Arab Americans reluctant to seek depression care from psychiatrists

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– A new study, the first of its kind, finds that Arab Americans in a Michigan community are among least likely ethnic groups to seek help for depression from a mental health specialist. But they’re especially likely to look for assistance from a primary care physician.

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– A new study, the first of its kind, finds that Arab Americans in a Michigan community are among least likely ethnic groups to seek help for depression from a mental health specialist. But they’re especially likely to look for assistance from a primary care physician.

 

– A new study, the first of its kind, finds that Arab Americans in a Michigan community are among least likely ethnic groups to seek help for depression from a mental health specialist. But they’re especially likely to look for assistance from a primary care physician.

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Apomorphine pump dramatically decreases ‘off’ time in Parkinson’s

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BOSTON – The most rigorous study of its kind suggests that apomorphine subcutaneous infusion (APO) via pump can substantially reduce ‘off’ time when conventional therapy fails to control dyskinesias in patients with Parkinson’s disease.

tupungato/Thinkstock
Dr. Katzenschlager presented the findings of the industry-funded phase III TOLEDO study at the annual meeting of the American Academy of Neurology.

According to the study authors, previous open-label research has supported the use of apomorphine to reduce dyskinesias, off time, and the need for levodopa.

For the new study, researchers recruited 106 patients aged at least 30 years with a diagnosis of idiopathic Parkinson’s disease and motor fluctuations that were not adequately controlled by medication. They all were taking L-dopa and had an average off time of at least 3 hours a day.

The subjects, who came from 23 centers in seven countries, were randomly assigned to receive apomorphine infusion while they were awake (16 hours; 8 or less mg/hour) or placebo saline infusion.

“Apomorphine is administered via bespoke pumps, which are produced by several manufacturers,” Dr. Katzenschlager said. “The pump used in the trial is a mechanical delivery system and has been in clinical use in Europe for many years for this purpose. The pump is worn outside the body; no surgical procedure is required. It delivers the drug continuously into the subcutaneous fatty tissue, usually abdomen or thighs, via a tube and a thin metal or Teflon needle.”

The pump is about the size of a mobile phone, Dr. Katzenschlager said, and typically worn in a pouch attached to a belt.

The study abstract does not note the dose of apomorphine, and Dr. Katzenschlager declined to say how much of the drug is given to patients. The trial information on clinicaltrials.gov states only that a 5-mg/mL solution of APO-go was to be provided via prefilled syringe. The hourly flow rate of apomorphine and dosages of other Parkinson’s disease medications were adjusted during the first 4 weeks of the trial for efficacy and tolerability purposes.

Researchers report that daily off time declined over the 12-week trial (–0.58 hours for placebo vs. –2.47 hours for apomorphine), accounting for a difference of –1.89 hours (95% CI, –3.16 to –0.62; P = .0025).

“This was highly statistically significant. This degree of improvement has been proven to be clinically relevant to the patients,” Dr. Katzenschlager said. “This was reflected in the patients’ own assessment of the overall treatment effect in the study.”

The study examined Patient Global Impression of Change in apomorphine vs. placebo. The abstract released at the AAN meeting does not report the full results but says that the apomorphine patients had higher scores at the end of the study (P less than .001).

Why might this infusion approach work? “Apomorphine infusion achieves more than injections, which are intended as a rescue therapy for off periods in addition to the patients’ oral medication,” Dr. Katzenschlager said. “The continuous delivery of apomorphine resembles the natural state of dopamine levels in the brain in persons without Parkinson’s disease, where this is mostly stable. The administration via the pump system usually enables oral drugs to be reduced. This may contribute to the improvement in dyskinesias often observed and is a benefit to the patients in itself.”

The study authors noted that apomorphine “was generally well tolerated and no unexpected adverse events were observed.” Dr. Katzenschlager declined to discuss cost.

Britannia Pharmaceuticals, which manufactures APO-go, funded the study. Dr. Katzenschlager reports multiple disclosures, including research support and speaking/consulting fees from Brittania Pharmaceuticals.

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BOSTON – The most rigorous study of its kind suggests that apomorphine subcutaneous infusion (APO) via pump can substantially reduce ‘off’ time when conventional therapy fails to control dyskinesias in patients with Parkinson’s disease.

tupungato/Thinkstock
Dr. Katzenschlager presented the findings of the industry-funded phase III TOLEDO study at the annual meeting of the American Academy of Neurology.

According to the study authors, previous open-label research has supported the use of apomorphine to reduce dyskinesias, off time, and the need for levodopa.

For the new study, researchers recruited 106 patients aged at least 30 years with a diagnosis of idiopathic Parkinson’s disease and motor fluctuations that were not adequately controlled by medication. They all were taking L-dopa and had an average off time of at least 3 hours a day.

The subjects, who came from 23 centers in seven countries, were randomly assigned to receive apomorphine infusion while they were awake (16 hours; 8 or less mg/hour) or placebo saline infusion.

“Apomorphine is administered via bespoke pumps, which are produced by several manufacturers,” Dr. Katzenschlager said. “The pump used in the trial is a mechanical delivery system and has been in clinical use in Europe for many years for this purpose. The pump is worn outside the body; no surgical procedure is required. It delivers the drug continuously into the subcutaneous fatty tissue, usually abdomen or thighs, via a tube and a thin metal or Teflon needle.”

The pump is about the size of a mobile phone, Dr. Katzenschlager said, and typically worn in a pouch attached to a belt.

The study abstract does not note the dose of apomorphine, and Dr. Katzenschlager declined to say how much of the drug is given to patients. The trial information on clinicaltrials.gov states only that a 5-mg/mL solution of APO-go was to be provided via prefilled syringe. The hourly flow rate of apomorphine and dosages of other Parkinson’s disease medications were adjusted during the first 4 weeks of the trial for efficacy and tolerability purposes.

Researchers report that daily off time declined over the 12-week trial (–0.58 hours for placebo vs. –2.47 hours for apomorphine), accounting for a difference of –1.89 hours (95% CI, –3.16 to –0.62; P = .0025).

“This was highly statistically significant. This degree of improvement has been proven to be clinically relevant to the patients,” Dr. Katzenschlager said. “This was reflected in the patients’ own assessment of the overall treatment effect in the study.”

The study examined Patient Global Impression of Change in apomorphine vs. placebo. The abstract released at the AAN meeting does not report the full results but says that the apomorphine patients had higher scores at the end of the study (P less than .001).

Why might this infusion approach work? “Apomorphine infusion achieves more than injections, which are intended as a rescue therapy for off periods in addition to the patients’ oral medication,” Dr. Katzenschlager said. “The continuous delivery of apomorphine resembles the natural state of dopamine levels in the brain in persons without Parkinson’s disease, where this is mostly stable. The administration via the pump system usually enables oral drugs to be reduced. This may contribute to the improvement in dyskinesias often observed and is a benefit to the patients in itself.”

The study authors noted that apomorphine “was generally well tolerated and no unexpected adverse events were observed.” Dr. Katzenschlager declined to discuss cost.

Britannia Pharmaceuticals, which manufactures APO-go, funded the study. Dr. Katzenschlager reports multiple disclosures, including research support and speaking/consulting fees from Brittania Pharmaceuticals.

 

BOSTON – The most rigorous study of its kind suggests that apomorphine subcutaneous infusion (APO) via pump can substantially reduce ‘off’ time when conventional therapy fails to control dyskinesias in patients with Parkinson’s disease.

tupungato/Thinkstock
Dr. Katzenschlager presented the findings of the industry-funded phase III TOLEDO study at the annual meeting of the American Academy of Neurology.

According to the study authors, previous open-label research has supported the use of apomorphine to reduce dyskinesias, off time, and the need for levodopa.

For the new study, researchers recruited 106 patients aged at least 30 years with a diagnosis of idiopathic Parkinson’s disease and motor fluctuations that were not adequately controlled by medication. They all were taking L-dopa and had an average off time of at least 3 hours a day.

The subjects, who came from 23 centers in seven countries, were randomly assigned to receive apomorphine infusion while they were awake (16 hours; 8 or less mg/hour) or placebo saline infusion.

“Apomorphine is administered via bespoke pumps, which are produced by several manufacturers,” Dr. Katzenschlager said. “The pump used in the trial is a mechanical delivery system and has been in clinical use in Europe for many years for this purpose. The pump is worn outside the body; no surgical procedure is required. It delivers the drug continuously into the subcutaneous fatty tissue, usually abdomen or thighs, via a tube and a thin metal or Teflon needle.”

The pump is about the size of a mobile phone, Dr. Katzenschlager said, and typically worn in a pouch attached to a belt.

The study abstract does not note the dose of apomorphine, and Dr. Katzenschlager declined to say how much of the drug is given to patients. The trial information on clinicaltrials.gov states only that a 5-mg/mL solution of APO-go was to be provided via prefilled syringe. The hourly flow rate of apomorphine and dosages of other Parkinson’s disease medications were adjusted during the first 4 weeks of the trial for efficacy and tolerability purposes.

Researchers report that daily off time declined over the 12-week trial (–0.58 hours for placebo vs. –2.47 hours for apomorphine), accounting for a difference of –1.89 hours (95% CI, –3.16 to –0.62; P = .0025).

“This was highly statistically significant. This degree of improvement has been proven to be clinically relevant to the patients,” Dr. Katzenschlager said. “This was reflected in the patients’ own assessment of the overall treatment effect in the study.”

The study examined Patient Global Impression of Change in apomorphine vs. placebo. The abstract released at the AAN meeting does not report the full results but says that the apomorphine patients had higher scores at the end of the study (P less than .001).

Why might this infusion approach work? “Apomorphine infusion achieves more than injections, which are intended as a rescue therapy for off periods in addition to the patients’ oral medication,” Dr. Katzenschlager said. “The continuous delivery of apomorphine resembles the natural state of dopamine levels in the brain in persons without Parkinson’s disease, where this is mostly stable. The administration via the pump system usually enables oral drugs to be reduced. This may contribute to the improvement in dyskinesias often observed and is a benefit to the patients in itself.”

The study authors noted that apomorphine “was generally well tolerated and no unexpected adverse events were observed.” Dr. Katzenschlager declined to discuss cost.

Britannia Pharmaceuticals, which manufactures APO-go, funded the study. Dr. Katzenschlager reports multiple disclosures, including research support and speaking/consulting fees from Brittania Pharmaceuticals.

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Key clinical point: Apomorphine subcutaneous infusion via pump dramatically decreases ‘off’ time in Parkinson’s patients whose muscle movements are not well controlled by medication.

Major finding: Daily ‘off’ time declined over 12 weeks by –0.58 hours for placebo vs. –2.47 hours for apomorphine, accounting for a difference of –1.89 hours (95% CI, –3.16 to –0.62; P = .0025).

Data source: Double-blind, randomized, placebo-controlled, phase III study of 106 Parkinson’s disease patients.

Disclosures: Britannia Pharmaceuticals, which manufactures APO-go, funded the study.

Most veterans with schizophrenia or bipolar I report suicide attempts

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– A new study reports that about half of assessed U.S. veterans with schizophrenia or bipolar I disorder have tried to kill themselves. Nearly 70% of those with schizophrenia had documented suicidal behavior or ideation, as did more than 82% of those with bipolar I disorder.

