Michele G. Sullivan

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

[email protected]

On Twitter @alz_gal

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

[email protected]

On Twitter @alz_gal

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

[email protected]

On Twitter @alz_gal

People with type 2 diabetes are up to 55% more likely to experience hospital-treated infections and up to 30% more likely to receive an antibiotic prescription in the community setting, compared with the general population, but these associations moderated over an 8-year period – a phenomenon that could be at least partly related to better treatment of diabetes and an overall improvement in mean blood glucose levels, according to results of a large population-based study.

“These findings may be driven by earlier detection and treatment of milder type 2 diabetes cases over time,” or by improved therapy of hyperglycemia and other risk factors, wrote Anil Mor, MD, of Aarhus University Hospital, Denmark, and his associates (Clin Infect Dis. 2016 June 26. doi: 10.1093/cid/ciw345).

©moodboard/Thinkstock

The study ran from 2004 to 2012 and used data from the Danish National Patient Registry. It tracked community- and hospital-treated infections in approximately 774,017 controls; of these, 155,158 had type 2 diabetes. Patients with diabetes were more likely to have serious medical comorbidities compared with controls (29% vs. 21%). These included myocardial infarction (5% vs. 3%), heart failure (4% vs. 2%), cerebrovascular diseases (7% vs. 5%), peripheral vascular diseases (4% vs. 2%), and chronic pulmonary disease (6% vs. 2%).

Over the study period, 62% of the diabetes patients received an antibiotic, compared with 55% of the controls – a 24% increased relative risk in a model that adjusted for factors such as alcohol use, Charlson comorbidity index, and cardiovascular and renal comorbidities. Cephalosporins were the most commonly prescribed drugs, followed by antimycobacterial agents, quinolones, and antibiotics commonly used for urinary tract and Staphylococcus aureus infections.

Hospital-treated infections were significantly more common among patients with diabetes, with 19% having at least one such infection compared with 13% of controls (RR 1.55). On a larger scale, at a median follow-up of 2.8 years, the hospital-treated rate among diabetes patients was 58 per 1,000 person/years vs. 39 per 1,000 person/years among controls – a relative risk of 1.49.

Patients were at highest risk for emphysematous cholecystitis (adjusted rate ratio 1.74) and abscesses, tuberculosis, and meningococcal infections. Pneumonia was approximately 30% more likely among patients.

The risk of a hospital-treated infection was highest among younger patients aged 40-50 years (RR 1.77) and lowest among those older than 80 years (RR 1.29). It was also higher among those with higher comorbidity scores. Statin use appeared to attenuate some of the risk, the authors noted. The authors did not discuss the possible cause of this association.

The annual risk of a hospital-treated infection among patients declined from a high of 1.89 in 2004 to 1.59 in 2011. The risk of receiving a community-based antibiotic prescription declined as well, from 1.31 in 2004 to 1.26 in 2011.

These changes were not seen in the control group, suggesting that patients with diabetes were experiencing a unique improvement in infections – earlier detection and treatment of type 2 diabetes, and better comorbidity management could be explanations, the investigators speculated.

The study was sponsored by the Danish Centre for Strategic Research in Type 2 Diabetes and the Program for Clinical Research Infrastructure established by the Lundbeck Foundation and the Novo Nordisk Foundation. Several of the coauthors reported financial ties with various pharmaceutical companies.

People with type 2 diabetes are up to 55% more likely to experience hospital-treated infections and up to 30% more likely to receive an antibiotic prescription in the community setting, compared with the general population, but these associations moderated over an 8-year period – a phenomenon that could be at least partly related to better treatment of diabetes and an overall improvement in mean blood glucose levels, according to results of a large population-based study.

“These findings may be driven by earlier detection and treatment of milder type 2 diabetes cases over time,” or by improved therapy of hyperglycemia and other risk factors, wrote Anil Mor, MD, of Aarhus University Hospital, Denmark, and his associates (Clin Infect Dis. 2016 June 26. doi: 10.1093/cid/ciw345).

©moodboard/Thinkstock

The study ran from 2004 to 2012 and used data from the Danish National Patient Registry. It tracked community- and hospital-treated infections in approximately 774,017 controls; of these, 155,158 had type 2 diabetes. Patients with diabetes were more likely to have serious medical comorbidities compared with controls (29% vs. 21%). These included myocardial infarction (5% vs. 3%), heart failure (4% vs. 2%), cerebrovascular diseases (7% vs. 5%), peripheral vascular diseases (4% vs. 2%), and chronic pulmonary disease (6% vs. 2%).

Over the study period, 62% of the diabetes patients received an antibiotic, compared with 55% of the controls – a 24% increased relative risk in a model that adjusted for factors such as alcohol use, Charlson comorbidity index, and cardiovascular and renal comorbidities. Cephalosporins were the most commonly prescribed drugs, followed by antimycobacterial agents, quinolones, and antibiotics commonly used for urinary tract and Staphylococcus aureus infections.

Hospital-treated infections were significantly more common among patients with diabetes, with 19% having at least one such infection compared with 13% of controls (RR 1.55). On a larger scale, at a median follow-up of 2.8 years, the hospital-treated rate among diabetes patients was 58 per 1,000 person/years vs. 39 per 1,000 person/years among controls – a relative risk of 1.49.

Patients were at highest risk for emphysematous cholecystitis (adjusted rate ratio 1.74) and abscesses, tuberculosis, and meningococcal infections. Pneumonia was approximately 30% more likely among patients.

The risk of a hospital-treated infection was highest among younger patients aged 40-50 years (RR 1.77) and lowest among those older than 80 years (RR 1.29). It was also higher among those with higher comorbidity scores. Statin use appeared to attenuate some of the risk, the authors noted. The authors did not discuss the possible cause of this association.

The annual risk of a hospital-treated infection among patients declined from a high of 1.89 in 2004 to 1.59 in 2011. The risk of receiving a community-based antibiotic prescription declined as well, from 1.31 in 2004 to 1.26 in 2011.

These changes were not seen in the control group, suggesting that patients with diabetes were experiencing a unique improvement in infections – earlier detection and treatment of type 2 diabetes, and better comorbidity management could be explanations, the investigators speculated.

The study was sponsored by the Danish Centre for Strategic Research in Type 2 Diabetes and the Program for Clinical Research Infrastructure established by the Lundbeck Foundation and the Novo Nordisk Foundation. Several of the coauthors reported financial ties with various pharmaceutical companies.

People with type 2 diabetes are up to 55% more likely to experience hospital-treated infections and up to 30% more likely to receive an antibiotic prescription in the community setting, compared with the general population, but these associations moderated over an 8-year period – a phenomenon that could be at least partly related to better treatment of diabetes and an overall improvement in mean blood glucose levels, according to results of a large population-based study.

“These findings may be driven by earlier detection and treatment of milder type 2 diabetes cases over time,” or by improved therapy of hyperglycemia and other risk factors, wrote Anil Mor, MD, of Aarhus University Hospital, Denmark, and his associates (Clin Infect Dis. 2016 June 26. doi: 10.1093/cid/ciw345).

©moodboard/Thinkstock

The study ran from 2004 to 2012 and used data from the Danish National Patient Registry. It tracked community- and hospital-treated infections in approximately 774,017 controls; of these, 155,158 had type 2 diabetes. Patients with diabetes were more likely to have serious medical comorbidities compared with controls (29% vs. 21%). These included myocardial infarction (5% vs. 3%), heart failure (4% vs. 2%), cerebrovascular diseases (7% vs. 5%), peripheral vascular diseases (4% vs. 2%), and chronic pulmonary disease (6% vs. 2%).

Over the study period, 62% of the diabetes patients received an antibiotic, compared with 55% of the controls – a 24% increased relative risk in a model that adjusted for factors such as alcohol use, Charlson comorbidity index, and cardiovascular and renal comorbidities. Cephalosporins were the most commonly prescribed drugs, followed by antimycobacterial agents, quinolones, and antibiotics commonly used for urinary tract and Staphylococcus aureus infections.

Hospital-treated infections were significantly more common among patients with diabetes, with 19% having at least one such infection compared with 13% of controls (RR 1.55). On a larger scale, at a median follow-up of 2.8 years, the hospital-treated rate among diabetes patients was 58 per 1,000 person/years vs. 39 per 1,000 person/years among controls – a relative risk of 1.49.

Patients were at highest risk for emphysematous cholecystitis (adjusted rate ratio 1.74) and abscesses, tuberculosis, and meningococcal infections. Pneumonia was approximately 30% more likely among patients.

The risk of a hospital-treated infection was highest among younger patients aged 40-50 years (RR 1.77) and lowest among those older than 80 years (RR 1.29). It was also higher among those with higher comorbidity scores. Statin use appeared to attenuate some of the risk, the authors noted. The authors did not discuss the possible cause of this association.

The annual risk of a hospital-treated infection among patients declined from a high of 1.89 in 2004 to 1.59 in 2011. The risk of receiving a community-based antibiotic prescription declined as well, from 1.31 in 2004 to 1.26 in 2011.

