Patrice Wendling

PARIS – In patients with a first recurrence of pericarditis, adding low-dose colchicine to standard therapy halved the risk of subsequent episodes of pericarditis.

Among 120 patients with a first recurrence of pericarditis in the Study of Colchicine to Treat and Prevent Recurrent Pericarditis (CORP) trial, the rate at 18 months of another recurrence was 24% with colchicine and standard therapy and 55% with placebo and standard therapy (P value less than .001).

The relative risk reduction associated with adjuvant colchicine was 56% and the number needed to treat to prevent one recurrence was three, Dr. Massimo Imazio reported at the annual congress of the European Society of Cardiology.

Colchicine (Colcrys) has been used for years to treat gout, and is the first drug to be shown in a double-blind, randomized placebo-controlled trial to prevent recurrent pericarditis.

"Following an initial episode of recurrent pericarditis, colchicine, as an adjunct to anti-inflammatory therapy, appears to be an inexpensive and safe means to hasten symptom resolution, improving remission rates by one week, and to reduce further recurrences during follow-up," said Dr. Imazio of the Maria Vittoria Hospital in Turin, Italy.

Invited discussant Dr. Andre Keren, director of the Heart Failure and Heart Muscle Disease Center at the Heart Institute at Hadassah University Hospital in Jerusalem, described CORP as a well-designed and carefully performed trial. Its results strongly support the use of low-dose colchicine as a safe, well-tolerated, and effective first-line adjuvant to standard treatment in patients with recurrent pericarditis.

"I really believe that the time has arrived that colchicine should be more freely used," he said.

Both Dr. Imazio and Dr. Keren observed that the results may not be applicable to all patients with pericarditis since the trial excluded those patients with neoplastic or bacterial etiologies for their pericarditis as well as patients with multiple recurrences of pericarditis.

In addition, the drug’s "remarkable" safety and tolerability profile might have been influenced by careful patient selection and the low doses employed in the study, Dr. Keren said.

Based on nonrandomized observational findings and expert opinion, the European Society of Cardiology guidelines recommend colchicine 2 mg/day for 1 to 2 days, followed by a maintenance dose of 1 mg/day for the treatment of recurrent pericarditis.

The CORP investigators randomized patients from four Italian centers to conventional therapy plus placebo or colchicine for 6 months at the recommended doses for patients weighing at least 70 kg, but reduced the initial dose to 1 mg/day and the maintenance dose to 0.5 mg/day for those weighing less than 70 kg.

Conventional therapy was aspirin 800 mg-1,000 mg or ibuprofen 600 mg every 8 hours for 7-10 days, with the second choice being prednisone 0.2-0.5 mg/kg of body weight per day for 4 weeks and then gradually tapered.

Dr. Keren pointed out that the dose as well as the frequency of corticosteroids was lower in CORP than the researchers’ earlier CORE trial, in which prednisone was dosed at 1.0-1.5 mg/kg of body weight per day for 4 weeks, and 35% of patients had received steroids during the initial episode of pericarditis. In contrast, only 10% of placebo and 8% of colchicine patients in CORP had previously received corticosteroids.

"This might also reflect, in my view, a change in our perception that steroids can actually be deleterious in decreasing the recurrence rate," Dr. Keren said.

Symptom persistence at 72 hours was significantly lower in the colchicine group than in the placebo group (23% vs. 53%, P = .001), as was the rate of remission at 1 week (48% vs. 82%, P less than .001), Dr. Imazio said.

The mean number of recurrences was significantly lower in the colchicine-treated group than in the placebo group (0.1 vs. 1.0), and the time to first recurrence was also significantly longer at 2.5 months vs. 1 month (both P less than .001).

No significant differences were observed between the two groups in rates of readmission (5% vs. 13%), tamponade (0% vs. 2%), or constriction (0% both).

Gastrointestinal intolerance was the most common side effect, reported in four colchicine- and five placebo-treated patients. No severe side effects were observed in either group. Treatment discontinuation occurred in five colchicine and four placebo patients, Dr. Imazio said.

Full results of CORP are available online in the Annals of Internal Medicine (Ann. Intern. Med. 2011 Aug. 28 [Epub ahead of print]).

Dr. Imazio and his coauthors report no study sponsorship or conflicts. Dr. Keren reports no disclosures.

PARIS – In patients with a first recurrence of pericarditis, adding low-dose colchicine to standard therapy halved the risk of subsequent episodes of pericarditis.

Among 120 patients with a first recurrence of pericarditis in the Study of Colchicine to Treat and Prevent Recurrent Pericarditis (CORP) trial, the rate at 18 months of another recurrence was 24% with colchicine and standard therapy and 55% with placebo and standard therapy (P value less than .001).

The relative risk reduction associated with adjuvant colchicine was 56% and the number needed to treat to prevent one recurrence was three, Dr. Massimo Imazio reported at the annual congress of the European Society of Cardiology.

Colchicine (Colcrys) has been used for years to treat gout, and is the first drug to be shown in a double-blind, randomized placebo-controlled trial to prevent recurrent pericarditis.

"Following an initial episode of recurrent pericarditis, colchicine, as an adjunct to anti-inflammatory therapy, appears to be an inexpensive and safe means to hasten symptom resolution, improving remission rates by one week, and to reduce further recurrences during follow-up," said Dr. Imazio of the Maria Vittoria Hospital in Turin, Italy.

Invited discussant Dr. Andre Keren, director of the Heart Failure and Heart Muscle Disease Center at the Heart Institute at Hadassah University Hospital in Jerusalem, described CORP as a well-designed and carefully performed trial. Its results strongly support the use of low-dose colchicine as a safe, well-tolerated, and effective first-line adjuvant to standard treatment in patients with recurrent pericarditis.

"I really believe that the time has arrived that colchicine should be more freely used," he said.

Both Dr. Imazio and Dr. Keren observed that the results may not be applicable to all patients with pericarditis since the trial excluded those patients with neoplastic or bacterial etiologies for their pericarditis as well as patients with multiple recurrences of pericarditis.

In addition, the drug’s "remarkable" safety and tolerability profile might have been influenced by careful patient selection and the low doses employed in the study, Dr. Keren said.

Based on nonrandomized observational findings and expert opinion, the European Society of Cardiology guidelines recommend colchicine 2 mg/day for 1 to 2 days, followed by a maintenance dose of 1 mg/day for the treatment of recurrent pericarditis.

The CORP investigators randomized patients from four Italian centers to conventional therapy plus placebo or colchicine for 6 months at the recommended doses for patients weighing at least 70 kg, but reduced the initial dose to 1 mg/day and the maintenance dose to 0.5 mg/day for those weighing less than 70 kg.

Conventional therapy was aspirin 800 mg-1,000 mg or ibuprofen 600 mg every 8 hours for 7-10 days, with the second choice being prednisone 0.2-0.5 mg/kg of body weight per day for 4 weeks and then gradually tapered.

Dr. Keren pointed out that the dose as well as the frequency of corticosteroids was lower in CORP than the researchers’ earlier CORE trial, in which prednisone was dosed at 1.0-1.5 mg/kg of body weight per day for 4 weeks, and 35% of patients had received steroids during the initial episode of pericarditis. In contrast, only 10% of placebo and 8% of colchicine patients in CORP had previously received corticosteroids.

"This might also reflect, in my view, a change in our perception that steroids can actually be deleterious in decreasing the recurrence rate," Dr. Keren said.

Symptom persistence at 72 hours was significantly lower in the colchicine group than in the placebo group (23% vs. 53%, P = .001), as was the rate of remission at 1 week (48% vs. 82%, P less than .001), Dr. Imazio said.

The mean number of recurrences was significantly lower in the colchicine-treated group than in the placebo group (0.1 vs. 1.0), and the time to first recurrence was also significantly longer at 2.5 months vs. 1 month (both P less than .001).

No significant differences were observed between the two groups in rates of readmission (5% vs. 13%), tamponade (0% vs. 2%), or constriction (0% both).

Gastrointestinal intolerance was the most common side effect, reported in four colchicine- and five placebo-treated patients. No severe side effects were observed in either group. Treatment discontinuation occurred in five colchicine and four placebo patients, Dr. Imazio said.

Full results of CORP are available online in the Annals of Internal Medicine (Ann. Intern. Med. 2011 Aug. 28 [Epub ahead of print]).

