Bianca Nogrady

Migraines are associated with a significantly greater risk of Alzheimer’s disease and all forms of dementia except vascular dementia, according to research published online Sept. 4 in the International Journal of Geriatric Psychiatry.

In the Manitoba Study of Health and Aging, a population-based, prospective cohort study, 679 community-dwelling adults with a mean age of 75.9 years were followed for 5 years. Participants screened as cognitively intact at baseline had complete data on migraine history and all covariates at baseline and were assessed for cognitive outcomes 5 years later.

The study showed that a history of migraines was associated with a 2.97-fold greater likelihood of dementia, after adjustment for age, education, and a history of stroke, compared with individuals without a history of migraine. Individuals with Alzheimer’s disease were more than four times more likely to have a history of migraines (odds ratio 4.22).

However, researchers found no significant association between vascular dementia and a history of migraines, either before or after adjusting for confounders but particularly after incorporating a history of stroke into the model.

Lead investigator Suzanne L. Tyas, PhD, associate professor in the School of Public Health and Health Systems at the University of Waterloo, Ont., and coauthors suggested that the association between migraine and dementia was largely driven by the strong association between migraines and Alzheimer’s disease.

“This interpretation is supported by the weaker association for dementia than for Alzheimer’s disease, reflecting a dilution of the association with migraines across all types of dementia including vascular dementia, where a significant association was not found,” the researchers wrote.

The study population was 61.9% female, and no men reporting a history of migraine were diagnosed with dementia. While the study reflected a strong association between migraine and dementia in women, the researchers said they were unable to assess potential gender differences in this association.

Commenting on possible mechanisms behind the association, the authors wrote that there were overlaps underlying the biological mechanisms of migraine and dementia. Vascular risk factors such as diabetes, hypertension, heart attack, and stroke are associated with the development of dementia, and a relationship of these risk factors and migraine also has been seen.

“Many of the mechanisms involved in migraine neurophysiology, such as inflammation and reduced cerebral blood flow, are also underlying causes of dementia,” they wrote. “Repeated activation of these pathways in chronic migraineurs has been shown to cause permanent neurological and vascular damage.”

They also observed that the association could be influenced by genetic factors, as individuals with presenilin-1 mutations, which predispose them to Alzheimer’s disease, are more likely to experience migraines or recurrent headaches.

They suggested their findings could inform preventive strategies and treatments for Alzheimer’s disease, as well as interventions such as earlier screening for cognitive decline in individuals who experience migraines.

The study was funded by Manitoba Health and the National Health Research and Development Program of Health Canada. No conflicts of interest were declared.
 

SOURCE: Morton R et al. Int J Geriatr Psychiatry, 2019 Sep 4. doi: 10.1002/gps.5180.

Migraines are associated with a significantly greater risk of Alzheimer’s disease and all forms of dementia except vascular dementia, according to research published online Sept. 4 in the International Journal of Geriatric Psychiatry.

In the Manitoba Study of Health and Aging, a population-based, prospective cohort study, 679 community-dwelling adults with a mean age of 75.9 years were followed for 5 years. Participants screened as cognitively intact at baseline had complete data on migraine history and all covariates at baseline and were assessed for cognitive outcomes 5 years later.

The study showed that a history of migraines was associated with a 2.97-fold greater likelihood of dementia, after adjustment for age, education, and a history of stroke, compared with individuals without a history of migraine. Individuals with Alzheimer’s disease were more than four times more likely to have a history of migraines (odds ratio 4.22).

However, researchers found no significant association between vascular dementia and a history of migraines, either before or after adjusting for confounders but particularly after incorporating a history of stroke into the model.

Lead investigator Suzanne L. Tyas, PhD, associate professor in the School of Public Health and Health Systems at the University of Waterloo, Ont., and coauthors suggested that the association between migraine and dementia was largely driven by the strong association between migraines and Alzheimer’s disease.

“This interpretation is supported by the weaker association for dementia than for Alzheimer’s disease, reflecting a dilution of the association with migraines across all types of dementia including vascular dementia, where a significant association was not found,” the researchers wrote.

The study population was 61.9% female, and no men reporting a history of migraine were diagnosed with dementia. While the study reflected a strong association between migraine and dementia in women, the researchers said they were unable to assess potential gender differences in this association.

Commenting on possible mechanisms behind the association, the authors wrote that there were overlaps underlying the biological mechanisms of migraine and dementia. Vascular risk factors such as diabetes, hypertension, heart attack, and stroke are associated with the development of dementia, and a relationship of these risk factors and migraine also has been seen.

“Many of the mechanisms involved in migraine neurophysiology, such as inflammation and reduced cerebral blood flow, are also underlying causes of dementia,” they wrote. “Repeated activation of these pathways in chronic migraineurs has been shown to cause permanent neurological and vascular damage.”

They also observed that the association could be influenced by genetic factors, as individuals with presenilin-1 mutations, which predispose them to Alzheimer’s disease, are more likely to experience migraines or recurrent headaches.

They suggested their findings could inform preventive strategies and treatments for Alzheimer’s disease, as well as interventions such as earlier screening for cognitive decline in individuals who experience migraines.

The study was funded by Manitoba Health and the National Health Research and Development Program of Health Canada. No conflicts of interest were declared.
 

SOURCE: Morton R et al. Int J Geriatr Psychiatry, 2019 Sep 4. doi: 10.1002/gps.5180.

Migraines are associated with a significantly greater risk of Alzheimer’s disease and all forms of dementia except vascular dementia, according to research published online Sept. 4 in the International Journal of Geriatric Psychiatry.

In the Manitoba Study of Health and Aging, a population-based, prospective cohort study, 679 community-dwelling adults with a mean age of 75.9 years were followed for 5 years. Participants screened as cognitively intact at baseline had complete data on migraine history and all covariates at baseline and were assessed for cognitive outcomes 5 years later.

The study showed that a history of migraines was associated with a 2.97-fold greater likelihood of dementia, after adjustment for age, education, and a history of stroke, compared with individuals without a history of migraine. Individuals with Alzheimer’s disease were more than four times more likely to have a history of migraines (odds ratio 4.22).

However, researchers found no significant association between vascular dementia and a history of migraines, either before or after adjusting for confounders but particularly after incorporating a history of stroke into the model.

Lead investigator Suzanne L. Tyas, PhD, associate professor in the School of Public Health and Health Systems at the University of Waterloo, Ont., and coauthors suggested that the association between migraine and dementia was largely driven by the strong association between migraines and Alzheimer’s disease.

“This interpretation is supported by the weaker association for dementia than for Alzheimer’s disease, reflecting a dilution of the association with migraines across all types of dementia including vascular dementia, where a significant association was not found,” the researchers wrote.

The study population was 61.9% female, and no men reporting a history of migraine were diagnosed with dementia. While the study reflected a strong association between migraine and dementia in women, the researchers said they were unable to assess potential gender differences in this association.

Commenting on possible mechanisms behind the association, the authors wrote that there were overlaps underlying the biological mechanisms of migraine and dementia. Vascular risk factors such as diabetes, hypertension, heart attack, and stroke are associated with the development of dementia, and a relationship of these risk factors and migraine also has been seen.

“Many of the mechanisms involved in migraine neurophysiology, such as inflammation and reduced cerebral blood flow, are also underlying causes of dementia,” they wrote. “Repeated activation of these pathways in chronic migraineurs has been shown to cause permanent neurological and vascular damage.”

They also observed that the association could be influenced by genetic factors, as individuals with presenilin-1 mutations, which predispose them to Alzheimer’s disease, are more likely to experience migraines or recurrent headaches.

They suggested their findings could inform preventive strategies and treatments for Alzheimer’s disease, as well as interventions such as earlier screening for cognitive decline in individuals who experience migraines.

The study was funded by Manitoba Health and the National Health Research and Development Program of Health Canada. No conflicts of interest were declared.
 

SOURCE: Morton R et al. Int J Geriatr Psychiatry, 2019 Sep 4. doi: 10.1002/gps.5180.

Four modifiable lifestyle risk factors account for a substantial proportion of gout cases in the United States, suggesting greater public health efforts could reduce the frequency of the condition, according to a paper published Sept. 4 in Arthritis & Rheumatology.

Hyon K. Choi, MD, DrPH, of the department of medicine at Massachusetts General Hospital, Boston, and his coauthors analyzed data from 14,624 adults involved in the third National Health and Nutrition Examination Survey. From this, they calculated prevalence ratios for hyperuricemia, the population attributable risks, and the variance associated with the risk factors of body mass index, alcohol intake, nonadherence to a Dietary Approaches to Stop Hypertension (DASH) diet, and diuretic use.

They found that 21% of men and 19% of women in the study were hyperuricemic, which they defined as having a serum urate level greater than 417 micromol/L (7.0 mg/dL) for men and greater than 340 micromol/L (5.7 mg/dL) for women.

BMI was the most important risk factor for hyperuricemia, accounting for 44% of cases overall. The prevalence of hyperuricemia was 85% higher in individuals with a BMI of 25.0-29.9 kg/m2, 2.72-fold higher in those with a BMI of 30.0-34.9, and 3.53-fold higher for those with a BMI of 35.0 or above when compared against people with a BMI less than 25.0.

The researchers found that adherence to a DASH-style diet could have prevented 9% of hyperuricemia cases, as those in the lowest quintile of DASH-style dietary score had a 22% higher prevalence of hyperuricemia, compared with those in the highest quintile.

There was also a dose-response relationship between alcohol intake and hyperuricemia prevalence, and the authors calculated that 8% of cases could have been avoided through abstaining from alcohol consumption.

Individuals taking diuretics had a 2.24-fold greater risk of gout, and the population attributable risk for diuretic use was 12%.

