M. Alexander Otto

SAN FRANCISCO – Almost a third of 196 patients (61) were smoke free a year after starting 12 weeks of varenicline therapy and having smoking-cessation counseling in a randomized Australian trial. Only 21% (42) of 196 patients given counseling alone stopped smoking.

The varenicline-plus-counseling results are impressive because the study included people who were on antidepressants and those with depression histories, both of whom had been excluded from several earlier studies of varenicline (Chantix), said lead investigator Dr. Brian Smith of the respiratory medicine unit at the Queen Elizabeth Hospital in Woodville, Australia.

But the most important take-home message of the study was its setup, he said at an international conference of the American Thoracic Society.

The participants had all been hospitalized for at least 1 day for cardiac, respiratory, neurologic, or vascular smoking-related complications. Instead of handing them a quit-smoking hotline card as they walked out the door – the general practice in many hospitals – the investigators had them make their initial counseling service call from the bedside table while they were still in the hospital, Dr. Smith said.

"Only about 6% of patients will make that call" from home. "[We took] the opportunity while they were still inpatients – a captive audience, if you like – to use the bedside phone to make the call. Instead of a 6% success rate, [we had a] 100% success rate," he said.

Patients found a friendly counselor on the other end of the line who emphasized the benefits of quitting instead of the dangers of continuing to smoke. Patients could arrange calls for days when they knew they would be particularly stressed. Counselors would call then to "pull them through," Dr. Smith said.

Both groups got the same standard 5A counseling (ask, advise, assess, assist, and arrange). Patients had the option, if they desired, of several calls a week, but that option wasn’t popular. The mean number of phone calls in the varenicline-plus-counseling arm was 3.8, and in the counseling-only arm it was 4.1.

Varenicline was titrated from 0.5 mg daily to 1 mg twice daily, based largely on nausea. Overall, varenicline patients reported more problems with insomnia (5.1% vs. 2.0% in the counseling-alone group), headache (6.1% vs. 1.5%), vomiting (4.1% vs. 0.5%), and abnormal dreams (6.1% vs. 1.0%).

Despite concerns about the drug, the investigators found no evidence of increased cardiovascular or psychiatric problems in the varenicline group.

"The novel thing of our study is [that we] grabbed the opportunity while these patients were in hospital to get them to make the phone call that otherwise [they] would have been reluctant to make. [We got] them over that hump, got the medication going, [and made] sure they were tolerating it well," Dr. Smith said.

Dr. Smith said he had no disclosures. Pfizer, the maker of Chantix, did not fund and was not involved in the trial, he said. Patients covered at least part of the cost of the drug themselves.

SAN FRANCISCO – Almost a third of 196 patients (61) were smoke free a year after starting 12 weeks of varenicline therapy and having smoking-cessation counseling in a randomized Australian trial. Only 21% (42) of 196 patients given counseling alone stopped smoking.

The varenicline-plus-counseling results are impressive because the study included people who were on antidepressants and those with depression histories, both of whom had been excluded from several earlier studies of varenicline (Chantix), said lead investigator Dr. Brian Smith of the respiratory medicine unit at the Queen Elizabeth Hospital in Woodville, Australia.

But the most important take-home message of the study was its setup, he said at an international conference of the American Thoracic Society.

The participants had all been hospitalized for at least 1 day for cardiac, respiratory, neurologic, or vascular smoking-related complications. Instead of handing them a quit-smoking hotline card as they walked out the door – the general practice in many hospitals – the investigators had them make their initial counseling service call from the bedside table while they were still in the hospital, Dr. Smith said.

"Only about 6% of patients will make that call" from home. "[We took] the opportunity while they were still inpatients – a captive audience, if you like – to use the bedside phone to make the call. Instead of a 6% success rate, [we had a] 100% success rate," he said.

Patients found a friendly counselor on the other end of the line who emphasized the benefits of quitting instead of the dangers of continuing to smoke. Patients could arrange calls for days when they knew they would be particularly stressed. Counselors would call then to "pull them through," Dr. Smith said.

Both groups got the same standard 5A counseling (ask, advise, assess, assist, and arrange). Patients had the option, if they desired, of several calls a week, but that option wasn’t popular. The mean number of phone calls in the varenicline-plus-counseling arm was 3.8, and in the counseling-only arm it was 4.1.

Varenicline was titrated from 0.5 mg daily to 1 mg twice daily, based largely on nausea. Overall, varenicline patients reported more problems with insomnia (5.1% vs. 2.0% in the counseling-alone group), headache (6.1% vs. 1.5%), vomiting (4.1% vs. 0.5%), and abnormal dreams (6.1% vs. 1.0%).

Despite concerns about the drug, the investigators found no evidence of increased cardiovascular or psychiatric problems in the varenicline group.

"The novel thing of our study is [that we] grabbed the opportunity while these patients were in hospital to get them to make the phone call that otherwise [they] would have been reluctant to make. [We got] them over that hump, got the medication going, [and made] sure they were tolerating it well," Dr. Smith said.

Dr. Smith said he had no disclosures. Pfizer, the maker of Chantix, did not fund and was not involved in the trial, he said. Patients covered at least part of the cost of the drug themselves.

SAN FRANCISCO – Almost a third of 196 patients (61) were smoke free a year after starting 12 weeks of varenicline therapy and having smoking-cessation counseling in a randomized Australian trial. Only 21% (42) of 196 patients given counseling alone stopped smoking.

The varenicline-plus-counseling results are impressive because the study included people who were on antidepressants and those with depression histories, both of whom had been excluded from several earlier studies of varenicline (Chantix), said lead investigator Dr. Brian Smith of the respiratory medicine unit at the Queen Elizabeth Hospital in Woodville, Australia.

But the most important take-home message of the study was its setup, he said at an international conference of the American Thoracic Society.

The participants had all been hospitalized for at least 1 day for cardiac, respiratory, neurologic, or vascular smoking-related complications. Instead of handing them a quit-smoking hotline card as they walked out the door – the general practice in many hospitals – the investigators had them make their initial counseling service call from the bedside table while they were still in the hospital, Dr. Smith said.

"Only about 6% of patients will make that call" from home. "[We took] the opportunity while they were still inpatients – a captive audience, if you like – to use the bedside phone to make the call. Instead of a 6% success rate, [we had a] 100% success rate," he said.

Patients found a friendly counselor on the other end of the line who emphasized the benefits of quitting instead of the dangers of continuing to smoke. Patients could arrange calls for days when they knew they would be particularly stressed. Counselors would call then to "pull them through," Dr. Smith said.

Both groups got the same standard 5A counseling (ask, advise, assess, assist, and arrange). Patients had the option, if they desired, of several calls a week, but that option wasn’t popular. The mean number of phone calls in the varenicline-plus-counseling arm was 3.8, and in the counseling-only arm it was 4.1.

Varenicline was titrated from 0.5 mg daily to 1 mg twice daily, based largely on nausea. Overall, varenicline patients reported more problems with insomnia (5.1% vs. 2.0% in the counseling-alone group), headache (6.1% vs. 1.5%), vomiting (4.1% vs. 0.5%), and abnormal dreams (6.1% vs. 1.0%).

Despite concerns about the drug, the investigators found no evidence of increased cardiovascular or psychiatric problems in the varenicline group.

"The novel thing of our study is [that we] grabbed the opportunity while these patients were in hospital to get them to make the phone call that otherwise [they] would have been reluctant to make. [We got] them over that hump, got the medication going, [and made] sure they were tolerating it well," Dr. Smith said.

Dr. Smith said he had no disclosures. Pfizer, the maker of Chantix, did not fund and was not involved in the trial, he said. Patients covered at least part of the cost of the drug themselves.

SAN FRANCISCO – Underlying pulmonary fungal colonization or infection may be the reason that some children with severe asthma don’t respond fully to conventional treatments.

Severe asthma with fungal sensitization (SAFS) has been recognized only recently. In adults, SAFS has been found to respond to oral itraconazole (Am. J. Respir. Crit. Care Med. 2009;179:11-8).

CDC/Dr. Lucille K. Georg

SAFS also occurs in children, according to Dr. Alfin G. Vicencio, chief of pediatric pulmonology and cystic fibrosis at Cohen Children’s Medical Center in New Hyde Park, N.Y., and his colleagues.

The researchers looked at 41 children, teens, and young adults (aged 2-21 years) with severe asthma who were failing level 4 or greater combination asthma therapy, and found that 17 (41.5%) had serum fungal IgE levels above 100 IU/mL and evidence of fungal sensitization on radioallergosorbent or skin-prick tests, indicating SAFS.

Eleven (65%) of those patients were sensitive to more than one fungal species. Aspergillus was the most commonly implicated species, followed by Alternaria, Candida, Cladosporium, Setomelanomma, Mucor, and Penicillium, Dr. Vicencio said at an international conference of the American Thoracic Society.

Boys and girls were affected equally, but SAFS patients tended to be older and have worse results on pulmonary function tests (PFTs) than their peers did, with forced expiratory volume in 1 second (FEV₁) at 73.33% of predicted, for instance, compared with 91.60% in those without SAFS. Some of the children who didn’t meet the criteria for SAFS diagnosis had high IgE levels but no evidence of fungal sensitization, or evidence of fungal sensitivity but normal IgE levels.

"The contribution of fungi to poorly controlled asthma in children is likely to be underestimated, as is the number of patients who might benefit from antifungal therapy," Dr. Vicencio said.

So far, he’s treated about a dozen pediatric SAFS patients with itraconazole. "About half of them have done very well. Their asthma is better controlled. We have documented some PFT improvements. Their IgE levels are variable; some of them are dropping dramatically, and some are not," he said.

Overall, "what it looks like is that fungal sensitization is a risk factor for severe persistent disease. We do believe that there is going to be a role for antifungal agents in certain select populations," he said.

The ongoing series now includes about 60 children with severe, poorly controlled asthma. "Something on the order of 60% actually have fungal sensitization," Dr. Vicencio said.

Sputum testing or bronchoalveolar lavage is planned to see if young SAFS patients actually have fungus in their lungs.

Genotyping is also underway to see if these patients have a mutation in the CHIT1 gene, which encodes for chitotriosidase, a kind of natural antifungal found in mammals. Dr. Vicencio has published a case series in which the mutation was present in six pediatric SAFS patients tested for it. Of the three treated with itraconazole, two responded well and one responded "dramatically" (Pediatrics 2010;126:e982-5).

About a third of the general population has the mutation, and it doesn’t cause disease in most. However, in someone with asthma and fungal exposure, "we believe the mutation" might cause "a perfect storm for asthma," he said.

Dr. Vicencio said he has no relevant disclosures.

SAN FRANCISCO – Underlying pulmonary fungal colonization or infection may be the reason that some children with severe asthma don’t respond fully to conventional treatments.