“The VA struggles to predict suicidal ideation and behavior,” said study lead author Philip D. Harvey, PhD, of the Carter VA Medical Center in Miami, in an interview. “These data suggest that having one of these diagnoses is a major risk factor. Regular assessment makes considerable sense.”

Dr. Harvey released the study findings in a poster at the annual meeting of the American Psychiatric Association.

For the study, Dr. Harvey and his colleagues examined findings from a VA research project into the genetics behind functional disability in schizophrenia and bipolar illness.

“We know that suicide risk is higher in veterans than in the general population. We also know that the current focus is on returning veterans who were deployed in combat operations,” said Dr. Harvey, who also is affiliated with the University of Miami. “We wanted to evaluate the risk for suicidal ideation and behavior in the segment of the veteran population who have recently or ever been exposed to military trauma.”

The project assessed VA patients with schizophrenia (N = 3,941) or bipolar I disorder (N = 5,414) through in-person evaluations regarding issues like cognitive and functional status, and history of posttraumatic stress disorder. All of the subjects were outpatients at 26 VA medical centers.

Combined, the mean age of the study participants was 53.6 years, plus or minus 11 years, and 86.2% were male. Whites made up 57.4% of the sample, followed by blacks (37.0%) and other (5.6%). A total of 27% had no comorbid psychiatric conditions.

The study authors found documented suicidal ideation or suicidal behavior in 69.9% of veterans with schizophrenia and 82.3% of those with bipolar disorder; the percentages who reported making actual suicide attempts was 46.1% schizophrenia and 54.5% bipolar disorder.

The risk of suicidal ideation was lower in schizophrenia vs. bipolar disorder (odds ratio, 0.82; 95% confidence interval, 0.71-0.95), as was suicidal behavior (OR, 0.81; 95% CI, 0.71-0.93).

Dr. Harvey said this is not surprising. “The combination of a history of euphoric mood and significant depression [characteristic of bipolar disorder] is very challenging.”

Other factors lowered risk: College education vs. high school or less (OR, 0.82; 95% CI, 0.67-1.00 for ideation; OR, 0.70; 95% CI, 0.58-0.84 for behavior). In addition, lower risk was found among black vs. white patients (OR, 0.72; 95% CI, 0.63-0.84 for ideation; OR, 0.82; 95% CI, 0.72-0.93, for behavior).

These factors boosted risk: multiple psychiatric comorbidities vs. none (OR, 2.61; 95% CI, 2.22-3.07 for ideation; OR, 3.82; 95% CI, 3.30-4.41, for behavior), and those with a history of being ever vs. never married (OR, 1.18; 95% CI, 1.02-1.37 for ideation; OR, 1.36; 95% CI, 1.19-1.55, for behavior). Most of those who had been married later were divorced.

“These findings underscore the need for continuous monitoring for suicidality in veteran populations, regardless of age or psychiatric diagnosis, and especially with multiple psychiatric comorbidities,” the authors wrote.

The study was funded by the Department of Veterans Affairs Cooperative Study Program. Dr. Harvey reported no relevant disclosures.
 

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– A new study reports that about half of assessed U.S. veterans with schizophrenia or bipolar I disorder have tried to kill themselves. Nearly 70% of those with schizophrenia had documented suicidal behavior or ideation, as did more than 82% of those with bipolar I disorder.

“The VA struggles to predict suicidal ideation and behavior,” said study lead author Philip D. Harvey, PhD, of the Carter VA Medical Center in Miami, in an interview. “These data suggest that having one of these diagnoses is a major risk factor. Regular assessment makes considerable sense.”

Dr. Harvey released the study findings in a poster at the annual meeting of the American Psychiatric Association.

For the study, Dr. Harvey and his colleagues examined findings from a VA research project into the genetics behind functional disability in schizophrenia and bipolar illness.

“We know that suicide risk is higher in veterans than in the general population. We also know that the current focus is on returning veterans who were deployed in combat operations,” said Dr. Harvey, who also is affiliated with the University of Miami. “We wanted to evaluate the risk for suicidal ideation and behavior in the segment of the veteran population who have recently or ever been exposed to military trauma.”

The project assessed VA patients with schizophrenia (N = 3,941) or bipolar I disorder (N = 5,414) through in-person evaluations regarding issues like cognitive and functional status, and history of posttraumatic stress disorder. All of the subjects were outpatients at 26 VA medical centers.

Combined, the mean age of the study participants was 53.6 years, plus or minus 11 years, and 86.2% were male. Whites made up 57.4% of the sample, followed by blacks (37.0%) and other (5.6%). A total of 27% had no comorbid psychiatric conditions.

The study authors found documented suicidal ideation or suicidal behavior in 69.9% of veterans with schizophrenia and 82.3% of those with bipolar disorder; the percentages who reported making actual suicide attempts was 46.1% schizophrenia and 54.5% bipolar disorder.

The risk of suicidal ideation was lower in schizophrenia vs. bipolar disorder (odds ratio, 0.82; 95% confidence interval, 0.71-0.95), as was suicidal behavior (OR, 0.81; 95% CI, 0.71-0.93).

Dr. Harvey said this is not surprising. “The combination of a history of euphoric mood and significant depression [characteristic of bipolar disorder] is very challenging.”

Other factors lowered risk: College education vs. high school or less (OR, 0.82; 95% CI, 0.67-1.00 for ideation; OR, 0.70; 95% CI, 0.58-0.84 for behavior). In addition, lower risk was found among black vs. white patients (OR, 0.72; 95% CI, 0.63-0.84 for ideation; OR, 0.82; 95% CI, 0.72-0.93, for behavior).

These factors boosted risk: multiple psychiatric comorbidities vs. none (OR, 2.61; 95% CI, 2.22-3.07 for ideation; OR, 3.82; 95% CI, 3.30-4.41, for behavior), and those with a history of being ever vs. never married (OR, 1.18; 95% CI, 1.02-1.37 for ideation; OR, 1.36; 95% CI, 1.19-1.55, for behavior). Most of those who had been married later were divorced.

“These findings underscore the need for continuous monitoring for suicidality in veteran populations, regardless of age or psychiatric diagnosis, and especially with multiple psychiatric comorbidities,” the authors wrote.

The study was funded by the Department of Veterans Affairs Cooperative Study Program. Dr. Harvey reported no relevant disclosures.
 

 

– A new study reports that about half of assessed U.S. veterans with schizophrenia or bipolar I disorder have tried to kill themselves. Nearly 70% of those with schizophrenia had documented suicidal behavior or ideation, as did more than 82% of those with bipolar I disorder.

“The VA struggles to predict suicidal ideation and behavior,” said study lead author Philip D. Harvey, PhD, of the Carter VA Medical Center in Miami, in an interview. “These data suggest that having one of these diagnoses is a major risk factor. Regular assessment makes considerable sense.”

Dr. Harvey released the study findings in a poster at the annual meeting of the American Psychiatric Association.

For the study, Dr. Harvey and his colleagues examined findings from a VA research project into the genetics behind functional disability in schizophrenia and bipolar illness.

“We know that suicide risk is higher in veterans than in the general population. We also know that the current focus is on returning veterans who were deployed in combat operations,” said Dr. Harvey, who also is affiliated with the University of Miami. “We wanted to evaluate the risk for suicidal ideation and behavior in the segment of the veteran population who have recently or ever been exposed to military trauma.”

The project assessed VA patients with schizophrenia (N = 3,941) or bipolar I disorder (N = 5,414) through in-person evaluations regarding issues like cognitive and functional status, and history of posttraumatic stress disorder. All of the subjects were outpatients at 26 VA medical centers.

Combined, the mean age of the study participants was 53.6 years, plus or minus 11 years, and 86.2% were male. Whites made up 57.4% of the sample, followed by blacks (37.0%) and other (5.6%). A total of 27% had no comorbid psychiatric conditions.

The study authors found documented suicidal ideation or suicidal behavior in 69.9% of veterans with schizophrenia and 82.3% of those with bipolar disorder; the percentages who reported making actual suicide attempts was 46.1% schizophrenia and 54.5% bipolar disorder.

The risk of suicidal ideation was lower in schizophrenia vs. bipolar disorder (odds ratio, 0.82; 95% confidence interval, 0.71-0.95), as was suicidal behavior (OR, 0.81; 95% CI, 0.71-0.93).

Dr. Harvey said this is not surprising. “The combination of a history of euphoric mood and significant depression [characteristic of bipolar disorder] is very challenging.”

Other factors lowered risk: College education vs. high school or less (OR, 0.82; 95% CI, 0.67-1.00 for ideation; OR, 0.70; 95% CI, 0.58-0.84 for behavior). In addition, lower risk was found among black vs. white patients (OR, 0.72; 95% CI, 0.63-0.84 for ideation; OR, 0.82; 95% CI, 0.72-0.93, for behavior).

These factors boosted risk: multiple psychiatric comorbidities vs. none (OR, 2.61; 95% CI, 2.22-3.07 for ideation; OR, 3.82; 95% CI, 3.30-4.41, for behavior), and those with a history of being ever vs. never married (OR, 1.18; 95% CI, 1.02-1.37 for ideation; OR, 1.36; 95% CI, 1.19-1.55, for behavior). Most of those who had been married later were divorced.

“These findings underscore the need for continuous monitoring for suicidality in veteran populations, regardless of age or psychiatric diagnosis, and especially with multiple psychiatric comorbidities,” the authors wrote.

The study was funded by the Department of Veterans Affairs Cooperative Study Program. Dr. Harvey reported no relevant disclosures.
 

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Key clinical point: Roughly half of U.S. veterans with schizophrenia or bipolar I disorder have tried to kill themselves, and most of these veterans have histories of suicidal ideation or behavior.

Major finding: Suicide attempts are reported in 46.1% of patients with schizophrenia and 54.5% of those with bipolar I disorder. Documented suicidal ideation or behavior is reported in 69.9% of veterans with schizophrenia and 82.3% of those with bipolar disorder.

Data source: A genomic study with in-person assessments of VA patients with schizophrenia (N = 3,941) or bipolar disorder (N = 5,414). The mean age was 53.6 years, plus or minus 11 years; 86.2% were male, and 57.4% were white.

Disclosures: The study was funded by the Department of Veterans Affairs Cooperative Study Program.

Consistent weight benefits seen in empagliflozin use

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– In a follow-up to the blockbuster trial results linking the type 2 diabetes drug empagliflozin (Jardiance) to a dramatically lower risk of cardiac death, researchers report that the drug improved weight-related measures in multiple groups.

Two daily doses of empagliflozin, 10 mg and 25 mg, “had consistent and robust effects on lowering weight, waist circumference, and other markers of body fat across most patients regardless of their age, sex, or degree of abdominal obesity,” study lead author Ian J. Neeland, MD, of the department of medicine at UT Southwestern Medical Center, Dallas, said in an interview. “Our next step is to determine if these effects may contribute to the improvement in cardiovascular risk seen with the drug.”

Dr. Ian J. Neeland
Dr. Neeland presented the findings, a secondary analysis of the landmark EMPA-REG OUTCOME study, at the annual scientific sessions of the American Diabetes Association.

“In the EMPA-REG OUTCOME study, empagliflozin treatment significantly reduced the risk of cardiovascular death by 38%,” Dr. Neeland said. “We also observed that patients treated with empagliflozin had improvements in markers of body fatness such as weight, waist circumference, and estimated total body fat. Since we know that obesity is a major risk factor for cardiovascular disease, we were interested in finding out if the improvements in weight and other markers of body fatness may have contributed to the observed cardiovascular benefits of empagliflozin in the study. One part of this was to examine whether the drug had consistent effects on body fat according to other important cardiovascular risk factors.”

