Bianca Nogrady

Suboptimal dosing of renin-angiotensin-aldosterone system (RAAS) inhibitors to reduce the risk of hyperkalemia could increase the risk of major adverse cardiac events (MACE) and all-cause mortality in patients with chronic kidney disease (CKD) or heart failure.

HYWARDS/Thinkstock

Researchers reported the outcomes of an observational study that explored the real-world associations between RAAS inhibitor dose, hyperkalemia, and clinical outcomes.

RAAS inhibitors – such as ACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists – are known to reduce potassium excretion and therefore increase the risk of high potassium levels.

Dr. Cecilia Linde, from the Karolinska University Hospital and Karolinska Institutet in Stockholm, and coauthors wrote that management of serum potassium levels often requires reducing the dosage of RAAS inhibitors or stopping them altogether. However, this is also associated with risks in patients with heart failure or CKD.

In this study, researchers looked at data from 100,572 people with nondialysis CKD and 13,113 with new-onset heart failure who were prescribed RAAS inhibitors during 2006-2015.

Overall, 58% of patients with CKD and 63% of patients with heart failure spent the majority of follow-up on prescribed optimal doses of RAAS inhibitors – defined as at least 50% of the guidelines-recommended dose.

Patients with hyperkalemia were more likely to have down-titrations or discontinue their RAAS inhibitors, and this increased with increasing hyperkalemia severity.

The study found consistently lower mortality rates among patients who spent most of their follow-up time on at least 50% of the guideline-recommended dose of RAAS inhibitors.

In patients with CKD, mortality rates were 7.2 deaths per 1,000 patient-years in those taking at least 50% of the recommended dose, compared with 57.7 deaths per 1,000 patient-years for those on suboptimal doses. The rates of MACE were 73 and 130 per 1,000 patient-years, respectively.

The differences were even more pronounced in patients with heart failure. Those taking at least 50% of the recommended dose had mortality rates of 12.5 per 1000 patient-years, compared with 141.7 among those on suboptimal doses. The rates of MACE were 148.5 and 290.4, respectively.

“The results highlight the potential negative impact of suboptimal RAASi dosing, indicate the generalizability of [European Society of Cardiology–recommended] RAASi doses in HF to CKD patients, and emphasize the need for strategies that allow patients to be maintained on appropriate therapy, avoiding RAASi dose modification or discontinuation,” the authors wrote.

The study was funded by AstraZeneca. One author was an employee and stockholder of AstraZeneca, and five authors declared funding and support from the pharmaceutical sector, including AstraZeneca.

SOURCE: Linde C et al. J Am Heart Assoc. 2019 Nov 12. doi: 10.1161/JAHA.119.012655.

Suboptimal dosing of renin-angiotensin-aldosterone system (RAAS) inhibitors to reduce the risk of hyperkalemia could increase the risk of major adverse cardiac events (MACE) and all-cause mortality in patients with chronic kidney disease (CKD) or heart failure.

HYWARDS/Thinkstock

Researchers reported the outcomes of an observational study that explored the real-world associations between RAAS inhibitor dose, hyperkalemia, and clinical outcomes.

RAAS inhibitors – such as ACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists – are known to reduce potassium excretion and therefore increase the risk of high potassium levels.

Dr. Cecilia Linde, from the Karolinska University Hospital and Karolinska Institutet in Stockholm, and coauthors wrote that management of serum potassium levels often requires reducing the dosage of RAAS inhibitors or stopping them altogether. However, this is also associated with risks in patients with heart failure or CKD.

In this study, researchers looked at data from 100,572 people with nondialysis CKD and 13,113 with new-onset heart failure who were prescribed RAAS inhibitors during 2006-2015.

Overall, 58% of patients with CKD and 63% of patients with heart failure spent the majority of follow-up on prescribed optimal doses of RAAS inhibitors – defined as at least 50% of the guidelines-recommended dose.

Patients with hyperkalemia were more likely to have down-titrations or discontinue their RAAS inhibitors, and this increased with increasing hyperkalemia severity.

The study found consistently lower mortality rates among patients who spent most of their follow-up time on at least 50% of the guideline-recommended dose of RAAS inhibitors.

In patients with CKD, mortality rates were 7.2 deaths per 1,000 patient-years in those taking at least 50% of the recommended dose, compared with 57.7 deaths per 1,000 patient-years for those on suboptimal doses. The rates of MACE were 73 and 130 per 1,000 patient-years, respectively.

The differences were even more pronounced in patients with heart failure. Those taking at least 50% of the recommended dose had mortality rates of 12.5 per 1000 patient-years, compared with 141.7 among those on suboptimal doses. The rates of MACE were 148.5 and 290.4, respectively.

“The results highlight the potential negative impact of suboptimal RAASi dosing, indicate the generalizability of [European Society of Cardiology–recommended] RAASi doses in HF to CKD patients, and emphasize the need for strategies that allow patients to be maintained on appropriate therapy, avoiding RAASi dose modification or discontinuation,” the authors wrote.

The study was funded by AstraZeneca. One author was an employee and stockholder of AstraZeneca, and five authors declared funding and support from the pharmaceutical sector, including AstraZeneca.

SOURCE: Linde C et al. J Am Heart Assoc. 2019 Nov 12. doi: 10.1161/JAHA.119.012655.

Suboptimal dosing of renin-angiotensin-aldosterone system (RAAS) inhibitors to reduce the risk of hyperkalemia could increase the risk of major adverse cardiac events (MACE) and all-cause mortality in patients with chronic kidney disease (CKD) or heart failure.

HYWARDS/Thinkstock

Researchers reported the outcomes of an observational study that explored the real-world associations between RAAS inhibitor dose, hyperkalemia, and clinical outcomes.

RAAS inhibitors – such as ACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists – are known to reduce potassium excretion and therefore increase the risk of high potassium levels.

Dr. Cecilia Linde, from the Karolinska University Hospital and Karolinska Institutet in Stockholm, and coauthors wrote that management of serum potassium levels often requires reducing the dosage of RAAS inhibitors or stopping them altogether. However, this is also associated with risks in patients with heart failure or CKD.

In this study, researchers looked at data from 100,572 people with nondialysis CKD and 13,113 with new-onset heart failure who were prescribed RAAS inhibitors during 2006-2015.

Overall, 58% of patients with CKD and 63% of patients with heart failure spent the majority of follow-up on prescribed optimal doses of RAAS inhibitors – defined as at least 50% of the guidelines-recommended dose.

Patients with hyperkalemia were more likely to have down-titrations or discontinue their RAAS inhibitors, and this increased with increasing hyperkalemia severity.

The study found consistently lower mortality rates among patients who spent most of their follow-up time on at least 50% of the guideline-recommended dose of RAAS inhibitors.

In patients with CKD, mortality rates were 7.2 deaths per 1,000 patient-years in those taking at least 50% of the recommended dose, compared with 57.7 deaths per 1,000 patient-years for those on suboptimal doses. The rates of MACE were 73 and 130 per 1,000 patient-years, respectively.

The differences were even more pronounced in patients with heart failure. Those taking at least 50% of the recommended dose had mortality rates of 12.5 per 1000 patient-years, compared with 141.7 among those on suboptimal doses. The rates of MACE were 148.5 and 290.4, respectively.

“The results highlight the potential negative impact of suboptimal RAASi dosing, indicate the generalizability of [European Society of Cardiology–recommended] RAASi doses in HF to CKD patients, and emphasize the need for strategies that allow patients to be maintained on appropriate therapy, avoiding RAASi dose modification or discontinuation,” the authors wrote.

The study was funded by AstraZeneca. One author was an employee and stockholder of AstraZeneca, and five authors declared funding and support from the pharmaceutical sector, including AstraZeneca.

SOURCE: Linde C et al. J Am Heart Assoc. 2019 Nov 12. doi: 10.1161/JAHA.119.012655.

The greater reduction in major adverse cardiovascular events with complete revascularization for ST-segment elevation myocardial infarction, compared with target-lesion only, persists for many years after the procedure, a study has found.

American Heart Association

In the Journal of the American College of Cardiology, researchers report the outcomes of long-term follow-up of 272 patients admitted with ST-segment elevation myocardial infarction, who were enrolled in CvLPRIT (Complete Versus Lesion-Only Primary PCI Trial).

The trial randomized patients to complete revascularization or infarct-related artery revascularization only, with a median follow-up of 5.6 years after randomization.

Anthony H. Gershlick, MD, from the University of Leicester (England) and NIHR Leicester Biomedical Research Centre, and coauthors highlighted conflicting evidence on the relative benefit of complete revascularization, compared with revascularization focused on the culprit artery only.

“The aim of this study was, for the first time, to determine if there is a sustained benefit in favor of multivessel percutaneous coronary intervention [PCI] in the longer term,” they wrote.

In the group of patients who underwent complete revascularization, the composite major adverse cardiovascular event rate at 5.6 years was 43% lower than in the infarct-related artery revascularization group (24.0 vs. 37.7%; P = .0079), according to the intention-to-treat analysis.

The complete revascularization group also showed a significantly lower rate of the secondary composite endpoint of death or MI, which was 10% in the complete revascularization group and 18.5% in the target lesion group (hazard ratio, 0.47; P = .0175).

“Our data suggest that total revascularization, known to have benefits in various cohorts with coronary artery disease, should now probably be considered the standard of care in suitable patients with STEMI with multivessel disease,” they wrote.

However they did find that the rates of ischemia-driven revascularization were not significantly different between the two groups at the long-term follow-up.

The authors also did an analysis of outcomes from the end of the original 12-month study to the final follow-up point. This showed a nonsignificant trend toward a lower rate of major adverse cardiovascular events in the group who underwent complete revascularization; 17.1%, compared with 23.3% in the infarct-related artery revascularization group. The rates of the individual components of that primary endpoint also trended toward lower rates in individuals with complete revascularization.

Similarly, the rates of ischemia-driven revascularization were similar in both groups when analyzed after the 12-month mark, and the authors noted that the need for ischemia-driven revascularization was equally spread between infarct-related arteries and non–infarct-related arteries.