Dr. Imazio and his coauthors report no study sponsorship or conflicts. Dr. Keren reports no disclosures.

PARIS – In patients with a first recurrence of pericarditis, adding low-dose colchicine to standard therapy halved the risk of subsequent episodes of pericarditis.

Among 120 patients with a first recurrence of pericarditis in the Study of Colchicine to Treat and Prevent Recurrent Pericarditis (CORP) trial, the rate at 18 months of another recurrence was 24% with colchicine and standard therapy and 55% with placebo and standard therapy (P value less than .001).

The relative risk reduction associated with adjuvant colchicine was 56% and the number needed to treat to prevent one recurrence was three, Dr. Massimo Imazio reported at the annual congress of the European Society of Cardiology.

Colchicine (Colcrys) has been used for years to treat gout, and is the first drug to be shown in a double-blind, randomized placebo-controlled trial to prevent recurrent pericarditis.

"Following an initial episode of recurrent pericarditis, colchicine, as an adjunct to anti-inflammatory therapy, appears to be an inexpensive and safe means to hasten symptom resolution, improving remission rates by one week, and to reduce further recurrences during follow-up," said Dr. Imazio of the Maria Vittoria Hospital in Turin, Italy.

Invited discussant Dr. Andre Keren, director of the Heart Failure and Heart Muscle Disease Center at the Heart Institute at Hadassah University Hospital in Jerusalem, described CORP as a well-designed and carefully performed trial. Its results strongly support the use of low-dose colchicine as a safe, well-tolerated, and effective first-line adjuvant to standard treatment in patients with recurrent pericarditis.

"I really believe that the time has arrived that colchicine should be more freely used," he said.

Both Dr. Imazio and Dr. Keren observed that the results may not be applicable to all patients with pericarditis since the trial excluded those patients with neoplastic or bacterial etiologies for their pericarditis as well as patients with multiple recurrences of pericarditis.

In addition, the drug’s "remarkable" safety and tolerability profile might have been influenced by careful patient selection and the low doses employed in the study, Dr. Keren said.

Based on nonrandomized observational findings and expert opinion, the European Society of Cardiology guidelines recommend colchicine 2 mg/day for 1 to 2 days, followed by a maintenance dose of 1 mg/day for the treatment of recurrent pericarditis.

The CORP investigators randomized patients from four Italian centers to conventional therapy plus placebo or colchicine for 6 months at the recommended doses for patients weighing at least 70 kg, but reduced the initial dose to 1 mg/day and the maintenance dose to 0.5 mg/day for those weighing less than 70 kg.

Conventional therapy was aspirin 800 mg-1,000 mg or ibuprofen 600 mg every 8 hours for 7-10 days, with the second choice being prednisone 0.2-0.5 mg/kg of body weight per day for 4 weeks and then gradually tapered.

Dr. Keren pointed out that the dose as well as the frequency of corticosteroids was lower in CORP than the researchers’ earlier CORE trial, in which prednisone was dosed at 1.0-1.5 mg/kg of body weight per day for 4 weeks, and 35% of patients had received steroids during the initial episode of pericarditis. In contrast, only 10% of placebo and 8% of colchicine patients in CORP had previously received corticosteroids.

"This might also reflect, in my view, a change in our perception that steroids can actually be deleterious in decreasing the recurrence rate," Dr. Keren said.

Symptom persistence at 72 hours was significantly lower in the colchicine group than in the placebo group (23% vs. 53%, P = .001), as was the rate of remission at 1 week (48% vs. 82%, P less than .001), Dr. Imazio said.

The mean number of recurrences was significantly lower in the colchicine-treated group than in the placebo group (0.1 vs. 1.0), and the time to first recurrence was also significantly longer at 2.5 months vs. 1 month (both P less than .001).

No significant differences were observed between the two groups in rates of readmission (5% vs. 13%), tamponade (0% vs. 2%), or constriction (0% both).

Gastrointestinal intolerance was the most common side effect, reported in four colchicine- and five placebo-treated patients. No severe side effects were observed in either group. Treatment discontinuation occurred in five colchicine and four placebo patients, Dr. Imazio said.

Full results of CORP are available online in the Annals of Internal Medicine (Ann. Intern. Med. 2011 Aug. 28 [Epub ahead of print]).

Dr. Imazio and his coauthors report no study sponsorship or conflicts. Dr. Keren reports no disclosures.

PARIS – A neuronal nitric oxide synthase gene polymorphism appears protective against alcohol consumption in adolescents and young adults, new research shows.

The culprit was not, however, what researchers had expected.

Previous research has shown that the neuronal nitric oxide synthase 1 (NOS1) gene promoter polymorphism, EX1f-VNTR (exon 1f-variable number tandem repeats), influences both impulsivity and psychopathology. The short allele, which has lower transcriptional activity, is considered the "risk" allele, compared with the long allele.

Given the link between impulsivity and alcohol consumption, the short allele of NOS1 Ex1f-VNTR was presumed to be the risk allele for alcohol consumption in humans.

Even after controlling for impulsivity among 593 young adults, researchers in Estonia and Germany found that carriers of the long allele were significantly more likely to drink at an earlier age, consume more alcohol, and experience stronger effects of alcohol.

"Usually where some of these activities are related to impulsivity or anxiety or some psychopathology, there is always substance abuse in the same direction, but the data shows that, in this case, it might be opposite," lead author Dr. Kariina Laas said in an interview at the annual congress of the European College of Neuropsychopharmacology.

Long-allele carriers had their first drink at a median age of 14 years vs. 15 years for those with the short-allele (P = .033).

They also reported more often that a hangover is likely when drinking (P = .003). The hangover finding did not emerge because of drinking more, as controlling for total alcohol did not change the genotype effect, reported Dr. Laas of the Estonian Centre of Behavioural and Health Sciences, University of Tartu, Estonia.

The sample was the older cohort of the Estonian Children Personality, Behaviour, and Health Study, a population-representative sample of young adults who were asked to self-report alcohol use at ages 15, 18, and 25 years and to complete the Adaptive and Maladaptive Impulsivity Scale questionnaire at ages 18 and 25 years. Genotyping was also conducted.

At age 15, there was no effect of NOS1 Ex1f-VNTR genotype on alcohol consumption.

At age 18, a NOS1 Ex1f-VNTR and sex signal appeared, she said. Male long-allele carriers consumed significantly more per drinking session and were significantly more likely to be frequent alcohol users and in the upper quartiles of total alcohol consumption.

At age 25, long-allele carriers consumed more alcohol regardless of gender.

The reasons why the short allele – which is impulsivity related – is protective against alcohol consumption are unclear, Dr. Laas said. She speculated that short-allele carriers in the study may represent a unique subset or that they may exhibit more pathological features that could limit their social network.

"The influence of friends is huge on when they start [drinking]," she said.

The findings are also in concordance with animal studies where inhibition of NOS1 attenuates alcohol consumption in mice (Alcohol 2009;43:285-91), the authors noted.

The authors report no conflicts. The study was supported by a grant from the Estonian Ministry of Education and Science.

PARIS – A neuronal nitric oxide synthase gene polymorphism appears protective against alcohol consumption in adolescents and young adults, new research shows.

The culprit was not, however, what researchers had expected.

Previous research has shown that the neuronal nitric oxide synthase 1 (NOS1) gene promoter polymorphism, EX1f-VNTR (exon 1f-variable number tandem repeats), influences both impulsivity and psychopathology. The short allele, which has lower transcriptional activity, is considered the "risk" allele, compared with the long allele.

Given the link between impulsivity and alcohol consumption, the short allele of NOS1 Ex1f-VNTR was presumed to be the risk allele for alcohol consumption in humans.

Even after controlling for impulsivity among 593 young adults, researchers in Estonia and Germany found that carriers of the long allele were significantly more likely to drink at an earlier age, consume more alcohol, and experience stronger effects of alcohol.

"Usually where some of these activities are related to impulsivity or anxiety or some psychopathology, there is always substance abuse in the same direction, but the data shows that, in this case, it might be opposite," lead author Dr. Kariina Laas said in an interview at the annual congress of the European College of Neuropsychopharmacology.

Long-allele carriers had their first drink at a median age of 14 years vs. 15 years for those with the short-allele (P = .033).