The researchers analyzed changes in body weight, waist circumference, index of central obesity, and estimated total body fat from baseline to week 164 in a study that randomly assigned participants with type 2 diabetes and cardiovascular disease to placebo or 10 mg or 25 mg of empagliflozin. The number of patients in the groups were 2,333, 2,345 and 2,342, respectively, and their mean baseline weight was around 86.0 kg.

In general, researchers found that across groups, weight measures improved more in drug-treated patients than those treated with placebo. The higher dose (25 mg) often had a greater effect; the two available doses of the drug are 10 mg and 20 mg.

For example, the placebo-adjusted mean reduction in weight was –1.70 kg in men (95% confidence interval, –2.14 to –1.27) in the 10-mg group and 2.18 kg (95% CI, –2.61 to –1.75) in the 25-mg group. For women, the reduction was –1.32 kg (95% CI, –2.02 to –0.62) in the 10-mg group and –1.44 kg (95% CI, –2.15 to –0.73) in the 25-mg group.

“Patients lost on average 1.5-2 kg of weight – about 4 pounds – with empagliflozin, compared with placebo,” Dr. Neeland said. “Although quality of life and other metrics of better health were not systematically collected, we do know that people who lose weight and waist circumference tend to feel better, have fewer health problems, and live longer, compared with people who remain obese.”

Dr. Neeland said researchers still need to understand whether the improvements in obesity markers contribute to the drug’s positive cardiac effects.

Study funding was not reported. The original EMPA-REG OUTCOME trial was funded by Boehringer Ingelheim and Eli Lilly. Dr. Neeland disclosed consultant/speakers bureau support from Boehringer Ingelheim. He is a scientific advisory board member for Advanced MR Analytics AB.
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– In a follow-up to the blockbuster trial results linking the type 2 diabetes drug empagliflozin (Jardiance) to a dramatically lower risk of cardiac death, researchers report that the drug improved weight-related measures in multiple groups.

Two daily doses of empagliflozin, 10 mg and 25 mg, “had consistent and robust effects on lowering weight, waist circumference, and other markers of body fat across most patients regardless of their age, sex, or degree of abdominal obesity,” study lead author Ian J. Neeland, MD, of the department of medicine at UT Southwestern Medical Center, Dallas, said in an interview. “Our next step is to determine if these effects may contribute to the improvement in cardiovascular risk seen with the drug.”

Dr. Ian J. Neeland
Dr. Neeland presented the findings, a secondary analysis of the landmark EMPA-REG OUTCOME study, at the annual scientific sessions of the American Diabetes Association.

“In the EMPA-REG OUTCOME study, empagliflozin treatment significantly reduced the risk of cardiovascular death by 38%,” Dr. Neeland said. “We also observed that patients treated with empagliflozin had improvements in markers of body fatness such as weight, waist circumference, and estimated total body fat. Since we know that obesity is a major risk factor for cardiovascular disease, we were interested in finding out if the improvements in weight and other markers of body fatness may have contributed to the observed cardiovascular benefits of empagliflozin in the study. One part of this was to examine whether the drug had consistent effects on body fat according to other important cardiovascular risk factors.”

The researchers analyzed changes in body weight, waist circumference, index of central obesity, and estimated total body fat from baseline to week 164 in a study that randomly assigned participants with type 2 diabetes and cardiovascular disease to placebo or 10 mg or 25 mg of empagliflozin. The number of patients in the groups were 2,333, 2,345 and 2,342, respectively, and their mean baseline weight was around 86.0 kg.

In general, researchers found that across groups, weight measures improved more in drug-treated patients than those treated with placebo. The higher dose (25 mg) often had a greater effect; the two available doses of the drug are 10 mg and 20 mg.

For example, the placebo-adjusted mean reduction in weight was –1.70 kg in men (95% confidence interval, –2.14 to –1.27) in the 10-mg group and 2.18 kg (95% CI, –2.61 to –1.75) in the 25-mg group. For women, the reduction was –1.32 kg (95% CI, –2.02 to –0.62) in the 10-mg group and –1.44 kg (95% CI, –2.15 to –0.73) in the 25-mg group.

“Patients lost on average 1.5-2 kg of weight – about 4 pounds – with empagliflozin, compared with placebo,” Dr. Neeland said. “Although quality of life and other metrics of better health were not systematically collected, we do know that people who lose weight and waist circumference tend to feel better, have fewer health problems, and live longer, compared with people who remain obese.”

Dr. Neeland said researchers still need to understand whether the improvements in obesity markers contribute to the drug’s positive cardiac effects.

Study funding was not reported. The original EMPA-REG OUTCOME trial was funded by Boehringer Ingelheim and Eli Lilly. Dr. Neeland disclosed consultant/speakers bureau support from Boehringer Ingelheim. He is a scientific advisory board member for Advanced MR Analytics AB.

 

– In a follow-up to the blockbuster trial results linking the type 2 diabetes drug empagliflozin (Jardiance) to a dramatically lower risk of cardiac death, researchers report that the drug improved weight-related measures in multiple groups.

Two daily doses of empagliflozin, 10 mg and 25 mg, “had consistent and robust effects on lowering weight, waist circumference, and other markers of body fat across most patients regardless of their age, sex, or degree of abdominal obesity,” study lead author Ian J. Neeland, MD, of the department of medicine at UT Southwestern Medical Center, Dallas, said in an interview. “Our next step is to determine if these effects may contribute to the improvement in cardiovascular risk seen with the drug.”

Dr. Ian J. Neeland
Dr. Neeland presented the findings, a secondary analysis of the landmark EMPA-REG OUTCOME study, at the annual scientific sessions of the American Diabetes Association.

“In the EMPA-REG OUTCOME study, empagliflozin treatment significantly reduced the risk of cardiovascular death by 38%,” Dr. Neeland said. “We also observed that patients treated with empagliflozin had improvements in markers of body fatness such as weight, waist circumference, and estimated total body fat. Since we know that obesity is a major risk factor for cardiovascular disease, we were interested in finding out if the improvements in weight and other markers of body fatness may have contributed to the observed cardiovascular benefits of empagliflozin in the study. One part of this was to examine whether the drug had consistent effects on body fat according to other important cardiovascular risk factors.”

The researchers analyzed changes in body weight, waist circumference, index of central obesity, and estimated total body fat from baseline to week 164 in a study that randomly assigned participants with type 2 diabetes and cardiovascular disease to placebo or 10 mg or 25 mg of empagliflozin. The number of patients in the groups were 2,333, 2,345 and 2,342, respectively, and their mean baseline weight was around 86.0 kg.

In general, researchers found that across groups, weight measures improved more in drug-treated patients than those treated with placebo. The higher dose (25 mg) often had a greater effect; the two available doses of the drug are 10 mg and 20 mg.

For example, the placebo-adjusted mean reduction in weight was –1.70 kg in men (95% confidence interval, –2.14 to –1.27) in the 10-mg group and 2.18 kg (95% CI, –2.61 to –1.75) in the 25-mg group. For women, the reduction was –1.32 kg (95% CI, –2.02 to –0.62) in the 10-mg group and –1.44 kg (95% CI, –2.15 to –0.73) in the 25-mg group.

“Patients lost on average 1.5-2 kg of weight – about 4 pounds – with empagliflozin, compared with placebo,” Dr. Neeland said. “Although quality of life and other metrics of better health were not systematically collected, we do know that people who lose weight and waist circumference tend to feel better, have fewer health problems, and live longer, compared with people who remain obese.”

Dr. Neeland said researchers still need to understand whether the improvements in obesity markers contribute to the drug’s positive cardiac effects.

Study funding was not reported. The original EMPA-REG OUTCOME trial was funded by Boehringer Ingelheim and Eli Lilly. Dr. Neeland disclosed consultant/speakers bureau support from Boehringer Ingelheim. He is a scientific advisory board member for Advanced MR Analytics AB.
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Key clinical point: With few exceptions, empagliflozin improved weight-related measures across age, sex, and waist circumference.

Major finding: Placebo-adjusted mean reduction in weight was –1.70 kg in men for daily 10-mg dose group and –2.18 kg in daily 25-mg group. For women, the losses were –1.32 kg in the 10-mg group and –1.44 kg in the 25-mg group.

Data source: Secondary analysis of 164-week randomized, double-blind, placebo-controlled study of patients with type 2 diabetes and cardiovascular disease assigned to placebo or 10-mg or 25-mg doses of empagliflozin.

Disclosures: Study funding was not reported. The original EMPA-REG OUTCOME trial was funded by Boehringer Ingelheim and Eli Lilly.

Vets with TBIs are more likely to develop Parkinson’s

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– New research finds that military veterans who suffered mild traumatic brain injuries (TBIs) faced more than 1.5 times the risk of developing Parkinson’s disease (PD), compared with other veterans over up to 12 years of follow-up. The risk doubled for those who suffered moderate to severe TBIs.

The findings don’t confirm a link between brain injury and PD, and the number of PD diagnoses remained small even among those who’d suffered the worst TBIs.

Still, the findings suggest that “mild TBI may have long-term consequences, including PD,” said study lead author Raquel C. Gardner, MD, a neurologist whose findings were released at the annual meeting of the American Academy of Neurology. “We need to ramp up efforts to prevent TBI and also make sure we are carefully screening TBI-exposed patients for some of these long-term consequences, for which we may be able to offer therapies to improve quality of life.”

3283197d_273/Thinkstock
Previous research has linked moderate to severe TBI to PD, said Dr. Gardner of the University of California, San Francisco.

Most recently, a 2016 study found signs of a link between previous TBIs that caused more than an hour of unconsciousness and PD (hazard ratio, 3.56; 95% confidence interval, 1.52-8.28; JAMA Neurol. 2016;73[9]:1062-9).

As for mild TBI, a 2014 systematic review examined five studies and found that only one linked it to PD (OR, 1.5; 95% CI, 1.4-1.7).

For the new study, researchers analyzed records of patients served by the Veterans Health Administration from 2002 to 2014. They age matched 162,935 veterans who had suffered TBIs (half mild, half moderate to severe) to 162,935 veterans who had not (a 2% sample of all veterans served by the VHA).

Mild TBIs are defined as those that caused loss of consciousness of less than 30 minutes. Mild to moderate TBIs caused more than 30 minutes of unconsciousness.

The study participants hadn’t been diagnosed with PD or dementia at baseline or over the following year. Their average age was 48 years.

Compared with those who hadn’t suffered TBIs, those who did were more likely to be male (92% vs. 85%) and to suffer from hypertension (12% vs. 8%), cerebrovascular disease (4% vs. 1%), posttraumatic stress disorder (21% vs. 4%), and depression (24% vs. 9%; P less than .001).

“Prior studies have determined that TBI is a risk factor for depression and PTSD,” Dr. Gardner said. “Thus, higher rates of these outcomes among the patient with TBI in our study may represent sequelae of the TBI.”

Indications of education and income were similar among the two groups (P = .94 and P = .29, respectively). Those who suffered TBIs were more likely to be white than those who didn’t (73% vs. 67%) and less likely to be of other or unknown race (7% vs. 13%; P less than .001).

The percentages of veterans who developed PD were 0.31% (no TBI), 0.58% (any TBI), 0.47% (mild TBI), and 0.75% (moderate/severe TBI).