The authors commented that the event rate curves for the two groups remained separated even to the median follow-up point of 5.6 years, showing that the highly significant difference in major adverse cardiovascular event rates between the two groups persists.

“All of these data suggest that lower rates of events seen within 12 months do translate into longer-term benefit, predominantly through nonattenuation of benefit,” they wrote.

They speculated that the longer-term benefit of early complete revascularization could be the result of improvement in blood flow to areas around the original site of ischemia, and because it managed lesions in nontarget vessels in patients with disease in multiple arteries.

“Certainly, given that both the MRI and nuclear medicine substudies of CvLPRIT showed no difference between the groups in infarct size (at 1 week) and no difference in ischemic burden at 6 weeks, the benefit we have demonstrated does not appear to be explained simply in terms of ischemic burden being dealt with prophylactically in the complete group,” they wrote.

Commenting on the study’s limitations, the authors noted that the overall numbers of patients were small, and that the use of all-cause mortality rather than cardiovascular mortality may affect the interpretation of results.

The CvLPRIT study was funded by the British Heart Foundation, with support from the National Institute for Health Research Comprehensive Local Research Networks. No conflicts of interest were declared.

SOURCE: Gershlick A et al. J Am Coll Cardiol. 2019 Dec 16;74:3083-9.

The greater reduction in major adverse cardiovascular events with complete revascularization for ST-segment elevation myocardial infarction, compared with target-lesion only, persists for many years after the procedure, a study has found.

American Heart Association

In the Journal of the American College of Cardiology, researchers report the outcomes of long-term follow-up of 272 patients admitted with ST-segment elevation myocardial infarction, who were enrolled in CvLPRIT (Complete Versus Lesion-Only Primary PCI Trial).

The trial randomized patients to complete revascularization or infarct-related artery revascularization only, with a median follow-up of 5.6 years after randomization.

Anthony H. Gershlick, MD, from the University of Leicester (England) and NIHR Leicester Biomedical Research Centre, and coauthors highlighted conflicting evidence on the relative benefit of complete revascularization, compared with revascularization focused on the culprit artery only.

“The aim of this study was, for the first time, to determine if there is a sustained benefit in favor of multivessel percutaneous coronary intervention [PCI] in the longer term,” they wrote.

In the group of patients who underwent complete revascularization, the composite major adverse cardiovascular event rate at 5.6 years was 43% lower than in the infarct-related artery revascularization group (24.0 vs. 37.7%; P = .0079), according to the intention-to-treat analysis.

The complete revascularization group also showed a significantly lower rate of the secondary composite endpoint of death or MI, which was 10% in the complete revascularization group and 18.5% in the target lesion group (hazard ratio, 0.47; P = .0175).

“Our data suggest that total revascularization, known to have benefits in various cohorts with coronary artery disease, should now probably be considered the standard of care in suitable patients with STEMI with multivessel disease,” they wrote.

However they did find that the rates of ischemia-driven revascularization were not significantly different between the two groups at the long-term follow-up.

The authors also did an analysis of outcomes from the end of the original 12-month study to the final follow-up point. This showed a nonsignificant trend toward a lower rate of major adverse cardiovascular events in the group who underwent complete revascularization; 17.1%, compared with 23.3% in the infarct-related artery revascularization group. The rates of the individual components of that primary endpoint also trended toward lower rates in individuals with complete revascularization.

Similarly, the rates of ischemia-driven revascularization were similar in both groups when analyzed after the 12-month mark, and the authors noted that the need for ischemia-driven revascularization was equally spread between infarct-related arteries and non–infarct-related arteries.

The authors commented that the event rate curves for the two groups remained separated even to the median follow-up point of 5.6 years, showing that the highly significant difference in major adverse cardiovascular event rates between the two groups persists.

“All of these data suggest that lower rates of events seen within 12 months do translate into longer-term benefit, predominantly through nonattenuation of benefit,” they wrote.

They speculated that the longer-term benefit of early complete revascularization could be the result of improvement in blood flow to areas around the original site of ischemia, and because it managed lesions in nontarget vessels in patients with disease in multiple arteries.

“Certainly, given that both the MRI and nuclear medicine substudies of CvLPRIT showed no difference between the groups in infarct size (at 1 week) and no difference in ischemic burden at 6 weeks, the benefit we have demonstrated does not appear to be explained simply in terms of ischemic burden being dealt with prophylactically in the complete group,” they wrote.

Commenting on the study’s limitations, the authors noted that the overall numbers of patients were small, and that the use of all-cause mortality rather than cardiovascular mortality may affect the interpretation of results.

The CvLPRIT study was funded by the British Heart Foundation, with support from the National Institute for Health Research Comprehensive Local Research Networks. No conflicts of interest were declared.

SOURCE: Gershlick A et al. J Am Coll Cardiol. 2019 Dec 16;74:3083-9.

The greater reduction in major adverse cardiovascular events with complete revascularization for ST-segment elevation myocardial infarction, compared with target-lesion only, persists for many years after the procedure, a study has found.

American Heart Association

In the Journal of the American College of Cardiology, researchers report the outcomes of long-term follow-up of 272 patients admitted with ST-segment elevation myocardial infarction, who were enrolled in CvLPRIT (Complete Versus Lesion-Only Primary PCI Trial).

The trial randomized patients to complete revascularization or infarct-related artery revascularization only, with a median follow-up of 5.6 years after randomization.

Anthony H. Gershlick, MD, from the University of Leicester (England) and NIHR Leicester Biomedical Research Centre, and coauthors highlighted conflicting evidence on the relative benefit of complete revascularization, compared with revascularization focused on the culprit artery only.

“The aim of this study was, for the first time, to determine if there is a sustained benefit in favor of multivessel percutaneous coronary intervention [PCI] in the longer term,” they wrote.

In the group of patients who underwent complete revascularization, the composite major adverse cardiovascular event rate at 5.6 years was 43% lower than in the infarct-related artery revascularization group (24.0 vs. 37.7%; P = .0079), according to the intention-to-treat analysis.

The complete revascularization group also showed a significantly lower rate of the secondary composite endpoint of death or MI, which was 10% in the complete revascularization group and 18.5% in the target lesion group (hazard ratio, 0.47; P = .0175).

“Our data suggest that total revascularization, known to have benefits in various cohorts with coronary artery disease, should now probably be considered the standard of care in suitable patients with STEMI with multivessel disease,” they wrote.

However they did find that the rates of ischemia-driven revascularization were not significantly different between the two groups at the long-term follow-up.

The authors also did an analysis of outcomes from the end of the original 12-month study to the final follow-up point. This showed a nonsignificant trend toward a lower rate of major adverse cardiovascular events in the group who underwent complete revascularization; 17.1%, compared with 23.3% in the infarct-related artery revascularization group. The rates of the individual components of that primary endpoint also trended toward lower rates in individuals with complete revascularization.

Similarly, the rates of ischemia-driven revascularization were similar in both groups when analyzed after the 12-month mark, and the authors noted that the need for ischemia-driven revascularization was equally spread between infarct-related arteries and non–infarct-related arteries.

The authors commented that the event rate curves for the two groups remained separated even to the median follow-up point of 5.6 years, showing that the highly significant difference in major adverse cardiovascular event rates between the two groups persists.

“All of these data suggest that lower rates of events seen within 12 months do translate into longer-term benefit, predominantly through nonattenuation of benefit,” they wrote.

They speculated that the longer-term benefit of early complete revascularization could be the result of improvement in blood flow to areas around the original site of ischemia, and because it managed lesions in nontarget vessels in patients with disease in multiple arteries.

“Certainly, given that both the MRI and nuclear medicine substudies of CvLPRIT showed no difference between the groups in infarct size (at 1 week) and no difference in ischemic burden at 6 weeks, the benefit we have demonstrated does not appear to be explained simply in terms of ischemic burden being dealt with prophylactically in the complete group,” they wrote.

Commenting on the study’s limitations, the authors noted that the overall numbers of patients were small, and that the use of all-cause mortality rather than cardiovascular mortality may affect the interpretation of results.

The CvLPRIT study was funded by the British Heart Foundation, with support from the National Institute for Health Research Comprehensive Local Research Networks. No conflicts of interest were declared.

SOURCE: Gershlick A et al. J Am Coll Cardiol. 2019 Dec 16;74:3083-9.

Moderate reductions in kidney function in older women are associated with an increased short-term risk of fractures, according to a study published in Osteoporosis International.

However, the longitudinal, population-based cohort study did not find an association with fracture risk either in women older than 80 years or in those with worse kidney function.

“Since the kidneys regulate homeostasis of PTH [parathyroid hormone], phosphate, calcium, and vitamin D, any disruption in function can be expected to disturb bone remodeling and have implications for skeletal health,” wrote Linnea Malmgren, MD, and colleagues from Skåne University Hospital in Malmö, Sweden.

Previous studies have found that a large proportion of older women have reduced kidney function equivalent to a diagnosis of chronic kidney disease and that it is associated with bone loss. However, there have been few studies exploring that association in a population without a diagnosis of chronic kidney disease.

In their study, Dr. Malmgren and colleagues followed 981 women aged 75 years and 685 women aged 80 years, who underwent assessment of kidney function and bone mineral density and were followed up for fracture.

They found that women who experienced an osteoporotic fracture between the ages of 75 and 80 years had significantly lower baseline kidney function, compared with those who did not experience a fracture.

Compared with women with normal kidney function at age 75, women with intermediate kidney function (estimated glomerular filtration rate 45-59 mL/min per 1.73m²⁾ had a significant 2.21-fold higher risk of osteoporotic fracture within 2 years, a 1.51-fold higher risk up to 5 years, and an elevated risk of hip fracture.

A similar trend was seen in women with poor kidney function (eGFR less than 45 mL/min per 1.73m²), but it was not statistically significant.

The analysis also found that kidney function at age 80 years was not significantly associated with long-term fracture risk, nor was there a significant association for 10-year fracture risk in those aged 75 years.

Reduced kidney function was also associated with a higher fracture risk even in women without osteoporosis.