They also reported more often that a hangover is likely when drinking (P = .003). The hangover finding did not emerge because of drinking more, as controlling for total alcohol did not change the genotype effect, reported Dr. Laas of the Estonian Centre of Behavioural and Health Sciences, University of Tartu, Estonia.

The sample was the older cohort of the Estonian Children Personality, Behaviour, and Health Study, a population-representative sample of young adults who were asked to self-report alcohol use at ages 15, 18, and 25 years and to complete the Adaptive and Maladaptive Impulsivity Scale questionnaire at ages 18 and 25 years. Genotyping was also conducted.

At age 15, there was no effect of NOS1 Ex1f-VNTR genotype on alcohol consumption.

At age 18, a NOS1 Ex1f-VNTR and sex signal appeared, she said. Male long-allele carriers consumed significantly more per drinking session and were significantly more likely to be frequent alcohol users and in the upper quartiles of total alcohol consumption.

At age 25, long-allele carriers consumed more alcohol regardless of gender.

The reasons why the short allele – which is impulsivity related – is protective against alcohol consumption are unclear, Dr. Laas said. She speculated that short-allele carriers in the study may represent a unique subset or that they may exhibit more pathological features that could limit their social network.

"The influence of friends is huge on when they start [drinking]," she said.

The findings are also in concordance with animal studies where inhibition of NOS1 attenuates alcohol consumption in mice (Alcohol 2009;43:285-91), the authors noted.

The authors report no conflicts. The study was supported by a grant from the Estonian Ministry of Education and Science.

PARIS – A neuronal nitric oxide synthase gene polymorphism appears protective against alcohol consumption in adolescents and young adults, new research shows.

The culprit was not, however, what researchers had expected.

Previous research has shown that the neuronal nitric oxide synthase 1 (NOS1) gene promoter polymorphism, EX1f-VNTR (exon 1f-variable number tandem repeats), influences both impulsivity and psychopathology. The short allele, which has lower transcriptional activity, is considered the "risk" allele, compared with the long allele.

Given the link between impulsivity and alcohol consumption, the short allele of NOS1 Ex1f-VNTR was presumed to be the risk allele for alcohol consumption in humans.

Even after controlling for impulsivity among 593 young adults, researchers in Estonia and Germany found that carriers of the long allele were significantly more likely to drink at an earlier age, consume more alcohol, and experience stronger effects of alcohol.

"Usually where some of these activities are related to impulsivity or anxiety or some psychopathology, there is always substance abuse in the same direction, but the data shows that, in this case, it might be opposite," lead author Dr. Kariina Laas said in an interview at the annual congress of the European College of Neuropsychopharmacology.

Long-allele carriers had their first drink at a median age of 14 years vs. 15 years for those with the short-allele (P = .033).

They also reported more often that a hangover is likely when drinking (P = .003). The hangover finding did not emerge because of drinking more, as controlling for total alcohol did not change the genotype effect, reported Dr. Laas of the Estonian Centre of Behavioural and Health Sciences, University of Tartu, Estonia.

The sample was the older cohort of the Estonian Children Personality, Behaviour, and Health Study, a population-representative sample of young adults who were asked to self-report alcohol use at ages 15, 18, and 25 years and to complete the Adaptive and Maladaptive Impulsivity Scale questionnaire at ages 18 and 25 years. Genotyping was also conducted.

At age 15, there was no effect of NOS1 Ex1f-VNTR genotype on alcohol consumption.

At age 18, a NOS1 Ex1f-VNTR and sex signal appeared, she said. Male long-allele carriers consumed significantly more per drinking session and were significantly more likely to be frequent alcohol users and in the upper quartiles of total alcohol consumption.

At age 25, long-allele carriers consumed more alcohol regardless of gender.

The reasons why the short allele – which is impulsivity related – is protective against alcohol consumption are unclear, Dr. Laas said. She speculated that short-allele carriers in the study may represent a unique subset or that they may exhibit more pathological features that could limit their social network.

"The influence of friends is huge on when they start [drinking]," she said.

The findings are also in concordance with animal studies where inhibition of NOS1 attenuates alcohol consumption in mice (Alcohol 2009;43:285-91), the authors noted.

The authors report no conflicts. The study was supported by a grant from the Estonian Ministry of Education and Science.

PARIS  – The overall burden of mental health remains steady in Europe, but patients continue to struggle to receive appropriate treatment, according to a new report.

"There has been tremendous improvement in terms of recognition, but recognition is senseless, if no appropriate treatment follows," lead author Dr. Hans-Ulrich Wittchen said in an interview. "And there’s no indication that the rate of minimally adequate treatment has been improving over the last 10 years."

It is estimated that 38.2% or 164.8 million Europeans suffer each year from at least one mental disorder, according to the 2011 report by the European College of Neuropsychopharmacology (ECNP) and European Brain Council (EBC). Still, despite all efforts, only 10% are treated.

When the group published its initial report in 2005, the annual burden was 27.4%, representing 82 million affected adults, aged 18-65 years, among 301.7 million European Union (EU) residents.

The increased prevalence today is attributable to a larger EU reference population of 514 million residents, and the inclusion of 14 additional disorders covering children/adolescents and the elderly, Dr. Wittchen explained at the annual congress of the ECNP where the data were presented. Without the additional diagnoses, the overall prevalence rate would have been comparable, at 27.1%.

The current figures are a conservative estimate since many disorders could not be included, and only cases meeting full diagnostic criteria were considered, he said.

Anxiety disorders were the most common, affecting 14% of the population, followed by insomnia (7%), major depression (6.9%), somatoform disorders (6.3%), alcohol and drug dependence (less than 4%), attention-deficit/hyperactivity disorders among the young (5%), and dementia at 1% among those 60-65 years, but 30% in those 85 and older.

The lack of adequate treatment is particularly worrisome for affected children and adolescents. Notably, the first onset of anxiety disorders is almost invariably in childhood or adolescence, but with early recognition the risk of later onset depression can be reduced by more than 50%, said Dr. Wittchen, chair and director of the Institute of Clinical Psychology and Psychotherapy and Center of Clinical Epidemiology and Longitudinal Studies at Dresden University of Technology in Dresden, Germany

He suggests that the poor provision of mental health services is likely tied to underrecognition of the scope of mental and neurologic disorders, scarce resources and an inadequate number of providers with sufficient expertise.

"It would be unacceptable to other disciplines in medicine like cardiology if such complex treatment plans that we have developed for most mental disorders would be simply applied by primary care," Dr. Wittchen said.

Immediate ECNP past-president Prof. David Nutt said that with some disorders, patients have to overcome three hurdles in order to receive adequate care. Many patients do not know they are ill or think it’s their fault, their primary care provider fails to provide adequate treatment, or there is no approved therapy once the see a psychiatrist and the proper diagnosis is made.

Current political winds may only worsen the situation for patients with mental disorders in the United States and Europe, often envied by Americans for its universal insurance coverage. Both men cited proposed legislation in Denmark that would require only those patients with mental disorders to pay for their treatment. In Britain, the conservative government wants to redefine addiction as a lifestyle choice, said Dr. Nutt, professor of neuropsychopharmacology at the Imperial College in London.

"If we lose, we’re going to go back into the dark ages," he said. "It could set us back 30, 40 years."

The authors note that frequent and high degrees of impairment and disability can be directly linked to deficient treatment provision. Unlike other diseases, mental disorders are costly because of high indirect costs and not because of direct treatment costs.

The report, which covers residents in all 27 countries in the EU plus Switzerland, Iceland, and Norway, includes recommendations for political action. They include strengthening and broadening existing programs, improving allocation of scarce resources to mental disorders, boosting research and research support from industry and investors, and training for all health professions on disorders of the brain and their appropriate treatments.

The report was simultaneously published in the September issue of the journal, European Neuropsychopharmacology (2011;21:655-79).

Dr. Wittchen and Dr. Nutt reported no disclosures.

PARIS  – The overall burden of mental health remains steady in Europe, but patients continue to struggle to receive appropriate treatment, according to a new report.

"There has been tremendous improvement in terms of recognition, but recognition is senseless, if no appropriate treatment follows," lead author Dr. Hans-Ulrich Wittchen said in an interview. "And there’s no indication that the rate of minimally adequate treatment has been improving over the last 10 years."

It is estimated that 38.2% or 164.8 million Europeans suffer each year from at least one mental disorder, according to the 2011 report by the European College of Neuropsychopharmacology (ECNP) and European Brain Council (EBC). Still, despite all efforts, only 10% are treated.

