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Involuntary commitment sought in 5% of anorexia admissions
SAN DIEGO – Court orders were sought to force 5% of patients admitted for anorexia nervosa disorders to remain involuntarily under hospital care, according to findings from a 4-year study of patients treated at a Colorado clinic.
Nearly all of the patients declined to fight those efforts. However, the orders were withdrawn in about one-quarter of cases because treatment was deemed to be futile.
The study findings point to the importance of seeking civil commitment early in the course of illness in patients with anorexia nervosa when it can do the most good, study author Patricia Westmoreland, MD, attending psychiatrist at the Eating Recovery Center in Denver, said in an interview.
Dr. Westmoreland presented the findings at the annual meeting of the American Psychiatric Association, where she contended that anorexia nervosa has the highest mortality of any psychiatric disorder. “If patients are not treated earlier in the course of their illness and when they’re at a younger age,” she said, “they develop severe and enduring eating disorders.”
Anorexia nervosa is estimated to have a prevalence rate of 0.3% in young women. Research suggests that 20% of people with the disease kill themselves (Int J Eat Disord. 2003 Dec;34[4]:383-96), (Arch Gen Psychiatry. 2011;68[7]:724-31).
For the new study, Dr. Westmoreland and her colleagues tracked 2,106 admissions of patients who were treated for two conditions – anorexia nervosa restricting subtype and anorexia nervosa binge purge subtype – at the Eating Recovery Center from April 2012 to March 2016. The ages and genders of the subjects were not available.
Officials sought involuntary care in 109, or 5.2%, of the admissions, including 11 patients who were recommitted at least once.
Of the 109 admissions:
• 85% waived the right to a hearing (94% of those who fought commitment ultimately were committed involuntarily).
• 31% successfully completed treatment.
• 24% had their commitments – also known as certifications – terminated because treatment appeared to be futile.
“These are patients for whom certification is only helpful to a point, beyond which it becomes harmful, i.e., patients harming themselves to leave a locked facility, patients pulling out NG tubes so many times they cause injury, patients who purge continuously despite being tube fed,” Dr. Westmoreland said in an interview. “In other cases, the team evaluated the patient and determined he or she is, in general, being harmed more than helped by trying to attain goal weight. This is where harm reduction may prove useful. And failing that, palliative or hospice care for a patient who has had many treatments over the years and has never recovered for any meaningful period of time.”
Dr. Westmoreland defined harm reduction in this context as “having patient being managed at an agreed-upon weight that is lower than an ideal body weight, but nonetheless a weight at which they can function and have some quality of life, even if that quality of life is not optimal.”
This also means that the patient must regularly check with an outpatient treatment team – dietitian, psychiatrist, and therapist – and be monitored for signs of unacceptable levels of weight loss or abnormal lab results, she said. These problems, she added, will trigger hospitalization.
Dr. Westmoreland reported no relevant disclosures.
SAN DIEGO – Court orders were sought to force 5% of patients admitted for anorexia nervosa disorders to remain involuntarily under hospital care, according to findings from a 4-year study of patients treated at a Colorado clinic.
Nearly all of the patients declined to fight those efforts. However, the orders were withdrawn in about one-quarter of cases because treatment was deemed to be futile.
The study findings point to the importance of seeking civil commitment early in the course of illness in patients with anorexia nervosa when it can do the most good, study author Patricia Westmoreland, MD, attending psychiatrist at the Eating Recovery Center in Denver, said in an interview.
Dr. Westmoreland presented the findings at the annual meeting of the American Psychiatric Association, where she contended that anorexia nervosa has the highest mortality of any psychiatric disorder. “If patients are not treated earlier in the course of their illness and when they’re at a younger age,” she said, “they develop severe and enduring eating disorders.”
Anorexia nervosa is estimated to have a prevalence rate of 0.3% in young women. Research suggests that 20% of people with the disease kill themselves (Int J Eat Disord. 2003 Dec;34[4]:383-96), (Arch Gen Psychiatry. 2011;68[7]:724-31).
For the new study, Dr. Westmoreland and her colleagues tracked 2,106 admissions of patients who were treated for two conditions – anorexia nervosa restricting subtype and anorexia nervosa binge purge subtype – at the Eating Recovery Center from April 2012 to March 2016. The ages and genders of the subjects were not available.
Officials sought involuntary care in 109, or 5.2%, of the admissions, including 11 patients who were recommitted at least once.
Of the 109 admissions:
• 85% waived the right to a hearing (94% of those who fought commitment ultimately were committed involuntarily).
• 31% successfully completed treatment.
• 24% had their commitments – also known as certifications – terminated because treatment appeared to be futile.
“These are patients for whom certification is only helpful to a point, beyond which it becomes harmful, i.e., patients harming themselves to leave a locked facility, patients pulling out NG tubes so many times they cause injury, patients who purge continuously despite being tube fed,” Dr. Westmoreland said in an interview. “In other cases, the team evaluated the patient and determined he or she is, in general, being harmed more than helped by trying to attain goal weight. This is where harm reduction may prove useful. And failing that, palliative or hospice care for a patient who has had many treatments over the years and has never recovered for any meaningful period of time.”
Dr. Westmoreland defined harm reduction in this context as “having patient being managed at an agreed-upon weight that is lower than an ideal body weight, but nonetheless a weight at which they can function and have some quality of life, even if that quality of life is not optimal.”
This also means that the patient must regularly check with an outpatient treatment team – dietitian, psychiatrist, and therapist – and be monitored for signs of unacceptable levels of weight loss or abnormal lab results, she said. These problems, she added, will trigger hospitalization.
Dr. Westmoreland reported no relevant disclosures.
SAN DIEGO – Court orders were sought to force 5% of patients admitted for anorexia nervosa disorders to remain involuntarily under hospital care, according to findings from a 4-year study of patients treated at a Colorado clinic.
Nearly all of the patients declined to fight those efforts. However, the orders were withdrawn in about one-quarter of cases because treatment was deemed to be futile.
The study findings point to the importance of seeking civil commitment early in the course of illness in patients with anorexia nervosa when it can do the most good, study author Patricia Westmoreland, MD, attending psychiatrist at the Eating Recovery Center in Denver, said in an interview.
Dr. Westmoreland presented the findings at the annual meeting of the American Psychiatric Association, where she contended that anorexia nervosa has the highest mortality of any psychiatric disorder. “If patients are not treated earlier in the course of their illness and when they’re at a younger age,” she said, “they develop severe and enduring eating disorders.”
Anorexia nervosa is estimated to have a prevalence rate of 0.3% in young women. Research suggests that 20% of people with the disease kill themselves (Int J Eat Disord. 2003 Dec;34[4]:383-96), (Arch Gen Psychiatry. 2011;68[7]:724-31).
For the new study, Dr. Westmoreland and her colleagues tracked 2,106 admissions of patients who were treated for two conditions – anorexia nervosa restricting subtype and anorexia nervosa binge purge subtype – at the Eating Recovery Center from April 2012 to March 2016. The ages and genders of the subjects were not available.
Officials sought involuntary care in 109, or 5.2%, of the admissions, including 11 patients who were recommitted at least once.
Of the 109 admissions:
• 85% waived the right to a hearing (94% of those who fought commitment ultimately were committed involuntarily).
• 31% successfully completed treatment.
• 24% had their commitments – also known as certifications – terminated because treatment appeared to be futile.
“These are patients for whom certification is only helpful to a point, beyond which it becomes harmful, i.e., patients harming themselves to leave a locked facility, patients pulling out NG tubes so many times they cause injury, patients who purge continuously despite being tube fed,” Dr. Westmoreland said in an interview. “In other cases, the team evaluated the patient and determined he or she is, in general, being harmed more than helped by trying to attain goal weight. This is where harm reduction may prove useful. And failing that, palliative or hospice care for a patient who has had many treatments over the years and has never recovered for any meaningful period of time.”
Dr. Westmoreland defined harm reduction in this context as “having patient being managed at an agreed-upon weight that is lower than an ideal body weight, but nonetheless a weight at which they can function and have some quality of life, even if that quality of life is not optimal.”
This also means that the patient must regularly check with an outpatient treatment team – dietitian, psychiatrist, and therapist – and be monitored for signs of unacceptable levels of weight loss or abnormal lab results, she said. These problems, she added, will trigger hospitalization.
Dr. Westmoreland reported no relevant disclosures.
AT APA
Higher ADHD risk seen in children with migraine
BOSTON – Children aged 5-12 years with signs of migraine headache were as much as seven times as likely as other children to also appear to have attention-deficit/hyperactivity disorder (ADHD), but those with tension-type headaches didn’t face a higher risk of ADHD, a Brazilian study showed.
It’s not clear why the apparent link between migraines and ADHD exists. However, lead study author Marco Antônio Arruda, MD, PhD, a pediatric neurologist in São Paulo (Brazil) University, said in an interview that other research has linked migraine to mental health problems.
The study, presented at the annual meeting of the American Academy of Neurology and published online in the Journal of Attention Disorders (2017. doi: 10.1177/1087054717710767), was launched to better understand the connection between migraine and ADHD, which are thought to each affect as many as 1 in 10 children.
The study analyzes data from mothers and teachers of 5,671 children aged 5-12 years who answered questions as part of a Brazil-wide epidemiologic study called the Attention Brazil Project. Just over half of the participants were boys, and about half were from the Brazilian middle class.
Based on answers from mothers and teachers, the researchers estimated that 9% of the children had episodic migraine and 0.6% had chronic migraine. The level of episodic tension-type headache was estimated at 12.8%, with a lower rate in the two poorest vs. the two richest quintiles (8.6% vs. 14.4%, respectively; relative risk, 0.6; 95% confidence interval, 0.5-0.8).
The researchers estimated that 5.3% of the children overall showed signs of ADHD (7.5% in boys vs. 3.1% in girls; RR, 2.4; 95% CI, 1.9-3.1).
There was no sign that children with tension-type headaches had a significantly higher risk of ADHD than other children. However, compared with controls, those with various types of migraine headaches did have a higher risk of ADHD. Nearly 11% of those with migraine overall showed signs of ADHD, compared with 2.6% of the control group (RR, 4.1; 95% CI, 2.7-6.2). The numbers for episodic migraine were nearly identical to those for migraine overall: 10.2% vs. 2.6% (RR, 3.8; 95% CI, 2.5-5.9).
Just over 19% of kids in a third migraine group – those with chronic migraine, defined as headaches appearing more than 14 days per month for the last 3 months – showed signs of ADHD, compared with just 2.6% of the control group (RR = 7.3; 95% CI, 3.5-15.5).
“A number of risk factors to the association were identified, including male gender, prenatal exposure to tobacco, high headache frequency, and below average school performance,” Dr. Arruda said. “However, we did not find a significant influence of age, race, city density, national region where a child lives, income class, and prenatal exposure to alcohol in the comorbidity of ADHD and migraine in this sample. These results help us to identify risk groups allowing early interventions.”