“As expected, fracture risk was high among those with osteoporosis, but risk seemed to further increase in women with both osteoporosis and reduced kidney function, compared with those with osteoporosis and normal function,” the authors reported.

“These findings indicate that implications for bone health and fracture risk might occur in the very common modest reduction of kidney function in the elderly, and also possibly before a diagnosis of CKD-MBD [chronic kidney disease–mineral and bone disorder].”

The study was supported by Lund University; the Swedish Research Council; Forte, Greta and Johan Kock Foundation; A. Påhlsson Foundation; A. Osterlund Foundation; H Järnhardt Foundation; King Gustav V 80-year Fund; Thelma Zoegas Foundation; Swedish Rheumatism Foundation; Skåne University Hospital Research Fund; and the Research and Development Council of Region Skåne, Sweden. No conflicts of interest were declared.

SOURCE: Malmgren L et al. Osteoporos Int. 2019 Nov 21. doi: 10.1007/s00198-019-05152-x.

Moderate reductions in kidney function in older women are associated with an increased short-term risk of fractures, according to a study published in Osteoporosis International.

However, the longitudinal, population-based cohort study did not find an association with fracture risk either in women older than 80 years or in those with worse kidney function.

“Since the kidneys regulate homeostasis of PTH [parathyroid hormone], phosphate, calcium, and vitamin D, any disruption in function can be expected to disturb bone remodeling and have implications for skeletal health,” wrote Linnea Malmgren, MD, and colleagues from Skåne University Hospital in Malmö, Sweden.

Previous studies have found that a large proportion of older women have reduced kidney function equivalent to a diagnosis of chronic kidney disease and that it is associated with bone loss. However, there have been few studies exploring that association in a population without a diagnosis of chronic kidney disease.

In their study, Dr. Malmgren and colleagues followed 981 women aged 75 years and 685 women aged 80 years, who underwent assessment of kidney function and bone mineral density and were followed up for fracture.

They found that women who experienced an osteoporotic fracture between the ages of 75 and 80 years had significantly lower baseline kidney function, compared with those who did not experience a fracture.

Compared with women with normal kidney function at age 75, women with intermediate kidney function (estimated glomerular filtration rate 45-59 mL/min per 1.73m²⁾ had a significant 2.21-fold higher risk of osteoporotic fracture within 2 years, a 1.51-fold higher risk up to 5 years, and an elevated risk of hip fracture.

A similar trend was seen in women with poor kidney function (eGFR less than 45 mL/min per 1.73m²), but it was not statistically significant.

The analysis also found that kidney function at age 80 years was not significantly associated with long-term fracture risk, nor was there a significant association for 10-year fracture risk in those aged 75 years.

Reduced kidney function was also associated with a higher fracture risk even in women without osteoporosis.

“As expected, fracture risk was high among those with osteoporosis, but risk seemed to further increase in women with both osteoporosis and reduced kidney function, compared with those with osteoporosis and normal function,” the authors reported.

“These findings indicate that implications for bone health and fracture risk might occur in the very common modest reduction of kidney function in the elderly, and also possibly before a diagnosis of CKD-MBD [chronic kidney disease–mineral and bone disorder].”

The study was supported by Lund University; the Swedish Research Council; Forte, Greta and Johan Kock Foundation; A. Påhlsson Foundation; A. Osterlund Foundation; H Järnhardt Foundation; King Gustav V 80-year Fund; Thelma Zoegas Foundation; Swedish Rheumatism Foundation; Skåne University Hospital Research Fund; and the Research and Development Council of Region Skåne, Sweden. No conflicts of interest were declared.

SOURCE: Malmgren L et al. Osteoporos Int. 2019 Nov 21. doi: 10.1007/s00198-019-05152-x.

Moderate reductions in kidney function in older women are associated with an increased short-term risk of fractures, according to a study published in Osteoporosis International.

However, the longitudinal, population-based cohort study did not find an association with fracture risk either in women older than 80 years or in those with worse kidney function.

“Since the kidneys regulate homeostasis of PTH [parathyroid hormone], phosphate, calcium, and vitamin D, any disruption in function can be expected to disturb bone remodeling and have implications for skeletal health,” wrote Linnea Malmgren, MD, and colleagues from Skåne University Hospital in Malmö, Sweden.

Previous studies have found that a large proportion of older women have reduced kidney function equivalent to a diagnosis of chronic kidney disease and that it is associated with bone loss. However, there have been few studies exploring that association in a population without a diagnosis of chronic kidney disease.

In their study, Dr. Malmgren and colleagues followed 981 women aged 75 years and 685 women aged 80 years, who underwent assessment of kidney function and bone mineral density and were followed up for fracture.

They found that women who experienced an osteoporotic fracture between the ages of 75 and 80 years had significantly lower baseline kidney function, compared with those who did not experience a fracture.

Compared with women with normal kidney function at age 75, women with intermediate kidney function (estimated glomerular filtration rate 45-59 mL/min per 1.73m²⁾ had a significant 2.21-fold higher risk of osteoporotic fracture within 2 years, a 1.51-fold higher risk up to 5 years, and an elevated risk of hip fracture.

A similar trend was seen in women with poor kidney function (eGFR less than 45 mL/min per 1.73m²), but it was not statistically significant.

The analysis also found that kidney function at age 80 years was not significantly associated with long-term fracture risk, nor was there a significant association for 10-year fracture risk in those aged 75 years.

Reduced kidney function was also associated with a higher fracture risk even in women without osteoporosis.

“As expected, fracture risk was high among those with osteoporosis, but risk seemed to further increase in women with both osteoporosis and reduced kidney function, compared with those with osteoporosis and normal function,” the authors reported.

“These findings indicate that implications for bone health and fracture risk might occur in the very common modest reduction of kidney function in the elderly, and also possibly before a diagnosis of CKD-MBD [chronic kidney disease–mineral and bone disorder].”

The study was supported by Lund University; the Swedish Research Council; Forte, Greta and Johan Kock Foundation; A. Påhlsson Foundation; A. Osterlund Foundation; H Järnhardt Foundation; King Gustav V 80-year Fund; Thelma Zoegas Foundation; Swedish Rheumatism Foundation; Skåne University Hospital Research Fund; and the Research and Development Council of Region Skåne, Sweden. No conflicts of interest were declared.

SOURCE: Malmgren L et al. Osteoporos Int. 2019 Nov 21. doi: 10.1007/s00198-019-05152-x.

Linking cancer registry data to health insurance claims databases could significantly improve the capture of cancer treatment data, investigators report.

“As the number of new chemotherapy agents and targeted drugs approved for cancer treatment increases, estimating the population-based survival differences related to these treatments is increasingly important,” wrote Mia Hashibe, PhD, from the Utah Cancer Registry, and coauthors in JCO Cancer Clinical Informatics.

In this study, researchers identified 13,533 reportable cancer diagnoses in the Utah Cancer Registry between January 2013 and June 2014, of which 10,759 (79.1%) had health claims data in the Utah all-payer claims database.

Among these 10,759 patients, 24.1% had identifiable claims for chemotherapy. By linking the registry with the health claims database, researchers were able to identify an additional 497 patients in the registry who received chemotherapy, 590 treated with hormone therapy, 326 treated with radiation therapy, and 1,190 treated with immunotherapy.

The addition of the health claims data increased the proportion of patients treated with chemotherapy to 27.6%, the proportion of patients treated hormone therapy increased from 14.1% to 18.8%, immunotherapy increased from 4.3% to 13.2%, and radiation therapy increased from 24.9% to 27.5%.

The health claims data was particularly comprehensive when it came to information about hormone therapy for breast cancer, chemotherapy for lung or colorectal cancer, radiation therapy in patients with lung or prostate cancer, and biologic therapy in patients with melanoma.

The health claims data was also able to provide more information about the chemotherapy agents used and the duration of treatment, the authors reported.

“Even after augmenting with APCD [all-payer claims data], there was an indication of under-reporting of chemotherapy for breast cancer by the cancer registry variable compared with abstraction,” the authors wrote. “A factor contributing to cancers that were coded as treated through the augmented cancer registry variable, but not from abstraction, was when the therapy was determined by the abstractor to not be the first course.”

However, the cancer registry did have some data about patient therapy that was not found in the health claims database.

The authors noted that this was a pilot study to see whether claims data could improve information on cancer treatment and link that data to information in cancer registries.

“Next steps will include routine linkage for additional years of diagnosis and incorporation of APCD information into registry treatment variables.”

The study was supported by the National Cancer Institute, the Centers for Disease Control and Prevention, the Huntsman Cancer Foundation, and the University of Utah, Salt Lake City. One author declared institutional funding from a pharmaceutical company. No other conflicts of interest were declared.

SOURCE: Hashibe M et al. JCO Clin Cancer Inform. 2019 Oct. doi: 10.1200/CCI.19.00027.

Linking cancer registry data to health insurance claims databases could significantly improve the capture of cancer treatment data, investigators report.

“As the number of new chemotherapy agents and targeted drugs approved for cancer treatment increases, estimating the population-based survival differences related to these treatments is increasingly important,” wrote Mia Hashibe, PhD, from the Utah Cancer Registry, and coauthors in JCO Cancer Clinical Informatics.

In this study, researchers identified 13,533 reportable cancer diagnoses in the Utah Cancer Registry between January 2013 and June 2014, of which 10,759 (79.1%) had health claims data in the Utah all-payer claims database.

Among these 10,759 patients, 24.1% had identifiable claims for chemotherapy. By linking the registry with the health claims database, researchers were able to identify an additional 497 patients in the registry who received chemotherapy, 590 treated with hormone therapy, 326 treated with radiation therapy, and 1,190 treated with immunotherapy.

The addition of the health claims data increased the proportion of patients treated with chemotherapy to 27.6%, the proportion of patients treated hormone therapy increased from 14.1% to 18.8%, immunotherapy increased from 4.3% to 13.2%, and radiation therapy increased from 24.9% to 27.5%.