The unadjusted hazard ratios for PD were 1.81 (1.63-2.01) for any TBI, 1.59 (1.39-1.82) for mild TBI, and 2.01 (1.78-2.26) for moderate/severe TBI (P less than .0001).

Hazard ratios adjusted for demographics and comorbidities were 1.71 (1.53-1.92) for any TBI, 1.56 (1.35-1.80) for mild TBI, and 1.83 (1.61-2.07) for mild/moderate TBI (P less than .0001).

“The vast majority of people in this study did not develop PD,” Dr. Gardner said. “However, those with TBI had about a 50%-60% increased risk of PD that was statistically significant. While the P value is very small, the important numbers are really the confidence intervals around the estimate. According to our confidence intervals, we are very confident that the true estimate is between about 35% and 80% increased risk.”

Researchers also found that TBI sufferers who developed PD were 2 years younger at diagnosis than those who didn’t suffer TBIs (70 vs. 72; P = .003).

To limit the possibility of reverse causation, researchers tried excluding veterans who were diagnosed with PD within 4 years after baseline. The results remained similar.

The study has limitations. It’s not clear when the TBIs occurred. Also, the study doesn’t take the causes of TBIs into account. “In this veteran population, particularly among the younger veterans of Operation Iraqi Freedom and Operation Enduring Freedom, many are likely blast-related TBIs,” Dr. Gardner said.

The study is also limited because of the sample, said Paul K. Crane, MD, of the University of Washington, Seattle, in an interview. He was lead author of a 2016 study into links between TBI and PD and other neurodegenerative conditions (JAMA Neurol. 2016;73[9]:1062-9).

“People treated at the VA are not a representative sample of anyone other than people treated at the VA,” he said. “The ability to generalize beyond the large convenience sample is difficult.”

He added that “many people who do not have a diagnosis of mild TBI in the VA medical system nevertheless have had a mild TBI. Medical records for TBI are very incomplete. Perhaps this is especially true for veterans, who are at extremely high risk of TBI.”

Still, the research “reinforces the idea that TBI, including so-called ‘mild’ TBI – and in this case, that means mild TBI that has resulted in electronic data codes in a health records system – is definitely not innocuous, and, in particular, there is a relationship between TBI exposure and risk for Parkinson’s disease.”

How could this research be useful? Dr. Crane said it shouldn’t change practice. “We should avoid head injuries, but we should have done so before. We should diagnose Parkinson’s disease because it can be treated,” he said. “The individual risk for PD is not tons more among those with a history of head injury as defined in this paper, so I doubt we would find that heightened awareness of PD in that group is warranted.”

However, he added that “this kind of research is useful in helping us to conceptualize the downstream consequences of TBI and reinforce a strong and growing literature that finds links between TBI exposure and PD risk. Much remains to be learned.”

The study was supported by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the American Federation for Aging Research, the Weill Institute for Neurosciences, and the U.S. Departments of Defense and Veterans Affairs. Dr. Gardner reported no relevant disclosures. Dr. Lane reported receiving funding from the Alzheimer’s Association, the National Institutes of Health, and the Department of Defense.

 

 

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– New research finds that military veterans who suffered mild traumatic brain injuries (TBIs) faced more than 1.5 times the risk of developing Parkinson’s disease (PD), compared with other veterans over up to 12 years of follow-up. The risk doubled for those who suffered moderate to severe TBIs.

The findings don’t confirm a link between brain injury and PD, and the number of PD diagnoses remained small even among those who’d suffered the worst TBIs.

Still, the findings suggest that “mild TBI may have long-term consequences, including PD,” said study lead author Raquel C. Gardner, MD, a neurologist whose findings were released at the annual meeting of the American Academy of Neurology. “We need to ramp up efforts to prevent TBI and also make sure we are carefully screening TBI-exposed patients for some of these long-term consequences, for which we may be able to offer therapies to improve quality of life.”

3283197d_273/Thinkstock
Previous research has linked moderate to severe TBI to PD, said Dr. Gardner of the University of California, San Francisco.

Most recently, a 2016 study found signs of a link between previous TBIs that caused more than an hour of unconsciousness and PD (hazard ratio, 3.56; 95% confidence interval, 1.52-8.28; JAMA Neurol. 2016;73[9]:1062-9).

As for mild TBI, a 2014 systematic review examined five studies and found that only one linked it to PD (OR, 1.5; 95% CI, 1.4-1.7).

For the new study, researchers analyzed records of patients served by the Veterans Health Administration from 2002 to 2014. They age matched 162,935 veterans who had suffered TBIs (half mild, half moderate to severe) to 162,935 veterans who had not (a 2% sample of all veterans served by the VHA).

Mild TBIs are defined as those that caused loss of consciousness of less than 30 minutes. Mild to moderate TBIs caused more than 30 minutes of unconsciousness.

The study participants hadn’t been diagnosed with PD or dementia at baseline or over the following year. Their average age was 48 years.

Compared with those who hadn’t suffered TBIs, those who did were more likely to be male (92% vs. 85%) and to suffer from hypertension (12% vs. 8%), cerebrovascular disease (4% vs. 1%), posttraumatic stress disorder (21% vs. 4%), and depression (24% vs. 9%; P less than .001).

“Prior studies have determined that TBI is a risk factor for depression and PTSD,” Dr. Gardner said. “Thus, higher rates of these outcomes among the patient with TBI in our study may represent sequelae of the TBI.”

Indications of education and income were similar among the two groups (P = .94 and P = .29, respectively). Those who suffered TBIs were more likely to be white than those who didn’t (73% vs. 67%) and less likely to be of other or unknown race (7% vs. 13%; P less than .001).

The percentages of veterans who developed PD were 0.31% (no TBI), 0.58% (any TBI), 0.47% (mild TBI), and 0.75% (moderate/severe TBI).

The unadjusted hazard ratios for PD were 1.81 (1.63-2.01) for any TBI, 1.59 (1.39-1.82) for mild TBI, and 2.01 (1.78-2.26) for moderate/severe TBI (P less than .0001).

Hazard ratios adjusted for demographics and comorbidities were 1.71 (1.53-1.92) for any TBI, 1.56 (1.35-1.80) for mild TBI, and 1.83 (1.61-2.07) for mild/moderate TBI (P less than .0001).

“The vast majority of people in this study did not develop PD,” Dr. Gardner said. “However, those with TBI had about a 50%-60% increased risk of PD that was statistically significant. While the P value is very small, the important numbers are really the confidence intervals around the estimate. According to our confidence intervals, we are very confident that the true estimate is between about 35% and 80% increased risk.”

Researchers also found that TBI sufferers who developed PD were 2 years younger at diagnosis than those who didn’t suffer TBIs (70 vs. 72; P = .003).

To limit the possibility of reverse causation, researchers tried excluding veterans who were diagnosed with PD within 4 years after baseline. The results remained similar.

The study has limitations. It’s not clear when the TBIs occurred. Also, the study doesn’t take the causes of TBIs into account. “In this veteran population, particularly among the younger veterans of Operation Iraqi Freedom and Operation Enduring Freedom, many are likely blast-related TBIs,” Dr. Gardner said.

The study is also limited because of the sample, said Paul K. Crane, MD, of the University of Washington, Seattle, in an interview. He was lead author of a 2016 study into links between TBI and PD and other neurodegenerative conditions (JAMA Neurol. 2016;73[9]:1062-9).

“People treated at the VA are not a representative sample of anyone other than people treated at the VA,” he said. “The ability to generalize beyond the large convenience sample is difficult.”

He added that “many people who do not have a diagnosis of mild TBI in the VA medical system nevertheless have had a mild TBI. Medical records for TBI are very incomplete. Perhaps this is especially true for veterans, who are at extremely high risk of TBI.”

Still, the research “reinforces the idea that TBI, including so-called ‘mild’ TBI – and in this case, that means mild TBI that has resulted in electronic data codes in a health records system – is definitely not innocuous, and, in particular, there is a relationship between TBI exposure and risk for Parkinson’s disease.”

How could this research be useful? Dr. Crane said it shouldn’t change practice. “We should avoid head injuries, but we should have done so before. We should diagnose Parkinson’s disease because it can be treated,” he said. “The individual risk for PD is not tons more among those with a history of head injury as defined in this paper, so I doubt we would find that heightened awareness of PD in that group is warranted.”

However, he added that “this kind of research is useful in helping us to conceptualize the downstream consequences of TBI and reinforce a strong and growing literature that finds links between TBI exposure and PD risk. Much remains to be learned.”

The study was supported by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the American Federation for Aging Research, the Weill Institute for Neurosciences, and the U.S. Departments of Defense and Veterans Affairs. Dr. Gardner reported no relevant disclosures. Dr. Lane reported receiving funding from the Alzheimer’s Association, the National Institutes of Health, and the Department of Defense.

 

 

 

– New research finds that military veterans who suffered mild traumatic brain injuries (TBIs) faced more than 1.5 times the risk of developing Parkinson’s disease (PD), compared with other veterans over up to 12 years of follow-up. The risk doubled for those who suffered moderate to severe TBIs.

The findings don’t confirm a link between brain injury and PD, and the number of PD diagnoses remained small even among those who’d suffered the worst TBIs.

Still, the findings suggest that “mild TBI may have long-term consequences, including PD,” said study lead author Raquel C. Gardner, MD, a neurologist whose findings were released at the annual meeting of the American Academy of Neurology. “We need to ramp up efforts to prevent TBI and also make sure we are carefully screening TBI-exposed patients for some of these long-term consequences, for which we may be able to offer therapies to improve quality of life.”

3283197d_273/Thinkstock
Previous research has linked moderate to severe TBI to PD, said Dr. Gardner of the University of California, San Francisco.

Most recently, a 2016 study found signs of a link between previous TBIs that caused more than an hour of unconsciousness and PD (hazard ratio, 3.56; 95% confidence interval, 1.52-8.28; JAMA Neurol. 2016;73[9]:1062-9).

As for mild TBI, a 2014 systematic review examined five studies and found that only one linked it to PD (OR, 1.5; 95% CI, 1.4-1.7).

For the new study, researchers analyzed records of patients served by the Veterans Health Administration from 2002 to 2014. They age matched 162,935 veterans who had suffered TBIs (half mild, half moderate to severe) to 162,935 veterans who had not (a 2% sample of all veterans served by the VHA).

Mild TBIs are defined as those that caused loss of consciousness of less than 30 minutes. Mild to moderate TBIs caused more than 30 minutes of unconsciousness.

The study participants hadn’t been diagnosed with PD or dementia at baseline or over the following year. Their average age was 48 years.

Compared with those who hadn’t suffered TBIs, those who did were more likely to be male (92% vs. 85%) and to suffer from hypertension (12% vs. 8%), cerebrovascular disease (4% vs. 1%), posttraumatic stress disorder (21% vs. 4%), and depression (24% vs. 9%; P less than .001).

“Prior studies have determined that TBI is a risk factor for depression and PTSD,” Dr. Gardner said. “Thus, higher rates of these outcomes among the patient with TBI in our study may represent sequelae of the TBI.”

Indications of education and income were similar among the two groups (P = .94 and P = .29, respectively). Those who suffered TBIs were more likely to be white than those who didn’t (73% vs. 67%) and less likely to be of other or unknown race (7% vs. 13%; P less than .001).