However the authors noted that the serum urate variance explained by these individual risk factors was very small; for example, the serum urate variance attributed to the DASH diet was just 0.1%.

“How can dietary changes over time (together with a Western lifestyle) be associated with obesity and gout epidemics, yet also paradoxically appear extremely insignificant according to the variance measure?” they asked. “This occurs because the variance measure does not incorporate how common the exposure is (i.e., its prevalence).”

In contrast, the population attributable risk of these factors did reflect the contribution of effect size as well as the high prevalence, particularly with respect to dietary factors, where less than 1% of the U.S. population is believed to be adherent to the DASH diet.

“These data collectively indicate there is substantial room for improvement in dietary factors to help prevent hyperuricemia and gout, as well as hypertension and related cardiovascular outcomes.”

The study and one author were supported by the National Institutes of Health. Two authors were also supported by awards from the Canadian Institutes of Health Research. No conflicts of interest were declared.

SOURCE: Choi H et al. Arthritis Rheumatol. 2019 Sep 4. doi: 10.1002/art.41067.

Four modifiable lifestyle risk factors account for a substantial proportion of gout cases in the United States, suggesting greater public health efforts could reduce the frequency of the condition, according to a paper published Sept. 4 in Arthritis & Rheumatology.

Hyon K. Choi, MD, DrPH, of the department of medicine at Massachusetts General Hospital, Boston, and his coauthors analyzed data from 14,624 adults involved in the third National Health and Nutrition Examination Survey. From this, they calculated prevalence ratios for hyperuricemia, the population attributable risks, and the variance associated with the risk factors of body mass index, alcohol intake, nonadherence to a Dietary Approaches to Stop Hypertension (DASH) diet, and diuretic use.

They found that 21% of men and 19% of women in the study were hyperuricemic, which they defined as having a serum urate level greater than 417 micromol/L (7.0 mg/dL) for men and greater than 340 micromol/L (5.7 mg/dL) for women.

BMI was the most important risk factor for hyperuricemia, accounting for 44% of cases overall. The prevalence of hyperuricemia was 85% higher in individuals with a BMI of 25.0-29.9 kg/m2, 2.72-fold higher in those with a BMI of 30.0-34.9, and 3.53-fold higher for those with a BMI of 35.0 or above when compared against people with a BMI less than 25.0.

The researchers found that adherence to a DASH-style diet could have prevented 9% of hyperuricemia cases, as those in the lowest quintile of DASH-style dietary score had a 22% higher prevalence of hyperuricemia, compared with those in the highest quintile.

There was also a dose-response relationship between alcohol intake and hyperuricemia prevalence, and the authors calculated that 8% of cases could have been avoided through abstaining from alcohol consumption.

Individuals taking diuretics had a 2.24-fold greater risk of gout, and the population attributable risk for diuretic use was 12%.

However the authors noted that the serum urate variance explained by these individual risk factors was very small; for example, the serum urate variance attributed to the DASH diet was just 0.1%.

“How can dietary changes over time (together with a Western lifestyle) be associated with obesity and gout epidemics, yet also paradoxically appear extremely insignificant according to the variance measure?” they asked. “This occurs because the variance measure does not incorporate how common the exposure is (i.e., its prevalence).”

In contrast, the population attributable risk of these factors did reflect the contribution of effect size as well as the high prevalence, particularly with respect to dietary factors, where less than 1% of the U.S. population is believed to be adherent to the DASH diet.

“These data collectively indicate there is substantial room for improvement in dietary factors to help prevent hyperuricemia and gout, as well as hypertension and related cardiovascular outcomes.”

The study and one author were supported by the National Institutes of Health. Two authors were also supported by awards from the Canadian Institutes of Health Research. No conflicts of interest were declared.

SOURCE: Choi H et al. Arthritis Rheumatol. 2019 Sep 4. doi: 10.1002/art.41067.

Four modifiable lifestyle risk factors account for a substantial proportion of gout cases in the United States, suggesting greater public health efforts could reduce the frequency of the condition, according to a paper published Sept. 4 in Arthritis & Rheumatology.

Hyon K. Choi, MD, DrPH, of the department of medicine at Massachusetts General Hospital, Boston, and his coauthors analyzed data from 14,624 adults involved in the third National Health and Nutrition Examination Survey. From this, they calculated prevalence ratios for hyperuricemia, the population attributable risks, and the variance associated with the risk factors of body mass index, alcohol intake, nonadherence to a Dietary Approaches to Stop Hypertension (DASH) diet, and diuretic use.

They found that 21% of men and 19% of women in the study were hyperuricemic, which they defined as having a serum urate level greater than 417 micromol/L (7.0 mg/dL) for men and greater than 340 micromol/L (5.7 mg/dL) for women.

BMI was the most important risk factor for hyperuricemia, accounting for 44% of cases overall. The prevalence of hyperuricemia was 85% higher in individuals with a BMI of 25.0-29.9 kg/m2, 2.72-fold higher in those with a BMI of 30.0-34.9, and 3.53-fold higher for those with a BMI of 35.0 or above when compared against people with a BMI less than 25.0.

The researchers found that adherence to a DASH-style diet could have prevented 9% of hyperuricemia cases, as those in the lowest quintile of DASH-style dietary score had a 22% higher prevalence of hyperuricemia, compared with those in the highest quintile.

There was also a dose-response relationship between alcohol intake and hyperuricemia prevalence, and the authors calculated that 8% of cases could have been avoided through abstaining from alcohol consumption.

Individuals taking diuretics had a 2.24-fold greater risk of gout, and the population attributable risk for diuretic use was 12%.

However the authors noted that the serum urate variance explained by these individual risk factors was very small; for example, the serum urate variance attributed to the DASH diet was just 0.1%.

“How can dietary changes over time (together with a Western lifestyle) be associated with obesity and gout epidemics, yet also paradoxically appear extremely insignificant according to the variance measure?” they asked. “This occurs because the variance measure does not incorporate how common the exposure is (i.e., its prevalence).”

In contrast, the population attributable risk of these factors did reflect the contribution of effect size as well as the high prevalence, particularly with respect to dietary factors, where less than 1% of the U.S. population is believed to be adherent to the DASH diet.

“These data collectively indicate there is substantial room for improvement in dietary factors to help prevent hyperuricemia and gout, as well as hypertension and related cardiovascular outcomes.”

The study and one author were supported by the National Institutes of Health. Two authors were also supported by awards from the Canadian Institutes of Health Research. No conflicts of interest were declared.

SOURCE: Choi H et al. Arthritis Rheumatol. 2019 Sep 4. doi: 10.1002/art.41067.

A new oral antidepressant that targets the gamma-aminobutyric acid type A (GABA_A) receptors in the brain has been found to achieve a reduction in symptoms in adult patients with moderate to severe major depressive disorder, with no serious safety signals, results of a double-blind, phase 2 trial show.

The study involved 89 participants with major depression, excluding those with a history of treatment-resistant depression, who were randomized either to a once-daily dose of 30 mg of SAGE-217, a synthetic neurosteroid that acts as a positive allosteric modulator of GABA_A receptors, or placebo for 14 days. Thirty-six of the 45 patients in the SAGE-217 group were black, as were 28 of the 44 patients in the placebo group, reported Handan Gunduz-Bruce, MD, of Sage Therapeutics and coauthors. Their study was published in the New England Journal of Medicine.

“One hypothesis for the mechanism of depression implicates deficits in gamma-aminobutyric acid and downstream alterations in monoaminergic neurotransmission,” wrote Dr. Gunduz-Bruce and coauthors. “Preclinical studies have shown that the naturally occurring neurosteroid allopregnanolone is a positive allosteric modulator of synaptic and extrasynaptic GABA_A receptors that affects both phasic and tonic inhibition of neurons.”

At day 15 of the study, there was a significantly greater mean change from baseline in Hamilton Depression Rating Scale scores in the treatment group, compared with the placebo group (–17.4 vs. –10.3, P less than .001), and 79% of participants in the treatment arm showed a greater than 50% reduction in depression scores, compared with 41% of the placebo group.

At day 28, 62% of the treatment group and 46% of the placebo group had a reduction of more than 50% from baseline depression scores.

No serious or severe adverse events were seen in either group, and the most common adverse events in the SAGE-217 group included headache (18%), dizziness (11%), and nausea (11%). One patient in the treatment arm also reported euphoria.

The authors commented that somnolence and sedation were expected adverse events, based on the pharmacological properties of SAGE-217.

Six patients in the treatment arm also had dose reductions as a result of adverse events. Two patients in the SAGE-217 arm stopped treatment because they met prespecified criteria for discontinuation; the investigators reported nausea, dizziness, and headache in one patient, and increased levels of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in the other. However, the second patient had shown mildly elevated values of these at baseline, was asymptomatic throughout the trial, and the patient’s values returned to baseline or near-baseline after stopping treatment.

About one-quarter of both the SAGE-217 and placebo groups were receiving antidepressant treatment at baseline (27% and 23% respectively), with the duration of prior treatment ranging from 2 to 48 months. Investigators also gave three patients in the treatment arm and 11 in the placebo arm concomitant antidepressants during the follow-up period.

The small sample size and limited racial diversity among the participants were cited as limitations.

The study was supported by SAGE-217 manufacturer Sage Therapeutics. Ten authors were employees or directors of Sage Therapeutics, with stock options and patent interests. Three authors declared grants, personal fees, or advisory board positions with the pharmaceutical sector, including from Sage, and one also declared interest in a range of patents outside the study. One author had no disclosures.

SOURCE: Gunduz-Bruce H et al. N Engl J Med. 2019 Sep 5;381:903-11. doi: 10.1056/NEJMoa1815981.

A new oral antidepressant that targets the gamma-aminobutyric acid type A (GABA_A) receptors in the brain has been found to achieve a reduction in symptoms in adult patients with moderate to severe major depressive disorder, with no serious safety signals, results of a double-blind, phase 2 trial show.

