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Juvenile dermatomyositis derails growth and pubertal development
Children with juvenile dermatomyositis showed significant growth failure and pubertal delay, based on data from a longitudinal cohort study.
“Both the inflammatory activity of this severe chronic rheumatic disease and the well-known side effects of corticosteroid treatment may interfere with normal growth and pubertal development of children,” wrote Ellen Nordal, MD, of the University Hospital of Northern Norway, Tromsø, and colleagues.
The goal in treating juvenile dermatomyositis (JDM) is to achieve inactive disease and prevent permanent damage, but long-term data on growth and puberty in JDM patients are limited, they wrote.
In a study published in Arthritis Care & Research, the investigators reviewed data from 196 children and followed them for 2 years. The patients were part of the Paediatric Rheumatology International Trials Organisation (PRINTO) observational cohort study.
Overall, the researchers identified growth failure, height deflection, and/or delayed puberty in 94 children (48%) at the last study visit.
Growth failure was present at baseline in 17% of girls and 10% of boys. Over the 2-year study period, height deflection increased to 25% of girls and 31% of boys, but this change was not significant. Height deflection was defined as a change in the height z score of less than –0.25 per year from baseline. However, body mass index increased significantly from baseline during the study.
Catch-up growth had occurred by the final study visit in some patients, based on parent-adjusted z scores over time. Girls with a disease duration of 12 months or more showed no catch-up growth at 2 years and had significantly lower parent-adjusted height z scores.
In addition, the researchers observed a delay in the onset of puberty (including pubertal tempo and menarche) in approximately 36% of both boys and girls. However, neither growth failure nor height deflection was significantly associated with delayed puberty in either sex.
“In follow-up, clinicians should therefore be aware of both the pubertal development and the growth of the child, assess the milestones of development, and ensure that the children reach as much as possible of their genetic potential,” the researchers wrote.
The study participants were younger than 18 years at study enrollment, and all were in an active disease phase, defined as needing to start or receive a major dose increase of corticosteroids and/or immunosuppressants. Patients were assessed at baseline, at 6 months and/or at 12 months, and during a final visit at approximately 26 months. During the study, approximately half of the participants (50.5%) received methotrexate, 30 (15.3%) received cyclosporine A, 10 (5.1%) received cyclophosphamide, and 27 (13.8%) received intravenous immunoglobulin.
The study findings were limited by several factors, including the short follow-up period for assessing pubertal development and the inability to analyze any impact of corticosteroid use prior to the study, the researchers noted. However, “the overall frequency of growth failure was not significantly higher at the final study visit 2 years after baseline, indicating that the very high doses of corticosteroid treatment given during the study period is reasonably well tolerated with regards to growth,” they wrote. But monitoring remains essential, especially for children with previous growth failure or with disease onset early in pubertal development.
The study was supported by the European Union, Helse Nord Research grants, and by IRCCS Istituto Giannina Gaslini. Five authors of the study reported financial relationships with pharmaceutical companies.
SOURCE: Nordal E et al. Arthritis Care Res. 2019 Sep 10. doi: 10.1002/acr.24065.
Children with juvenile dermatomyositis showed significant growth failure and pubertal delay, based on data from a longitudinal cohort study.
“Both the inflammatory activity of this severe chronic rheumatic disease and the well-known side effects of corticosteroid treatment may interfere with normal growth and pubertal development of children,” wrote Ellen Nordal, MD, of the University Hospital of Northern Norway, Tromsø, and colleagues.
The goal in treating juvenile dermatomyositis (JDM) is to achieve inactive disease and prevent permanent damage, but long-term data on growth and puberty in JDM patients are limited, they wrote.
In a study published in Arthritis Care & Research, the investigators reviewed data from 196 children and followed them for 2 years. The patients were part of the Paediatric Rheumatology International Trials Organisation (PRINTO) observational cohort study.
Overall, the researchers identified growth failure, height deflection, and/or delayed puberty in 94 children (48%) at the last study visit.
Growth failure was present at baseline in 17% of girls and 10% of boys. Over the 2-year study period, height deflection increased to 25% of girls and 31% of boys, but this change was not significant. Height deflection was defined as a change in the height z score of less than –0.25 per year from baseline. However, body mass index increased significantly from baseline during the study.
Catch-up growth had occurred by the final study visit in some patients, based on parent-adjusted z scores over time. Girls with a disease duration of 12 months or more showed no catch-up growth at 2 years and had significantly lower parent-adjusted height z scores.
In addition, the researchers observed a delay in the onset of puberty (including pubertal tempo and menarche) in approximately 36% of both boys and girls. However, neither growth failure nor height deflection was significantly associated with delayed puberty in either sex.
“In follow-up, clinicians should therefore be aware of both the pubertal development and the growth of the child, assess the milestones of development, and ensure that the children reach as much as possible of their genetic potential,” the researchers wrote.
The study participants were younger than 18 years at study enrollment, and all were in an active disease phase, defined as needing to start or receive a major dose increase of corticosteroids and/or immunosuppressants. Patients were assessed at baseline, at 6 months and/or at 12 months, and during a final visit at approximately 26 months. During the study, approximately half of the participants (50.5%) received methotrexate, 30 (15.3%) received cyclosporine A, 10 (5.1%) received cyclophosphamide, and 27 (13.8%) received intravenous immunoglobulin.
The study findings were limited by several factors, including the short follow-up period for assessing pubertal development and the inability to analyze any impact of corticosteroid use prior to the study, the researchers noted. However, “the overall frequency of growth failure was not significantly higher at the final study visit 2 years after baseline, indicating that the very high doses of corticosteroid treatment given during the study period is reasonably well tolerated with regards to growth,” they wrote. But monitoring remains essential, especially for children with previous growth failure or with disease onset early in pubertal development.
The study was supported by the European Union, Helse Nord Research grants, and by IRCCS Istituto Giannina Gaslini. Five authors of the study reported financial relationships with pharmaceutical companies.
SOURCE: Nordal E et al. Arthritis Care Res. 2019 Sep 10. doi: 10.1002/acr.24065.
Children with juvenile dermatomyositis showed significant growth failure and pubertal delay, based on data from a longitudinal cohort study.
“Both the inflammatory activity of this severe chronic rheumatic disease and the well-known side effects of corticosteroid treatment may interfere with normal growth and pubertal development of children,” wrote Ellen Nordal, MD, of the University Hospital of Northern Norway, Tromsø, and colleagues.
The goal in treating juvenile dermatomyositis (JDM) is to achieve inactive disease and prevent permanent damage, but long-term data on growth and puberty in JDM patients are limited, they wrote.
In a study published in Arthritis Care & Research, the investigators reviewed data from 196 children and followed them for 2 years. The patients were part of the Paediatric Rheumatology International Trials Organisation (PRINTO) observational cohort study.
Overall, the researchers identified growth failure, height deflection, and/or delayed puberty in 94 children (48%) at the last study visit.
Growth failure was present at baseline in 17% of girls and 10% of boys. Over the 2-year study period, height deflection increased to 25% of girls and 31% of boys, but this change was not significant. Height deflection was defined as a change in the height z score of less than –0.25 per year from baseline. However, body mass index increased significantly from baseline during the study.
Catch-up growth had occurred by the final study visit in some patients, based on parent-adjusted z scores over time. Girls with a disease duration of 12 months or more showed no catch-up growth at 2 years and had significantly lower parent-adjusted height z scores.
In addition, the researchers observed a delay in the onset of puberty (including pubertal tempo and menarche) in approximately 36% of both boys and girls. However, neither growth failure nor height deflection was significantly associated with delayed puberty in either sex.
“In follow-up, clinicians should therefore be aware of both the pubertal development and the growth of the child, assess the milestones of development, and ensure that the children reach as much as possible of their genetic potential,” the researchers wrote.
The study participants were younger than 18 years at study enrollment, and all were in an active disease phase, defined as needing to start or receive a major dose increase of corticosteroids and/or immunosuppressants. Patients were assessed at baseline, at 6 months and/or at 12 months, and during a final visit at approximately 26 months. During the study, approximately half of the participants (50.5%) received methotrexate, 30 (15.3%) received cyclosporine A, 10 (5.1%) received cyclophosphamide, and 27 (13.8%) received intravenous immunoglobulin.
The study findings were limited by several factors, including the short follow-up period for assessing pubertal development and the inability to analyze any impact of corticosteroid use prior to the study, the researchers noted. However, “the overall frequency of growth failure was not significantly higher at the final study visit 2 years after baseline, indicating that the very high doses of corticosteroid treatment given during the study period is reasonably well tolerated with regards to growth,” they wrote. But monitoring remains essential, especially for children with previous growth failure or with disease onset early in pubertal development.
The study was supported by the European Union, Helse Nord Research grants, and by IRCCS Istituto Giannina Gaslini. Five authors of the study reported financial relationships with pharmaceutical companies.
SOURCE: Nordal E et al. Arthritis Care Res. 2019 Sep 10. doi: 10.1002/acr.24065.
FROM ARTHRITIS CARE & RESEARCH
Benefits of peanut desensitization may not last
based on data from a phase 2 randomized trial of individuals with confirmed peanut allergies.
Previous studies have shown that desensitization to peanuts can be successful, but sustained response to oral immunotherapy after treatment reduction or discontinuation has not been well studied, wrote R. Sharon Chinthrajah, MD, of Stanford (Calif.)University, and colleagues.
“We found that OIT with peanut was able to desensitise people with peanut allergy to 4,000 mg of peanut protein, but that discontinuation of peanut, or even a reduction to 300 mg daily, increased the likelihood of regaining clinical reactivity to peanut,” they wrote. “With peanut allergy therapies in varying stages of clinical development, and some nearing [Food and Drug Administration] approval, vital questions remain regarding the durability of treatment effects and the appropriate maintenance doses.”
In the Peanut Oral Immunotherapy Study: Safety Efficacy and Discovery (POISED), published in The Lancet, the researchers randomized 120 participants to three groups:
• 60 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by total discontinuation (peanut-0).
• 35 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by a 300-mg maintenance dose of peanut protein in the form of peanut flour (peanut-300).
• 25 patients to an oat flour placebo.
All participants were trained on how and when to use epinephrine autoinjector devices to treat allergic symptoms such as respiratory problems (cough, shortness of breath, or change in voice), widespread hives or erythema, repetitive vomiting, persistent abdominal pain, angioedema of the face, or feeling faint.
The primary outcome was passing a double-blind, placebo-controlled, food challenge (DBPCFC) to 4,000 mg of peanut protein, which was measured at baseline and at weeks 104, 117, 130, 143, and 156.
Overall, 35% of the peanut-0 group passed the challenge at 104 and 117 weeks, compared with 4% of the placebo group. At week 156 after discontinuing OIT, 13% of the peanut-0 group met the DBPCFC challenge, compared with 4% of the placebo group. However, 37% of participants randomized to a reduced peanut protein dose of 300 mg passed the challenge at 156 weeks, suggesting that more data are needed on optimal maintenance dosing strategies.
Baseline demographics were similar across all groups. The median age at study enrollment was 11 years and the median allergy duration was 9 years. The most common adverse events were mild gastrointestinal and respiratory problems. Adverse events decreased over time in all three groups.