Regarding an explanation for the links between migraines and ADHD, Dr. Arruda pointed to genetic and epigenetic factors that affect brain neurotransmitters and said he believes that stress and other stimuli could be influencing dopamine and noradrenergic processes.
Dr. Arruda said his next step is to examine whether stimulant drugs – the class used to treat ADHD – may help reduce headaches too.
“My clinical experience strongly indicates that psychostimulants have a highly positive effect on migraine prophylaxis, although headache occurs in the very beginning of the treatment,” Dr. Arruda said. “So, we are looking for financial support to conduct a randomized, double-blind, placebo control study to check this hypothesis.”
The study received no specific funding, and Dr. Arruda reported no relevant financial disclosures.
BOSTON – Children aged 5-12 years with signs of migraine headache were as much as seven times as likely as other children to also appear to have attention-deficit/hyperactivity disorder (ADHD), but those with tension-type headaches didn’t face a higher risk of ADHD, a Brazilian study showed.
It’s not clear why the apparent link between migraines and ADHD exists. However, lead study author Marco Antônio Arruda, MD, PhD, a pediatric neurologist in São Paulo (Brazil) University, said in an interview that other research has linked migraine to mental health problems.
The study, presented at the annual meeting of the American Academy of Neurology and published online in the Journal of Attention Disorders (2017. doi: 10.1177/1087054717710767), was launched to better understand the connection between migraine and ADHD, which are thought to each affect as many as 1 in 10 children.
The study analyzes data from mothers and teachers of 5,671 children aged 5-12 years who answered questions as part of a Brazil-wide epidemiologic study called the Attention Brazil Project. Just over half of the participants were boys, and about half were from the Brazilian middle class.
Based on answers from mothers and teachers, the researchers estimated that 9% of the children had episodic migraine and 0.6% had chronic migraine. The level of episodic tension-type headache was estimated at 12.8%, with a lower rate in the two poorest vs. the two richest quintiles (8.6% vs. 14.4%, respectively; relative risk, 0.6; 95% confidence interval, 0.5-0.8).
The researchers estimated that 5.3% of the children overall showed signs of ADHD (7.5% in boys vs. 3.1% in girls; RR, 2.4; 95% CI, 1.9-3.1).
There was no sign that children with tension-type headaches had a significantly higher risk of ADHD than other children. However, compared with controls, those with various types of migraine headaches did have a higher risk of ADHD. Nearly 11% of those with migraine overall showed signs of ADHD, compared with 2.6% of the control group (RR, 4.1; 95% CI, 2.7-6.2). The numbers for episodic migraine were nearly identical to those for migraine overall: 10.2% vs. 2.6% (RR, 3.8; 95% CI, 2.5-5.9).
Just over 19% of kids in a third migraine group – those with chronic migraine, defined as headaches appearing more than 14 days per month for the last 3 months – showed signs of ADHD, compared with just 2.6% of the control group (RR = 7.3; 95% CI, 3.5-15.5).
“A number of risk factors to the association were identified, including male gender, prenatal exposure to tobacco, high headache frequency, and below average school performance,” Dr. Arruda said. “However, we did not find a significant influence of age, race, city density, national region where a child lives, income class, and prenatal exposure to alcohol in the comorbidity of ADHD and migraine in this sample. These results help us to identify risk groups allowing early interventions.”
Regarding an explanation for the links between migraines and ADHD, Dr. Arruda pointed to genetic and epigenetic factors that affect brain neurotransmitters and said he believes that stress and other stimuli could be influencing dopamine and noradrenergic processes.
Dr. Arruda said his next step is to examine whether stimulant drugs – the class used to treat ADHD – may help reduce headaches too.
“My clinical experience strongly indicates that psychostimulants have a highly positive effect on migraine prophylaxis, although headache occurs in the very beginning of the treatment,” Dr. Arruda said. “So, we are looking for financial support to conduct a randomized, double-blind, placebo control study to check this hypothesis.”
The study received no specific funding, and Dr. Arruda reported no relevant financial disclosures.
BOSTON – Children aged 5-12 years with signs of migraine headache were as much as seven times as likely as other children to also appear to have attention-deficit/hyperactivity disorder (ADHD), but those with tension-type headaches didn’t face a higher risk of ADHD, a Brazilian study showed.
It’s not clear why the apparent link between migraines and ADHD exists. However, lead study author Marco Antônio Arruda, MD, PhD, a pediatric neurologist in São Paulo (Brazil) University, said in an interview that other research has linked migraine to mental health problems.
The study, presented at the annual meeting of the American Academy of Neurology and published online in the Journal of Attention Disorders (2017. doi: 10.1177/1087054717710767), was launched to better understand the connection between migraine and ADHD, which are thought to each affect as many as 1 in 10 children.
The study analyzes data from mothers and teachers of 5,671 children aged 5-12 years who answered questions as part of a Brazil-wide epidemiologic study called the Attention Brazil Project. Just over half of the participants were boys, and about half were from the Brazilian middle class.
Based on answers from mothers and teachers, the researchers estimated that 9% of the children had episodic migraine and 0.6% had chronic migraine. The level of episodic tension-type headache was estimated at 12.8%, with a lower rate in the two poorest vs. the two richest quintiles (8.6% vs. 14.4%, respectively; relative risk, 0.6; 95% confidence interval, 0.5-0.8).
The researchers estimated that 5.3% of the children overall showed signs of ADHD (7.5% in boys vs. 3.1% in girls; RR, 2.4; 95% CI, 1.9-3.1).
There was no sign that children with tension-type headaches had a significantly higher risk of ADHD than other children. However, compared with controls, those with various types of migraine headaches did have a higher risk of ADHD. Nearly 11% of those with migraine overall showed signs of ADHD, compared with 2.6% of the control group (RR, 4.1; 95% CI, 2.7-6.2). The numbers for episodic migraine were nearly identical to those for migraine overall: 10.2% vs. 2.6% (RR, 3.8; 95% CI, 2.5-5.9).
Just over 19% of kids in a third migraine group – those with chronic migraine, defined as headaches appearing more than 14 days per month for the last 3 months – showed signs of ADHD, compared with just 2.6% of the control group (RR = 7.3; 95% CI, 3.5-15.5).
“A number of risk factors to the association were identified, including male gender, prenatal exposure to tobacco, high headache frequency, and below average school performance,” Dr. Arruda said. “However, we did not find a significant influence of age, race, city density, national region where a child lives, income class, and prenatal exposure to alcohol in the comorbidity of ADHD and migraine in this sample. These results help us to identify risk groups allowing early interventions.”
Regarding an explanation for the links between migraines and ADHD, Dr. Arruda pointed to genetic and epigenetic factors that affect brain neurotransmitters and said he believes that stress and other stimuli could be influencing dopamine and noradrenergic processes.
Dr. Arruda said his next step is to examine whether stimulant drugs – the class used to treat ADHD – may help reduce headaches too.
“My clinical experience strongly indicates that psychostimulants have a highly positive effect on migraine prophylaxis, although headache occurs in the very beginning of the treatment,” Dr. Arruda said. “So, we are looking for financial support to conduct a randomized, double-blind, placebo control study to check this hypothesis.”
The study received no specific funding, and Dr. Arruda reported no relevant financial disclosures.
AT AAN 2017
Key clinical point: , but there’s no excess risk in children with tension-type headaches.
Major finding: Of children with chronic migraine, 19.4% (0.6% of the total) showed signs of ADHD, vs. 2.6% of the control group (RR, 7.3; 95% CI, 3.5-15.5).
Data source: Surveys of mothers and teachers of 5,671 Brazilian children aged 5-12 years.
Disclosures: The study received no specific funding, and Dr. Arruda reported no relevant financial disclosures.
As designer drugs multiply, toxicologists spring into action
SAN DIEGO – Forensic toxicologist Donna Papsun spends her days with drugs, but she doesn’t see patients or try to make anyone better. Still, her work is crucial to every medical professional who needs to know which new illicit drugs their patients have been taking.
In Willow Grove, Pa., a suburb of Philadelphia, Ms. Papsun and her colleagues at NMS Labs develop screening tests for designer drugs that have just appeared on the black market or crossed the Drug Enforcement Administration’s (DEA) radar.
As Ms. Papsun told an audience at the annual meeting of the American Psychiatric Association, she faced a unique obstacle last summer, when an elephant tranquilizer called carfentanil, a derivative of fentanyl, began to make headlines. The obstacle? The U.S.-Canada border.
She wanted to develop a test for the opioid but couldn’t start until she got a reference sample of the controlled substance from carfentanil’s only manufacturer, a firm in Canada. It took months. “Crossing an international border caused all sorts of problems,” she said.
New designer drugs are constantly hitting the market. They’re often especially appealing – and especially risky – because routine drug tests can’t detect them, at least not yet.
In an interview, Ms. Papsun talked about the challenges of trying to keep up with the drug makers – and users.
“Designer drug testing developed back in 2008 will not catch anything that is seen in today’s designer drug market,” she said. “Designer drug testing requires constant attention, assessment, resources, and updating.”
Question: How long does it typically take to create a test for a new strain of illicit drug?
Answer: This can take anywhere from 3 to 9 months, and potentially longer, and it depends on many factors. Once a new drug has hit the market, we check to see if there is certified reference material available. If there is, then we can start to develop a test. Development includes identifying a successful chemical extraction technique – isolating the drug in question from biological matrix such as blood or urine – as well as a platform that reliably detects the drug without falsely reporting positives.
After development, the test has to go through a process called validation, which is a series of experiments to prove that the developed method works rigorously, day after day, and provides the same results. This is very important in forensic toxicology, because our results may be involved in criminal and civil litigation and must stand up to the rigors of court.
Q: What are some examples of the types of drugs that you’ve had to develop tests for?
A: Just in the past year, we have developed tests for new designer opioids (including carfentanil, furanylfentanyl, acrylfentanyl, and U-47700), designer benzodiazepines (including etizolam, diclazepam, flubromazolam, and flubromazepam) and new designer stimulants (including n-ethyl pentylone and dibutylone).
We have a synthetic cannabinoid test that was developed for the first time back in 2010. That test has been redeveloped several times since then, because we constantly have to update the test to keep up with the rapid changes in market availability of substances.
Q: What are some of the challenges that you face in terms of getting samples of human fluids that you can test for the drugs?
A: Most of the samples we see are from either death investigation cases or driving-under-the-influence cases. Samples from intoxications at hospitals are important, because those data help [us] understand the concentrations of drugs at which people can survive. But often, if the patients survive, their biological specimens are not forwarded for specialized toxicology testing. Most hospital systems do not have the analytical capabilities to detect designer drugs, and most lack the resources to seek out the causal agent for an intoxication or apparent overdose.