The health claims data was particularly comprehensive when it came to information about hormone therapy for breast cancer, chemotherapy for lung or colorectal cancer, radiation therapy in patients with lung or prostate cancer, and biologic therapy in patients with melanoma.

The health claims data was also able to provide more information about the chemotherapy agents used and the duration of treatment, the authors reported.

“Even after augmenting with APCD [all-payer claims data], there was an indication of under-reporting of chemotherapy for breast cancer by the cancer registry variable compared with abstraction,” the authors wrote. “A factor contributing to cancers that were coded as treated through the augmented cancer registry variable, but not from abstraction, was when the therapy was determined by the abstractor to not be the first course.”

However, the cancer registry did have some data about patient therapy that was not found in the health claims database.

The authors noted that this was a pilot study to see whether claims data could improve information on cancer treatment and link that data to information in cancer registries.

“Next steps will include routine linkage for additional years of diagnosis and incorporation of APCD information into registry treatment variables.”

The study was supported by the National Cancer Institute, the Centers for Disease Control and Prevention, the Huntsman Cancer Foundation, and the University of Utah, Salt Lake City. One author declared institutional funding from a pharmaceutical company. No other conflicts of interest were declared.

SOURCE: Hashibe M et al. JCO Clin Cancer Inform. 2019 Oct. doi: 10.1200/CCI.19.00027.

Linking cancer registry data to health insurance claims databases could significantly improve the capture of cancer treatment data, investigators report.

“As the number of new chemotherapy agents and targeted drugs approved for cancer treatment increases, estimating the population-based survival differences related to these treatments is increasingly important,” wrote Mia Hashibe, PhD, from the Utah Cancer Registry, and coauthors in JCO Cancer Clinical Informatics.

In this study, researchers identified 13,533 reportable cancer diagnoses in the Utah Cancer Registry between January 2013 and June 2014, of which 10,759 (79.1%) had health claims data in the Utah all-payer claims database.

Among these 10,759 patients, 24.1% had identifiable claims for chemotherapy. By linking the registry with the health claims database, researchers were able to identify an additional 497 patients in the registry who received chemotherapy, 590 treated with hormone therapy, 326 treated with radiation therapy, and 1,190 treated with immunotherapy.

The addition of the health claims data increased the proportion of patients treated with chemotherapy to 27.6%, the proportion of patients treated hormone therapy increased from 14.1% to 18.8%, immunotherapy increased from 4.3% to 13.2%, and radiation therapy increased from 24.9% to 27.5%.

The health claims data was particularly comprehensive when it came to information about hormone therapy for breast cancer, chemotherapy for lung or colorectal cancer, radiation therapy in patients with lung or prostate cancer, and biologic therapy in patients with melanoma.

The health claims data was also able to provide more information about the chemotherapy agents used and the duration of treatment, the authors reported.

“Even after augmenting with APCD [all-payer claims data], there was an indication of under-reporting of chemotherapy for breast cancer by the cancer registry variable compared with abstraction,” the authors wrote. “A factor contributing to cancers that were coded as treated through the augmented cancer registry variable, but not from abstraction, was when the therapy was determined by the abstractor to not be the first course.”

However, the cancer registry did have some data about patient therapy that was not found in the health claims database.

The authors noted that this was a pilot study to see whether claims data could improve information on cancer treatment and link that data to information in cancer registries.

“Next steps will include routine linkage for additional years of diagnosis and incorporation of APCD information into registry treatment variables.”

The study was supported by the National Cancer Institute, the Centers for Disease Control and Prevention, the Huntsman Cancer Foundation, and the University of Utah, Salt Lake City. One author declared institutional funding from a pharmaceutical company. No other conflicts of interest were declared.

SOURCE: Hashibe M et al. JCO Clin Cancer Inform. 2019 Oct. doi: 10.1200/CCI.19.00027.

Women are more likely to experience acute toxic effects from chemoradiotherapy for rectal cancer than men, but this does not appear to negatively impact treatment adherence or outcomes, research suggests.

In a research letter published in JAMA Oncology, Markus Diefenhardt, MD, from the University of Frankfurt and coauthors wrote that, while the risk of toxic chemotherapy effects was known to be greater in women for a number of cancers, this association was relatively unexplored for rectal cancer.

The researchers performed a pooled analysis of data from two phase 3, randomized clinical trials, involving 1,016 patients with rectal cancer – 28.6% of whom were female – treated with fluorouracil-based chemoradiotherapy followed by surgery and adjuvant fluorouracil.

They found that women experienced significantly higher rates of leukopenia and diarrhea than men. Grade 3-4 leukopenia was experienced by 28.6% of women, compared with 20.5% of men, and grades 3-4 diarrhea was experienced by 17.2% of women, compared with 8.1% of men.

Despite this, the study found similar rates of adherence to treatment between men and women both for neoadjuvant and adjuvant chemoradiotherapy. Women also had similar rates of disease-free survival and overall survival as men, and there were no significant differences in local recurrence or distant metastases.

“Although to our knowledge no data support using different chemotherapy regimens for men and women with rectal cancer, increased awareness of a higher risk of toxic effects among women may facilitate refinement of fluorouracil-based chemoradiotherapy and adjuvant chemotherapy, such as tailored patient education, closer monitoring of adverse effects, and earlier introduction of supportive measures,” the authors wrote.

The authors proposed several possible explanations for the higher rate of toxic effects in women. For example, women may have lower levels of the enzyme dihydropyridine dehydrogenase, which catabolizes fluorouracil, which could result in overdosing of fluorouracil. Similarly, sex-specific body fat composition could also contribute to fluorouracil overdosing in women.

The study also saw fewer postoperative complications in women, which the authors suggested could be related to the lower rate of abdominoperineal resections in women.

The two clinical trials included in the study were funded by German Cancer Aid. One author declared funding from German Cancer Aid, another declared a range of honoraria, research fees and institutional funding from the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Diefendhardt M et al. JAMA Oncol. 2019 Dec 5. doi: 10.1001/jamaoncol.2019.5102.

Women are more likely to experience acute toxic effects from chemoradiotherapy for rectal cancer than men, but this does not appear to negatively impact treatment adherence or outcomes, research suggests.

In a research letter published in JAMA Oncology, Markus Diefenhardt, MD, from the University of Frankfurt and coauthors wrote that, while the risk of toxic chemotherapy effects was known to be greater in women for a number of cancers, this association was relatively unexplored for rectal cancer.

The researchers performed a pooled analysis of data from two phase 3, randomized clinical trials, involving 1,016 patients with rectal cancer – 28.6% of whom were female – treated with fluorouracil-based chemoradiotherapy followed by surgery and adjuvant fluorouracil.

They found that women experienced significantly higher rates of leukopenia and diarrhea than men. Grade 3-4 leukopenia was experienced by 28.6% of women, compared with 20.5% of men, and grades 3-4 diarrhea was experienced by 17.2% of women, compared with 8.1% of men.

Despite this, the study found similar rates of adherence to treatment between men and women both for neoadjuvant and adjuvant chemoradiotherapy. Women also had similar rates of disease-free survival and overall survival as men, and there were no significant differences in local recurrence or distant metastases.

“Although to our knowledge no data support using different chemotherapy regimens for men and women with rectal cancer, increased awareness of a higher risk of toxic effects among women may facilitate refinement of fluorouracil-based chemoradiotherapy and adjuvant chemotherapy, such as tailored patient education, closer monitoring of adverse effects, and earlier introduction of supportive measures,” the authors wrote.

The authors proposed several possible explanations for the higher rate of toxic effects in women. For example, women may have lower levels of the enzyme dihydropyridine dehydrogenase, which catabolizes fluorouracil, which could result in overdosing of fluorouracil. Similarly, sex-specific body fat composition could also contribute to fluorouracil overdosing in women.

The study also saw fewer postoperative complications in women, which the authors suggested could be related to the lower rate of abdominoperineal resections in women.

The two clinical trials included in the study were funded by German Cancer Aid. One author declared funding from German Cancer Aid, another declared a range of honoraria, research fees and institutional funding from the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Diefendhardt M et al. JAMA Oncol. 2019 Dec 5. doi: 10.1001/jamaoncol.2019.5102.

Women are more likely to experience acute toxic effects from chemoradiotherapy for rectal cancer than men, but this does not appear to negatively impact treatment adherence or outcomes, research suggests.

In a research letter published in JAMA Oncology, Markus Diefenhardt, MD, from the University of Frankfurt and coauthors wrote that, while the risk of toxic chemotherapy effects was known to be greater in women for a number of cancers, this association was relatively unexplored for rectal cancer.

The researchers performed a pooled analysis of data from two phase 3, randomized clinical trials, involving 1,016 patients with rectal cancer – 28.6% of whom were female – treated with fluorouracil-based chemoradiotherapy followed by surgery and adjuvant fluorouracil.

They found that women experienced significantly higher rates of leukopenia and diarrhea than men. Grade 3-4 leukopenia was experienced by 28.6% of women, compared with 20.5% of men, and grades 3-4 diarrhea was experienced by 17.2% of women, compared with 8.1% of men.

Despite this, the study found similar rates of adherence to treatment between men and women both for neoadjuvant and adjuvant chemoradiotherapy. Women also had similar rates of disease-free survival and overall survival as men, and there were no significant differences in local recurrence or distant metastases.

“Although to our knowledge no data support using different chemotherapy regimens for men and women with rectal cancer, increased awareness of a higher risk of toxic effects among women may facilitate refinement of fluorouracil-based chemoradiotherapy and adjuvant chemotherapy, such as tailored patient education, closer monitoring of adverse effects, and earlier introduction of supportive measures,” the authors wrote.

The authors proposed several possible explanations for the higher rate of toxic effects in women. For example, women may have lower levels of the enzyme dihydropyridine dehydrogenase, which catabolizes fluorouracil, which could result in overdosing of fluorouracil. Similarly, sex-specific body fat composition could also contribute to fluorouracil overdosing in women.

The study also saw fewer postoperative complications in women, which the authors suggested could be related to the lower rate of abdominoperineal resections in women.