“Higher levels of peanut-specific IgE to total IgE ratio, peanut sIgE, Ara h 1, Ara h 2, and Ara h 1 IgE to peanut-specific IgE ratio at baseline in participants were associated with increased frequencies of adverse events during active peanut OIT,” the researchers noted.
The study findings were limited by several factors including the ability of participants to tolerate 4,000 mg of peanut protein after achieving a maintenance dose but conducting serial testing only for those who passed the challenge. In addition, the results may be limited to peanut and not generalizable to other food allergies, the researchers said.
However, the results suggest that OIT remains a promising treatment for peanut allergies, and the association of biomarkers with clinical outcomes “might help the practitioner in identifying good candidates for OIT and those individuals who warrant increased vigilance against allergic reactions during OIT,” they said.
The National Institutes of Health supported the study. The researchers had no financial conflicts to disclose.
SOURCE: Chinthrajah RS et al. Lancet. 2019 Sep 12. doi: 10.1016/S0140-6736(19)31793-3.
based on data from a phase 2 randomized trial of individuals with confirmed peanut allergies.
Previous studies have shown that desensitization to peanuts can be successful, but sustained response to oral immunotherapy after treatment reduction or discontinuation has not been well studied, wrote R. Sharon Chinthrajah, MD, of Stanford (Calif.)University, and colleagues.
“We found that OIT with peanut was able to desensitise people with peanut allergy to 4,000 mg of peanut protein, but that discontinuation of peanut, or even a reduction to 300 mg daily, increased the likelihood of regaining clinical reactivity to peanut,” they wrote. “With peanut allergy therapies in varying stages of clinical development, and some nearing [Food and Drug Administration] approval, vital questions remain regarding the durability of treatment effects and the appropriate maintenance doses.”
In the Peanut Oral Immunotherapy Study: Safety Efficacy and Discovery (POISED), published in The Lancet, the researchers randomized 120 participants to three groups:
• 60 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by total discontinuation (peanut-0).
• 35 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by a 300-mg maintenance dose of peanut protein in the form of peanut flour (peanut-300).
• 25 patients to an oat flour placebo.
All participants were trained on how and when to use epinephrine autoinjector devices to treat allergic symptoms such as respiratory problems (cough, shortness of breath, or change in voice), widespread hives or erythema, repetitive vomiting, persistent abdominal pain, angioedema of the face, or feeling faint.
The primary outcome was passing a double-blind, placebo-controlled, food challenge (DBPCFC) to 4,000 mg of peanut protein, which was measured at baseline and at weeks 104, 117, 130, 143, and 156.
Overall, 35% of the peanut-0 group passed the challenge at 104 and 117 weeks, compared with 4% of the placebo group. At week 156 after discontinuing OIT, 13% of the peanut-0 group met the DBPCFC challenge, compared with 4% of the placebo group. However, 37% of participants randomized to a reduced peanut protein dose of 300 mg passed the challenge at 156 weeks, suggesting that more data are needed on optimal maintenance dosing strategies.
Baseline demographics were similar across all groups. The median age at study enrollment was 11 years and the median allergy duration was 9 years. The most common adverse events were mild gastrointestinal and respiratory problems. Adverse events decreased over time in all three groups.
“Higher levels of peanut-specific IgE to total IgE ratio, peanut sIgE, Ara h 1, Ara h 2, and Ara h 1 IgE to peanut-specific IgE ratio at baseline in participants were associated with increased frequencies of adverse events during active peanut OIT,” the researchers noted.
The study findings were limited by several factors including the ability of participants to tolerate 4,000 mg of peanut protein after achieving a maintenance dose but conducting serial testing only for those who passed the challenge. In addition, the results may be limited to peanut and not generalizable to other food allergies, the researchers said.
However, the results suggest that OIT remains a promising treatment for peanut allergies, and the association of biomarkers with clinical outcomes “might help the practitioner in identifying good candidates for OIT and those individuals who warrant increased vigilance against allergic reactions during OIT,” they said.
The National Institutes of Health supported the study. The researchers had no financial conflicts to disclose.
SOURCE: Chinthrajah RS et al. Lancet. 2019 Sep 12. doi: 10.1016/S0140-6736(19)31793-3.
based on data from a phase 2 randomized trial of individuals with confirmed peanut allergies.
Previous studies have shown that desensitization to peanuts can be successful, but sustained response to oral immunotherapy after treatment reduction or discontinuation has not been well studied, wrote R. Sharon Chinthrajah, MD, of Stanford (Calif.)University, and colleagues.
“We found that OIT with peanut was able to desensitise people with peanut allergy to 4,000 mg of peanut protein, but that discontinuation of peanut, or even a reduction to 300 mg daily, increased the likelihood of regaining clinical reactivity to peanut,” they wrote. “With peanut allergy therapies in varying stages of clinical development, and some nearing [Food and Drug Administration] approval, vital questions remain regarding the durability of treatment effects and the appropriate maintenance doses.”
In the Peanut Oral Immunotherapy Study: Safety Efficacy and Discovery (POISED), published in The Lancet, the researchers randomized 120 participants to three groups:
• 60 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by total discontinuation (peanut-0).
• 35 patients built up to a maintenance dose of 4,000 mg of peanut protein for 104 weeks followed by a 300-mg maintenance dose of peanut protein in the form of peanut flour (peanut-300).
• 25 patients to an oat flour placebo.
All participants were trained on how and when to use epinephrine autoinjector devices to treat allergic symptoms such as respiratory problems (cough, shortness of breath, or change in voice), widespread hives or erythema, repetitive vomiting, persistent abdominal pain, angioedema of the face, or feeling faint.
The primary outcome was passing a double-blind, placebo-controlled, food challenge (DBPCFC) to 4,000 mg of peanut protein, which was measured at baseline and at weeks 104, 117, 130, 143, and 156.
Overall, 35% of the peanut-0 group passed the challenge at 104 and 117 weeks, compared with 4% of the placebo group. At week 156 after discontinuing OIT, 13% of the peanut-0 group met the DBPCFC challenge, compared with 4% of the placebo group. However, 37% of participants randomized to a reduced peanut protein dose of 300 mg passed the challenge at 156 weeks, suggesting that more data are needed on optimal maintenance dosing strategies.
Baseline demographics were similar across all groups. The median age at study enrollment was 11 years and the median allergy duration was 9 years. The most common adverse events were mild gastrointestinal and respiratory problems. Adverse events decreased over time in all three groups.
“Higher levels of peanut-specific IgE to total IgE ratio, peanut sIgE, Ara h 1, Ara h 2, and Ara h 1 IgE to peanut-specific IgE ratio at baseline in participants were associated with increased frequencies of adverse events during active peanut OIT,” the researchers noted.
The study findings were limited by several factors including the ability of participants to tolerate 4,000 mg of peanut protein after achieving a maintenance dose but conducting serial testing only for those who passed the challenge. In addition, the results may be limited to peanut and not generalizable to other food allergies, the researchers said.
However, the results suggest that OIT remains a promising treatment for peanut allergies, and the association of biomarkers with clinical outcomes “might help the practitioner in identifying good candidates for OIT and those individuals who warrant increased vigilance against allergic reactions during OIT,” they said.
The National Institutes of Health supported the study. The researchers had no financial conflicts to disclose.
SOURCE: Chinthrajah RS et al. Lancet. 2019 Sep 12. doi: 10.1016/S0140-6736(19)31793-3.
FROM THE LANCET
Presumptive style of conversation boosts HPV vaccination rates in adolescents
A majority of primary care physicians recommended the human papillomavirus (HPV) vaccine to children aged 11-12 years and older, and about half of them used a presumptive style to recommend the vaccine, based on survey responses from 530 clinicians.
“Because of the crucial role of provider recommendation in parental decisions to vaccinate, a great deal of research and intervention efforts have been focused on improving provider communication regarding HPV vaccination,” Allison Kempe, MD, of the University of Colorado and Children’s Hospital Colorado, Aurora, and her colleagues wrote in Pediatrics.
“A presumptive style of initiating HPV vaccine discussions uses words that convey an assumption of vaccination and does not discuss the HPV vaccine in a different manner than other adolescent vaccines,” the authors explained. By contrast, “a conversational style engages parents in an open-ended discussion about the HPV vaccine without linguistic presupposition of vaccination.” Findings from multiple studies have shown that the presumptive approach is associated with higher acceptance of the HPV vaccine, compared with the conversational approach.
The researchers examined survey responses from a nationally representative sample of 302 pediatricians and 228 family physicians. Almost all clinicians in both specialties (99% of pediatricians, 90% of FPs) said they strongly recommended the HPV vaccine for girls aged 15 years and older. Strong recommendations for the HPV vaccine were lowest in both specialties for boys aged 11-12 years (83% of pediatricians, 66% of FPs).
Significantly more pediatricians than FPs reported using a presumptive style when discussing the HPV vaccine (65% vs. 42%, respectively; P <.0001). Overall, 40% of the survey respondents used standing orders for HPV vaccination and 42% had electronic alerts in patients’ medical records to prompt an HPV vaccine discussion.
The proportion of pediatricians who reported a vaccine refusal or deferral rate of 50% or higher for patients aged 11-12 years was 10% for girls and 23% for boys; among FPs, those percentages were 27% for girls and 36% for boys.
In multivariate analysis, the factors associated with a 50% or higher refusal or deferral rate among 11- to 12-year-olds were similar for both genders and included “not strongly recommending [the vaccine] to 11- to 12-year-old patients, not … always using a presumptive recommendation style, strongly agreeing that they encounter less resistance to HPV vaccination from patients aged 13 years versus patients aged 11 years, and anticipating an uncomfortable discussion when recommending to 11- to 12-year-old patients,” the researchers wrote.
More physicians in both specialties made stronger recommendations for HPV vaccination for patients aged 13 years and older than for those aged 11 and 12 years. However, physicians might overestimate parent and patient resistance to a strong recommendation for the HPV vaccine. A strong recommendation, “delivered in the same way as for other adolescent vaccines and on same day as other adolescent vaccines, may be key to increasing acceptance among parents of 11- to 12-year-old patients,” Dr. Kempe and associates said.
The current two-dose vaccine schedule also promoted complete vaccination, according to a majority of pediatricians and FPs.
The study findings were limited by several factors, including the use of self-reports and the potential lack of generalizability of the survey responses. The results, however, were strengthened by the large, nationally representative sample and suggest that the number of physicians who strongly recommend HPV vaccination to 11- and 12-year-olds has increased over the past 5 years, they said.
“Increased use of available communication training materials and applications, as well as further development of evidence-based messages for parents, may be helpful in improving the way HPV is introduced,” the investigators concluded.
The study was supported by the Centers for Disease Control and Prevention. The researchers reported that they had no financial conflicts.
SOURCE: Kempe A et al. Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-1475.
A majority of primary care physicians recommended the human papillomavirus (HPV) vaccine to children aged 11-12 years and older, and about half of them used a presumptive style to recommend the vaccine, based on survey responses from 530 clinicians.
“Because of the crucial role of provider recommendation in parental decisions to vaccinate, a great deal of research and intervention efforts have been focused on improving provider communication regarding HPV vaccination,” Allison Kempe, MD, of the University of Colorado and Children’s Hospital Colorado, Aurora, and her colleagues wrote in Pediatrics.