These changes were not seen in the control group, suggesting that patients with diabetes were experiencing a unique improvement in infections – earlier detection and treatment of type 2 diabetes, and better comorbidity management could be explanations, the investigators speculated.

The study was sponsored by the Danish Centre for Strategic Research in Type 2 Diabetes and the Program for Clinical Research Infrastructure established by the Lundbeck Foundation and the Novo Nordisk Foundation. Several of the coauthors reported financial ties with various pharmaceutical companies.

People with type 2 diabetes are up to 55% more likely to experience hospital-treated infections and up to 30% more likely to receive an antibiotic prescription in the community setting, compared with the general population, but these associations moderated over an 8-year period – a phenomenon that could be at least partly related to better treatment of diabetes and an overall improvement in mean blood glucose levels, according to results of a large population-based study.

“These findings may be driven by earlier detection and treatment of milder type 2 diabetes cases over time,” or by improved therapy of hyperglycemia and other risk factors, wrote Anil Mor, MD, of Aarhus University Hospital, Denmark, and his associates (Clin Infect Dis. 2016 June 26. doi: 10.1093/cid/ciw345).

©moodboard/Thinkstock

The study ran from 2004 to 2012 and used data from the Danish National Patient Registry. It tracked community- and hospital-treated infections in approximately 774,017 controls; of these, 155,158 had type 2 diabetes. Patients with diabetes were more likely to have serious medical comorbidities compared with controls (29% vs. 21%). These included myocardial infarction (5% vs. 3%), heart failure (4% vs. 2%), cerebrovascular diseases (7% vs. 5%), peripheral vascular diseases (4% vs. 2%), and chronic pulmonary disease (6% vs. 2%).

Over the study period, 62% of the diabetes patients received an antibiotic, compared with 55% of the controls – a 24% increased relative risk in a model that adjusted for factors such as alcohol use, Charlson comorbidity index, and cardiovascular and renal comorbidities. Cephalosporins were the most commonly prescribed drugs, followed by antimycobacterial agents, quinolones, and antibiotics commonly used for urinary tract and Staphylococcus aureus infections.

Hospital-treated infections were significantly more common among patients with diabetes, with 19% having at least one such infection compared with 13% of controls (RR 1.55). On a larger scale, at a median follow-up of 2.8 years, the hospital-treated rate among diabetes patients was 58 per 1,000 person/years vs. 39 per 1,000 person/years among controls – a relative risk of 1.49.

Patients were at highest risk for emphysematous cholecystitis (adjusted rate ratio 1.74) and abscesses, tuberculosis, and meningococcal infections. Pneumonia was approximately 30% more likely among patients.

The risk of a hospital-treated infection was highest among younger patients aged 40-50 years (RR 1.77) and lowest among those older than 80 years (RR 1.29). It was also higher among those with higher comorbidity scores. Statin use appeared to attenuate some of the risk, the authors noted. The authors did not discuss the possible cause of this association.

The annual risk of a hospital-treated infection among patients declined from a high of 1.89 in 2004 to 1.59 in 2011. The risk of receiving a community-based antibiotic prescription declined as well, from 1.31 in 2004 to 1.26 in 2011.

These changes were not seen in the control group, suggesting that patients with diabetes were experiencing a unique improvement in infections – earlier detection and treatment of type 2 diabetes, and better comorbidity management could be explanations, the investigators speculated.

The study was sponsored by the Danish Centre for Strategic Research in Type 2 Diabetes and the Program for Clinical Research Infrastructure established by the Lundbeck Foundation and the Novo Nordisk Foundation. Several of the coauthors reported financial ties with various pharmaceutical companies.

[email protected]

On Twitter @Alz_Gal

People with type 2 diabetes are up to 55% more likely to experience hospital-treated infections and up to 30% more likely to receive an antibiotic prescription in the community setting, compared with the general population, but these associations moderated over an 8-year period – a phenomenon that could be at least partly related to better treatment of diabetes and an overall improvement in mean blood glucose levels, according to results of a large population-based study.

“These findings may be driven by earlier detection and treatment of milder type 2 diabetes cases over time,” or by improved therapy of hyperglycemia and other risk factors, wrote Anil Mor, MD, of Aarhus University Hospital, Denmark, and his associates (Clin Infect Dis. 2016 June 26. doi: 10.1093/cid/ciw345).

©moodboard/Thinkstock

The study ran from 2004 to 2012 and used data from the Danish National Patient Registry. It tracked community- and hospital-treated infections in approximately 774,017 controls; of these, 155,158 had type 2 diabetes. Patients with diabetes were more likely to have serious medical comorbidities compared with controls (29% vs. 21%). These included myocardial infarction (5% vs. 3%), heart failure (4% vs. 2%), cerebrovascular diseases (7% vs. 5%), peripheral vascular diseases (4% vs. 2%), and chronic pulmonary disease (6% vs. 2%).

Over the study period, 62% of the diabetes patients received an antibiotic, compared with 55% of the controls – a 24% increased relative risk in a model that adjusted for factors such as alcohol use, Charlson comorbidity index, and cardiovascular and renal comorbidities. Cephalosporins were the most commonly prescribed drugs, followed by antimycobacterial agents, quinolones, and antibiotics commonly used for urinary tract and Staphylococcus aureus infections.

Hospital-treated infections were significantly more common among patients with diabetes, with 19% having at least one such infection compared with 13% of controls (RR 1.55). On a larger scale, at a median follow-up of 2.8 years, the hospital-treated rate among diabetes patients was 58 per 1,000 person/years vs. 39 per 1,000 person/years among controls – a relative risk of 1.49.

Patients were at highest risk for emphysematous cholecystitis (adjusted rate ratio 1.74) and abscesses, tuberculosis, and meningococcal infections. Pneumonia was approximately 30% more likely among patients.

The risk of a hospital-treated infection was highest among younger patients aged 40-50 years (RR 1.77) and lowest among those older than 80 years (RR 1.29). It was also higher among those with higher comorbidity scores. Statin use appeared to attenuate some of the risk, the authors noted. The authors did not discuss the possible cause of this association.

The annual risk of a hospital-treated infection among patients declined from a high of 1.89 in 2004 to 1.59 in 2011. The risk of receiving a community-based antibiotic prescription declined as well, from 1.31 in 2004 to 1.26 in 2011.

These changes were not seen in the control group, suggesting that patients with diabetes were experiencing a unique improvement in infections – earlier detection and treatment of type 2 diabetes, and better comorbidity management could be explanations, the investigators speculated.

The study was sponsored by the Danish Centre for Strategic Research in Type 2 Diabetes and the Program for Clinical Research Infrastructure established by the Lundbeck Foundation and the Novo Nordisk Foundation. Several of the coauthors reported financial ties with various pharmaceutical companies.

[email protected]

On Twitter @Alz_Gal

People with type 2 diabetes are up to 55% more likely to experience hospital-treated infections and up to 30% more likely to receive an antibiotic prescription in the community setting, compared with the general population, but these associations moderated over an 8-year period – a phenomenon that could be at least partly related to better treatment of diabetes and an overall improvement in mean blood glucose levels, according to results of a large population-based study.

“These findings may be driven by earlier detection and treatment of milder type 2 diabetes cases over time,” or by improved therapy of hyperglycemia and other risk factors, wrote Anil Mor, MD, of Aarhus University Hospital, Denmark, and his associates (Clin Infect Dis. 2016 June 26. doi: 10.1093/cid/ciw345).

©moodboard/Thinkstock

The study ran from 2004 to 2012 and used data from the Danish National Patient Registry. It tracked community- and hospital-treated infections in approximately 774,017 controls; of these, 155,158 had type 2 diabetes. Patients with diabetes were more likely to have serious medical comorbidities compared with controls (29% vs. 21%). These included myocardial infarction (5% vs. 3%), heart failure (4% vs. 2%), cerebrovascular diseases (7% vs. 5%), peripheral vascular diseases (4% vs. 2%), and chronic pulmonary disease (6% vs. 2%).

Over the study period, 62% of the diabetes patients received an antibiotic, compared with 55% of the controls – a 24% increased relative risk in a model that adjusted for factors such as alcohol use, Charlson comorbidity index, and cardiovascular and renal comorbidities. Cephalosporins were the most commonly prescribed drugs, followed by antimycobacterial agents, quinolones, and antibiotics commonly used for urinary tract and Staphylococcus aureus infections.

Hospital-treated infections were significantly more common among patients with diabetes, with 19% having at least one such infection compared with 13% of controls (RR 1.55). On a larger scale, at a median follow-up of 2.8 years, the hospital-treated rate among diabetes patients was 58 per 1,000 person/years vs. 39 per 1,000 person/years among controls – a relative risk of 1.49.

Patients were at highest risk for emphysematous cholecystitis (adjusted rate ratio 1.74) and abscesses, tuberculosis, and meningococcal infections. Pneumonia was approximately 30% more likely among patients.