Severe asthma with fungal sensitization (SAFS) has been recognized only recently. In adults, SAFS has been found to respond to oral itraconazole (Am. J. Respir. Crit. Care Med. 2009;179:11-8).

CDC/Dr. Lucille K. Georg

SAFS also occurs in children, according to Dr. Alfin G. Vicencio, chief of pediatric pulmonology and cystic fibrosis at Cohen Children’s Medical Center in New Hyde Park, N.Y., and his colleagues.

The researchers looked at 41 children, teens, and young adults (aged 2-21 years) with severe asthma who were failing level 4 or greater combination asthma therapy, and found that 17 (41.5%) had serum fungal IgE levels above 100 IU/mL and evidence of fungal sensitization on radioallergosorbent or skin-prick tests, indicating SAFS.

Eleven (65%) of those patients were sensitive to more than one fungal species. Aspergillus was the most commonly implicated species, followed by Alternaria, Candida, Cladosporium, Setomelanomma, Mucor, and Penicillium, Dr. Vicencio said at an international conference of the American Thoracic Society.

Boys and girls were affected equally, but SAFS patients tended to be older and have worse results on pulmonary function tests (PFTs) than their peers did, with forced expiratory volume in 1 second (FEV₁) at 73.33% of predicted, for instance, compared with 91.60% in those without SAFS. Some of the children who didn’t meet the criteria for SAFS diagnosis had high IgE levels but no evidence of fungal sensitization, or evidence of fungal sensitivity but normal IgE levels.

"The contribution of fungi to poorly controlled asthma in children is likely to be underestimated, as is the number of patients who might benefit from antifungal therapy," Dr. Vicencio said.

So far, he’s treated about a dozen pediatric SAFS patients with itraconazole. "About half of them have done very well. Their asthma is better controlled. We have documented some PFT improvements. Their IgE levels are variable; some of them are dropping dramatically, and some are not," he said.

Overall, "what it looks like is that fungal sensitization is a risk factor for severe persistent disease. We do believe that there is going to be a role for antifungal agents in certain select populations," he said.

The ongoing series now includes about 60 children with severe, poorly controlled asthma. "Something on the order of 60% actually have fungal sensitization," Dr. Vicencio said.

Sputum testing or bronchoalveolar lavage is planned to see if young SAFS patients actually have fungus in their lungs.

Genotyping is also underway to see if these patients have a mutation in the CHIT1 gene, which encodes for chitotriosidase, a kind of natural antifungal found in mammals. Dr. Vicencio has published a case series in which the mutation was present in six pediatric SAFS patients tested for it. Of the three treated with itraconazole, two responded well and one responded "dramatically" (Pediatrics 2010;126:e982-5).

About a third of the general population has the mutation, and it doesn’t cause disease in most. However, in someone with asthma and fungal exposure, "we believe the mutation" might cause "a perfect storm for asthma," he said.

Dr. Vicencio said he has no relevant disclosures.

SAN FRANCISCO – Underlying pulmonary fungal colonization or infection may be the reason that some children with severe asthma don’t respond fully to conventional treatments.

Severe asthma with fungal sensitization (SAFS) has been recognized only recently. In adults, SAFS has been found to respond to oral itraconazole (Am. J. Respir. Crit. Care Med. 2009;179:11-8).

CDC/Dr. Lucille K. Georg

SAFS also occurs in children, according to Dr. Alfin G. Vicencio, chief of pediatric pulmonology and cystic fibrosis at Cohen Children’s Medical Center in New Hyde Park, N.Y., and his colleagues.

The researchers looked at 41 children, teens, and young adults (aged 2-21 years) with severe asthma who were failing level 4 or greater combination asthma therapy, and found that 17 (41.5%) had serum fungal IgE levels above 100 IU/mL and evidence of fungal sensitization on radioallergosorbent or skin-prick tests, indicating SAFS.

Eleven (65%) of those patients were sensitive to more than one fungal species. Aspergillus was the most commonly implicated species, followed by Alternaria, Candida, Cladosporium, Setomelanomma, Mucor, and Penicillium, Dr. Vicencio said at an international conference of the American Thoracic Society.

Boys and girls were affected equally, but SAFS patients tended to be older and have worse results on pulmonary function tests (PFTs) than their peers did, with forced expiratory volume in 1 second (FEV₁) at 73.33% of predicted, for instance, compared with 91.60% in those without SAFS. Some of the children who didn’t meet the criteria for SAFS diagnosis had high IgE levels but no evidence of fungal sensitization, or evidence of fungal sensitivity but normal IgE levels.

"The contribution of fungi to poorly controlled asthma in children is likely to be underestimated, as is the number of patients who might benefit from antifungal therapy," Dr. Vicencio said.

So far, he’s treated about a dozen pediatric SAFS patients with itraconazole. "About half of them have done very well. Their asthma is better controlled. We have documented some PFT improvements. Their IgE levels are variable; some of them are dropping dramatically, and some are not," he said.

Overall, "what it looks like is that fungal sensitization is a risk factor for severe persistent disease. We do believe that there is going to be a role for antifungal agents in certain select populations," he said.

The ongoing series now includes about 60 children with severe, poorly controlled asthma. "Something on the order of 60% actually have fungal sensitization," Dr. Vicencio said.

Sputum testing or bronchoalveolar lavage is planned to see if young SAFS patients actually have fungus in their lungs.

Genotyping is also underway to see if these patients have a mutation in the CHIT1 gene, which encodes for chitotriosidase, a kind of natural antifungal found in mammals. Dr. Vicencio has published a case series in which the mutation was present in six pediatric SAFS patients tested for it. Of the three treated with itraconazole, two responded well and one responded "dramatically" (Pediatrics 2010;126:e982-5).

About a third of the general population has the mutation, and it doesn’t cause disease in most. However, in someone with asthma and fungal exposure, "we believe the mutation" might cause "a perfect storm for asthma," he said.

Dr. Vicencio said he has no relevant disclosures.

SAN DIEGO – Metronidazole-induced encephalopathy should be considered when patients on the antibiotic are worked up for suspected multiple sclerosis, according to a case study and literature review from researchers at the Mount Sinai School of Medicine in New York.

A Crohn’s disease patient in his mid-30s who had been on metronidazole for almost 7 years presented there with a years-long diagnosis of multiple sclerosis, but MS wasn’t his problem. Doctors at the center figured out he had metronidazole-induced encephalopathy (MIE).

He had been started on 500 mg three times daily for a few months in early 2004, and then restarted on the same regimen in mid-2005. His first neurologic attack – primarily gait ataxia and dysarthria, along with nonenhancing T2 hyperintensities on MRI – came about a month later. Nonetheless, he remained on 250 mg twice daily to 500 mg three times daily until early 2011, and suffered several more attacks, notably after dosage increases. His cumulative metronidazole dose was 2,133.5 g.

Forty-one days after the patient stopped taking metronidazole, his ataxia and dysarthria were almost completely resolved; 7 months later, he was almost clear on brain MRI, with only small residua. His sole remaining complaints were poor memory, attention, and motivation.

"Neurologists should be alert to the possibility of metronidazole-induced encephalopathy in the differential diagnosis of demyelinating disease, especially in view of its potential reversibility," said lead investigator Dr. Corey McGraw, a neurologist at the school’s Corinne Goldsmith Dickinson Center for Multiple Sclerosis.

It’s widely known that metronidazole can cause peripheral neuropathy, but it is much less known that it can also cause toxic encephalopathy that mimics demyelination, he said at the Fourth Cooperative Meeting on Multiple Sclerosis.

"This is an under-recognized neurologic disease among American neurologists. Most of the [63 reported] cases have been in Korea and India, where it may be more recognized. I and my much-more-senior colleagues had never heard of metronidazole-induced encephalopathy before this case. Neurologists are probably missing it," Dr. McGraw said.

The giveaway in the Crohn’s patient’s case was that he had the same signs and symptoms with each attack, whereas MS tends to migrate around the body.

In many ways, he was a typical MIE patient.

Of the 63 cases reviewed by Dr. McGraw, 44 (70%) had MRI T2 hyperintensities of the cerebellar dentate nuclei that were the same as those found in the Crohn’s disease patient, and 19 (30%) had T2 hyperintensities of the corpus callosum splenium. Those and other MIE findings are "classic for a toxic encephalopathy," he said at the meeting, which was sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dysarthria and gait ataxia are common, too, as well as problems with mentation, arm coordination, leg strength, and seizures.

The cumulative mean metronidazole dose in the 63 cases was 106.1 g (range, 3-1,095 g). The mean time from first dose to first neurologic attack was 67 days (range, 2-730 days). Symptoms resolved in anywhere from 1 to 420 days after metronidazole was stopped.

The "wide ranges in time to clinical manifestations and total cumulative doses may obscure the appropriate diagnosis," Dr. McGraw noted.

Dr. McGraw said that he had no relevant disclosures.

SAN DIEGO – Metronidazole-induced encephalopathy should be considered when patients on the antibiotic are worked up for suspected multiple sclerosis, according to a case study and literature review from researchers at the Mount Sinai School of Medicine in New York.

A Crohn’s disease patient in his mid-30s who had been on metronidazole for almost 7 years presented there with a years-long diagnosis of multiple sclerosis, but MS wasn’t his problem. Doctors at the center figured out he had metronidazole-induced encephalopathy (MIE).

He had been started on 500 mg three times daily for a few months in early 2004, and then restarted on the same regimen in mid-2005. His first neurologic attack – primarily gait ataxia and dysarthria, along with nonenhancing T2 hyperintensities on MRI – came about a month later. Nonetheless, he remained on 250 mg twice daily to 500 mg three times daily until early 2011, and suffered several more attacks, notably after dosage increases. His cumulative metronidazole dose was 2,133.5 g.

Forty-one days after the patient stopped taking metronidazole, his ataxia and dysarthria were almost completely resolved; 7 months later, he was almost clear on brain MRI, with only small residua. His sole remaining complaints were poor memory, attention, and motivation.

"Neurologists should be alert to the possibility of metronidazole-induced encephalopathy in the differential diagnosis of demyelinating disease, especially in view of its potential reversibility," said lead investigator Dr. Corey McGraw, a neurologist at the school’s Corinne Goldsmith Dickinson Center for Multiple Sclerosis.

It’s widely known that metronidazole can cause peripheral neuropathy, but it is much less known that it can also cause toxic encephalopathy that mimics demyelination, he said at the Fourth Cooperative Meeting on Multiple Sclerosis.

"This is an under-recognized neurologic disease among American neurologists. Most of the [63 reported] cases have been in Korea and India, where it may be more recognized. I and my much-more-senior colleagues had never heard of metronidazole-induced encephalopathy before this case. Neurologists are probably missing it," Dr. McGraw said.

The giveaway in the Crohn’s patient’s case was that he had the same signs and symptoms with each attack, whereas MS tends to migrate around the body.

