These drugs have turned around the lives of kids with SJIA. They used to suffer through all our ineffective treatments for years, with terrible joint destruction and a pretty high mortality rate. These are great drugs for this disease, and we certainly don’t want to limit them,” she said.
Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.
MAUI, HAWAII – Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.
In addition to detailing the autoantibody red flags for ILD in juvenile dermatomyositis (JDM), she called for “hypervigilance” in patients with systemic juvenile idiopathic arthritis (SJIA) who exhibit any of a series of risk factors for ILD.
“Most of the lung disease in kids with systemic JIA is asymptomatic until very late, but it can be reversible if we treat it. So it’s worth finding and monitoring and giving everyone PCP [pneumocystis pneumonia] prophylaxis, because they have a high incidence of PCP if they have any of those risk factors,” observed Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
Autoantibodies predict ILD in JDM
Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 12% of 25 patients with juvenile polymyositis and in 18% of 44 youths with an overlap of juvenile connective tissue disease and myositis. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: Namely, 9% of the cohort were positive for antimelanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl tRNA synthestase (anti-Jo-1) autoantibodies were present in 4%.
A total of 33 of the 371 juvenile myositis patients had ILD based upon CT imaging, chest X-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo-1. After controlling for the presence of these other myositis-specific autoantibodies, auto-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.
Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52- and anti-Jo-1 positive.
Patients with anti-Ro52 autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
Novel potential treatment for ILD in JDM: JAK inhibitors
Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, intravenous immunoglobulin (IVIG), and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody-positive disease, according to Dr. Stevens.
For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody-positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near-resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.
Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals.
Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than did the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms.
The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.
Risk factors for ILD in SJIA
In the past half-dozen years or so, pediatric rheumatologists have become increasingly aware of and concerned about a new development in SJIA: the occurrence of comorbid ILD. This is a poor-prognosis disease: In a cohort from the United Kingdom, 5-year mortality from the time of diagnosis was 41%, fully 40-fold higher than in patients with SJIA only.
Patient cohorts with SJIA and ILD have unusual clinical and laboratory features that aren’t part of the typical picture in SJIA. These include acute clubbing, lymphopenia, a fixed pruritic rash, unexplained abdominal pain, peripheral eosinophilia, facial swelling, and an increased ferritin level, a hallmark of acute macrophage activation syndrome. Onset of SJIA before 2 years of age is another red flag associated with increased risk for ILD. So is trisomy 21, which is up to 50 times more prevalent in patients with SJIA and ILD than in the general population or in patients with SJIA only. Another clue is an adverse reaction to tocilizumab (Actemra).
Any of these findings warrant hypervigilance: “Be on high alert and monitor these patients for ILD much more closely,” Dr. Stevens advised.
This means ordering a CT scan, prescribing PCP prophylaxis, and regularly measuring pulmonary function, admittedly a challenge in children under 7 years old. In these younger kids, practical solutions include measuring their oxygen saturation before and after running around the room to see if it drops. A 6-minute walk test and sleep oximetry are other options.
The explanation for the abrupt arrival of ILD as part of the picture in SJIA during the past decade remains unclear. The timing coincides with a major advance in the treatment of SJIA: the arrival of biologic agents blocking interleukin-1 and -6. Could this be a serious treatment side effect?
“It’s all association so far, and we’re not really sure why we’re seeing this association. Is it because we’re using a lot [fewer] corticosteroids now, and maybe those were preventing lung disease in the past?” Dr. Stevens speculated.
At this point, she and her fellow pediatric rheumatologists are awaiting further evidence before discussing a curb in their use of IL-1 or -6 inhibitors in patients with SJIA.
“These drugs have turned around the lives of kids with SJIA. They used to suffer through all our ineffective treatments for years, with terrible joint destruction and a pretty high mortality rate. These are great drugs for this disease, and we certainly don’t want to limit them,” she said.
Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.
REPORTING FROM RWCS 2020
Are CRMO and SAPHO syndrome one and the same?
MAUI, HAWAII – Chronic recurrent multifocal osteomyelitis (CRMO) in children and SAPHO syndrome in adults may well be a single clinical syndrome.
That contention, recently put forth by Austrian investigators, resonates with Anne M. Stevens, MD, PhD, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
“Is CRMO just for kids? No,” she asserted at the 2020 Rheumatology Winter Clinical Symposium.
First off, she noted that the nomenclature is shifting: The more familiar acronym CRMO is giving way to CNO (chronic nonbacterial osteomyelitis) in light of evidence that roughly 30% of patients with CRMO start out with a single characteristic bone lesion, with the disease turning multifocal in the subsequent 4 years in the great majority of cases.
SAPHO syndrome – an acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis – a formerly obscure disease entity first described in 1987 in France, has suddenly become a trendy research topic, with three small studies presented at the 2019 annual meeting of the American College of Rheumatology.
CNO is a pediatric autoinflammatory bone disease characterized by sterile bone lesions, most often on the clavicle, spine, mandible, and lower extremities. It is marked by prominent focal bone and/or joint pain, worse at night, with or without swelling. With no agreed-upon diagnostic criteria or biomarkers, CNO is a diagnosis of exclusion. Two-thirds of the time the condition is initially misdiagnosed as bacterial osteomyelitis or a malignant tumor.
Austrian investigators at the University of Graz recently conducted a retrospective comparison of 24 pediatric patients diagnosed with CNO and 10 adults with SAPHO syndrome. The median age at diagnosis of CNO was 12.3 years versus 32.5 years for SAPHO syndrome. The two groups shared compelling similarities in mean number of bone lesions, prevalence of skin involvement, and other aspects of initial clinical presentation, as well as laboratory and histopathologic findings on bone biopsy.
There were, however, several notable clinical differences in this small dataset: CNO bone lesions affected mainly the lower extremities, clavicle, spine, and mandible, while SAPHO syndrome more commonly involved the sternum (50% vs. 8%) and vertebrae (50% vs. 21%). Also, the most frequent cutaneous manifestation was palmoplantar pustulosis in adults with SAPHO syndrome, while severe acne predominated in children with CNO. In both children and adults, the skin lesions most often arose after the bone symptoms, making early diagnosis a challenge.
Another similarity: Although there have been no randomized treatment trials in either CNO or SAPHO syndrome, case series suggest the same treatments are effective for both, with NSAIDs as first line, followed by nonbiologic disease-modifying antirheumatic drugs, tumor necrosis factor (TNF) inhibitors, or bisphosphonates.
CNO diagnosis, treatment, and follow-up
Various investigators have pegged the sensitivity of physical examination for diagnosis of CNO at 31%, radiographs at a lowly 13%, and bone scintigraphy at 74%, all in comparison with MRI.
“Our go-to now is MRI with STIR [short tau inversion recovery],” according to Dr. Stevens. “There’s no contrast – so no IV – no radiation, and it’s fast, 20 minutes for a whole body MRI in a little kid, 45 minutes in a big one.”
Insurers are reluctant to pay for serial whole-body MRIs for patient follow-up, so it’s often necessary to order a series of images covering different body parts.
Her University of Washington colleague Dan Zhao, MD, PhD, is developing infrared thermal imaging as an inexpensive, convenient alternative to MRI which could theoretically be done at home. In a pilot study in 30 children with CNO and 31 controls, inflamed leg segments showed significantly higher temperatures. Larger studies are planned.
Dr. Stevens advised leaning towards a diagnosis of CNO with avoidance of bone biopsy in a patient with multifocal osteomyelitis at the typical sites, a normal CBC, the typical extraosseous manifestations, and normal or only mildly elevated erythrocyte sedimentation rate and C-reactive protein in an otherwise well-appearing child. In contrast, strongly consider a bone biopsy to rule out malignancy or infection if the child has unexplained highly elevated C-reactive protein and erythrocyte sedimentation rate, cytopenia, high fever, excessive pain, lymphadenopathy, hepatosplenomegaly, or suspicious imaging findings.
German rheumatologists have developed a clinical score for diagnosis of CNO. A normal blood cell count gets 13 points; symmetric bone lesions 10; lesions with marginal sclerosis 10; a normal body temperature 9; two or more radiologically proven lesions 7; a C-reactive protein of 1 mg/dL or greater 6; and vertebral, clavicular, or sternal lesions 8. A score of 39 points or more out of a possible 63 had a 97% positive predictive value for CNO in a retrospective study of 224 children with CNO, proven bacterial osteomyelitis, or malignant bone tumors. A score of 28 points or less had a 97% negative predictive value for CNO. An indeterminate score of 29-38 warrants close monitoring.
The scoring system hasn’t been validated, but most pediatric rheumatologists agree that it’s useful, according to Dr. Stevens.
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) is in the process of developing standardized diagnostic and classification criteria and treatment plans for CNO. Dr. Zhao was first author of a CARRA consensus treatment plan for CNO refractory to NSAID monotherapy. The plan for the first 12 months includes three options: methotrexate or sulfasalazine, TNF inhibitors with or without methotrexate, and bisphosphonates.
“The main point of this is you try a medicine and then wait 3 months. If they’re not responding then, switch medicines or add another drug. Monitor every 3 months based upon pain,” she said.
Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.
MAUI, HAWAII – Chronic recurrent multifocal osteomyelitis (CRMO) in children and SAPHO syndrome in adults may well be a single clinical syndrome.