The risk of a hospital-treated infection was highest among younger patients aged 40-50 years (RR 1.77) and lowest among those older than 80 years (RR 1.29). It was also higher among those with higher comorbidity scores. Statin use appeared to attenuate some of the risk, the authors noted. The authors did not discuss the possible cause of this association.

The annual risk of a hospital-treated infection among patients declined from a high of 1.89 in 2004 to 1.59 in 2011. The risk of receiving a community-based antibiotic prescription declined as well, from 1.31 in 2004 to 1.26 in 2011.

These changes were not seen in the control group, suggesting that patients with diabetes were experiencing a unique improvement in infections – earlier detection and treatment of type 2 diabetes, and better comorbidity management could be explanations, the investigators speculated.

The study was sponsored by the Danish Centre for Strategic Research in Type 2 Diabetes and the Program for Clinical Research Infrastructure established by the Lundbeck Foundation and the Novo Nordisk Foundation. Several of the coauthors reported financial ties with various pharmaceutical companies.

[email protected]

On Twitter @Alz_Gal

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

[email protected]

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

[email protected]

Despite achieving significant improvements in blood pressure and cholesterol levels, obese Americans continue to grow fatter, with worsening blood glucose and an increasing incidence of diabetes.

From 1998 to 2014, national health data showed that mean diastolic and systolic blood pressures decreased in obese men and women in all racial and ethnic groups. Mean lipid measurements improved as well, including a “marked” 21-mg/dL decrease in total cholesterol and a significant increase in HDL cholesterol.

But markers of blood glucose health continued to decline over the same period, contributing to an overall worsening of metabolic health and a increase from 11% to 19% in the rate of diabetes, Fangjian Guo, MD, and W. Timothy Garvey, MD, reported in July 13 issue of the Journal of the American Heart Association (J Am Heart Assoc. 2016 Jul 13. 5:e003619 doi: 10.1161/JAHA.116.003619).

The rate of obese adults free of these three cardiovascular disease risk factors – diabetes, elevated cholesterol, and blood pressure – remained stable over the study period at about 15%. But the rate of obese adults with all three risk factors increased by 37% over the same period. By 2014, 22% reported having all three of those risk factors.

“The deteriorated blood glucose health among obese adults in the United States calls for lifestyle interventions (diet and exercise) on a national scale,” wrote Dr. Garvey, chair of nutrition science at the University of Alabama, Birmingham. “Community-based public health intervention programs may help increase physical activity and diet quality to alleviate the problem.”

The investigators examined trends in cardiometabolic health among 18,626 obese adults who participated in National Health and Nutrition Examination Surveys from 1988 to 2014. Over this period, mean body mass index increased significantly, from 34.7 to 36 kg/m². Waist circumference increased as well, from 110 to 114.8 cm.

The picture was much better for blood pressure. Mean systolic pressures decreased about 2 points – from 126.1 to 124.4 mm Hg – in all age, racial and ethnic groups, and in both sexes. Mean diastolic blood pressure also decreased, dropping from 76.6 to 72.5 mm Hg. By 2014, 44% of the men and 51% of the women were below the blood pressure risk threshold.

Lipids also improved over the years, the investigators noted, with significant decreases in mean total cholesterol, from 214.5 to 193.7 mg/dL, and increases in HDL cholesterol, from 45.4 to 47.4 mg/dL.

Blood glucose worsened significantly, however. The mean hemoglobin A1c increased from 5.7% to 5.9%. The measurement rose in all ages, both sexes, and in all racial and ethnic groups except for non-Hispanic blacks.

Perhaps not surprisingly, the incidence of diabetes (a self-reported HbA_1c of 6.5% or more) increased from 11% to 19% from 1988 to 2014. The increase occurred in all age groups and both sexes except for young adults aged 20-39 years. No racial or ethnic group was exempt from the increase.

The number of people having all three risk factors (hypertension, hypercholesterolemia, and hyperglycemia) increased from 16% in 1988 to 22% in 2014.

“The increase occurred in parallel with a decline in the prevalence of healthy blood glucose, which is the predominant explanation accounting for the rise in the prevalence of presence of all three risk factors,” the investigators said.

Only 15% of the study population was free from all of these risk factors – a percentage that remained unchanged during 1988-2014.

The findings should be a wake-up call for physicians and their patients, and a national call for action to improve cardiovascular health among obese adults, the team wrote.

“The increasing trend of obese people with all three cardiovascular risk factors, commensurate with a decline in those with one or two risk factors, suggests an overall deterioration in health among people with obesity. ... These patterns of worsening metabolic health constitute an increase in risk of type 2 diabetes mellitus and underlie increasing prevalence rates for diabetes mellitus,” the investigators wrote.

Aggressive treatment will be necessary to reverse these trends. This might include treatment with weight-loss medications in conjunction with lifestyle interventions, which should be especially targeted at obese individuals who are already metabolically unhealthy and in those who have complications or are at risk for developing them.

“In the context of the current data, those obese adults who are metabolically unhealthy or perhaps those with suboptimal metabolic health represent patients who will benefit most from intensive obesity management … coordinated efforts aligning cardiovascular disease prevention and control activities across the public and private sectors in the United States are needed reduce the burden of cardiovascular disease among the obese population,” Dr. Garvey concluded.

The study was supported by the Department of Veterans Affairs, the National Institutes of Health, and the University of Alabama Diabetes Research Center.

Dr. Guo had no financial disclosures. Dr. Garvey disclosed relationships with multiple pharmaceutical companies.

[email protected]

Exposure to violence significantly increases the chance that a person will commit a violent crime in the subsequent week – whether or not that person has an existing mental illness.

Absolute risk was highest among people with schizophrenia, with a violent crime rate of 177 per 10,000 individuals, compared with 22 per 10,000 before the trigger event. But although that was significantly higher than the rate seen among patients with bipolar disorder and normal controls, those groups also experienced significant increases in violent behavior after a violent experience (83 vs. 13 per 10,000 and 70 vs. 9 per 10,000, respectively), Amir Sariaslan, PhD, wrote July 13 online in JAMA Psychiatry (doi: 10.1001/jamapsychiatry.2016.1349).

The Swedish national study, which comprised more than 3 million people, found other triggers for transient violent criminality among both patients and controls. These included traumatic brain injuries, unintentional injuries, self-harm, substance intoxication, and parental bereavement, wrote Dr. Sariaslan of the University of Oxford (England), and his colleagues.

“We also observed that the triggers had less effect as follow-up time increased,” the team noted. “These findings support the hypothesis that recent exposure to a stressful life event, an intentional or unintentional injury, or having been diagnosed with substance intoxication increases the short-term risk of interpersonal violence.”

The study comprised 64,595 patients diagnosed with psychotic disorders and in 2.76 million controls. Since it spanned 13 years, each person also was able to serve as his own individual control as well. The model examined both absolute and relative risks, and controlled for a large number of sociodemographic, clinical, and psychosocial variables.

Exposure to violence was the strongest precipitating factor for violent crime, exerting an increased relative risk of almost 13-fold among patients with schizophrenia, and 8-fold among both patients with bipolar disorder and controls.

The increased risks associated with traumatic brain injury were 6.7 for those with schizophrenia, 4.3 for those with bipolar disorder and almost 8 for controls. For self-harm, the risk hovered around fourfold for all groups.

The risks for unintentional injuries ranged from 3.5-4.8; and for substance intoxication, from 3.0-4.0.

The increased risks associated with parental bereavement showed a slightly different pattern, being sharply increased among those with schizophrenia, compared with controls (5.0 vs. 1.7), the investigators wrote.

“An explanation for this finding is that elevated levels of social support from family members and close friends in the controls may be protective against violence,” they suggested.

The study also determined that the effects of these triggers weakened over time. Again, this observation was most obvious with exposure to violence, and in the group with schizophrenia. The increased risk of committing a violent crime dropped from a high of 12.7 in the first week to baseline by the second week.

The finding of an increased risk of violent behavior after an incident of self-harm is a novel one, the investigators added.

“Our findings suggest that self-harming patients, particularly those with psychoses, are an important group to be assessed for interpersonal violence in addition to the routinely examined risk of suicide,” they wrote.

The study was supported by the Wellcome Trust, and grants from Swedish governmental agencies. None of the authors had any financial disclosures.

[email protected]

Exposure to violence significantly increases the chance that a person will commit a violent crime in the subsequent week – whether or not that person has an existing mental illness.

Absolute risk was highest among people with schizophrenia, with a violent crime rate of 177 per 10,000 individuals, compared with 22 per 10,000 before the trigger event. But although that was significantly higher than the rate seen among patients with bipolar disorder and normal controls, those groups also experienced significant increases in violent behavior after a violent experience (83 vs. 13 per 10,000 and 70 vs. 9 per 10,000, respectively), Amir Sariaslan, PhD, wrote July 13 online in JAMA Psychiatry (doi: 10.1001/jamapsychiatry.2016.1349).