Q: At the APA meeting, you talked about the risk that you’ll hear about a strain from the DEA, develop a test and find out it’s obsolete because the drug isn’t used anymore. Does that happen very often?
A: Yes. The problem with designer drugs is that there are so many, so you can spend a lot of time, money, and other resources dedicated to developing and validating a test for a drug that may or may not even be popular.
As a business, you have to make decisions regarding prioritization: Do we build a test for a drug that has only been reported once, or do we focus our efforts on a substance that has been reported dozens of times?
We certainly have spent time and resources developing a test that became obsolete, or never reported a positive case. For example, we developed a test for desomorphine, and we have never chemically confirmed desomorphine in a biological specimen. It definitely is hit or miss, but we spend a lot of time and research a lot of different avenues to make educated decisions regarding the substances we develop tests for.
SAN DIEGO – Forensic toxicologist Donna Papsun spends her days with drugs, but she doesn’t see patients or try to make anyone better. Still, her work is crucial to every medical professional who needs to know which new illicit drugs their patients have been taking.
In Willow Grove, Pa., a suburb of Philadelphia, Ms. Papsun and her colleagues at NMS Labs develop screening tests for designer drugs that have just appeared on the black market or crossed the Drug Enforcement Administration’s (DEA) radar.
As Ms. Papsun told an audience at the annual meeting of the American Psychiatric Association, she faced a unique obstacle last summer, when an elephant tranquilizer called carfentanil, a derivative of fentanyl, began to make headlines. The obstacle? The U.S.-Canada border.
She wanted to develop a test for the opioid but couldn’t start until she got a reference sample of the controlled substance from carfentanil’s only manufacturer, a firm in Canada. It took months. “Crossing an international border caused all sorts of problems,” she said.
New designer drugs are constantly hitting the market. They’re often especially appealing – and especially risky – because routine drug tests can’t detect them, at least not yet.
In an interview, Ms. Papsun talked about the challenges of trying to keep up with the drug makers – and users.
“Designer drug testing developed back in 2008 will not catch anything that is seen in today’s designer drug market,” she said. “Designer drug testing requires constant attention, assessment, resources, and updating.”
Question: How long does it typically take to create a test for a new strain of illicit drug?
Answer: This can take anywhere from 3 to 9 months, and potentially longer, and it depends on many factors. Once a new drug has hit the market, we check to see if there is certified reference material available. If there is, then we can start to develop a test. Development includes identifying a successful chemical extraction technique – isolating the drug in question from biological matrix such as blood or urine – as well as a platform that reliably detects the drug without falsely reporting positives.
After development, the test has to go through a process called validation, which is a series of experiments to prove that the developed method works rigorously, day after day, and provides the same results. This is very important in forensic toxicology, because our results may be involved in criminal and civil litigation and must stand up to the rigors of court.
Q: What are some examples of the types of drugs that you’ve had to develop tests for?
A: Just in the past year, we have developed tests for new designer opioids (including carfentanil, furanylfentanyl, acrylfentanyl, and U-47700), designer benzodiazepines (including etizolam, diclazepam, flubromazolam, and flubromazepam) and new designer stimulants (including n-ethyl pentylone and dibutylone).
We have a synthetic cannabinoid test that was developed for the first time back in 2010. That test has been redeveloped several times since then, because we constantly have to update the test to keep up with the rapid changes in market availability of substances.
Q: What are some of the challenges that you face in terms of getting samples of human fluids that you can test for the drugs?
A: Most of the samples we see are from either death investigation cases or driving-under-the-influence cases. Samples from intoxications at hospitals are important, because those data help [us] understand the concentrations of drugs at which people can survive. But often, if the patients survive, their biological specimens are not forwarded for specialized toxicology testing. Most hospital systems do not have the analytical capabilities to detect designer drugs, and most lack the resources to seek out the causal agent for an intoxication or apparent overdose.
Q: At the APA meeting, you talked about the risk that you’ll hear about a strain from the DEA, develop a test and find out it’s obsolete because the drug isn’t used anymore. Does that happen very often?
A: Yes. The problem with designer drugs is that there are so many, so you can spend a lot of time, money, and other resources dedicated to developing and validating a test for a drug that may or may not even be popular.
As a business, you have to make decisions regarding prioritization: Do we build a test for a drug that has only been reported once, or do we focus our efforts on a substance that has been reported dozens of times?
We certainly have spent time and resources developing a test that became obsolete, or never reported a positive case. For example, we developed a test for desomorphine, and we have never chemically confirmed desomorphine in a biological specimen. It definitely is hit or miss, but we spend a lot of time and research a lot of different avenues to make educated decisions regarding the substances we develop tests for.
SAN DIEGO – Forensic toxicologist Donna Papsun spends her days with drugs, but she doesn’t see patients or try to make anyone better. Still, her work is crucial to every medical professional who needs to know which new illicit drugs their patients have been taking.
In Willow Grove, Pa., a suburb of Philadelphia, Ms. Papsun and her colleagues at NMS Labs develop screening tests for designer drugs that have just appeared on the black market or crossed the Drug Enforcement Administration’s (DEA) radar.
As Ms. Papsun told an audience at the annual meeting of the American Psychiatric Association, she faced a unique obstacle last summer, when an elephant tranquilizer called carfentanil, a derivative of fentanyl, began to make headlines. The obstacle? The U.S.-Canada border.
She wanted to develop a test for the opioid but couldn’t start until she got a reference sample of the controlled substance from carfentanil’s only manufacturer, a firm in Canada. It took months. “Crossing an international border caused all sorts of problems,” she said.
New designer drugs are constantly hitting the market. They’re often especially appealing – and especially risky – because routine drug tests can’t detect them, at least not yet.
In an interview, Ms. Papsun talked about the challenges of trying to keep up with the drug makers – and users.
“Designer drug testing developed back in 2008 will not catch anything that is seen in today’s designer drug market,” she said. “Designer drug testing requires constant attention, assessment, resources, and updating.”
Question: How long does it typically take to create a test for a new strain of illicit drug?
Answer: This can take anywhere from 3 to 9 months, and potentially longer, and it depends on many factors. Once a new drug has hit the market, we check to see if there is certified reference material available. If there is, then we can start to develop a test. Development includes identifying a successful chemical extraction technique – isolating the drug in question from biological matrix such as blood or urine – as well as a platform that reliably detects the drug without falsely reporting positives.
After development, the test has to go through a process called validation, which is a series of experiments to prove that the developed method works rigorously, day after day, and provides the same results. This is very important in forensic toxicology, because our results may be involved in criminal and civil litigation and must stand up to the rigors of court.
Q: What are some examples of the types of drugs that you’ve had to develop tests for?
A: Just in the past year, we have developed tests for new designer opioids (including carfentanil, furanylfentanyl, acrylfentanyl, and U-47700), designer benzodiazepines (including etizolam, diclazepam, flubromazolam, and flubromazepam) and new designer stimulants (including n-ethyl pentylone and dibutylone).
We have a synthetic cannabinoid test that was developed for the first time back in 2010. That test has been redeveloped several times since then, because we constantly have to update the test to keep up with the rapid changes in market availability of substances.
Q: What are some of the challenges that you face in terms of getting samples of human fluids that you can test for the drugs?
A: Most of the samples we see are from either death investigation cases or driving-under-the-influence cases. Samples from intoxications at hospitals are important, because those data help [us] understand the concentrations of drugs at which people can survive. But often, if the patients survive, their biological specimens are not forwarded for specialized toxicology testing. Most hospital systems do not have the analytical capabilities to detect designer drugs, and most lack the resources to seek out the causal agent for an intoxication or apparent overdose.
Q: At the APA meeting, you talked about the risk that you’ll hear about a strain from the DEA, develop a test and find out it’s obsolete because the drug isn’t used anymore. Does that happen very often?
A: Yes. The problem with designer drugs is that there are so many, so you can spend a lot of time, money, and other resources dedicated to developing and validating a test for a drug that may or may not even be popular.
As a business, you have to make decisions regarding prioritization: Do we build a test for a drug that has only been reported once, or do we focus our efforts on a substance that has been reported dozens of times?
We certainly have spent time and resources developing a test that became obsolete, or never reported a positive case. For example, we developed a test for desomorphine, and we have never chemically confirmed desomorphine in a biological specimen. It definitely is hit or miss, but we spend a lot of time and research a lot of different avenues to make educated decisions regarding the substances we develop tests for.
EXPERT ANALYSIS FROM APA
Gene therapy for spinal muscular atrophy shows promise in early study
BOSTON – Promising results were evident in an ongoing phase I study of a gene therapy for spinal muscular atrophy type 1 (SMA1), with children in the trial walking, talking, and moving.
After a single intravenous infusion of the therapy, AVXS-101, children in the industry-funded study achieved unexpected progress in terms of physical achievement ad survival, researchers reported at the annual meeting of the American Academy of Neurology.
Video clips showed children in the trial rolling, sitting unassisted, and showing normal levels of hand and fine motor control. No other children with SMA1 have been reported to reach any major motor milestone.
In one clip, an 18-month-old boy toddles down a hallway and carries an electronic toy to an elevator where he reaches up to press the button. “He’s basically completely back to normal. You see and examine him; it just about takes your breath away,” said the study’s lead investigator, Jerry R. Mendell, MD, a neurologist at Nationwide Children’s Hospital, Columbus, Ohio.
All 15 patients in the study were alive as of the AAN presentation, with six older than aged 2 years. Previous studies have reported various life expectancies for SMA1 patients: A 2010 Korean study of 14 SMA1 patients reported that the average lifespan was 22.8 ± 2.0 months (Korean J Pediatr. 2010 Nov;53[11]:965-70), while a 2007 Hong Kong study (n = 22) found that only 30% survived to aged 4 years and all survivors were venilator-dependent (Pediatrics. 2004 Nov;114[5]:e548-53).
The open label phase I dose-escalating study recruited 15 patients (nine under aged 9 months; six 6 under aged 6 months) with SMA1 as defined by genetic criteria and onset between birth and 6 months. All received a one-time intravenous infusion of AVXS-101 after a 1-mg/1-kg dose of prednisolone the previous day. AVXS-101 is designed to boost levels of the SMN protein via delivery of a functional human SMN gene into motor neuron cells.
The first cohort of three patients received one dose. All survived to greater than aged 30 months, although one did require respiratory assistance at about 30 months, said Dr. Mendell, professor of pediatrics, neurology, pathology, and physiology and cell Biology at Ohio State University, Columbus.
Researchers moved to a larger dose, “the highest amount of virus that’s ever been given in any clinical trial,” Dr. Mendell said. The first patient has passed 30 months of age, and 9 patients have reached at least 20 months, he noted.
In this second cohort, all patients “are able to bring hand to mouth, which is obviously important for feeding. Eleven of the 12 have good head control, and 9 of the patients can roll over. And 11 can sit without assistance,” he said.