“A presumptive style of initiating HPV vaccine discussions uses words that convey an assumption of vaccination and does not discuss the HPV vaccine in a different manner than other adolescent vaccines,” the authors explained. By contrast, “a conversational style engages parents in an open-ended discussion about the HPV vaccine without linguistic presupposition of vaccination.” Findings from multiple studies have shown that the presumptive approach is associated with higher acceptance of the HPV vaccine, compared with the conversational approach.
The researchers examined survey responses from a nationally representative sample of 302 pediatricians and 228 family physicians. Almost all clinicians in both specialties (99% of pediatricians, 90% of FPs) said they strongly recommended the HPV vaccine for girls aged 15 years and older. Strong recommendations for the HPV vaccine were lowest in both specialties for boys aged 11-12 years (83% of pediatricians, 66% of FPs).
Significantly more pediatricians than FPs reported using a presumptive style when discussing the HPV vaccine (65% vs. 42%, respectively; P <.0001). Overall, 40% of the survey respondents used standing orders for HPV vaccination and 42% had electronic alerts in patients’ medical records to prompt an HPV vaccine discussion.
The proportion of pediatricians who reported a vaccine refusal or deferral rate of 50% or higher for patients aged 11-12 years was 10% for girls and 23% for boys; among FPs, those percentages were 27% for girls and 36% for boys.
In multivariate analysis, the factors associated with a 50% or higher refusal or deferral rate among 11- to 12-year-olds were similar for both genders and included “not strongly recommending [the vaccine] to 11- to 12-year-old patients, not … always using a presumptive recommendation style, strongly agreeing that they encounter less resistance to HPV vaccination from patients aged 13 years versus patients aged 11 years, and anticipating an uncomfortable discussion when recommending to 11- to 12-year-old patients,” the researchers wrote.
More physicians in both specialties made stronger recommendations for HPV vaccination for patients aged 13 years and older than for those aged 11 and 12 years. However, physicians might overestimate parent and patient resistance to a strong recommendation for the HPV vaccine. A strong recommendation, “delivered in the same way as for other adolescent vaccines and on same day as other adolescent vaccines, may be key to increasing acceptance among parents of 11- to 12-year-old patients,” Dr. Kempe and associates said.
The current two-dose vaccine schedule also promoted complete vaccination, according to a majority of pediatricians and FPs.
The study findings were limited by several factors, including the use of self-reports and the potential lack of generalizability of the survey responses. The results, however, were strengthened by the large, nationally representative sample and suggest that the number of physicians who strongly recommend HPV vaccination to 11- and 12-year-olds has increased over the past 5 years, they said.
“Increased use of available communication training materials and applications, as well as further development of evidence-based messages for parents, may be helpful in improving the way HPV is introduced,” the investigators concluded.
The study was supported by the Centers for Disease Control and Prevention. The researchers reported that they had no financial conflicts.
SOURCE: Kempe A et al. Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-1475.
A majority of primary care physicians recommended the human papillomavirus (HPV) vaccine to children aged 11-12 years and older, and about half of them used a presumptive style to recommend the vaccine, based on survey responses from 530 clinicians.
“Because of the crucial role of provider recommendation in parental decisions to vaccinate, a great deal of research and intervention efforts have been focused on improving provider communication regarding HPV vaccination,” Allison Kempe, MD, of the University of Colorado and Children’s Hospital Colorado, Aurora, and her colleagues wrote in Pediatrics.
“A presumptive style of initiating HPV vaccine discussions uses words that convey an assumption of vaccination and does not discuss the HPV vaccine in a different manner than other adolescent vaccines,” the authors explained. By contrast, “a conversational style engages parents in an open-ended discussion about the HPV vaccine without linguistic presupposition of vaccination.” Findings from multiple studies have shown that the presumptive approach is associated with higher acceptance of the HPV vaccine, compared with the conversational approach.
The researchers examined survey responses from a nationally representative sample of 302 pediatricians and 228 family physicians. Almost all clinicians in both specialties (99% of pediatricians, 90% of FPs) said they strongly recommended the HPV vaccine for girls aged 15 years and older. Strong recommendations for the HPV vaccine were lowest in both specialties for boys aged 11-12 years (83% of pediatricians, 66% of FPs).
Significantly more pediatricians than FPs reported using a presumptive style when discussing the HPV vaccine (65% vs. 42%, respectively; P <.0001). Overall, 40% of the survey respondents used standing orders for HPV vaccination and 42% had electronic alerts in patients’ medical records to prompt an HPV vaccine discussion.
The proportion of pediatricians who reported a vaccine refusal or deferral rate of 50% or higher for patients aged 11-12 years was 10% for girls and 23% for boys; among FPs, those percentages were 27% for girls and 36% for boys.
In multivariate analysis, the factors associated with a 50% or higher refusal or deferral rate among 11- to 12-year-olds were similar for both genders and included “not strongly recommending [the vaccine] to 11- to 12-year-old patients, not … always using a presumptive recommendation style, strongly agreeing that they encounter less resistance to HPV vaccination from patients aged 13 years versus patients aged 11 years, and anticipating an uncomfortable discussion when recommending to 11- to 12-year-old patients,” the researchers wrote.
More physicians in both specialties made stronger recommendations for HPV vaccination for patients aged 13 years and older than for those aged 11 and 12 years. However, physicians might overestimate parent and patient resistance to a strong recommendation for the HPV vaccine. A strong recommendation, “delivered in the same way as for other adolescent vaccines and on same day as other adolescent vaccines, may be key to increasing acceptance among parents of 11- to 12-year-old patients,” Dr. Kempe and associates said.
The current two-dose vaccine schedule also promoted complete vaccination, according to a majority of pediatricians and FPs.
The study findings were limited by several factors, including the use of self-reports and the potential lack of generalizability of the survey responses. The results, however, were strengthened by the large, nationally representative sample and suggest that the number of physicians who strongly recommend HPV vaccination to 11- and 12-year-olds has increased over the past 5 years, they said.
“Increased use of available communication training materials and applications, as well as further development of evidence-based messages for parents, may be helpful in improving the way HPV is introduced,” the investigators concluded.
The study was supported by the Centers for Disease Control and Prevention. The researchers reported that they had no financial conflicts.
SOURCE: Kempe A et al. Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-1475.
FROM PEDIATRICS
Key clinical point: A presumptive style of conversation and a two-dose vaccination schedule can increase HPV vaccination rates in adolescents.
Major finding: Overall, 65% of pediatricians and 42% of FPs reported using a presumptive style to discuss HPV vaccination.
Study details: National survey of 302 pediatricians and 228 family physicians conducted July-September 2018.
Disclosures: The study was supported by the Centers for Disease Control and Prevention. The researchers reported that they had no financial conflicts.
Source: Kempe A et al. Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-1475.
Latest suicide prevention research highlights roles for clinicians, teachers, and parents
Joan Asarnow, PhD, said in a webinar presented on World Suicide Prevention Day, Sept. 10, 2019, to raise awareness of the latest research in suicide prevention and risk factors.
“Primary care doctors are the most trusted doctors for our teenagers,” Dr. Asarnow said during a question-and-answer session. Primary care can be the first-line screening to identify risk factors for suicide, and a close link with primary care “can make a very big difference in helping kids get through tough times.”
Other studies have shown that when doctors and nurses are able to recognize suicidality and link to behavioral health when needed, suicide attempts and ideation are reduced. Strategies including dialectical behavioral therapy and cognitive-behavior therapy have demonstrated success in reducing self -harm, she noted.
Schools have a role in suicide prevention as well, said Dr. Asarnow of the University of California, Los Angeles, and editor of a special issue of the Journal of Child Psychology and Psychiatry on suicide and self-harm.
She cited data from the Saving and Empowering Young Lives in Europe (SEYLE) study, a longitudinal study of school-based suicide prevention interventions, in which suicide attempts were significantly lower among teens who were exposed to a school-based program (Youth Aware of Mental Health) than they were among controls.
Additional findings from the SEYLE study recently were published in the Journal of Child Psychology and Psychiatry (2019. doi: 10.1111/jcpp.13119).
The authors investigated the interaction of three interventions with a certain model of suicide risk. The three interventions were Youth Aware of Mental Health (YAM); Question, Persuade and Refer (QPR); and ProfScreen. The latter two are established interventions for use by teachers. In the study, 11,110 high school students from 10 countries in the European Union completed questionnaires to assess baseline feelings of being a burden to others and feelings of loneliness and isolation from family and peers. The questionnaires also assessed health risk behaviors, self-injury, suicide ideation, and suicide attempts (SA), which were factors in the model being investigated. The participants were randomized to one of the interventions or to a control group that received educational posters with information about mental health resources.
In a reassessment of 8,972 adolescents 12 months later, the interventions all significantly reduced the association between repeated suicide attempts and the baseline interaction of self-injury and suicide ideation, compared with the control group.
“Among each of the three intervention groups, [suicide ideation] at baseline did not increase the risk of self-injury to be associated with repeated [suicide attempt]” at follow-up, Shira Barzilay, PhD, of Tel Aviv University, and coauthors said.
In addition, the researchers’ model found that “belongingness to parents” predicted lower odds of SI after controlling for depression, anxiety, and internalizing symptoms, and this prediction was similar across the intervention and control groups, although good relations with peers and lack of feeling like a burden on others were not significantly associated with lower odds of SI.
The study findings were limited by several factors including the limits of the model to fully capture the measures of belongingness or burdensomeness, and the use of a 12-month follow-up, which was too long to examine certain patterns of SA, the researchers noted. However, the results suggest that interventions can help reduce risk behaviors or self-harm that could lead to suicide. Areas for further study include examining spikes in risk variables that might have preceded suicide attempts, elevated stress, or interpersonal conflicts.
“The implications for suicide prevention, in both community and clinical settings, are to monitor youth who may be engaged in risky behaviors regardless of [suicide ideation] presentation and provide them with mental health education,” Dr. Barzilay and coauthors concluded.
The ongoing mission, Dr. Asarnow said, is “to send messages of hope, and that there is help out there.”
This is particularly important in the United States and the United Kingdom because, while suicide rates in adolescents have declined in some countries, they have increased in others, notably the two countries aforementioned, Dennis Ougrin, MD, said at the webinar.
Males are more likely to commit suicide than females by a ratio of 3 or 4 to 1 in most Western countries, said Dr. Ougrin, a child and adolescent psychiatrist at South London and Maudsley National Health Service Foundation Trust, leading the Child and Adolescent Mental Health Services Enhanced Treatment Service.
Although hanging is the most common method for suicides in most countries, followed by poisoning, more than 50% of suicides in the United States are caused by firearms, he noted.
Risk factors for completed suicide include male sex, low social status, restricted educational achievement, parental mental disorder, individual mental disorder, family history of suicidal behavior, problems with interpersonal relationships, drug and alcohol misuse, and feelings of hopelessness, said Dr. Ougrin, citing data from a 2012 study published in the Lancet (2012 Jun 23. doi: 10.1016/S0140-6736[12]60322-5).