The Swedish national study, which comprised more than 3 million people, found other triggers for transient violent criminality among both patients and controls. These included traumatic brain injuries, unintentional injuries, self-harm, substance intoxication, and parental bereavement, wrote Dr. Sariaslan of the University of Oxford (England), and his colleagues.

“We also observed that the triggers had less effect as follow-up time increased,” the team noted. “These findings support the hypothesis that recent exposure to a stressful life event, an intentional or unintentional injury, or having been diagnosed with substance intoxication increases the short-term risk of interpersonal violence.”

The study comprised 64,595 patients diagnosed with psychotic disorders and in 2.76 million controls. Since it spanned 13 years, each person also was able to serve as his own individual control as well. The model examined both absolute and relative risks, and controlled for a large number of sociodemographic, clinical, and psychosocial variables.

Exposure to violence was the strongest precipitating factor for violent crime, exerting an increased relative risk of almost 13-fold among patients with schizophrenia, and 8-fold among both patients with bipolar disorder and controls.

The increased risks associated with traumatic brain injury were 6.7 for those with schizophrenia, 4.3 for those with bipolar disorder and almost 8 for controls. For self-harm, the risk hovered around fourfold for all groups.

The risks for unintentional injuries ranged from 3.5-4.8; and for substance intoxication, from 3.0-4.0.

The increased risks associated with parental bereavement showed a slightly different pattern, being sharply increased among those with schizophrenia, compared with controls (5.0 vs. 1.7), the investigators wrote.

“An explanation for this finding is that elevated levels of social support from family members and close friends in the controls may be protective against violence,” they suggested.

The study also determined that the effects of these triggers weakened over time. Again, this observation was most obvious with exposure to violence, and in the group with schizophrenia. The increased risk of committing a violent crime dropped from a high of 12.7 in the first week to baseline by the second week.

The finding of an increased risk of violent behavior after an incident of self-harm is a novel one, the investigators added.

“Our findings suggest that self-harming patients, particularly those with psychoses, are an important group to be assessed for interpersonal violence in addition to the routinely examined risk of suicide,” they wrote.

The study was supported by the Wellcome Trust, and grants from Swedish governmental agencies. None of the authors had any financial disclosures.

[email protected]

Exposure to violence significantly increases the chance that a person will commit a violent crime in the subsequent week – whether or not that person has an existing mental illness.

Absolute risk was highest among people with schizophrenia, with a violent crime rate of 177 per 10,000 individuals, compared with 22 per 10,000 before the trigger event. But although that was significantly higher than the rate seen among patients with bipolar disorder and normal controls, those groups also experienced significant increases in violent behavior after a violent experience (83 vs. 13 per 10,000 and 70 vs. 9 per 10,000, respectively), Amir Sariaslan, PhD, wrote July 13 online in JAMA Psychiatry (doi: 10.1001/jamapsychiatry.2016.1349).

The Swedish national study, which comprised more than 3 million people, found other triggers for transient violent criminality among both patients and controls. These included traumatic brain injuries, unintentional injuries, self-harm, substance intoxication, and parental bereavement, wrote Dr. Sariaslan of the University of Oxford (England), and his colleagues.

“We also observed that the triggers had less effect as follow-up time increased,” the team noted. “These findings support the hypothesis that recent exposure to a stressful life event, an intentional or unintentional injury, or having been diagnosed with substance intoxication increases the short-term risk of interpersonal violence.”

The study comprised 64,595 patients diagnosed with psychotic disorders and in 2.76 million controls. Since it spanned 13 years, each person also was able to serve as his own individual control as well. The model examined both absolute and relative risks, and controlled for a large number of sociodemographic, clinical, and psychosocial variables.

Exposure to violence was the strongest precipitating factor for violent crime, exerting an increased relative risk of almost 13-fold among patients with schizophrenia, and 8-fold among both patients with bipolar disorder and controls.

The increased risks associated with traumatic brain injury were 6.7 for those with schizophrenia, 4.3 for those with bipolar disorder and almost 8 for controls. For self-harm, the risk hovered around fourfold for all groups.

The risks for unintentional injuries ranged from 3.5-4.8; and for substance intoxication, from 3.0-4.0.

The increased risks associated with parental bereavement showed a slightly different pattern, being sharply increased among those with schizophrenia, compared with controls (5.0 vs. 1.7), the investigators wrote.

“An explanation for this finding is that elevated levels of social support from family members and close friends in the controls may be protective against violence,” they suggested.

The study also determined that the effects of these triggers weakened over time. Again, this observation was most obvious with exposure to violence, and in the group with schizophrenia. The increased risk of committing a violent crime dropped from a high of 12.7 in the first week to baseline by the second week.

The finding of an increased risk of violent behavior after an incident of self-harm is a novel one, the investigators added.

“Our findings suggest that self-harming patients, particularly those with psychoses, are an important group to be assessed for interpersonal violence in addition to the routinely examined risk of suicide,” they wrote.

The study was supported by the Wellcome Trust, and grants from Swedish governmental agencies. None of the authors had any financial disclosures.

[email protected]

FROM CIRCULATION: CARDIOVASCULAR QUALITY OUTCOMES

Insufficient evidence exists to routinely recommend surgical closure of the left atrial appendage, either surgically or with a LAA exclusion device, for patients who have atrial fibrillation, a large data review has concluded.

None of the devices so far examined is more effective than oral anticoagulation therapy in reducing AF-related stroke risk, but they appear to be riskier, with up to 1 in 15 patients experiencing a serious adverse event during or after percutaneous placement, North Noelck, MD, and his colleagues wrote (Circ Cardiovasc Qual Outcomes. 2016 Jul 12. doi: 10.1161/CIRCOUTCOMES.115.002539).

Surgical studies, which also have found no benefit, are poor in quality and provide no strong data in favor of any technique, wrote Dr. Noelck of Oregon Health and Science University, Portland.

The meta-analysis comprised 13 studies of the benefits and risks of percutaneous LAA exclusion and 7 of the benefits and harms of surgical LAA closure.

The team found “limited evidence” that one device, the Watchman (Boston Scientific), may be an effective alternative to long-term oral anticoagulation treatment in some patients. But the Watchman was also associated with “significant, procedural-related harms,” in almost 11% of patients in one large study, PROTECT-AF. These included pericardial effusions with and without associated tamponade, bleeding, device thrombus, and device embolization. However, the benefit conferred by the device appeared marginal. Neither PROTECT-AF nor the subsequent PREVAIL studies of the Watchman found that it conferred significant clinical benefit above the comparator arm of warfarin therapy. Indeed, in PREVAIL, a composite outcome of death, ischemic/hemorrhagic stroke, or systemic embolism occurred in 5.2% of the device group and in 2.9% of the warfarin group.

Three randomized studies and two observational studies examined surgical LAA closure relative to usual medical care. The authors said the randomized studies were underpowered to show clinical benefit. Neither of the observational studies showed significant advantages in stroke-free survival, but the team noted, “data such as information about anticoagulation use among the groups [were] lacking.”

“Overall, there is insufficient evidence to support the routine use of surgical LAA exclusion to reduce stroke risk or the future need for anticoagulant therapy,” wrote Dr. Noelck and his coinvestigators. However, they said, several ongoing studies “should add substantively to this body of evidence during the next several years.”

The study was funded by the Department of Veterans Affairs. None of the authors had any relevant financial disclosure.

[email protected]

FROM CIRCULATION: CARDIOVASCULAR QUALITY OUTCOMES

Insufficient evidence exists to routinely recommend surgical closure of the left atrial appendage, either surgically or with a LAA exclusion device, for patients who have atrial fibrillation, a large data review has concluded.

None of the devices so far examined is more effective than oral anticoagulation therapy in reducing AF-related stroke risk, but they appear to be riskier, with up to 1 in 15 patients experiencing a serious adverse event during or after percutaneous placement, North Noelck, MD, and his colleagues wrote (Circ Cardiovasc Qual Outcomes. 2016 Jul 12. doi: 10.1161/CIRCOUTCOMES.115.002539).

Surgical studies, which also have found no benefit, are poor in quality and provide no strong data in favor of any technique, wrote Dr. Noelck of Oregon Health and Science University, Portland.

The meta-analysis comprised 13 studies of the benefits and risks of percutaneous LAA exclusion and 7 of the benefits and harms of surgical LAA closure.

The team found “limited evidence” that one device, the Watchman (Boston Scientific), may be an effective alternative to long-term oral anticoagulation treatment in some patients. But the Watchman was also associated with “significant, procedural-related harms,” in almost 11% of patients in one large study, PROTECT-AF. These included pericardial effusions with and without associated tamponade, bleeding, device thrombus, and device embolization. However, the benefit conferred by the device appeared marginal. Neither PROTECT-AF nor the subsequent PREVAIL studies of the Watchman found that it conferred significant clinical benefit above the comparator arm of warfarin therapy. Indeed, in PREVAIL, a composite outcome of death, ischemic/hemorrhagic stroke, or systemic embolism occurred in 5.2% of the device group and in 2.9% of the warfarin group.