In many ways, he was a typical MIE patient.

Of the 63 cases reviewed by Dr. McGraw, 44 (70%) had MRI T2 hyperintensities of the cerebellar dentate nuclei that were the same as those found in the Crohn’s disease patient, and 19 (30%) had T2 hyperintensities of the corpus callosum splenium. Those and other MIE findings are "classic for a toxic encephalopathy," he said at the meeting, which was sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dysarthria and gait ataxia are common, too, as well as problems with mentation, arm coordination, leg strength, and seizures.

The cumulative mean metronidazole dose in the 63 cases was 106.1 g (range, 3-1,095 g). The mean time from first dose to first neurologic attack was 67 days (range, 2-730 days). Symptoms resolved in anywhere from 1 to 420 days after metronidazole was stopped.

The "wide ranges in time to clinical manifestations and total cumulative doses may obscure the appropriate diagnosis," Dr. McGraw noted.

Dr. McGraw said that he had no relevant disclosures.

SAN DIEGO – Metronidazole-induced encephalopathy should be considered when patients on the antibiotic are worked up for suspected multiple sclerosis, according to a case study and literature review from researchers at the Mount Sinai School of Medicine in New York.

A Crohn’s disease patient in his mid-30s who had been on metronidazole for almost 7 years presented there with a years-long diagnosis of multiple sclerosis, but MS wasn’t his problem. Doctors at the center figured out he had metronidazole-induced encephalopathy (MIE).

He had been started on 500 mg three times daily for a few months in early 2004, and then restarted on the same regimen in mid-2005. His first neurologic attack – primarily gait ataxia and dysarthria, along with nonenhancing T2 hyperintensities on MRI – came about a month later. Nonetheless, he remained on 250 mg twice daily to 500 mg three times daily until early 2011, and suffered several more attacks, notably after dosage increases. His cumulative metronidazole dose was 2,133.5 g.

Forty-one days after the patient stopped taking metronidazole, his ataxia and dysarthria were almost completely resolved; 7 months later, he was almost clear on brain MRI, with only small residua. His sole remaining complaints were poor memory, attention, and motivation.

"Neurologists should be alert to the possibility of metronidazole-induced encephalopathy in the differential diagnosis of demyelinating disease, especially in view of its potential reversibility," said lead investigator Dr. Corey McGraw, a neurologist at the school’s Corinne Goldsmith Dickinson Center for Multiple Sclerosis.

It’s widely known that metronidazole can cause peripheral neuropathy, but it is much less known that it can also cause toxic encephalopathy that mimics demyelination, he said at the Fourth Cooperative Meeting on Multiple Sclerosis.

"This is an under-recognized neurologic disease among American neurologists. Most of the [63 reported] cases have been in Korea and India, where it may be more recognized. I and my much-more-senior colleagues had never heard of metronidazole-induced encephalopathy before this case. Neurologists are probably missing it," Dr. McGraw said.

The giveaway in the Crohn’s patient’s case was that he had the same signs and symptoms with each attack, whereas MS tends to migrate around the body.

In many ways, he was a typical MIE patient.

Of the 63 cases reviewed by Dr. McGraw, 44 (70%) had MRI T2 hyperintensities of the cerebellar dentate nuclei that were the same as those found in the Crohn’s disease patient, and 19 (30%) had T2 hyperintensities of the corpus callosum splenium. Those and other MIE findings are "classic for a toxic encephalopathy," he said at the meeting, which was sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dysarthria and gait ataxia are common, too, as well as problems with mentation, arm coordination, leg strength, and seizures.

The cumulative mean metronidazole dose in the 63 cases was 106.1 g (range, 3-1,095 g). The mean time from first dose to first neurologic attack was 67 days (range, 2-730 days). Symptoms resolved in anywhere from 1 to 420 days after metronidazole was stopped.

The "wide ranges in time to clinical manifestations and total cumulative doses may obscure the appropriate diagnosis," Dr. McGraw noted.

Dr. McGraw said that he had no relevant disclosures.

SAN FRANCISCO – Clinicians may have become too enthusiastic about using noninvasive ventilation in lieu of intubation and mechanical ventilation, according to a nationwide database study from the Boston University Pulmonary Center.

Noninvasive ventilation (NIV) use tripled during 2000-2009 for acute respiratory failure (ARF) caused by chronic obstructive pulmonary disease, for which there is good evidence of a mortality benefit (Cochrane Database Syst. Rev. 2004;1:CD004104).

But in the same period, use increased 3.4-fold for ARF caused by conditions for which there is little evidence to support its use, including asthma, pneumonia, neurologic diseases, and nonpulmonary sepsis. Currently, about half of ARF patients receiving NIV have COPD, while half have other conditions.

The investigators found that patients are more likely to fail NIV – and subsequently receive mechanical ventilation – when it’s used for those conditions instead of COPD (odds ratio, 1.12; 95% confidence interval, 1.08-1.16). Overall, 12% of COPD patients failed NIV, compared with 18% of non-COPD patients (P less than .001).

Of the study patients who failed NIV, 37% died, compared with 35% who received mechanical ventilation alone (P = .002).

The researchers analyzed approximately 11 million hospital records from 2000-2009 coded for ARF in the Agency for Healthcare Research and Quality’s Nationwide Inpatient Sample (NIS) database, excluding patients with sleep apnea.

"People might have a little too much faith in noninvasive ventilation. They see it work really well in COPD, so they think it might work well in everyone," said lead investigator Dr. Allan J. Walkey, director of pulmonary and critical care education at Boston University.

He said the study’s take-home message is to "think twice if you are going to put a noninvasive ventilator on someone without COPD or acute cardiogenic pulmonary edema," for which there is also strong evidence of benefit (Cochrane Database Syst. Rev. 2008;3:CD005351). In other patients, "there’s generally not good evidence to support use of noninvasive ventilation, and [our study suggests] it may be associated with worse outcomes. [Those patients] need to be monitored closely, and if they are showing signs of failure, they need to be intubated," he said at an international conference of the American Thoracic Society.

It’s unclear why NIV might be problematic for some. Perhaps not being able to suction secretions out of an endotracheal tube leads to problems in pneumonia. Maybe fading sensorium in other conditions increases the likelihood of gastric aspiration if there’s no tube in place to protect the airway, Dr. Walkey said.

Although the NIS database does not include vital signs, lab reports, and other patient-level clinical data, the researchers used an algorithm to assess and control for disease severity. "There is growing evidence that the adjustment of disease severity using data you do have in large databases" – such as information on comorbidities, billing codes, and demographics – "is actually as accurate as those based on disease severity scores," Dr. Walkey said (Crit. Care Med. 2011;39:2425-30).

The researchers also found wide regional variations in NIV use, with the heaviest use in the Northeast and the lowest in the Midwest; use was roughly equal in teaching and nonteaching hospitals.

Insurance claims for acute respiratory failure increased from 818,781 in 2000 to 1,531,352 in 2009, with an associated 25% decrease in ARF mortality over that period.

Dr. Walkey said he had no financial disclosures.

SAN FRANCISCO – Clinicians may have become too enthusiastic about using noninvasive ventilation in lieu of intubation and mechanical ventilation, according to a nationwide database study from the Boston University Pulmonary Center.

Noninvasive ventilation (NIV) use tripled during 2000-2009 for acute respiratory failure (ARF) caused by chronic obstructive pulmonary disease, for which there is good evidence of a mortality benefit (Cochrane Database Syst. Rev. 2004;1:CD004104).

But in the same period, use increased 3.4-fold for ARF caused by conditions for which there is little evidence to support its use, including asthma, pneumonia, neurologic diseases, and nonpulmonary sepsis. Currently, about half of ARF patients receiving NIV have COPD, while half have other conditions.

The investigators found that patients are more likely to fail NIV – and subsequently receive mechanical ventilation – when it’s used for those conditions instead of COPD (odds ratio, 1.12; 95% confidence interval, 1.08-1.16). Overall, 12% of COPD patients failed NIV, compared with 18% of non-COPD patients (P less than .001).

Of the study patients who failed NIV, 37% died, compared with 35% who received mechanical ventilation alone (P = .002).

The researchers analyzed approximately 11 million hospital records from 2000-2009 coded for ARF in the Agency for Healthcare Research and Quality’s Nationwide Inpatient Sample (NIS) database, excluding patients with sleep apnea.

"People might have a little too much faith in noninvasive ventilation. They see it work really well in COPD, so they think it might work well in everyone," said lead investigator Dr. Allan J. Walkey, director of pulmonary and critical care education at Boston University.

He said the study’s take-home message is to "think twice if you are going to put a noninvasive ventilator on someone without COPD or acute cardiogenic pulmonary edema," for which there is also strong evidence of benefit (Cochrane Database Syst. Rev. 2008;3:CD005351). In other patients, "there’s generally not good evidence to support use of noninvasive ventilation, and [our study suggests] it may be associated with worse outcomes. [Those patients] need to be monitored closely, and if they are showing signs of failure, they need to be intubated," he said at an international conference of the American Thoracic Society.

It’s unclear why NIV might be problematic for some. Perhaps not being able to suction secretions out of an endotracheal tube leads to problems in pneumonia. Maybe fading sensorium in other conditions increases the likelihood of gastric aspiration if there’s no tube in place to protect the airway, Dr. Walkey said.

Although the NIS database does not include vital signs, lab reports, and other patient-level clinical data, the researchers used an algorithm to assess and control for disease severity. "There is growing evidence that the adjustment of disease severity using data you do have in large databases" – such as information on comorbidities, billing codes, and demographics – "is actually as accurate as those based on disease severity scores," Dr. Walkey said (Crit. Care Med. 2011;39:2425-30).

The researchers also found wide regional variations in NIV use, with the heaviest use in the Northeast and the lowest in the Midwest; use was roughly equal in teaching and nonteaching hospitals.

Insurance claims for acute respiratory failure increased from 818,781 in 2000 to 1,531,352 in 2009, with an associated 25% decrease in ARF mortality over that period.

Dr. Walkey said he had no financial disclosures.

SAN FRANCISCO – Clinicians may have become too enthusiastic about using noninvasive ventilation in lieu of intubation and mechanical ventilation, according to a nationwide database study from the Boston University Pulmonary Center.

Noninvasive ventilation (NIV) use tripled during 2000-2009 for acute respiratory failure (ARF) caused by chronic obstructive pulmonary disease, for which there is good evidence of a mortality benefit (Cochrane Database Syst. Rev. 2004;1:CD004104).

But in the same period, use increased 3.4-fold for ARF caused by conditions for which there is little evidence to support its use, including asthma, pneumonia, neurologic diseases, and nonpulmonary sepsis. Currently, about half of ARF patients receiving NIV have COPD, while half have other conditions.