That contention, recently put forth by Austrian investigators, resonates with Anne M. Stevens, MD, PhD, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
“Is CRMO just for kids? No,” she asserted at the 2020 Rheumatology Winter Clinical Symposium.
First off, she noted that the nomenclature is shifting: The more familiar acronym CRMO is giving way to CNO (chronic nonbacterial osteomyelitis) in light of evidence that roughly 30% of patients with CRMO start out with a single characteristic bone lesion, with the disease turning multifocal in the subsequent 4 years in the great majority of cases.
SAPHO syndrome – an acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis – a formerly obscure disease entity first described in 1987 in France, has suddenly become a trendy research topic, with three small studies presented at the 2019 annual meeting of the American College of Rheumatology.
CNO is a pediatric autoinflammatory bone disease characterized by sterile bone lesions, most often on the clavicle, spine, mandible, and lower extremities. It is marked by prominent focal bone and/or joint pain, worse at night, with or without swelling. With no agreed-upon diagnostic criteria or biomarkers, CNO is a diagnosis of exclusion. Two-thirds of the time the condition is initially misdiagnosed as bacterial osteomyelitis or a malignant tumor.
Austrian investigators at the University of Graz recently conducted a retrospective comparison of 24 pediatric patients diagnosed with CNO and 10 adults with SAPHO syndrome. The median age at diagnosis of CNO was 12.3 years versus 32.5 years for SAPHO syndrome. The two groups shared compelling similarities in mean number of bone lesions, prevalence of skin involvement, and other aspects of initial clinical presentation, as well as laboratory and histopathologic findings on bone biopsy.
There were, however, several notable clinical differences in this small dataset: CNO bone lesions affected mainly the lower extremities, clavicle, spine, and mandible, while SAPHO syndrome more commonly involved the sternum (50% vs. 8%) and vertebrae (50% vs. 21%). Also, the most frequent cutaneous manifestation was palmoplantar pustulosis in adults with SAPHO syndrome, while severe acne predominated in children with CNO. In both children and adults, the skin lesions most often arose after the bone symptoms, making early diagnosis a challenge.
Another similarity: Although there have been no randomized treatment trials in either CNO or SAPHO syndrome, case series suggest the same treatments are effective for both, with NSAIDs as first line, followed by nonbiologic disease-modifying antirheumatic drugs, tumor necrosis factor (TNF) inhibitors, or bisphosphonates.
CNO diagnosis, treatment, and follow-up
Various investigators have pegged the sensitivity of physical examination for diagnosis of CNO at 31%, radiographs at a lowly 13%, and bone scintigraphy at 74%, all in comparison with MRI.
“Our go-to now is MRI with STIR [short tau inversion recovery],” according to Dr. Stevens. “There’s no contrast – so no IV – no radiation, and it’s fast, 20 minutes for a whole body MRI in a little kid, 45 minutes in a big one.”
Insurers are reluctant to pay for serial whole-body MRIs for patient follow-up, so it’s often necessary to order a series of images covering different body parts.
Her University of Washington colleague Dan Zhao, MD, PhD, is developing infrared thermal imaging as an inexpensive, convenient alternative to MRI which could theoretically be done at home. In a pilot study in 30 children with CNO and 31 controls, inflamed leg segments showed significantly higher temperatures. Larger studies are planned.
Dr. Stevens advised leaning towards a diagnosis of CNO with avoidance of bone biopsy in a patient with multifocal osteomyelitis at the typical sites, a normal CBC, the typical extraosseous manifestations, and normal or only mildly elevated erythrocyte sedimentation rate and C-reactive protein in an otherwise well-appearing child. In contrast, strongly consider a bone biopsy to rule out malignancy or infection if the child has unexplained highly elevated C-reactive protein and erythrocyte sedimentation rate, cytopenia, high fever, excessive pain, lymphadenopathy, hepatosplenomegaly, or suspicious imaging findings.
German rheumatologists have developed a clinical score for diagnosis of CNO. A normal blood cell count gets 13 points; symmetric bone lesions 10; lesions with marginal sclerosis 10; a normal body temperature 9; two or more radiologically proven lesions 7; a C-reactive protein of 1 mg/dL or greater 6; and vertebral, clavicular, or sternal lesions 8. A score of 39 points or more out of a possible 63 had a 97% positive predictive value for CNO in a retrospective study of 224 children with CNO, proven bacterial osteomyelitis, or malignant bone tumors. A score of 28 points or less had a 97% negative predictive value for CNO. An indeterminate score of 29-38 warrants close monitoring.
The scoring system hasn’t been validated, but most pediatric rheumatologists agree that it’s useful, according to Dr. Stevens.
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) is in the process of developing standardized diagnostic and classification criteria and treatment plans for CNO. Dr. Zhao was first author of a CARRA consensus treatment plan for CNO refractory to NSAID monotherapy. The plan for the first 12 months includes three options: methotrexate or sulfasalazine, TNF inhibitors with or without methotrexate, and bisphosphonates.
“The main point of this is you try a medicine and then wait 3 months. If they’re not responding then, switch medicines or add another drug. Monitor every 3 months based upon pain,” she said.
Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.
MAUI, HAWAII – Chronic recurrent multifocal osteomyelitis (CRMO) in children and SAPHO syndrome in adults may well be a single clinical syndrome.
That contention, recently put forth by Austrian investigators, resonates with Anne M. Stevens, MD, PhD, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
“Is CRMO just for kids? No,” she asserted at the 2020 Rheumatology Winter Clinical Symposium.
First off, she noted that the nomenclature is shifting: The more familiar acronym CRMO is giving way to CNO (chronic nonbacterial osteomyelitis) in light of evidence that roughly 30% of patients with CRMO start out with a single characteristic bone lesion, with the disease turning multifocal in the subsequent 4 years in the great majority of cases.
SAPHO syndrome – an acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis – a formerly obscure disease entity first described in 1987 in France, has suddenly become a trendy research topic, with three small studies presented at the 2019 annual meeting of the American College of Rheumatology.
CNO is a pediatric autoinflammatory bone disease characterized by sterile bone lesions, most often on the clavicle, spine, mandible, and lower extremities. It is marked by prominent focal bone and/or joint pain, worse at night, with or without swelling. With no agreed-upon diagnostic criteria or biomarkers, CNO is a diagnosis of exclusion. Two-thirds of the time the condition is initially misdiagnosed as bacterial osteomyelitis or a malignant tumor.
Austrian investigators at the University of Graz recently conducted a retrospective comparison of 24 pediatric patients diagnosed with CNO and 10 adults with SAPHO syndrome. The median age at diagnosis of CNO was 12.3 years versus 32.5 years for SAPHO syndrome. The two groups shared compelling similarities in mean number of bone lesions, prevalence of skin involvement, and other aspects of initial clinical presentation, as well as laboratory and histopathologic findings on bone biopsy.
There were, however, several notable clinical differences in this small dataset: CNO bone lesions affected mainly the lower extremities, clavicle, spine, and mandible, while SAPHO syndrome more commonly involved the sternum (50% vs. 8%) and vertebrae (50% vs. 21%). Also, the most frequent cutaneous manifestation was palmoplantar pustulosis in adults with SAPHO syndrome, while severe acne predominated in children with CNO. In both children and adults, the skin lesions most often arose after the bone symptoms, making early diagnosis a challenge.
Another similarity: Although there have been no randomized treatment trials in either CNO or SAPHO syndrome, case series suggest the same treatments are effective for both, with NSAIDs as first line, followed by nonbiologic disease-modifying antirheumatic drugs, tumor necrosis factor (TNF) inhibitors, or bisphosphonates.
CNO diagnosis, treatment, and follow-up
Various investigators have pegged the sensitivity of physical examination for diagnosis of CNO at 31%, radiographs at a lowly 13%, and bone scintigraphy at 74%, all in comparison with MRI.
“Our go-to now is MRI with STIR [short tau inversion recovery],” according to Dr. Stevens. “There’s no contrast – so no IV – no radiation, and it’s fast, 20 minutes for a whole body MRI in a little kid, 45 minutes in a big one.”
Insurers are reluctant to pay for serial whole-body MRIs for patient follow-up, so it’s often necessary to order a series of images covering different body parts.
Her University of Washington colleague Dan Zhao, MD, PhD, is developing infrared thermal imaging as an inexpensive, convenient alternative to MRI which could theoretically be done at home. In a pilot study in 30 children with CNO and 31 controls, inflamed leg segments showed significantly higher temperatures. Larger studies are planned.
Dr. Stevens advised leaning towards a diagnosis of CNO with avoidance of bone biopsy in a patient with multifocal osteomyelitis at the typical sites, a normal CBC, the typical extraosseous manifestations, and normal or only mildly elevated erythrocyte sedimentation rate and C-reactive protein in an otherwise well-appearing child. In contrast, strongly consider a bone biopsy to rule out malignancy or infection if the child has unexplained highly elevated C-reactive protein and erythrocyte sedimentation rate, cytopenia, high fever, excessive pain, lymphadenopathy, hepatosplenomegaly, or suspicious imaging findings.
German rheumatologists have developed a clinical score for diagnosis of CNO. A normal blood cell count gets 13 points; symmetric bone lesions 10; lesions with marginal sclerosis 10; a normal body temperature 9; two or more radiologically proven lesions 7; a C-reactive protein of 1 mg/dL or greater 6; and vertebral, clavicular, or sternal lesions 8. A score of 39 points or more out of a possible 63 had a 97% positive predictive value for CNO in a retrospective study of 224 children with CNO, proven bacterial osteomyelitis, or malignant bone tumors. A score of 28 points or less had a 97% negative predictive value for CNO. An indeterminate score of 29-38 warrants close monitoring.