Three randomized studies and two observational studies examined surgical LAA closure relative to usual medical care. The authors said the randomized studies were underpowered to show clinical benefit. Neither of the observational studies showed significant advantages in stroke-free survival, but the team noted, “data such as information about anticoagulation use among the groups [were] lacking.”

“Overall, there is insufficient evidence to support the routine use of surgical LAA exclusion to reduce stroke risk or the future need for anticoagulant therapy,” wrote Dr. Noelck and his coinvestigators. However, they said, several ongoing studies “should add substantively to this body of evidence during the next several years.”

The study was funded by the Department of Veterans Affairs. None of the authors had any relevant financial disclosure.

[email protected]

FROM CIRCULATION: CARDIOVASCULAR QUALITY OUTCOMES

Insufficient evidence exists to routinely recommend surgical closure of the left atrial appendage, either surgically or with a LAA exclusion device, for patients who have atrial fibrillation, a large data review has concluded.

None of the devices so far examined is more effective than oral anticoagulation therapy in reducing AF-related stroke risk, but they appear to be riskier, with up to 1 in 15 patients experiencing a serious adverse event during or after percutaneous placement, North Noelck, MD, and his colleagues wrote (Circ Cardiovasc Qual Outcomes. 2016 Jul 12. doi: 10.1161/CIRCOUTCOMES.115.002539).

Surgical studies, which also have found no benefit, are poor in quality and provide no strong data in favor of any technique, wrote Dr. Noelck of Oregon Health and Science University, Portland.

The meta-analysis comprised 13 studies of the benefits and risks of percutaneous LAA exclusion and 7 of the benefits and harms of surgical LAA closure.

The team found “limited evidence” that one device, the Watchman (Boston Scientific), may be an effective alternative to long-term oral anticoagulation treatment in some patients. But the Watchman was also associated with “significant, procedural-related harms,” in almost 11% of patients in one large study, PROTECT-AF. These included pericardial effusions with and without associated tamponade, bleeding, device thrombus, and device embolization. However, the benefit conferred by the device appeared marginal. Neither PROTECT-AF nor the subsequent PREVAIL studies of the Watchman found that it conferred significant clinical benefit above the comparator arm of warfarin therapy. Indeed, in PREVAIL, a composite outcome of death, ischemic/hemorrhagic stroke, or systemic embolism occurred in 5.2% of the device group and in 2.9% of the warfarin group.

Three randomized studies and two observational studies examined surgical LAA closure relative to usual medical care. The authors said the randomized studies were underpowered to show clinical benefit. Neither of the observational studies showed significant advantages in stroke-free survival, but the team noted, “data such as information about anticoagulation use among the groups [were] lacking.”

“Overall, there is insufficient evidence to support the routine use of surgical LAA exclusion to reduce stroke risk or the future need for anticoagulant therapy,” wrote Dr. Noelck and his coinvestigators. However, they said, several ongoing studies “should add substantively to this body of evidence during the next several years.”

The study was funded by the Department of Veterans Affairs. None of the authors had any relevant financial disclosure.

[email protected]

An implanted vagus nerve stimulator like that used for epilepsy treatment reduced inflammatory markers and significantly improved symptoms and function in a small cohort of patients with rheumatoid arthritis.

After 42 days, almost 30% of patients had achieved disease remission, Frieda A. Koopman, MD, and her colleagues reported in the July issue of the Proceedings of the National Academy of Science (doi: 10.1073/pnas.1605635113). The improvements disappeared rapidly when the devices were turned off, but were quickly reestablished after stimulation resumed.

“This first-in-class study supports a conceptual framework for further studies of electronic medical devices in diseases currently treated with drugs, an approach termed ‘bioelectronic medicine,’” wrote Dr. Koopman of the University of Amsterdam, and her coauthors.

The team built on evidence of what they termed a “reflex neural circuit” in the vagus that strongly influences the production of inflammatory cytokines. Animal studies showed that electrical stimulation of the vagus nerve encouraged choline acetyltransferase–positive T cells to secrete acetylcholine in the spleen and other tissues. Acetylcholine binds to a class of nicotinic receptors on monocytes, macrophages, and stromal cells, and inhibits their inflammatory response.

“Inflammatory reflex signaling, which is enhanced by electrically stimulating the vagus nerve, significantly reduces cytokine production and attenuates disease severity in experimental models of endotoxemia, sepsis, colitis, and other preclinical animal models of inflammatory syndromes,” the team noted.

The group reported on two human studies, totaling 25 patients. The first comprised seven patients with epilepsy who received the implanted vagus nerve stimulator for medically refractory seizures. None of these patients had a history of RA or any other inflammatory disease. The second group was all patients with active RA.

Each epilepsy patient contributed peripheral blood for study, which was collected before, during and after the implantation surgery. The team studied inflammatory markers by adding endotoxin to the samples. Those collected after the patient had been exposed to a single 30-second stimulation at 20 Hertz showed significantly inhibited production of TNF-alpha, compared with that seen in unexposed blood. Interleukin (IL)-6 and IL-1beta was also inhibited significantly by vagus nerve stimulation.

The next study involved 17 patients who had active RA, but not epilepsy. Of these, seven had failed methotrexate but were naïve to biologics; the rest had failed methotrexate and at least two biologics from different classes. Their average disease duration was 11 years.

The 86-day study gradually titrated the stimulation dose, but even at its highest, stimulation was far less than what is typically employed in epilepsy, “in which current is delivered at 60-second intervals, followed by an off interval of 5-180 minutes, repeated continuously,” the investigators wrote. “Thus, epilepsy patients may receive electrical current delivery for up to 240 minutes daily. Preclinical studies have established that stimulation of the inflammatory reflex for as little as 60 seconds confers significant inhibition of cytokine production for up to 24 hours.”

There was a 14-day post-implantation washout period with no stimulation, followed by 28 days of treatment titration. During that time, stimulation was ramped up from single 60-second stimulation with electric pulses of 250-microseconds duration at 10 Hertz and an output current between 0.25-2.0 milliamps, to the highest amperage tolerated (up to 2.0 milliamps).

That dose was the treatment target, and delivered once daily for 60 seconds in 250-microsecond pulse widths at 10 Hertz. At day 28, patients who had not had good clinical response according to EULAR response criteria, had their stimulation increased to four times daily.

In the group of seven methotrexate-resistant patients, two received electric current pulses four times daily. In the group of 10 methotrexate- and biologic-resistant patients, 6 received the four-dose stimulation.

On day 42, TNF-alpha levels in cultured peripheral blood were significantly reduced from baseline.

At that time, the vagus nerve stimulator was turned off for 14 days. By the end of the silent period, TNF-alpha levels had risen significantly from the day 42 levels. The stimulator was restarted on day 56. By day 84, after 28 more days of stimulation, TNF-alpha levels had again decreased significantly.

Symptoms and function as measured by the Disease Activity Score 28 followed a similar trajectory, improving during the initial treatment, worsening during the period of no stimulation, and improving again when stimulation was restarted. Symptom and function scores correlated positively with change in TNF levels.

The investigators also assessed the response rates according to American College of Rheumatology criteria. At day 42, 71% of those in the methotrexate-resistant group had achieved a 20% response; 57% a 50% response; and 28.6% a 70% response. Response was not as dramatic in the group resistant to both drug classes: rates were 70%, 30%, and 0%.

By day 42, nearly 30% of patients overall achieved remission, which was defined as a DAS28 score of less than 2.6. This constituted improvement in all the score components, including tender joint count, swollen joint count, patient’s assessment of pain, patient’s global assessment, physician’s global assessment, and C-reactive protein.

Finally, the investigators noted decreased levels of most serum cytokines. Most, including serum TNF, IL-10, IL-12p70, IL-13, IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, and TNF-a-beta, were below 1 pg/ml.

Adverse events were common (16 patients) but reported as mild-moderate. The included hoarseness (5), hypoesthesia (4), parasthesia (2), dyspnea (2), and bradycardia (1), among others. There were no implantation-related infections. One patient reported postimplantation pain.

SetPoint Medical, of Valencia, Calif., makes the device and conducted the study. Dr. Koopman made no financial disclosures. However, several of the other authors are employees of Set Point, and of GlaxoSmithKline, which holds equity interest in the company.

[email protected]

On Twitter @Alz_Gal

An implanted vagus nerve stimulator like that used for epilepsy treatment reduced inflammatory markers and significantly improved symptoms and function in a small cohort of patients with rheumatoid arthritis.

After 42 days, almost 30% of patients had achieved disease remission, Frieda A. Koopman, MD, and her colleagues reported in the July issue of the Proceedings of the National Academy of Science (doi: 10.1073/pnas.1605635113). The improvements disappeared rapidly when the devices were turned off, but were quickly reestablished after stimulation resumed.