In addition, eight can sit more than 30 seconds, and two can crawl, stand, and walk independently. Eight of 12 patients are speaking, and 11 of 12 are feeding orally.
To date, five treatment-related adverse events in four patients have been reported – all asymptomatic increases in liver function enzymes, which resolved.
The study is funded by AveXis, the company developing this gene therapy. Dr. Mendell reported compensation for consulting and research support from AveXis and Sarepta Therapeutics.
BOSTON – Promising results were evident in an ongoing phase I study of a gene therapy for spinal muscular atrophy type 1 (SMA1), with children in the trial walking, talking, and moving.
After a single intravenous infusion of the therapy, AVXS-101, children in the industry-funded study achieved unexpected progress in terms of physical achievement ad survival, researchers reported at the annual meeting of the American Academy of Neurology.
Video clips showed children in the trial rolling, sitting unassisted, and showing normal levels of hand and fine motor control. No other children with SMA1 have been reported to reach any major motor milestone.
In one clip, an 18-month-old boy toddles down a hallway and carries an electronic toy to an elevator where he reaches up to press the button. “He’s basically completely back to normal. You see and examine him; it just about takes your breath away,” said the study’s lead investigator, Jerry R. Mendell, MD, a neurologist at Nationwide Children’s Hospital, Columbus, Ohio.
All 15 patients in the study were alive as of the AAN presentation, with six older than aged 2 years. Previous studies have reported various life expectancies for SMA1 patients: A 2010 Korean study of 14 SMA1 patients reported that the average lifespan was 22.8 ± 2.0 months (Korean J Pediatr. 2010 Nov;53[11]:965-70), while a 2007 Hong Kong study (n = 22) found that only 30% survived to aged 4 years and all survivors were venilator-dependent (Pediatrics. 2004 Nov;114[5]:e548-53).
The open label phase I dose-escalating study recruited 15 patients (nine under aged 9 months; six 6 under aged 6 months) with SMA1 as defined by genetic criteria and onset between birth and 6 months. All received a one-time intravenous infusion of AVXS-101 after a 1-mg/1-kg dose of prednisolone the previous day. AVXS-101 is designed to boost levels of the SMN protein via delivery of a functional human SMN gene into motor neuron cells.
The first cohort of three patients received one dose. All survived to greater than aged 30 months, although one did require respiratory assistance at about 30 months, said Dr. Mendell, professor of pediatrics, neurology, pathology, and physiology and cell Biology at Ohio State University, Columbus.
Researchers moved to a larger dose, “the highest amount of virus that’s ever been given in any clinical trial,” Dr. Mendell said. The first patient has passed 30 months of age, and 9 patients have reached at least 20 months, he noted.
In this second cohort, all patients “are able to bring hand to mouth, which is obviously important for feeding. Eleven of the 12 have good head control, and 9 of the patients can roll over. And 11 can sit without assistance,” he said.
In addition, eight can sit more than 30 seconds, and two can crawl, stand, and walk independently. Eight of 12 patients are speaking, and 11 of 12 are feeding orally.
To date, five treatment-related adverse events in four patients have been reported – all asymptomatic increases in liver function enzymes, which resolved.
The study is funded by AveXis, the company developing this gene therapy. Dr. Mendell reported compensation for consulting and research support from AveXis and Sarepta Therapeutics.
BOSTON – Promising results were evident in an ongoing phase I study of a gene therapy for spinal muscular atrophy type 1 (SMA1), with children in the trial walking, talking, and moving.
After a single intravenous infusion of the therapy, AVXS-101, children in the industry-funded study achieved unexpected progress in terms of physical achievement ad survival, researchers reported at the annual meeting of the American Academy of Neurology.
Video clips showed children in the trial rolling, sitting unassisted, and showing normal levels of hand and fine motor control. No other children with SMA1 have been reported to reach any major motor milestone.
In one clip, an 18-month-old boy toddles down a hallway and carries an electronic toy to an elevator where he reaches up to press the button. “He’s basically completely back to normal. You see and examine him; it just about takes your breath away,” said the study’s lead investigator, Jerry R. Mendell, MD, a neurologist at Nationwide Children’s Hospital, Columbus, Ohio.
All 15 patients in the study were alive as of the AAN presentation, with six older than aged 2 years. Previous studies have reported various life expectancies for SMA1 patients: A 2010 Korean study of 14 SMA1 patients reported that the average lifespan was 22.8 ± 2.0 months (Korean J Pediatr. 2010 Nov;53[11]:965-70), while a 2007 Hong Kong study (n = 22) found that only 30% survived to aged 4 years and all survivors were venilator-dependent (Pediatrics. 2004 Nov;114[5]:e548-53).
The open label phase I dose-escalating study recruited 15 patients (nine under aged 9 months; six 6 under aged 6 months) with SMA1 as defined by genetic criteria and onset between birth and 6 months. All received a one-time intravenous infusion of AVXS-101 after a 1-mg/1-kg dose of prednisolone the previous day. AVXS-101 is designed to boost levels of the SMN protein via delivery of a functional human SMN gene into motor neuron cells.
The first cohort of three patients received one dose. All survived to greater than aged 30 months, although one did require respiratory assistance at about 30 months, said Dr. Mendell, professor of pediatrics, neurology, pathology, and physiology and cell Biology at Ohio State University, Columbus.
Researchers moved to a larger dose, “the highest amount of virus that’s ever been given in any clinical trial,” Dr. Mendell said. The first patient has passed 30 months of age, and 9 patients have reached at least 20 months, he noted.
In this second cohort, all patients “are able to bring hand to mouth, which is obviously important for feeding. Eleven of the 12 have good head control, and 9 of the patients can roll over. And 11 can sit without assistance,” he said.
In addition, eight can sit more than 30 seconds, and two can crawl, stand, and walk independently. Eight of 12 patients are speaking, and 11 of 12 are feeding orally.
To date, five treatment-related adverse events in four patients have been reported – all asymptomatic increases in liver function enzymes, which resolved.
The study is funded by AveXis, the company developing this gene therapy. Dr. Mendell reported compensation for consulting and research support from AveXis and Sarepta Therapeutics.
AT AAN 2017
Red flags for type 2 diabetes seen 25 years before diagnosis
SAN DIEGO – Based on their analysis of a cohort of more than half a million people, Swedish researchers now believe that mildly elevated fasting plasma glucose and triglyceride levels could indicate an increased risk for type 2 diabetes a quarter-century before diagnosis.
“Previous studies have shown that risk factors for type 2 diabetes, including obesity and elevated fasting glucose, may be present up to 10 years before disease onset. Our study extends this period to more than 20 years before diagnosis,” said the study’s lead author Håkan Malmström, PhD, an epidemiologist with the Karolinska Institute, Stockholm. “Even small elevations in subjects over time early in life may be important to recognize, in particular for people who are overweight or obese.” The study findings were presented in an oral presentation at the scientific sessions of the American Diabetes Association.
The researchers identified 47,997 new type 2 diabetes cases in a Swedish cohort of 537,119 people tracked from 1985-2012. For each case, they compared risk factors from clinical examinations performed from 1985-1996 with those of five matched controls.
They found that on average, several risk factors were more common among individuals with type 2 diabetes, compared with the matched controls “many years before the diagnosis,” Dr. Malmström said. “In particular, BMI [body mass index], fasting triglycerides, fasting glucose, the apo B/apo A-I ratio and inflammatory markers were increased up to 25 years before the diagnosis.”
For example, 25 years before diagnosis, mean fasting plasma glucose in the type 2 diabetes group was higher than controls at 90 mg/dL vs. 86 mg/dL, respectively. By 10 years before diagnosis, that gap had widened to 98 mg/dL vs. 88 mg/dL. At 1 year before diagnosis, the levels were 106 mg/dl vs. 90 mg/dL.
As for fasting triglycerides, high levels earlier in life appeared to be especially risky: Individuals with levels over 124 mg/dL were more likely to develop type 2 diabetes 20 years later, even if they weren’t overweight or had elevated mean fasting glucose levels.
At 25 years before diagnosis, the type 2 diabetes group had mean fasting triglyceride levels of 120 mg/dL vs. 89 mg/dL in the control group. And at 1 year before diagnosis, the difference had widened to 146 mg/dL vs. 106 mg/dL.
Researchers found signs of higher levels of fructosamine – a marker of glycemic levels over an extended period of time (2-3 weeks) – at about 15 years before diagnosis. According to Dr. Malmström, this finding suggests that “glucose metabolism was starting to become more disturbed later than the changes in fasting glucose, but still many years before the type 2 diabetes diagnosis.”
He speculated that early signs of type 2 diabetes revealed by the study are related to genetic predisposition. “The risk of developing the disease presents early with increased BMI and dyslipidemia, which in turn leads to successively decreased insulin sensitivity,” he said.
One step for future research, he added, would be to “elaborate on these early changes in risk factors and create a risk score based on a few easily available factors in clinical settings.”
The study was funded by Sweden’s Gunnar and Ingmar Jungner Foundation for Laboratory Medicine. Dr. Malmström reported no relevant disclosures.
SAN DIEGO – Based on their analysis of a cohort of more than half a million people, Swedish researchers now believe that mildly elevated fasting plasma glucose and triglyceride levels could indicate an increased risk for type 2 diabetes a quarter-century before diagnosis.
“Previous studies have shown that risk factors for type 2 diabetes, including obesity and elevated fasting glucose, may be present up to 10 years before disease onset. Our study extends this period to more than 20 years before diagnosis,” said the study’s lead author Håkan Malmström, PhD, an epidemiologist with the Karolinska Institute, Stockholm. “Even small elevations in subjects over time early in life may be important to recognize, in particular for people who are overweight or obese.” The study findings were presented in an oral presentation at the scientific sessions of the American Diabetes Association.
The researchers identified 47,997 new type 2 diabetes cases in a Swedish cohort of 537,119 people tracked from 1985-2012. For each case, they compared risk factors from clinical examinations performed from 1985-1996 with those of five matched controls.
They found that on average, several risk factors were more common among individuals with type 2 diabetes, compared with the matched controls “many years before the diagnosis,” Dr. Malmström said. “In particular, BMI [body mass index], fasting triglycerides, fasting glucose, the apo B/apo A-I ratio and inflammatory markers were increased up to 25 years before the diagnosis.”
For example, 25 years before diagnosis, mean fasting plasma glucose in the type 2 diabetes group was higher than controls at 90 mg/dL vs. 86 mg/dL, respectively. By 10 years before diagnosis, that gap had widened to 98 mg/dL vs. 88 mg/dL. At 1 year before diagnosis, the levels were 106 mg/dl vs. 90 mg/dL.