The webinar was sponsored by Wiley partnership with the World Federation of Science Journalists and the Association of Health Care Journalists. Dr. Asarnow and Dr. Ougrin had no financial conflicts to disclose. The SEYLE project is supported by the European Union through the Seventh Framework Program. Dr. Barzilay and coauthors of the SEYLE study had no financial conflicts to disclose.
Joan Asarnow, PhD, said in a webinar presented on World Suicide Prevention Day, Sept. 10, 2019, to raise awareness of the latest research in suicide prevention and risk factors.
“Primary care doctors are the most trusted doctors for our teenagers,” Dr. Asarnow said during a question-and-answer session. Primary care can be the first-line screening to identify risk factors for suicide, and a close link with primary care “can make a very big difference in helping kids get through tough times.”
Other studies have shown that when doctors and nurses are able to recognize suicidality and link to behavioral health when needed, suicide attempts and ideation are reduced. Strategies including dialectical behavioral therapy and cognitive-behavior therapy have demonstrated success in reducing self -harm, she noted.
Schools have a role in suicide prevention as well, said Dr. Asarnow of the University of California, Los Angeles, and editor of a special issue of the Journal of Child Psychology and Psychiatry on suicide and self-harm.
She cited data from the Saving and Empowering Young Lives in Europe (SEYLE) study, a longitudinal study of school-based suicide prevention interventions, in which suicide attempts were significantly lower among teens who were exposed to a school-based program (Youth Aware of Mental Health) than they were among controls.
Additional findings from the SEYLE study recently were published in the Journal of Child Psychology and Psychiatry (2019. doi: 10.1111/jcpp.13119).
The authors investigated the interaction of three interventions with a certain model of suicide risk. The three interventions were Youth Aware of Mental Health (YAM); Question, Persuade and Refer (QPR); and ProfScreen. The latter two are established interventions for use by teachers. In the study, 11,110 high school students from 10 countries in the European Union completed questionnaires to assess baseline feelings of being a burden to others and feelings of loneliness and isolation from family and peers. The questionnaires also assessed health risk behaviors, self-injury, suicide ideation, and suicide attempts (SA), which were factors in the model being investigated. The participants were randomized to one of the interventions or to a control group that received educational posters with information about mental health resources.
In a reassessment of 8,972 adolescents 12 months later, the interventions all significantly reduced the association between repeated suicide attempts and the baseline interaction of self-injury and suicide ideation, compared with the control group.
“Among each of the three intervention groups, [suicide ideation] at baseline did not increase the risk of self-injury to be associated with repeated [suicide attempt]” at follow-up, Shira Barzilay, PhD, of Tel Aviv University, and coauthors said.
In addition, the researchers’ model found that “belongingness to parents” predicted lower odds of SI after controlling for depression, anxiety, and internalizing symptoms, and this prediction was similar across the intervention and control groups, although good relations with peers and lack of feeling like a burden on others were not significantly associated with lower odds of SI.
The study findings were limited by several factors including the limits of the model to fully capture the measures of belongingness or burdensomeness, and the use of a 12-month follow-up, which was too long to examine certain patterns of SA, the researchers noted. However, the results suggest that interventions can help reduce risk behaviors or self-harm that could lead to suicide. Areas for further study include examining spikes in risk variables that might have preceded suicide attempts, elevated stress, or interpersonal conflicts.
“The implications for suicide prevention, in both community and clinical settings, are to monitor youth who may be engaged in risky behaviors regardless of [suicide ideation] presentation and provide them with mental health education,” Dr. Barzilay and coauthors concluded.
The ongoing mission, Dr. Asarnow said, is “to send messages of hope, and that there is help out there.”
This is particularly important in the United States and the United Kingdom because, while suicide rates in adolescents have declined in some countries, they have increased in others, notably the two countries aforementioned, Dennis Ougrin, MD, said at the webinar.
Males are more likely to commit suicide than females by a ratio of 3 or 4 to 1 in most Western countries, said Dr. Ougrin, a child and adolescent psychiatrist at South London and Maudsley National Health Service Foundation Trust, leading the Child and Adolescent Mental Health Services Enhanced Treatment Service.
Although hanging is the most common method for suicides in most countries, followed by poisoning, more than 50% of suicides in the United States are caused by firearms, he noted.
Risk factors for completed suicide include male sex, low social status, restricted educational achievement, parental mental disorder, individual mental disorder, family history of suicidal behavior, problems with interpersonal relationships, drug and alcohol misuse, and feelings of hopelessness, said Dr. Ougrin, citing data from a 2012 study published in the Lancet (2012 Jun 23. doi: 10.1016/S0140-6736[12]60322-5).
The webinar was sponsored by Wiley partnership with the World Federation of Science Journalists and the Association of Health Care Journalists. Dr. Asarnow and Dr. Ougrin had no financial conflicts to disclose. The SEYLE project is supported by the European Union through the Seventh Framework Program. Dr. Barzilay and coauthors of the SEYLE study had no financial conflicts to disclose.
Joan Asarnow, PhD, said in a webinar presented on World Suicide Prevention Day, Sept. 10, 2019, to raise awareness of the latest research in suicide prevention and risk factors.
“Primary care doctors are the most trusted doctors for our teenagers,” Dr. Asarnow said during a question-and-answer session. Primary care can be the first-line screening to identify risk factors for suicide, and a close link with primary care “can make a very big difference in helping kids get through tough times.”
Other studies have shown that when doctors and nurses are able to recognize suicidality and link to behavioral health when needed, suicide attempts and ideation are reduced. Strategies including dialectical behavioral therapy and cognitive-behavior therapy have demonstrated success in reducing self -harm, she noted.
Schools have a role in suicide prevention as well, said Dr. Asarnow of the University of California, Los Angeles, and editor of a special issue of the Journal of Child Psychology and Psychiatry on suicide and self-harm.
She cited data from the Saving and Empowering Young Lives in Europe (SEYLE) study, a longitudinal study of school-based suicide prevention interventions, in which suicide attempts were significantly lower among teens who were exposed to a school-based program (Youth Aware of Mental Health) than they were among controls.
Additional findings from the SEYLE study recently were published in the Journal of Child Psychology and Psychiatry (2019. doi: 10.1111/jcpp.13119).
The authors investigated the interaction of three interventions with a certain model of suicide risk. The three interventions were Youth Aware of Mental Health (YAM); Question, Persuade and Refer (QPR); and ProfScreen. The latter two are established interventions for use by teachers. In the study, 11,110 high school students from 10 countries in the European Union completed questionnaires to assess baseline feelings of being a burden to others and feelings of loneliness and isolation from family and peers. The questionnaires also assessed health risk behaviors, self-injury, suicide ideation, and suicide attempts (SA), which were factors in the model being investigated. The participants were randomized to one of the interventions or to a control group that received educational posters with information about mental health resources.
In a reassessment of 8,972 adolescents 12 months later, the interventions all significantly reduced the association between repeated suicide attempts and the baseline interaction of self-injury and suicide ideation, compared with the control group.
“Among each of the three intervention groups, [suicide ideation] at baseline did not increase the risk of self-injury to be associated with repeated [suicide attempt]” at follow-up, Shira Barzilay, PhD, of Tel Aviv University, and coauthors said.
In addition, the researchers’ model found that “belongingness to parents” predicted lower odds of SI after controlling for depression, anxiety, and internalizing symptoms, and this prediction was similar across the intervention and control groups, although good relations with peers and lack of feeling like a burden on others were not significantly associated with lower odds of SI.
The study findings were limited by several factors including the limits of the model to fully capture the measures of belongingness or burdensomeness, and the use of a 12-month follow-up, which was too long to examine certain patterns of SA, the researchers noted. However, the results suggest that interventions can help reduce risk behaviors or self-harm that could lead to suicide. Areas for further study include examining spikes in risk variables that might have preceded suicide attempts, elevated stress, or interpersonal conflicts.
“The implications for suicide prevention, in both community and clinical settings, are to monitor youth who may be engaged in risky behaviors regardless of [suicide ideation] presentation and provide them with mental health education,” Dr. Barzilay and coauthors concluded.
The ongoing mission, Dr. Asarnow said, is “to send messages of hope, and that there is help out there.”
This is particularly important in the United States and the United Kingdom because, while suicide rates in adolescents have declined in some countries, they have increased in others, notably the two countries aforementioned, Dennis Ougrin, MD, said at the webinar.
Males are more likely to commit suicide than females by a ratio of 3 or 4 to 1 in most Western countries, said Dr. Ougrin, a child and adolescent psychiatrist at South London and Maudsley National Health Service Foundation Trust, leading the Child and Adolescent Mental Health Services Enhanced Treatment Service.
Although hanging is the most common method for suicides in most countries, followed by poisoning, more than 50% of suicides in the United States are caused by firearms, he noted.
Risk factors for completed suicide include male sex, low social status, restricted educational achievement, parental mental disorder, individual mental disorder, family history of suicidal behavior, problems with interpersonal relationships, drug and alcohol misuse, and feelings of hopelessness, said Dr. Ougrin, citing data from a 2012 study published in the Lancet (2012 Jun 23. doi: 10.1016/S0140-6736[12]60322-5).
The webinar was sponsored by Wiley partnership with the World Federation of Science Journalists and the Association of Health Care Journalists. Dr. Asarnow and Dr. Ougrin had no financial conflicts to disclose. The SEYLE project is supported by the European Union through the Seventh Framework Program. Dr. Barzilay and coauthors of the SEYLE study had no financial conflicts to disclose.
FROM A SCIENCE TALKS WEBINAR
Long-term advantages may not endure after early tight control in psoriatic arthritis
, based on data from 110 patients in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) study.
In the original study, significantly more adults with psoriatic arthritis (PsA) who were randomized to a tight control, treat-to-target group achieved minimal disease activity criteria after 48 weeks, compared with a standard care group (40% vs. 25%).
“Following exit from this study, we hypothesized that this advantage would translate to a clinical advantage in the medium term,” wrote Laura C. Coates, MBChB, PhD, of the University of Oxford (England) and colleagues.
In a study published in Rheumatology, the researchers examined data from 54 patients in the tight control arm of TICOPA and 56 patients in the standard care arm.
At 5 years after the completion of the TICOPA study, 69% of patients in the tight control group and 76% of patients in the standard care group were considered to be in low disease activity. In addition, methotrexate use after 5 years was similar between the tight control and standard care groups (44% and 54%, respectively) and both groups had reduced methotrexate use since the study’s end.
Overall use of biologic drugs was similar between the tight control and standard care groups after 5 years (54% and 52%, respectively), although overall use of biologics was higher in the tight control group at the end of the original study, compared with the standard care group (33% vs. 9%).
The findings were limited by several factors, notably the lack of intention to continue treatment or observations beyond the end of the original TICOPA study, and the patients’ status at 5 years was based on routine clinician notes with no formal assessment of minimal disease activity or objective measure of disease status, the researchers noted.
However, “this result reflects clinical practice in routine rheumatology care,” and any benefit of early tight control on later disease activity could not be determined, they added.
The current study was funded by the National Institute for Health Research infrastructure at Leeds and Oxford (England). The original TICOPA study was funded by Arthritis Research UK (now called Versus Arthritis) and Pfizer. Some of the investigators disclosed financial relationships with companies that market drugs for PsA.