“This first-in-class study supports a conceptual framework for further studies of electronic medical devices in diseases currently treated with drugs, an approach termed ‘bioelectronic medicine,’” wrote Dr. Koopman of the University of Amsterdam, and her coauthors.

The team built on evidence of what they termed a “reflex neural circuit” in the vagus that strongly influences the production of inflammatory cytokines. Animal studies showed that electrical stimulation of the vagus nerve encouraged choline acetyltransferase–positive T cells to secrete acetylcholine in the spleen and other tissues. Acetylcholine binds to a class of nicotinic receptors on monocytes, macrophages, and stromal cells, and inhibits their inflammatory response.

“Inflammatory reflex signaling, which is enhanced by electrically stimulating the vagus nerve, significantly reduces cytokine production and attenuates disease severity in experimental models of endotoxemia, sepsis, colitis, and other preclinical animal models of inflammatory syndromes,” the team noted.

The group reported on two human studies, totaling 25 patients. The first comprised seven patients with epilepsy who received the implanted vagus nerve stimulator for medically refractory seizures. None of these patients had a history of RA or any other inflammatory disease. The second group was all patients with active RA.

Each epilepsy patient contributed peripheral blood for study, which was collected before, during and after the implantation surgery. The team studied inflammatory markers by adding endotoxin to the samples. Those collected after the patient had been exposed to a single 30-second stimulation at 20 Hertz showed significantly inhibited production of TNF-alpha, compared with that seen in unexposed blood. Interleukin (IL)-6 and IL-1beta was also inhibited significantly by vagus nerve stimulation.

The next study involved 17 patients who had active RA, but not epilepsy. Of these, seven had failed methotrexate but were naïve to biologics; the rest had failed methotrexate and at least two biologics from different classes. Their average disease duration was 11 years.

The 86-day study gradually titrated the stimulation dose, but even at its highest, stimulation was far less than what is typically employed in epilepsy, “in which current is delivered at 60-second intervals, followed by an off interval of 5-180 minutes, repeated continuously,” the investigators wrote. “Thus, epilepsy patients may receive electrical current delivery for up to 240 minutes daily. Preclinical studies have established that stimulation of the inflammatory reflex for as little as 60 seconds confers significant inhibition of cytokine production for up to 24 hours.”

There was a 14-day post-implantation washout period with no stimulation, followed by 28 days of treatment titration. During that time, stimulation was ramped up from single 60-second stimulation with electric pulses of 250-microseconds duration at 10 Hertz and an output current between 0.25-2.0 milliamps, to the highest amperage tolerated (up to 2.0 milliamps).

That dose was the treatment target, and delivered once daily for 60 seconds in 250-microsecond pulse widths at 10 Hertz. At day 28, patients who had not had good clinical response according to EULAR response criteria, had their stimulation increased to four times daily.

In the group of seven methotrexate-resistant patients, two received electric current pulses four times daily. In the group of 10 methotrexate- and biologic-resistant patients, 6 received the four-dose stimulation.

On day 42, TNF-alpha levels in cultured peripheral blood were significantly reduced from baseline.

At that time, the vagus nerve stimulator was turned off for 14 days. By the end of the silent period, TNF-alpha levels had risen significantly from the day 42 levels. The stimulator was restarted on day 56. By day 84, after 28 more days of stimulation, TNF-alpha levels had again decreased significantly.

Symptoms and function as measured by the Disease Activity Score 28 followed a similar trajectory, improving during the initial treatment, worsening during the period of no stimulation, and improving again when stimulation was restarted. Symptom and function scores correlated positively with change in TNF levels.

The investigators also assessed the response rates according to American College of Rheumatology criteria. At day 42, 71% of those in the methotrexate-resistant group had achieved a 20% response; 57% a 50% response; and 28.6% a 70% response. Response was not as dramatic in the group resistant to both drug classes: rates were 70%, 30%, and 0%.

By day 42, nearly 30% of patients overall achieved remission, which was defined as a DAS28 score of less than 2.6. This constituted improvement in all the score components, including tender joint count, swollen joint count, patient’s assessment of pain, patient’s global assessment, physician’s global assessment, and C-reactive protein.

Finally, the investigators noted decreased levels of most serum cytokines. Most, including serum TNF, IL-10, IL-12p70, IL-13, IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, and TNF-a-beta, were below 1 pg/ml.

Adverse events were common (16 patients) but reported as mild-moderate. The included hoarseness (5), hypoesthesia (4), parasthesia (2), dyspnea (2), and bradycardia (1), among others. There were no implantation-related infections. One patient reported postimplantation pain.

SetPoint Medical, of Valencia, Calif., makes the device and conducted the study. Dr. Koopman made no financial disclosures. However, several of the other authors are employees of Set Point, and of GlaxoSmithKline, which holds equity interest in the company.

[email protected]

On Twitter @Alz_Gal

An implanted vagus nerve stimulator like that used for epilepsy treatment reduced inflammatory markers and significantly improved symptoms and function in a small cohort of patients with rheumatoid arthritis.

After 42 days, almost 30% of patients had achieved disease remission, Frieda A. Koopman, MD, and her colleagues reported in the July issue of the Proceedings of the National Academy of Science (doi: 10.1073/pnas.1605635113). The improvements disappeared rapidly when the devices were turned off, but were quickly reestablished after stimulation resumed.

“This first-in-class study supports a conceptual framework for further studies of electronic medical devices in diseases currently treated with drugs, an approach termed ‘bioelectronic medicine,’” wrote Dr. Koopman of the University of Amsterdam, and her coauthors.

The team built on evidence of what they termed a “reflex neural circuit” in the vagus that strongly influences the production of inflammatory cytokines. Animal studies showed that electrical stimulation of the vagus nerve encouraged choline acetyltransferase–positive T cells to secrete acetylcholine in the spleen and other tissues. Acetylcholine binds to a class of nicotinic receptors on monocytes, macrophages, and stromal cells, and inhibits their inflammatory response.

“Inflammatory reflex signaling, which is enhanced by electrically stimulating the vagus nerve, significantly reduces cytokine production and attenuates disease severity in experimental models of endotoxemia, sepsis, colitis, and other preclinical animal models of inflammatory syndromes,” the team noted.

The group reported on two human studies, totaling 25 patients. The first comprised seven patients with epilepsy who received the implanted vagus nerve stimulator for medically refractory seizures. None of these patients had a history of RA or any other inflammatory disease. The second group was all patients with active RA.

Each epilepsy patient contributed peripheral blood for study, which was collected before, during and after the implantation surgery. The team studied inflammatory markers by adding endotoxin to the samples. Those collected after the patient had been exposed to a single 30-second stimulation at 20 Hertz showed significantly inhibited production of TNF-alpha, compared with that seen in unexposed blood. Interleukin (IL)-6 and IL-1beta was also inhibited significantly by vagus nerve stimulation.

The next study involved 17 patients who had active RA, but not epilepsy. Of these, seven had failed methotrexate but were naïve to biologics; the rest had failed methotrexate and at least two biologics from different classes. Their average disease duration was 11 years.

The 86-day study gradually titrated the stimulation dose, but even at its highest, stimulation was far less than what is typically employed in epilepsy, “in which current is delivered at 60-second intervals, followed by an off interval of 5-180 minutes, repeated continuously,” the investigators wrote. “Thus, epilepsy patients may receive electrical current delivery for up to 240 minutes daily. Preclinical studies have established that stimulation of the inflammatory reflex for as little as 60 seconds confers significant inhibition of cytokine production for up to 24 hours.”

There was a 14-day post-implantation washout period with no stimulation, followed by 28 days of treatment titration. During that time, stimulation was ramped up from single 60-second stimulation with electric pulses of 250-microseconds duration at 10 Hertz and an output current between 0.25-2.0 milliamps, to the highest amperage tolerated (up to 2.0 milliamps).

That dose was the treatment target, and delivered once daily for 60 seconds in 250-microsecond pulse widths at 10 Hertz. At day 28, patients who had not had good clinical response according to EULAR response criteria, had their stimulation increased to four times daily.

In the group of seven methotrexate-resistant patients, two received electric current pulses four times daily. In the group of 10 methotrexate- and biologic-resistant patients, 6 received the four-dose stimulation.

On day 42, TNF-alpha levels in cultured peripheral blood were significantly reduced from baseline.

At that time, the vagus nerve stimulator was turned off for 14 days. By the end of the silent period, TNF-alpha levels had risen significantly from the day 42 levels. The stimulator was restarted on day 56. By day 84, after 28 more days of stimulation, TNF-alpha levels had again decreased significantly.

Symptoms and function as measured by the Disease Activity Score 28 followed a similar trajectory, improving during the initial treatment, worsening during the period of no stimulation, and improving again when stimulation was restarted. Symptom and function scores correlated positively with change in TNF levels.

The investigators also assessed the response rates according to American College of Rheumatology criteria. At day 42, 71% of those in the methotrexate-resistant group had achieved a 20% response; 57% a 50% response; and 28.6% a 70% response. Response was not as dramatic in the group resistant to both drug classes: rates were 70%, 30%, and 0%.