The study involved 89 participants with major depression, excluding those with a history of treatment-resistant depression, who were randomized either to a once-daily dose of 30 mg of SAGE-217, a synthetic neurosteroid that acts as a positive allosteric modulator of GABA_A receptors, or placebo for 14 days. Thirty-six of the 45 patients in the SAGE-217 group were black, as were 28 of the 44 patients in the placebo group, reported Handan Gunduz-Bruce, MD, of Sage Therapeutics and coauthors. Their study was published in the New England Journal of Medicine.

“One hypothesis for the mechanism of depression implicates deficits in gamma-aminobutyric acid and downstream alterations in monoaminergic neurotransmission,” wrote Dr. Gunduz-Bruce and coauthors. “Preclinical studies have shown that the naturally occurring neurosteroid allopregnanolone is a positive allosteric modulator of synaptic and extrasynaptic GABA_A receptors that affects both phasic and tonic inhibition of neurons.”

At day 15 of the study, there was a significantly greater mean change from baseline in Hamilton Depression Rating Scale scores in the treatment group, compared with the placebo group (–17.4 vs. –10.3, P less than .001), and 79% of participants in the treatment arm showed a greater than 50% reduction in depression scores, compared with 41% of the placebo group.

At day 28, 62% of the treatment group and 46% of the placebo group had a reduction of more than 50% from baseline depression scores.

No serious or severe adverse events were seen in either group, and the most common adverse events in the SAGE-217 group included headache (18%), dizziness (11%), and nausea (11%). One patient in the treatment arm also reported euphoria.

The authors commented that somnolence and sedation were expected adverse events, based on the pharmacological properties of SAGE-217.

Six patients in the treatment arm also had dose reductions as a result of adverse events. Two patients in the SAGE-217 arm stopped treatment because they met prespecified criteria for discontinuation; the investigators reported nausea, dizziness, and headache in one patient, and increased levels of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in the other. However, the second patient had shown mildly elevated values of these at baseline, was asymptomatic throughout the trial, and the patient’s values returned to baseline or near-baseline after stopping treatment.

About one-quarter of both the SAGE-217 and placebo groups were receiving antidepressant treatment at baseline (27% and 23% respectively), with the duration of prior treatment ranging from 2 to 48 months. Investigators also gave three patients in the treatment arm and 11 in the placebo arm concomitant antidepressants during the follow-up period.

The small sample size and limited racial diversity among the participants were cited as limitations.

The study was supported by SAGE-217 manufacturer Sage Therapeutics. Ten authors were employees or directors of Sage Therapeutics, with stock options and patent interests. Three authors declared grants, personal fees, or advisory board positions with the pharmaceutical sector, including from Sage, and one also declared interest in a range of patents outside the study. One author had no disclosures.

SOURCE: Gunduz-Bruce H et al. N Engl J Med. 2019 Sep 5;381:903-11. doi: 10.1056/NEJMoa1815981.

A new oral antidepressant that targets the gamma-aminobutyric acid type A (GABA_A) receptors in the brain has been found to achieve a reduction in symptoms in adult patients with moderate to severe major depressive disorder, with no serious safety signals, results of a double-blind, phase 2 trial show.

The study involved 89 participants with major depression, excluding those with a history of treatment-resistant depression, who were randomized either to a once-daily dose of 30 mg of SAGE-217, a synthetic neurosteroid that acts as a positive allosteric modulator of GABA_A receptors, or placebo for 14 days. Thirty-six of the 45 patients in the SAGE-217 group were black, as were 28 of the 44 patients in the placebo group, reported Handan Gunduz-Bruce, MD, of Sage Therapeutics and coauthors. Their study was published in the New England Journal of Medicine.

“One hypothesis for the mechanism of depression implicates deficits in gamma-aminobutyric acid and downstream alterations in monoaminergic neurotransmission,” wrote Dr. Gunduz-Bruce and coauthors. “Preclinical studies have shown that the naturally occurring neurosteroid allopregnanolone is a positive allosteric modulator of synaptic and extrasynaptic GABA_A receptors that affects both phasic and tonic inhibition of neurons.”

At day 15 of the study, there was a significantly greater mean change from baseline in Hamilton Depression Rating Scale scores in the treatment group, compared with the placebo group (–17.4 vs. –10.3, P less than .001), and 79% of participants in the treatment arm showed a greater than 50% reduction in depression scores, compared with 41% of the placebo group.

At day 28, 62% of the treatment group and 46% of the placebo group had a reduction of more than 50% from baseline depression scores.

No serious or severe adverse events were seen in either group, and the most common adverse events in the SAGE-217 group included headache (18%), dizziness (11%), and nausea (11%). One patient in the treatment arm also reported euphoria.

The authors commented that somnolence and sedation were expected adverse events, based on the pharmacological properties of SAGE-217.

Six patients in the treatment arm also had dose reductions as a result of adverse events. Two patients in the SAGE-217 arm stopped treatment because they met prespecified criteria for discontinuation; the investigators reported nausea, dizziness, and headache in one patient, and increased levels of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in the other. However, the second patient had shown mildly elevated values of these at baseline, was asymptomatic throughout the trial, and the patient’s values returned to baseline or near-baseline after stopping treatment.

About one-quarter of both the SAGE-217 and placebo groups were receiving antidepressant treatment at baseline (27% and 23% respectively), with the duration of prior treatment ranging from 2 to 48 months. Investigators also gave three patients in the treatment arm and 11 in the placebo arm concomitant antidepressants during the follow-up period.

The small sample size and limited racial diversity among the participants were cited as limitations.

The study was supported by SAGE-217 manufacturer Sage Therapeutics. Ten authors were employees or directors of Sage Therapeutics, with stock options and patent interests. Three authors declared grants, personal fees, or advisory board positions with the pharmaceutical sector, including from Sage, and one also declared interest in a range of patents outside the study. One author had no disclosures.

SOURCE: Gunduz-Bruce H et al. N Engl J Med. 2019 Sep 5;381:903-11. doi: 10.1056/NEJMoa1815981.

Single-cell sequencing of tissues from patients with Crohn’s disease has revealed a new pathogenic cellular module associated with failure of anti–tumor necrosis factor (TNF) therapy.

A paper published in the Aug. 29 online edition of Cell presented the results of a study that mapped the transcriptome – the RNA activity that reveals the patterns of gene expression for a cell – of lamina propria cells taken from biopsies of uninflamed and inflamed ileal tissues from 11 patients with ileal Crohn’s disease.

Jérôme C. Martin, PharmD, PhD, from the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, and coauthors wrote that while genome-wide association studies, tissue analyses, and animal models have revealed much about the immune and inflammatory processes that contribute to inflammatory bowel disease, there still remain unanswered questions about why some patients don’t respond to immune biotherapies.

“Current approaches restricted to well-established antibody panels based on prior knowledge preclude the identification of novel pathogenic cell populations in the diseased intestine,” they wrote.

Analysis of gene expression revealed significant cellular differences in the immune and stromal cells from inflamed compared to uninflamed ileum tissues. Researchers identified a group of cell subtypes that were highly correlated across inflamed ileums, and which included activated dendritic cells, activated fibroblasts, highly activated T cells, IgG plasma cells, inflammatory macrophages, inflammatory mononuclear phagocytes, and atypical chemokine receptor 1⁺-activated endothelial cells.

This so-called GIMATS module was present in only five of the patients, but it was independent of pathology severity, disease duration, and systemic markers of inflammation. The authors suggested that the module was associated with a positive feedback loop that increased the clustering of inflammatory mononuclear phagocytes in inflamed tissues.

“Taken together, our results identified a unique cellular organization in inflamed tissues of a subset of patients, thus revealing different pathogenic responses between patients despite similar pathological severity and systemic inflammatory markers,” the authors wrote.

The authors then looked for GIMATS expression in a larger cohort of 441 patients with ileal Crohn’s disease – including children aged over 2 years but excluding individuals with mutations that are associated with development of anti-TNF–resistant lesions early in life.

Given that 20%-30% of patients with ileal Crohn’s disease never respond to anti-TNF therapy, and require surgical intervention for uncontrolled bowel disease, the authors examined whether the GIMATs module might affect patient response to anti-TNF therapy.

They found that enrichment of this module was evident in the early stages of the disease, before the use of biologics therapy, and there were significant differences between treatment responders and nonresponders in their GIMATS module score at baseline. The authors said this suggested TNF blockade might not be enough to affect the inflammatory response associated with the GIMATS module.

“It is interesting that TNF was produced mainly by T cells in patients with low GIMATS module scores, while it was produced both by T cells and inflammatory [mononuclear phagocytes] in patients with a high module scores,” they wrote. “By providing a comprehensive network of the cellular and molecular basis for resistance to anti-TNF blockade, our study thus opens novel opportunities for therapeutic discoveries tailored for combination with anti-TNF antibody blockade.”

They also found that the GIMATs score did not correlate with disease activity in pediatric patients at diagnosis.

“As was observed in the discovery cohort, patients with high or low GIMATS module score had similar markers of systemic inflammation, indicating that the GIMATS score conveys information regarding response to biologic therapy that is not provided by standard [Crohn’s disease] biomarkers,” they wrote.

The study was partly supported by an author grant from Boehringer Ingelheim. Three authors also declared advisory board positions, consultancies, and research funding from the pharmaceutical industry, including Boehringer Ingelheim. No other conflicts of interest were declared.

SOURCE: Martin J et al. Cell. 2019 Aug 29. doi: 10.1016/j.cell.2019.08.008.

Single-cell sequencing of tissues from patients with Crohn’s disease has revealed a new pathogenic cellular module associated with failure of anti–tumor necrosis factor (TNF) therapy.