When the group published its initial report in 2005, the annual burden was 27.4%, representing 82 million affected adults, aged 18-65 years, among 301.7 million European Union (EU) residents.

The increased prevalence today is attributable to a larger EU reference population of 514 million residents, and the inclusion of 14 additional disorders covering children/adolescents and the elderly, Dr. Wittchen explained at the annual congress of the ECNP where the data were presented. Without the additional diagnoses, the overall prevalence rate would have been comparable, at 27.1%.

The current figures are a conservative estimate since many disorders could not be included, and only cases meeting full diagnostic criteria were considered, he said.

Anxiety disorders were the most common, affecting 14% of the population, followed by insomnia (7%), major depression (6.9%), somatoform disorders (6.3%), alcohol and drug dependence (less than 4%), attention-deficit/hyperactivity disorders among the young (5%), and dementia at 1% among those 60-65 years, but 30% in those 85 and older.

The lack of adequate treatment is particularly worrisome for affected children and adolescents. Notably, the first onset of anxiety disorders is almost invariably in childhood or adolescence, but with early recognition the risk of later onset depression can be reduced by more than 50%, said Dr. Wittchen, chair and director of the Institute of Clinical Psychology and Psychotherapy and Center of Clinical Epidemiology and Longitudinal Studies at Dresden University of Technology in Dresden, Germany

He suggests that the poor provision of mental health services is likely tied to underrecognition of the scope of mental and neurologic disorders, scarce resources and an inadequate number of providers with sufficient expertise.

"It would be unacceptable to other disciplines in medicine like cardiology if such complex treatment plans that we have developed for most mental disorders would be simply applied by primary care," Dr. Wittchen said.

Immediate ECNP past-president Prof. David Nutt said that with some disorders, patients have to overcome three hurdles in order to receive adequate care. Many patients do not know they are ill or think it’s their fault, their primary care provider fails to provide adequate treatment, or there is no approved therapy once the see a psychiatrist and the proper diagnosis is made.

Current political winds may only worsen the situation for patients with mental disorders in the United States and Europe, often envied by Americans for its universal insurance coverage. Both men cited proposed legislation in Denmark that would require only those patients with mental disorders to pay for their treatment. In Britain, the conservative government wants to redefine addiction as a lifestyle choice, said Dr. Nutt, professor of neuropsychopharmacology at the Imperial College in London.

"If we lose, we’re going to go back into the dark ages," he said. "It could set us back 30, 40 years."

The authors note that frequent and high degrees of impairment and disability can be directly linked to deficient treatment provision. Unlike other diseases, mental disorders are costly because of high indirect costs and not because of direct treatment costs.

The report, which covers residents in all 27 countries in the EU plus Switzerland, Iceland, and Norway, includes recommendations for political action. They include strengthening and broadening existing programs, improving allocation of scarce resources to mental disorders, boosting research and research support from industry and investors, and training for all health professions on disorders of the brain and their appropriate treatments.

The report was simultaneously published in the September issue of the journal, European Neuropsychopharmacology (2011;21:655-79).

Dr. Wittchen and Dr. Nutt reported no disclosures.

PARIS  – The overall burden of mental health remains steady in Europe, but patients continue to struggle to receive appropriate treatment, according to a new report.

"There has been tremendous improvement in terms of recognition, but recognition is senseless, if no appropriate treatment follows," lead author Dr. Hans-Ulrich Wittchen said in an interview. "And there’s no indication that the rate of minimally adequate treatment has been improving over the last 10 years."

It is estimated that 38.2% or 164.8 million Europeans suffer each year from at least one mental disorder, according to the 2011 report by the European College of Neuropsychopharmacology (ECNP) and European Brain Council (EBC). Still, despite all efforts, only 10% are treated.

When the group published its initial report in 2005, the annual burden was 27.4%, representing 82 million affected adults, aged 18-65 years, among 301.7 million European Union (EU) residents.

The increased prevalence today is attributable to a larger EU reference population of 514 million residents, and the inclusion of 14 additional disorders covering children/adolescents and the elderly, Dr. Wittchen explained at the annual congress of the ECNP where the data were presented. Without the additional diagnoses, the overall prevalence rate would have been comparable, at 27.1%.

The current figures are a conservative estimate since many disorders could not be included, and only cases meeting full diagnostic criteria were considered, he said.

Anxiety disorders were the most common, affecting 14% of the population, followed by insomnia (7%), major depression (6.9%), somatoform disorders (6.3%), alcohol and drug dependence (less than 4%), attention-deficit/hyperactivity disorders among the young (5%), and dementia at 1% among those 60-65 years, but 30% in those 85 and older.

The lack of adequate treatment is particularly worrisome for affected children and adolescents. Notably, the first onset of anxiety disorders is almost invariably in childhood or adolescence, but with early recognition the risk of later onset depression can be reduced by more than 50%, said Dr. Wittchen, chair and director of the Institute of Clinical Psychology and Psychotherapy and Center of Clinical Epidemiology and Longitudinal Studies at Dresden University of Technology in Dresden, Germany

He suggests that the poor provision of mental health services is likely tied to underrecognition of the scope of mental and neurologic disorders, scarce resources and an inadequate number of providers with sufficient expertise.

"It would be unacceptable to other disciplines in medicine like cardiology if such complex treatment plans that we have developed for most mental disorders would be simply applied by primary care," Dr. Wittchen said.

Immediate ECNP past-president Prof. David Nutt said that with some disorders, patients have to overcome three hurdles in order to receive adequate care. Many patients do not know they are ill or think it’s their fault, their primary care provider fails to provide adequate treatment, or there is no approved therapy once the see a psychiatrist and the proper diagnosis is made.

Current political winds may only worsen the situation for patients with mental disorders in the United States and Europe, often envied by Americans for its universal insurance coverage. Both men cited proposed legislation in Denmark that would require only those patients with mental disorders to pay for their treatment. In Britain, the conservative government wants to redefine addiction as a lifestyle choice, said Dr. Nutt, professor of neuropsychopharmacology at the Imperial College in London.

"If we lose, we’re going to go back into the dark ages," he said. "It could set us back 30, 40 years."

The authors note that frequent and high degrees of impairment and disability can be directly linked to deficient treatment provision. Unlike other diseases, mental disorders are costly because of high indirect costs and not because of direct treatment costs.

The report, which covers residents in all 27 countries in the EU plus Switzerland, Iceland, and Norway, includes recommendations for political action. They include strengthening and broadening existing programs, improving allocation of scarce resources to mental disorders, boosting research and research support from industry and investors, and training for all health professions on disorders of the brain and their appropriate treatments.

The report was simultaneously published in the September issue of the journal, European Neuropsychopharmacology (2011;21:655-79).

Dr. Wittchen and Dr. Nutt reported no disclosures.

PARIS – Researchers have identified a series of metabolites strongly involved with neurodevelopment and memory that are unique to patients with schizophrenia.

Among 265 patients with schizophrenia and 216 healthy controls, 22 metabolites differed significantly between the schizophrenia and control groups (P value less than 3.8 x 10^-4), Dr. Dan Rujescu said at the annual congress of the European College of Neuropsychopharmacology. Of the 163 possible metabolites initially evaluated, 92 involved glycerophospholipids.

(c) Patrice G. Wendling/IMNG

Stepwise regression analysis that included age, sex, and body mass index (BMI) further whittled the field down to a panel of seven candidate metabolites: ornithine, arginine, glutamine, histidine, phosphatidylcholine acyl-alkyl C38:2, dodecenoyl carnitine, and octenoyl carnitine. Only ornithine was downregulated in patients with schizophrenia, with the remaining upregulated.

"The panel had fairly high discriminatory power," said Dr. Rujescu, with the University of Munich.

The researchers then constructed a schizophrenia gene-metabolite network consisting of 13 schizophrenia genes associated with five metabolites. In all, 52% of the networks were related to neurodevelopment and learning or memory, he said. Impaired memory and cognitive function are increasingly being recognized as hallmarks of schizophrenia.

The use of metabolomics is new in schizophrenia, and its application to pharmacology even newer. Pharmacometabolomics measures both the disease and the environmental effects, so is highly dynamic, compared with genetics, Dr. Rujescu said. Moreover, not all patients correct their aberrant metabolic profiles upon treatment. Thus, metabolic profiling could be used as an additional tool to complement clinical evaluation in defining drug response phenotypes, he said.