SOURCE: Coates LC et al. Rheumatology. 2019 Aug 31. doi: 10.1093/rheumatology/kez369.
, based on data from 110 patients in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) study.
In the original study, significantly more adults with psoriatic arthritis (PsA) who were randomized to a tight control, treat-to-target group achieved minimal disease activity criteria after 48 weeks, compared with a standard care group (40% vs. 25%).
“Following exit from this study, we hypothesized that this advantage would translate to a clinical advantage in the medium term,” wrote Laura C. Coates, MBChB, PhD, of the University of Oxford (England) and colleagues.
In a study published in Rheumatology, the researchers examined data from 54 patients in the tight control arm of TICOPA and 56 patients in the standard care arm.
At 5 years after the completion of the TICOPA study, 69% of patients in the tight control group and 76% of patients in the standard care group were considered to be in low disease activity. In addition, methotrexate use after 5 years was similar between the tight control and standard care groups (44% and 54%, respectively) and both groups had reduced methotrexate use since the study’s end.
Overall use of biologic drugs was similar between the tight control and standard care groups after 5 years (54% and 52%, respectively), although overall use of biologics was higher in the tight control group at the end of the original study, compared with the standard care group (33% vs. 9%).
The findings were limited by several factors, notably the lack of intention to continue treatment or observations beyond the end of the original TICOPA study, and the patients’ status at 5 years was based on routine clinician notes with no formal assessment of minimal disease activity or objective measure of disease status, the researchers noted.
However, “this result reflects clinical practice in routine rheumatology care,” and any benefit of early tight control on later disease activity could not be determined, they added.
The current study was funded by the National Institute for Health Research infrastructure at Leeds and Oxford (England). The original TICOPA study was funded by Arthritis Research UK (now called Versus Arthritis) and Pfizer. Some of the investigators disclosed financial relationships with companies that market drugs for PsA.
SOURCE: Coates LC et al. Rheumatology. 2019 Aug 31. doi: 10.1093/rheumatology/kez369.
, based on data from 110 patients in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) study.
In the original study, significantly more adults with psoriatic arthritis (PsA) who were randomized to a tight control, treat-to-target group achieved minimal disease activity criteria after 48 weeks, compared with a standard care group (40% vs. 25%).
“Following exit from this study, we hypothesized that this advantage would translate to a clinical advantage in the medium term,” wrote Laura C. Coates, MBChB, PhD, of the University of Oxford (England) and colleagues.
In a study published in Rheumatology, the researchers examined data from 54 patients in the tight control arm of TICOPA and 56 patients in the standard care arm.
At 5 years after the completion of the TICOPA study, 69% of patients in the tight control group and 76% of patients in the standard care group were considered to be in low disease activity. In addition, methotrexate use after 5 years was similar between the tight control and standard care groups (44% and 54%, respectively) and both groups had reduced methotrexate use since the study’s end.
Overall use of biologic drugs was similar between the tight control and standard care groups after 5 years (54% and 52%, respectively), although overall use of biologics was higher in the tight control group at the end of the original study, compared with the standard care group (33% vs. 9%).
The findings were limited by several factors, notably the lack of intention to continue treatment or observations beyond the end of the original TICOPA study, and the patients’ status at 5 years was based on routine clinician notes with no formal assessment of minimal disease activity or objective measure of disease status, the researchers noted.
However, “this result reflects clinical practice in routine rheumatology care,” and any benefit of early tight control on later disease activity could not be determined, they added.
The current study was funded by the National Institute for Health Research infrastructure at Leeds and Oxford (England). The original TICOPA study was funded by Arthritis Research UK (now called Versus Arthritis) and Pfizer. Some of the investigators disclosed financial relationships with companies that market drugs for PsA.
SOURCE: Coates LC et al. Rheumatology. 2019 Aug 31. doi: 10.1093/rheumatology/kez369.
FROM RHEUMATOLOGY
Key clinical point: Patients in a psoriatic arthritis study comparing tight control and standard care showed no significant difference in disease activity 5 years later.
Major finding: At 5 years after the end of the TICOPA trial, 69% in the tight control group vs. 76% in the standard care group were considered to be in low disease activity.
Study details: The data come from a follow-up of 110 patients from the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) study.
Disclosures: The current study was funded by the National Institute for Health Research infrastructure at Leeds and Oxford (England). The original TICOPA study was funded by Arthritis Research UK (now called Versus Arthritis) and Pfizer. Some of the investigators disclosed financial relationships with companies that market drugs for PsA.
Source: Coates LC et al. Rheumatology. 2019 Aug 31. doi: 10.1093/rheumatology/kez369.
Two uveitis treatment options yield similar success
in an international, multicenter, open-label, randomized trial.
“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.
Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.
In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.
Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.
Overall, 64 patients given methotrexate (67%) and 56 of those given mycophenolate (57%) achieved treatment success at 6 months. Treatment success included inflammation control defined as “less than or equal to 0.5+ anterior chamber cells by Standardization of Uveitis Nomenclature criteria, less than or equal to 0.5+ vitreous haze clinical grading using the National Eye Institute scale, and no active retinal or choroidal lesions,” as well as needing no more than 7.5 mg of prednisone daily and two drops or less of prednisolone acetate 1% per day, and reporting no intolerability or safety concerns requiring study discontinuation.
Adverse events were similar between the groups. The most common nonserious adverse events were fatigue and headaches, and the most common nonserious laboratory adverse event was elevated liver enzymes. Fourteen serious adverse events occurred during the study period; three in the methotrexate group and two in the mycophenolate group were deemed drug related and all were elevated liver function tests.
The study findings had several limitations, including lack of masking of the patients to the medication and an inability to compare between types of uveitis, the researchers noted. Avenues for further research include whether one of the drugs is more effective based on the uveitis subtype, they added.
The study was supported in part by the National Eye Institute and study drugs were provided by the University of California San Francisco Pharmacy. Dr. Rathinam disclosed grants from Aravind Eye Hospital, and several coauthors disclosed relationships with AbbVie, Allergan, Novartis, Novotech, and Bayer.
SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.
in an international, multicenter, open-label, randomized trial.
“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.
Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.
In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.
Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.
Overall, 64 patients given methotrexate (67%) and 56 of those given mycophenolate (57%) achieved treatment success at 6 months. Treatment success included inflammation control defined as “less than or equal to 0.5+ anterior chamber cells by Standardization of Uveitis Nomenclature criteria, less than or equal to 0.5+ vitreous haze clinical grading using the National Eye Institute scale, and no active retinal or choroidal lesions,” as well as needing no more than 7.5 mg of prednisone daily and two drops or less of prednisolone acetate 1% per day, and reporting no intolerability or safety concerns requiring study discontinuation.
Adverse events were similar between the groups. The most common nonserious adverse events were fatigue and headaches, and the most common nonserious laboratory adverse event was elevated liver enzymes. Fourteen serious adverse events occurred during the study period; three in the methotrexate group and two in the mycophenolate group were deemed drug related and all were elevated liver function tests.
The study findings had several limitations, including lack of masking of the patients to the medication and an inability to compare between types of uveitis, the researchers noted. Avenues for further research include whether one of the drugs is more effective based on the uveitis subtype, they added.
The study was supported in part by the National Eye Institute and study drugs were provided by the University of California San Francisco Pharmacy. Dr. Rathinam disclosed grants from Aravind Eye Hospital, and several coauthors disclosed relationships with AbbVie, Allergan, Novartis, Novotech, and Bayer.
SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.
in an international, multicenter, open-label, randomized trial.
“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.
Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.
In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.
Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.
Overall, 64 patients given methotrexate (67%) and 56 of those given mycophenolate (57%) achieved treatment success at 6 months. Treatment success included inflammation control defined as “less than or equal to 0.5+ anterior chamber cells by Standardization of Uveitis Nomenclature criteria, less than or equal to 0.5+ vitreous haze clinical grading using the National Eye Institute scale, and no active retinal or choroidal lesions,” as well as needing no more than 7.5 mg of prednisone daily and two drops or less of prednisolone acetate 1% per day, and reporting no intolerability or safety concerns requiring study discontinuation.
Adverse events were similar between the groups. The most common nonserious adverse events were fatigue and headaches, and the most common nonserious laboratory adverse event was elevated liver enzymes. Fourteen serious adverse events occurred during the study period; three in the methotrexate group and two in the mycophenolate group were deemed drug related and all were elevated liver function tests.
The study findings had several limitations, including lack of masking of the patients to the medication and an inability to compare between types of uveitis, the researchers noted. Avenues for further research include whether one of the drugs is more effective based on the uveitis subtype, they added.
The study was supported in part by the National Eye Institute and study drugs were provided by the University of California San Francisco Pharmacy. Dr. Rathinam disclosed grants from Aravind Eye Hospital, and several coauthors disclosed relationships with AbbVie, Allergan, Novartis, Novotech, and Bayer.
SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.
FROM JAMA
Key clinical point: Mycophenolate mofetil and methotrexate were similar as corticosteroid-sparing treatment in patients with uveitis.
Major finding: Among uveitis patients, 67% of those given methotrexate and 57% of those given mycophenolate achieved corticosteroid-sparing control of inflammation.
Study details: The data come from a randomized trial of 216 adults with noninfectious uveitis at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico.
Disclosures: The study was supported in part by the National Eye Institute and study drugs were provided by the University of California San Francisco Pharmacy. Dr. Rathinam disclosed grants from Aravind Eye Hospital, and several coauthors disclosed relationships with AbbVie, Allergan, Novartis, Novotech, and Bayer.
Source: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.
New evidence supports immune system involvement in hidradenitis suppurativa
Immune dysregulation is a substantial feature of hidradenitis suppurativa in African American patients, according to data from 16 adults.
The etiology of hidradenitis suppurativa (HS) remains unknown, but neutrophils are prominent in affected areas of skin, wrote Angel S. Byrd, MD, PhD, of Johns Hopkins University, Baltimore, and colleagues.
“Among the several functions of neutrophils, these cells have the ability to form neutrophil extracellular traps (NETs) after exposure to certain microbes or sterile stimuli,” the researchers noted. These NETs are weblike structures that have been shown to activate several types of immune responses and promote inflammation.
In a study published in Science Translational Medicine, the researchers analyzed biospecimens from African American HS patients. They determined that NET structures were present in the lesional skin of HS patients, but not in control skin. Additionally, serum from HS patients did not properly degrade healthy control NETs in an in vitro examination.
A significant correlation (P less than .0001) occurred between the amount of NETs released in hidradenitis suppurativa lesions and hidradenitis suppurativa severity.
“Together, these results indicate that NET formation is enhanced in HS, both systemically and in lesional skin, in association with disease severity and that NET degradation mechanisms may be impaired in this disease,” the researchers wrote.
The researchers also found that total immunoglobulin G was significantly increased in the sera of HS patients, compared with that of healthy volunteers (P = .0011), and that enzymes involved in skin citrullination were elevated in the skin of HS patients, compared with controls’ skin.
Previous studies have shown that NETs can promote type I interferon (IFN) signatures in the blood of patients with autoimmune and chronic inflammatory conditions, and in this study, several type I IFN–regulated genes had increased expression in HS skin, including IFI44L, MX1, CXCL10, RSAD2, and IFI27.