The percentages of veterans who developed PD were 0.31% (no TBI), 0.58% (any TBI), 0.47% (mild TBI), and 0.75% (moderate/severe TBI).

The unadjusted hazard ratios for PD were 1.81 (1.63-2.01) for any TBI, 1.59 (1.39-1.82) for mild TBI, and 2.01 (1.78-2.26) for moderate/severe TBI (P less than .0001).

Hazard ratios adjusted for demographics and comorbidities were 1.71 (1.53-1.92) for any TBI, 1.56 (1.35-1.80) for mild TBI, and 1.83 (1.61-2.07) for mild/moderate TBI (P less than .0001).

“The vast majority of people in this study did not develop PD,” Dr. Gardner said. “However, those with TBI had about a 50%-60% increased risk of PD that was statistically significant. While the P value is very small, the important numbers are really the confidence intervals around the estimate. According to our confidence intervals, we are very confident that the true estimate is between about 35% and 80% increased risk.”

Researchers also found that TBI sufferers who developed PD were 2 years younger at diagnosis than those who didn’t suffer TBIs (70 vs. 72; P = .003).

To limit the possibility of reverse causation, researchers tried excluding veterans who were diagnosed with PD within 4 years after baseline. The results remained similar.

The study has limitations. It’s not clear when the TBIs occurred. Also, the study doesn’t take the causes of TBIs into account. “In this veteran population, particularly among the younger veterans of Operation Iraqi Freedom and Operation Enduring Freedom, many are likely blast-related TBIs,” Dr. Gardner said.

The study is also limited because of the sample, said Paul K. Crane, MD, of the University of Washington, Seattle, in an interview. He was lead author of a 2016 study into links between TBI and PD and other neurodegenerative conditions (JAMA Neurol. 2016;73[9]:1062-9).

“People treated at the VA are not a representative sample of anyone other than people treated at the VA,” he said. “The ability to generalize beyond the large convenience sample is difficult.”

He added that “many people who do not have a diagnosis of mild TBI in the VA medical system nevertheless have had a mild TBI. Medical records for TBI are very incomplete. Perhaps this is especially true for veterans, who are at extremely high risk of TBI.”

Still, the research “reinforces the idea that TBI, including so-called ‘mild’ TBI – and in this case, that means mild TBI that has resulted in electronic data codes in a health records system – is definitely not innocuous, and, in particular, there is a relationship between TBI exposure and risk for Parkinson’s disease.”

How could this research be useful? Dr. Crane said it shouldn’t change practice. “We should avoid head injuries, but we should have done so before. We should diagnose Parkinson’s disease because it can be treated,” he said. “The individual risk for PD is not tons more among those with a history of head injury as defined in this paper, so I doubt we would find that heightened awareness of PD in that group is warranted.”

However, he added that “this kind of research is useful in helping us to conceptualize the downstream consequences of TBI and reinforce a strong and growing literature that finds links between TBI exposure and PD risk. Much remains to be learned.”

The study was supported by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the American Federation for Aging Research, the Weill Institute for Neurosciences, and the U.S. Departments of Defense and Veterans Affairs. Dr. Gardner reported no relevant disclosures. Dr. Lane reported receiving funding from the Alzheimer’s Association, the National Institutes of Health, and the Department of Defense.

 

 

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Key clinical point: Military veterans who suffered traumatic brain injuries (TBIs) were more likely to develop Parkinson’s disease over a 12-year period.

Major finding: Veterans who’d suffered any TBI were more likely to develop PD (adjusted HR, 1.71; 95% CI, 1.53-1.92; P less than .0001).

Data source: A retrospective cohort study of age-matched veterans (162,935 who had suffered TBIs and 162,935 who had not) who received care from the Veterans Health Administration from 2002 to 2014.

Disclosures: The study was supported by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the American Federation for Aging Research, the Weill Institute for Neurosciences, and the U.S. Departments of Defense and Veterans Affairs. Dr. Gardner reports no relevant disclosures. Dr. Lane reported receiving funding from the Alzheimer’s Association, the National Institutes of Health, and the Department of Defense.

REMOVAL: Metformin may reduce cardiac risk in type 1 diabetes but doesn’t improve glucose control

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– Findings from the landmark 3-year REMOVAL trial find that metformin could hold potential as a tool to reduce cardiovascular disease (CVD) risk in patients with type 1 diabetes. But – in a challenge to current British and American guidelines – findings from the study suggest that the drug doesn’t meaningfully improve glycemic control.

 

 

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– Findings from the landmark 3-year REMOVAL trial find that metformin could hold potential as a tool to reduce cardiovascular disease (CVD) risk in patients with type 1 diabetes. But – in a challenge to current British and American guidelines – findings from the study suggest that the drug doesn’t meaningfully improve glycemic control.

 

 

 

– Findings from the landmark 3-year REMOVAL trial find that metformin could hold potential as a tool to reduce cardiovascular disease (CVD) risk in patients with type 1 diabetes. But – in a challenge to current British and American guidelines – findings from the study suggest that the drug doesn’t meaningfully improve glycemic control.

 

 

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Key clinical point: Metformin may reduce cardiac risk in adult type 1 patients, but it doesn’t improve glycemic control. Discontinuation is common.

Major finding: Maximal carotid artery intima-media thickness (cIMT), a surrogate measure for atherosclerosis progression, fell by a mean –0.013 mm per year (95% CI, –0.024 to –0.003; P = .0093), although a similar measure, mean cIMT, dropped by just –0.005 mm per year (95% CI, –0.012-0.002; P = .1664). HbA1c in the metformin group fell by –0.13% (95% CI, –0.22 to –0.037; P = .0060). Of metformin patients, 27% discontinued treatment, compared with 12% of placebo patients (P = .0002).

Data source: A 3-year double-blind, randomized, placebo-controlled trial in patients, aged 40+ years with type 1 diabetes and at least 3 of 10 cardiac risk factors, assigned to oral metformin 1,000 mg twice daily (n = 219) or placebo (209).

Disclosures: The Juvenile Diabetes Research Foundation funded the study. Merck Germany KGaA provided medication and shipping for free. Itamar Medical donated equipment and services. Dr. Sataar reported consulting fees and/or research support from Amgen, Boehringer Ingelheim, Eli Lilly, Janssen, and Novo Nordisk. Dr. Colhoun and Dr. Hramiak reported multiple disclosures, including advisory panel, research support, and speaker’s bureau and stock/shareholder relationships.

Quality measures and diabetic foot care: What endos need to know

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– As quality measures in health care continue to grow in importance, it behooves endocrinologists to pay more attention to the mental as well as physical well-being of patients with diabetic foot conditions before and after treatment.

“We’re on a path from volume-based practice to really showing that what we’re doing actually works, and diabetic foot is going to be caught up in there. It’s really important that we understand how [the diabetic foot] is affecting our patients physically and mentally. We’ll have to measure what we do and see it if improves,” said Dane K. Wukich, MD, professor and Dr. Charles F. Gregory distinguished chair of the department of orthopedic surgery at University of Texas Southwestern Medical Center, Dallas, in a presentation at the annual scientific sessions of the American Diabetes Association.

Courtesy Dr. Dane K. Wukich
Dr. Dane K. Wukich
Foot problems are extremely common in people with diabetes. According to one analysis of Medicare beneficiaries, 6% of patients with diabetes were treated for foot ulcers each year; these patients faced an 11% annual mortality.

Foot amputations are becoming less common but remain a dreaded complication of diabetes. The Centers for Disease Control and Prevention has estimated that hospital discharges for lower-extremity amputation among people with diabetes declined dramatically – by as much as 50% or more depending on the type – from 2003 to 2009. Still, in 2009, the levels were 1.8 cases per 1,000 patients for toe amputation, 0.5 cases per 1,000 patients for foot amputation, and 0.9 and 0.4 cases per 1,000 for below- and above-knee amputation, respectively.

The commonly used 36-Item Short Form Quality of Life Survey (SF-36 QOL) may offer useful insight into quality of life in diabetic foot patients after treatment, but it is not precise enough to gauge patients’ mental health issues.

Patient-reported outcomes will become more important in diabetic foot treatments, Dr. Wukich said, “but sometimes a successful outcome in what we do does not always equate to an improvement in quality of life.”

For example, he said, it’s true that patients with diabetic foot disease fear losing their legs more than death. He led a study published earlier this year that found patients with diabetic foot conditions were 79% more likely to say amputation is their greatest fear, topping even death (odds ratio, 1.79; 96% confidence interval, 1.13-2.81; P = .01 [Foot Ankle Spec. 2017 Feb 1]).

But “saving a foot that’s not in a good position” can be devastating for a patient, even worse than amputation, he said.

Quality of life measurements will provide insight for doctors and insurers as they track the success of diabetic foot treatments. But Dr. Wukich said there’s a big mystery about one aspect of quality of life (QOL) measurements: Why don’t diabetic foot problems significantly disrupt the mental component of quality of life measures?

He coauthored a 2014 study – of 50 patients with diabetes and Charcot foot and 56 patients with diabetes only – that found a significant gap in physical QOL measures (P less than .001) but nearly identical measures in mental QOL (P less than .644) (Foot Ankle Int. 2014;35[3]195-200).

He asked: “How could somebody have a Charcot problem with a deformed foot, walking around in a boot for years and not have it affect their mental quality of life?”

One possibility is that neuropathy reduces the mental burden of pain because it hurts less, he suggested. But the answer could lie in the strategies used in calculating scores commonly used in the SF-36 QOL tool, he said. Recent unpublished research suggests that the orthogonal calculation may artificially increase mental QOL scores in these cases, he said. The oblique method may be more accurate, he said, but more study is needed.

In the big picture, he said, “assessing quality of life can help us establish the optimal methods of treatment, evaluate treatment outcomes, and identify patients at risk of mortality, admission, and depression. It’s going to guide us in the pay-for-performance arena.”

During the meeting, Dr. Wukich was presented with the American Diabetes Associations 2017 Roger Pecoraro Award, which recognizes a researcher “who has made significant scientific contributions and demonstrates an untiring commitment to improving the understanding of the detection, treatment, and prevention of diabetic foot complications.”

Dr. Wukich reported that he has no relevant financial disclosures.
 
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– As quality measures in health care continue to grow in importance, it behooves endocrinologists to pay more attention to the mental as well as physical well-being of patients with diabetic foot conditions before and after treatment.

“We’re on a path from volume-based practice to really showing that what we’re doing actually works, and diabetic foot is going to be caught up in there. It’s really important that we understand how [the diabetic foot] is affecting our patients physically and mentally. We’ll have to measure what we do and see it if improves,” said Dane K. Wukich, MD, professor and Dr. Charles F. Gregory distinguished chair of the department of orthopedic surgery at University of Texas Southwestern Medical Center, Dallas, in a presentation at the annual scientific sessions of the American Diabetes Association.

Courtesy Dr. Dane K. Wukich
Dr. Dane K. Wukich
Foot problems are extremely common in people with diabetes. According to one analysis of Medicare beneficiaries, 6% of patients with diabetes were treated for foot ulcers each year; these patients faced an 11% annual mortality.

Foot amputations are becoming less common but remain a dreaded complication of diabetes. The Centers for Disease Control and Prevention has estimated that hospital discharges for lower-extremity amputation among people with diabetes declined dramatically – by as much as 50% or more depending on the type – from 2003 to 2009. Still, in 2009, the levels were 1.8 cases per 1,000 patients for toe amputation, 0.5 cases per 1,000 patients for foot amputation, and 0.9 and 0.4 cases per 1,000 for below- and above-knee amputation, respectively.