As for fasting triglycerides, high levels earlier in life appeared to be especially risky: Individuals with levels over 124 mg/dL were more likely to develop type 2 diabetes 20 years later, even if they weren’t overweight or had elevated mean fasting glucose levels.
At 25 years before diagnosis, the type 2 diabetes group had mean fasting triglyceride levels of 120 mg/dL vs. 89 mg/dL in the control group. And at 1 year before diagnosis, the difference had widened to 146 mg/dL vs. 106 mg/dL.
Researchers found signs of higher levels of fructosamine – a marker of glycemic levels over an extended period of time (2-3 weeks) – at about 15 years before diagnosis. According to Dr. Malmström, this finding suggests that “glucose metabolism was starting to become more disturbed later than the changes in fasting glucose, but still many years before the type 2 diabetes diagnosis.”
He speculated that early signs of type 2 diabetes revealed by the study are related to genetic predisposition. “The risk of developing the disease presents early with increased BMI and dyslipidemia, which in turn leads to successively decreased insulin sensitivity,” he said.
One step for future research, he added, would be to “elaborate on these early changes in risk factors and create a risk score based on a few easily available factors in clinical settings.”
The study was funded by Sweden’s Gunnar and Ingmar Jungner Foundation for Laboratory Medicine. Dr. Malmström reported no relevant disclosures.
SAN DIEGO – Based on their analysis of a cohort of more than half a million people, Swedish researchers now believe that mildly elevated fasting plasma glucose and triglyceride levels could indicate an increased risk for type 2 diabetes a quarter-century before diagnosis.
“Previous studies have shown that risk factors for type 2 diabetes, including obesity and elevated fasting glucose, may be present up to 10 years before disease onset. Our study extends this period to more than 20 years before diagnosis,” said the study’s lead author Håkan Malmström, PhD, an epidemiologist with the Karolinska Institute, Stockholm. “Even small elevations in subjects over time early in life may be important to recognize, in particular for people who are overweight or obese.” The study findings were presented in an oral presentation at the scientific sessions of the American Diabetes Association.
The researchers identified 47,997 new type 2 diabetes cases in a Swedish cohort of 537,119 people tracked from 1985-2012. For each case, they compared risk factors from clinical examinations performed from 1985-1996 with those of five matched controls.
They found that on average, several risk factors were more common among individuals with type 2 diabetes, compared with the matched controls “many years before the diagnosis,” Dr. Malmström said. “In particular, BMI [body mass index], fasting triglycerides, fasting glucose, the apo B/apo A-I ratio and inflammatory markers were increased up to 25 years before the diagnosis.”
For example, 25 years before diagnosis, mean fasting plasma glucose in the type 2 diabetes group was higher than controls at 90 mg/dL vs. 86 mg/dL, respectively. By 10 years before diagnosis, that gap had widened to 98 mg/dL vs. 88 mg/dL. At 1 year before diagnosis, the levels were 106 mg/dl vs. 90 mg/dL.
As for fasting triglycerides, high levels earlier in life appeared to be especially risky: Individuals with levels over 124 mg/dL were more likely to develop type 2 diabetes 20 years later, even if they weren’t overweight or had elevated mean fasting glucose levels.
At 25 years before diagnosis, the type 2 diabetes group had mean fasting triglyceride levels of 120 mg/dL vs. 89 mg/dL in the control group. And at 1 year before diagnosis, the difference had widened to 146 mg/dL vs. 106 mg/dL.
Researchers found signs of higher levels of fructosamine – a marker of glycemic levels over an extended period of time (2-3 weeks) – at about 15 years before diagnosis. According to Dr. Malmström, this finding suggests that “glucose metabolism was starting to become more disturbed later than the changes in fasting glucose, but still many years before the type 2 diabetes diagnosis.”
He speculated that early signs of type 2 diabetes revealed by the study are related to genetic predisposition. “The risk of developing the disease presents early with increased BMI and dyslipidemia, which in turn leads to successively decreased insulin sensitivity,” he said.
One step for future research, he added, would be to “elaborate on these early changes in risk factors and create a risk score based on a few easily available factors in clinical settings.”
The study was funded by Sweden’s Gunnar and Ingmar Jungner Foundation for Laboratory Medicine. Dr. Malmström reported no relevant disclosures.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
TB meningitis cases in U.S. are fewer but more complicated
BOSTON – The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.
However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.
The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”
According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.
TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.
For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).
Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.
“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”
However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).
• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).
• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).
• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.
Dr. Merkler said it’s not clear why these rates are going up, but it may be because patients have more complications as a result of living longer. Another theory is that a form of drug-resistant TB is boosting the level of these complications, Dr. Merkler said, but he’s skeptical of that idea: “I don’t know why drug resistance would lead to more neurological complications.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
BOSTON – The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.
However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.
The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”
According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.
TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.
For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).
Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.
“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”
However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).
• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).
• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).
• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.
Dr. Merkler said it’s not clear why these rates are going up, but it may be because patients have more complications as a result of living longer. Another theory is that a form of drug-resistant TB is boosting the level of these complications, Dr. Merkler said, but he’s skeptical of that idea: “I don’t know why drug resistance would lead to more neurological complications.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
BOSTON – The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.
However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.
The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”
According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.
TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.
For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).
Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.
“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”
However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).
• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).
• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).
• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.
Dr. Merkler said it’s not clear why these rates are going up, but it may be because patients have more complications as a result of living longer. Another theory is that a form of drug-resistant TB is boosting the level of these complications, Dr. Merkler said, but he’s skeptical of that idea: “I don’t know why drug resistance would lead to more neurological complications.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
AT AAN 2017
Key clinical point:
Major finding: The rate of TB meningitis hospitalizations fell from 6.2 to 1.9 per million people (rate difference, 4.3; 95% CI, 2.1-6.5; P less than .001).
Data source: The Nationwide Inpatient Sample database, which revealed 16,196 new cases of TB meningitis from 1993 to 2013.
Disclosures: The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
App allows monitoring of drug effects in Parkinson’s
BOSTON – The developers of a free app that tests mental and physical symptoms in patients with Parkinson’s disease (PD) report that their software allows the monitoring of responses to treatment.
“We can track markers of medication,” Larsson Omberg, PhD, vice president of systems biology at the nonprofit Sage Bionetworks, said in an interview. “We can statistically predict whether someone has taken their medication or not, and we can even subdivide populations into strong responders to l-dopa and individuals who don’t necessarily have strong responses to medication but have strong fluctuations based on the time of day.”
A total of 10,326 participants (86%) served as a control group of people who do not have PD. Their average age was 32 (interquartile range, 23-38). The other 14% of participants (n = 2,373) disclosed that they have PD. Their average age was 60 (IQR, 54-68), and they reported having the disease for an average of 8 years (IQR, 4-10).
Overall, 80% of the control participants were male, as were 64% of the PD participants.
Researchers found that 96% of the PD participants were taking PD medications, and 10% reported having had deep brain stimulation.
Participants were asked to use the app’s surveys and tests to measure things such as tremor, sleep quality, frequency of gait, tapping ability, and voice jitter.
“We ask them to perform these active tasks, things they might do in the clinic,” Dr. Omberg said. “The difference is that we are capturing measurements using the sensors in the phone. It’s relatively easy so we can track changes over a day and from day to day.”
For example, one of the tests measures how quickly users can tap the screen over a 20-second interval. “It is a two-finger tap between two fingers and two buttons on the screen,” Dr. Omberg said. “Finger tapping is associated with the severity of the disease.”
The researchers found that they could track patient variability throughout the day and connect the data to the times when patients took medication. In half of the PD patients, the data showed a correlation between medication use and performance of at least one of five types of activities – gait, balance, voice, memory, and tapping.
The app and the information it has provided have limitations, he said. While one participant has used the app at least three times a day for 2 years, many users tried it out for a short time and became inactive. And while users can access some of their own data, it’s not very helpful yet: “It’s very raw and probably not the most useful to a clinician,” Dr. Omberg said.
Regarding whether the app could be used to reveal early signs of PD, Dr. Omberg cautioned that it wasn’t designed for that purpose. Still, “I’m pretty sure applications like mPower would be technically able to do this at some point in the future,” he said. “But there is a lot of validation work that will have to be done first.”
For now, the app remains available for free for iOS devices, and researchers are working on a new version. Meanwhile, Dr. Omberg said the app is serving as a research tool to collect baseline and trial data in the Safety of Urate Elevation in Parkinson’s Disease (SURE-PD) study, which is examining the use of oral inosine to boost serum urate in PD patients.
The study was funded by the Robert Wood Johnson Foundation.
BOSTON – The developers of a free app that tests mental and physical symptoms in patients with Parkinson’s disease (PD) report that their software allows the monitoring of responses to treatment.
“We can track markers of medication,” Larsson Omberg, PhD, vice president of systems biology at the nonprofit Sage Bionetworks, said in an interview. “We can statistically predict whether someone has taken their medication or not, and we can even subdivide populations into strong responders to l-dopa and individuals who don’t necessarily have strong responses to medication but have strong fluctuations based on the time of day.”
A total of 10,326 participants (86%) served as a control group of people who do not have PD. Their average age was 32 (interquartile range, 23-38). The other 14% of participants (n = 2,373) disclosed that they have PD. Their average age was 60 (IQR, 54-68), and they reported having the disease for an average of 8 years (IQR, 4-10).
Overall, 80% of the control participants were male, as were 64% of the PD participants.
Researchers found that 96% of the PD participants were taking PD medications, and 10% reported having had deep brain stimulation.
Participants were asked to use the app’s surveys and tests to measure things such as tremor, sleep quality, frequency of gait, tapping ability, and voice jitter.
“We ask them to perform these active tasks, things they might do in the clinic,” Dr. Omberg said. “The difference is that we are capturing measurements using the sensors in the phone. It’s relatively easy so we can track changes over a day and from day to day.”
For example, one of the tests measures how quickly users can tap the screen over a 20-second interval. “It is a two-finger tap between two fingers and two buttons on the screen,” Dr. Omberg said. “Finger tapping is associated with the severity of the disease.”
The researchers found that they could track patient variability throughout the day and connect the data to the times when patients took medication. In half of the PD patients, the data showed a correlation between medication use and performance of at least one of five types of activities – gait, balance, voice, memory, and tapping.
The app and the information it has provided have limitations, he said. While one participant has used the app at least three times a day for 2 years, many users tried it out for a short time and became inactive. And while users can access some of their own data, it’s not very helpful yet: “It’s very raw and probably not the most useful to a clinician,” Dr. Omberg said.
Regarding whether the app could be used to reveal early signs of PD, Dr. Omberg cautioned that it wasn’t designed for that purpose. Still, “I’m pretty sure applications like mPower would be technically able to do this at some point in the future,” he said. “But there is a lot of validation work that will have to be done first.”