The two clinical trials included in the study were funded by German Cancer Aid. One author declared funding from German Cancer Aid, another declared a range of honoraria, research fees and institutional funding from the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Diefendhardt M et al. JAMA Oncol. 2019 Dec 5. doi: 10.1001/jamaoncol.2019.5102.

Certain types of oral antibiotics seem to be associated with an elevated risk of Parkinson’s disease with a delay that is consistent with the proposed duration of a prodromal period, according to a report published in Movement Disorders. Associations were found for broad-spectrum antibiotics and those that act against anaerobic bacteria and fungi. The timing of antibiotic exposure also seemed to matter.

In a nationwide case-control study, Finnish researchers compared data on antibiotic use in 13,976 individuals diagnosed with Parkinson’s disease between 1998 and 2014 with antibiotic-use data from 40,697 controls. The strongest connection with Parkinson’s disease risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10-15 years before the index date, and antifungal medications 1-5 years before the index date were positively associated with Parkinson’s disease risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics.

Tuomas H. Mertsalmi, MD, from the Helsinki University Hospital and coauthors reported that this was the first study to explore a possible connection between antimicrobial use and Parkinson’s disease.

“In Parkinson’s disease, several studies have described alterations of gut microbiota composition, and changes in fecal microbiota abundance have been found to be associated with gastrointestinal and motor symptoms,” they wrote.

Commenting on the delay between the exposure and diagnosis for the most strongly associated antimicrobials, the authors noted that this 10-15 year lag was comparable with what has been found between the peripheral initiation of Parkinson’s disease and its motor manifestation.

“This would also explain the lack of association between antibiotic exposure 1-5 years before index date – if antibiotic exposure could induce or contribute to the pathogenesis of Parkinson’s disease in the gastrointestinal tract, it would probably take several years before the clinical manifestation of Parkinson’s disease,” they wrote.

With regards to the association seen for sulfonamides and trimethoprim – which was 1-5 years before the index date – they speculated this could reflect treatment for urinary tract infections, which individuals with Parkinson’s disease might be more susceptible to in the prodromal phase of the disease.

The authors noted that infectious disease has also been associated with Parkinson’s disease, and that their analysis did not include information about why the antimicrobial agents were prescribed. However, they pointed out that the associations were only for certain antibiotic classes, which makes it unlikely that the association was related to greater burden of infectious disease among individuals with Parkinson’s disease.

The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to Parkinson’s disease. “The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients the pathology of Parkinson’s disease may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson’s disease motor symptoms such as slowness, muscle stiffness, and shaking of the extremities. It was known that bacterial composition of the intestine in patients with Parkinson’s disease is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor,” said lead investigator Filip Scheperjans, MD, PhD, from the department of neurology at Helsinki University Hospital.

The findings may have implications for antibiotic prescribing practices in the future, said Dr. Scheperjans. “In addition to the problem of antibiotic resistance, antimicrobial prescribing should also take into account their potentially long-lasting effects on the gut microbiome and the development of certain diseases.”

The study was funded by the Finnish Parkinson Foundation, the Finnish Medical Foundation, the Maire Taponen Foundation, and the Academy of Finland. One author declared relevant patents and his position as founder and chief executive of a private company. No other conflicts of interest were declared.

SOURCE: Mertsalmi TH et al. Mov Disord. 2019 Nov 18. doi: 10.1002/mds.27924.

Certain types of oral antibiotics seem to be associated with an elevated risk of Parkinson’s disease with a delay that is consistent with the proposed duration of a prodromal period, according to a report published in Movement Disorders. Associations were found for broad-spectrum antibiotics and those that act against anaerobic bacteria and fungi. The timing of antibiotic exposure also seemed to matter.

In a nationwide case-control study, Finnish researchers compared data on antibiotic use in 13,976 individuals diagnosed with Parkinson’s disease between 1998 and 2014 with antibiotic-use data from 40,697 controls. The strongest connection with Parkinson’s disease risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10-15 years before the index date, and antifungal medications 1-5 years before the index date were positively associated with Parkinson’s disease risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics.

Tuomas H. Mertsalmi, MD, from the Helsinki University Hospital and coauthors reported that this was the first study to explore a possible connection between antimicrobial use and Parkinson’s disease.

“In Parkinson’s disease, several studies have described alterations of gut microbiota composition, and changes in fecal microbiota abundance have been found to be associated with gastrointestinal and motor symptoms,” they wrote.

Commenting on the delay between the exposure and diagnosis for the most strongly associated antimicrobials, the authors noted that this 10-15 year lag was comparable with what has been found between the peripheral initiation of Parkinson’s disease and its motor manifestation.

“This would also explain the lack of association between antibiotic exposure 1-5 years before index date – if antibiotic exposure could induce or contribute to the pathogenesis of Parkinson’s disease in the gastrointestinal tract, it would probably take several years before the clinical manifestation of Parkinson’s disease,” they wrote.

With regards to the association seen for sulfonamides and trimethoprim – which was 1-5 years before the index date – they speculated this could reflect treatment for urinary tract infections, which individuals with Parkinson’s disease might be more susceptible to in the prodromal phase of the disease.

The authors noted that infectious disease has also been associated with Parkinson’s disease, and that their analysis did not include information about why the antimicrobial agents were prescribed. However, they pointed out that the associations were only for certain antibiotic classes, which makes it unlikely that the association was related to greater burden of infectious disease among individuals with Parkinson’s disease.

The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to Parkinson’s disease. “The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients the pathology of Parkinson’s disease may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson’s disease motor symptoms such as slowness, muscle stiffness, and shaking of the extremities. It was known that bacterial composition of the intestine in patients with Parkinson’s disease is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor,” said lead investigator Filip Scheperjans, MD, PhD, from the department of neurology at Helsinki University Hospital.

The findings may have implications for antibiotic prescribing practices in the future, said Dr. Scheperjans. “In addition to the problem of antibiotic resistance, antimicrobial prescribing should also take into account their potentially long-lasting effects on the gut microbiome and the development of certain diseases.”

The study was funded by the Finnish Parkinson Foundation, the Finnish Medical Foundation, the Maire Taponen Foundation, and the Academy of Finland. One author declared relevant patents and his position as founder and chief executive of a private company. No other conflicts of interest were declared.

SOURCE: Mertsalmi TH et al. Mov Disord. 2019 Nov 18. doi: 10.1002/mds.27924.

Certain types of oral antibiotics seem to be associated with an elevated risk of Parkinson’s disease with a delay that is consistent with the proposed duration of a prodromal period, according to a report published in Movement Disorders. Associations were found for broad-spectrum antibiotics and those that act against anaerobic bacteria and fungi. The timing of antibiotic exposure also seemed to matter.

In a nationwide case-control study, Finnish researchers compared data on antibiotic use in 13,976 individuals diagnosed with Parkinson’s disease between 1998 and 2014 with antibiotic-use data from 40,697 controls. The strongest connection with Parkinson’s disease risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10-15 years before the index date, and antifungal medications 1-5 years before the index date were positively associated with Parkinson’s disease risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics.

Tuomas H. Mertsalmi, MD, from the Helsinki University Hospital and coauthors reported that this was the first study to explore a possible connection between antimicrobial use and Parkinson’s disease.

“In Parkinson’s disease, several studies have described alterations of gut microbiota composition, and changes in fecal microbiota abundance have been found to be associated with gastrointestinal and motor symptoms,” they wrote.

Commenting on the delay between the exposure and diagnosis for the most strongly associated antimicrobials, the authors noted that this 10-15 year lag was comparable with what has been found between the peripheral initiation of Parkinson’s disease and its motor manifestation.

“This would also explain the lack of association between antibiotic exposure 1-5 years before index date – if antibiotic exposure could induce or contribute to the pathogenesis of Parkinson’s disease in the gastrointestinal tract, it would probably take several years before the clinical manifestation of Parkinson’s disease,” they wrote.

With regards to the association seen for sulfonamides and trimethoprim – which was 1-5 years before the index date – they speculated this could reflect treatment for urinary tract infections, which individuals with Parkinson’s disease might be more susceptible to in the prodromal phase of the disease.

The authors noted that infectious disease has also been associated with Parkinson’s disease, and that their analysis did not include information about why the antimicrobial agents were prescribed. However, they pointed out that the associations were only for certain antibiotic classes, which makes it unlikely that the association was related to greater burden of infectious disease among individuals with Parkinson’s disease.

The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to Parkinson’s disease. “The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients the pathology of Parkinson’s disease may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson’s disease motor symptoms such as slowness, muscle stiffness, and shaking of the extremities. It was known that bacterial composition of the intestine in patients with Parkinson’s disease is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor,” said lead investigator Filip Scheperjans, MD, PhD, from the department of neurology at Helsinki University Hospital.

The findings may have implications for antibiotic prescribing practices in the future, said Dr. Scheperjans. “In addition to the problem of antibiotic resistance, antimicrobial prescribing should also take into account their potentially long-lasting effects on the gut microbiome and the development of certain diseases.”

The study was funded by the Finnish Parkinson Foundation, the Finnish Medical Foundation, the Maire Taponen Foundation, and the Academy of Finland. One author declared relevant patents and his position as founder and chief executive of a private company. No other conflicts of interest were declared.

SOURCE: Mertsalmi TH et al. Mov Disord. 2019 Nov 18. doi: 10.1002/mds.27924.

Nearly one in five adolescents and one in four young adults in the United States have prediabetes, with a higher prevalence among males, a study has found.

copyright Martynasfoto/Thinkstock

Linda J. Andes, PhD, from the Centers for Disease Control and Prevention and coauthors reported in JAMA Pediatrics their analysis of data from 2,606 adolescent (12-18 years) and 3,180 young adult (19-34 years) participants in the 2005-2016 National Health and Nutrition Examination Surveys.

This found that the percentage with prediabetes – defined as either impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or increased hemoglobin A_1c (HbA_1c) level – was 18% among adolescents and 24% among young adults.