The scoring system hasn’t been validated, but most pediatric rheumatologists agree that it’s useful, according to Dr. Stevens.
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) is in the process of developing standardized diagnostic and classification criteria and treatment plans for CNO. Dr. Zhao was first author of a CARRA consensus treatment plan for CNO refractory to NSAID monotherapy. The plan for the first 12 months includes three options: methotrexate or sulfasalazine, TNF inhibitors with or without methotrexate, and bisphosphonates.
“The main point of this is you try a medicine and then wait 3 months. If they’re not responding then, switch medicines or add another drug. Monitor every 3 months based upon pain,” she said.
Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.
EXPERT ANALYSIS FROM RWCS 2020
Osteoporosis, fracture risk higher in patients with IBD
MAUI, HAWAII –
In the general population, those who develop osteoporosis are typically women who are thin and postmenopausal, and family history, smoking status, and alcohol use usually play a role, Long said at the Gastroenterology Updates, IBD, Liver Disease Conference.
But in the population with IBD, the risk for osteoporosis is similar in women and men, age plays a large role, and corticosteroid use seems to be a driving factor in the development of the disease, she explained.
A previous study that looked at fractures in patients with IBD showed that the risk “is 40% greater than in the general population,” Long reported. In patients younger than 40 years, the risk for fracture was 37% higher than in the general population, and this rate increased with age.
Preventing fractures
Fractures to the hip and spine are linked to significant morbidity, including hospitalization, major surgery, and even death, Long noted. But they are one of the preventable downstream effects of IBD, and patients need to understand that there’s something they can do about their elevated risk.
Patients should be educated on the importance of weight-bearing exercise and quitting smoking, she said.
“We need to think of preventive measures for anyone on more than 5 mg of prednisone a day for a time period of about 3 months,” she added. “Unfortunately, most of our patients meet this criterion.”
Patients with IBD should undergo dual-energy x-ray absorptiometry (DXA) to calculate bone density and establish the need for calcium and vitamin D supplementation.
“One of the things I’m starting to do in my practice is check vitamin D levels annually on my patients. I do this in the springtime and try to optimize their levels,” Long said.
Higher risk for herpes zoster
The risk for infection is also elevated in patients with IBD, including the risk for herpes zoster, which is already high, affecting one in three people in the general population.
In fact, the risk for herpes zoster in patients with IBD in their 20s is similar to the risk for people in their 50s in the general population. This is “something we need to be addressing in all of our patients,” said Long.
Physicians should emphasize the need for zoster vaccination in patients at least 50 years of age, and potentially younger patients on certain therapies, she added.
But because the Shingrix shingles vaccine (GlaxoSmithKline) is so much more powerful than the previous live vaccine, some have wondered whether it could stimulate an immune response, causing the IBD to flare after vaccination, she said.
However, a recent study of IBD patients followed for 207 days after shingles vaccination showed that only one of the 67 study participants (1.5%) experienced a flare. But fever is fairly common after the shot.
“I counsel my patients that they may feel pretty wiped out for 24 hours; they may have myalgias,” Long reported. “If you have someone who has to travel for work, you want them to time this vaccination so they can have a day of rest afterward. It’s the real deal.”
Screening for TB
Screening to rule out latent tuberculosis (TB) is also important in IBD.
“We should be looking at whether they’ve had close contact with active TB or people from endemic areas,” said Long. “The reason we really care about this is that the risk of serious infection is doubled with anti-TNF therapy.”
The treatment of latent TB prior to the initiation of an anti-TNF “reduces the incidence of active TB by over 80%. This is why it’s imperative to screen prior to initiation, and then periodically based on risk factors,” she explained.
“It’s profound how much maintenance is required for patients with IBD,” said Christopher Stanke, MD, from the Oregon Medical Group in Eugene.
He said he is particularly struck by the collective risks for younger patients with IBD.
“Young people look to us as their only doctor. They don’t even see their primary care physicians very often. We have to take over a lot of this stuff,” he told Medscape Medical News.
And osteoporosis doesn’t often get the attention it needs in gastroenterologists’ offices, he acknowledged.
“I often check it on people as they get close to 50 or 60,” said Stanke, who added that Long’s presentation is a good reminder that younger patients, especially those who have been on steroids for a while, need more attention.
This article first appeared on Medscape.com.
MAUI, HAWAII –
In the general population, those who develop osteoporosis are typically women who are thin and postmenopausal, and family history, smoking status, and alcohol use usually play a role, Long said at the Gastroenterology Updates, IBD, Liver Disease Conference.
But in the population with IBD, the risk for osteoporosis is similar in women and men, age plays a large role, and corticosteroid use seems to be a driving factor in the development of the disease, she explained.
A previous study that looked at fractures in patients with IBD showed that the risk “is 40% greater than in the general population,” Long reported. In patients younger than 40 years, the risk for fracture was 37% higher than in the general population, and this rate increased with age.
Preventing fractures
Fractures to the hip and spine are linked to significant morbidity, including hospitalization, major surgery, and even death, Long noted. But they are one of the preventable downstream effects of IBD, and patients need to understand that there’s something they can do about their elevated risk.
Patients should be educated on the importance of weight-bearing exercise and quitting smoking, she said.
“We need to think of preventive measures for anyone on more than 5 mg of prednisone a day for a time period of about 3 months,” she added. “Unfortunately, most of our patients meet this criterion.”
Patients with IBD should undergo dual-energy x-ray absorptiometry (DXA) to calculate bone density and establish the need for calcium and vitamin D supplementation.
“One of the things I’m starting to do in my practice is check vitamin D levels annually on my patients. I do this in the springtime and try to optimize their levels,” Long said.
Higher risk for herpes zoster
The risk for infection is also elevated in patients with IBD, including the risk for herpes zoster, which is already high, affecting one in three people in the general population.
In fact, the risk for herpes zoster in patients with IBD in their 20s is similar to the risk for people in their 50s in the general population. This is “something we need to be addressing in all of our patients,” said Long.
Physicians should emphasize the need for zoster vaccination in patients at least 50 years of age, and potentially younger patients on certain therapies, she added.
But because the Shingrix shingles vaccine (GlaxoSmithKline) is so much more powerful than the previous live vaccine, some have wondered whether it could stimulate an immune response, causing the IBD to flare after vaccination, she said.
However, a recent study of IBD patients followed for 207 days after shingles vaccination showed that only one of the 67 study participants (1.5%) experienced a flare. But fever is fairly common after the shot.
“I counsel my patients that they may feel pretty wiped out for 24 hours; they may have myalgias,” Long reported. “If you have someone who has to travel for work, you want them to time this vaccination so they can have a day of rest afterward. It’s the real deal.”
Screening for TB
Screening to rule out latent tuberculosis (TB) is also important in IBD.
“We should be looking at whether they’ve had close contact with active TB or people from endemic areas,” said Long. “The reason we really care about this is that the risk of serious infection is doubled with anti-TNF therapy.”
The treatment of latent TB prior to the initiation of an anti-TNF “reduces the incidence of active TB by over 80%. This is why it’s imperative to screen prior to initiation, and then periodically based on risk factors,” she explained.
“It’s profound how much maintenance is required for patients with IBD,” said Christopher Stanke, MD, from the Oregon Medical Group in Eugene.
He said he is particularly struck by the collective risks for younger patients with IBD.
“Young people look to us as their only doctor. They don’t even see their primary care physicians very often. We have to take over a lot of this stuff,” he told Medscape Medical News.
And osteoporosis doesn’t often get the attention it needs in gastroenterologists’ offices, he acknowledged.
“I often check it on people as they get close to 50 or 60,” said Stanke, who added that Long’s presentation is a good reminder that younger patients, especially those who have been on steroids for a while, need more attention.
This article first appeared on Medscape.com.
MAUI, HAWAII –
In the general population, those who develop osteoporosis are typically women who are thin and postmenopausal, and family history, smoking status, and alcohol use usually play a role, Long said at the Gastroenterology Updates, IBD, Liver Disease Conference.
But in the population with IBD, the risk for osteoporosis is similar in women and men, age plays a large role, and corticosteroid use seems to be a driving factor in the development of the disease, she explained.
A previous study that looked at fractures in patients with IBD showed that the risk “is 40% greater than in the general population,” Long reported. In patients younger than 40 years, the risk for fracture was 37% higher than in the general population, and this rate increased with age.
Preventing fractures
Fractures to the hip and spine are linked to significant morbidity, including hospitalization, major surgery, and even death, Long noted. But they are one of the preventable downstream effects of IBD, and patients need to understand that there’s something they can do about their elevated risk.
Patients should be educated on the importance of weight-bearing exercise and quitting smoking, she said.
“We need to think of preventive measures for anyone on more than 5 mg of prednisone a day for a time period of about 3 months,” she added. “Unfortunately, most of our patients meet this criterion.”
Patients with IBD should undergo dual-energy x-ray absorptiometry (DXA) to calculate bone density and establish the need for calcium and vitamin D supplementation.
“One of the things I’m starting to do in my practice is check vitamin D levels annually on my patients. I do this in the springtime and try to optimize their levels,” Long said.