The investigators found that patients are more likely to fail NIV – and subsequently receive mechanical ventilation – when it’s used for those conditions instead of COPD (odds ratio, 1.12; 95% confidence interval, 1.08-1.16). Overall, 12% of COPD patients failed NIV, compared with 18% of non-COPD patients (P less than .001).

Of the study patients who failed NIV, 37% died, compared with 35% who received mechanical ventilation alone (P = .002).

The researchers analyzed approximately 11 million hospital records from 2000-2009 coded for ARF in the Agency for Healthcare Research and Quality’s Nationwide Inpatient Sample (NIS) database, excluding patients with sleep apnea.

"People might have a little too much faith in noninvasive ventilation. They see it work really well in COPD, so they think it might work well in everyone," said lead investigator Dr. Allan J. Walkey, director of pulmonary and critical care education at Boston University.

He said the study’s take-home message is to "think twice if you are going to put a noninvasive ventilator on someone without COPD or acute cardiogenic pulmonary edema," for which there is also strong evidence of benefit (Cochrane Database Syst. Rev. 2008;3:CD005351). In other patients, "there’s generally not good evidence to support use of noninvasive ventilation, and [our study suggests] it may be associated with worse outcomes. [Those patients] need to be monitored closely, and if they are showing signs of failure, they need to be intubated," he said at an international conference of the American Thoracic Society.

It’s unclear why NIV might be problematic for some. Perhaps not being able to suction secretions out of an endotracheal tube leads to problems in pneumonia. Maybe fading sensorium in other conditions increases the likelihood of gastric aspiration if there’s no tube in place to protect the airway, Dr. Walkey said.

Although the NIS database does not include vital signs, lab reports, and other patient-level clinical data, the researchers used an algorithm to assess and control for disease severity. "There is growing evidence that the adjustment of disease severity using data you do have in large databases" – such as information on comorbidities, billing codes, and demographics – "is actually as accurate as those based on disease severity scores," Dr. Walkey said (Crit. Care Med. 2011;39:2425-30).

The researchers also found wide regional variations in NIV use, with the heaviest use in the Northeast and the lowest in the Midwest; use was roughly equal in teaching and nonteaching hospitals.

Insurance claims for acute respiratory failure increased from 818,781 in 2000 to 1,531,352 in 2009, with an associated 25% decrease in ARF mortality over that period.

Dr. Walkey said he had no financial disclosures.

SAN DIEGO – Tetrahydrocannabinol, the main active ingredient in marijuana, did not slow the progression of multiple sclerosis in a 3-year, randomized trial of 493 British patients with primary or secondary progressive forms of the disease.

Some patients with lower baseline EDSS (Expanded Disability Status Scale) scores appeared to have delayed progression, but the trial did not have enough statistical power to allow comparison of subgroups.

©ron hilton/iStockphoto.com

In the Cannabinoid Use in Progressive Inflammatory Brain Disease (CUPID) trial, investigators randomized 329 patients to 14-28 mg of tetrahydrocannabinol (THC)/day in capsule form based on weight, and 164 to placebo. Their mean baseline EDSS score was about 5.8 (range, 4.0-6.5). Patients were, on average, 52 years old; and about 60% were women.

None were on disease-modifying therapies, but most were on pain relievers and other medications for symptom relief. The patients agreed to otherwise abstain from marijuana during the study.

Compared with placebo, the hazard ratio for EDSS progression in the THC group – defined as a 1-point increase for patients starting at or below 5, and a half-point increase for those starting above – was 0.92 (95% CI, 0.68-1.23) after adjustment for disease type, age, and other variables.

There were no statistical differences in brain volume loss on MRI, Multiple Sclerosis Impact Scale scores, and several secondary outcomes, including the 25-foot timed walk and 9-hole peg tests.

On post hoc analysis, there was a hint of delayed progression in patients with baseline EDSS scores below 6; 26 (76%) of 34 placebo patients in that group progressed, compared with only 44 (58%) of 76 in the THC group.

"The lower EDSS scores do seem to suggest a treatment effect, but we did not have much power to detect that effect. I do think that there are probably going to be subgroups that do respond more than others," said lead investigator Dr. John Zajicek, a professor of clinical neuroscience at Plymouth (England) University.

Overall, he called the results "disappointing." Although "there is sufficient evidence to use cannabinoids" for relieving muscle stiffness, spasticity, pain, urinary disturbances, and other MS symptoms, it could be that THC simply does not slow progression in primary or secondary progressive MS. No drug has yet been proven to do so, Dr. Zajicek said at the Fourth Cooperative Meeting on Multiple Sclerosis.

The results might also have been obscured because there was very little progression in either the THC or placebo groups. "We were expecting 70% progression, but we got just over 40%, so most of the outcome measures did not change very much over 3 years. It’s very difficult to find a treatment effect when your outcome measures aren’t changing," he said.

About 60% of the THC patients complained of dizziness or lightheadedness, and 51% of thought or perception changes, both far more common than in the placebo group, but fewer THC patients reported musculoskeletal pain (26% vs. 37% in the placebo group) and fewer developed urinary tract infections (26% vs. 35%).

The meeting was sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis. Dr. Zajicek said he had no relevant disclosures.

SAN DIEGO – Tetrahydrocannabinol, the main active ingredient in marijuana, did not slow the progression of multiple sclerosis in a 3-year, randomized trial of 493 British patients with primary or secondary progressive forms of the disease.

Some patients with lower baseline EDSS (Expanded Disability Status Scale) scores appeared to have delayed progression, but the trial did not have enough statistical power to allow comparison of subgroups.

©ron hilton/iStockphoto.com

In the Cannabinoid Use in Progressive Inflammatory Brain Disease (CUPID) trial, investigators randomized 329 patients to 14-28 mg of tetrahydrocannabinol (THC)/day in capsule form based on weight, and 164 to placebo. Their mean baseline EDSS score was about 5.8 (range, 4.0-6.5). Patients were, on average, 52 years old; and about 60% were women.

None were on disease-modifying therapies, but most were on pain relievers and other medications for symptom relief. The patients agreed to otherwise abstain from marijuana during the study.

Compared with placebo, the hazard ratio for EDSS progression in the THC group – defined as a 1-point increase for patients starting at or below 5, and a half-point increase for those starting above – was 0.92 (95% CI, 0.68-1.23) after adjustment for disease type, age, and other variables.

There were no statistical differences in brain volume loss on MRI, Multiple Sclerosis Impact Scale scores, and several secondary outcomes, including the 25-foot timed walk and 9-hole peg tests.

On post hoc analysis, there was a hint of delayed progression in patients with baseline EDSS scores below 6; 26 (76%) of 34 placebo patients in that group progressed, compared with only 44 (58%) of 76 in the THC group.

"The lower EDSS scores do seem to suggest a treatment effect, but we did not have much power to detect that effect. I do think that there are probably going to be subgroups that do respond more than others," said lead investigator Dr. John Zajicek, a professor of clinical neuroscience at Plymouth (England) University.

Overall, he called the results "disappointing." Although "there is sufficient evidence to use cannabinoids" for relieving muscle stiffness, spasticity, pain, urinary disturbances, and other MS symptoms, it could be that THC simply does not slow progression in primary or secondary progressive MS. No drug has yet been proven to do so, Dr. Zajicek said at the Fourth Cooperative Meeting on Multiple Sclerosis.

The results might also have been obscured because there was very little progression in either the THC or placebo groups. "We were expecting 70% progression, but we got just over 40%, so most of the outcome measures did not change very much over 3 years. It’s very difficult to find a treatment effect when your outcome measures aren’t changing," he said.

About 60% of the THC patients complained of dizziness or lightheadedness, and 51% of thought or perception changes, both far more common than in the placebo group, but fewer THC patients reported musculoskeletal pain (26% vs. 37% in the placebo group) and fewer developed urinary tract infections (26% vs. 35%).

The meeting was sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis. Dr. Zajicek said he had no relevant disclosures.

SAN DIEGO – Tetrahydrocannabinol, the main active ingredient in marijuana, did not slow the progression of multiple sclerosis in a 3-year, randomized trial of 493 British patients with primary or secondary progressive forms of the disease.

Some patients with lower baseline EDSS (Expanded Disability Status Scale) scores appeared to have delayed progression, but the trial did not have enough statistical power to allow comparison of subgroups.

©ron hilton/iStockphoto.com

In the Cannabinoid Use in Progressive Inflammatory Brain Disease (CUPID) trial, investigators randomized 329 patients to 14-28 mg of tetrahydrocannabinol (THC)/day in capsule form based on weight, and 164 to placebo. Their mean baseline EDSS score was about 5.8 (range, 4.0-6.5). Patients were, on average, 52 years old; and about 60% were women.

None were on disease-modifying therapies, but most were on pain relievers and other medications for symptom relief. The patients agreed to otherwise abstain from marijuana during the study.

Compared with placebo, the hazard ratio for EDSS progression in the THC group – defined as a 1-point increase for patients starting at or below 5, and a half-point increase for those starting above – was 0.92 (95% CI, 0.68-1.23) after adjustment for disease type, age, and other variables.

There were no statistical differences in brain volume loss on MRI, Multiple Sclerosis Impact Scale scores, and several secondary outcomes, including the 25-foot timed walk and 9-hole peg tests.

On post hoc analysis, there was a hint of delayed progression in patients with baseline EDSS scores below 6; 26 (76%) of 34 placebo patients in that group progressed, compared with only 44 (58%) of 76 in the THC group.

"The lower EDSS scores do seem to suggest a treatment effect, but we did not have much power to detect that effect. I do think that there are probably going to be subgroups that do respond more than others," said lead investigator Dr. John Zajicek, a professor of clinical neuroscience at Plymouth (England) University.

Overall, he called the results "disappointing." Although "there is sufficient evidence to use cannabinoids" for relieving muscle stiffness, spasticity, pain, urinary disturbances, and other MS symptoms, it could be that THC simply does not slow progression in primary or secondary progressive MS. No drug has yet been proven to do so, Dr. Zajicek said at the Fourth Cooperative Meeting on Multiple Sclerosis.

The results might also have been obscured because there was very little progression in either the THC or placebo groups. "We were expecting 70% progression, but we got just over 40%, so most of the outcome measures did not change very much over 3 years. It’s very difficult to find a treatment effect when your outcome measures aren’t changing," he said.

About 60% of the THC patients complained of dizziness or lightheadedness, and 51% of thought or perception changes, both far more common than in the placebo group, but fewer THC patients reported musculoskeletal pain (26% vs. 37% in the placebo group) and fewer developed urinary tract infections (26% vs. 35%).

The meeting was sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis. Dr. Zajicek said he had no relevant disclosures.

NEW ORLEANS – Advanced Parkinson’s disease patients had significantly less "off" time – without increased dyskinesia – when they were treated with levodopa-carbidopa intestinal gel rather than immediate-release oral levodopa-carbidopa in a phase III, randomized trial sponsored by the gel’s maker, Abbott Laboratories.