The commonly used 36-Item Short Form Quality of Life Survey (SF-36 QOL) may offer useful insight into quality of life in diabetic foot patients after treatment, but it is not precise enough to gauge patients’ mental health issues.

Patient-reported outcomes will become more important in diabetic foot treatments, Dr. Wukich said, “but sometimes a successful outcome in what we do does not always equate to an improvement in quality of life.”

For example, he said, it’s true that patients with diabetic foot disease fear losing their legs more than death. He led a study published earlier this year that found patients with diabetic foot conditions were 79% more likely to say amputation is their greatest fear, topping even death (odds ratio, 1.79; 96% confidence interval, 1.13-2.81; P = .01 [Foot Ankle Spec. 2017 Feb 1]).

But “saving a foot that’s not in a good position” can be devastating for a patient, even worse than amputation, he said.

Quality of life measurements will provide insight for doctors and insurers as they track the success of diabetic foot treatments. But Dr. Wukich said there’s a big mystery about one aspect of quality of life (QOL) measurements: Why don’t diabetic foot problems significantly disrupt the mental component of quality of life measures?

He coauthored a 2014 study – of 50 patients with diabetes and Charcot foot and 56 patients with diabetes only – that found a significant gap in physical QOL measures (P less than .001) but nearly identical measures in mental QOL (P less than .644) (Foot Ankle Int. 2014;35[3]195-200).

He asked: “How could somebody have a Charcot problem with a deformed foot, walking around in a boot for years and not have it affect their mental quality of life?”

One possibility is that neuropathy reduces the mental burden of pain because it hurts less, he suggested. But the answer could lie in the strategies used in calculating scores commonly used in the SF-36 QOL tool, he said. Recent unpublished research suggests that the orthogonal calculation may artificially increase mental QOL scores in these cases, he said. The oblique method may be more accurate, he said, but more study is needed.

In the big picture, he said, “assessing quality of life can help us establish the optimal methods of treatment, evaluate treatment outcomes, and identify patients at risk of mortality, admission, and depression. It’s going to guide us in the pay-for-performance arena.”

During the meeting, Dr. Wukich was presented with the American Diabetes Associations 2017 Roger Pecoraro Award, which recognizes a researcher “who has made significant scientific contributions and demonstrates an untiring commitment to improving the understanding of the detection, treatment, and prevention of diabetic foot complications.”

Dr. Wukich reported that he has no relevant financial disclosures.
 

 

– As quality measures in health care continue to grow in importance, it behooves endocrinologists to pay more attention to the mental as well as physical well-being of patients with diabetic foot conditions before and after treatment.

“We’re on a path from volume-based practice to really showing that what we’re doing actually works, and diabetic foot is going to be caught up in there. It’s really important that we understand how [the diabetic foot] is affecting our patients physically and mentally. We’ll have to measure what we do and see it if improves,” said Dane K. Wukich, MD, professor and Dr. Charles F. Gregory distinguished chair of the department of orthopedic surgery at University of Texas Southwestern Medical Center, Dallas, in a presentation at the annual scientific sessions of the American Diabetes Association.

Courtesy Dr. Dane K. Wukich
Dr. Dane K. Wukich
Foot problems are extremely common in people with diabetes. According to one analysis of Medicare beneficiaries, 6% of patients with diabetes were treated for foot ulcers each year; these patients faced an 11% annual mortality.

Foot amputations are becoming less common but remain a dreaded complication of diabetes. The Centers for Disease Control and Prevention has estimated that hospital discharges for lower-extremity amputation among people with diabetes declined dramatically – by as much as 50% or more depending on the type – from 2003 to 2009. Still, in 2009, the levels were 1.8 cases per 1,000 patients for toe amputation, 0.5 cases per 1,000 patients for foot amputation, and 0.9 and 0.4 cases per 1,000 for below- and above-knee amputation, respectively.

The commonly used 36-Item Short Form Quality of Life Survey (SF-36 QOL) may offer useful insight into quality of life in diabetic foot patients after treatment, but it is not precise enough to gauge patients’ mental health issues.

Patient-reported outcomes will become more important in diabetic foot treatments, Dr. Wukich said, “but sometimes a successful outcome in what we do does not always equate to an improvement in quality of life.”

For example, he said, it’s true that patients with diabetic foot disease fear losing their legs more than death. He led a study published earlier this year that found patients with diabetic foot conditions were 79% more likely to say amputation is their greatest fear, topping even death (odds ratio, 1.79; 96% confidence interval, 1.13-2.81; P = .01 [Foot Ankle Spec. 2017 Feb 1]).

But “saving a foot that’s not in a good position” can be devastating for a patient, even worse than amputation, he said.

Quality of life measurements will provide insight for doctors and insurers as they track the success of diabetic foot treatments. But Dr. Wukich said there’s a big mystery about one aspect of quality of life (QOL) measurements: Why don’t diabetic foot problems significantly disrupt the mental component of quality of life measures?

He coauthored a 2014 study – of 50 patients with diabetes and Charcot foot and 56 patients with diabetes only – that found a significant gap in physical QOL measures (P less than .001) but nearly identical measures in mental QOL (P less than .644) (Foot Ankle Int. 2014;35[3]195-200).

He asked: “How could somebody have a Charcot problem with a deformed foot, walking around in a boot for years and not have it affect their mental quality of life?”

One possibility is that neuropathy reduces the mental burden of pain because it hurts less, he suggested. But the answer could lie in the strategies used in calculating scores commonly used in the SF-36 QOL tool, he said. Recent unpublished research suggests that the orthogonal calculation may artificially increase mental QOL scores in these cases, he said. The oblique method may be more accurate, he said, but more study is needed.

In the big picture, he said, “assessing quality of life can help us establish the optimal methods of treatment, evaluate treatment outcomes, and identify patients at risk of mortality, admission, and depression. It’s going to guide us in the pay-for-performance arena.”

During the meeting, Dr. Wukich was presented with the American Diabetes Associations 2017 Roger Pecoraro Award, which recognizes a researcher “who has made significant scientific contributions and demonstrates an untiring commitment to improving the understanding of the detection, treatment, and prevention of diabetic foot complications.”

Dr. Wukich reported that he has no relevant financial disclosures.
 
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Should convicted sex offender get penile prosthetic implant?

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– Should a man with a distant history of pedophilia be allowed to get a penile prosthetic implant to treat his erectile dysfunction? Mental health professionals at a Veterans Affairs medical center in San Diego recently faced this question and decided the risk was too great. They denied his request.

 

 

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– Should a man with a distant history of pedophilia be allowed to get a penile prosthetic implant to treat his erectile dysfunction? Mental health professionals at a Veterans Affairs medical center in San Diego recently faced this question and decided the risk was too great. They denied his request.

 

 

 

– Should a man with a distant history of pedophilia be allowed to get a penile prosthetic implant to treat his erectile dysfunction? Mental health professionals at a Veterans Affairs medical center in San Diego recently faced this question and decided the risk was too great. They denied his request.

 

 

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VIDEO: Phase III results show promise for erenumab as migraine prevention drug

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– Two phase III trials of the investigational monoclonal antibody erenumab show promising results in reducing – but not eliminating – days affected by migraines and related disruptions in daily life with limited side effects, representing “an entirely new way forward” in migraine prevention, according to Peter Goadsby, MD.

In May, shortly after the results were released at the annual meeting of the American Academy of Neurology, Amgen filed regulatory documents for erenumab with the Food and Drug Administration.

Erenumab, also known as AMG 334, “is going to be the first mechanism-specific, migraine-targeted preventive treatment approach ever,” Dr. Goadsby, a University of California, San Francisco, neurologist, predicted at the annual meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that is designed to block the calcitonin gene-related peptide (CGRP) receptor, which is linked to migraine.

Several drug makers are investigating CGRP-modulating treatments for migraine. Results suggest that the medications are “effective for episodic and migraine patients,” said Amaal Starling, MD, of the Mayo Clinic, Scottsdale, Ariz., who spoke about the drugs in a plenary session at the meeting. “They have rapid onset of efficacy, minimal side effects, and infrequent administration. All of these things may improve adherence.”

Dr. Goadsby is the lead author of the study reporting phase III results from the 24-week STRIVE trial, which tested two monthly subcutaneous doses of erenumab (70 mg and 140 mg) against placebo in a 1:1:1 ratio in 955 patients. The patients all had suffered from episodic migraine for at least a year.

“STRIVE has shown that the 70-mg and 140-mg doses are better than placebo at the regulatory endpoint and clinically relevant endpoints,” Dr. Goadsby said, “and there are improvements in function, everyday activities, and physical impairment. The overall frequency of adverse and serious events were comparable, even the same.”

The participants reported an average of 8.3 monthly migraine days (MMDs) at the beginning of the study. At the end, the number declined significantly by an average of 3.2 days (70-mg dose), 3.7 days (140-mg dose), and 1.8 days (placebo; P less than .001).

Half of those in the 140-mg group achieved at least a 50% reduction in MMDs, compared with 43% and 27% for the 70-mg and placebo groups, respectively (P less than .001).

The researchers also examined changes in scores regarding Physical Impairment (PI) and Impact on Everyday Activities (EA) as determined by the Migraine Physical Function Impact Diary. PI scores improved by 4.2, 4.8, and 2.4 points in the 70-mg, 140-mg, and placebo groups, respectively. EA scores improved by 5.5, 5.9, and 3.3 points, respectively (P less than .001).

The study authors reported that tolerability was similar for placebo and the drug. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and sinusitis.

The researchers at the AAN meeting also released the results of a second study known as ARISE, led by David W. Dodick, MD, of the Mayo Clinic, Phoenix, Ariz. This double-blind, 12-week trial randomly assigned 577 adults with episodic migraine to a monthly subcutaneous dose of a placebo or 70 mg of erenumab.

The patients reported an average of 8.3 MMDs at the beginning of the trial. Those who took the medication reported an average 2.9 fewer MMDs while those who took the placebo reported 1.8 fewer MMDs (P less than .001) at 9-12 weeks.

Forty percent of those who took the drug saw a decrease of at least half in MMDs, compared with 30% of those who took placebo (odds ratio, 1.6; P = .010).

The PI levels declined by at least 5 points in 27% of placebo patients and 33% of erenumab patients (P = .13). EA levels declined by at least 5 points in 36% of placebo patients and 40% of erenumab patients (P = .26)

There were similar levels of adverse events in both drug and placebo groups, led by upper respiratory tract infection, injection site pain, and nasopharyngitis.

The Mayo Clinic’s Dr. Starling said anti-CGRP medications may dramatically improve the world of preventive migraine treatments, which are recommended for a third of migraine patients. Only about 3%-13% use them, she said.

In the future, it may be possible to be able to identify and target “super-responders” whose MMDs dip by 75% or more in some cases.

But there are questions, she said. The drugs’ specific mechanism for blocking migraine is not yet clear, and it’s also not clear if the CGRP antagonists could push patients at risk of TIA or cardiac angina to have a stroke instead.

Dr. Starling discussed some of the implications of the CGRP antagonists in development in a video interview.

Both studies were funded by Amgen. Dr. Goadsby reported numerous grants and personal fees from multiple drug makers, including Amgen. Dr. Starling reported support from Amgen, eNeura, and Eli Lilly. Dr. Dodick disclosed many relationships with pharmaceutical companies developing or marketing drugs for headache and migraine, including Amgen.