The study findings were limited by the small sample size and homogenous population, the researchers noted. Future research should include “the role that neutrophil/type I IFN dysregulation plays in the clinical manifestations of the disease, and how these abnormalities in immune responses regulate other innate and adaptive immune cell types in HS,” which could affect the development of new treatments, they wrote.
The study was supported in part by the National Institutes of Health, the Johns Hopkins School of Medicine Physician Scientist Training Program, and the Danby Hidradenitis Suppurativa Foundation. Dr. Byrd disclosed participating in the Johns Hopkins Ethnic Skin Fellowship, which was supported in part by Valeant. Dr. Byrd also disclosed serving as a former investigator for Eli Lilly.
SOURCE: Byrd AS et al. Sci Transl Med. 2019 Sep 4. doi: 10.1126/scitranslmed.aav5908.
Immune dysregulation is a substantial feature of hidradenitis suppurativa in African American patients, according to data from 16 adults.
The etiology of hidradenitis suppurativa (HS) remains unknown, but neutrophils are prominent in affected areas of skin, wrote Angel S. Byrd, MD, PhD, of Johns Hopkins University, Baltimore, and colleagues.
“Among the several functions of neutrophils, these cells have the ability to form neutrophil extracellular traps (NETs) after exposure to certain microbes or sterile stimuli,” the researchers noted. These NETs are weblike structures that have been shown to activate several types of immune responses and promote inflammation.
In a study published in Science Translational Medicine, the researchers analyzed biospecimens from African American HS patients. They determined that NET structures were present in the lesional skin of HS patients, but not in control skin. Additionally, serum from HS patients did not properly degrade healthy control NETs in an in vitro examination.
A significant correlation (P less than .0001) occurred between the amount of NETs released in hidradenitis suppurativa lesions and hidradenitis suppurativa severity.
“Together, these results indicate that NET formation is enhanced in HS, both systemically and in lesional skin, in association with disease severity and that NET degradation mechanisms may be impaired in this disease,” the researchers wrote.
The researchers also found that total immunoglobulin G was significantly increased in the sera of HS patients, compared with that of healthy volunteers (P = .0011), and that enzymes involved in skin citrullination were elevated in the skin of HS patients, compared with controls’ skin.
Previous studies have shown that NETs can promote type I interferon (IFN) signatures in the blood of patients with autoimmune and chronic inflammatory conditions, and in this study, several type I IFN–regulated genes had increased expression in HS skin, including IFI44L, MX1, CXCL10, RSAD2, and IFI27.
The study findings were limited by the small sample size and homogenous population, the researchers noted. Future research should include “the role that neutrophil/type I IFN dysregulation plays in the clinical manifestations of the disease, and how these abnormalities in immune responses regulate other innate and adaptive immune cell types in HS,” which could affect the development of new treatments, they wrote.
The study was supported in part by the National Institutes of Health, the Johns Hopkins School of Medicine Physician Scientist Training Program, and the Danby Hidradenitis Suppurativa Foundation. Dr. Byrd disclosed participating in the Johns Hopkins Ethnic Skin Fellowship, which was supported in part by Valeant. Dr. Byrd also disclosed serving as a former investigator for Eli Lilly.
SOURCE: Byrd AS et al. Sci Transl Med. 2019 Sep 4. doi: 10.1126/scitranslmed.aav5908.
Immune dysregulation is a substantial feature of hidradenitis suppurativa in African American patients, according to data from 16 adults.
The etiology of hidradenitis suppurativa (HS) remains unknown, but neutrophils are prominent in affected areas of skin, wrote Angel S. Byrd, MD, PhD, of Johns Hopkins University, Baltimore, and colleagues.
“Among the several functions of neutrophils, these cells have the ability to form neutrophil extracellular traps (NETs) after exposure to certain microbes or sterile stimuli,” the researchers noted. These NETs are weblike structures that have been shown to activate several types of immune responses and promote inflammation.
In a study published in Science Translational Medicine, the researchers analyzed biospecimens from African American HS patients. They determined that NET structures were present in the lesional skin of HS patients, but not in control skin. Additionally, serum from HS patients did not properly degrade healthy control NETs in an in vitro examination.
A significant correlation (P less than .0001) occurred between the amount of NETs released in hidradenitis suppurativa lesions and hidradenitis suppurativa severity.
“Together, these results indicate that NET formation is enhanced in HS, both systemically and in lesional skin, in association with disease severity and that NET degradation mechanisms may be impaired in this disease,” the researchers wrote.
The researchers also found that total immunoglobulin G was significantly increased in the sera of HS patients, compared with that of healthy volunteers (P = .0011), and that enzymes involved in skin citrullination were elevated in the skin of HS patients, compared with controls’ skin.
Previous studies have shown that NETs can promote type I interferon (IFN) signatures in the blood of patients with autoimmune and chronic inflammatory conditions, and in this study, several type I IFN–regulated genes had increased expression in HS skin, including IFI44L, MX1, CXCL10, RSAD2, and IFI27.
The study findings were limited by the small sample size and homogenous population, the researchers noted. Future research should include “the role that neutrophil/type I IFN dysregulation plays in the clinical manifestations of the disease, and how these abnormalities in immune responses regulate other innate and adaptive immune cell types in HS,” which could affect the development of new treatments, they wrote.
The study was supported in part by the National Institutes of Health, the Johns Hopkins School of Medicine Physician Scientist Training Program, and the Danby Hidradenitis Suppurativa Foundation. Dr. Byrd disclosed participating in the Johns Hopkins Ethnic Skin Fellowship, which was supported in part by Valeant. Dr. Byrd also disclosed serving as a former investigator for Eli Lilly.
SOURCE: Byrd AS et al. Sci Transl Med. 2019 Sep 4. doi: 10.1126/scitranslmed.aav5908.
FROM SCIENCE TRANSLATIONAL MEDICINE
USPSTF recommends preventive breast cancer medications only for women at risk
Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.
“Although evidence on the best interval at which to reassess risk and indications for risk-reducing medications is not available, a pragmatic approach would be to repeat risk assessment when there is a significant change in breast cancer risk factors; for instance, when a family member is diagnosed with breast cancer or when there is a new diagnosis of atypical hyperplasia or lobular carcinoma in situ on breast biopsy,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University and members of the task force.
The recommendation applies to asymptomatic women aged 35 years and older, including women with a history of benign breast lesions, but does not apply to women with current or previous breast cancer or ductal carcinoma in situ. The recommendation remains essentially unchanged from the 2013 version, with the addition of aromatase inhibitors (AIs) in the list of options for risk-reducing medications.
In an evidence report accompanying the recommendation, researchers reviewed data from 46 studies including 82 articles and more than 5 million individuals. Overall, among 10 placebo-controlled trials, tamoxifen, raloxifene, and AIs were associated with lower incidence of invasive breast cancer, with risk ratios of 0.69, 0.44, and 0.45, respectively.
However, based on the risk of adverse effects including thromboembolic events, endometrial cancer, and cataracts, the task force determined that the benefits of these medications were no greater than small in women with no risk factors. In addition, 18 risk assessments in 25 studies showed low levels of accuracy in predicting breast cancer risk.
Data from the studies reviewed by the USPSTF showed that the harms of AIs included vasomotor symptoms, GI symptoms, musculoskeletal pain, and potential increased risk of cardiovascular events and fractures. Potential harms of other medications to help prevent breast cancer (tamoxifen and raloxifene) included increased risk for venous thromboembolic events, endometrial cancer, cataracts, and hot flashes.
The findings were limited by several factors including possible publication bias, variation in risk assessment studies, and inability to conduct subgroup analysis, wrote Heidi D. Nelson, MD, of Oregon Health & Sciences University, Portland, and colleagues in the evidence report.
“Although most results are consistent with the 2013 USPSTF review, this update provides additional evidence of the inaccuracy of risk assessment methods,” they noted.
“The USPSTF recommendations, and the accompanying systematic evidence review by Nelson and colleagues rightfully focus on the need to identify women for whom the benefits are likely to outweigh harms, but they also underscore persistent uncertainties about how to accomplish that goal,” wrote Lydia E. Pace, MD, and Nancy L. Keating, MD, both of Brigham and Women’s Hospital in Boston, in an accompanying editorial (JAMA. 2019 Sept 3;322:821-23).
“Identifying safer and more effective preventive medications would help mitigate the low discriminatory accuracy of existing breast cancer risk models,” the editorialists wrote. “Meanwhile, considering risk-reducing medications for women with 5-year risk greater than 3% seems reasonable, as well as for women with atypical hyperplasia and [lobular carcinoma in situ].”
The research was funded by the Agency for Healthcare Research and Quality. Neither the task force researchers nor the editorialists reported relevant financial conflicts.
SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.
Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.
“Although evidence on the best interval at which to reassess risk and indications for risk-reducing medications is not available, a pragmatic approach would be to repeat risk assessment when there is a significant change in breast cancer risk factors; for instance, when a family member is diagnosed with breast cancer or when there is a new diagnosis of atypical hyperplasia or lobular carcinoma in situ on breast biopsy,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University and members of the task force.
The recommendation applies to asymptomatic women aged 35 years and older, including women with a history of benign breast lesions, but does not apply to women with current or previous breast cancer or ductal carcinoma in situ. The recommendation remains essentially unchanged from the 2013 version, with the addition of aromatase inhibitors (AIs) in the list of options for risk-reducing medications.
In an evidence report accompanying the recommendation, researchers reviewed data from 46 studies including 82 articles and more than 5 million individuals. Overall, among 10 placebo-controlled trials, tamoxifen, raloxifene, and AIs were associated with lower incidence of invasive breast cancer, with risk ratios of 0.69, 0.44, and 0.45, respectively.
However, based on the risk of adverse effects including thromboembolic events, endometrial cancer, and cataracts, the task force determined that the benefits of these medications were no greater than small in women with no risk factors. In addition, 18 risk assessments in 25 studies showed low levels of accuracy in predicting breast cancer risk.
Data from the studies reviewed by the USPSTF showed that the harms of AIs included vasomotor symptoms, GI symptoms, musculoskeletal pain, and potential increased risk of cardiovascular events and fractures. Potential harms of other medications to help prevent breast cancer (tamoxifen and raloxifene) included increased risk for venous thromboembolic events, endometrial cancer, cataracts, and hot flashes.
The findings were limited by several factors including possible publication bias, variation in risk assessment studies, and inability to conduct subgroup analysis, wrote Heidi D. Nelson, MD, of Oregon Health & Sciences University, Portland, and colleagues in the evidence report.
“Although most results are consistent with the 2013 USPSTF review, this update provides additional evidence of the inaccuracy of risk assessment methods,” they noted.
“The USPSTF recommendations, and the accompanying systematic evidence review by Nelson and colleagues rightfully focus on the need to identify women for whom the benefits are likely to outweigh harms, but they also underscore persistent uncertainties about how to accomplish that goal,” wrote Lydia E. Pace, MD, and Nancy L. Keating, MD, both of Brigham and Women’s Hospital in Boston, in an accompanying editorial (JAMA. 2019 Sept 3;322:821-23).
“Identifying safer and more effective preventive medications would help mitigate the low discriminatory accuracy of existing breast cancer risk models,” the editorialists wrote. “Meanwhile, considering risk-reducing medications for women with 5-year risk greater than 3% seems reasonable, as well as for women with atypical hyperplasia and [lobular carcinoma in situ].”