By day 42, nearly 30% of patients overall achieved remission, which was defined as a DAS28 score of less than 2.6. This constituted improvement in all the score components, including tender joint count, swollen joint count, patient’s assessment of pain, patient’s global assessment, physician’s global assessment, and C-reactive protein.

Finally, the investigators noted decreased levels of most serum cytokines. Most, including serum TNF, IL-10, IL-12p70, IL-13, IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, and TNF-a-beta, were below 1 pg/ml.

Adverse events were common (16 patients) but reported as mild-moderate. The included hoarseness (5), hypoesthesia (4), parasthesia (2), dyspnea (2), and bradycardia (1), among others. There were no implantation-related infections. One patient reported postimplantation pain.

SetPoint Medical, of Valencia, Calif., makes the device and conducted the study. Dr. Koopman made no financial disclosures. However, several of the other authors are employees of Set Point, and of GlaxoSmithKline, which holds equity interest in the company.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Encouraging data on an external vagal nerve stimulator and a minimally invasive system that targets the sphenopalatine ganglion are propelling the two neuromodulation devices toward approval for headache, Stewart J. Tepper, MD, said at the Summit in Neurology & Psychiatry.

“This would bring to four the number of devices we now have available to us to treat headache,” said Dr. Tepper, director of research at the Dartmouth Headache Clinic, Lebanon, N.H. Two types are already available in the United States: a trigeminal nerve stimulator approved for migraine prevention and two brands of transcranial magnetic stimulators approved for acute treatment of migraine with aura.

Noninvasive vagal nerve stimulator

The gammaCore device (electroCore Medical) could be approved for cluster headache this year, Dr. Tepper said. A company spokesman said the company submitted its pivotal trial data to the Food and Drug Administration in 2015, but couldn’t offer any insight into how far the process has progressed.

©Christopher Robbins/Thinkstockphotos.com

“That application is currently under review, and we look forward to the FDA’s decision when it comes,” Eric Liebler, electroCore vice president for scientific, medical, and governmental affairs, said in an interview.

The gammaCore device is an external vagal nerve stimulator already approved in Canada and Europe for the treatment of primary headache disorders. In April 2016, it was approved in the United Kingdom as well, Dr. Tepper said at the meeting, sponsored by the Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.

The device is a small, handheld unit that the patient uses twice each day, and which transmits mild current to the vagal nerve. It’s activated over the carotid pulse point on the neck for about 90 seconds. It’s thought to work by suppressing excessive extracellular glutamate and suppressing cortical spreading depression, Dr. Tepper said.

The most recent data for the gammaCore device, presented at the annual meeting of the American Headache Society (AHS) in June, suggest that it could also be beneficial in chronic headache and in menstrual migraine.

A 12-week, open-label study of 51 women with menstrual migraine looked at pain intensity, analgesic use, and migraine disability. Women used the device prophylactically, six stimulations each day for 3 days before and after the onset of menstruation. The mean number of menstrual migraine days each month declined significantly from 7.2 to 4.7. About 40% of the group had at least a 50% reduction in migraine days. Pain intensity also decreased significantly, as well as did the number of doses of analgesics. There were significant improvements on both the Headache Impact Test and Migraine Disability Assessment. One subject discontinued treatment due to dizziness during stimulation.

An 8-week study on cluster headache was published in May and updated at the AHS meeting. Investigators randomized 87 patients with cluster headache to standard therapy alone or plus the gammaCore device. The PREVA (Prevention and Acute treatment of chronic cluster headache) study determined that dual therapy reduced the number of weekly attacks by four, compared with standard therapy. A total of 40% of patients experienced at least a 50% response rate, compared with 8% of controls. A subanalysis presented at the AHS meeting showed that 18% of the dual-therapy group experienced at least a 75% response rate.

Implantable sphenopalatine ganglion stimulator

Dr. Tepper is particularly excited about the Pulsante device, an implantable, wireless sphenopalatine ganglion (SPG) stimulator manufactured by Autonomic Technologies, which he called “a dramatic change in paradigm,” for the treatment of cluster headaches.

The system consists of a neurostimulator about the size of an almond and a lead with six electrodes. It’s inserted under local anesthetic via a small incision in the upper gum on the side in which the patient experiences symptoms. The electrodes are positioned along the SPG nerve and the neurostimulator is affixed to the zygomatic process.

A handheld wireless controller placed against the cheek activates the device and controls the intensity of stimulation, which is thought to work by blocking signals to the postganglionic parasympathetic fibers. Those fibers innervate facial structures and the cerebral and meningeal blood vessels and are implicated in the pain and accompanying autonomic symptoms of a cluster headache attack.

“You can literally see this device working right before your eyes,” he said. “Patients having a cluster attack will exhibit ptosis, red watering eyes, nose running, and as soon as the device is turned on, you see the lid come up, the eye turn white, and the tearing and runny nose stop. This is an objective correlate to a subjective pain response. It’s dramatic and exciting.”

The pivotal Pathway CH-1study that led to European Union approval was small – just 43 patients – but found that half the cluster attacks could be terminated within 15 minutes of onset. About half of the patients, who had a decades-long history of cluster headaches, experienced close to a 90% reduction in attack frequency.

The latest Pulsante data were also presented in June at the AHS meeting. Two papers – one with 24-month data from the pivotal trial, and one with 12-month data from an ongoing registry study – were overwhelmingly positive, Dr. Tepper said.

The 24-month follow-up data to the pivotal study found that 61% of patients experienced a therapeutic response to SPG stimulation. Most attacks (79%) responded to stimulation alone without the need for abortive therapy. Most patients (64%) also experienced clinical improvements in preventive medication use. Twenty-one were able to reduce or even eliminate the use of preventive medications.

The registry study provided data on 85 patients. Of these, 68% experienced at least a 50% reduction in attack frequency; some reported close to a 90% reduction. A third of patients actually experienced some period of remission, and some patients who were not initially responders became responders after a year of treatment. Acute medication use declined by 52% overall and by 82% in those considered therapeutic responders.

“These data are extremely encouraging,” Dr. Tepper said.

Adverse events are minimal and most are related to implantation. A safety study of 99 patients found that adverse events included sensory disbranch, pain, and swelling, which resolved in 90 days.

The U.S. Pathway CH-2 Cluster Headache Study is now underway and aims to enroll 120 patients. “If the data are positive on this, the company will go ahead and pursue U.S. approval,” Dr. Tepper said.

Dr. Tepper has received personal remuneration and research funding from a number of pharmaceutical companies. He holds stock in Autonomic Technologies.

[email protected]

On Twitter @alz_gal

WASHINGTON – Encouraging data on an external vagal nerve stimulator and a minimally invasive system that targets the sphenopalatine ganglion are propelling the two neuromodulation devices toward approval for headache, Stewart J. Tepper, MD, said at the Summit in Neurology & Psychiatry.

“This would bring to four the number of devices we now have available to us to treat headache,” said Dr. Tepper, director of research at the Dartmouth Headache Clinic, Lebanon, N.H. Two types are already available in the United States: a trigeminal nerve stimulator approved for migraine prevention and two brands of transcranial magnetic stimulators approved for acute treatment of migraine with aura.

Noninvasive vagal nerve stimulator

The gammaCore device (electroCore Medical) could be approved for cluster headache this year, Dr. Tepper said. A company spokesman said the company submitted its pivotal trial data to the Food and Drug Administration in 2015, but couldn’t offer any insight into how far the process has progressed.

©Christopher Robbins/Thinkstockphotos.com

“That application is currently under review, and we look forward to the FDA’s decision when it comes,” Eric Liebler, electroCore vice president for scientific, medical, and governmental affairs, said in an interview.

The gammaCore device is an external vagal nerve stimulator already approved in Canada and Europe for the treatment of primary headache disorders. In April 2016, it was approved in the United Kingdom as well, Dr. Tepper said at the meeting, sponsored by the Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.

The device is a small, handheld unit that the patient uses twice each day, and which transmits mild current to the vagal nerve. It’s activated over the carotid pulse point on the neck for about 90 seconds. It’s thought to work by suppressing excessive extracellular glutamate and suppressing cortical spreading depression, Dr. Tepper said.

The most recent data for the gammaCore device, presented at the annual meeting of the American Headache Society (AHS) in June, suggest that it could also be beneficial in chronic headache and in menstrual migraine.

A 12-week, open-label study of 51 women with menstrual migraine looked at pain intensity, analgesic use, and migraine disability. Women used the device prophylactically, six stimulations each day for 3 days before and after the onset of menstruation. The mean number of menstrual migraine days each month declined significantly from 7.2 to 4.7. About 40% of the group had at least a 50% reduction in migraine days. Pain intensity also decreased significantly, as well as did the number of doses of analgesics. There were significant improvements on both the Headache Impact Test and Migraine Disability Assessment. One subject discontinued treatment due to dizziness during stimulation.