An analysis in 117 patients on monotherapy, however, was unable to distinguish between treatment arms, although the patient numbers were small, Dr. Rujescu said. Clozapine, quetiapine, and risperidone were the most frequently used drugs, followed by olanzapine, amisulpride, and haloperidol. The patients were not on any other drugs whatsoever, including aspirin. They also were not smokers.

Four of the seven identified metabolites – histidine, arginine, ornithine and glutamine – are related to genes involved in arginine-glutamine metabolism and nitrogen compound biosynthesis. One of the involved genes, TCF4, is involved in arginine metabolism and is essential for normal brain development, Dr. Rujescu said.

A marker in intron four of transcription factor 4 (TCF4) on chromosome 18q21.2 was among seven markers previously identified through genomics, by a team of researchers including Dr. Rujescu, as being significantly associated with schizophrenia (Nature 2009; 460:744-7). Another marker located upstream of the neurogranin gene on chromosome 11q24.2 also pointed to disturbances in pathways involved in brain development, memory, and cognition. The remaining markers spanned the major histocompatibility complex region on chromosome 6p21.3-22.1, supporting the potential role for an autoimmune component in schizophrenia.

The next step for the researchers is to identifiy pharmacometabolomic signatures for response and side effects among 350 medication-naïve patients with schizophrenia whose first episode of psychosis was treated with amisulpride in the ongoing OPTIMISE (Optimization of Treatment and Management of Schizophrenia in Europe) trial. The trial (www.optimisetrial.eu) is being conducted by a consortium of 18 European psychiatric institutes, including the Helmholtz Center Munich, and has enrolled 350 patients to date.

The authors report no disclosures.

PARIS – Researchers have identified a series of metabolites strongly involved with neurodevelopment and memory that are unique to patients with schizophrenia.

Among 265 patients with schizophrenia and 216 healthy controls, 22 metabolites differed significantly between the schizophrenia and control groups (P value less than 3.8 x 10^-4), Dr. Dan Rujescu said at the annual congress of the European College of Neuropsychopharmacology. Of the 163 possible metabolites initially evaluated, 92 involved glycerophospholipids.

(c) Patrice G. Wendling/IMNG

Stepwise regression analysis that included age, sex, and body mass index (BMI) further whittled the field down to a panel of seven candidate metabolites: ornithine, arginine, glutamine, histidine, phosphatidylcholine acyl-alkyl C38:2, dodecenoyl carnitine, and octenoyl carnitine. Only ornithine was downregulated in patients with schizophrenia, with the remaining upregulated.

"The panel had fairly high discriminatory power," said Dr. Rujescu, with the University of Munich.

The researchers then constructed a schizophrenia gene-metabolite network consisting of 13 schizophrenia genes associated with five metabolites. In all, 52% of the networks were related to neurodevelopment and learning or memory, he said. Impaired memory and cognitive function are increasingly being recognized as hallmarks of schizophrenia.

The use of metabolomics is new in schizophrenia, and its application to pharmacology even newer. Pharmacometabolomics measures both the disease and the environmental effects, so is highly dynamic, compared with genetics, Dr. Rujescu said. Moreover, not all patients correct their aberrant metabolic profiles upon treatment. Thus, metabolic profiling could be used as an additional tool to complement clinical evaluation in defining drug response phenotypes, he said.

An analysis in 117 patients on monotherapy, however, was unable to distinguish between treatment arms, although the patient numbers were small, Dr. Rujescu said. Clozapine, quetiapine, and risperidone were the most frequently used drugs, followed by olanzapine, amisulpride, and haloperidol. The patients were not on any other drugs whatsoever, including aspirin. They also were not smokers.

Four of the seven identified metabolites – histidine, arginine, ornithine and glutamine – are related to genes involved in arginine-glutamine metabolism and nitrogen compound biosynthesis. One of the involved genes, TCF4, is involved in arginine metabolism and is essential for normal brain development, Dr. Rujescu said.

A marker in intron four of transcription factor 4 (TCF4) on chromosome 18q21.2 was among seven markers previously identified through genomics, by a team of researchers including Dr. Rujescu, as being significantly associated with schizophrenia (Nature 2009; 460:744-7). Another marker located upstream of the neurogranin gene on chromosome 11q24.2 also pointed to disturbances in pathways involved in brain development, memory, and cognition. The remaining markers spanned the major histocompatibility complex region on chromosome 6p21.3-22.1, supporting the potential role for an autoimmune component in schizophrenia.

The next step for the researchers is to identifiy pharmacometabolomic signatures for response and side effects among 350 medication-naïve patients with schizophrenia whose first episode of psychosis was treated with amisulpride in the ongoing OPTIMISE (Optimization of Treatment and Management of Schizophrenia in Europe) trial. The trial (www.optimisetrial.eu) is being conducted by a consortium of 18 European psychiatric institutes, including the Helmholtz Center Munich, and has enrolled 350 patients to date.

The authors report no disclosures.

PARIS – Researchers have identified a series of metabolites strongly involved with neurodevelopment and memory that are unique to patients with schizophrenia.

Among 265 patients with schizophrenia and 216 healthy controls, 22 metabolites differed significantly between the schizophrenia and control groups (P value less than 3.8 x 10^-4), Dr. Dan Rujescu said at the annual congress of the European College of Neuropsychopharmacology. Of the 163 possible metabolites initially evaluated, 92 involved glycerophospholipids.

(c) Patrice G. Wendling/IMNG

Stepwise regression analysis that included age, sex, and body mass index (BMI) further whittled the field down to a panel of seven candidate metabolites: ornithine, arginine, glutamine, histidine, phosphatidylcholine acyl-alkyl C38:2, dodecenoyl carnitine, and octenoyl carnitine. Only ornithine was downregulated in patients with schizophrenia, with the remaining upregulated.

"The panel had fairly high discriminatory power," said Dr. Rujescu, with the University of Munich.

The researchers then constructed a schizophrenia gene-metabolite network consisting of 13 schizophrenia genes associated with five metabolites. In all, 52% of the networks were related to neurodevelopment and learning or memory, he said. Impaired memory and cognitive function are increasingly being recognized as hallmarks of schizophrenia.

The use of metabolomics is new in schizophrenia, and its application to pharmacology even newer. Pharmacometabolomics measures both the disease and the environmental effects, so is highly dynamic, compared with genetics, Dr. Rujescu said. Moreover, not all patients correct their aberrant metabolic profiles upon treatment. Thus, metabolic profiling could be used as an additional tool to complement clinical evaluation in defining drug response phenotypes, he said.

An analysis in 117 patients on monotherapy, however, was unable to distinguish between treatment arms, although the patient numbers were small, Dr. Rujescu said. Clozapine, quetiapine, and risperidone were the most frequently used drugs, followed by olanzapine, amisulpride, and haloperidol. The patients were not on any other drugs whatsoever, including aspirin. They also were not smokers.

Four of the seven identified metabolites – histidine, arginine, ornithine and glutamine – are related to genes involved in arginine-glutamine metabolism and nitrogen compound biosynthesis. One of the involved genes, TCF4, is involved in arginine metabolism and is essential for normal brain development, Dr. Rujescu said.

A marker in intron four of transcription factor 4 (TCF4) on chromosome 18q21.2 was among seven markers previously identified through genomics, by a team of researchers including Dr. Rujescu, as being significantly associated with schizophrenia (Nature 2009; 460:744-7). Another marker located upstream of the neurogranin gene on chromosome 11q24.2 also pointed to disturbances in pathways involved in brain development, memory, and cognition. The remaining markers spanned the major histocompatibility complex region on chromosome 6p21.3-22.1, supporting the potential role for an autoimmune component in schizophrenia.

The next step for the researchers is to identifiy pharmacometabolomic signatures for response and side effects among 350 medication-naïve patients with schizophrenia whose first episode of psychosis was treated with amisulpride in the ongoing OPTIMISE (Optimization of Treatment and Management of Schizophrenia in Europe) trial. The trial (www.optimisetrial.eu) is being conducted by a consortium of 18 European psychiatric institutes, including the Helmholtz Center Munich, and has enrolled 350 patients to date.

The authors report no disclosures.

CHICAGO – Even though the numbers remain small, fluconazole-resistant Candida albicans vulvovaginitis appears to be emerging as a thorny clinical problem, one expert suggests.