The trial is part of Abbott’s phase III development program for the drug; the company plans to submit an approval package to the Food and Drug Administration this year. The gel has been on the market for several years in Europe and elsewhere, where it has been sold under the name Duodopa.

Commenting on his blog, the medical director of the National Parkinson Foundation, Dr. Michael Okun, wrote, "Duodopa will likely be a great choice for many patients with on-off fluctuations, and will in most cases allow discontinuation of oral PD drugs."

"However, Duodopa does require a very attentive caregiver who will need to attend to device management, skin management (for the tube), and also attend to medication refills. Early studies of Duodopa have revealed high rates of device-related problems with the intestinal tube," such as clogging, kinking, and moving out of the correct location, said Dr. Okun, codirector of the center for movement disorders and neurorestoration at the University of Florida, Gainesville.

The idea is that by infusing levodopa-carbidopa continuously, patients can avoid the fluctuating plasma levodopa levels associated with oral formulations.

Perhaps those fluctuating levels induce molecular and physiological changes in dopamine receptors "that ultimately result in motor complications. This has led to the theory that if you can deliver levodopa more continuously, it would be more physiologic and might avoid these problems," said lead investigator Dr. Warren Olanow, director of the Bendheim Parkinson Center at the Mount Sinai Medical Center in New York City. He presented the findings on behalf of Abbott.

The gel is delivered through a surgically placed gastrojejunostomy tube, which is connected to a portable pump that is worn around the waist for 16 hours a day.

In the 12-week trial, 37 patients with motor complications that were inadequately controlled by oral medications were randomized to levodopa-carbidopa intestinal gel (LCIG) plus placebo capsules; 34 were randomized to levodopa-carbidopa immediate release (LC-IR) tablets plus placebo gel infusions.

The LCIG group had a mean 1.91 hours less "off" time each day than did the LC-IR group (P = .0015), and a mean 1.86 hours more daily "on" time without troublesome dyskinesia (P = .0059).

But the tube placement caused complications in about half of the patients, and 23 (32.4%) had pain with the procedure. In all, 19 (51%) LCIG patients and 11 (32%) LC-IR patients complained of abdominal pain; 11 (30%) LCIG patients and 7 (21%) LC-IR patients complained of nausea. Although common, the side effects were mostly transient, Dr. Olanow said.

Overall, the benefits of the gel "in a patient group that cannot be satisfactorily controlled with standard levodopa represent an important step forward in our efforts to treat advanced PD patients," he said.

With several years of use in Europe and elsewhere, the gel already has a fairly robust body of published literature. In a small, randomized, pharmacokinetics study that compared it to sustained-release oral levodopa-carbidopa, the gel patients had steadier levodopa plasma concentrations and greater "on" time (Clin. Neuropharmacol. 2003;26:156-63).

Another trial compared subthalamic nucleus deep brain stimulation (DBS) in 20 patients to Duodopa in 20 others who were unsuitable for DBS neurosurgery. Both groups had a significant improvement in Unified Parkinson’s Disease Rating Scale scores and considerable off-time reduction. Only the DBS group had a significant improvement in dyskinesia duration and disability, but also a significant drop in verbal fluency that was not seen with Duodopa. Duodopa, however, had more procedure-related complications (Mov. Disord. 2011;26:664-70).

Dr. Olanow has received personal compensation for activities with Abbott, Teva/Lundbeck, Novartis/Orion, Ceregene, Merck Serono, Ipsen, and Impax. He holds stock or stock options in Clintrex and Ceregene. Dr. Okun has no current, relevant disclosures.

NEW ORLEANS – Advanced Parkinson’s disease patients had significantly less "off" time – without increased dyskinesia – when they were treated with levodopa-carbidopa intestinal gel rather than immediate-release oral levodopa-carbidopa in a phase III, randomized trial sponsored by the gel’s maker, Abbott Laboratories.

The trial is part of Abbott’s phase III development program for the drug; the company plans to submit an approval package to the Food and Drug Administration this year. The gel has been on the market for several years in Europe and elsewhere, where it has been sold under the name Duodopa.

Commenting on his blog, the medical director of the National Parkinson Foundation, Dr. Michael Okun, wrote, "Duodopa will likely be a great choice for many patients with on-off fluctuations, and will in most cases allow discontinuation of oral PD drugs."

"However, Duodopa does require a very attentive caregiver who will need to attend to device management, skin management (for the tube), and also attend to medication refills. Early studies of Duodopa have revealed high rates of device-related problems with the intestinal tube," such as clogging, kinking, and moving out of the correct location, said Dr. Okun, codirector of the center for movement disorders and neurorestoration at the University of Florida, Gainesville.

The idea is that by infusing levodopa-carbidopa continuously, patients can avoid the fluctuating plasma levodopa levels associated with oral formulations.

Perhaps those fluctuating levels induce molecular and physiological changes in dopamine receptors "that ultimately result in motor complications. This has led to the theory that if you can deliver levodopa more continuously, it would be more physiologic and might avoid these problems," said lead investigator Dr. Warren Olanow, director of the Bendheim Parkinson Center at the Mount Sinai Medical Center in New York City. He presented the findings on behalf of Abbott.

The gel is delivered through a surgically placed gastrojejunostomy tube, which is connected to a portable pump that is worn around the waist for 16 hours a day.

In the 12-week trial, 37 patients with motor complications that were inadequately controlled by oral medications were randomized to levodopa-carbidopa intestinal gel (LCIG) plus placebo capsules; 34 were randomized to levodopa-carbidopa immediate release (LC-IR) tablets plus placebo gel infusions.

The LCIG group had a mean 1.91 hours less "off" time each day than did the LC-IR group (P = .0015), and a mean 1.86 hours more daily "on" time without troublesome dyskinesia (P = .0059).

But the tube placement caused complications in about half of the patients, and 23 (32.4%) had pain with the procedure. In all, 19 (51%) LCIG patients and 11 (32%) LC-IR patients complained of abdominal pain; 11 (30%) LCIG patients and 7 (21%) LC-IR patients complained of nausea. Although common, the side effects were mostly transient, Dr. Olanow said.

Overall, the benefits of the gel "in a patient group that cannot be satisfactorily controlled with standard levodopa represent an important step forward in our efforts to treat advanced PD patients," he said.

With several years of use in Europe and elsewhere, the gel already has a fairly robust body of published literature. In a small, randomized, pharmacokinetics study that compared it to sustained-release oral levodopa-carbidopa, the gel patients had steadier levodopa plasma concentrations and greater "on" time (Clin. Neuropharmacol. 2003;26:156-63).

Another trial compared subthalamic nucleus deep brain stimulation (DBS) in 20 patients to Duodopa in 20 others who were unsuitable for DBS neurosurgery. Both groups had a significant improvement in Unified Parkinson’s Disease Rating Scale scores and considerable off-time reduction. Only the DBS group had a significant improvement in dyskinesia duration and disability, but also a significant drop in verbal fluency that was not seen with Duodopa. Duodopa, however, had more procedure-related complications (Mov. Disord. 2011;26:664-70).

Dr. Olanow has received personal compensation for activities with Abbott, Teva/Lundbeck, Novartis/Orion, Ceregene, Merck Serono, Ipsen, and Impax. He holds stock or stock options in Clintrex and Ceregene. Dr. Okun has no current, relevant disclosures.

NEW ORLEANS – Advanced Parkinson’s disease patients had significantly less "off" time – without increased dyskinesia – when they were treated with levodopa-carbidopa intestinal gel rather than immediate-release oral levodopa-carbidopa in a phase III, randomized trial sponsored by the gel’s maker, Abbott Laboratories.

The trial is part of Abbott’s phase III development program for the drug; the company plans to submit an approval package to the Food and Drug Administration this year. The gel has been on the market for several years in Europe and elsewhere, where it has been sold under the name Duodopa.

Commenting on his blog, the medical director of the National Parkinson Foundation, Dr. Michael Okun, wrote, "Duodopa will likely be a great choice for many patients with on-off fluctuations, and will in most cases allow discontinuation of oral PD drugs."

"However, Duodopa does require a very attentive caregiver who will need to attend to device management, skin management (for the tube), and also attend to medication refills. Early studies of Duodopa have revealed high rates of device-related problems with the intestinal tube," such as clogging, kinking, and moving out of the correct location, said Dr. Okun, codirector of the center for movement disorders and neurorestoration at the University of Florida, Gainesville.

The idea is that by infusing levodopa-carbidopa continuously, patients can avoid the fluctuating plasma levodopa levels associated with oral formulations.

Perhaps those fluctuating levels induce molecular and physiological changes in dopamine receptors "that ultimately result in motor complications. This has led to the theory that if you can deliver levodopa more continuously, it would be more physiologic and might avoid these problems," said lead investigator Dr. Warren Olanow, director of the Bendheim Parkinson Center at the Mount Sinai Medical Center in New York City. He presented the findings on behalf of Abbott.

The gel is delivered through a surgically placed gastrojejunostomy tube, which is connected to a portable pump that is worn around the waist for 16 hours a day.

In the 12-week trial, 37 patients with motor complications that were inadequately controlled by oral medications were randomized to levodopa-carbidopa intestinal gel (LCIG) plus placebo capsules; 34 were randomized to levodopa-carbidopa immediate release (LC-IR) tablets plus placebo gel infusions.

The LCIG group had a mean 1.91 hours less "off" time each day than did the LC-IR group (P = .0015), and a mean 1.86 hours more daily "on" time without troublesome dyskinesia (P = .0059).

But the tube placement caused complications in about half of the patients, and 23 (32.4%) had pain with the procedure. In all, 19 (51%) LCIG patients and 11 (32%) LC-IR patients complained of abdominal pain; 11 (30%) LCIG patients and 7 (21%) LC-IR patients complained of nausea. Although common, the side effects were mostly transient, Dr. Olanow said.

Overall, the benefits of the gel "in a patient group that cannot be satisfactorily controlled with standard levodopa represent an important step forward in our efforts to treat advanced PD patients," he said.

With several years of use in Europe and elsewhere, the gel already has a fairly robust body of published literature. In a small, randomized, pharmacokinetics study that compared it to sustained-release oral levodopa-carbidopa, the gel patients had steadier levodopa plasma concentrations and greater "on" time (Clin. Neuropharmacol. 2003;26:156-63).

Another trial compared subthalamic nucleus deep brain stimulation (DBS) in 20 patients to Duodopa in 20 others who were unsuitable for DBS neurosurgery. Both groups had a significant improvement in Unified Parkinson’s Disease Rating Scale scores and considerable off-time reduction. Only the DBS group had a significant improvement in dyskinesia duration and disability, but also a significant drop in verbal fluency that was not seen with Duodopa. Duodopa, however, had more procedure-related complications (Mov. Disord. 2011;26:664-70).