Higher risk for herpes zoster
The risk for infection is also elevated in patients with IBD, including the risk for herpes zoster, which is already high, affecting one in three people in the general population.
In fact, the risk for herpes zoster in patients with IBD in their 20s is similar to the risk for people in their 50s in the general population. This is “something we need to be addressing in all of our patients,” said Long.
Physicians should emphasize the need for zoster vaccination in patients at least 50 years of age, and potentially younger patients on certain therapies, she added.
But because the Shingrix shingles vaccine (GlaxoSmithKline) is so much more powerful than the previous live vaccine, some have wondered whether it could stimulate an immune response, causing the IBD to flare after vaccination, she said.
However, a recent study of IBD patients followed for 207 days after shingles vaccination showed that only one of the 67 study participants (1.5%) experienced a flare. But fever is fairly common after the shot.
“I counsel my patients that they may feel pretty wiped out for 24 hours; they may have myalgias,” Long reported. “If you have someone who has to travel for work, you want them to time this vaccination so they can have a day of rest afterward. It’s the real deal.”
Screening for TB
Screening to rule out latent tuberculosis (TB) is also important in IBD.
“We should be looking at whether they’ve had close contact with active TB or people from endemic areas,” said Long. “The reason we really care about this is that the risk of serious infection is doubled with anti-TNF therapy.”
The treatment of latent TB prior to the initiation of an anti-TNF “reduces the incidence of active TB by over 80%. This is why it’s imperative to screen prior to initiation, and then periodically based on risk factors,” she explained.
“It’s profound how much maintenance is required for patients with IBD,” said Christopher Stanke, MD, from the Oregon Medical Group in Eugene.
He said he is particularly struck by the collective risks for younger patients with IBD.
“Young people look to us as their only doctor. They don’t even see their primary care physicians very often. We have to take over a lot of this stuff,” he told Medscape Medical News.
And osteoporosis doesn’t often get the attention it needs in gastroenterologists’ offices, he acknowledged.
“I often check it on people as they get close to 50 or 60,” said Stanke, who added that Long’s presentation is a good reminder that younger patients, especially those who have been on steroids for a while, need more attention.
This article first appeared on Medscape.com.
REPORTING FROM GUILD 2020
Get familiar with evidence on these supplements
NEW ORLEANS – With more than 10% of children receiving complementary or alternative medicine (CAM), you should be familiar with what does and doesn’t work when it comes to using supplements for various medical issues, said Cora Breuner, MD, a professor of pediatrics at the University of Washington, Seattle, and attending physician at Seattle Children’s Hospital.
Dr. Breuner presented an overview of more than a dozen popular supplements with their uses and evidence at the American Academy of Pediatrics annual meeting. Most of the evidence comes from studies in adults, not children, and the evidence overall is sometimes scant, but it can guide physicians in discussing options with parents interested in CAM.
Butterbur
This root primarily is used to treat migraines via anti-inflammatory effects. The ideal dose is 50-75 mg daily in 2-3 divided doses for children aged 8-9 years and 100-150 mg daily in 2-3 divided doses for those aged 10 and older (Headache. 2005 Mar;45:196-203; Eur J Pain. 2008;12:301-13; Neurology. 2012 Apr 24;78[17]:1346-53).
Adverse effects are mostly gastrointestinal, such as diarrhea and stomach upset, and dermal/allergic reactions, such as itchy eyes, asthma, and itching.
Caffeine
Caffeine is the most popular drug of choice for reducing drowsiness and increasing alertness and has the strongest evidence base, including for improving sports and work performance (J Strength Cond Res. 2010 Jan;24[1]:257-65). Regular caffeine use can lead to dependence, however, and it can cause anxiety, nervousness, irritability, insomnia, peptic ulcers, palpitations, gastroesophageal reflux disease (GERD), and tremors. Withdrawal can involve headaches, irritability, and anxiety.
Cannabidiol
Marijuana has more than 80 cannabinoids, and a nonpsychoactive one, cannabidiol, makes up about 40% of cannabis extracts, Dr. Breuner said. It’s been used as an anticonvulsant and to combat anxiety, psychosis, nausea and rheumatoid arthritis pain. In a study using a rat model for arthritis, inflammation and pain-related behaviors decreased in rats that received cannabidiol (Eur J Pain. 2016 Jul;20[6]:936-48).
A human dose would be about 160-300 mg daily, but side effects can include dry mouth, hypotension, lightheadedness, psychomotor slowing, sedation, and sleepiness.
Coenzyme Q10
This antioxidant is fat-soluble and has a chemical structure similar to vitamin K. It has been used in people with autism, chronic fatigue syndrome, fatigue from chemotherapy, Lyme disease, and muscular dystrophy, but the evidence focuses on fibromyalgia. One study of patients with fibromyalgia found that a 300-mg daily dose for 40 days reduced pain by 52%-56%, fatigue by 47%, morning tiredness by 56%, and tender points by 44%, compared with baseline (Antioxid Redox Signal. 2013;19[12]:1356-61.)
In another, 200 mg of coenzyme Q10 with 200 mg ginkgo daily for 3 months resulted in improvement of quality of life measures, including physical fitness levels, emotional feelings, social activities, overall health, and pain (J Int Med Res. 2002;30:195-9).
Potential adverse effects of coenzyme Q10 include nausea, vomiting, diarrhea, appetite suppression, and heartburn, albeit typically in less than 1% of patients.
Echinacea
Echinacea actually is approved in Germany for supportive therapy in treating upper respiratory tract infections, urogenital infections, and wound healing, Dr. Breuner said. Hypothesized mechanisms of action include stimulation of the alternate complement pathway, immune-modulating effects, activating nonspecific T cells, inhibiting viral replication, and enhancing phagocytosis.
However, in clinical studies, echinacea did not reduce the duration or severity of upper respiratory tract infections or the occurrence or severity of infection, compared with placebo (JAMA. 2003 Dec 3;290[21]:2824-30; N Engl J Med. 2005 Jul 28;353[4]:341-8); this was tested in children aged 2-11 years in the first study, and the mean age of the subjects in the second study was 21 years. A 2014 Cochrane review found no overall benefits for treating common colds but noted the possibility of “a weak benefit from some echinacea products” based on individual trials with consistently positive, yet nonsignificant, trends, albeit with “questionable clinical relevance” (Cochrane Database Syst Rev. 2014 Feb 20;[2]:CD000530).
People with autoimmune conditions or who are immunocompromised should not use echinacea.
Magnesium
Magnesium also is used to treat migraines with a dose of 300-500 mg daily, although also it can be consumed in food, such as soy beans, black beans, tofu, seeds, nuts, whole grains, and shellfish (Expert Rev Neurother. 2009 Mar;9[3]:369-79; Neurology. 2012 Apr 24;78[17]:1346-53).
Side effects can include diarrhea and interactions with bisphosphonates, antibiotics] and diuretics. Taking proton pump inhibitors also may reduce magnesium levels.
Melatonin
Melatonin, a synthetic version of the hormone produced in humans to signal the onset of nighttime, has been studied extensively for jet lag, insomnia, shift-work disorder, circadian rhythm disorders, and withdrawal from benzodiazepine and nicotine.
Research shows that melatonin can improve sleep onset, duration, and quality. Some research has shown increased total sleep time (PLoS One. 2013 May 17;8(5):e63773).
Some evidence suggests it has endocrine-disrupting adverse effects, such as inhibiting ovulation and impairing glucose utilization.
N-acetyl cysteine (NAC)
Although it’s primarily an antidote for acetaminophen and carbon monoxide poisoning, NAC has been used for a wide range of conditions, including reducing lipoprotein levels with hyperlipidemia and reducing risk of cardiovascular events in people with end-stage renal disease and other conditions. It also has been used in people with bipolar disorder, schizophrenia, PTSD, substance disorders, and Tourette syndrome.
“Some clinical research shows that taking NAC 900 mg daily for 4 weeks, followed by 900 mg twice daily for 4 weeks and then 900 mg three times daily for 4 weeks improves symptoms of irritability in children with autism,” Dr. Breuner said. Other research showed reduced irritability in children with autism when they took 1,200 mg of NAC daily with risperidone, compared with risperidone alone. One study also has found “that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents” (Iran J Psychiatry. 2017 Apr;12[2]:134-141).
Side effects can include diarrhea, nausea, and heartburn.
Omega-3 fatty acids: DHA and EHA
Docosahexanoic acid (DHA) and eicosapentanoic acid (EHA) have been used to treat ADHD, depression, heart disease, and also to lower the risk of macular degeneration.
A systematic review of 25 randomized controlled trials of more than 3,600 subjects found that “omega-3 supplementation generally correlated with improvements in blood biomarkers” (Nutrients. 2018 Aug 15;10[8]. pii: E1094). A small study in children with Tourette syndrome found that omega-3 fatty acids did not reduce tic scores, but “may be beneficial in reduction of tic-related impairment” for some children and teens (Pediatrics. 2012 Jun;129[6]:e1493-500).
Possible adverse effects include fishy taste, belching, nosebleeds, nausea, loose stools, and – at higher doses – decreased blood coagulation.
St. John’s wort
This herb has long been used to treat depression and appears to work by inhibiting serotonin reuptake, monoamine oxidase (MAO), 5-hydroxytryptamine (5-HT), dopamine, noradrenaline, gamma aminobutyric acid (GABA), and glutamate. A 2005 Cochrane review found St. John’s wort to work better than placebo with similar effectiveness as standard antidepressants for mild to moderate depression, but its benefit for major depression is questionable (Cochrane Database Syst Rev. 2005 Apr 18;[2]:CD000448).