For now, the app remains available for free for iOS devices, and researchers are working on a new version. Meanwhile, Dr. Omberg said the app is serving as a research tool to collect baseline and trial data in the Safety of Urate Elevation in Parkinson’s Disease (SURE-PD) study, which is examining the use of oral inosine to boost serum urate in PD patients.
The study was funded by the Robert Wood Johnson Foundation.
BOSTON – The developers of a free app that tests mental and physical symptoms in patients with Parkinson’s disease (PD) report that their software allows the monitoring of responses to treatment.
“We can track markers of medication,” Larsson Omberg, PhD, vice president of systems biology at the nonprofit Sage Bionetworks, said in an interview. “We can statistically predict whether someone has taken their medication or not, and we can even subdivide populations into strong responders to l-dopa and individuals who don’t necessarily have strong responses to medication but have strong fluctuations based on the time of day.”
A total of 10,326 participants (86%) served as a control group of people who do not have PD. Their average age was 32 (interquartile range, 23-38). The other 14% of participants (n = 2,373) disclosed that they have PD. Their average age was 60 (IQR, 54-68), and they reported having the disease for an average of 8 years (IQR, 4-10).
Overall, 80% of the control participants were male, as were 64% of the PD participants.
Researchers found that 96% of the PD participants were taking PD medications, and 10% reported having had deep brain stimulation.
Participants were asked to use the app’s surveys and tests to measure things such as tremor, sleep quality, frequency of gait, tapping ability, and voice jitter.
“We ask them to perform these active tasks, things they might do in the clinic,” Dr. Omberg said. “The difference is that we are capturing measurements using the sensors in the phone. It’s relatively easy so we can track changes over a day and from day to day.”
For example, one of the tests measures how quickly users can tap the screen over a 20-second interval. “It is a two-finger tap between two fingers and two buttons on the screen,” Dr. Omberg said. “Finger tapping is associated with the severity of the disease.”
The researchers found that they could track patient variability throughout the day and connect the data to the times when patients took medication. In half of the PD patients, the data showed a correlation between medication use and performance of at least one of five types of activities – gait, balance, voice, memory, and tapping.
The app and the information it has provided have limitations, he said. While one participant has used the app at least three times a day for 2 years, many users tried it out for a short time and became inactive. And while users can access some of their own data, it’s not very helpful yet: “It’s very raw and probably not the most useful to a clinician,” Dr. Omberg said.
Regarding whether the app could be used to reveal early signs of PD, Dr. Omberg cautioned that it wasn’t designed for that purpose. Still, “I’m pretty sure applications like mPower would be technically able to do this at some point in the future,” he said. “But there is a lot of validation work that will have to be done first.”
For now, the app remains available for free for iOS devices, and researchers are working on a new version. Meanwhile, Dr. Omberg said the app is serving as a research tool to collect baseline and trial data in the Safety of Urate Elevation in Parkinson’s Disease (SURE-PD) study, which is examining the use of oral inosine to boost serum urate in PD patients.
The study was funded by the Robert Wood Johnson Foundation.
AT AAN 2017
Promising phase II results for Rytary reformulation for Parkinson’s
BOSTON – The results of a small phase II trial confirm that IPX203, an investigational reformulation of the extended-release carbidopa-levodopa combination called Rytary, holds the potential to greatly extend “on” time in Parkinson’s disease patients.
While it’s early in the research process, “this is a promising new formulation,” said Mark Stacy, MD, who led the trial that pitted IPX203 against immediate-release (IR) carbidopa-levodopa (CD-LD) and Rytary.
Dr. Stacy, professor of neurology and vice dean for clinical research at Duke University, Durham, N.C., and his colleagues released the phase II results at the annual meeting of the American Academy of Neurology.
Parkinson’s disease patients often aren’t adherent to their drugs despite the risk that they’ll see symptoms return. “It’s been demonstrated that they miss medicines as often as in any other disease,” Dr. Stacy said in an interview.
Rytary, which was approved by the Food and Drug Administration in 2015, has improved adherence in Parkinson’s disease patients by allowing them to reduce the number of doses they need to separately take every day to four. “If this new formulation is able to last 8 hours, you could essentially take that at bedtime and have medication in your system when you awaken,” Dr. Stacy said. “Then you could take it twice more during the day.”
The new, open-label, crossover trial randomly assigned 26 patients on stable IR regimens (at least 400 mg LD/day, at least 4 doses a day) to single doses of IR, Rytary, and IPX203. For 10 hours after dose, raters evaluated every 30 minutes whether the subjects were on (with troublesome dyskinesia) or off (without troublesome dyskinesia).
All but one subject finished the trial. Over the first hour, the patients fared about the same in terms of converting to on status. Overall, PX203 significantly decreased average off time (4.5 hours), compared with IR (7.2 hours; P less than .0001) and Rytary (5.4 hours; P less than .05).
Researchers also found that IPX203 had the highest duration of a 4-point improvement in the Unified Parkinson’s Disease Rating Scale Part III score at 6.1 hours, compared with IR (3.7 hours; P less than .0001) and Rytary (5.2 hours; P less than .05). In addition, 13-point improvements were higher for IPX203 at 4.8 hours, compared with IR (2.2 hours; P less than .0001) and Rytary (3.6 hours; P less than .05).
No serious adverse events were reported. Nausea, dizziness, and hypertension occurred in two or more patients in each treatment group and were more common with IR (28.0%) and IPX203 (19.2%) than with Rytary (8.0%).
The study was funded by Impax Laboratories. Dr. Stacy reported several disclosures, including consulting work for numerous drug makers.
BOSTON – The results of a small phase II trial confirm that IPX203, an investigational reformulation of the extended-release carbidopa-levodopa combination called Rytary, holds the potential to greatly extend “on” time in Parkinson’s disease patients.
While it’s early in the research process, “this is a promising new formulation,” said Mark Stacy, MD, who led the trial that pitted IPX203 against immediate-release (IR) carbidopa-levodopa (CD-LD) and Rytary.
Dr. Stacy, professor of neurology and vice dean for clinical research at Duke University, Durham, N.C., and his colleagues released the phase II results at the annual meeting of the American Academy of Neurology.
Parkinson’s disease patients often aren’t adherent to their drugs despite the risk that they’ll see symptoms return. “It’s been demonstrated that they miss medicines as often as in any other disease,” Dr. Stacy said in an interview.
Rytary, which was approved by the Food and Drug Administration in 2015, has improved adherence in Parkinson’s disease patients by allowing them to reduce the number of doses they need to separately take every day to four. “If this new formulation is able to last 8 hours, you could essentially take that at bedtime and have medication in your system when you awaken,” Dr. Stacy said. “Then you could take it twice more during the day.”
The new, open-label, crossover trial randomly assigned 26 patients on stable IR regimens (at least 400 mg LD/day, at least 4 doses a day) to single doses of IR, Rytary, and IPX203. For 10 hours after dose, raters evaluated every 30 minutes whether the subjects were on (with troublesome dyskinesia) or off (without troublesome dyskinesia).
All but one subject finished the trial. Over the first hour, the patients fared about the same in terms of converting to on status. Overall, PX203 significantly decreased average off time (4.5 hours), compared with IR (7.2 hours; P less than .0001) and Rytary (5.4 hours; P less than .05).
Researchers also found that IPX203 had the highest duration of a 4-point improvement in the Unified Parkinson’s Disease Rating Scale Part III score at 6.1 hours, compared with IR (3.7 hours; P less than .0001) and Rytary (5.2 hours; P less than .05). In addition, 13-point improvements were higher for IPX203 at 4.8 hours, compared with IR (2.2 hours; P less than .0001) and Rytary (3.6 hours; P less than .05).
No serious adverse events were reported. Nausea, dizziness, and hypertension occurred in two or more patients in each treatment group and were more common with IR (28.0%) and IPX203 (19.2%) than with Rytary (8.0%).
The study was funded by Impax Laboratories. Dr. Stacy reported several disclosures, including consulting work for numerous drug makers.
BOSTON – The results of a small phase II trial confirm that IPX203, an investigational reformulation of the extended-release carbidopa-levodopa combination called Rytary, holds the potential to greatly extend “on” time in Parkinson’s disease patients.
While it’s early in the research process, “this is a promising new formulation,” said Mark Stacy, MD, who led the trial that pitted IPX203 against immediate-release (IR) carbidopa-levodopa (CD-LD) and Rytary.
Dr. Stacy, professor of neurology and vice dean for clinical research at Duke University, Durham, N.C., and his colleagues released the phase II results at the annual meeting of the American Academy of Neurology.
Parkinson’s disease patients often aren’t adherent to their drugs despite the risk that they’ll see symptoms return. “It’s been demonstrated that they miss medicines as often as in any other disease,” Dr. Stacy said in an interview.
Rytary, which was approved by the Food and Drug Administration in 2015, has improved adherence in Parkinson’s disease patients by allowing them to reduce the number of doses they need to separately take every day to four. “If this new formulation is able to last 8 hours, you could essentially take that at bedtime and have medication in your system when you awaken,” Dr. Stacy said. “Then you could take it twice more during the day.”
The new, open-label, crossover trial randomly assigned 26 patients on stable IR regimens (at least 400 mg LD/day, at least 4 doses a day) to single doses of IR, Rytary, and IPX203. For 10 hours after dose, raters evaluated every 30 minutes whether the subjects were on (with troublesome dyskinesia) or off (without troublesome dyskinesia).
All but one subject finished the trial. Over the first hour, the patients fared about the same in terms of converting to on status. Overall, PX203 significantly decreased average off time (4.5 hours), compared with IR (7.2 hours; P less than .0001) and Rytary (5.4 hours; P less than .05).
Researchers also found that IPX203 had the highest duration of a 4-point improvement in the Unified Parkinson’s Disease Rating Scale Part III score at 6.1 hours, compared with IR (3.7 hours; P less than .0001) and Rytary (5.2 hours; P less than .05). In addition, 13-point improvements were higher for IPX203 at 4.8 hours, compared with IR (2.2 hours; P less than .0001) and Rytary (3.6 hours; P less than .05).
No serious adverse events were reported. Nausea, dizziness, and hypertension occurred in two or more patients in each treatment group and were more common with IR (28.0%) and IPX203 (19.2%) than with Rytary (8.0%).
The study was funded by Impax Laboratories. Dr. Stacy reported several disclosures, including consulting work for numerous drug makers.
AT AAN 2017
Key clinical point: Investigational drug IPX203, a reformulation of Rytary (extended release carbidopa-levodopa), holds promise as an improved extended-release Parkinson’s disease medication.
Major finding: After one dose, PX203 significantly decreased average off time (4.5 hours), compared with immediate-release carbidopa-levodopa (7.2 hours; P less than .0001) and Rytary (5.4 hours; P less than .05).
Data source: Open-label, rater-blinded, randomized, crossover study of 25 Parkinson’s disease patients
Disclosures: The study was funded by Impax Laboratories. The presenter reported several disclosures, including consulting work for numerous drug makers.