Dr. Olanow has received personal compensation for activities with Abbott, Teva/Lundbeck, Novartis/Orion, Ceregene, Merck Serono, Ipsen, and Impax. He holds stock or stock options in Clintrex and Ceregene. Dr. Okun has no current, relevant disclosures.

SAN FRANCISCO – Outpatient sleep apnea management by primary care physicians and nurses works as well as management by specialists in a sleep center and is less expensive, Australian researchers reported at the International Conference of the American Thoracic Society.

The team randomized 155 patients with symptomatic, moderate to severe obstructive sleep apnea (OSA) – all with baseline Epworth Sleepiness Scale (ESS) scores of at least 8 – to either standard management by sleep specialists with sleep-lab testing or outpatient management by their primary care doctor and a community-based nurse. Primary care management often involved home-based, autotitrating CPAP (continuous positive airway pressure), but providers in both arms were free to prescribe whatever treatment they thought best.

Obstructive sleep apnea had first been diagnosed by the primary care doctors using screening and ESS questionnaires, plus home oximetry testing with the ApneaLink device, manufactured by ResMed. They and the nurses had six hours of OSA training before the trial, plus training about common sleep disorders and their differential diagnoses. Nurses had an additional week of training at a sleep center.

After 6 months, patients managed by the primary care group had a mean ESS improvement of 4.9 points and a mean Functional Outcomes of Sleep Questionnaire (FOSQ) improvement of 2.3 points. The mean ESS improvement in the specialist group was 5.1, and the mean FOSQ improvement was 2.7. The differences were not statistically significant.

CPAP machines were being used a mean of 4.8 hours per day at 6 months in the primary care group and a mean of 5.4 hours per day in the specialist group. Again, the difference was not significant.

Outpatient OSA management saved more than $2,000 (AUS) per patient, as well.

"Our results show that using a simplified, ambulatory approach for the treatment of OSA in primary care is not clinically inferior to management of these patients in a specialist sleep center," said lead investigator Dr. Ching Li Chai-Coetzer of the Adelaide Institute for Sleep Health at the Repatriation General Hospital in Adelaide, Australia.

"We think in rural, remote areas and in the developing world, as obesity emerges and sleep apnea becomes more of a clinical issue, the traditional models of care are not going to be available to all patients. We think these results may have some important implications in these areas," said Dr. Nicholas Antic, also an investigator from the Adelaide Institute for Sleep Health.

Dr. Chai-Coetzer and Dr. Antic said they had no relevant financial conflicts. The equipment used in the study was donated by ResMed, Philips Respironics, and SomnoMed.

SAN FRANCISCO – Outpatient sleep apnea management by primary care physicians and nurses works as well as management by specialists in a sleep center and is less expensive, Australian researchers reported at the International Conference of the American Thoracic Society.

The team randomized 155 patients with symptomatic, moderate to severe obstructive sleep apnea (OSA) – all with baseline Epworth Sleepiness Scale (ESS) scores of at least 8 – to either standard management by sleep specialists with sleep-lab testing or outpatient management by their primary care doctor and a community-based nurse. Primary care management often involved home-based, autotitrating CPAP (continuous positive airway pressure), but providers in both arms were free to prescribe whatever treatment they thought best.

Obstructive sleep apnea had first been diagnosed by the primary care doctors using screening and ESS questionnaires, plus home oximetry testing with the ApneaLink device, manufactured by ResMed. They and the nurses had six hours of OSA training before the trial, plus training about common sleep disorders and their differential diagnoses. Nurses had an additional week of training at a sleep center.

After 6 months, patients managed by the primary care group had a mean ESS improvement of 4.9 points and a mean Functional Outcomes of Sleep Questionnaire (FOSQ) improvement of 2.3 points. The mean ESS improvement in the specialist group was 5.1, and the mean FOSQ improvement was 2.7. The differences were not statistically significant.

CPAP machines were being used a mean of 4.8 hours per day at 6 months in the primary care group and a mean of 5.4 hours per day in the specialist group. Again, the difference was not significant.

Outpatient OSA management saved more than $2,000 (AUS) per patient, as well.

"Our results show that using a simplified, ambulatory approach for the treatment of OSA in primary care is not clinically inferior to management of these patients in a specialist sleep center," said lead investigator Dr. Ching Li Chai-Coetzer of the Adelaide Institute for Sleep Health at the Repatriation General Hospital in Adelaide, Australia.

"We think in rural, remote areas and in the developing world, as obesity emerges and sleep apnea becomes more of a clinical issue, the traditional models of care are not going to be available to all patients. We think these results may have some important implications in these areas," said Dr. Nicholas Antic, also an investigator from the Adelaide Institute for Sleep Health.

Dr. Chai-Coetzer and Dr. Antic said they had no relevant financial conflicts. The equipment used in the study was donated by ResMed, Philips Respironics, and SomnoMed.

SAN FRANCISCO – Outpatient sleep apnea management by primary care physicians and nurses works as well as management by specialists in a sleep center and is less expensive, Australian researchers reported at the International Conference of the American Thoracic Society.

The team randomized 155 patients with symptomatic, moderate to severe obstructive sleep apnea (OSA) – all with baseline Epworth Sleepiness Scale (ESS) scores of at least 8 – to either standard management by sleep specialists with sleep-lab testing or outpatient management by their primary care doctor and a community-based nurse. Primary care management often involved home-based, autotitrating CPAP (continuous positive airway pressure), but providers in both arms were free to prescribe whatever treatment they thought best.

Obstructive sleep apnea had first been diagnosed by the primary care doctors using screening and ESS questionnaires, plus home oximetry testing with the ApneaLink device, manufactured by ResMed. They and the nurses had six hours of OSA training before the trial, plus training about common sleep disorders and their differential diagnoses. Nurses had an additional week of training at a sleep center.

After 6 months, patients managed by the primary care group had a mean ESS improvement of 4.9 points and a mean Functional Outcomes of Sleep Questionnaire (FOSQ) improvement of 2.3 points. The mean ESS improvement in the specialist group was 5.1, and the mean FOSQ improvement was 2.7. The differences were not statistically significant.

CPAP machines were being used a mean of 4.8 hours per day at 6 months in the primary care group and a mean of 5.4 hours per day in the specialist group. Again, the difference was not significant.

Outpatient OSA management saved more than $2,000 (AUS) per patient, as well.

"Our results show that using a simplified, ambulatory approach for the treatment of OSA in primary care is not clinically inferior to management of these patients in a specialist sleep center," said lead investigator Dr. Ching Li Chai-Coetzer of the Adelaide Institute for Sleep Health at the Repatriation General Hospital in Adelaide, Australia.

"We think in rural, remote areas and in the developing world, as obesity emerges and sleep apnea becomes more of a clinical issue, the traditional models of care are not going to be available to all patients. We think these results may have some important implications in these areas," said Dr. Nicholas Antic, also an investigator from the Adelaide Institute for Sleep Health.

Dr. Chai-Coetzer and Dr. Antic said they had no relevant financial conflicts. The equipment used in the study was donated by ResMed, Philips Respironics, and SomnoMed.

SAN FRANCISCO – More than a decade after the event, asthma, chronic obstructive pulmonary disease, and other respiratory symptoms are more common among lower Manhattan residents whose homes were covered with dust from the 9/11 attacks.

"All of these [respiratory] symptoms and diseases have elevated rates in this population," said Dr. Vinicius Antao of the Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry, who led an investigation into the issue.

Photo Andrea Booher/ FEMA News Photo

"We found that after controlling for variables" such as age, sex, and smoking, "they are at least 50% more likely to report these [problems than are] those who didn’t have any damage done to their homes," he said.

People who cleaned up the dust with a wet mop, instead of a broom and dustpan, have fewer respiratory problems today. Wet mopping probably kept dust particles from resuspending.

"Now we know" that even brief catastrophic dust exposure can cause "symptoms for a long time," Dr. Antao said.

That finding "will inform public health decision making in terms of emergency preparedness. We need to evacuate a population in a circumstance like this," he said.

His team linked the self-reported health status of 6,463 people in the World Trade Center Health Registry, a longitudinal project that tracks outcomes for 9/11 survivors with the amount of damage they said the attacks did to their homes. The respondents all lived below Canal Street in lower Manhattan on Sept. 11, 2001. The research is ongoing, but the data analyzed were from 2003 to 2007.

Dr. Antao and his colleagues excluded people who helped with the cleanup at ground zero, and controlled for people caught up in the dust cloud that billowed through Manhattan after the towers came down. The dust was a mixture of fine powdered concrete products, metals, and minerals, including asbestos, among other things.

People who said there was a heavy dust layer in their home – so much dust, for instance, that they couldn’t read a newspaper that was covered with it – were more likely than were those with no dust in their homes to report shortness of breath (odds ratio, 1.74; 95% confidence interval, 1.45-2.10), wheezing (OR, 1.68; 95% CI, 1.36-2.08), chronic cough (OR, 1.58; 95% CI, 1.23-2.01), upper respiratory symptoms (OR, 1.37; 95% CI, 1.17-1.60), asthma (OR, 1.30; 95% CI, 1.01-1.70), and COPD (OR, 1.37; 95% CI, 1.02-1.84).

Their rates of asthma and COPD are "slightly higher" than rates in the general population, Dr. Antao said.

His team also found a significant, but less pervasive, association with respiratory symptoms in people who said the shock wave from the towers’ collapse blew out their windows or damaged their furniture.

Dr. Antao said he doesn’t think recall bias is at work, especially since years have passed since the 9/11 attacks, meaning that the shock of the event has worn off to some extent and is less likely to color survivors’ perceptions of its effects on their health. "We’ve looked at different aspects of that, and most of the results that we have indicate that these data are real," he said.

Dr. Antao said he has no relevant financial disclosures.

SAN FRANCISCO – More than a decade after the event, asthma, chronic obstructive pulmonary disease, and other respiratory symptoms are more common among lower Manhattan residents whose homes were covered with dust from the 9/11 attacks.

"All of these [respiratory] symptoms and diseases have elevated rates in this population," said Dr. Vinicius Antao of the Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry, who led an investigation into the issue.

Photo Andrea Booher/ FEMA News Photo

"We found that after controlling for variables" such as age, sex, and smoking, "they are at least 50% more likely to report these [problems than are] those who didn’t have any damage done to their homes," he said.

People who cleaned up the dust with a wet mop, instead of a broom and dustpan, have fewer respiratory problems today. Wet mopping probably kept dust particles from resuspending.

"Now we know" that even brief catastrophic dust exposure can cause "symptoms for a long time," Dr. Antao said.

That finding "will inform public health decision making in terms of emergency preparedness. We need to evacuate a population in a circumstance like this," he said.