The most common condition was IFG, which was seen in 11% of adolescents and 16% of young adults. The rate of IGT was 4% in adolescents and 6% of young adults, while elevated HbA_1c levels were seen in 5% of adolescents and 8% of young adults.

This information is important because “In adults, these three phenotypes increase the risk of developing type 2 diabetes as well as cardiovascular diseases,” Dr. Andes and coauthors wrote. “In 2011-2012, the overall prevalence of prediabetes among U.S. adults, defined as the presence of any of the three glucose metabolism dysregulation phenotypes, was 38% and it increased to about 50% in persons 65 years and older.”

Dr. Andes and associates noted that isolated IFG was the most common glucose dysregulation seen in both adolescents and young adults. “While individuals with IFG are at increased risk for type 2 diabetes, few primary prevention trials have included individuals selected for the presence of IFG and none have been conducted in adolescents with IFG or IGT to our knowledge.”

The study saw some key gender differences in prevalence. For example, the prevalence of IFG was significantly lower in adolescent girls than in boys (7% vs. 15%; P less than .001), and in young women, compared with young men (10% vs. 22%; P less than .001).

“These findings are consistent with those of other studies in adults; however, the underlying mechanisms for explaining this discrepancy are still unclear,” Dr. Andes and coauthors wrote.

Ethnicity also appeared to influence risk, with the prevalence of IFG significantly lower in non-Hispanic black adolescents, compared with Hispanic adolescents. However, increased HbA_1c levels were significantly more prevalent in non-Hispanic black adolescents, compared with Hispanic or non-Hispanic white adolescents.

“These findings highlight the need for additional studies on the long-term consequences and preventive strategies of abnormal glucose metabolism as measured by HbA_1c levels in adolescents and young adults, especially of minority racial/ethnic groups,” the authors wrote.

Adolescents with prediabetes had significantly higher systolic blood pressure, non-HDL cholesterol, waist-to-height ratio, higher body mass index, and lower insulin sensitivity, compared with those with normal glucose tolerance. Among young adults with prediabetes, there was significantly higher systolic blood pressure and non-HDL cholesterol, compared with individuals with normal glucose tolerance.

No funding or conflicts of interest were declared.

SOURCE: Andes LJ et al. JAMA Pediatr. 2019 Dec 2. doi: 10.1001/jamapediatrics.2019.4498.

Nearly one in five adolescents and one in four young adults in the United States have prediabetes, with a higher prevalence among males, a study has found.

copyright Martynasfoto/Thinkstock

Linda J. Andes, PhD, from the Centers for Disease Control and Prevention and coauthors reported in JAMA Pediatrics their analysis of data from 2,606 adolescent (12-18 years) and 3,180 young adult (19-34 years) participants in the 2005-2016 National Health and Nutrition Examination Surveys.

This found that the percentage with prediabetes – defined as either impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or increased hemoglobin A_1c (HbA_1c) level – was 18% among adolescents and 24% among young adults.

The most common condition was IFG, which was seen in 11% of adolescents and 16% of young adults. The rate of IGT was 4% in adolescents and 6% of young adults, while elevated HbA_1c levels were seen in 5% of adolescents and 8% of young adults.

This information is important because “In adults, these three phenotypes increase the risk of developing type 2 diabetes as well as cardiovascular diseases,” Dr. Andes and coauthors wrote. “In 2011-2012, the overall prevalence of prediabetes among U.S. adults, defined as the presence of any of the three glucose metabolism dysregulation phenotypes, was 38% and it increased to about 50% in persons 65 years and older.”

Dr. Andes and associates noted that isolated IFG was the most common glucose dysregulation seen in both adolescents and young adults. “While individuals with IFG are at increased risk for type 2 diabetes, few primary prevention trials have included individuals selected for the presence of IFG and none have been conducted in adolescents with IFG or IGT to our knowledge.”

The study saw some key gender differences in prevalence. For example, the prevalence of IFG was significantly lower in adolescent girls than in boys (7% vs. 15%; P less than .001), and in young women, compared with young men (10% vs. 22%; P less than .001).

“These findings are consistent with those of other studies in adults; however, the underlying mechanisms for explaining this discrepancy are still unclear,” Dr. Andes and coauthors wrote.

Ethnicity also appeared to influence risk, with the prevalence of IFG significantly lower in non-Hispanic black adolescents, compared with Hispanic adolescents. However, increased HbA_1c levels were significantly more prevalent in non-Hispanic black adolescents, compared with Hispanic or non-Hispanic white adolescents.

“These findings highlight the need for additional studies on the long-term consequences and preventive strategies of abnormal glucose metabolism as measured by HbA_1c levels in adolescents and young adults, especially of minority racial/ethnic groups,” the authors wrote.

Adolescents with prediabetes had significantly higher systolic blood pressure, non-HDL cholesterol, waist-to-height ratio, higher body mass index, and lower insulin sensitivity, compared with those with normal glucose tolerance. Among young adults with prediabetes, there was significantly higher systolic blood pressure and non-HDL cholesterol, compared with individuals with normal glucose tolerance.

No funding or conflicts of interest were declared.

SOURCE: Andes LJ et al. JAMA Pediatr. 2019 Dec 2. doi: 10.1001/jamapediatrics.2019.4498.

Nearly one in five adolescents and one in four young adults in the United States have prediabetes, with a higher prevalence among males, a study has found.

copyright Martynasfoto/Thinkstock

Linda J. Andes, PhD, from the Centers for Disease Control and Prevention and coauthors reported in JAMA Pediatrics their analysis of data from 2,606 adolescent (12-18 years) and 3,180 young adult (19-34 years) participants in the 2005-2016 National Health and Nutrition Examination Surveys.

This found that the percentage with prediabetes – defined as either impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or increased hemoglobin A_1c (HbA_1c) level – was 18% among adolescents and 24% among young adults.

The most common condition was IFG, which was seen in 11% of adolescents and 16% of young adults. The rate of IGT was 4% in adolescents and 6% of young adults, while elevated HbA_1c levels were seen in 5% of adolescents and 8% of young adults.

This information is important because “In adults, these three phenotypes increase the risk of developing type 2 diabetes as well as cardiovascular diseases,” Dr. Andes and coauthors wrote. “In 2011-2012, the overall prevalence of prediabetes among U.S. adults, defined as the presence of any of the three glucose metabolism dysregulation phenotypes, was 38% and it increased to about 50% in persons 65 years and older.”

Dr. Andes and associates noted that isolated IFG was the most common glucose dysregulation seen in both adolescents and young adults. “While individuals with IFG are at increased risk for type 2 diabetes, few primary prevention trials have included individuals selected for the presence of IFG and none have been conducted in adolescents with IFG or IGT to our knowledge.”

The study saw some key gender differences in prevalence. For example, the prevalence of IFG was significantly lower in adolescent girls than in boys (7% vs. 15%; P less than .001), and in young women, compared with young men (10% vs. 22%; P less than .001).

“These findings are consistent with those of other studies in adults; however, the underlying mechanisms for explaining this discrepancy are still unclear,” Dr. Andes and coauthors wrote.

Ethnicity also appeared to influence risk, with the prevalence of IFG significantly lower in non-Hispanic black adolescents, compared with Hispanic adolescents. However, increased HbA_1c levels were significantly more prevalent in non-Hispanic black adolescents, compared with Hispanic or non-Hispanic white adolescents.

“These findings highlight the need for additional studies on the long-term consequences and preventive strategies of abnormal glucose metabolism as measured by HbA_1c levels in adolescents and young adults, especially of minority racial/ethnic groups,” the authors wrote.

Adolescents with prediabetes had significantly higher systolic blood pressure, non-HDL cholesterol, waist-to-height ratio, higher body mass index, and lower insulin sensitivity, compared with those with normal glucose tolerance. Among young adults with prediabetes, there was significantly higher systolic blood pressure and non-HDL cholesterol, compared with individuals with normal glucose tolerance.

No funding or conflicts of interest were declared.

SOURCE: Andes LJ et al. JAMA Pediatr. 2019 Dec 2. doi: 10.1001/jamapediatrics.2019.4498.

Individuals with autism spectrum disorder might be at significantly higher risk of bipolar disorder, anxiety, and depression, a new study suggests.

“This study supports the importance of early, ongoing surveillance, and targeted treatments to address the psychiatric needs of individuals with ASD,” wrote lead author Alexandra C. Kirsch, PhD, and associates. The report was published in JAMA Pediatrics.

Dr. Kirsch and associates reported the outcomes of a population-based cohort study involving 1,014 individuals with autism spectrum disorder and 2,028 age-and sex-matched controls without autism spectrum disorder. They found that individuals with autism spectrum disorder were more than nine times more likely to be diagnosed with bipolar disorder, 2.81 times more likely to be diagnosed with depression, and 3.45 times more likely to be diagnosed with anxiety, compared with controls.

“Significant psychosocial sequelae associated with having ASD, including difficulties developing and maintaining relationships, challenges succeeding academically and vocationally, and behaviors that can be problematic to manage, particularly increase risk for mood and anxiety symptoms in individuals with ASD,” wrote Dr. Kirsch of the department of psychiatry and psychology at the Mayo Clinic, Rochester, Minn., and associates. “Individuals with ASD also experience greater rates of other mental health challenges, including attention-deficit/hyperactivity disorder and substance abuse.”

Individuals with autism spectrum disorder who received a diagnosis of depression, anxiety, or bipolar disorder also were more likely to be diagnosed at a younger age than were those without autism. In the case of depression, the median age of diagnosis was 15.7 years, compared with 18.1 years among controls. For anxiety, the median age of diagnosis among individuals with autism spectrum disorder was 15.2 years, compared with 20.3 years for controls. For bipolar disorder, it was 20.3 years, compared with 27 years although the small number of individuals meant this was not statistically significant.

The authors suggested that the earlier age at diagnosis might reflect that individuals with autism spectrum disorder generally are monitored more closely, and are more likely to be connected to screening and diagnostic resources because of their original diagnosis.

The researchers also found that the increased risk of depression and anxiety was even higher among men with autism spectrum disorder, even though the cumulative incidence of these conditions was greater in women both with and without autism. In addition, the researchers noted that individuals with autism spectrum disorder were more likely to be diagnosed with multiple psychiatric conditions than were those without autism.