An ideal dose is 300 mg daily, but physicians should be aware of the herb’s potential for certain drug interactions. It may increase metabolism of warfarin, cyclosporin, HIV protease inhibitors, theophylline, digoxin, and oral contraceptives (Expert Opin Drug Metab Toxicol. 2012 Jun;8[6]:691-708). Other potential side effects include decreased platelet aggregation, serotonin syndrome, and photosensitivity.
Turmeric (curcumin)
Turmeric is an anti-inflammatory agent used for a wide range of complaints, but research primarily has focused on its use for pain. No studies exist in children, but a handful of studies have found reduction in joint pain and rheumatoid arthritis symptoms in adults with 500-mg doses twice daily (Phytother Res. 2012 Nov;26[11]:1719-25; J Med Food. 2017 Oct;20[10]:1022-30). One of these studies focused on a specific product, Instaflex, that contained turmeric among multiple other active ingredients (Nutr J. 2013 Nov 25;12[1]:154).
Potential adverse effects of turmeric/curcumin include constipation, dyspepsia, diarrhea, dissension, reflux, nausea, vomiting, itching, and hives.
Zinc
Like echinacea, zinc is commonly used to treat the common cold. A 2013 Cochrane review of randomized, controlled trials found that taking zinc “within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people, but some caution is needed due to the heterogeneity of the data” (Cochrane Database Syst Rev. 2013 Jun 18;[6]:CD001364). The dose is 75 mg a day, and potential adverse effects include bad taste, nausea, and anosmia.
Dr. Breuner said she had no relevant financial disclosures.
NEW ORLEANS – With more than 10% of children receiving complementary or alternative medicine (CAM), you should be familiar with what does and doesn’t work when it comes to using supplements for various medical issues, said Cora Breuner, MD, a professor of pediatrics at the University of Washington, Seattle, and attending physician at Seattle Children’s Hospital.
Dr. Breuner presented an overview of more than a dozen popular supplements with their uses and evidence at the American Academy of Pediatrics annual meeting. Most of the evidence comes from studies in adults, not children, and the evidence overall is sometimes scant, but it can guide physicians in discussing options with parents interested in CAM.
Butterbur
This root primarily is used to treat migraines via anti-inflammatory effects. The ideal dose is 50-75 mg daily in 2-3 divided doses for children aged 8-9 years and 100-150 mg daily in 2-3 divided doses for those aged 10 and older (Headache. 2005 Mar;45:196-203; Eur J Pain. 2008;12:301-13; Neurology. 2012 Apr 24;78[17]:1346-53).
Adverse effects are mostly gastrointestinal, such as diarrhea and stomach upset, and dermal/allergic reactions, such as itchy eyes, asthma, and itching.
Caffeine
Caffeine is the most popular drug of choice for reducing drowsiness and increasing alertness and has the strongest evidence base, including for improving sports and work performance (J Strength Cond Res. 2010 Jan;24[1]:257-65). Regular caffeine use can lead to dependence, however, and it can cause anxiety, nervousness, irritability, insomnia, peptic ulcers, palpitations, gastroesophageal reflux disease (GERD), and tremors. Withdrawal can involve headaches, irritability, and anxiety.
Cannabidiol
Marijuana has more than 80 cannabinoids, and a nonpsychoactive one, cannabidiol, makes up about 40% of cannabis extracts, Dr. Breuner said. It’s been used as an anticonvulsant and to combat anxiety, psychosis, nausea and rheumatoid arthritis pain. In a study using a rat model for arthritis, inflammation and pain-related behaviors decreased in rats that received cannabidiol (Eur J Pain. 2016 Jul;20[6]:936-48).
A human dose would be about 160-300 mg daily, but side effects can include dry mouth, hypotension, lightheadedness, psychomotor slowing, sedation, and sleepiness.
Coenzyme Q10
This antioxidant is fat-soluble and has a chemical structure similar to vitamin K. It has been used in people with autism, chronic fatigue syndrome, fatigue from chemotherapy, Lyme disease, and muscular dystrophy, but the evidence focuses on fibromyalgia. One study of patients with fibromyalgia found that a 300-mg daily dose for 40 days reduced pain by 52%-56%, fatigue by 47%, morning tiredness by 56%, and tender points by 44%, compared with baseline (Antioxid Redox Signal. 2013;19[12]:1356-61.)
In another, 200 mg of coenzyme Q10 with 200 mg ginkgo daily for 3 months resulted in improvement of quality of life measures, including physical fitness levels, emotional feelings, social activities, overall health, and pain (J Int Med Res. 2002;30:195-9).
Potential adverse effects of coenzyme Q10 include nausea, vomiting, diarrhea, appetite suppression, and heartburn, albeit typically in less than 1% of patients.
Echinacea
Echinacea actually is approved in Germany for supportive therapy in treating upper respiratory tract infections, urogenital infections, and wound healing, Dr. Breuner said. Hypothesized mechanisms of action include stimulation of the alternate complement pathway, immune-modulating effects, activating nonspecific T cells, inhibiting viral replication, and enhancing phagocytosis.
However, in clinical studies, echinacea did not reduce the duration or severity of upper respiratory tract infections or the occurrence or severity of infection, compared with placebo (JAMA. 2003 Dec 3;290[21]:2824-30; N Engl J Med. 2005 Jul 28;353[4]:341-8); this was tested in children aged 2-11 years in the first study, and the mean age of the subjects in the second study was 21 years. A 2014 Cochrane review found no overall benefits for treating common colds but noted the possibility of “a weak benefit from some echinacea products” based on individual trials with consistently positive, yet nonsignificant, trends, albeit with “questionable clinical relevance” (Cochrane Database Syst Rev. 2014 Feb 20;[2]:CD000530).
People with autoimmune conditions or who are immunocompromised should not use echinacea.
Magnesium
Magnesium also is used to treat migraines with a dose of 300-500 mg daily, although also it can be consumed in food, such as soy beans, black beans, tofu, seeds, nuts, whole grains, and shellfish (Expert Rev Neurother. 2009 Mar;9[3]:369-79; Neurology. 2012 Apr 24;78[17]:1346-53).
Side effects can include diarrhea and interactions with bisphosphonates, antibiotics] and diuretics. Taking proton pump inhibitors also may reduce magnesium levels.
Melatonin
Melatonin, a synthetic version of the hormone produced in humans to signal the onset of nighttime, has been studied extensively for jet lag, insomnia, shift-work disorder, circadian rhythm disorders, and withdrawal from benzodiazepine and nicotine.
Research shows that melatonin can improve sleep onset, duration, and quality. Some research has shown increased total sleep time (PLoS One. 2013 May 17;8(5):e63773).
Some evidence suggests it has endocrine-disrupting adverse effects, such as inhibiting ovulation and impairing glucose utilization.
N-acetyl cysteine (NAC)
Although it’s primarily an antidote for acetaminophen and carbon monoxide poisoning, NAC has been used for a wide range of conditions, including reducing lipoprotein levels with hyperlipidemia and reducing risk of cardiovascular events in people with end-stage renal disease and other conditions. It also has been used in people with bipolar disorder, schizophrenia, PTSD, substance disorders, and Tourette syndrome.
“Some clinical research shows that taking NAC 900 mg daily for 4 weeks, followed by 900 mg twice daily for 4 weeks and then 900 mg three times daily for 4 weeks improves symptoms of irritability in children with autism,” Dr. Breuner said. Other research showed reduced irritability in children with autism when they took 1,200 mg of NAC daily with risperidone, compared with risperidone alone. One study also has found “that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents” (Iran J Psychiatry. 2017 Apr;12[2]:134-141).
Side effects can include diarrhea, nausea, and heartburn.
Omega-3 fatty acids: DHA and EHA
Docosahexanoic acid (DHA) and eicosapentanoic acid (EHA) have been used to treat ADHD, depression, heart disease, and also to lower the risk of macular degeneration.
A systematic review of 25 randomized controlled trials of more than 3,600 subjects found that “omega-3 supplementation generally correlated with improvements in blood biomarkers” (Nutrients. 2018 Aug 15;10[8]. pii: E1094). A small study in children with Tourette syndrome found that omega-3 fatty acids did not reduce tic scores, but “may be beneficial in reduction of tic-related impairment” for some children and teens (Pediatrics. 2012 Jun;129[6]:e1493-500).
Possible adverse effects include fishy taste, belching, nosebleeds, nausea, loose stools, and – at higher doses – decreased blood coagulation.
St. John’s wort
This herb has long been used to treat depression and appears to work by inhibiting serotonin reuptake, monoamine oxidase (MAO), 5-hydroxytryptamine (5-HT), dopamine, noradrenaline, gamma aminobutyric acid (GABA), and glutamate. A 2005 Cochrane review found St. John’s wort to work better than placebo with similar effectiveness as standard antidepressants for mild to moderate depression, but its benefit for major depression is questionable (Cochrane Database Syst Rev. 2005 Apr 18;[2]:CD000448).
An ideal dose is 300 mg daily, but physicians should be aware of the herb’s potential for certain drug interactions. It may increase metabolism of warfarin, cyclosporin, HIV protease inhibitors, theophylline, digoxin, and oral contraceptives (Expert Opin Drug Metab Toxicol. 2012 Jun;8[6]:691-708). Other potential side effects include decreased platelet aggregation, serotonin syndrome, and photosensitivity.