A paper published in the Aug. 29 online edition of Cell presented the results of a study that mapped the transcriptome – the RNA activity that reveals the patterns of gene expression for a cell – of lamina propria cells taken from biopsies of uninflamed and inflamed ileal tissues from 11 patients with ileal Crohn’s disease.

Jérôme C. Martin, PharmD, PhD, from the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, and coauthors wrote that while genome-wide association studies, tissue analyses, and animal models have revealed much about the immune and inflammatory processes that contribute to inflammatory bowel disease, there still remain unanswered questions about why some patients don’t respond to immune biotherapies.

“Current approaches restricted to well-established antibody panels based on prior knowledge preclude the identification of novel pathogenic cell populations in the diseased intestine,” they wrote.

Analysis of gene expression revealed significant cellular differences in the immune and stromal cells from inflamed compared to uninflamed ileum tissues. Researchers identified a group of cell subtypes that were highly correlated across inflamed ileums, and which included activated dendritic cells, activated fibroblasts, highly activated T cells, IgG plasma cells, inflammatory macrophages, inflammatory mononuclear phagocytes, and atypical chemokine receptor 1⁺-activated endothelial cells.

This so-called GIMATS module was present in only five of the patients, but it was independent of pathology severity, disease duration, and systemic markers of inflammation. The authors suggested that the module was associated with a positive feedback loop that increased the clustering of inflammatory mononuclear phagocytes in inflamed tissues.

“Taken together, our results identified a unique cellular organization in inflamed tissues of a subset of patients, thus revealing different pathogenic responses between patients despite similar pathological severity and systemic inflammatory markers,” the authors wrote.

The authors then looked for GIMATS expression in a larger cohort of 441 patients with ileal Crohn’s disease – including children aged over 2 years but excluding individuals with mutations that are associated with development of anti-TNF–resistant lesions early in life.

Given that 20%-30% of patients with ileal Crohn’s disease never respond to anti-TNF therapy, and require surgical intervention for uncontrolled bowel disease, the authors examined whether the GIMATs module might affect patient response to anti-TNF therapy.

They found that enrichment of this module was evident in the early stages of the disease, before the use of biologics therapy, and there were significant differences between treatment responders and nonresponders in their GIMATS module score at baseline. The authors said this suggested TNF blockade might not be enough to affect the inflammatory response associated with the GIMATS module.

“It is interesting that TNF was produced mainly by T cells in patients with low GIMATS module scores, while it was produced both by T cells and inflammatory [mononuclear phagocytes] in patients with a high module scores,” they wrote. “By providing a comprehensive network of the cellular and molecular basis for resistance to anti-TNF blockade, our study thus opens novel opportunities for therapeutic discoveries tailored for combination with anti-TNF antibody blockade.”

They also found that the GIMATs score did not correlate with disease activity in pediatric patients at diagnosis.

“As was observed in the discovery cohort, patients with high or low GIMATS module score had similar markers of systemic inflammation, indicating that the GIMATS score conveys information regarding response to biologic therapy that is not provided by standard [Crohn’s disease] biomarkers,” they wrote.

The study was partly supported by an author grant from Boehringer Ingelheim. Three authors also declared advisory board positions, consultancies, and research funding from the pharmaceutical industry, including Boehringer Ingelheim. No other conflicts of interest were declared.

SOURCE: Martin J et al. Cell. 2019 Aug 29. doi: 10.1016/j.cell.2019.08.008.

Single-cell sequencing of tissues from patients with Crohn’s disease has revealed a new pathogenic cellular module associated with failure of anti–tumor necrosis factor (TNF) therapy.

A paper published in the Aug. 29 online edition of Cell presented the results of a study that mapped the transcriptome – the RNA activity that reveals the patterns of gene expression for a cell – of lamina propria cells taken from biopsies of uninflamed and inflamed ileal tissues from 11 patients with ileal Crohn’s disease.

Jérôme C. Martin, PharmD, PhD, from the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, and coauthors wrote that while genome-wide association studies, tissue analyses, and animal models have revealed much about the immune and inflammatory processes that contribute to inflammatory bowel disease, there still remain unanswered questions about why some patients don’t respond to immune biotherapies.

“Current approaches restricted to well-established antibody panels based on prior knowledge preclude the identification of novel pathogenic cell populations in the diseased intestine,” they wrote.

Analysis of gene expression revealed significant cellular differences in the immune and stromal cells from inflamed compared to uninflamed ileum tissues. Researchers identified a group of cell subtypes that were highly correlated across inflamed ileums, and which included activated dendritic cells, activated fibroblasts, highly activated T cells, IgG plasma cells, inflammatory macrophages, inflammatory mononuclear phagocytes, and atypical chemokine receptor 1⁺-activated endothelial cells.

This so-called GIMATS module was present in only five of the patients, but it was independent of pathology severity, disease duration, and systemic markers of inflammation. The authors suggested that the module was associated with a positive feedback loop that increased the clustering of inflammatory mononuclear phagocytes in inflamed tissues.

“Taken together, our results identified a unique cellular organization in inflamed tissues of a subset of patients, thus revealing different pathogenic responses between patients despite similar pathological severity and systemic inflammatory markers,” the authors wrote.

The authors then looked for GIMATS expression in a larger cohort of 441 patients with ileal Crohn’s disease – including children aged over 2 years but excluding individuals with mutations that are associated with development of anti-TNF–resistant lesions early in life.

Given that 20%-30% of patients with ileal Crohn’s disease never respond to anti-TNF therapy, and require surgical intervention for uncontrolled bowel disease, the authors examined whether the GIMATs module might affect patient response to anti-TNF therapy.

They found that enrichment of this module was evident in the early stages of the disease, before the use of biologics therapy, and there were significant differences between treatment responders and nonresponders in their GIMATS module score at baseline. The authors said this suggested TNF blockade might not be enough to affect the inflammatory response associated with the GIMATS module.

“It is interesting that TNF was produced mainly by T cells in patients with low GIMATS module scores, while it was produced both by T cells and inflammatory [mononuclear phagocytes] in patients with a high module scores,” they wrote. “By providing a comprehensive network of the cellular and molecular basis for resistance to anti-TNF blockade, our study thus opens novel opportunities for therapeutic discoveries tailored for combination with anti-TNF antibody blockade.”

They also found that the GIMATs score did not correlate with disease activity in pediatric patients at diagnosis.

“As was observed in the discovery cohort, patients with high or low GIMATS module score had similar markers of systemic inflammation, indicating that the GIMATS score conveys information regarding response to biologic therapy that is not provided by standard [Crohn’s disease] biomarkers,” they wrote.

The study was partly supported by an author grant from Boehringer Ingelheim. Three authors also declared advisory board positions, consultancies, and research funding from the pharmaceutical industry, including Boehringer Ingelheim. No other conflicts of interest were declared.

SOURCE: Martin J et al. Cell. 2019 Aug 29. doi: 10.1016/j.cell.2019.08.008.

Weight-loss surgery in people with type 2 diabetes and obesity is associated with significant reductions in major adverse cardiovascular events, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.

The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.

At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).

The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA_1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.

Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).

In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.

In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m² or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.

The surgery was also associated with significantly greater reductions in HbA_1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.

The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.

In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.

“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.

“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.

The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.

“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.

The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.

SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.

Weight-loss surgery in people with type 2 diabetes and obesity is associated with significant reductions in major adverse cardiovascular events, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.

The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.

At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).

The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA_1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.

Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).

In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.

In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m² or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.

The surgery was also associated with significantly greater reductions in HbA_1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.

The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.

In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.

“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.

“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.

The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.

“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.

The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.

SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.

Weight-loss surgery in people with type 2 diabetes and obesity is associated with significant reductions in major adverse cardiovascular events, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.

The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.

At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).

The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA_1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.

Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).

In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.

In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m² or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.

The surgery was also associated with significantly greater reductions in HbA_1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.

The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.

In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.

“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.

“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.

The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.

“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.

The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.

SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.

Revascularization of more than just the culprit lesion in patients with ST-elevation myocardial infarctions could significantly reduce their risk of cardiovascular death or myocardial infarction, according to results of the COMPLETE trial, presented at the annual congress of the European Society of Cardiology.

The report, simultaneously published online in the New England Journal of Medicine, detailed the outcomes of COMPLETE (the Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI), a study in 4,041 patients who had experienced an ST-elevation myocardial infarction (STEMI), who had multi-vessel coronary artery disease, and who had undergone successful percutaneous coronary intervention of the culprit lesion.

Participants were randomized either to complete revascularization of all angiographically significant nonculprit lesions, or to no further revascularization, and were followed for a median of 3 years.

Of the patients who underwent complete revascularization, 7.8% experienced either cardiovascular death or another myocardial infarction, compared with 10.5% of those who only had revascularization of the culprit lesion, representing a significant 26% reduction (P = .004) in the incidence of this composite coprimary outcome.

The decrease in events was driven by a significant 32% reduction in the incidence of new myocardial infarction – particularly non-STEMI, new STEMI, and myocardial infarction type 1 – in the complete revascularization group, with only a 7% reduction in the incidence of death from cardiovascular causes.

With the second coprimary outcome of a composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization, this was seen in 8.9% of patients in the complete revascularization group compared with 16.7% of patients with the culprit-lesion-only group; a significant 49% reduction in incidence (P less than .001).

The authors calculated that 37 complete revascularizations would need to be performed to prevent one incidence of cardiovascular death or myocardial infarction. To prevent cardiovascular death, myocardial infarction, or ischemia-driven revascularization, the number needed to treat was 13.

The timing of complete revascularization did not appear to affect the benefits of the procedure, which were consistent among patients who underwent complete revascularization during their index hospitalization and in those who underwent the procedure after hospital discharge. Investigators had to specify before randomization whether the patient would undergo complete revascularization during the index hospitalization or after discharge but within 45 days.