Dr. Kirsch and associates cited several limitations. One is that the population studied came from Olmsted County, Minn., which is wealthier and less diverse than the general population. Nevertheless, the results could help guide treatments for patients with ASD.

“Given the high rates of comorbidity, researchers and practitioners should develop tools that are specific to the unique needs of this population and effective medications and treatments for mood and anxiety concerns, which remain limited in this population,” they wrote.

The study was funded by grants from the National Institutes of Health and the U.S. Public Health Service. No conflicts of interest were disclosed.

SOURCE: Kirsch A et al. JAMA Pediatr. 2019 Dec 2. doi: 10.1001/jamapediatrics.2019.4368.

Individuals with autism spectrum disorder might be at significantly higher risk of bipolar disorder, anxiety, and depression, a new study suggests.

“This study supports the importance of early, ongoing surveillance, and targeted treatments to address the psychiatric needs of individuals with ASD,” wrote lead author Alexandra C. Kirsch, PhD, and associates. The report was published in JAMA Pediatrics.

Dr. Kirsch and associates reported the outcomes of a population-based cohort study involving 1,014 individuals with autism spectrum disorder and 2,028 age-and sex-matched controls without autism spectrum disorder. They found that individuals with autism spectrum disorder were more than nine times more likely to be diagnosed with bipolar disorder, 2.81 times more likely to be diagnosed with depression, and 3.45 times more likely to be diagnosed with anxiety, compared with controls.

“Significant psychosocial sequelae associated with having ASD, including difficulties developing and maintaining relationships, challenges succeeding academically and vocationally, and behaviors that can be problematic to manage, particularly increase risk for mood and anxiety symptoms in individuals with ASD,” wrote Dr. Kirsch of the department of psychiatry and psychology at the Mayo Clinic, Rochester, Minn., and associates. “Individuals with ASD also experience greater rates of other mental health challenges, including attention-deficit/hyperactivity disorder and substance abuse.”

Individuals with autism spectrum disorder who received a diagnosis of depression, anxiety, or bipolar disorder also were more likely to be diagnosed at a younger age than were those without autism. In the case of depression, the median age of diagnosis was 15.7 years, compared with 18.1 years among controls. For anxiety, the median age of diagnosis among individuals with autism spectrum disorder was 15.2 years, compared with 20.3 years for controls. For bipolar disorder, it was 20.3 years, compared with 27 years although the small number of individuals meant this was not statistically significant.

The authors suggested that the earlier age at diagnosis might reflect that individuals with autism spectrum disorder generally are monitored more closely, and are more likely to be connected to screening and diagnostic resources because of their original diagnosis.

The researchers also found that the increased risk of depression and anxiety was even higher among men with autism spectrum disorder, even though the cumulative incidence of these conditions was greater in women both with and without autism. In addition, the researchers noted that individuals with autism spectrum disorder were more likely to be diagnosed with multiple psychiatric conditions than were those without autism.

Dr. Kirsch and associates cited several limitations. One is that the population studied came from Olmsted County, Minn., which is wealthier and less diverse than the general population. Nevertheless, the results could help guide treatments for patients with ASD.

“Given the high rates of comorbidity, researchers and practitioners should develop tools that are specific to the unique needs of this population and effective medications and treatments for mood and anxiety concerns, which remain limited in this population,” they wrote.

The study was funded by grants from the National Institutes of Health and the U.S. Public Health Service. No conflicts of interest were disclosed.

SOURCE: Kirsch A et al. JAMA Pediatr. 2019 Dec 2. doi: 10.1001/jamapediatrics.2019.4368.

Individuals with autism spectrum disorder might be at significantly higher risk of bipolar disorder, anxiety, and depression, a new study suggests.

“This study supports the importance of early, ongoing surveillance, and targeted treatments to address the psychiatric needs of individuals with ASD,” wrote lead author Alexandra C. Kirsch, PhD, and associates. The report was published in JAMA Pediatrics.

Dr. Kirsch and associates reported the outcomes of a population-based cohort study involving 1,014 individuals with autism spectrum disorder and 2,028 age-and sex-matched controls without autism spectrum disorder. They found that individuals with autism spectrum disorder were more than nine times more likely to be diagnosed with bipolar disorder, 2.81 times more likely to be diagnosed with depression, and 3.45 times more likely to be diagnosed with anxiety, compared with controls.

“Significant psychosocial sequelae associated with having ASD, including difficulties developing and maintaining relationships, challenges succeeding academically and vocationally, and behaviors that can be problematic to manage, particularly increase risk for mood and anxiety symptoms in individuals with ASD,” wrote Dr. Kirsch of the department of psychiatry and psychology at the Mayo Clinic, Rochester, Minn., and associates. “Individuals with ASD also experience greater rates of other mental health challenges, including attention-deficit/hyperactivity disorder and substance abuse.”

Individuals with autism spectrum disorder who received a diagnosis of depression, anxiety, or bipolar disorder also were more likely to be diagnosed at a younger age than were those without autism. In the case of depression, the median age of diagnosis was 15.7 years, compared with 18.1 years among controls. For anxiety, the median age of diagnosis among individuals with autism spectrum disorder was 15.2 years, compared with 20.3 years for controls. For bipolar disorder, it was 20.3 years, compared with 27 years although the small number of individuals meant this was not statistically significant.

The authors suggested that the earlier age at diagnosis might reflect that individuals with autism spectrum disorder generally are monitored more closely, and are more likely to be connected to screening and diagnostic resources because of their original diagnosis.

The researchers also found that the increased risk of depression and anxiety was even higher among men with autism spectrum disorder, even though the cumulative incidence of these conditions was greater in women both with and without autism. In addition, the researchers noted that individuals with autism spectrum disorder were more likely to be diagnosed with multiple psychiatric conditions than were those without autism.

Dr. Kirsch and associates cited several limitations. One is that the population studied came from Olmsted County, Minn., which is wealthier and less diverse than the general population. Nevertheless, the results could help guide treatments for patients with ASD.

“Given the high rates of comorbidity, researchers and practitioners should develop tools that are specific to the unique needs of this population and effective medications and treatments for mood and anxiety concerns, which remain limited in this population,” they wrote.

The study was funded by grants from the National Institutes of Health and the U.S. Public Health Service. No conflicts of interest were disclosed.

SOURCE: Kirsch A et al. JAMA Pediatr. 2019 Dec 2. doi: 10.1001/jamapediatrics.2019.4368.

The nootropic drug piracetam is widely available in dietary supplements marketed for cognitive enhancement, despite the lack of evidence for its efficacy and lack of approval by the U.S. Food and Drug Administration, according to an analysis of products sold online.

Sales of so-called ‘brain enhancement’ supplements exceeded $640 million in 2015 in the United States alone, but little is known about the risks of these dietary supplements, Pieter A. Cohen, MD, of the Cambridge Health Alliance in Somerville, Mass., and his coauthors wrote in a research letter published online Nov. 25 in JAMA Internal Medicine.

Piracetam is prescribed in many European countries for cognitive impairment and other disorders, the authors said. There is limited evidence for its efficacy, and the United States does not permit its sale as a dietary supplement.

Using the search terms “piracetam” and “dietary supplement,” researchers identified five brands of supplements sold online and analyzed 10 samples from these. Their chemical analysis revealed that eight samples from four brands contained piracetam, ranging from 831 mg to 1,452 mg per recommended serving size, and 85%-118% of the amount on the product’s label.

“Our findings demonstrate that, even after the FDA rejected an application to market piracetam as a new supplement ingredient, the drug was nevertheless introduced into the marketplace,” the authors wrote.

The authors calculated that, if consumers followed the recommended dosage on the labels of these products, they could be exposed to up to 11,283 mg of piracetam per day.

For comparison, prescription piracetam in Europe is commonly found in 800-mg and 1,200-mg tablets, and the recommended daily dose for cognitive disorders ranges from 2,400 to 4,800 mg per day, adjusted for renal function.

The authors commented that piracetam is associated with side effects at pharmaceutical dosages, including anxiety, insomnia, agitation, depression, drowsiness, and weight gain. However, the risk associated with higher doses, particularly in the elderly and those with renal insufficiency, are unknown.

“Until the law governing supplements is reformed such that products adulterated with drugs can be effectively removed from the market, clinicians should advise patients that supplements marketed as cognitive enhancers may contain prohibited drugs at supratherapeutic doses,” the authors wrote.

One author declared research support from two organizations unrelated to the study. No conflicts of interest were declared.

SOURCE: Cohen P et al. JAMA Int Med. 2019 Nov 25. doi: 10.1001/jamainternmed.2019.5507.

The nootropic drug piracetam is widely available in dietary supplements marketed for cognitive enhancement, despite the lack of evidence for its efficacy and lack of approval by the U.S. Food and Drug Administration, according to an analysis of products sold online.

Sales of so-called ‘brain enhancement’ supplements exceeded $640 million in 2015 in the United States alone, but little is known about the risks of these dietary supplements, Pieter A. Cohen, MD, of the Cambridge Health Alliance in Somerville, Mass., and his coauthors wrote in a research letter published online Nov. 25 in JAMA Internal Medicine.

Piracetam is prescribed in many European countries for cognitive impairment and other disorders, the authors said. There is limited evidence for its efficacy, and the United States does not permit its sale as a dietary supplement.

Using the search terms “piracetam” and “dietary supplement,” researchers identified five brands of supplements sold online and analyzed 10 samples from these. Their chemical analysis revealed that eight samples from four brands contained piracetam, ranging from 831 mg to 1,452 mg per recommended serving size, and 85%-118% of the amount on the product’s label.

“Our findings demonstrate that, even after the FDA rejected an application to market piracetam as a new supplement ingredient, the drug was nevertheless introduced into the marketplace,” the authors wrote.

The authors calculated that, if consumers followed the recommended dosage on the labels of these products, they could be exposed to up to 11,283 mg of piracetam per day.