His team linked the self-reported health status of 6,463 people in the World Trade Center Health Registry, a longitudinal project that tracks outcomes for 9/11 survivors with the amount of damage they said the attacks did to their homes. The respondents all lived below Canal Street in lower Manhattan on Sept. 11, 2001. The research is ongoing, but the data analyzed were from 2003 to 2007.

Dr. Antao and his colleagues excluded people who helped with the cleanup at ground zero, and controlled for people caught up in the dust cloud that billowed through Manhattan after the towers came down. The dust was a mixture of fine powdered concrete products, metals, and minerals, including asbestos, among other things.

People who said there was a heavy dust layer in their home – so much dust, for instance, that they couldn’t read a newspaper that was covered with it – were more likely than were those with no dust in their homes to report shortness of breath (odds ratio, 1.74; 95% confidence interval, 1.45-2.10), wheezing (OR, 1.68; 95% CI, 1.36-2.08), chronic cough (OR, 1.58; 95% CI, 1.23-2.01), upper respiratory symptoms (OR, 1.37; 95% CI, 1.17-1.60), asthma (OR, 1.30; 95% CI, 1.01-1.70), and COPD (OR, 1.37; 95% CI, 1.02-1.84).

Their rates of asthma and COPD are "slightly higher" than rates in the general population, Dr. Antao said.

His team also found a significant, but less pervasive, association with respiratory symptoms in people who said the shock wave from the towers’ collapse blew out their windows or damaged their furniture.

Dr. Antao said he doesn’t think recall bias is at work, especially since years have passed since the 9/11 attacks, meaning that the shock of the event has worn off to some extent and is less likely to color survivors’ perceptions of its effects on their health. "We’ve looked at different aspects of that, and most of the results that we have indicate that these data are real," he said.

Dr. Antao said he has no relevant financial disclosures.

SAN FRANCISCO – More than a decade after the event, asthma, chronic obstructive pulmonary disease, and other respiratory symptoms are more common among lower Manhattan residents whose homes were covered with dust from the 9/11 attacks.

"All of these [respiratory] symptoms and diseases have elevated rates in this population," said Dr. Vinicius Antao of the Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry, who led an investigation into the issue.

Photo Andrea Booher/ FEMA News Photo

"We found that after controlling for variables" such as age, sex, and smoking, "they are at least 50% more likely to report these [problems than are] those who didn’t have any damage done to their homes," he said.

People who cleaned up the dust with a wet mop, instead of a broom and dustpan, have fewer respiratory problems today. Wet mopping probably kept dust particles from resuspending.

"Now we know" that even brief catastrophic dust exposure can cause "symptoms for a long time," Dr. Antao said.

That finding "will inform public health decision making in terms of emergency preparedness. We need to evacuate a population in a circumstance like this," he said.

His team linked the self-reported health status of 6,463 people in the World Trade Center Health Registry, a longitudinal project that tracks outcomes for 9/11 survivors with the amount of damage they said the attacks did to their homes. The respondents all lived below Canal Street in lower Manhattan on Sept. 11, 2001. The research is ongoing, but the data analyzed were from 2003 to 2007.

Dr. Antao and his colleagues excluded people who helped with the cleanup at ground zero, and controlled for people caught up in the dust cloud that billowed through Manhattan after the towers came down. The dust was a mixture of fine powdered concrete products, metals, and minerals, including asbestos, among other things.

People who said there was a heavy dust layer in their home – so much dust, for instance, that they couldn’t read a newspaper that was covered with it – were more likely than were those with no dust in their homes to report shortness of breath (odds ratio, 1.74; 95% confidence interval, 1.45-2.10), wheezing (OR, 1.68; 95% CI, 1.36-2.08), chronic cough (OR, 1.58; 95% CI, 1.23-2.01), upper respiratory symptoms (OR, 1.37; 95% CI, 1.17-1.60), asthma (OR, 1.30; 95% CI, 1.01-1.70), and COPD (OR, 1.37; 95% CI, 1.02-1.84).

Their rates of asthma and COPD are "slightly higher" than rates in the general population, Dr. Antao said.

His team also found a significant, but less pervasive, association with respiratory symptoms in people who said the shock wave from the towers’ collapse blew out their windows or damaged their furniture.

Dr. Antao said he doesn’t think recall bias is at work, especially since years have passed since the 9/11 attacks, meaning that the shock of the event has worn off to some extent and is less likely to color survivors’ perceptions of its effects on their health. "We’ve looked at different aspects of that, and most of the results that we have indicate that these data are real," he said.

Dr. Antao said he has no relevant financial disclosures.

SAN DIEGO – An emergency department at an academic medical institution with a multiple sclerosis center missed diagnosing multiple sclerosis in nearly 40% of patients who were later diagnosed with the disease, calling into question what the rate of missed cases might be at smaller centers staffed by fewer specialists.

The retrospective study analyzed assessments for neurologic symptoms during 49 emergency department (ED) visits at the Mount Sinai School of Medicine in New York that were made by 49 people who were later diagnosed with MS. The researchers judged most of those presentations to be initial manifestations of the disease.

Just 30 of the visits (61%) resulted in a diagnosis of MS or demyelinating disease, either in the ED or on subsequent admission, Dr. Stephen Krieger said at the Fourth Cooperative Meeting on Multiple Sclerosis, which was sponsored by the Consortium of Multiple Sclerosis Centers and the America’s Committee for Treatment and Research in Multiple Sclerosis.

The diagnosis was missed in the remaining 19 (39%) visits, an important finding because early diagnosis and treatment leads to better MS outcomes. About a third of the patients involved in those visits still hadn’t been diagnosed 6 months later. It took more than a year to diagnose a few of them. "Those are the patients we have to look at to see what could have been done differently," said senior investigator Dr. Krieger, an MS specialist at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai.

The risk of delayed diagnosis seemed to be greatest for men, the middle aged, and those with vague neurologic symptoms – all of whom are nontraditional MS patients – but the study didn’t have enough patients to demonstrate those findings statistically. Patients who were admitted from the ED, however, were more likely to be diagnosed quickly than were nonadmitted patients.

"Emergency department presentations for acute neurologic symptoms are an important opportunity to diagnose and treat clinically isolated syndrome and MS. There’s room to make that diagnosis more rapidly," Dr. Krieger said.

Even though the project was a single-center study, Dr. Krieger noted that Mount Sinai is an academic center with a busy neurology department, a neurology residency, and a multiple sclerosis center. In short, "we are sort of a best case scenario. A lot of other emergency departments without as much access to MS specialists may" have a harder time making a prompt diagnosis, he said.

His team plans to analyze demographic data and symptom presentations to develop robust predictive factors for delayed MS diagnoses.

Although the findings are concerning, Dr. Lael Stone, an MS specialist at the Cleveland Clinic, noted that the situation has improved in recent years. "It used to be that [the elapsed time between] first symptoms [and] diagnosis was on the order of 9 years. That has gone down dramatically," she said.

Even so, "we have a ways to go in terms of picking up MS in the [emergency department], which we should be able to do," she said at the meeting.

Vague and confusing neurologic symptoms remain a problem. The demyelinating disease neuromyelitis optica, for example, can present with month-long intractable vomiting, years before the condition is diagnosed.

"The intractable vomiting goes to the GI doctor or to the [ED]. I doubt that the [ED or GI specialist] thinks this might be neuromyelitis optica," she said.

Among the 49 ED visits for neurologic symptoms at Mount Sinai, almost half were for sensory symptoms; the remainder were for vision changes, weakness, balance problems, diplopia, and vertigo.

Bayer Healthcare Pharmaceuticals funded for the study. Dr. Krieger said he is a paid consultant for Acorda Therapeutics, Bayer Healthcare Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme, Novartis, and Questcor. He receives fees from Teva Neuroscience for non-CME services. Dr. Stone said she has no relevant disclosures.

SAN DIEGO – An emergency department at an academic medical institution with a multiple sclerosis center missed diagnosing multiple sclerosis in nearly 40% of patients who were later diagnosed with the disease, calling into question what the rate of missed cases might be at smaller centers staffed by fewer specialists.

The retrospective study analyzed assessments for neurologic symptoms during 49 emergency department (ED) visits at the Mount Sinai School of Medicine in New York that were made by 49 people who were later diagnosed with MS. The researchers judged most of those presentations to be initial manifestations of the disease.

Just 30 of the visits (61%) resulted in a diagnosis of MS or demyelinating disease, either in the ED or on subsequent admission, Dr. Stephen Krieger said at the Fourth Cooperative Meeting on Multiple Sclerosis, which was sponsored by the Consortium of Multiple Sclerosis Centers and the America’s Committee for Treatment and Research in Multiple Sclerosis.

The diagnosis was missed in the remaining 19 (39%) visits, an important finding because early diagnosis and treatment leads to better MS outcomes. About a third of the patients involved in those visits still hadn’t been diagnosed 6 months later. It took more than a year to diagnose a few of them. "Those are the patients we have to look at to see what could have been done differently," said senior investigator Dr. Krieger, an MS specialist at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai.

The risk of delayed diagnosis seemed to be greatest for men, the middle aged, and those with vague neurologic symptoms – all of whom are nontraditional MS patients – but the study didn’t have enough patients to demonstrate those findings statistically. Patients who were admitted from the ED, however, were more likely to be diagnosed quickly than were nonadmitted patients.

"Emergency department presentations for acute neurologic symptoms are an important opportunity to diagnose and treat clinically isolated syndrome and MS. There’s room to make that diagnosis more rapidly," Dr. Krieger said.

Even though the project was a single-center study, Dr. Krieger noted that Mount Sinai is an academic center with a busy neurology department, a neurology residency, and a multiple sclerosis center. In short, "we are sort of a best case scenario. A lot of other emergency departments without as much access to MS specialists may" have a harder time making a prompt diagnosis, he said.

His team plans to analyze demographic data and symptom presentations to develop robust predictive factors for delayed MS diagnoses.

Although the findings are concerning, Dr. Lael Stone, an MS specialist at the Cleveland Clinic, noted that the situation has improved in recent years. "It used to be that [the elapsed time between] first symptoms [and] diagnosis was on the order of 9 years. That has gone down dramatically," she said.

Even so, "we have a ways to go in terms of picking up MS in the [emergency department], which we should be able to do," she said at the meeting.

Vague and confusing neurologic symptoms remain a problem. The demyelinating disease neuromyelitis optica, for example, can present with month-long intractable vomiting, years before the condition is diagnosed.

"The intractable vomiting goes to the GI doctor or to the [ED]. I doubt that the [ED or GI specialist] thinks this might be neuromyelitis optica," she said.

Among the 49 ED visits for neurologic symptoms at Mount Sinai, almost half were for sensory symptoms; the remainder were for vision changes, weakness, balance problems, diplopia, and vertigo.