An 8-week study on cluster headache was published in May and updated at the AHS meeting. Investigators randomized 87 patients with cluster headache to standard therapy alone or plus the gammaCore device. The PREVA (Prevention and Acute treatment of chronic cluster headache) study determined that dual therapy reduced the number of weekly attacks by four, compared with standard therapy. A total of 40% of patients experienced at least a 50% response rate, compared with 8% of controls. A subanalysis presented at the AHS meeting showed that 18% of the dual-therapy group experienced at least a 75% response rate.

Implantable sphenopalatine ganglion stimulator

Dr. Tepper is particularly excited about the Pulsante device, an implantable, wireless sphenopalatine ganglion (SPG) stimulator manufactured by Autonomic Technologies, which he called “a dramatic change in paradigm,” for the treatment of cluster headaches.

The system consists of a neurostimulator about the size of an almond and a lead with six electrodes. It’s inserted under local anesthetic via a small incision in the upper gum on the side in which the patient experiences symptoms. The electrodes are positioned along the SPG nerve and the neurostimulator is affixed to the zygomatic process.

A handheld wireless controller placed against the cheek activates the device and controls the intensity of stimulation, which is thought to work by blocking signals to the postganglionic parasympathetic fibers. Those fibers innervate facial structures and the cerebral and meningeal blood vessels and are implicated in the pain and accompanying autonomic symptoms of a cluster headache attack.

“You can literally see this device working right before your eyes,” he said. “Patients having a cluster attack will exhibit ptosis, red watering eyes, nose running, and as soon as the device is turned on, you see the lid come up, the eye turn white, and the tearing and runny nose stop. This is an objective correlate to a subjective pain response. It’s dramatic and exciting.”

The pivotal Pathway CH-1study that led to European Union approval was small – just 43 patients – but found that half the cluster attacks could be terminated within 15 minutes of onset. About half of the patients, who had a decades-long history of cluster headaches, experienced close to a 90% reduction in attack frequency.

The latest Pulsante data were also presented in June at the AHS meeting. Two papers – one with 24-month data from the pivotal trial, and one with 12-month data from an ongoing registry study – were overwhelmingly positive, Dr. Tepper said.

The 24-month follow-up data to the pivotal study found that 61% of patients experienced a therapeutic response to SPG stimulation. Most attacks (79%) responded to stimulation alone without the need for abortive therapy. Most patients (64%) also experienced clinical improvements in preventive medication use. Twenty-one were able to reduce or even eliminate the use of preventive medications.

The registry study provided data on 85 patients. Of these, 68% experienced at least a 50% reduction in attack frequency; some reported close to a 90% reduction. A third of patients actually experienced some period of remission, and some patients who were not initially responders became responders after a year of treatment. Acute medication use declined by 52% overall and by 82% in those considered therapeutic responders.

“These data are extremely encouraging,” Dr. Tepper said.

Adverse events are minimal and most are related to implantation. A safety study of 99 patients found that adverse events included sensory disbranch, pain, and swelling, which resolved in 90 days.

The U.S. Pathway CH-2 Cluster Headache Study is now underway and aims to enroll 120 patients. “If the data are positive on this, the company will go ahead and pursue U.S. approval,” Dr. Tepper said.

Dr. Tepper has received personal remuneration and research funding from a number of pharmaceutical companies. He holds stock in Autonomic Technologies.

[email protected]

On Twitter @alz_gal

WASHINGTON – Encouraging data on an external vagal nerve stimulator and a minimally invasive system that targets the sphenopalatine ganglion are propelling the two neuromodulation devices toward approval for headache, Stewart J. Tepper, MD, said at the Summit in Neurology & Psychiatry.

“This would bring to four the number of devices we now have available to us to treat headache,” said Dr. Tepper, director of research at the Dartmouth Headache Clinic, Lebanon, N.H. Two types are already available in the United States: a trigeminal nerve stimulator approved for migraine prevention and two brands of transcranial magnetic stimulators approved for acute treatment of migraine with aura.

Noninvasive vagal nerve stimulator

The gammaCore device (electroCore Medical) could be approved for cluster headache this year, Dr. Tepper said. A company spokesman said the company submitted its pivotal trial data to the Food and Drug Administration in 2015, but couldn’t offer any insight into how far the process has progressed.

©Christopher Robbins/Thinkstockphotos.com

“That application is currently under review, and we look forward to the FDA’s decision when it comes,” Eric Liebler, electroCore vice president for scientific, medical, and governmental affairs, said in an interview.

The gammaCore device is an external vagal nerve stimulator already approved in Canada and Europe for the treatment of primary headache disorders. In April 2016, it was approved in the United Kingdom as well, Dr. Tepper said at the meeting, sponsored by the Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.

The device is a small, handheld unit that the patient uses twice each day, and which transmits mild current to the vagal nerve. It’s activated over the carotid pulse point on the neck for about 90 seconds. It’s thought to work by suppressing excessive extracellular glutamate and suppressing cortical spreading depression, Dr. Tepper said.

The most recent data for the gammaCore device, presented at the annual meeting of the American Headache Society (AHS) in June, suggest that it could also be beneficial in chronic headache and in menstrual migraine.

A 12-week, open-label study of 51 women with menstrual migraine looked at pain intensity, analgesic use, and migraine disability. Women used the device prophylactically, six stimulations each day for 3 days before and after the onset of menstruation. The mean number of menstrual migraine days each month declined significantly from 7.2 to 4.7. About 40% of the group had at least a 50% reduction in migraine days. Pain intensity also decreased significantly, as well as did the number of doses of analgesics. There were significant improvements on both the Headache Impact Test and Migraine Disability Assessment. One subject discontinued treatment due to dizziness during stimulation.

An 8-week study on cluster headache was published in May and updated at the AHS meeting. Investigators randomized 87 patients with cluster headache to standard therapy alone or plus the gammaCore device. The PREVA (Prevention and Acute treatment of chronic cluster headache) study determined that dual therapy reduced the number of weekly attacks by four, compared with standard therapy. A total of 40% of patients experienced at least a 50% response rate, compared with 8% of controls. A subanalysis presented at the AHS meeting showed that 18% of the dual-therapy group experienced at least a 75% response rate.

Implantable sphenopalatine ganglion stimulator

Dr. Tepper is particularly excited about the Pulsante device, an implantable, wireless sphenopalatine ganglion (SPG) stimulator manufactured by Autonomic Technologies, which he called “a dramatic change in paradigm,” for the treatment of cluster headaches.

The system consists of a neurostimulator about the size of an almond and a lead with six electrodes. It’s inserted under local anesthetic via a small incision in the upper gum on the side in which the patient experiences symptoms. The electrodes are positioned along the SPG nerve and the neurostimulator is affixed to the zygomatic process.

A handheld wireless controller placed against the cheek activates the device and controls the intensity of stimulation, which is thought to work by blocking signals to the postganglionic parasympathetic fibers. Those fibers innervate facial structures and the cerebral and meningeal blood vessels and are implicated in the pain and accompanying autonomic symptoms of a cluster headache attack.

“You can literally see this device working right before your eyes,” he said. “Patients having a cluster attack will exhibit ptosis, red watering eyes, nose running, and as soon as the device is turned on, you see the lid come up, the eye turn white, and the tearing and runny nose stop. This is an objective correlate to a subjective pain response. It’s dramatic and exciting.”

The pivotal Pathway CH-1study that led to European Union approval was small – just 43 patients – but found that half the cluster attacks could be terminated within 15 minutes of onset. About half of the patients, who had a decades-long history of cluster headaches, experienced close to a 90% reduction in attack frequency.

The latest Pulsante data were also presented in June at the AHS meeting. Two papers – one with 24-month data from the pivotal trial, and one with 12-month data from an ongoing registry study – were overwhelmingly positive, Dr. Tepper said.

The 24-month follow-up data to the pivotal study found that 61% of patients experienced a therapeutic response to SPG stimulation. Most attacks (79%) responded to stimulation alone without the need for abortive therapy. Most patients (64%) also experienced clinical improvements in preventive medication use. Twenty-one were able to reduce or even eliminate the use of preventive medications.

The registry study provided data on 85 patients. Of these, 68% experienced at least a 50% reduction in attack frequency; some reported close to a 90% reduction. A third of patients actually experienced some period of remission, and some patients who were not initially responders became responders after a year of treatment. Acute medication use declined by 52% overall and by 82% in those considered therapeutic responders.

“These data are extremely encouraging,” Dr. Tepper said.

Adverse events are minimal and most are related to implantation. A safety study of 99 patients found that adverse events included sensory disbranch, pain, and swelling, which resolved in 90 days.

The U.S. Pathway CH-2 Cluster Headache Study is now underway and aims to enroll 120 patients. “If the data are positive on this, the company will go ahead and pursue U.S. approval,” Dr. Tepper said.

Dr. Tepper has received personal remuneration and research funding from a number of pharmaceutical companies. He holds stock in Autonomic Technologies.

[email protected]

On Twitter @alz_gal