Since its introduction in 1990 as a prophylactic antifungal agent after bone marrow transplantation, fluconazole (Diflucan) has become established as the dominant therapy for vulvovaginal candidiasis (VVC) worldwide. In North America alone, roughly 8 million cases of recurrent vulvovaginitis are reported annually, with more than 90% due to C. albicans.

"So the possibility of resistance is a tremendous problem and concern," asserted Dr. Jack D. Sobel, chief of the division of infectious diseases and professor of obstetrics and gynecology at Wayne State University in Detroit.

Women with recurrent vulvovaginitis are treated with induction and prolonged, low-dose maintenance fluconazole regimens to achieve an asymptomatic state. Successful control, not cure, is achieved in more than 90%. Susceptibility testing for C. albicans is not standard of care, so there is very little published data on prolonged fluconazole use, Dr. Sobel said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

He and his colleagues published the only study to address the issue of resistance, and it failed to identify any evidence of fluconazole resistance in isolates of C. albicans after just 1 year of follow-up (N. Engl. J. Med. 2004;351:876-83).

Clinicians at Wayne State’s Vaginitis Clinic, however, have observed an uptick in the frequency of refractory Candida vulvovaginitis cases in the last 10 years among the more than 500 women with recurrent vulvovaginitis that they follow. The women present either on a maintenance fluconazole regimen with a breakthrough of symptoms accompanied by positive cultures or fail to resolve acute symptomatic vulvovaginitis with multidose fluconazole and have increased minimum inhibitory concentration (MIC) in vitro, Dr. Sobel explained.

A retrospective review of patients referred to the Vaginitis Clinic between 2000 and 2010 revealed 25 patients with clinically refractory fluconazole-resistant vulvovaginitis with confirmed in vitro resistance, with an MIC at least 2 mcg/mL (median 8 mcg/mL).

"Two-thirds of these patients were seen in the last 5 years, so the incidence is increasing," he said.

Eight patients had an MIC of 2 mcg/mL and 17 had MICs ranging from 4-128 mcg/mL. Cross resistance to itraconazole (Sporanox) was present in five women and to ketoconazole (Nizoral) in four.

The cohort consists of married, insured Caucasian women with an average or above average socioeconomic status. Their mean age was 43 years (range 32-56 years). All patients had significant consumption of and recent exposure to fluconazole, with 64% on low-dose, weekly maintenance fluconazole.

Significant risk factors for refractory Candida VVC included more than 10 lifetime sexual partners, recent use of antibiotics, and for mycological failure included increased fluconazole exposure and older age of VVC onset.

Management

Management of refractory VVC is possible, but can be extremely difficult, Dr. Sobel acknowledged.

"When you can’t use fluconazole, the closet is pretty empty," he said.

Dr. Sobel recommends initially using boric acid 600 mg per day for 14 days until an MIC is available. For those with low-level resistance, defined by an MIC of 2-4 mcg/mL, clinicians should increase the fluconazole dose to 150-200 mg twice weekly. Eleven of the 25 patients in the study cohort were controlled on this regimen, with five eventually discontinuing fluconazole.

"In patients with high level resistance, treatment depends on the presence of azole cross-resistance," he said.

Among eight such patients, three were successfully controlled on 200 mg per day of itraconazole, and four of five were controlled on ketoconazole 100 mg per day, both typically for several months. One patient required daily gentian violet for 14 days, with cure, and three patients were controlled on boric acid three times per week.

The novel, oral broad-spectrum antifungal, voriconazole (Vfend) is a possibility, but is rarely used because it is so poorly tolerated, Dr. Sobel said. Audience members questioned whether flucytosine (Ancobon), a synthetic antimycotic, can be employed. Specialty pharmacies can formulate it, but at $1,500 to $2,000 per tube is out of reach for most women.

The antifungal antibiotic nystatin, which was patented back in 1957 as the world’s first antifungal, is a far cheaper alternative, but should be given at 100,000 units daily per vagina only, Dr. Sobel said.

Nystatin also upstaged newer antifungal agents when used to treat vulvovaginal candidiasis caused by Candida glabrata in sequential, prospective clinical trials.

On day 7 to day 14 of follow-up, mycological cure of C. glabrata vulvovaginitis was achieved by 15 of 16 women (94%) treated with a nystatin vaginal suppository, compared with 8 of 19 (42%) given a miconazole nitrate vaginal suppository, 5 of 9 (56%) given oral fluconazole and 7 of 15 (47%) given oral itraconazole.

At day 30 to day 35 of follow-up, mycological cure rates, based on a positive or negative Candida culture, were 94%, 33%, 56% and 40%, respectively.

"Nystatin vaginal suppository could be a therapy choice for vulvovaginal candidiasis caused by Candida glabrata," Dr. Shangrong Fan said.

While C. albicans is the most commonly isolated species, various studies have reported a shift towards infections caused by non-albicans Candida species such as C. glabrata.

The women were enrolled prospectively in separate, sequential, nonrandomized clinical trials and treated with nystatin vaginal suppository at 20 MU per day for 7 days or two 1,200 mg doses of miconazole vaginal suppositories 72 hours apart or oral fluconazole two 150 mg doses 72 hours apart or oral itraconazole 200 mg two times for 1 day.

Dr. Fan, an obstetrician/gynecologist and his colleagues in the department of laboratory sciences at Peking University Shenzhen Hospital in Shenzhen, China, also conducted an in vitro susceptibility study. All strains were identified using the API Candida System and susceptibility testing performed using a commercial (Rosco Diagnostica) agar diffusion method.

The in vitro susceptible rate of C. glabrata on nystatin was 100% (57/57), compared with 90% (51/57) for miconazole, 58% (40/69) for fluconazole, and 87% (58/67) for itraconazole.

The susceptible-dose-dependent rates were 0%, 11%, 39%, and 12%, respectively.

Resistance to nystatin or miconazole was not observed, and occurred in 3% of strains exposed to fluconazole and 1.5% exposed to itraconazole, Dr. Fan said.

Dr. Sobel, Dr. Fan, and their colleagues reported no relevant financial disclosures.

CHICAGO – Even though the numbers remain small, fluconazole-resistant Candida albicans vulvovaginitis appears to be emerging as a thorny clinical problem, one expert suggests.

Since its introduction in 1990 as a prophylactic antifungal agent after bone marrow transplantation, fluconazole (Diflucan) has become established as the dominant therapy for vulvovaginal candidiasis (VVC) worldwide. In North America alone, roughly 8 million cases of recurrent vulvovaginitis are reported annually, with more than 90% due to C. albicans.

"So the possibility of resistance is a tremendous problem and concern," asserted Dr. Jack D. Sobel, chief of the division of infectious diseases and professor of obstetrics and gynecology at Wayne State University in Detroit.

Women with recurrent vulvovaginitis are treated with induction and prolonged, low-dose maintenance fluconazole regimens to achieve an asymptomatic state. Successful control, not cure, is achieved in more than 90%. Susceptibility testing for C. albicans is not standard of care, so there is very little published data on prolonged fluconazole use, Dr. Sobel said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

He and his colleagues published the only study to address the issue of resistance, and it failed to identify any evidence of fluconazole resistance in isolates of C. albicans after just 1 year of follow-up (N. Engl. J. Med. 2004;351:876-83).

Clinicians at Wayne State’s Vaginitis Clinic, however, have observed an uptick in the frequency of refractory Candida vulvovaginitis cases in the last 10 years among the more than 500 women with recurrent vulvovaginitis that they follow. The women present either on a maintenance fluconazole regimen with a breakthrough of symptoms accompanied by positive cultures or fail to resolve acute symptomatic vulvovaginitis with multidose fluconazole and have increased minimum inhibitory concentration (MIC) in vitro, Dr. Sobel explained.

A retrospective review of patients referred to the Vaginitis Clinic between 2000 and 2010 revealed 25 patients with clinically refractory fluconazole-resistant vulvovaginitis with confirmed in vitro resistance, with an MIC at least 2 mcg/mL (median 8 mcg/mL).

"Two-thirds of these patients were seen in the last 5 years, so the incidence is increasing," he said.

Eight patients had an MIC of 2 mcg/mL and 17 had MICs ranging from 4-128 mcg/mL. Cross resistance to itraconazole (Sporanox) was present in five women and to ketoconazole (Nizoral) in four.