 

 

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
 
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– Two phase III trials of the investigational monoclonal antibody erenumab show promising results in reducing – but not eliminating – days affected by migraines and related disruptions in daily life with limited side effects, representing “an entirely new way forward” in migraine prevention, according to Peter Goadsby, MD.

In May, shortly after the results were released at the annual meeting of the American Academy of Neurology, Amgen filed regulatory documents for erenumab with the Food and Drug Administration.

Erenumab, also known as AMG 334, “is going to be the first mechanism-specific, migraine-targeted preventive treatment approach ever,” Dr. Goadsby, a University of California, San Francisco, neurologist, predicted at the annual meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that is designed to block the calcitonin gene-related peptide (CGRP) receptor, which is linked to migraine.

Several drug makers are investigating CGRP-modulating treatments for migraine. Results suggest that the medications are “effective for episodic and migraine patients,” said Amaal Starling, MD, of the Mayo Clinic, Scottsdale, Ariz., who spoke about the drugs in a plenary session at the meeting. “They have rapid onset of efficacy, minimal side effects, and infrequent administration. All of these things may improve adherence.”

Dr. Goadsby is the lead author of the study reporting phase III results from the 24-week STRIVE trial, which tested two monthly subcutaneous doses of erenumab (70 mg and 140 mg) against placebo in a 1:1:1 ratio in 955 patients. The patients all had suffered from episodic migraine for at least a year.

“STRIVE has shown that the 70-mg and 140-mg doses are better than placebo at the regulatory endpoint and clinically relevant endpoints,” Dr. Goadsby said, “and there are improvements in function, everyday activities, and physical impairment. The overall frequency of adverse and serious events were comparable, even the same.”

The participants reported an average of 8.3 monthly migraine days (MMDs) at the beginning of the study. At the end, the number declined significantly by an average of 3.2 days (70-mg dose), 3.7 days (140-mg dose), and 1.8 days (placebo; P less than .001).

Half of those in the 140-mg group achieved at least a 50% reduction in MMDs, compared with 43% and 27% for the 70-mg and placebo groups, respectively (P less than .001).

The researchers also examined changes in scores regarding Physical Impairment (PI) and Impact on Everyday Activities (EA) as determined by the Migraine Physical Function Impact Diary. PI scores improved by 4.2, 4.8, and 2.4 points in the 70-mg, 140-mg, and placebo groups, respectively. EA scores improved by 5.5, 5.9, and 3.3 points, respectively (P less than .001).

The study authors reported that tolerability was similar for placebo and the drug. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and sinusitis.

The researchers at the AAN meeting also released the results of a second study known as ARISE, led by David W. Dodick, MD, of the Mayo Clinic, Phoenix, Ariz. This double-blind, 12-week trial randomly assigned 577 adults with episodic migraine to a monthly subcutaneous dose of a placebo or 70 mg of erenumab.

The patients reported an average of 8.3 MMDs at the beginning of the trial. Those who took the medication reported an average 2.9 fewer MMDs while those who took the placebo reported 1.8 fewer MMDs (P less than .001) at 9-12 weeks.

Forty percent of those who took the drug saw a decrease of at least half in MMDs, compared with 30% of those who took placebo (odds ratio, 1.6; P = .010).

The PI levels declined by at least 5 points in 27% of placebo patients and 33% of erenumab patients (P = .13). EA levels declined by at least 5 points in 36% of placebo patients and 40% of erenumab patients (P = .26)

There were similar levels of adverse events in both drug and placebo groups, led by upper respiratory tract infection, injection site pain, and nasopharyngitis.

The Mayo Clinic’s Dr. Starling said anti-CGRP medications may dramatically improve the world of preventive migraine treatments, which are recommended for a third of migraine patients. Only about 3%-13% use them, she said.

In the future, it may be possible to be able to identify and target “super-responders” whose MMDs dip by 75% or more in some cases.

But there are questions, she said. The drugs’ specific mechanism for blocking migraine is not yet clear, and it’s also not clear if the CGRP antagonists could push patients at risk of TIA or cardiac angina to have a stroke instead.

Dr. Starling discussed some of the implications of the CGRP antagonists in development in a video interview.

Both studies were funded by Amgen. Dr. Goadsby reported numerous grants and personal fees from multiple drug makers, including Amgen. Dr. Starling reported support from Amgen, eNeura, and Eli Lilly. Dr. Dodick disclosed many relationships with pharmaceutical companies developing or marketing drugs for headache and migraine, including Amgen.

 

 

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
 

 

– Two phase III trials of the investigational monoclonal antibody erenumab show promising results in reducing – but not eliminating – days affected by migraines and related disruptions in daily life with limited side effects, representing “an entirely new way forward” in migraine prevention, according to Peter Goadsby, MD.

In May, shortly after the results were released at the annual meeting of the American Academy of Neurology, Amgen filed regulatory documents for erenumab with the Food and Drug Administration.

Erenumab, also known as AMG 334, “is going to be the first mechanism-specific, migraine-targeted preventive treatment approach ever,” Dr. Goadsby, a University of California, San Francisco, neurologist, predicted at the annual meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that is designed to block the calcitonin gene-related peptide (CGRP) receptor, which is linked to migraine.

Several drug makers are investigating CGRP-modulating treatments for migraine. Results suggest that the medications are “effective for episodic and migraine patients,” said Amaal Starling, MD, of the Mayo Clinic, Scottsdale, Ariz., who spoke about the drugs in a plenary session at the meeting. “They have rapid onset of efficacy, minimal side effects, and infrequent administration. All of these things may improve adherence.”

Dr. Goadsby is the lead author of the study reporting phase III results from the 24-week STRIVE trial, which tested two monthly subcutaneous doses of erenumab (70 mg and 140 mg) against placebo in a 1:1:1 ratio in 955 patients. The patients all had suffered from episodic migraine for at least a year.

“STRIVE has shown that the 70-mg and 140-mg doses are better than placebo at the regulatory endpoint and clinically relevant endpoints,” Dr. Goadsby said, “and there are improvements in function, everyday activities, and physical impairment. The overall frequency of adverse and serious events were comparable, even the same.”

The participants reported an average of 8.3 monthly migraine days (MMDs) at the beginning of the study. At the end, the number declined significantly by an average of 3.2 days (70-mg dose), 3.7 days (140-mg dose), and 1.8 days (placebo; P less than .001).

Half of those in the 140-mg group achieved at least a 50% reduction in MMDs, compared with 43% and 27% for the 70-mg and placebo groups, respectively (P less than .001).

The researchers also examined changes in scores regarding Physical Impairment (PI) and Impact on Everyday Activities (EA) as determined by the Migraine Physical Function Impact Diary. PI scores improved by 4.2, 4.8, and 2.4 points in the 70-mg, 140-mg, and placebo groups, respectively. EA scores improved by 5.5, 5.9, and 3.3 points, respectively (P less than .001).

The study authors reported that tolerability was similar for placebo and the drug. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and sinusitis.

The researchers at the AAN meeting also released the results of a second study known as ARISE, led by David W. Dodick, MD, of the Mayo Clinic, Phoenix, Ariz. This double-blind, 12-week trial randomly assigned 577 adults with episodic migraine to a monthly subcutaneous dose of a placebo or 70 mg of erenumab.

The patients reported an average of 8.3 MMDs at the beginning of the trial. Those who took the medication reported an average 2.9 fewer MMDs while those who took the placebo reported 1.8 fewer MMDs (P less than .001) at 9-12 weeks.

Forty percent of those who took the drug saw a decrease of at least half in MMDs, compared with 30% of those who took placebo (odds ratio, 1.6; P = .010).

The PI levels declined by at least 5 points in 27% of placebo patients and 33% of erenumab patients (P = .13). EA levels declined by at least 5 points in 36% of placebo patients and 40% of erenumab patients (P = .26)

There were similar levels of adverse events in both drug and placebo groups, led by upper respiratory tract infection, injection site pain, and nasopharyngitis.

The Mayo Clinic’s Dr. Starling said anti-CGRP medications may dramatically improve the world of preventive migraine treatments, which are recommended for a third of migraine patients. Only about 3%-13% use them, she said.

In the future, it may be possible to be able to identify and target “super-responders” whose MMDs dip by 75% or more in some cases.

But there are questions, she said. The drugs’ specific mechanism for blocking migraine is not yet clear, and it’s also not clear if the CGRP antagonists could push patients at risk of TIA or cardiac angina to have a stroke instead.

Dr. Starling discussed some of the implications of the CGRP antagonists in development in a video interview.

Both studies were funded by Amgen. Dr. Goadsby reported numerous grants and personal fees from multiple drug makers, including Amgen. Dr. Starling reported support from Amgen, eNeura, and Eli Lilly. Dr. Dodick disclosed many relationships with pharmaceutical companies developing or marketing drugs for headache and migraine, including Amgen.

 

 

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
 
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Long-acting injectables may be best at preventing relapse in psychosis

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– A new meta-analysis suggests that second-generation long-acting injectable antipsychotics (LAIs) are slightly better than oral antipsychotics at preventing relapse after a first psychotic incident.

The meta-analysis, released at the annual meeting of the American Psychiatric Association, is limited because it looks at only three studies. Still, study lead author Christine Tran-Boynes, DO, said the findings are useful for psychiatrists.

“For a long time, LAIs were associated with severely ill psychotic patients who were frequently hospitalized and not compliant with their oral meds,” Dr. Tran-Boynes, a resident at the University of Maryland, Baltimore, said in an interview. “The purpose of this paper is to change the perception of LAIs. They are not just a medication of last resort in those with severe, chronic psychosis but, instead, can be used in the early stages of psychosis as prophylaxis against relapse.”

Injectable antipsychotics are more commonly used in Europe, where “there also seemed to be a greater willingness among patients to receive this treatment,” said Peter F. Buckley, MD, dean of the medical school at Virginia Commonwealth University, Richmond.

The APA’s schizophrenia treatment guidelines recommend LAIs for patients with “recurrent relapses related to nonadherence” and patients who prefer the shots. Dr. Tran-Boynes notes that “the most common cause of relapse in patients with schizophrenia is partial adherence or nonadherence to oral antipsychotics. If LAIs can improve adherence in patients and monitoring of adherence for clinicians, they could have a role in preventing relapse during this critical period in psychosis.”

The meta-analysis examines three randomized controlled studies – two from 2015 and one from 2013 – that compare second-generation LAIs to first- and second-generation oral antipsychotics after first episodes of psychosis. Dr. Tran-Boynes said researchers could not find any studies comparing first-generation long-acting antipsychotics to oral antipsychotics.

The largest study had 769 participants; the others had 85 and 86. The subjects, all adults, had diagnoses of schizophrenia, schizoaffective disorder, or schizophreniform disorder. Their diagnoses must have been made within the previous 5 years.

According to the meta-analysis, relapses after first-episode psychosis were more likely (relative risk, 1.078; 95% confidence interval, 1.007-1.154; P = 0.012) in patients taking first- or second-generation oral antipsychotics, compared with those on second-generation LAIs.

“There was an 8% greater efficacy for LAIs preventing relapse after early psychosis, compared to oral antipsychotics,” Dr. Tran-Boynes said. She calculated the number needed to treat as 14.