Turmeric (curcumin)
Turmeric is an anti-inflammatory agent used for a wide range of complaints, but research primarily has focused on its use for pain. No studies exist in children, but a handful of studies have found reduction in joint pain and rheumatoid arthritis symptoms in adults with 500-mg doses twice daily (Phytother Res. 2012 Nov;26[11]:1719-25; J Med Food. 2017 Oct;20[10]:1022-30). One of these studies focused on a specific product, Instaflex, that contained turmeric among multiple other active ingredients (Nutr J. 2013 Nov 25;12[1]:154).
Potential adverse effects of turmeric/curcumin include constipation, dyspepsia, diarrhea, dissension, reflux, nausea, vomiting, itching, and hives.
Zinc
Like echinacea, zinc is commonly used to treat the common cold. A 2013 Cochrane review of randomized, controlled trials found that taking zinc “within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people, but some caution is needed due to the heterogeneity of the data” (Cochrane Database Syst Rev. 2013 Jun 18;[6]:CD001364). The dose is 75 mg a day, and potential adverse effects include bad taste, nausea, and anosmia.
Dr. Breuner said she had no relevant financial disclosures.
NEW ORLEANS – With more than 10% of children receiving complementary or alternative medicine (CAM), you should be familiar with what does and doesn’t work when it comes to using supplements for various medical issues, said Cora Breuner, MD, a professor of pediatrics at the University of Washington, Seattle, and attending physician at Seattle Children’s Hospital.
Dr. Breuner presented an overview of more than a dozen popular supplements with their uses and evidence at the American Academy of Pediatrics annual meeting. Most of the evidence comes from studies in adults, not children, and the evidence overall is sometimes scant, but it can guide physicians in discussing options with parents interested in CAM.
Butterbur
This root primarily is used to treat migraines via anti-inflammatory effects. The ideal dose is 50-75 mg daily in 2-3 divided doses for children aged 8-9 years and 100-150 mg daily in 2-3 divided doses for those aged 10 and older (Headache. 2005 Mar;45:196-203; Eur J Pain. 2008;12:301-13; Neurology. 2012 Apr 24;78[17]:1346-53).
Adverse effects are mostly gastrointestinal, such as diarrhea and stomach upset, and dermal/allergic reactions, such as itchy eyes, asthma, and itching.
Caffeine
Caffeine is the most popular drug of choice for reducing drowsiness and increasing alertness and has the strongest evidence base, including for improving sports and work performance (J Strength Cond Res. 2010 Jan;24[1]:257-65). Regular caffeine use can lead to dependence, however, and it can cause anxiety, nervousness, irritability, insomnia, peptic ulcers, palpitations, gastroesophageal reflux disease (GERD), and tremors. Withdrawal can involve headaches, irritability, and anxiety.
Cannabidiol
Marijuana has more than 80 cannabinoids, and a nonpsychoactive one, cannabidiol, makes up about 40% of cannabis extracts, Dr. Breuner said. It’s been used as an anticonvulsant and to combat anxiety, psychosis, nausea and rheumatoid arthritis pain. In a study using a rat model for arthritis, inflammation and pain-related behaviors decreased in rats that received cannabidiol (Eur J Pain. 2016 Jul;20[6]:936-48).
A human dose would be about 160-300 mg daily, but side effects can include dry mouth, hypotension, lightheadedness, psychomotor slowing, sedation, and sleepiness.
Coenzyme Q10
This antioxidant is fat-soluble and has a chemical structure similar to vitamin K. It has been used in people with autism, chronic fatigue syndrome, fatigue from chemotherapy, Lyme disease, and muscular dystrophy, but the evidence focuses on fibromyalgia. One study of patients with fibromyalgia found that a 300-mg daily dose for 40 days reduced pain by 52%-56%, fatigue by 47%, morning tiredness by 56%, and tender points by 44%, compared with baseline (Antioxid Redox Signal. 2013;19[12]:1356-61.)
In another, 200 mg of coenzyme Q10 with 200 mg ginkgo daily for 3 months resulted in improvement of quality of life measures, including physical fitness levels, emotional feelings, social activities, overall health, and pain (J Int Med Res. 2002;30:195-9).
Potential adverse effects of coenzyme Q10 include nausea, vomiting, diarrhea, appetite suppression, and heartburn, albeit typically in less than 1% of patients.
Echinacea
Echinacea actually is approved in Germany for supportive therapy in treating upper respiratory tract infections, urogenital infections, and wound healing, Dr. Breuner said. Hypothesized mechanisms of action include stimulation of the alternate complement pathway, immune-modulating effects, activating nonspecific T cells, inhibiting viral replication, and enhancing phagocytosis.
However, in clinical studies, echinacea did not reduce the duration or severity of upper respiratory tract infections or the occurrence or severity of infection, compared with placebo (JAMA. 2003 Dec 3;290[21]:2824-30; N Engl J Med. 2005 Jul 28;353[4]:341-8); this was tested in children aged 2-11 years in the first study, and the mean age of the subjects in the second study was 21 years. A 2014 Cochrane review found no overall benefits for treating common colds but noted the possibility of “a weak benefit from some echinacea products” based on individual trials with consistently positive, yet nonsignificant, trends, albeit with “questionable clinical relevance” (Cochrane Database Syst Rev. 2014 Feb 20;[2]:CD000530).
People with autoimmune conditions or who are immunocompromised should not use echinacea.
Magnesium
Magnesium also is used to treat migraines with a dose of 300-500 mg daily, although also it can be consumed in food, such as soy beans, black beans, tofu, seeds, nuts, whole grains, and shellfish (Expert Rev Neurother. 2009 Mar;9[3]:369-79; Neurology. 2012 Apr 24;78[17]:1346-53).
Side effects can include diarrhea and interactions with bisphosphonates, antibiotics] and diuretics. Taking proton pump inhibitors also may reduce magnesium levels.
Melatonin
Melatonin, a synthetic version of the hormone produced in humans to signal the onset of nighttime, has been studied extensively for jet lag, insomnia, shift-work disorder, circadian rhythm disorders, and withdrawal from benzodiazepine and nicotine.
Research shows that melatonin can improve sleep onset, duration, and quality. Some research has shown increased total sleep time (PLoS One. 2013 May 17;8(5):e63773).
Some evidence suggests it has endocrine-disrupting adverse effects, such as inhibiting ovulation and impairing glucose utilization.
N-acetyl cysteine (NAC)
Although it’s primarily an antidote for acetaminophen and carbon monoxide poisoning, NAC has been used for a wide range of conditions, including reducing lipoprotein levels with hyperlipidemia and reducing risk of cardiovascular events in people with end-stage renal disease and other conditions. It also has been used in people with bipolar disorder, schizophrenia, PTSD, substance disorders, and Tourette syndrome.
“Some clinical research shows that taking NAC 900 mg daily for 4 weeks, followed by 900 mg twice daily for 4 weeks and then 900 mg three times daily for 4 weeks improves symptoms of irritability in children with autism,” Dr. Breuner said. Other research showed reduced irritability in children with autism when they took 1,200 mg of NAC daily with risperidone, compared with risperidone alone. One study also has found “that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents” (Iran J Psychiatry. 2017 Apr;12[2]:134-141).
Side effects can include diarrhea, nausea, and heartburn.
Omega-3 fatty acids: DHA and EHA
Docosahexanoic acid (DHA) and eicosapentanoic acid (EHA) have been used to treat ADHD, depression, heart disease, and also to lower the risk of macular degeneration.
A systematic review of 25 randomized controlled trials of more than 3,600 subjects found that “omega-3 supplementation generally correlated with improvements in blood biomarkers” (Nutrients. 2018 Aug 15;10[8]. pii: E1094). A small study in children with Tourette syndrome found that omega-3 fatty acids did not reduce tic scores, but “may be beneficial in reduction of tic-related impairment” for some children and teens (Pediatrics. 2012 Jun;129[6]:e1493-500).
Possible adverse effects include fishy taste, belching, nosebleeds, nausea, loose stools, and – at higher doses – decreased blood coagulation.
St. John’s wort
This herb has long been used to treat depression and appears to work by inhibiting serotonin reuptake, monoamine oxidase (MAO), 5-hydroxytryptamine (5-HT), dopamine, noradrenaline, gamma aminobutyric acid (GABA), and glutamate. A 2005 Cochrane review found St. John’s wort to work better than placebo with similar effectiveness as standard antidepressants for mild to moderate depression, but its benefit for major depression is questionable (Cochrane Database Syst Rev. 2005 Apr 18;[2]:CD000448).
An ideal dose is 300 mg daily, but physicians should be aware of the herb’s potential for certain drug interactions. It may increase metabolism of warfarin, cyclosporin, HIV protease inhibitors, theophylline, digoxin, and oral contraceptives (Expert Opin Drug Metab Toxicol. 2012 Jun;8[6]:691-708). Other potential side effects include decreased platelet aggregation, serotonin syndrome, and photosensitivity.
Turmeric (curcumin)
Turmeric is an anti-inflammatory agent used for a wide range of complaints, but research primarily has focused on its use for pain. No studies exist in children, but a handful of studies have found reduction in joint pain and rheumatoid arthritis symptoms in adults with 500-mg doses twice daily (Phytother Res. 2012 Nov;26[11]:1719-25; J Med Food. 2017 Oct;20[10]:1022-30). One of these studies focused on a specific product, Instaflex, that contained turmeric among multiple other active ingredients (Nutr J. 2013 Nov 25;12[1]:154).