The cohort consists of married, insured Caucasian women with an average or above average socioeconomic status. Their mean age was 43 years (range 32-56 years). All patients had significant consumption of and recent exposure to fluconazole, with 64% on low-dose, weekly maintenance fluconazole.

Significant risk factors for refractory Candida VVC included more than 10 lifetime sexual partners, recent use of antibiotics, and for mycological failure included increased fluconazole exposure and older age of VVC onset.

Management

Management of refractory VVC is possible, but can be extremely difficult, Dr. Sobel acknowledged.

"When you can’t use fluconazole, the closet is pretty empty," he said.

Dr. Sobel recommends initially using boric acid 600 mg per day for 14 days until an MIC is available. For those with low-level resistance, defined by an MIC of 2-4 mcg/mL, clinicians should increase the fluconazole dose to 150-200 mg twice weekly. Eleven of the 25 patients in the study cohort were controlled on this regimen, with five eventually discontinuing fluconazole.

"In patients with high level resistance, treatment depends on the presence of azole cross-resistance," he said.

Among eight such patients, three were successfully controlled on 200 mg per day of itraconazole, and four of five were controlled on ketoconazole 100 mg per day, both typically for several months. One patient required daily gentian violet for 14 days, with cure, and three patients were controlled on boric acid three times per week.

The novel, oral broad-spectrum antifungal, voriconazole (Vfend) is a possibility, but is rarely used because it is so poorly tolerated, Dr. Sobel said. Audience members questioned whether flucytosine (Ancobon), a synthetic antimycotic, can be employed. Specialty pharmacies can formulate it, but at $1,500 to $2,000 per tube is out of reach for most women.

The antifungal antibiotic nystatin, which was patented back in 1957 as the world’s first antifungal, is a far cheaper alternative, but should be given at 100,000 units daily per vagina only, Dr. Sobel said.

Nystatin also upstaged newer antifungal agents when used to treat vulvovaginal candidiasis caused by Candida glabrata in sequential, prospective clinical trials.

On day 7 to day 14 of follow-up, mycological cure of C. glabrata vulvovaginitis was achieved by 15 of 16 women (94%) treated with a nystatin vaginal suppository, compared with 8 of 19 (42%) given a miconazole nitrate vaginal suppository, 5 of 9 (56%) given oral fluconazole and 7 of 15 (47%) given oral itraconazole.

At day 30 to day 35 of follow-up, mycological cure rates, based on a positive or negative Candida culture, were 94%, 33%, 56% and 40%, respectively.

"Nystatin vaginal suppository could be a therapy choice for vulvovaginal candidiasis caused by Candida glabrata," Dr. Shangrong Fan said.

While C. albicans is the most commonly isolated species, various studies have reported a shift towards infections caused by non-albicans Candida species such as C. glabrata.

The women were enrolled prospectively in separate, sequential, nonrandomized clinical trials and treated with nystatin vaginal suppository at 20 MU per day for 7 days or two 1,200 mg doses of miconazole vaginal suppositories 72 hours apart or oral fluconazole two 150 mg doses 72 hours apart or oral itraconazole 200 mg two times for 1 day.

Dr. Fan, an obstetrician/gynecologist and his colleagues in the department of laboratory sciences at Peking University Shenzhen Hospital in Shenzhen, China, also conducted an in vitro susceptibility study. All strains were identified using the API Candida System and susceptibility testing performed using a commercial (Rosco Diagnostica) agar diffusion method.

The in vitro susceptible rate of C. glabrata on nystatin was 100% (57/57), compared with 90% (51/57) for miconazole, 58% (40/69) for fluconazole, and 87% (58/67) for itraconazole.

The susceptible-dose-dependent rates were 0%, 11%, 39%, and 12%, respectively.

Resistance to nystatin or miconazole was not observed, and occurred in 3% of strains exposed to fluconazole and 1.5% exposed to itraconazole, Dr. Fan said.

Dr. Sobel, Dr. Fan, and their colleagues reported no relevant financial disclosures.

CHICAGO – Even though the numbers remain small, fluconazole-resistant Candida albicans vulvovaginitis appears to be emerging as a thorny clinical problem, one expert suggests.

Since its introduction in 1990 as a prophylactic antifungal agent after bone marrow transplantation, fluconazole (Diflucan) has become established as the dominant therapy for vulvovaginal candidiasis (VVC) worldwide. In North America alone, roughly 8 million cases of recurrent vulvovaginitis are reported annually, with more than 90% due to C. albicans.

"So the possibility of resistance is a tremendous problem and concern," asserted Dr. Jack D. Sobel, chief of the division of infectious diseases and professor of obstetrics and gynecology at Wayne State University in Detroit.

Women with recurrent vulvovaginitis are treated with induction and prolonged, low-dose maintenance fluconazole regimens to achieve an asymptomatic state. Successful control, not cure, is achieved in more than 90%. Susceptibility testing for C. albicans is not standard of care, so there is very little published data on prolonged fluconazole use, Dr. Sobel said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

He and his colleagues published the only study to address the issue of resistance, and it failed to identify any evidence of fluconazole resistance in isolates of C. albicans after just 1 year of follow-up (N. Engl. J. Med. 2004;351:876-83).

Clinicians at Wayne State’s Vaginitis Clinic, however, have observed an uptick in the frequency of refractory Candida vulvovaginitis cases in the last 10 years among the more than 500 women with recurrent vulvovaginitis that they follow. The women present either on a maintenance fluconazole regimen with a breakthrough of symptoms accompanied by positive cultures or fail to resolve acute symptomatic vulvovaginitis with multidose fluconazole and have increased minimum inhibitory concentration (MIC) in vitro, Dr. Sobel explained.

A retrospective review of patients referred to the Vaginitis Clinic between 2000 and 2010 revealed 25 patients with clinically refractory fluconazole-resistant vulvovaginitis with confirmed in vitro resistance, with an MIC at least 2 mcg/mL (median 8 mcg/mL).

"Two-thirds of these patients were seen in the last 5 years, so the incidence is increasing," he said.

Eight patients had an MIC of 2 mcg/mL and 17 had MICs ranging from 4-128 mcg/mL. Cross resistance to itraconazole (Sporanox) was present in five women and to ketoconazole (Nizoral) in four.

The cohort consists of married, insured Caucasian women with an average or above average socioeconomic status. Their mean age was 43 years (range 32-56 years). All patients had significant consumption of and recent exposure to fluconazole, with 64% on low-dose, weekly maintenance fluconazole.

Significant risk factors for refractory Candida VVC included more than 10 lifetime sexual partners, recent use of antibiotics, and for mycological failure included increased fluconazole exposure and older age of VVC onset.

Management

Management of refractory VVC is possible, but can be extremely difficult, Dr. Sobel acknowledged.

"When you can’t use fluconazole, the closet is pretty empty," he said.

Dr. Sobel recommends initially using boric acid 600 mg per day for 14 days until an MIC is available. For those with low-level resistance, defined by an MIC of 2-4 mcg/mL, clinicians should increase the fluconazole dose to 150-200 mg twice weekly. Eleven of the 25 patients in the study cohort were controlled on this regimen, with five eventually discontinuing fluconazole.

"In patients with high level resistance, treatment depends on the presence of azole cross-resistance," he said.

Among eight such patients, three were successfully controlled on 200 mg per day of itraconazole, and four of five were controlled on ketoconazole 100 mg per day, both typically for several months. One patient required daily gentian violet for 14 days, with cure, and three patients were controlled on boric acid three times per week.

The novel, oral broad-spectrum antifungal, voriconazole (Vfend) is a possibility, but is rarely used because it is so poorly tolerated, Dr. Sobel said. Audience members questioned whether flucytosine (Ancobon), a synthetic antimycotic, can be employed. Specialty pharmacies can formulate it, but at $1,500 to $2,000 per tube is out of reach for most women.

The antifungal antibiotic nystatin, which was patented back in 1957 as the world’s first antifungal, is a far cheaper alternative, but should be given at 100,000 units daily per vagina only, Dr. Sobel said.

Nystatin also upstaged newer antifungal agents when used to treat vulvovaginal candidiasis caused by Candida glabrata in sequential, prospective clinical trials.