The study also did not find any significant differences between the two groups in the risks of major bleeding, stroke, or stent thrombosis. However, the complete revascularization group did experience a nonsignificant 59% higher odds of contrast-associated acute kidney injury, which was attributed to the nonculprit lesion revascularization in seven patients in the complete revascularization group.

Dr. Shamir R. Mehta, of the Population Health Research Institute at McMaster University, Ontario, and coauthors noted that previous trials of complete-revascularization strategies in patients with STEMI were smaller and had included revascularization as part of a composite primary outcome.

“In the absence of a reduction in irreversible events such as cardiovascular death or new myocardial infarction, the clinical relevance of performing early nonculprit-lesion PCI in all patients with multivessel coronary artery disease to prevent later PCI in a smaller number of those patients is debatable,” they wrote. “We have now found that routine nonculprit-lesion PCI with the goal of complete revascularization confers a reduction in the long-term risk of cardiovascular death or myocardial infarction.”

No patients with cardiogenic shock were enrolled in the study, so the results could not be extrapolated to that patient group.

SOURCE: Mehta S et al. N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMoa1907775.

Revascularization of more than just the culprit lesion in patients with ST-elevation myocardial infarctions could significantly reduce their risk of cardiovascular death or myocardial infarction, according to results of the COMPLETE trial, presented at the annual congress of the European Society of Cardiology.

The report, simultaneously published online in the New England Journal of Medicine, detailed the outcomes of COMPLETE (the Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI), a study in 4,041 patients who had experienced an ST-elevation myocardial infarction (STEMI), who had multi-vessel coronary artery disease, and who had undergone successful percutaneous coronary intervention of the culprit lesion.

Participants were randomized either to complete revascularization of all angiographically significant nonculprit lesions, or to no further revascularization, and were followed for a median of 3 years.

Of the patients who underwent complete revascularization, 7.8% experienced either cardiovascular death or another myocardial infarction, compared with 10.5% of those who only had revascularization of the culprit lesion, representing a significant 26% reduction (P = .004) in the incidence of this composite coprimary outcome.

The decrease in events was driven by a significant 32% reduction in the incidence of new myocardial infarction – particularly non-STEMI, new STEMI, and myocardial infarction type 1 – in the complete revascularization group, with only a 7% reduction in the incidence of death from cardiovascular causes.

With the second coprimary outcome of a composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization, this was seen in 8.9% of patients in the complete revascularization group compared with 16.7% of patients with the culprit-lesion-only group; a significant 49% reduction in incidence (P less than .001).

The authors calculated that 37 complete revascularizations would need to be performed to prevent one incidence of cardiovascular death or myocardial infarction. To prevent cardiovascular death, myocardial infarction, or ischemia-driven revascularization, the number needed to treat was 13.

The timing of complete revascularization did not appear to affect the benefits of the procedure, which were consistent among patients who underwent complete revascularization during their index hospitalization and in those who underwent the procedure after hospital discharge. Investigators had to specify before randomization whether the patient would undergo complete revascularization during the index hospitalization or after discharge but within 45 days.

The study also did not find any significant differences between the two groups in the risks of major bleeding, stroke, or stent thrombosis. However, the complete revascularization group did experience a nonsignificant 59% higher odds of contrast-associated acute kidney injury, which was attributed to the nonculprit lesion revascularization in seven patients in the complete revascularization group.

Dr. Shamir R. Mehta, of the Population Health Research Institute at McMaster University, Ontario, and coauthors noted that previous trials of complete-revascularization strategies in patients with STEMI were smaller and had included revascularization as part of a composite primary outcome.

“In the absence of a reduction in irreversible events such as cardiovascular death or new myocardial infarction, the clinical relevance of performing early nonculprit-lesion PCI in all patients with multivessel coronary artery disease to prevent later PCI in a smaller number of those patients is debatable,” they wrote. “We have now found that routine nonculprit-lesion PCI with the goal of complete revascularization confers a reduction in the long-term risk of cardiovascular death or myocardial infarction.”

No patients with cardiogenic shock were enrolled in the study, so the results could not be extrapolated to that patient group.

SOURCE: Mehta S et al. N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMoa1907775.

Revascularization of more than just the culprit lesion in patients with ST-elevation myocardial infarctions could significantly reduce their risk of cardiovascular death or myocardial infarction, according to results of the COMPLETE trial, presented at the annual congress of the European Society of Cardiology.

The report, simultaneously published online in the New England Journal of Medicine, detailed the outcomes of COMPLETE (the Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI), a study in 4,041 patients who had experienced an ST-elevation myocardial infarction (STEMI), who had multi-vessel coronary artery disease, and who had undergone successful percutaneous coronary intervention of the culprit lesion.

Participants were randomized either to complete revascularization of all angiographically significant nonculprit lesions, or to no further revascularization, and were followed for a median of 3 years.

Of the patients who underwent complete revascularization, 7.8% experienced either cardiovascular death or another myocardial infarction, compared with 10.5% of those who only had revascularization of the culprit lesion, representing a significant 26% reduction (P = .004) in the incidence of this composite coprimary outcome.

The decrease in events was driven by a significant 32% reduction in the incidence of new myocardial infarction – particularly non-STEMI, new STEMI, and myocardial infarction type 1 – in the complete revascularization group, with only a 7% reduction in the incidence of death from cardiovascular causes.

With the second coprimary outcome of a composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization, this was seen in 8.9% of patients in the complete revascularization group compared with 16.7% of patients with the culprit-lesion-only group; a significant 49% reduction in incidence (P less than .001).

The authors calculated that 37 complete revascularizations would need to be performed to prevent one incidence of cardiovascular death or myocardial infarction. To prevent cardiovascular death, myocardial infarction, or ischemia-driven revascularization, the number needed to treat was 13.

The timing of complete revascularization did not appear to affect the benefits of the procedure, which were consistent among patients who underwent complete revascularization during their index hospitalization and in those who underwent the procedure after hospital discharge. Investigators had to specify before randomization whether the patient would undergo complete revascularization during the index hospitalization or after discharge but within 45 days.

The study also did not find any significant differences between the two groups in the risks of major bleeding, stroke, or stent thrombosis. However, the complete revascularization group did experience a nonsignificant 59% higher odds of contrast-associated acute kidney injury, which was attributed to the nonculprit lesion revascularization in seven patients in the complete revascularization group.

Dr. Shamir R. Mehta, of the Population Health Research Institute at McMaster University, Ontario, and coauthors noted that previous trials of complete-revascularization strategies in patients with STEMI were smaller and had included revascularization as part of a composite primary outcome.

“In the absence of a reduction in irreversible events such as cardiovascular death or new myocardial infarction, the clinical relevance of performing early nonculprit-lesion PCI in all patients with multivessel coronary artery disease to prevent later PCI in a smaller number of those patients is debatable,” they wrote. “We have now found that routine nonculprit-lesion PCI with the goal of complete revascularization confers a reduction in the long-term risk of cardiovascular death or myocardial infarction.”

No patients with cardiogenic shock were enrolled in the study, so the results could not be extrapolated to that patient group.

SOURCE: Mehta S et al. N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMoa1907775.

Individuals who are carriers of hemophilia genes and have reduced clotting factor activity have at least a twofold higher risk of joint-related comorbidities, compared with the general population, according to new research.

decade3d/Thinkstock

In a population-based cohort study using patient registry data, Swedish researchers identified 539 potential carriers of impaired factor VIII or IX gene in the X chromosome – 213 of whom had documented factor activity – and paired them with sex‐ and birthdate‐matched controls from the general population.

They found that carriers with reduced factor activity had a 2.3-fold higher risk of a joint diagnosis, compared with the general population (95% confidence interval, 1.1-4.5). Carriers with normal factor activity did not show a statistically significant increase in joint diagnosis hazard, however carriers with unknown factor activity had a 2.4-fold higher risk of joint diagnosis, compared with controls (95% CI, 1.8-3.2). The findings were published in Haemophilia.

By the age of 60 years, around 37% of carriers with reduced or unknown factor activity had received a joint diagnosis, compared with 23% of carriers with normal factor activity.

The most common joint diagnoses across carriers and controls were knee related, including gonarthrosis and internal derangement, but these were more common among carriers. Five carriers also recorded a diagnosis of hemophilic arthropathy or systemic disorders of connective tissue in diseases classified elsewhere.

Researchers also saw a 10-fold higher risk of joint surgery (95% CI, 1.0-3.7) among carriers with reduced factor activity – although the numbers were small – and even among carriers with normal factor activity, there was a nearly twofold higher rate (95% CI, 0.9-4.6), compared with the control population.

Carriers with reduced or unknown factor activity also had a higher risk of outpatient hospitalization, compared with the general population, although no effect was seen in carriers with normal factor activity.

“Although the frequency of joint comorbidities overall was relatively low, our results clearly indicate and confirm a higher burden of joint afflictions, including an earlier age at joint diagnosis, for carriers with reduced or unknown factor activity compared with the general population, as well as more joint surgeries and related hospitalizations,” wrote Mehdi Osooli, PhD, from the Skåne University Hospital in Malmö, Sweden, and his coauthors.

The authors noted that the findings correlated with their earlier research on the incidence of arthropathy among males with mild hemophilia, who have previously been found to have a ninefold higher incidence of arthropathy‐related hospital admissions and a 16‐fold higher incidence of joint disease.

“The relatively higher incidence in the male population compared with the carriers in the current study may be explained by the lower median factor activity level, for example, levels between 5% and 40% in males with mild haemophilia compared with a median overall of 50% in carriers,” they wrote.

All authors declared that they had no conflict of interest related to the study findings. Four of the authors reported financial ties to companies including Novo Nordisk, Shire, and Bayer.