Potential adverse effects of turmeric/curcumin include constipation, dyspepsia, diarrhea, dissension, reflux, nausea, vomiting, itching, and hives.
Zinc
Like echinacea, zinc is commonly used to treat the common cold. A 2013 Cochrane review of randomized, controlled trials found that taking zinc “within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people, but some caution is needed due to the heterogeneity of the data” (Cochrane Database Syst Rev. 2013 Jun 18;[6]:CD001364). The dose is 75 mg a day, and potential adverse effects include bad taste, nausea, and anosmia.
Dr. Breuner said she had no relevant financial disclosures.
EXPERT ANALYSIS FROM AAP 19
Sarcopenia associated with increased cardiometabolic risk
LOS ANGELES –
“Loss of lean body mass and function with aging decreases the amount of metabolically active tissue, which can lead to insulin resistance,” Elena Volpi, MD, said at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease. “Insulin resistance reduces muscle protein anabolism and accelerates sarcopenia, perpetuating a vicious cycle.”
Sarcopenia, the involuntary loss of muscle mass and function that occurs with aging, is an ICD-10 codable condition that can be diagnosed by measuring muscle strength and quality, said Dr. Volpi, director of the Sealy Center on Aging at the University of Texas Medical Branch at Galveston. In the Health, Aging and Body Composition Study (Health ABC), researchers followed 2,292 relatively healthy adults aged 70-79 years for an average of 4.9 years (J Gerontol A Biol Sci Med. 2006;61[1]:72-7). The researchers used isokinetic dynamometry to measure knee extension strength, isometric dynamometry to measure grip strength, CT scan to measure thigh muscle area, and dual X-ray absorptiometry to determine leg and arm lean soft-tissue mass. “Those individuals who started with the highest levels of muscle strength had the greatest survival, while those who had the lowest levels of muscle strength died earlier,” said Dr. Volpi, who was not affiliated with the study. “That was true for both men and women.”
More recently, researchers conducted a pooled analysis of nine cohort studies involving 34,485 community-dwelling older individuals who were tested with gait speed and followed for 6-21 years (JAMA. 2011;305[1]:50-8). They found that a higher gait speed was associated with higher survival at 5 and 10 years (P less than .001). “Muscle mass also appears to be associated in part with mortality and survival, although the association is not as strong as measures of strength and gait speed,” Dr. Volpi said.
Data from the 2009 Korea National Health and Nutrition Examination Survey of 1,537 participants, aged 65 years and older, found that sarcopenia is independently associated with cardiovascular disease (PLoS One. 2013 Mar 22. doi: 10.1371/journal.pone.0060119). Most of the risk factors for cardiovascular disease – such as age, waist circumference, body mass index, fasting plasma glucose, and total cholesterol – showed significant negative correlations with the ratio between appendicular skeletal muscle mass and body weight. Multiple logistic regression analysis demonstrated that sarcopenia was associated with cardiovascular disease, independent of other well-documented risk factors, renal function, and medications (odds ratio, 1.77; P = .025).
In addition, data from the British Regional Heart Study, which followed 4,252 older men for a mean of 11.3 years, found an association of sarcopenia and adiposity with cardiovascular mortality and all-cause mortality (J Am Geriatr Soc. 2014;62[2]:253-60). Specifically, all-cause mortality risk was significantly greater in men in the sarcopenic and obese groups (HRs, 1.41 and 1.21, respectively), compared with those in the optimal reference group, with the highest risk in sarcopenic obese individuals (HR, 1.72) after adjustment for lifestyle characteristics.
“Diabetes also accelerates loss of lean body mass in older adults,” added Dr. Volpi. “Data from the Health ABC study showed that individuals who did not have diabetes at the beginning of the 6-year observation period ... lost the least amount of muscle, compared with those who had undiagnosed or already diagnosed diabetes.”
The precise way in which sarcopenia is linked to metabolic disease remains elusive, she continued, but current evidence suggests that sarcopenia is characterized by a reduction in the protein synthetic response to metabolic stimulation by amino acids, exercise, and insulin in skeletal muscle. “This reduction in the anabolic response to protein synthesis is called anabolic resistance of aging, and it is mediated by reduced acute activation of mTORC1 [mTOR complex 1] signaling,” Dr. Volpi said. “There’s another step upstream of the mTORC1, in which the amino acids and insulin have to cross the blood-muscle barrier. Amino acids need to be transported into the muscle actively, like glucose. That is an important unexplored area that may contribute to sarcopenia.”
Dr. Volpi went on to note that endothelial dysfunction underlies muscle anabolic resistance and cardiovascular risk and is likely to be a fundamental cause of both problems. Recent studies have shown that increased levels of physical activity improve endothelial function, enhance insulin sensitivity and anabolic sensitivity to nutrients, and reduce cardiovascular risk.
For example, in a cohort of 45 nonfrail older adults with a mean age of 72 years, Dr. Volpi and colleagues carried out a phase 1, double-blind, placebo-controlled, randomized clinical trial to determine if chronic essential amino acid supplementation, aerobic exercise training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis over the course of 24 weeks (J Gerontol A Biol Sci Med Sci. 2019;74[10]:1598-604). “We found that exercise supervised three times per week on a treadmill for 6 months improved physical function in both groups randomized to exercise,” Dr. Volpi said. “Disappointingly, there was no change in total lean mass with any of the interventions. There was a decrease in fat mass with exercise alone, and no change with exercise and amino acids. [Of note is that] the individuals who were randomized to the amino acids plus exercise group had a significant increase in leg strength, whereas the others did not.”
Preliminary findings from ongoing work by Dr. Volpi and colleagues suggest that, in diabetes, muscle protein synthesis and blood flow really “are not different in response to insulin in healthy older adults and diabetic older adults because they don’t change at all. However, we did find alterations in amino acid trafficking in diabetes. We found that older individuals with type 2 diabetes had a reduction of amino acid transport and a higher intracellular amino acid concentration, compared with age-matched, healthier individuals. The intracellular amino acid clearance improved in the healthy, nondiabetic older adults with hyperinsulinemia, whereas it did not change in diabetic older adults. As a result, the net muscle protein balance improved a little in the nondiabetic patients, but did not change in the diabetic patients.”
The researchers are evaluating older patients with type 2 diabetes to see whether there are alterations in vascular reactivity and protein synthesis and whether those can be overcome by resistance-exercise training. “Preliminary results show that flow-mediated dilation can actually increase in an older diabetic patient with resistance exercise training three times a week for 3 months,” she said. “Exercise can improve both endothelial dysfunction and sarcopenia and therefore improve physical function and reduce cardiovascular risk.”
Dr. Volpi reported having no relevant disclosures.
LOS ANGELES –
“Loss of lean body mass and function with aging decreases the amount of metabolically active tissue, which can lead to insulin resistance,” Elena Volpi, MD, said at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease. “Insulin resistance reduces muscle protein anabolism and accelerates sarcopenia, perpetuating a vicious cycle.”
Sarcopenia, the involuntary loss of muscle mass and function that occurs with aging, is an ICD-10 codable condition that can be diagnosed by measuring muscle strength and quality, said Dr. Volpi, director of the Sealy Center on Aging at the University of Texas Medical Branch at Galveston. In the Health, Aging and Body Composition Study (Health ABC), researchers followed 2,292 relatively healthy adults aged 70-79 years for an average of 4.9 years (J Gerontol A Biol Sci Med. 2006;61[1]:72-7). The researchers used isokinetic dynamometry to measure knee extension strength, isometric dynamometry to measure grip strength, CT scan to measure thigh muscle area, and dual X-ray absorptiometry to determine leg and arm lean soft-tissue mass. “Those individuals who started with the highest levels of muscle strength had the greatest survival, while those who had the lowest levels of muscle strength died earlier,” said Dr. Volpi, who was not affiliated with the study. “That was true for both men and women.”
More recently, researchers conducted a pooled analysis of nine cohort studies involving 34,485 community-dwelling older individuals who were tested with gait speed and followed for 6-21 years (JAMA. 2011;305[1]:50-8). They found that a higher gait speed was associated with higher survival at 5 and 10 years (P less than .001). “Muscle mass also appears to be associated in part with mortality and survival, although the association is not as strong as measures of strength and gait speed,” Dr. Volpi said.
Data from the 2009 Korea National Health and Nutrition Examination Survey of 1,537 participants, aged 65 years and older, found that sarcopenia is independently associated with cardiovascular disease (PLoS One. 2013 Mar 22. doi: 10.1371/journal.pone.0060119). Most of the risk factors for cardiovascular disease – such as age, waist circumference, body mass index, fasting plasma glucose, and total cholesterol – showed significant negative correlations with the ratio between appendicular skeletal muscle mass and body weight. Multiple logistic regression analysis demonstrated that sarcopenia was associated with cardiovascular disease, independent of other well-documented risk factors, renal function, and medications (odds ratio, 1.77; P = .025).
In addition, data from the British Regional Heart Study, which followed 4,252 older men for a mean of 11.3 years, found an association of sarcopenia and adiposity with cardiovascular mortality and all-cause mortality (J Am Geriatr Soc. 2014;62[2]:253-60). Specifically, all-cause mortality risk was significantly greater in men in the sarcopenic and obese groups (HRs, 1.41 and 1.21, respectively), compared with those in the optimal reference group, with the highest risk in sarcopenic obese individuals (HR, 1.72) after adjustment for lifestyle characteristics.