Dermatologist calls for paradigm shift on treating ocular rosacea
A partnership between ophthalmologists and dermatologists holds the potential to produce a better treatment for ocular rosacea, one of the few conditions that brings the two specialties together.
“Hopefully, the paradigm eventually shifts from treating symptoms and signs of ocular rosacea with oral antibiotics or reflexive referral to ophthalmology to approaching cutaneous treatment first,” said dermatologist Kara Capriotti, MD, who has been working with a team of ophthalmologists to develop a treatment that focuses on ocular rosacea as a “lid disease,” instead of as a primary ocular surface problem.
Eye scrubs, artificial tears, stress relief measures, and antibiotics are among the treatments used for the condition, which, however, can be treatment-resistant.
The key, she believes, is to move from a focus on ocular symptoms to an emphasis on lid and skin signs associated with ocular rosacea. “Almost all of the ophthalmology approaches to the disease start at the ocular surface, and these surface treatments are always a little bit [or very] toxic to the ocular surface,” she said. “By treating the lid signs first through a topical approach through the closed lid, we can eliminate a lot of the ocular surface symptoms without ever touching the ocular surface, thus preventing a lot of the associated toxicity and side effects you commonly see with topical ophthalmics.”
Dr. Capriotti and her colleagues have developed a topical treatment that contains dimethyl sulfoxide (DMSO) combined with dilute povidone iodine, which is applied to the lid margin of the closed eye.
In 2015, they published a case report describing the successful use of the treatment for a 78-year-old man with rosacea blepharoconjunctivitis, who had failed oral and topical treatments. He was treated with povidone iodine 10% solution in a DMSO vehicle, which was compounded into a topical gel by a pharmacy and administered twice a day, rubbed onto the lash line and eyelid.
After one week, “remarkable improvements were noted,” with reversal of much of the conjunctivitis, anterior lid erythema, and thickening, they wrote. One month later, after once daily application, “not only were the initial improvements conserved, but the posterior lid margin vessels and telangiectasias had begun to attenuate and involute. Moreover, meibomian capping was no longer present, secretions were less viscous, and tear break-up time normalized.”
DMSO is a skin penetration agent that is rarely used in ophthalmology and povidone iodine is a biocidal agent used in eye care, they pointed out in the case report. “This novel therapy may warrant further investigation in randomized, controlled clinical trials,” they concluded (Ophthalmol Ther. 2015 Dec;4[2]:143-50).
There are plans to start a clinical trial later in 2017, according to Dr. Capriottis, the cofounder of Veloce Biopharma, a company that is developing this product.
Until more specific treatments are available, what can dermatologists do now to improve their care of patients with ocular rosacea? “First and foremost, you have to be comfortable looking at the eyelids and ruling out anything that could be masquerading as blepharitis,” Dr. Capriotti commented. “We have a big disadvantage in dermatology because we don’t use slit-lamp biomicroscopy, but we are pretty good at looking at skin. If the patient has a lot of extraocular rosacea signs, I definitely think dermatologists can manage the prescription of a topical for the lids and evaluate the response.”
She cautioned, however, that referrals are in order in several situations: cases that are severe, those that involve the eye only, and those with which ocular symptoms seem to outweigh the lid signs.
Dr. Capriotti is also the senior vice president of dermatology at Veloce. In the study published in 2015, she and her three coauthors disclosed having financial interest in ALC Therapeutics, a company that was dissolved and restructured into Veloce.
A partnership between ophthalmologists and dermatologists holds the potential to produce a better treatment for ocular rosacea, one of the few conditions that brings the two specialties together.
“Hopefully, the paradigm eventually shifts from treating symptoms and signs of ocular rosacea with oral antibiotics or reflexive referral to ophthalmology to approaching cutaneous treatment first,” said dermatologist Kara Capriotti, MD, who has been working with a team of ophthalmologists to develop a treatment that focuses on ocular rosacea as a “lid disease,” instead of as a primary ocular surface problem.
Eye scrubs, artificial tears, stress relief measures, and antibiotics are among the treatments used for the condition, which, however, can be treatment-resistant.
The key, she believes, is to move from a focus on ocular symptoms to an emphasis on lid and skin signs associated with ocular rosacea. “Almost all of the ophthalmology approaches to the disease start at the ocular surface, and these surface treatments are always a little bit [or very] toxic to the ocular surface,” she said. “By treating the lid signs first through a topical approach through the closed lid, we can eliminate a lot of the ocular surface symptoms without ever touching the ocular surface, thus preventing a lot of the associated toxicity and side effects you commonly see with topical ophthalmics.”
Dr. Capriotti and her colleagues have developed a topical treatment that contains dimethyl sulfoxide (DMSO) combined with dilute povidone iodine, which is applied to the lid margin of the closed eye.
In 2015, they published a case report describing the successful use of the treatment for a 78-year-old man with rosacea blepharoconjunctivitis, who had failed oral and topical treatments. He was treated with povidone iodine 10% solution in a DMSO vehicle, which was compounded into a topical gel by a pharmacy and administered twice a day, rubbed onto the lash line and eyelid.
After one week, “remarkable improvements were noted,” with reversal of much of the conjunctivitis, anterior lid erythema, and thickening, they wrote. One month later, after once daily application, “not only were the initial improvements conserved, but the posterior lid margin vessels and telangiectasias had begun to attenuate and involute. Moreover, meibomian capping was no longer present, secretions were less viscous, and tear break-up time normalized.”
DMSO is a skin penetration agent that is rarely used in ophthalmology and povidone iodine is a biocidal agent used in eye care, they pointed out in the case report. “This novel therapy may warrant further investigation in randomized, controlled clinical trials,” they concluded (Ophthalmol Ther. 2015 Dec;4[2]:143-50).
There are plans to start a clinical trial later in 2017, according to Dr. Capriottis, the cofounder of Veloce Biopharma, a company that is developing this product.
Until more specific treatments are available, what can dermatologists do now to improve their care of patients with ocular rosacea? “First and foremost, you have to be comfortable looking at the eyelids and ruling out anything that could be masquerading as blepharitis,” Dr. Capriotti commented. “We have a big disadvantage in dermatology because we don’t use slit-lamp biomicroscopy, but we are pretty good at looking at skin. If the patient has a lot of extraocular rosacea signs, I definitely think dermatologists can manage the prescription of a topical for the lids and evaluate the response.”
She cautioned, however, that referrals are in order in several situations: cases that are severe, those that involve the eye only, and those with which ocular symptoms seem to outweigh the lid signs.
Dr. Capriotti is also the senior vice president of dermatology at Veloce. In the study published in 2015, she and her three coauthors disclosed having financial interest in ALC Therapeutics, a company that was dissolved and restructured into Veloce.
A partnership between ophthalmologists and dermatologists holds the potential to produce a better treatment for ocular rosacea, one of the few conditions that brings the two specialties together.
“Hopefully, the paradigm eventually shifts from treating symptoms and signs of ocular rosacea with oral antibiotics or reflexive referral to ophthalmology to approaching cutaneous treatment first,” said dermatologist Kara Capriotti, MD, who has been working with a team of ophthalmologists to develop a treatment that focuses on ocular rosacea as a “lid disease,” instead of as a primary ocular surface problem.
Eye scrubs, artificial tears, stress relief measures, and antibiotics are among the treatments used for the condition, which, however, can be treatment-resistant.
The key, she believes, is to move from a focus on ocular symptoms to an emphasis on lid and skin signs associated with ocular rosacea. “Almost all of the ophthalmology approaches to the disease start at the ocular surface, and these surface treatments are always a little bit [or very] toxic to the ocular surface,” she said. “By treating the lid signs first through a topical approach through the closed lid, we can eliminate a lot of the ocular surface symptoms without ever touching the ocular surface, thus preventing a lot of the associated toxicity and side effects you commonly see with topical ophthalmics.”
Dr. Capriotti and her colleagues have developed a topical treatment that contains dimethyl sulfoxide (DMSO) combined with dilute povidone iodine, which is applied to the lid margin of the closed eye.
In 2015, they published a case report describing the successful use of the treatment for a 78-year-old man with rosacea blepharoconjunctivitis, who had failed oral and topical treatments. He was treated with povidone iodine 10% solution in a DMSO vehicle, which was compounded into a topical gel by a pharmacy and administered twice a day, rubbed onto the lash line and eyelid.
After one week, “remarkable improvements were noted,” with reversal of much of the conjunctivitis, anterior lid erythema, and thickening, they wrote. One month later, after once daily application, “not only were the initial improvements conserved, but the posterior lid margin vessels and telangiectasias had begun to attenuate and involute. Moreover, meibomian capping was no longer present, secretions were less viscous, and tear break-up time normalized.”
DMSO is a skin penetration agent that is rarely used in ophthalmology and povidone iodine is a biocidal agent used in eye care, they pointed out in the case report. “This novel therapy may warrant further investigation in randomized, controlled clinical trials,” they concluded (Ophthalmol Ther. 2015 Dec;4[2]:143-50).
There are plans to start a clinical trial later in 2017, according to Dr. Capriottis, the cofounder of Veloce Biopharma, a company that is developing this product.
Until more specific treatments are available, what can dermatologists do now to improve their care of patients with ocular rosacea? “First and foremost, you have to be comfortable looking at the eyelids and ruling out anything that could be masquerading as blepharitis,” Dr. Capriotti commented. “We have a big disadvantage in dermatology because we don’t use slit-lamp biomicroscopy, but we are pretty good at looking at skin. If the patient has a lot of extraocular rosacea signs, I definitely think dermatologists can manage the prescription of a topical for the lids and evaluate the response.”
She cautioned, however, that referrals are in order in several situations: cases that are severe, those that involve the eye only, and those with which ocular symptoms seem to outweigh the lid signs.
Dr. Capriotti is also the senior vice president of dermatology at Veloce. In the study published in 2015, she and her three coauthors disclosed having financial interest in ALC Therapeutics, a company that was dissolved and restructured into Veloce.
Oral insulin matches glargine in phase II trial
SAN DIEGO – In an industry-funded phase II trial, researchers say they’ve shown for the first time that oral basal insulin tablets can safely decrease plasma glucose in patients with type 2 diabetes (T2DM).
“Oral basal insulin appears safe and efficacious in insulin-naive patients with type 2 [diabetes] insufficiently controlled with medications. It improves glycemic control to a similar extent as does glargine,” said study lead author Leona Plum-Mörschel, MD, CEO of the German clinical research organization Profil Mainz, in an oral presentation at the scientific sessions of the American Diabetes Association. A statement from Novo Nordisk, the maker of the investigational medication, says the company discontinued development of the product due to its low bioavailability and concerns about the costs of producing it.
According to Dr. Plum-Mörschel, researchers have been searching for an oral insulin treatment for almost a century without success.