SOURCE: Osooli M et al. Haemophilia. 2019 Aug 14. doi: 10.1111/hae.13831.

Individuals who are carriers of hemophilia genes and have reduced clotting factor activity have at least a twofold higher risk of joint-related comorbidities, compared with the general population, according to new research.

decade3d/Thinkstock

In a population-based cohort study using patient registry data, Swedish researchers identified 539 potential carriers of impaired factor VIII or IX gene in the X chromosome – 213 of whom had documented factor activity – and paired them with sex‐ and birthdate‐matched controls from the general population.

They found that carriers with reduced factor activity had a 2.3-fold higher risk of a joint diagnosis, compared with the general population (95% confidence interval, 1.1-4.5). Carriers with normal factor activity did not show a statistically significant increase in joint diagnosis hazard, however carriers with unknown factor activity had a 2.4-fold higher risk of joint diagnosis, compared with controls (95% CI, 1.8-3.2). The findings were published in Haemophilia.

By the age of 60 years, around 37% of carriers with reduced or unknown factor activity had received a joint diagnosis, compared with 23% of carriers with normal factor activity.

The most common joint diagnoses across carriers and controls were knee related, including gonarthrosis and internal derangement, but these were more common among carriers. Five carriers also recorded a diagnosis of hemophilic arthropathy or systemic disorders of connective tissue in diseases classified elsewhere.

Researchers also saw a 10-fold higher risk of joint surgery (95% CI, 1.0-3.7) among carriers with reduced factor activity – although the numbers were small – and even among carriers with normal factor activity, there was a nearly twofold higher rate (95% CI, 0.9-4.6), compared with the control population.

Carriers with reduced or unknown factor activity also had a higher risk of outpatient hospitalization, compared with the general population, although no effect was seen in carriers with normal factor activity.

“Although the frequency of joint comorbidities overall was relatively low, our results clearly indicate and confirm a higher burden of joint afflictions, including an earlier age at joint diagnosis, for carriers with reduced or unknown factor activity compared with the general population, as well as more joint surgeries and related hospitalizations,” wrote Mehdi Osooli, PhD, from the Skåne University Hospital in Malmö, Sweden, and his coauthors.

The authors noted that the findings correlated with their earlier research on the incidence of arthropathy among males with mild hemophilia, who have previously been found to have a ninefold higher incidence of arthropathy‐related hospital admissions and a 16‐fold higher incidence of joint disease.

“The relatively higher incidence in the male population compared with the carriers in the current study may be explained by the lower median factor activity level, for example, levels between 5% and 40% in males with mild haemophilia compared with a median overall of 50% in carriers,” they wrote.

All authors declared that they had no conflict of interest related to the study findings. Four of the authors reported financial ties to companies including Novo Nordisk, Shire, and Bayer.

SOURCE: Osooli M et al. Haemophilia. 2019 Aug 14. doi: 10.1111/hae.13831.

Individuals who are carriers of hemophilia genes and have reduced clotting factor activity have at least a twofold higher risk of joint-related comorbidities, compared with the general population, according to new research.

decade3d/Thinkstock

In a population-based cohort study using patient registry data, Swedish researchers identified 539 potential carriers of impaired factor VIII or IX gene in the X chromosome – 213 of whom had documented factor activity – and paired them with sex‐ and birthdate‐matched controls from the general population.

They found that carriers with reduced factor activity had a 2.3-fold higher risk of a joint diagnosis, compared with the general population (95% confidence interval, 1.1-4.5). Carriers with normal factor activity did not show a statistically significant increase in joint diagnosis hazard, however carriers with unknown factor activity had a 2.4-fold higher risk of joint diagnosis, compared with controls (95% CI, 1.8-3.2). The findings were published in Haemophilia.

By the age of 60 years, around 37% of carriers with reduced or unknown factor activity had received a joint diagnosis, compared with 23% of carriers with normal factor activity.

The most common joint diagnoses across carriers and controls were knee related, including gonarthrosis and internal derangement, but these were more common among carriers. Five carriers also recorded a diagnosis of hemophilic arthropathy or systemic disorders of connective tissue in diseases classified elsewhere.

Researchers also saw a 10-fold higher risk of joint surgery (95% CI, 1.0-3.7) among carriers with reduced factor activity – although the numbers were small – and even among carriers with normal factor activity, there was a nearly twofold higher rate (95% CI, 0.9-4.6), compared with the control population.

Carriers with reduced or unknown factor activity also had a higher risk of outpatient hospitalization, compared with the general population, although no effect was seen in carriers with normal factor activity.

“Although the frequency of joint comorbidities overall was relatively low, our results clearly indicate and confirm a higher burden of joint afflictions, including an earlier age at joint diagnosis, for carriers with reduced or unknown factor activity compared with the general population, as well as more joint surgeries and related hospitalizations,” wrote Mehdi Osooli, PhD, from the Skåne University Hospital in Malmö, Sweden, and his coauthors.

The authors noted that the findings correlated with their earlier research on the incidence of arthropathy among males with mild hemophilia, who have previously been found to have a ninefold higher incidence of arthropathy‐related hospital admissions and a 16‐fold higher incidence of joint disease.

“The relatively higher incidence in the male population compared with the carriers in the current study may be explained by the lower median factor activity level, for example, levels between 5% and 40% in males with mild haemophilia compared with a median overall of 50% in carriers,” they wrote.

All authors declared that they had no conflict of interest related to the study findings. Four of the authors reported financial ties to companies including Novo Nordisk, Shire, and Bayer.

SOURCE: Osooli M et al. Haemophilia. 2019 Aug 14. doi: 10.1111/hae.13831.

Endometriosis is associated with an increased risk of adverse pregnancy outcomes such as ectopic pregnancy, gestational diabetes, and preterm birth, a large study has found.

designer491/Thinkstock

Leslie V. Farland, ScD, of the University of Arizona, Tucson, and coauthors reported their analysis of data from 196,722 pregnancies in 116,429 women aged 25-42 years enrolled in the Nurses Health Study II cohort in Obstetrics & Gynecology.

Among the women with eligible pregnancies, 4.5% had laparoscopically confirmed endometriosis. These women were found to have a 40% higher risk of spontaneous abortion than were women without endometriosis (19.3% vs. 12.3%) and a 46% higher risk of ectopic pregnancy (1.8% vs. 0.8%). The risk of ectopic pregnancy was even more pronounced in women without a history of infertility.

Researchers also saw a 16% higher risk of preterm birth in women with endometriosis (12% in women with endometriosis vs. 8.1% in women without endometriosis), and a 16% greater risk of low-birth-weight babies (5.6% in women with endometriosis vs. 3.6% in women without endometriosis).

There also was the suggestion of an increased risk of stillbirth, although the researchers said this finding should be interpreted with caution because of the small sample size.

Women with endometriosis also had a 35% greater risk of gestational diabetes than did women without endometriosis. This association was stronger in women younger than age 35 years, in women without a history of infertility, and in women undergoing their second or later pregnancy. Endometriosis also was associated with a 30% greater risk of hypertensive disorders of pregnancy, particularly in second or later pregnancies.

Dr. Farland and associates wrote that recent research on the relationship between endometriosis and pregnancy outcomes had yielded “mixed results.”

“For example, much of the research to date has been conducted among women attending infertility clinics, which may conflate the influence of advanced maternal age, fertility treatment, and infertility itself with endometriosis, given the known elevated risk of adverse pregnancy outcomes in this population,” they wrote.

They suggested that one possible mechanism for the association between endometriosis and adverse pregnancy outcomes was progesterone resistance, which was hypothesized to affect genes important for embryo implantation and therefore contribute to pregnancy loss. Another mechanism could be increased inflammation, which may increase the risk of preterm birth and abnormal placentation.

“Elucidating mechanisms of association and possible pathways for intervention or screening procedures will be critical to improve the health of women with endometriosis and their children,” they wrote.

Katrina Mark, MD, commented in an interview, “This study, which identifies an increased risk of adverse pregnancy outcomes in women with endometriosis, is an important step in improving reproductive success.

“Although some explanations for these findings were postulated by the researchers, the next step will be to study the underlying physiology that leads to these complications so that interventions can be offered to improve outcomes,” said Dr. Mark, who is an associate professor of obstetrics, gynecology & reproductive sciences at the University of Maryland School of Medicine. Dr. Mark, who is not a coauthor of the study, was asked to comment on the study’s merit.

The study was supported by grants from the National Institutes of Health. Daniela A. Carusi, MD, received funding from UpToDate; Andrew W. Horne, MB, ChB, PhD, declared European government grants funding and consultancies with the pharmaceutical sector unrelated to the present study; Jorge E. Chavarro, MD, and Stacey A. Missmer, ScD, declared institutional funding from the NIH, and Dr. Missmer also received institutional funding from other funding bodies, as well as consulting fees. Dr. Farland and the remaining coauthors had no relevant financial disclosures. Dr. Mark has no relevant financial disclosures.
 

SOURCE: Farland LV et al. Obstetr Gynecol. 2019. doi: 10.1097/AOG.0000000000003410.

Endometriosis is associated with an increased risk of adverse pregnancy outcomes such as ectopic pregnancy, gestational diabetes, and preterm birth, a large study has found.

designer491/Thinkstock

Leslie V. Farland, ScD, of the University of Arizona, Tucson, and coauthors reported their analysis of data from 196,722 pregnancies in 116,429 women aged 25-42 years enrolled in the Nurses Health Study II cohort in Obstetrics & Gynecology.

Among the women with eligible pregnancies, 4.5% had laparoscopically confirmed endometriosis. These women were found to have a 40% higher risk of spontaneous abortion than were women without endometriosis (19.3% vs. 12.3%) and a 46% higher risk of ectopic pregnancy (1.8% vs. 0.8%). The risk of ectopic pregnancy was even more pronounced in women without a history of infertility.