“Diabetes also accelerates loss of lean body mass in older adults,” added Dr. Volpi. “Data from the Health ABC study showed that individuals who did not have diabetes at the beginning of the 6-year observation period ... lost the least amount of muscle, compared with those who had undiagnosed or already diagnosed diabetes.”
The precise way in which sarcopenia is linked to metabolic disease remains elusive, she continued, but current evidence suggests that sarcopenia is characterized by a reduction in the protein synthetic response to metabolic stimulation by amino acids, exercise, and insulin in skeletal muscle. “This reduction in the anabolic response to protein synthesis is called anabolic resistance of aging, and it is mediated by reduced acute activation of mTORC1 [mTOR complex 1] signaling,” Dr. Volpi said. “There’s another step upstream of the mTORC1, in which the amino acids and insulin have to cross the blood-muscle barrier. Amino acids need to be transported into the muscle actively, like glucose. That is an important unexplored area that may contribute to sarcopenia.”
Dr. Volpi went on to note that endothelial dysfunction underlies muscle anabolic resistance and cardiovascular risk and is likely to be a fundamental cause of both problems. Recent studies have shown that increased levels of physical activity improve endothelial function, enhance insulin sensitivity and anabolic sensitivity to nutrients, and reduce cardiovascular risk.
For example, in a cohort of 45 nonfrail older adults with a mean age of 72 years, Dr. Volpi and colleagues carried out a phase 1, double-blind, placebo-controlled, randomized clinical trial to determine if chronic essential amino acid supplementation, aerobic exercise training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis over the course of 24 weeks (J Gerontol A Biol Sci Med Sci. 2019;74[10]:1598-604). “We found that exercise supervised three times per week on a treadmill for 6 months improved physical function in both groups randomized to exercise,” Dr. Volpi said. “Disappointingly, there was no change in total lean mass with any of the interventions. There was a decrease in fat mass with exercise alone, and no change with exercise and amino acids. [Of note is that] the individuals who were randomized to the amino acids plus exercise group had a significant increase in leg strength, whereas the others did not.”
Preliminary findings from ongoing work by Dr. Volpi and colleagues suggest that, in diabetes, muscle protein synthesis and blood flow really “are not different in response to insulin in healthy older adults and diabetic older adults because they don’t change at all. However, we did find alterations in amino acid trafficking in diabetes. We found that older individuals with type 2 diabetes had a reduction of amino acid transport and a higher intracellular amino acid concentration, compared with age-matched, healthier individuals. The intracellular amino acid clearance improved in the healthy, nondiabetic older adults with hyperinsulinemia, whereas it did not change in diabetic older adults. As a result, the net muscle protein balance improved a little in the nondiabetic patients, but did not change in the diabetic patients.”
The researchers are evaluating older patients with type 2 diabetes to see whether there are alterations in vascular reactivity and protein synthesis and whether those can be overcome by resistance-exercise training. “Preliminary results show that flow-mediated dilation can actually increase in an older diabetic patient with resistance exercise training three times a week for 3 months,” she said. “Exercise can improve both endothelial dysfunction and sarcopenia and therefore improve physical function and reduce cardiovascular risk.”
Dr. Volpi reported having no relevant disclosures.
LOS ANGELES –
“Loss of lean body mass and function with aging decreases the amount of metabolically active tissue, which can lead to insulin resistance,” Elena Volpi, MD, said at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease. “Insulin resistance reduces muscle protein anabolism and accelerates sarcopenia, perpetuating a vicious cycle.”
Sarcopenia, the involuntary loss of muscle mass and function that occurs with aging, is an ICD-10 codable condition that can be diagnosed by measuring muscle strength and quality, said Dr. Volpi, director of the Sealy Center on Aging at the University of Texas Medical Branch at Galveston. In the Health, Aging and Body Composition Study (Health ABC), researchers followed 2,292 relatively healthy adults aged 70-79 years for an average of 4.9 years (J Gerontol A Biol Sci Med. 2006;61[1]:72-7). The researchers used isokinetic dynamometry to measure knee extension strength, isometric dynamometry to measure grip strength, CT scan to measure thigh muscle area, and dual X-ray absorptiometry to determine leg and arm lean soft-tissue mass. “Those individuals who started with the highest levels of muscle strength had the greatest survival, while those who had the lowest levels of muscle strength died earlier,” said Dr. Volpi, who was not affiliated with the study. “That was true for both men and women.”
More recently, researchers conducted a pooled analysis of nine cohort studies involving 34,485 community-dwelling older individuals who were tested with gait speed and followed for 6-21 years (JAMA. 2011;305[1]:50-8). They found that a higher gait speed was associated with higher survival at 5 and 10 years (P less than .001). “Muscle mass also appears to be associated in part with mortality and survival, although the association is not as strong as measures of strength and gait speed,” Dr. Volpi said.
Data from the 2009 Korea National Health and Nutrition Examination Survey of 1,537 participants, aged 65 years and older, found that sarcopenia is independently associated with cardiovascular disease (PLoS One. 2013 Mar 22. doi: 10.1371/journal.pone.0060119). Most of the risk factors for cardiovascular disease – such as age, waist circumference, body mass index, fasting plasma glucose, and total cholesterol – showed significant negative correlations with the ratio between appendicular skeletal muscle mass and body weight. Multiple logistic regression analysis demonstrated that sarcopenia was associated with cardiovascular disease, independent of other well-documented risk factors, renal function, and medications (odds ratio, 1.77; P = .025).
In addition, data from the British Regional Heart Study, which followed 4,252 older men for a mean of 11.3 years, found an association of sarcopenia and adiposity with cardiovascular mortality and all-cause mortality (J Am Geriatr Soc. 2014;62[2]:253-60). Specifically, all-cause mortality risk was significantly greater in men in the sarcopenic and obese groups (HRs, 1.41 and 1.21, respectively), compared with those in the optimal reference group, with the highest risk in sarcopenic obese individuals (HR, 1.72) after adjustment for lifestyle characteristics.
“Diabetes also accelerates loss of lean body mass in older adults,” added Dr. Volpi. “Data from the Health ABC study showed that individuals who did not have diabetes at the beginning of the 6-year observation period ... lost the least amount of muscle, compared with those who had undiagnosed or already diagnosed diabetes.”
The precise way in which sarcopenia is linked to metabolic disease remains elusive, she continued, but current evidence suggests that sarcopenia is characterized by a reduction in the protein synthetic response to metabolic stimulation by amino acids, exercise, and insulin in skeletal muscle. “This reduction in the anabolic response to protein synthesis is called anabolic resistance of aging, and it is mediated by reduced acute activation of mTORC1 [mTOR complex 1] signaling,” Dr. Volpi said. “There’s another step upstream of the mTORC1, in which the amino acids and insulin have to cross the blood-muscle barrier. Amino acids need to be transported into the muscle actively, like glucose. That is an important unexplored area that may contribute to sarcopenia.”
Dr. Volpi went on to note that endothelial dysfunction underlies muscle anabolic resistance and cardiovascular risk and is likely to be a fundamental cause of both problems. Recent studies have shown that increased levels of physical activity improve endothelial function, enhance insulin sensitivity and anabolic sensitivity to nutrients, and reduce cardiovascular risk.
For example, in a cohort of 45 nonfrail older adults with a mean age of 72 years, Dr. Volpi and colleagues carried out a phase 1, double-blind, placebo-controlled, randomized clinical trial to determine if chronic essential amino acid supplementation, aerobic exercise training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis over the course of 24 weeks (J Gerontol A Biol Sci Med Sci. 2019;74[10]:1598-604). “We found that exercise supervised three times per week on a treadmill for 6 months improved physical function in both groups randomized to exercise,” Dr. Volpi said. “Disappointingly, there was no change in total lean mass with any of the interventions. There was a decrease in fat mass with exercise alone, and no change with exercise and amino acids. [Of note is that] the individuals who were randomized to the amino acids plus exercise group had a significant increase in leg strength, whereas the others did not.”
Preliminary findings from ongoing work by Dr. Volpi and colleagues suggest that, in diabetes, muscle protein synthesis and blood flow really “are not different in response to insulin in healthy older adults and diabetic older adults because they don’t change at all. However, we did find alterations in amino acid trafficking in diabetes. We found that older individuals with type 2 diabetes had a reduction of amino acid transport and a higher intracellular amino acid concentration, compared with age-matched, healthier individuals. The intracellular amino acid clearance improved in the healthy, nondiabetic older adults with hyperinsulinemia, whereas it did not change in diabetic older adults. As a result, the net muscle protein balance improved a little in the nondiabetic patients, but did not change in the diabetic patients.”
The researchers are evaluating older patients with type 2 diabetes to see whether there are alterations in vascular reactivity and protein synthesis and whether those can be overcome by resistance-exercise training. “Preliminary results show that flow-mediated dilation can actually increase in an older diabetic patient with resistance exercise training three times a week for 3 months,” she said. “Exercise can improve both endothelial dysfunction and sarcopenia and therefore improve physical function and reduce cardiovascular risk.”
Dr. Volpi reported having no relevant disclosures.
EXPERT ANALYSIS FROM WCIRDC 2019