The percentages of patients who did not relapse while taking second-generation LAIs ranged from 73% (31 of 42 patients randomized to an injectable risperidone arm over 24 months) to 95% (38 of 40 patients over a 12-month study, also of injectable risperidone), Dr. Tran-Boynes said.

When asked about the meta-analysis, Robert Rosenheck, MD, expressed concern.

“While well done, it is based on too few studies to give useful guidance to practice,” said Dr. Rosenheck, professor of psychiatry, epidemiology and public health at Yale University, New Haven, Conn.

Dr. Buckley also noted that the meta-analysis includes a small number of studies. “The effect is sizable for a first-episode population, but other studies to date are more mixed,” he added. “For instance, in a study among a more chronic schizophrenic population, we found no difference between a group receiving long-acting injectable risperidone and oral second-generation antipsychotics” (Schizophr Bull. 2015 Mar;41[2]:449-59).

What should psychiatrists know when they consider prescribing LAIs to prevent psychotic relapse? “If a patient expresses willingness to take an oral antipsychotic on a daily basis and/or has someone to monitor his medication intake, then prescribing an oral antipsychotic would be the ideal route,” Dr. Tran-Boynes said. “However, I would recommend LAIs to patients who have demonstrated poor compliance with previous medications in general, poor awareness of psychosis, poor awareness of need for treatment, poor availability of social support to ensure that the patient will take his/her medication daily, and/or if a patient expresses preference for LAIs.”

She cautioned that LAIs have disadvantages. Compared with oral antipsychotics, it’s harder to adjust patients’ dosages in response to side effects or when they improve, she said. LAIs are also more expensive in the short term, she said.

However, LAIs also may have produced fewer side effects, and there aren’t any questions about compliance, she said. In addition, “there’s less pain at the injection site with second-generation LAIs, compared to first-generation LAIs, due to the water-based solution of the former. The oil-based solutions that are characteristic of first-generation LAIs have been shown in studies to be very painful.”

Dr. Tran-Boynes and Dr. Rosenheck reported no relevant disclosures. Dr. Buckley disclosed that he is a research consultant for the National Institute of Mental Health.

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– A new meta-analysis suggests that second-generation long-acting injectable antipsychotics (LAIs) are slightly better than oral antipsychotics at preventing relapse after a first psychotic incident.

The meta-analysis, released at the annual meeting of the American Psychiatric Association, is limited because it looks at only three studies. Still, study lead author Christine Tran-Boynes, DO, said the findings are useful for psychiatrists.

“For a long time, LAIs were associated with severely ill psychotic patients who were frequently hospitalized and not compliant with their oral meds,” Dr. Tran-Boynes, a resident at the University of Maryland, Baltimore, said in an interview. “The purpose of this paper is to change the perception of LAIs. They are not just a medication of last resort in those with severe, chronic psychosis but, instead, can be used in the early stages of psychosis as prophylaxis against relapse.”

Injectable antipsychotics are more commonly used in Europe, where “there also seemed to be a greater willingness among patients to receive this treatment,” said Peter F. Buckley, MD, dean of the medical school at Virginia Commonwealth University, Richmond.

The APA’s schizophrenia treatment guidelines recommend LAIs for patients with “recurrent relapses related to nonadherence” and patients who prefer the shots. Dr. Tran-Boynes notes that “the most common cause of relapse in patients with schizophrenia is partial adherence or nonadherence to oral antipsychotics. If LAIs can improve adherence in patients and monitoring of adherence for clinicians, they could have a role in preventing relapse during this critical period in psychosis.”

The meta-analysis examines three randomized controlled studies – two from 2015 and one from 2013 – that compare second-generation LAIs to first- and second-generation oral antipsychotics after first episodes of psychosis. Dr. Tran-Boynes said researchers could not find any studies comparing first-generation long-acting antipsychotics to oral antipsychotics.

The largest study had 769 participants; the others had 85 and 86. The subjects, all adults, had diagnoses of schizophrenia, schizoaffective disorder, or schizophreniform disorder. Their diagnoses must have been made within the previous 5 years.

According to the meta-analysis, relapses after first-episode psychosis were more likely (relative risk, 1.078; 95% confidence interval, 1.007-1.154; P = 0.012) in patients taking first- or second-generation oral antipsychotics, compared with those on second-generation LAIs.

“There was an 8% greater efficacy for LAIs preventing relapse after early psychosis, compared to oral antipsychotics,” Dr. Tran-Boynes said. She calculated the number needed to treat as 14.

The percentages of patients who did not relapse while taking second-generation LAIs ranged from 73% (31 of 42 patients randomized to an injectable risperidone arm over 24 months) to 95% (38 of 40 patients over a 12-month study, also of injectable risperidone), Dr. Tran-Boynes said.

When asked about the meta-analysis, Robert Rosenheck, MD, expressed concern.

“While well done, it is based on too few studies to give useful guidance to practice,” said Dr. Rosenheck, professor of psychiatry, epidemiology and public health at Yale University, New Haven, Conn.

Dr. Buckley also noted that the meta-analysis includes a small number of studies. “The effect is sizable for a first-episode population, but other studies to date are more mixed,” he added. “For instance, in a study among a more chronic schizophrenic population, we found no difference between a group receiving long-acting injectable risperidone and oral second-generation antipsychotics” (Schizophr Bull. 2015 Mar;41[2]:449-59).

What should psychiatrists know when they consider prescribing LAIs to prevent psychotic relapse? “If a patient expresses willingness to take an oral antipsychotic on a daily basis and/or has someone to monitor his medication intake, then prescribing an oral antipsychotic would be the ideal route,” Dr. Tran-Boynes said. “However, I would recommend LAIs to patients who have demonstrated poor compliance with previous medications in general, poor awareness of psychosis, poor awareness of need for treatment, poor availability of social support to ensure that the patient will take his/her medication daily, and/or if a patient expresses preference for LAIs.”

She cautioned that LAIs have disadvantages. Compared with oral antipsychotics, it’s harder to adjust patients’ dosages in response to side effects or when they improve, she said. LAIs are also more expensive in the short term, she said.

However, LAIs also may have produced fewer side effects, and there aren’t any questions about compliance, she said. In addition, “there’s less pain at the injection site with second-generation LAIs, compared to first-generation LAIs, due to the water-based solution of the former. The oil-based solutions that are characteristic of first-generation LAIs have been shown in studies to be very painful.”

Dr. Tran-Boynes and Dr. Rosenheck reported no relevant disclosures. Dr. Buckley disclosed that he is a research consultant for the National Institute of Mental Health.

 

– A new meta-analysis suggests that second-generation long-acting injectable antipsychotics (LAIs) are slightly better than oral antipsychotics at preventing relapse after a first psychotic incident.

The meta-analysis, released at the annual meeting of the American Psychiatric Association, is limited because it looks at only three studies. Still, study lead author Christine Tran-Boynes, DO, said the findings are useful for psychiatrists.

“For a long time, LAIs were associated with severely ill psychotic patients who were frequently hospitalized and not compliant with their oral meds,” Dr. Tran-Boynes, a resident at the University of Maryland, Baltimore, said in an interview. “The purpose of this paper is to change the perception of LAIs. They are not just a medication of last resort in those with severe, chronic psychosis but, instead, can be used in the early stages of psychosis as prophylaxis against relapse.”

Injectable antipsychotics are more commonly used in Europe, where “there also seemed to be a greater willingness among patients to receive this treatment,” said Peter F. Buckley, MD, dean of the medical school at Virginia Commonwealth University, Richmond.

The APA’s schizophrenia treatment guidelines recommend LAIs for patients with “recurrent relapses related to nonadherence” and patients who prefer the shots. Dr. Tran-Boynes notes that “the most common cause of relapse in patients with schizophrenia is partial adherence or nonadherence to oral antipsychotics. If LAIs can improve adherence in patients and monitoring of adherence for clinicians, they could have a role in preventing relapse during this critical period in psychosis.”

The meta-analysis examines three randomized controlled studies – two from 2015 and one from 2013 – that compare second-generation LAIs to first- and second-generation oral antipsychotics after first episodes of psychosis. Dr. Tran-Boynes said researchers could not find any studies comparing first-generation long-acting antipsychotics to oral antipsychotics.

The largest study had 769 participants; the others had 85 and 86. The subjects, all adults, had diagnoses of schizophrenia, schizoaffective disorder, or schizophreniform disorder. Their diagnoses must have been made within the previous 5 years.

According to the meta-analysis, relapses after first-episode psychosis were more likely (relative risk, 1.078; 95% confidence interval, 1.007-1.154; P = 0.012) in patients taking first- or second-generation oral antipsychotics, compared with those on second-generation LAIs.

“There was an 8% greater efficacy for LAIs preventing relapse after early psychosis, compared to oral antipsychotics,” Dr. Tran-Boynes said. She calculated the number needed to treat as 14.

The percentages of patients who did not relapse while taking second-generation LAIs ranged from 73% (31 of 42 patients randomized to an injectable risperidone arm over 24 months) to 95% (38 of 40 patients over a 12-month study, also of injectable risperidone), Dr. Tran-Boynes said.

When asked about the meta-analysis, Robert Rosenheck, MD, expressed concern.

“While well done, it is based on too few studies to give useful guidance to practice,” said Dr. Rosenheck, professor of psychiatry, epidemiology and public health at Yale University, New Haven, Conn.

Dr. Buckley also noted that the meta-analysis includes a small number of studies. “The effect is sizable for a first-episode population, but other studies to date are more mixed,” he added. “For instance, in a study among a more chronic schizophrenic population, we found no difference between a group receiving long-acting injectable risperidone and oral second-generation antipsychotics” (Schizophr Bull. 2015 Mar;41[2]:449-59).

What should psychiatrists know when they consider prescribing LAIs to prevent psychotic relapse? “If a patient expresses willingness to take an oral antipsychotic on a daily basis and/or has someone to monitor his medication intake, then prescribing an oral antipsychotic would be the ideal route,” Dr. Tran-Boynes said. “However, I would recommend LAIs to patients who have demonstrated poor compliance with previous medications in general, poor awareness of psychosis, poor awareness of need for treatment, poor availability of social support to ensure that the patient will take his/her medication daily, and/or if a patient expresses preference for LAIs.”

She cautioned that LAIs have disadvantages. Compared with oral antipsychotics, it’s harder to adjust patients’ dosages in response to side effects or when they improve, she said. LAIs are also more expensive in the short term, she said.

However, LAIs also may have produced fewer side effects, and there aren’t any questions about compliance, she said. In addition, “there’s less pain at the injection site with second-generation LAIs, compared to first-generation LAIs, due to the water-based solution of the former. The oil-based solutions that are characteristic of first-generation LAIs have been shown in studies to be very painful.”

Dr. Tran-Boynes and Dr. Rosenheck reported no relevant disclosures. Dr. Buckley disclosed that he is a research consultant for the National Institute of Mental Health.

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Key clinical point: Second-generation long-acting injectable antipsychotics (LAIs) may be better than oral antipsychotics at preventing relapse after first episode of psychosis.

Major finding: Relapses after first-episode psychosis were more likely (RR, 1.078; 95% CI, 1.007-1.154; P = 0.012) in patients on first- and second-generation oral antipsychotics, compared with second-generation LAIs.

Data source: Meta-analysis of three randomized controlled trials with 940 total patients.

Disclosures: Dr. Tran-Boynes reported having no relevant disclosures.