Researchers also saw a 16% higher risk of preterm birth in women with endometriosis (12% in women with endometriosis vs. 8.1% in women without endometriosis), and a 16% greater risk of low-birth-weight babies (5.6% in women with endometriosis vs. 3.6% in women without endometriosis).

There also was the suggestion of an increased risk of stillbirth, although the researchers said this finding should be interpreted with caution because of the small sample size.

Women with endometriosis also had a 35% greater risk of gestational diabetes than did women without endometriosis. This association was stronger in women younger than age 35 years, in women without a history of infertility, and in women undergoing their second or later pregnancy. Endometriosis also was associated with a 30% greater risk of hypertensive disorders of pregnancy, particularly in second or later pregnancies.

Dr. Farland and associates wrote that recent research on the relationship between endometriosis and pregnancy outcomes had yielded “mixed results.”

“For example, much of the research to date has been conducted among women attending infertility clinics, which may conflate the influence of advanced maternal age, fertility treatment, and infertility itself with endometriosis, given the known elevated risk of adverse pregnancy outcomes in this population,” they wrote.

They suggested that one possible mechanism for the association between endometriosis and adverse pregnancy outcomes was progesterone resistance, which was hypothesized to affect genes important for embryo implantation and therefore contribute to pregnancy loss. Another mechanism could be increased inflammation, which may increase the risk of preterm birth and abnormal placentation.

“Elucidating mechanisms of association and possible pathways for intervention or screening procedures will be critical to improve the health of women with endometriosis and their children,” they wrote.

Katrina Mark, MD, commented in an interview, “This study, which identifies an increased risk of adverse pregnancy outcomes in women with endometriosis, is an important step in improving reproductive success.

“Although some explanations for these findings were postulated by the researchers, the next step will be to study the underlying physiology that leads to these complications so that interventions can be offered to improve outcomes,” said Dr. Mark, who is an associate professor of obstetrics, gynecology & reproductive sciences at the University of Maryland School of Medicine. Dr. Mark, who is not a coauthor of the study, was asked to comment on the study’s merit.

The study was supported by grants from the National Institutes of Health. Daniela A. Carusi, MD, received funding from UpToDate; Andrew W. Horne, MB, ChB, PhD, declared European government grants funding and consultancies with the pharmaceutical sector unrelated to the present study; Jorge E. Chavarro, MD, and Stacey A. Missmer, ScD, declared institutional funding from the NIH, and Dr. Missmer also received institutional funding from other funding bodies, as well as consulting fees. Dr. Farland and the remaining coauthors had no relevant financial disclosures. Dr. Mark has no relevant financial disclosures.
 

SOURCE: Farland LV et al. Obstetr Gynecol. 2019. doi: 10.1097/AOG.0000000000003410.

Endometriosis is associated with an increased risk of adverse pregnancy outcomes such as ectopic pregnancy, gestational diabetes, and preterm birth, a large study has found.

designer491/Thinkstock

Leslie V. Farland, ScD, of the University of Arizona, Tucson, and coauthors reported their analysis of data from 196,722 pregnancies in 116,429 women aged 25-42 years enrolled in the Nurses Health Study II cohort in Obstetrics & Gynecology.

Among the women with eligible pregnancies, 4.5% had laparoscopically confirmed endometriosis. These women were found to have a 40% higher risk of spontaneous abortion than were women without endometriosis (19.3% vs. 12.3%) and a 46% higher risk of ectopic pregnancy (1.8% vs. 0.8%). The risk of ectopic pregnancy was even more pronounced in women without a history of infertility.

Researchers also saw a 16% higher risk of preterm birth in women with endometriosis (12% in women with endometriosis vs. 8.1% in women without endometriosis), and a 16% greater risk of low-birth-weight babies (5.6% in women with endometriosis vs. 3.6% in women without endometriosis).

There also was the suggestion of an increased risk of stillbirth, although the researchers said this finding should be interpreted with caution because of the small sample size.

Women with endometriosis also had a 35% greater risk of gestational diabetes than did women without endometriosis. This association was stronger in women younger than age 35 years, in women without a history of infertility, and in women undergoing their second or later pregnancy. Endometriosis also was associated with a 30% greater risk of hypertensive disorders of pregnancy, particularly in second or later pregnancies.

Dr. Farland and associates wrote that recent research on the relationship between endometriosis and pregnancy outcomes had yielded “mixed results.”

“For example, much of the research to date has been conducted among women attending infertility clinics, which may conflate the influence of advanced maternal age, fertility treatment, and infertility itself with endometriosis, given the known elevated risk of adverse pregnancy outcomes in this population,” they wrote.

They suggested that one possible mechanism for the association between endometriosis and adverse pregnancy outcomes was progesterone resistance, which was hypothesized to affect genes important for embryo implantation and therefore contribute to pregnancy loss. Another mechanism could be increased inflammation, which may increase the risk of preterm birth and abnormal placentation.

“Elucidating mechanisms of association and possible pathways for intervention or screening procedures will be critical to improve the health of women with endometriosis and their children,” they wrote.

Katrina Mark, MD, commented in an interview, “This study, which identifies an increased risk of adverse pregnancy outcomes in women with endometriosis, is an important step in improving reproductive success.

“Although some explanations for these findings were postulated by the researchers, the next step will be to study the underlying physiology that leads to these complications so that interventions can be offered to improve outcomes,” said Dr. Mark, who is an associate professor of obstetrics, gynecology & reproductive sciences at the University of Maryland School of Medicine. Dr. Mark, who is not a coauthor of the study, was asked to comment on the study’s merit.

The study was supported by grants from the National Institutes of Health. Daniela A. Carusi, MD, received funding from UpToDate; Andrew W. Horne, MB, ChB, PhD, declared European government grants funding and consultancies with the pharmaceutical sector unrelated to the present study; Jorge E. Chavarro, MD, and Stacey A. Missmer, ScD, declared institutional funding from the NIH, and Dr. Missmer also received institutional funding from other funding bodies, as well as consulting fees. Dr. Farland and the remaining coauthors had no relevant financial disclosures. Dr. Mark has no relevant financial disclosures.
 

SOURCE: Farland LV et al. Obstetr Gynecol. 2019. doi: 10.1097/AOG.0000000000003410.

Slightly more than half of adolescents in the United States have been fully vaccinated against the human papillomavirus, according to a report published in Morbidity and Mortality Weekly Report.

Joseph Abbott/Thinkstock

Researchers analyzed data from 18,700 adolescents aged 13-17 years – 48% of whom were female – in the 2018 National Immunization Survey–Teen to discover that 51% of adolescents were up to date with the human papillomavirus (HPV) vaccine, and 68% had received at least one dose of the vaccine.

There was an increase in HPV vaccination coverage from 2017 to 2018, but this was attributable to a 4.4 percentage point increase in males who were up to date, compared with a 0.6 percentage point increase in females.

“Although HPV vaccina­tion coverage improved, increases among all adolescents were modest compared with increases in previous years and were observed only among males,” wrote Tanja Y. Walker of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, and coauthors.

The number of adolescents who had at least one dose of the quadrivalent meningococ­cal conjugate (4MenB) vaccine increased by 1.5 percentage points to 86.6%, while among individuals aged 17 years, coverage with two or more doses of 4MenB vaccine increased by 6.5 percentage points to 50.8%. Tdap coverage remained the same at 89% (MMWR 2019;68(33):718-23).

Slightly more than half of adolescents in the United States have been fully vaccinated against the human papillomavirus, according to a report published in Morbidity and Mortality Weekly Report.

Joseph Abbott/Thinkstock

Researchers analyzed data from 18,700 adolescents aged 13-17 years – 48% of whom were female – in the 2018 National Immunization Survey–Teen to discover that 51% of adolescents were up to date with the human papillomavirus (HPV) vaccine, and 68% had received at least one dose of the vaccine.

There was an increase in HPV vaccination coverage from 2017 to 2018, but this was attributable to a 4.4 percentage point increase in males who were up to date, compared with a 0.6 percentage point increase in females.

“Although HPV vaccina­tion coverage improved, increases among all adolescents were modest compared with increases in previous years and were observed only among males,” wrote Tanja Y. Walker of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, and coauthors.

The number of adolescents who had at least one dose of the quadrivalent meningococ­cal conjugate (4MenB) vaccine increased by 1.5 percentage points to 86.6%, while among individuals aged 17 years, coverage with two or more doses of 4MenB vaccine increased by 6.5 percentage points to 50.8%. Tdap coverage remained the same at 89% (MMWR 2019;68(33):718-23).

Slightly more than half of adolescents in the United States have been fully vaccinated against the human papillomavirus, according to a report published in Morbidity and Mortality Weekly Report.

Joseph Abbott/Thinkstock

Researchers analyzed data from 18,700 adolescents aged 13-17 years – 48% of whom were female – in the 2018 National Immunization Survey–Teen to discover that 51% of adolescents were up to date with the human papillomavirus (HPV) vaccine, and 68% had received at least one dose of the vaccine.

There was an increase in HPV vaccination coverage from 2017 to 2018, but this was attributable to a 4.4 percentage point increase in males who were up to date, compared with a 0.6 percentage point increase in females.

“Although HPV vaccina­tion coverage improved, increases among all adolescents were modest compared with increases in previous years and were observed only among males,” wrote Tanja Y. Walker of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, and coauthors.

The number of adolescents who had at least one dose of the quadrivalent meningococ­cal conjugate (4MenB) vaccine increased by 1.5 percentage points to 86.6%, while among individuals aged 17 years, coverage with two or more doses of 4MenB vaccine increased by 6.5 percentage points to 50.8%. Tdap coverage remained the same at 89% (MMWR 2019;68(33):718-23).