The research was funded by the Agency for Healthcare Research and Quality. Neither the task force researchers nor the editorialists reported relevant financial conflicts.
SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.
Medication to help prevent breast cancer is not recommended for women without increased risk, but could benefit women at increased risk for the disease, according to an update from the U.S. Preventive Services Task Force.
“Although evidence on the best interval at which to reassess risk and indications for risk-reducing medications is not available, a pragmatic approach would be to repeat risk assessment when there is a significant change in breast cancer risk factors; for instance, when a family member is diagnosed with breast cancer or when there is a new diagnosis of atypical hyperplasia or lobular carcinoma in situ on breast biopsy,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University and members of the task force.
The recommendation applies to asymptomatic women aged 35 years and older, including women with a history of benign breast lesions, but does not apply to women with current or previous breast cancer or ductal carcinoma in situ. The recommendation remains essentially unchanged from the 2013 version, with the addition of aromatase inhibitors (AIs) in the list of options for risk-reducing medications.
In an evidence report accompanying the recommendation, researchers reviewed data from 46 studies including 82 articles and more than 5 million individuals. Overall, among 10 placebo-controlled trials, tamoxifen, raloxifene, and AIs were associated with lower incidence of invasive breast cancer, with risk ratios of 0.69, 0.44, and 0.45, respectively.
However, based on the risk of adverse effects including thromboembolic events, endometrial cancer, and cataracts, the task force determined that the benefits of these medications were no greater than small in women with no risk factors. In addition, 18 risk assessments in 25 studies showed low levels of accuracy in predicting breast cancer risk.
Data from the studies reviewed by the USPSTF showed that the harms of AIs included vasomotor symptoms, GI symptoms, musculoskeletal pain, and potential increased risk of cardiovascular events and fractures. Potential harms of other medications to help prevent breast cancer (tamoxifen and raloxifene) included increased risk for venous thromboembolic events, endometrial cancer, cataracts, and hot flashes.
The findings were limited by several factors including possible publication bias, variation in risk assessment studies, and inability to conduct subgroup analysis, wrote Heidi D. Nelson, MD, of Oregon Health & Sciences University, Portland, and colleagues in the evidence report.
“Although most results are consistent with the 2013 USPSTF review, this update provides additional evidence of the inaccuracy of risk assessment methods,” they noted.
“The USPSTF recommendations, and the accompanying systematic evidence review by Nelson and colleagues rightfully focus on the need to identify women for whom the benefits are likely to outweigh harms, but they also underscore persistent uncertainties about how to accomplish that goal,” wrote Lydia E. Pace, MD, and Nancy L. Keating, MD, both of Brigham and Women’s Hospital in Boston, in an accompanying editorial (JAMA. 2019 Sept 3;322:821-23).
“Identifying safer and more effective preventive medications would help mitigate the low discriminatory accuracy of existing breast cancer risk models,” the editorialists wrote. “Meanwhile, considering risk-reducing medications for women with 5-year risk greater than 3% seems reasonable, as well as for women with atypical hyperplasia and [lobular carcinoma in situ].”
The research was funded by the Agency for Healthcare Research and Quality. Neither the task force researchers nor the editorialists reported relevant financial conflicts.
SOURCEs: Owens DK et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.11885; Nelson HD et al. JAMA. 2019 Sept 3. doi: 10.1001/jama.2019.5780.
FROM JAMA
Community intervention curbs CV disease in hypertensive adults
A community-based care model to control hypertension led by nonphysician health care workers significantly reduced cardiovascular disease risk over 12 months, data from a cluster-controlled randomized study has shown.
Hypertension remains the most common risk factor for cardiovascular disease, but fewer than 20% of individuals with hypertension have their blood pressure controlled, wrote Jon-David Schwalm, MD, of McMaster University in Hamilton, Ont., and colleagues. To help control hypertension in underserved populations, the researchers tested a care model involving nonphysician health workers (NPHWs), primary care physicians, and family members.
The HOPE4 study, presented at the annual congress of the European Society of Cardiology and published simultaneously in the Lancet, included 1,371 adults aged 50 years and older with new or poorly controlled hypertension from 30 communities in Colombia and Malaysia. Sixteen communities were randomized to usual care and 14 to an intervention. The intervention included community screening and treatment of cardiovascular disease risk factors by NPHWs, free medications recommended by NPHWs under physician supervision, and family support for treatment adherence.
After 12 months, the Framingham Risk Scores for 10-year cardiovascular disease risk were significantly lower in the intervention group, compared with the control group (–11.17% vs. –6.40%). In addition, the intervention group showed a significant 11.45 mm Hg greater reduction in systolic blood pressure and a significant 0.41 mmol/L reduction in LDL cholesterol, compared with controls (P less than .0001 for both measures).
Baseline characteristics were similar between the two groups. Approximately 74% of the participants had a history of poorly controlled hypertension, while the remaining patients had new hypertension diagnoses.
“NPHWs were found to be consistently accurate in their ability to identify cardiovascular risk (patient identified by NPHWs as having poorly controlled blood pressure and medication was indicated) and recommend appropriate therapies (antihypertensives and statin as per the study algorithm) when compared with the assessment by local primary care physicians,” the researchers wrote. The study shows how effectively NPHWs can help reduce cardiovascular disease risk at the community level with proper training, effective community outreach, and task sharing with physicians and family members, they noted.
The findings were limited by the inability to assess the safety of specific medications, but no differences in adverse events were reported between the intervention and control groups. Other limitations included the screening of controls for cardiovascular disease risk at baseline, which meant that controls may have modified their behavior as a result, the researchers noted. In addition, the study was not blinded and surrogate outcomes were used because of the short study duration and relatively small sample size, they said.
However, the results support the use of a comprehensive, NPHW-led model, and “the HOPE 4 strategy could help to attain the UN General Assembly Action Plan for a one-third reduction in premature mortality from cardiovascular disease” by 2030, the researchers concluded.
The study was supported by the Canadian Institutes of Health Research; Grand Challenges Canada; Ontario SPOR Support Unit and the Ontario Ministry of Health and Long-Term Care; Boehringer Ingelheim; Department of Management of Non-Communicable Diseases, World Health Organization; and the Population Health Research Institute. Lead author Dr. Schwalm and several coauthors disclosed grants to their institutions for this study from the Canadian Institutes of Health Research, Ontario Ministry of Health and Long-Term Care, Boehringer Ingelheim, and the Department of Management of Non-Communicable Diseases, WHO.
SOURCE: Schwalm J-D et al. Lancet. 2019 Sept 2. doi: http://dx.doi.org/10.1016/ S0140-6736(19)31949-X.
A community-based care model to control hypertension led by nonphysician health care workers significantly reduced cardiovascular disease risk over 12 months, data from a cluster-controlled randomized study has shown.
Hypertension remains the most common risk factor for cardiovascular disease, but fewer than 20% of individuals with hypertension have their blood pressure controlled, wrote Jon-David Schwalm, MD, of McMaster University in Hamilton, Ont., and colleagues. To help control hypertension in underserved populations, the researchers tested a care model involving nonphysician health workers (NPHWs), primary care physicians, and family members.
The HOPE4 study, presented at the annual congress of the European Society of Cardiology and published simultaneously in the Lancet, included 1,371 adults aged 50 years and older with new or poorly controlled hypertension from 30 communities in Colombia and Malaysia. Sixteen communities were randomized to usual care and 14 to an intervention. The intervention included community screening and treatment of cardiovascular disease risk factors by NPHWs, free medications recommended by NPHWs under physician supervision, and family support for treatment adherence.
After 12 months, the Framingham Risk Scores for 10-year cardiovascular disease risk were significantly lower in the intervention group, compared with the control group (–11.17% vs. –6.40%). In addition, the intervention group showed a significant 11.45 mm Hg greater reduction in systolic blood pressure and a significant 0.41 mmol/L reduction in LDL cholesterol, compared with controls (P less than .0001 for both measures).
Baseline characteristics were similar between the two groups. Approximately 74% of the participants had a history of poorly controlled hypertension, while the remaining patients had new hypertension diagnoses.
“NPHWs were found to be consistently accurate in their ability to identify cardiovascular risk (patient identified by NPHWs as having poorly controlled blood pressure and medication was indicated) and recommend appropriate therapies (antihypertensives and statin as per the study algorithm) when compared with the assessment by local primary care physicians,” the researchers wrote. The study shows how effectively NPHWs can help reduce cardiovascular disease risk at the community level with proper training, effective community outreach, and task sharing with physicians and family members, they noted.
The findings were limited by the inability to assess the safety of specific medications, but no differences in adverse events were reported between the intervention and control groups. Other limitations included the screening of controls for cardiovascular disease risk at baseline, which meant that controls may have modified their behavior as a result, the researchers noted. In addition, the study was not blinded and surrogate outcomes were used because of the short study duration and relatively small sample size, they said.
However, the results support the use of a comprehensive, NPHW-led model, and “the HOPE 4 strategy could help to attain the UN General Assembly Action Plan for a one-third reduction in premature mortality from cardiovascular disease” by 2030, the researchers concluded.
The study was supported by the Canadian Institutes of Health Research; Grand Challenges Canada; Ontario SPOR Support Unit and the Ontario Ministry of Health and Long-Term Care; Boehringer Ingelheim; Department of Management of Non-Communicable Diseases, World Health Organization; and the Population Health Research Institute. Lead author Dr. Schwalm and several coauthors disclosed grants to their institutions for this study from the Canadian Institutes of Health Research, Ontario Ministry of Health and Long-Term Care, Boehringer Ingelheim, and the Department of Management of Non-Communicable Diseases, WHO.
SOURCE: Schwalm J-D et al. Lancet. 2019 Sept 2. doi: http://dx.doi.org/10.1016/ S0140-6736(19)31949-X.
A community-based care model to control hypertension led by nonphysician health care workers significantly reduced cardiovascular disease risk over 12 months, data from a cluster-controlled randomized study has shown.
Hypertension remains the most common risk factor for cardiovascular disease, but fewer than 20% of individuals with hypertension have their blood pressure controlled, wrote Jon-David Schwalm, MD, of McMaster University in Hamilton, Ont., and colleagues. To help control hypertension in underserved populations, the researchers tested a care model involving nonphysician health workers (NPHWs), primary care physicians, and family members.
The HOPE4 study, presented at the annual congress of the European Society of Cardiology and published simultaneously in the Lancet, included 1,371 adults aged 50 years and older with new or poorly controlled hypertension from 30 communities in Colombia and Malaysia. Sixteen communities were randomized to usual care and 14 to an intervention. The intervention included community screening and treatment of cardiovascular disease risk factors by NPHWs, free medications recommended by NPHWs under physician supervision, and family support for treatment adherence.
After 12 months, the Framingham Risk Scores for 10-year cardiovascular disease risk were significantly lower in the intervention group, compared with the control group (–11.17% vs. –6.40%). In addition, the intervention group showed a significant 11.45 mm Hg greater reduction in systolic blood pressure and a significant 0.41 mmol/L reduction in LDL cholesterol, compared with controls (P less than .0001 for both measures).