For comparison, prescription piracetam in Europe is commonly found in 800-mg and 1,200-mg tablets, and the recommended daily dose for cognitive disorders ranges from 2,400 to 4,800 mg per day, adjusted for renal function.

The authors commented that piracetam is associated with side effects at pharmaceutical dosages, including anxiety, insomnia, agitation, depression, drowsiness, and weight gain. However, the risk associated with higher doses, particularly in the elderly and those with renal insufficiency, are unknown.

“Until the law governing supplements is reformed such that products adulterated with drugs can be effectively removed from the market, clinicians should advise patients that supplements marketed as cognitive enhancers may contain prohibited drugs at supratherapeutic doses,” the authors wrote.

One author declared research support from two organizations unrelated to the study. No conflicts of interest were declared.

SOURCE: Cohen P et al. JAMA Int Med. 2019 Nov 25. doi: 10.1001/jamainternmed.2019.5507.

The nootropic drug piracetam is widely available in dietary supplements marketed for cognitive enhancement, despite the lack of evidence for its efficacy and lack of approval by the U.S. Food and Drug Administration, according to an analysis of products sold online.

Sales of so-called ‘brain enhancement’ supplements exceeded $640 million in 2015 in the United States alone, but little is known about the risks of these dietary supplements, Pieter A. Cohen, MD, of the Cambridge Health Alliance in Somerville, Mass., and his coauthors wrote in a research letter published online Nov. 25 in JAMA Internal Medicine.

Piracetam is prescribed in many European countries for cognitive impairment and other disorders, the authors said. There is limited evidence for its efficacy, and the United States does not permit its sale as a dietary supplement.

Using the search terms “piracetam” and “dietary supplement,” researchers identified five brands of supplements sold online and analyzed 10 samples from these. Their chemical analysis revealed that eight samples from four brands contained piracetam, ranging from 831 mg to 1,452 mg per recommended serving size, and 85%-118% of the amount on the product’s label.

“Our findings demonstrate that, even after the FDA rejected an application to market piracetam as a new supplement ingredient, the drug was nevertheless introduced into the marketplace,” the authors wrote.

The authors calculated that, if consumers followed the recommended dosage on the labels of these products, they could be exposed to up to 11,283 mg of piracetam per day.

For comparison, prescription piracetam in Europe is commonly found in 800-mg and 1,200-mg tablets, and the recommended daily dose for cognitive disorders ranges from 2,400 to 4,800 mg per day, adjusted for renal function.

The authors commented that piracetam is associated with side effects at pharmaceutical dosages, including anxiety, insomnia, agitation, depression, drowsiness, and weight gain. However, the risk associated with higher doses, particularly in the elderly and those with renal insufficiency, are unknown.

“Until the law governing supplements is reformed such that products adulterated with drugs can be effectively removed from the market, clinicians should advise patients that supplements marketed as cognitive enhancers may contain prohibited drugs at supratherapeutic doses,” the authors wrote.

One author declared research support from two organizations unrelated to the study. No conflicts of interest were declared.

SOURCE: Cohen P et al. JAMA Int Med. 2019 Nov 25. doi: 10.1001/jamainternmed.2019.5507.

Earlier onset of atopic dermatitis in children could signify more difficult to control and persistent disease, according to a study published in the Journal of the American Academy of Dermatology.

LucaLorenzelli/Thinkstock

Atopic dermatitis most commonly arises in infancy but also can emerge in later childhood and even adolescence, leading to a distinction between early- and late-onset disease, wrote Joy Wan, MD, of the University of Pennsylvania, Philadelphia, and coauthors.

“Early-onset, mid-onset, and late-onset AD appear to differ in the presence of active disease over time; however, whether these groups also differ in terms of the severity of AD is unknown,” they wrote.

In this observational cohort study, 8,015 individuals with childhood-onset atopic dermatitis – 53% of whom were female – were assessed twice-yearly for up to 10 years. Nearly three-quarters (72%) of the group had early-onset atopic dermatitis – defined as onset before 2 years of age – while 19% had mid-onset disease (3-7 years) and 9% had late-onset disease (8-17 years).

The study found that older age of onset was associated with better control, such that for each additional year of age at the onset of disease, there was a 7% reduction in the odds of poorer control of disease. Those who had mid-onset disease had a 29% lower odds of poorer control compared with those with early-onset, while those with late-onset disease had a 49% lower odds of poorer control.

The likelihood of atopic dermatitis persisting beyond childhood also appeared to be linked to the age of onset. Those with mid-onset disease had a 55% lower odds of persistent atopic dermatitis, compared with those with early-onset disease, while those with late-onset disease had an 81% lower odds.

“In all 3 groups, the proportion of subjects reporting persistent AD generally declined with older age, and the differences among the 3 onset age groups were most pronounced from early adolescence onward,” the authors wrote.

They noted that there was considerable research currently focused on identifying distinct atopic dermatitis phenotypes and endotypes, and their evidence on the different disease course for early-, mid-, and late-onset disease supported this idea of disease subtypes.

“However, additional research is needed to understand whether and how early-, mid-, and late-onset AD differ molecularly or immunologically, and whether they respond differentially to treatment,” they wrote. They also suggested that the timing of onset could help identify patients who were at greater risk of persistent or poorly controlled disease, and who benefits from more intensive monitoring or treatment.

The study was partly supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Dermatology Foundation. Three authors declared funding, consultancies, or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wan J et al. J Am Acad Dermatol. 2019 Dec;81(6):1292-9.

Earlier onset of atopic dermatitis in children could signify more difficult to control and persistent disease, according to a study published in the Journal of the American Academy of Dermatology.

LucaLorenzelli/Thinkstock

Atopic dermatitis most commonly arises in infancy but also can emerge in later childhood and even adolescence, leading to a distinction between early- and late-onset disease, wrote Joy Wan, MD, of the University of Pennsylvania, Philadelphia, and coauthors.

“Early-onset, mid-onset, and late-onset AD appear to differ in the presence of active disease over time; however, whether these groups also differ in terms of the severity of AD is unknown,” they wrote.

In this observational cohort study, 8,015 individuals with childhood-onset atopic dermatitis – 53% of whom were female – were assessed twice-yearly for up to 10 years. Nearly three-quarters (72%) of the group had early-onset atopic dermatitis – defined as onset before 2 years of age – while 19% had mid-onset disease (3-7 years) and 9% had late-onset disease (8-17 years).

The study found that older age of onset was associated with better control, such that for each additional year of age at the onset of disease, there was a 7% reduction in the odds of poorer control of disease. Those who had mid-onset disease had a 29% lower odds of poorer control compared with those with early-onset, while those with late-onset disease had a 49% lower odds of poorer control.

The likelihood of atopic dermatitis persisting beyond childhood also appeared to be linked to the age of onset. Those with mid-onset disease had a 55% lower odds of persistent atopic dermatitis, compared with those with early-onset disease, while those with late-onset disease had an 81% lower odds.

“In all 3 groups, the proportion of subjects reporting persistent AD generally declined with older age, and the differences among the 3 onset age groups were most pronounced from early adolescence onward,” the authors wrote.

They noted that there was considerable research currently focused on identifying distinct atopic dermatitis phenotypes and endotypes, and their evidence on the different disease course for early-, mid-, and late-onset disease supported this idea of disease subtypes.

“However, additional research is needed to understand whether and how early-, mid-, and late-onset AD differ molecularly or immunologically, and whether they respond differentially to treatment,” they wrote. They also suggested that the timing of onset could help identify patients who were at greater risk of persistent or poorly controlled disease, and who benefits from more intensive monitoring or treatment.

The study was partly supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Dermatology Foundation. Three authors declared funding, consultancies, or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wan J et al. J Am Acad Dermatol. 2019 Dec;81(6):1292-9.

Earlier onset of atopic dermatitis in children could signify more difficult to control and persistent disease, according to a study published in the Journal of the American Academy of Dermatology.

LucaLorenzelli/Thinkstock

Atopic dermatitis most commonly arises in infancy but also can emerge in later childhood and even adolescence, leading to a distinction between early- and late-onset disease, wrote Joy Wan, MD, of the University of Pennsylvania, Philadelphia, and coauthors.

“Early-onset, mid-onset, and late-onset AD appear to differ in the presence of active disease over time; however, whether these groups also differ in terms of the severity of AD is unknown,” they wrote.

In this observational cohort study, 8,015 individuals with childhood-onset atopic dermatitis – 53% of whom were female – were assessed twice-yearly for up to 10 years. Nearly three-quarters (72%) of the group had early-onset atopic dermatitis – defined as onset before 2 years of age – while 19% had mid-onset disease (3-7 years) and 9% had late-onset disease (8-17 years).

The study found that older age of onset was associated with better control, such that for each additional year of age at the onset of disease, there was a 7% reduction in the odds of poorer control of disease. Those who had mid-onset disease had a 29% lower odds of poorer control compared with those with early-onset, while those with late-onset disease had a 49% lower odds of poorer control.

The likelihood of atopic dermatitis persisting beyond childhood also appeared to be linked to the age of onset. Those with mid-onset disease had a 55% lower odds of persistent atopic dermatitis, compared with those with early-onset disease, while those with late-onset disease had an 81% lower odds.

“In all 3 groups, the proportion of subjects reporting persistent AD generally declined with older age, and the differences among the 3 onset age groups were most pronounced from early adolescence onward,” the authors wrote.

They noted that there was considerable research currently focused on identifying distinct atopic dermatitis phenotypes and endotypes, and their evidence on the different disease course for early-, mid-, and late-onset disease supported this idea of disease subtypes.

“However, additional research is needed to understand whether and how early-, mid-, and late-onset AD differ molecularly or immunologically, and whether they respond differentially to treatment,” they wrote. They also suggested that the timing of onset could help identify patients who were at greater risk of persistent or poorly controlled disease, and who benefits from more intensive monitoring or treatment.

The study was partly supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Dermatology Foundation. Three authors declared funding, consultancies, or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wan J et al. J Am Acad Dermatol. 2019 Dec;81(6):1292-9.