Bayer Healthcare Pharmaceuticals funded for the study. Dr. Krieger said he is a paid consultant for Acorda Therapeutics, Bayer Healthcare Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme, Novartis, and Questcor. He receives fees from Teva Neuroscience for non-CME services. Dr. Stone said she has no relevant disclosures.

SAN DIEGO – An emergency department at an academic medical institution with a multiple sclerosis center missed diagnosing multiple sclerosis in nearly 40% of patients who were later diagnosed with the disease, calling into question what the rate of missed cases might be at smaller centers staffed by fewer specialists.

The retrospective study analyzed assessments for neurologic symptoms during 49 emergency department (ED) visits at the Mount Sinai School of Medicine in New York that were made by 49 people who were later diagnosed with MS. The researchers judged most of those presentations to be initial manifestations of the disease.

Just 30 of the visits (61%) resulted in a diagnosis of MS or demyelinating disease, either in the ED or on subsequent admission, Dr. Stephen Krieger said at the Fourth Cooperative Meeting on Multiple Sclerosis, which was sponsored by the Consortium of Multiple Sclerosis Centers and the America’s Committee for Treatment and Research in Multiple Sclerosis.

The diagnosis was missed in the remaining 19 (39%) visits, an important finding because early diagnosis and treatment leads to better MS outcomes. About a third of the patients involved in those visits still hadn’t been diagnosed 6 months later. It took more than a year to diagnose a few of them. "Those are the patients we have to look at to see what could have been done differently," said senior investigator Dr. Krieger, an MS specialist at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai.

The risk of delayed diagnosis seemed to be greatest for men, the middle aged, and those with vague neurologic symptoms – all of whom are nontraditional MS patients – but the study didn’t have enough patients to demonstrate those findings statistically. Patients who were admitted from the ED, however, were more likely to be diagnosed quickly than were nonadmitted patients.

"Emergency department presentations for acute neurologic symptoms are an important opportunity to diagnose and treat clinically isolated syndrome and MS. There’s room to make that diagnosis more rapidly," Dr. Krieger said.

Even though the project was a single-center study, Dr. Krieger noted that Mount Sinai is an academic center with a busy neurology department, a neurology residency, and a multiple sclerosis center. In short, "we are sort of a best case scenario. A lot of other emergency departments without as much access to MS specialists may" have a harder time making a prompt diagnosis, he said.

His team plans to analyze demographic data and symptom presentations to develop robust predictive factors for delayed MS diagnoses.

Although the findings are concerning, Dr. Lael Stone, an MS specialist at the Cleveland Clinic, noted that the situation has improved in recent years. "It used to be that [the elapsed time between] first symptoms [and] diagnosis was on the order of 9 years. That has gone down dramatically," she said.

Even so, "we have a ways to go in terms of picking up MS in the [emergency department], which we should be able to do," she said at the meeting.

Vague and confusing neurologic symptoms remain a problem. The demyelinating disease neuromyelitis optica, for example, can present with month-long intractable vomiting, years before the condition is diagnosed.

"The intractable vomiting goes to the GI doctor or to the [ED]. I doubt that the [ED or GI specialist] thinks this might be neuromyelitis optica," she said.

Among the 49 ED visits for neurologic symptoms at Mount Sinai, almost half were for sensory symptoms; the remainder were for vision changes, weakness, balance problems, diplopia, and vertigo.

Bayer Healthcare Pharmaceuticals funded for the study. Dr. Krieger said he is a paid consultant for Acorda Therapeutics, Bayer Healthcare Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme, Novartis, and Questcor. He receives fees from Teva Neuroscience for non-CME services. Dr. Stone said she has no relevant disclosures.

NEW ORLEANS – Pregabalin proved better than pramipexole for relieving restless legs syndrome, and it caused less symptom augmentation, in a yearlong trial funded by Pfizer, the manufacturer of pregabalin.

Dopamine agonists such as pramipexole (Mirapex) are first-line agents for restless legs syndrome (RLS), but over time they can actually make symptoms worse.

That’s a problem because "we are going to use these treatments for most of the patient’s life," lead investigator Dr. Diego Garcia-Borreguero, director of the Sleep Disorders Institute in Madrid, said at the annual meeting of the American Academy of Neurology.

His team compared 300 mg/day of pregabalin (Lyrica), a calcium-channel modulator, in 182 RLS patients against 0.25 mg/day of pramipexole in 178 patients; 0.5 mg/day of pramipexole in 180; and placebo in 179.

After 12 weeks, placebo patients were randomized to an active treatment arm, and the trial continued for another 40 weeks. The mean age of patients was 55 years and their mean RLS duration was 5 years; more than half were women.

At 12 weeks, pregabalin patients were doing 3.96 points better on the 40-point international RLS rating scale (IRLS) than were patients on 0.25 mg/day of pramipexole, and 1.69 points better than were patients on 0.5 mg/day of pramipexole. At the end of the year, pregabalin patients were doing 3.8 points better on the IRLS than were the 0.25-mg/day pramipexole patients, and 3.06 points better than the 0.5-mg pramipexole patients.

Also at the end of the year, the rate of augmentation was 2.1% in the pregabalin group, 5.3% in the 0.25 mg pramipexole group (P value for difference with pregabalin = .083), and 7.7% in the 0.5 mg pramipexole group (P value for difference with pregabalin = .012).

Dizziness, somnolence, and weight gain were more common with pregabalin, whereas with pramipexole nausea and headache were more common.

"Pregabalin is more effective than pramipexole" for RLS, Dr. Garcia-Borreguero concluded. "It has less augmentation over the long term, and it has superior efficacy."

Even so, Pfizer has stated it currently does not plan to seek approval for the indication from the Food and Drug Administration or regulators in other countries.

In the United States, the drug is indicated for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, adjunctive therapy for adult patients with partial onset seizures, and fibromyalgia.

On May 4, the company halted a trial for neuropathic pain associated with HIV neuropathy after pregabalin proved no better than placebo.

Dr. Garcia-Borreguero has received personal compensation for activities with Pfizer, UCB Pharma, XenoPort, and Otsuka.

NEW ORLEANS – Pregabalin proved better than pramipexole for relieving restless legs syndrome, and it caused less symptom augmentation, in a yearlong trial funded by Pfizer, the manufacturer of pregabalin.

Dopamine agonists such as pramipexole (Mirapex) are first-line agents for restless legs syndrome (RLS), but over time they can actually make symptoms worse.

That’s a problem because "we are going to use these treatments for most of the patient’s life," lead investigator Dr. Diego Garcia-Borreguero, director of the Sleep Disorders Institute in Madrid, said at the annual meeting of the American Academy of Neurology.

His team compared 300 mg/day of pregabalin (Lyrica), a calcium-channel modulator, in 182 RLS patients against 0.25 mg/day of pramipexole in 178 patients; 0.5 mg/day of pramipexole in 180; and placebo in 179.

After 12 weeks, placebo patients were randomized to an active treatment arm, and the trial continued for another 40 weeks. The mean age of patients was 55 years and their mean RLS duration was 5 years; more than half were women.

At 12 weeks, pregabalin patients were doing 3.96 points better on the 40-point international RLS rating scale (IRLS) than were patients on 0.25 mg/day of pramipexole, and 1.69 points better than were patients on 0.5 mg/day of pramipexole. At the end of the year, pregabalin patients were doing 3.8 points better on the IRLS than were the 0.25-mg/day pramipexole patients, and 3.06 points better than the 0.5-mg pramipexole patients.

Also at the end of the year, the rate of augmentation was 2.1% in the pregabalin group, 5.3% in the 0.25 mg pramipexole group (P value for difference with pregabalin = .083), and 7.7% in the 0.5 mg pramipexole group (P value for difference with pregabalin = .012).

Dizziness, somnolence, and weight gain were more common with pregabalin, whereas with pramipexole nausea and headache were more common.

"Pregabalin is more effective than pramipexole" for RLS, Dr. Garcia-Borreguero concluded. "It has less augmentation over the long term, and it has superior efficacy."

Even so, Pfizer has stated it currently does not plan to seek approval for the indication from the Food and Drug Administration or regulators in other countries.

In the United States, the drug is indicated for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, adjunctive therapy for adult patients with partial onset seizures, and fibromyalgia.

On May 4, the company halted a trial for neuropathic pain associated with HIV neuropathy after pregabalin proved no better than placebo.

Dr. Garcia-Borreguero has received personal compensation for activities with Pfizer, UCB Pharma, XenoPort, and Otsuka.

NEW ORLEANS – Pregabalin proved better than pramipexole for relieving restless legs syndrome, and it caused less symptom augmentation, in a yearlong trial funded by Pfizer, the manufacturer of pregabalin.

Dopamine agonists such as pramipexole (Mirapex) are first-line agents for restless legs syndrome (RLS), but over time they can actually make symptoms worse.

That’s a problem because "we are going to use these treatments for most of the patient’s life," lead investigator Dr. Diego Garcia-Borreguero, director of the Sleep Disorders Institute in Madrid, said at the annual meeting of the American Academy of Neurology.

His team compared 300 mg/day of pregabalin (Lyrica), a calcium-channel modulator, in 182 RLS patients against 0.25 mg/day of pramipexole in 178 patients; 0.5 mg/day of pramipexole in 180; and placebo in 179.

After 12 weeks, placebo patients were randomized to an active treatment arm, and the trial continued for another 40 weeks. The mean age of patients was 55 years and their mean RLS duration was 5 years; more than half were women.

At 12 weeks, pregabalin patients were doing 3.96 points better on the 40-point international RLS rating scale (IRLS) than were patients on 0.25 mg/day of pramipexole, and 1.69 points better than were patients on 0.5 mg/day of pramipexole. At the end of the year, pregabalin patients were doing 3.8 points better on the IRLS than were the 0.25-mg/day pramipexole patients, and 3.06 points better than the 0.5-mg pramipexole patients.

Also at the end of the year, the rate of augmentation was 2.1% in the pregabalin group, 5.3% in the 0.25 mg pramipexole group (P value for difference with pregabalin = .083), and 7.7% in the 0.5 mg pramipexole group (P value for difference with pregabalin = .012).

Dizziness, somnolence, and weight gain were more common with pregabalin, whereas with pramipexole nausea and headache were more common.

"Pregabalin is more effective than pramipexole" for RLS, Dr. Garcia-Borreguero concluded. "It has less augmentation over the long term, and it has superior efficacy."

Even so, Pfizer has stated it currently does not plan to seek approval for the indication from the Food and Drug Administration or regulators in other countries.

In the United States, the drug is indicated for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, adjunctive therapy for adult patients with partial onset seizures, and fibromyalgia.

On May 4, the company halted a trial for neuropathic pain associated with HIV neuropathy after pregabalin proved no better than placebo.

Dr. Garcia-Borreguero has received personal compensation for activities with Pfizer, UCB Pharma, XenoPort, and Otsuka.