In the new phase IIa study, researchers tested a basal insulin analog tablet called OI338GT. It uses a technology platform called Gipet by Merrion Pharmaceuticals that aims to boost the absorption of injectable drugs when they are given in oral form.
Researchers recruited 50 insulin-naive patients with T2DM (mean age 61 ± 7 years, mean BMI 30.5 ± 3.7 kg/m²) whose diabetes wasn’t properly controlled by metformin by itself or in conjunction with other drugs. All had hemoglobin A1c (HbA1c) levels between 7% and 10%.
The patients were randomly assigned (1:1) to the investigational oral medication or subcutaneous insulin glargine (IGlar). They took the drugs once a day for 8 weeks in addition to their existing drug regimen.
The researchers increased the doses on a weekly basis with a goal of reaching fasting plasma glucose (FPG) of 80-126 mg/dL. Daily doses of the investigational drug (nmol/kg) began at a mean 30 ± 11 and reached 114 ± 51 by the end of the study; daily mean doses of IGlar (U/kg) began at 0.11 ± 0.03 and ended at 0.33 ± 0.15.
Both medications boosted glycemic control at about the same level, the researchers report, based on levels of FPG, HbA1c, and fructosamine levels at 8 weeks.
Mean FPG levels (mg/dL), the primary endpoint, declined in investigational medication and IGlar from 175 ± 50 and 164 ± 31, respectively, at baseline to 129 ± 33 and 121 ± 17, respectively, at end of treatment. The treatment difference (investigational medication – IGlar) was 5.2 mg/dL [–8.8;19.1], 95% CI, P = .4567.
In a post hoc analysis, mean HbA1c levels declined from 8.1 ± 0.6% and 8.2 ± 0.8% at baseline in investigational medication and IGlar, respectively, to 7.3 ± 0.8% and 7.1 ± 0.6%, respectively. The treatment difference (investigational medication – IGlar) was 0.30% [–0.03;0.63], 95% CI, P = .0774.
In another post hoc analysis, mean fructosamine levels (micromol/L) dipped from 275 ± 44 and 273 ± 50 in investigational medication and IGlar, respectively, to 235 ± 45 and 223 ± 34, respectively. The treatment difference (investigational medication – IGlar)
was 9.6 micromol/L [–11.7;30.9], 95% CI, P = .3700. None of the patients reported severe hypoglycemia. In the investigational group, 6 subjects suffered 7 events of hypoglycemia that emerged or worsened during treatment; 11 events occurred in 6 subjects in the IGlar group. Researchers report similar levels of adverse events in both groups: 31 in 15 patients treated with the investigational drug and 37 in 17 patients treated with IGlar.
“After termination of treatment, plasma glucose rebounded to baseline levels within a couple of weeks,” Dr. Plum-Mörschel said.
Novo Nordisk funded the trial. Dr. Plum-Mörschel reports no disclosures.
SAN DIEGO – In an industry-funded phase II trial, researchers say they’ve shown for the first time that oral basal insulin tablets can safely decrease plasma glucose in patients with type 2 diabetes (T2DM).
“Oral basal insulin appears safe and efficacious in insulin-naive patients with type 2 [diabetes] insufficiently controlled with medications. It improves glycemic control to a similar extent as does glargine,” said study lead author Leona Plum-Mörschel, MD, CEO of the German clinical research organization Profil Mainz, in an oral presentation at the scientific sessions of the American Diabetes Association. A statement from Novo Nordisk, the maker of the investigational medication, says the company discontinued development of the product due to its low bioavailability and concerns about the costs of producing it.
According to Dr. Plum-Mörschel, researchers have been searching for an oral insulin treatment for almost a century without success.
In the new phase IIa study, researchers tested a basal insulin analog tablet called OI338GT. It uses a technology platform called Gipet by Merrion Pharmaceuticals that aims to boost the absorption of injectable drugs when they are given in oral form.
Researchers recruited 50 insulin-naive patients with T2DM (mean age 61 ± 7 years, mean BMI 30.5 ± 3.7 kg/m²) whose diabetes wasn’t properly controlled by metformin by itself or in conjunction with other drugs. All had hemoglobin A1c (HbA1c) levels between 7% and 10%.
The patients were randomly assigned (1:1) to the investigational oral medication or subcutaneous insulin glargine (IGlar). They took the drugs once a day for 8 weeks in addition to their existing drug regimen.
The researchers increased the doses on a weekly basis with a goal of reaching fasting plasma glucose (FPG) of 80-126 mg/dL. Daily doses of the investigational drug (nmol/kg) began at a mean 30 ± 11 and reached 114 ± 51 by the end of the study; daily mean doses of IGlar (U/kg) began at 0.11 ± 0.03 and ended at 0.33 ± 0.15.
Both medications boosted glycemic control at about the same level, the researchers report, based on levels of FPG, HbA1c, and fructosamine levels at 8 weeks.
Mean FPG levels (mg/dL), the primary endpoint, declined in investigational medication and IGlar from 175 ± 50 and 164 ± 31, respectively, at baseline to 129 ± 33 and 121 ± 17, respectively, at end of treatment. The treatment difference (investigational medication – IGlar) was 5.2 mg/dL [–8.8;19.1], 95% CI, P = .4567.
In a post hoc analysis, mean HbA1c levels declined from 8.1 ± 0.6% and 8.2 ± 0.8% at baseline in investigational medication and IGlar, respectively, to 7.3 ± 0.8% and 7.1 ± 0.6%, respectively. The treatment difference (investigational medication – IGlar) was 0.30% [–0.03;0.63], 95% CI, P = .0774.
In another post hoc analysis, mean fructosamine levels (micromol/L) dipped from 275 ± 44 and 273 ± 50 in investigational medication and IGlar, respectively, to 235 ± 45 and 223 ± 34, respectively. The treatment difference (investigational medication – IGlar)
was 9.6 micromol/L [–11.7;30.9], 95% CI, P = .3700. None of the patients reported severe hypoglycemia. In the investigational group, 6 subjects suffered 7 events of hypoglycemia that emerged or worsened during treatment; 11 events occurred in 6 subjects in the IGlar group. Researchers report similar levels of adverse events in both groups: 31 in 15 patients treated with the investigational drug and 37 in 17 patients treated with IGlar.
“After termination of treatment, plasma glucose rebounded to baseline levels within a couple of weeks,” Dr. Plum-Mörschel said.
Novo Nordisk funded the trial. Dr. Plum-Mörschel reports no disclosures.
SAN DIEGO – In an industry-funded phase II trial, researchers say they’ve shown for the first time that oral basal insulin tablets can safely decrease plasma glucose in patients with type 2 diabetes (T2DM).
“Oral basal insulin appears safe and efficacious in insulin-naive patients with type 2 [diabetes] insufficiently controlled with medications. It improves glycemic control to a similar extent as does glargine,” said study lead author Leona Plum-Mörschel, MD, CEO of the German clinical research organization Profil Mainz, in an oral presentation at the scientific sessions of the American Diabetes Association. A statement from Novo Nordisk, the maker of the investigational medication, says the company discontinued development of the product due to its low bioavailability and concerns about the costs of producing it.
According to Dr. Plum-Mörschel, researchers have been searching for an oral insulin treatment for almost a century without success.
In the new phase IIa study, researchers tested a basal insulin analog tablet called OI338GT. It uses a technology platform called Gipet by Merrion Pharmaceuticals that aims to boost the absorption of injectable drugs when they are given in oral form.
Researchers recruited 50 insulin-naive patients with T2DM (mean age 61 ± 7 years, mean BMI 30.5 ± 3.7 kg/m²) whose diabetes wasn’t properly controlled by metformin by itself or in conjunction with other drugs. All had hemoglobin A1c (HbA1c) levels between 7% and 10%.
The patients were randomly assigned (1:1) to the investigational oral medication or subcutaneous insulin glargine (IGlar). They took the drugs once a day for 8 weeks in addition to their existing drug regimen.
The researchers increased the doses on a weekly basis with a goal of reaching fasting plasma glucose (FPG) of 80-126 mg/dL. Daily doses of the investigational drug (nmol/kg) began at a mean 30 ± 11 and reached 114 ± 51 by the end of the study; daily mean doses of IGlar (U/kg) began at 0.11 ± 0.03 and ended at 0.33 ± 0.15.
Both medications boosted glycemic control at about the same level, the researchers report, based on levels of FPG, HbA1c, and fructosamine levels at 8 weeks.
Mean FPG levels (mg/dL), the primary endpoint, declined in investigational medication and IGlar from 175 ± 50 and 164 ± 31, respectively, at baseline to 129 ± 33 and 121 ± 17, respectively, at end of treatment. The treatment difference (investigational medication – IGlar) was 5.2 mg/dL [–8.8;19.1], 95% CI, P = .4567.
In a post hoc analysis, mean HbA1c levels declined from 8.1 ± 0.6% and 8.2 ± 0.8% at baseline in investigational medication and IGlar, respectively, to 7.3 ± 0.8% and 7.1 ± 0.6%, respectively. The treatment difference (investigational medication – IGlar) was 0.30% [–0.03;0.63], 95% CI, P = .0774.
In another post hoc analysis, mean fructosamine levels (micromol/L) dipped from 275 ± 44 and 273 ± 50 in investigational medication and IGlar, respectively, to 235 ± 45 and 223 ± 34, respectively. The treatment difference (investigational medication – IGlar)
was 9.6 micromol/L [–11.7;30.9], 95% CI, P = .3700. None of the patients reported severe hypoglycemia. In the investigational group, 6 subjects suffered 7 events of hypoglycemia that emerged or worsened during treatment; 11 events occurred in 6 subjects in the IGlar group. Researchers report similar levels of adverse events in both groups: 31 in 15 patients treated with the investigational drug and 37 in 17 patients treated with IGlar.
“After termination of treatment, plasma glucose rebounded to baseline levels within a couple of weeks,” Dr. Plum-Mörschel said.
Novo Nordisk funded the trial. Dr. Plum-Mörschel reports no disclosures.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: In 8-week trial, oral insulin tablets produce similar glucose control to injectable glargine (IGlar) in patients with type 2 diabetes (T2DM).
Major finding: Mean levels fasting plasma glucose (FPG, mg/dL) declined from 175 ± 50 to 129 ± 33 (investigational medication) and from 164 ± 31 to 121 ± 17 (IGlar). The treatment difference (investigational medication – IGlar) was 5.2 mg/dL [–8.8;19.1], 95% CI, P = .4567.
Data source: 50 insulin-naive patients with T2DM randomly assigned (1:1) to daily doses of investigational oral medication or IGlar for 8 weeks, titrated to reach target FPG of 80-126 mg/dL.
Disclosures: Novo Nordisk funded the trial. Dr. Plum-Mörschel reports no disclosures.