Hidradenitis suppurativa is associated with more than a 600% higher risk of nonalcoholic fatty liver disease, independent of other metabolic risk factors, a study has found.

The results of the case-control study of 70 individuals with hidradenitis suppurativa (HS) and 150 age- and gender-matched controls were published in the Journal of the European Academy of Dermatology and Venereology. Using hepatic ultrasonography and transient elastography, the investigators found that 51 (72.9%) the participants with HS also had nonalcoholic fatty liver disease (NAFLD), compared with 37 (24.7%) of the controls (P less than .001).

Those with HS and NAFLD were more likely to be obese, have more central adiposity, and meet more of the criteria for metabolic syndrome than those with HS but without NAFLD. They also showed higher serum ALT levels, higher triglycerides, and higher controlled attenuation parameter scores, which is a surrogate marker of liver steatosis.

However, the HS plus NAFLD group had similar rates of active smoking, diabetes, dyslipidemia, hypertension, and cardiovascular events, compared with those who had HS only. They also showed no differences in hemoglobin A_1c, serum insulin, insulin resistance, or liver stiffness, compared with the HS-only group.

When researchers compared the participants with HS plus NAFLD with controls with NAFLD, they found the HS group had significantly higher levels of liver stiffness measurement, which is a surrogate marker of liver fibrosis and severity, but there were no differences in the degree of hepatic steatosis.

The individuals with HS plus NAFLD had significantly lower serum albumin, but significantly higher serum gamma–glutamyl transpeptidase and ferritin, compared with controls who had NAFLD. They were also more likely to have metabolic risk factors such as hypertension, dyslipidemia, and metabolic syndrome.

The multivariate analysis also showed that male sex was a protective factor, because the prevalence of obesity was higher in women.

After adjusting for classic cardiovascular and steatosis risk factors, the researchers calculated that HS was a significant and independent risk factor for NAFLD, with an odds ratio of 7.75 (P less than .001). The results provide “the first evidence that patients with HS have a significant high prevalence of NAFLD, which is independent of classic metabolic risk factors and, according to our results, probably not related to the severity of the disease,” wrote Carlos Durán-Vian, MD, from the department of dermatology at the University of Cantabria, Santander, Spain, and coauthors.

“We think that our findings might have potential clinical implications, and physicians involved in the care of patients with HS should be aware of the link between this entity and NAFLD, in order to improve the overall management of these patients,” they wrote, noting that HS is often associated with the same metabolic disorders that can promote fatty liver disease, such as obesity and metabolic syndrome. But the discovery that it is an independent risk factor demands other hypotheses to explain the association between the two conditions.

“In this sense, a possible explanation to deeper understanding the link between HS and NAFLD could be the presence of chronic inflammation due to persistent and abnormal secretion of adipokines (i.e. adiponectin, leptin, resistin) and several proinflammatory cytokines,” the authors wrote, pointing out that NAFLD is also common among people with immune-mediated inflammatory disorders.

The study had the limitation of being an observational, cross-sectional design, and the authors acknowledged that the cohort was relatively small. They also were unable to use liver biopsies to confirm the NAFLD diagnosis.

No funding or conflicts of interest were reported.

SOURCE: Durán-Vian C et al. J Eur Acad Dermatol Venereol. 2019 Jul 1. doi: 10.1111/jdv.15764.

Hidradenitis suppurativa is associated with more than a 600% higher risk of nonalcoholic fatty liver disease, independent of other metabolic risk factors, a study has found.

The results of the case-control study of 70 individuals with hidradenitis suppurativa (HS) and 150 age- and gender-matched controls were published in the Journal of the European Academy of Dermatology and Venereology. Using hepatic ultrasonography and transient elastography, the investigators found that 51 (72.9%) the participants with HS also had nonalcoholic fatty liver disease (NAFLD), compared with 37 (24.7%) of the controls (P less than .001).

Those with HS and NAFLD were more likely to be obese, have more central adiposity, and meet more of the criteria for metabolic syndrome than those with HS but without NAFLD. They also showed higher serum ALT levels, higher triglycerides, and higher controlled attenuation parameter scores, which is a surrogate marker of liver steatosis.

However, the HS plus NAFLD group had similar rates of active smoking, diabetes, dyslipidemia, hypertension, and cardiovascular events, compared with those who had HS only. They also showed no differences in hemoglobin A_1c, serum insulin, insulin resistance, or liver stiffness, compared with the HS-only group.

When researchers compared the participants with HS plus NAFLD with controls with NAFLD, they found the HS group had significantly higher levels of liver stiffness measurement, which is a surrogate marker of liver fibrosis and severity, but there were no differences in the degree of hepatic steatosis.

The individuals with HS plus NAFLD had significantly lower serum albumin, but significantly higher serum gamma–glutamyl transpeptidase and ferritin, compared with controls who had NAFLD. They were also more likely to have metabolic risk factors such as hypertension, dyslipidemia, and metabolic syndrome.

The multivariate analysis also showed that male sex was a protective factor, because the prevalence of obesity was higher in women.

After adjusting for classic cardiovascular and steatosis risk factors, the researchers calculated that HS was a significant and independent risk factor for NAFLD, with an odds ratio of 7.75 (P less than .001). The results provide “the first evidence that patients with HS have a significant high prevalence of NAFLD, which is independent of classic metabolic risk factors and, according to our results, probably not related to the severity of the disease,” wrote Carlos Durán-Vian, MD, from the department of dermatology at the University of Cantabria, Santander, Spain, and coauthors.

“We think that our findings might have potential clinical implications, and physicians involved in the care of patients with HS should be aware of the link between this entity and NAFLD, in order to improve the overall management of these patients,” they wrote, noting that HS is often associated with the same metabolic disorders that can promote fatty liver disease, such as obesity and metabolic syndrome. But the discovery that it is an independent risk factor demands other hypotheses to explain the association between the two conditions.

“In this sense, a possible explanation to deeper understanding the link between HS and NAFLD could be the presence of chronic inflammation due to persistent and abnormal secretion of adipokines (i.e. adiponectin, leptin, resistin) and several proinflammatory cytokines,” the authors wrote, pointing out that NAFLD is also common among people with immune-mediated inflammatory disorders.

The study had the limitation of being an observational, cross-sectional design, and the authors acknowledged that the cohort was relatively small. They also were unable to use liver biopsies to confirm the NAFLD diagnosis.

No funding or conflicts of interest were reported.

SOURCE: Durán-Vian C et al. J Eur Acad Dermatol Venereol. 2019 Jul 1. doi: 10.1111/jdv.15764.

Hidradenitis suppurativa is associated with more than a 600% higher risk of nonalcoholic fatty liver disease, independent of other metabolic risk factors, a study has found.

The results of the case-control study of 70 individuals with hidradenitis suppurativa (HS) and 150 age- and gender-matched controls were published in the Journal of the European Academy of Dermatology and Venereology. Using hepatic ultrasonography and transient elastography, the investigators found that 51 (72.9%) the participants with HS also had nonalcoholic fatty liver disease (NAFLD), compared with 37 (24.7%) of the controls (P less than .001).

Those with HS and NAFLD were more likely to be obese, have more central adiposity, and meet more of the criteria for metabolic syndrome than those with HS but without NAFLD. They also showed higher serum ALT levels, higher triglycerides, and higher controlled attenuation parameter scores, which is a surrogate marker of liver steatosis.

However, the HS plus NAFLD group had similar rates of active smoking, diabetes, dyslipidemia, hypertension, and cardiovascular events, compared with those who had HS only. They also showed no differences in hemoglobin A_1c, serum insulin, insulin resistance, or liver stiffness, compared with the HS-only group.

When researchers compared the participants with HS plus NAFLD with controls with NAFLD, they found the HS group had significantly higher levels of liver stiffness measurement, which is a surrogate marker of liver fibrosis and severity, but there were no differences in the degree of hepatic steatosis.

The individuals with HS plus NAFLD had significantly lower serum albumin, but significantly higher serum gamma–glutamyl transpeptidase and ferritin, compared with controls who had NAFLD. They were also more likely to have metabolic risk factors such as hypertension, dyslipidemia, and metabolic syndrome.

The multivariate analysis also showed that male sex was a protective factor, because the prevalence of obesity was higher in women.

After adjusting for classic cardiovascular and steatosis risk factors, the researchers calculated that HS was a significant and independent risk factor for NAFLD, with an odds ratio of 7.75 (P less than .001). The results provide “the first evidence that patients with HS have a significant high prevalence of NAFLD, which is independent of classic metabolic risk factors and, according to our results, probably not related to the severity of the disease,” wrote Carlos Durán-Vian, MD, from the department of dermatology at the University of Cantabria, Santander, Spain, and coauthors.

“We think that our findings might have potential clinical implications, and physicians involved in the care of patients with HS should be aware of the link between this entity and NAFLD, in order to improve the overall management of these patients,” they wrote, noting that HS is often associated with the same metabolic disorders that can promote fatty liver disease, such as obesity and metabolic syndrome. But the discovery that it is an independent risk factor demands other hypotheses to explain the association between the two conditions.

“In this sense, a possible explanation to deeper understanding the link between HS and NAFLD could be the presence of chronic inflammation due to persistent and abnormal secretion of adipokines (i.e. adiponectin, leptin, resistin) and several proinflammatory cytokines,” the authors wrote, pointing out that NAFLD is also common among people with immune-mediated inflammatory disorders.

The study had the limitation of being an observational, cross-sectional design, and the authors acknowledged that the cohort was relatively small. They also were unable to use liver biopsies to confirm the NAFLD diagnosis.

No funding or conflicts of interest were reported.

SOURCE: Durán-Vian C et al. J Eur Acad Dermatol Venereol. 2019 Jul 1. doi: 10.1111/jdv.15764.