Baseline characteristics were similar between the two groups. Approximately 74% of the participants had a history of poorly controlled hypertension, while the remaining patients had new hypertension diagnoses.
“NPHWs were found to be consistently accurate in their ability to identify cardiovascular risk (patient identified by NPHWs as having poorly controlled blood pressure and medication was indicated) and recommend appropriate therapies (antihypertensives and statin as per the study algorithm) when compared with the assessment by local primary care physicians,” the researchers wrote. The study shows how effectively NPHWs can help reduce cardiovascular disease risk at the community level with proper training, effective community outreach, and task sharing with physicians and family members, they noted.
The findings were limited by the inability to assess the safety of specific medications, but no differences in adverse events were reported between the intervention and control groups. Other limitations included the screening of controls for cardiovascular disease risk at baseline, which meant that controls may have modified their behavior as a result, the researchers noted. In addition, the study was not blinded and surrogate outcomes were used because of the short study duration and relatively small sample size, they said.
However, the results support the use of a comprehensive, NPHW-led model, and “the HOPE 4 strategy could help to attain the UN General Assembly Action Plan for a one-third reduction in premature mortality from cardiovascular disease” by 2030, the researchers concluded.
The study was supported by the Canadian Institutes of Health Research; Grand Challenges Canada; Ontario SPOR Support Unit and the Ontario Ministry of Health and Long-Term Care; Boehringer Ingelheim; Department of Management of Non-Communicable Diseases, World Health Organization; and the Population Health Research Institute. Lead author Dr. Schwalm and several coauthors disclosed grants to their institutions for this study from the Canadian Institutes of Health Research, Ontario Ministry of Health and Long-Term Care, Boehringer Ingelheim, and the Department of Management of Non-Communicable Diseases, WHO.
SOURCE: Schwalm J-D et al. Lancet. 2019 Sept 2. doi: http://dx.doi.org/10.1016/ S0140-6736(19)31949-X.
AT THE ESC CONGRESS 2019
Key clinical point: A community-based model for managing hypertension significantly improved blood pressure and reduced cardiovascular disease risk in adults with hypertension.
Major finding: Framingham Risk Scores decreased by –11.17% in the intervention group vs. –6.40% in the control group (P less than ·0001).
Study details: The data come from a community-based, randomized, controlled trial of 1,371 adults with new or poorly controlled hypertension.
Disclosures: The study was supported by the Canadian Institutes of Health Research: Grand Challenges Canada: Ontario SPOR Support Unit and the Ontario Ministry of Health and Long-Term Care; Boehringer Ingelheim; Department of Management of Non-Communicable Diseases, WHO; and Population Health Research Institute. Lead author Dr. Schwalm and several coauthors disclosed grants to their institutions for this study from the Canadian Institutes of Health Research, Ontario Ministry of Health and Long-Term Care, Boehringer Ingelheim, and the Department of Management of Non-Communicable Diseases, WHO.
Source: Schwalm J-D et al. Lancet. 2019 Sept 2. doi: http://dx.doi.org/10.1016/ S0140-6736(19)31949-X.
Prior DMARD use in RA may limit adalimumab treatment response
A history of using multiple conventional synthetic disease-modifying antirheumatic drugs (DMARDs) is a key predictor for poorer response to adalimumab therapy in rheumatoid arthritis patients, according to data from a pair of studies with a total of 274 patients.
Although patients with RA who have failed methotrexate or tumor necrosis factor inhibitor therapy respond less than methotrexate-naive patients, “it remains unknown if response to the first biologic DMARD, in particular a [tumor necrosis factor inhibitor], depends on disease duration or prior numbers of failed [conventional synthetic] DMARDs,” wrote Daniel Aletaha, MD, of the Medical University of Vienna and colleagues.
In a study published in Annals of the Rheumatic Diseases, the researchers reviewed data from two randomized, controlled trials of patients with RA. In the larger trial of 207 adults (known as DE019), past use of two or more conventional synthetic DMARDs was associated with less improvement in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) after 24 weeks of adalimumab (Humira), compared with use of one or no DMARDs (–1.8 vs. –2.2, respectively). Similarly, disease activity and disability scores improved significantly less in patients who had used two or more DMARDs, compared with those who used one or no DMARDs, according to the Simplified Disease Activity Index (SDAI; –22.1 vs. –26.9) and the Health Assessment Questionnaire Disability Index (HAQ-DI; –0.43 vs. –0.64).
The researchers also examined the role of disease duration on treatment response. Overall, patients with disease duration greater than 10 years showed more improvement at 24 weeks than did those with disease duration less than 1 year, based on HAQ-DI scores (1.1 vs. 0.7), but final scores on the SDAI and DAS28-CRP were not significantly different between those with disease duration greater than 10 years and those with duration of less than 1 year. These results suggest that the impact of DMARDs holds true regardless of disease duration, the researchers noted.
The findings were similar with regard to number of prior conventional synthetic DMARDs and the effects of disease duration in the second trial of 67 patients, known as the ARMADA study.
The study findings were limited by several factors, including the post hoc analysis design, use of only adalimumab data, and the small number of patients in several subgroups, the researchers noted. However, the results support the need for more standardized treatment guidelines and suggest that RA patients who fail to respond to methotrexate soon after RA diagnosis may benefit most from adding adalimumab, they said.
“Furthermore, these findings should be considered in future trials when defining inclusion criteria not only by duration of disease but also by number of prior DMARDs,” they concluded.
The study was sponsored by AbbVie, which markets adalimumab. Dr. Aletaha disclosed grants and consulting fees from AbbVie, as well as other pharmaceutical companies. Four of the authors were current or former employees of AbbVie, and some other authors also reported financial relationships with the company.
SOURCE: Aletaha D et al. Ann Rheum Dis. 2019 Aug 21. doi: 10.1136/annrheumdis-2018-214918.
A history of using multiple conventional synthetic disease-modifying antirheumatic drugs (DMARDs) is a key predictor for poorer response to adalimumab therapy in rheumatoid arthritis patients, according to data from a pair of studies with a total of 274 patients.
Although patients with RA who have failed methotrexate or tumor necrosis factor inhibitor therapy respond less than methotrexate-naive patients, “it remains unknown if response to the first biologic DMARD, in particular a [tumor necrosis factor inhibitor], depends on disease duration or prior numbers of failed [conventional synthetic] DMARDs,” wrote Daniel Aletaha, MD, of the Medical University of Vienna and colleagues.
In a study published in Annals of the Rheumatic Diseases, the researchers reviewed data from two randomized, controlled trials of patients with RA. In the larger trial of 207 adults (known as DE019), past use of two or more conventional synthetic DMARDs was associated with less improvement in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) after 24 weeks of adalimumab (Humira), compared with use of one or no DMARDs (–1.8 vs. –2.2, respectively). Similarly, disease activity and disability scores improved significantly less in patients who had used two or more DMARDs, compared with those who used one or no DMARDs, according to the Simplified Disease Activity Index (SDAI; –22.1 vs. –26.9) and the Health Assessment Questionnaire Disability Index (HAQ-DI; –0.43 vs. –0.64).
The researchers also examined the role of disease duration on treatment response. Overall, patients with disease duration greater than 10 years showed more improvement at 24 weeks than did those with disease duration less than 1 year, based on HAQ-DI scores (1.1 vs. 0.7), but final scores on the SDAI and DAS28-CRP were not significantly different between those with disease duration greater than 10 years and those with duration of less than 1 year. These results suggest that the impact of DMARDs holds true regardless of disease duration, the researchers noted.
The findings were similar with regard to number of prior conventional synthetic DMARDs and the effects of disease duration in the second trial of 67 patients, known as the ARMADA study.
The study findings were limited by several factors, including the post hoc analysis design, use of only adalimumab data, and the small number of patients in several subgroups, the researchers noted. However, the results support the need for more standardized treatment guidelines and suggest that RA patients who fail to respond to methotrexate soon after RA diagnosis may benefit most from adding adalimumab, they said.
“Furthermore, these findings should be considered in future trials when defining inclusion criteria not only by duration of disease but also by number of prior DMARDs,” they concluded.
The study was sponsored by AbbVie, which markets adalimumab. Dr. Aletaha disclosed grants and consulting fees from AbbVie, as well as other pharmaceutical companies. Four of the authors were current or former employees of AbbVie, and some other authors also reported financial relationships with the company.
SOURCE: Aletaha D et al. Ann Rheum Dis. 2019 Aug 21. doi: 10.1136/annrheumdis-2018-214918.
A history of using multiple conventional synthetic disease-modifying antirheumatic drugs (DMARDs) is a key predictor for poorer response to adalimumab therapy in rheumatoid arthritis patients, according to data from a pair of studies with a total of 274 patients.
Although patients with RA who have failed methotrexate or tumor necrosis factor inhibitor therapy respond less than methotrexate-naive patients, “it remains unknown if response to the first biologic DMARD, in particular a [tumor necrosis factor inhibitor], depends on disease duration or prior numbers of failed [conventional synthetic] DMARDs,” wrote Daniel Aletaha, MD, of the Medical University of Vienna and colleagues.
In a study published in Annals of the Rheumatic Diseases, the researchers reviewed data from two randomized, controlled trials of patients with RA. In the larger trial of 207 adults (known as DE019), past use of two or more conventional synthetic DMARDs was associated with less improvement in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) after 24 weeks of adalimumab (Humira), compared with use of one or no DMARDs (–1.8 vs. –2.2, respectively). Similarly, disease activity and disability scores improved significantly less in patients who had used two or more DMARDs, compared with those who used one or no DMARDs, according to the Simplified Disease Activity Index (SDAI; –22.1 vs. –26.9) and the Health Assessment Questionnaire Disability Index (HAQ-DI; –0.43 vs. –0.64).
The researchers also examined the role of disease duration on treatment response. Overall, patients with disease duration greater than 10 years showed more improvement at 24 weeks than did those with disease duration less than 1 year, based on HAQ-DI scores (1.1 vs. 0.7), but final scores on the SDAI and DAS28-CRP were not significantly different between those with disease duration greater than 10 years and those with duration of less than 1 year. These results suggest that the impact of DMARDs holds true regardless of disease duration, the researchers noted.
The findings were similar with regard to number of prior conventional synthetic DMARDs and the effects of disease duration in the second trial of 67 patients, known as the ARMADA study.
The study findings were limited by several factors, including the post hoc analysis design, use of only adalimumab data, and the small number of patients in several subgroups, the researchers noted. However, the results support the need for more standardized treatment guidelines and suggest that RA patients who fail to respond to methotrexate soon after RA diagnosis may benefit most from adding adalimumab, they said.
“Furthermore, these findings should be considered in future trials when defining inclusion criteria not only by duration of disease but also by number of prior DMARDs,” they concluded.
The study was sponsored by AbbVie, which markets adalimumab. Dr. Aletaha disclosed grants and consulting fees from AbbVie, as well as other pharmaceutical companies. Four of the authors were current or former employees of AbbVie, and some other authors also reported financial relationships with the company.
SOURCE: Aletaha D et al. Ann Rheum Dis. 2019 Aug 21. doi: 10.1136/annrheumdis-2018-214918.
FROM ANNALS OF THE RHEUMATIC DISEASES