On day 7 to day 14 of follow-up, mycological cure of C. glabrata vulvovaginitis was achieved by 15 of 16 women (94%) treated with a nystatin vaginal suppository, compared with 8 of 19 (42%) given a miconazole nitrate vaginal suppository, 5 of 9 (56%) given oral fluconazole and 7 of 15 (47%) given oral itraconazole.

At day 30 to day 35 of follow-up, mycological cure rates, based on a positive or negative Candida culture, were 94%, 33%, 56% and 40%, respectively.

"Nystatin vaginal suppository could be a therapy choice for vulvovaginal candidiasis caused by Candida glabrata," Dr. Shangrong Fan said.

While C. albicans is the most commonly isolated species, various studies have reported a shift towards infections caused by non-albicans Candida species such as C. glabrata.

The women were enrolled prospectively in separate, sequential, nonrandomized clinical trials and treated with nystatin vaginal suppository at 20 MU per day for 7 days or two 1,200 mg doses of miconazole vaginal suppositories 72 hours apart or oral fluconazole two 150 mg doses 72 hours apart or oral itraconazole 200 mg two times for 1 day.

Dr. Fan, an obstetrician/gynecologist and his colleagues in the department of laboratory sciences at Peking University Shenzhen Hospital in Shenzhen, China, also conducted an in vitro susceptibility study. All strains were identified using the API Candida System and susceptibility testing performed using a commercial (Rosco Diagnostica) agar diffusion method.

The in vitro susceptible rate of C. glabrata on nystatin was 100% (57/57), compared with 90% (51/57) for miconazole, 58% (40/69) for fluconazole, and 87% (58/67) for itraconazole.

The susceptible-dose-dependent rates were 0%, 11%, 39%, and 12%, respectively.

Resistance to nystatin or miconazole was not observed, and occurred in 3% of strains exposed to fluconazole and 1.5% exposed to itraconazole, Dr. Fan said.

Dr. Sobel, Dr. Fan, and their colleagues reported no relevant financial disclosures.

CHICAGO – H1N1 influenza infection during the 2009 pandemic did not impact pregnancy outcomes in a retrospective cohort study of 887 women.

Subtle differences were observed, however, among women with severe infection or delayed treatment, Dr. Amber Naresh reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

She presented a retrospective cohort study performed at three tertiary care medical centers of all inpatient and outpatient cases of pregnant women with laboratory-confirmed 2009 H1N1 influenza. For each case, five pregnant women who tested negative for H1N1 influenza or were untested were randomly chosen from each site’s database and matched by estimated date of confinement and site.

Based on a preliminary analysis, the 147 H1N1 cases and 740 controls had nearly identical birth weights (average 3,208 g vs. 3,219 g) and gestational ages at delivery (average 38.5 vs. 38.7 weeks).

After the investigators controlled for study site, age, race, multiples, primiparity, medical conditions, and smoking, the cases and controls also had similar rates of the following:

• Term low birth weight (5.6% vs. 3.6%; odds ratio, 1.45).

• Preterm delivery less than 37 weeks’ gestation (13.3% vs. 11.6%; OR, 1.10).

• Premature rupture of membranes (1.7% vs. 2.6%; OR, 0.61).

• Abruption (0.9% vs. 1.2%; OR, 0.49).

• Cesarean section (27.5% vs. 30%; OR, 0.82).

• Induction (36% vs. 39%; OR, 0.83).

• Fetal anomalies (4.7% vs. 4.9%; OR, 1.24).

• Hypertensive disorders of pregnancy (14.3% vs. 13.2%; OR, 0.98).

• Neonatal ICU admission (13% vs. 11%; OR, 1.21).

"There did not appear to be any significant differences in pregnancy outcomes between cases and controls," said Dr. Naresh of Magee-Women’s Hospital of the University of Pittsburgh.

Pregnancy outcomes also did not differ when stratified by trimester, although more infections occurred in the second trimester, followed by the third and first trimesters, she said.

Previous case series have suggested an increased rate of preterm delivery, reaching 30% in an early report of H1N1 influenza in pregnancy and 60% among critically ill women. A recent study also reported lower birth weights among 16 women with proven H1N1 infection, compared with 25 women with influenzalike illness (Am. J. Obstet. Gynecol. 2011;204[suppl. 1]:S58-63), she said.

A subgroup analysis of women in the current study with severe disease, defined as requiring hospitalization, identified a nonsignificant trend for lower birth weight, compared with controls (3,013 g vs. 3,219 g), and lower gestational age (37.9 weeks vs. 38.7 weeks).

The combined outcome of term low birth weight, preterm birth, and abruption was significantly more common among the severe H1N1 cases than controls after study site, age, race, multiples, primiparity, medical conditions, and smoking were controlled for (31.4% vs. 15.7%; OR, 2.45). In addition, more than 30% of women in the severe group had complications, compared with only 15% in the control group, Dr. Naresh said.

The researchers also looked at the influence of early antiviral administration, which has been reported to be associated with fewer maternal ICU admissions and fewer deaths (JAMA 2010;303:1517-25).

Gestational age at delivery was 1 week earlier among the 27 women receiving oseltamivir (Tamiflu) more than 48 hours after symptom onset compared with the 52 women receiving it in less than 48 hours, as recommended by the manufacturer (37.6 weeks vs. 38.6 weeks).

"It’s not clear how clinically significant that is, but it’s interesting nonetheless," Dr. Naresh said.

Birth weights among the delayed- and early-treatment groups were similar at 3,007 g and 3,160 g.

All cases of H1N1 infection were significantly more likely than controls to be black (27% vs. 19%), and to have prepregnancy diabetes (4% vs. 1%), seizure disorder (3.4% vs. 0.8%), and asthma (17% vs. 9%). The average age of the cohort was 28 years.

Limitations of the study are that some of the controls may have had influenza since many were untested and data on specific neonatal outcomes associated with ICU admission were limited.

Dr. Naresh said future steps include a small-for-gestational-age analysis and an evaluation of the role of socioeconomic status and of differences among the three sites: the University of Pittsburgh Medical Center, the University of Colorado at Denver, and the University of Washington Medical Center in Seattle.

Dr. Naresh and her coauthors reported no relevant financial disclosures.

CHICAGO – H1N1 influenza infection during the 2009 pandemic did not impact pregnancy outcomes in a retrospective cohort study of 887 women.

Subtle differences were observed, however, among women with severe infection or delayed treatment, Dr. Amber Naresh reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

She presented a retrospective cohort study performed at three tertiary care medical centers of all inpatient and outpatient cases of pregnant women with laboratory-confirmed 2009 H1N1 influenza. For each case, five pregnant women who tested negative for H1N1 influenza or were untested were randomly chosen from each site’s database and matched by estimated date of confinement and site.

Based on a preliminary analysis, the 147 H1N1 cases and 740 controls had nearly identical birth weights (average 3,208 g vs. 3,219 g) and gestational ages at delivery (average 38.5 vs. 38.7 weeks).

After the investigators controlled for study site, age, race, multiples, primiparity, medical conditions, and smoking, the cases and controls also had similar rates of the following:

• Term low birth weight (5.6% vs. 3.6%; odds ratio, 1.45).

• Preterm delivery less than 37 weeks’ gestation (13.3% vs. 11.6%; OR, 1.10).

• Premature rupture of membranes (1.7% vs. 2.6%; OR, 0.61).

• Abruption (0.9% vs. 1.2%; OR, 0.49).

• Cesarean section (27.5% vs. 30%; OR, 0.82).

• Induction (36% vs. 39%; OR, 0.83).

• Fetal anomalies (4.7% vs. 4.9%; OR, 1.24).

• Hypertensive disorders of pregnancy (14.3% vs. 13.2%; OR, 0.98).

• Neonatal ICU admission (13% vs. 11%; OR, 1.21).

"There did not appear to be any significant differences in pregnancy outcomes between cases and controls," said Dr. Naresh of Magee-Women’s Hospital of the University of Pittsburgh.

Pregnancy outcomes also did not differ when stratified by trimester, although more infections occurred in the second trimester, followed by the third and first trimesters, she said.

Previous case series have suggested an increased rate of preterm delivery, reaching 30% in an early report of H1N1 influenza in pregnancy and 60% among critically ill women. A recent study also reported lower birth weights among 16 women with proven H1N1 infection, compared with 25 women with influenzalike illness (Am. J. Obstet. Gynecol. 2011;204[suppl. 1]:S58-63), she said.

A subgroup analysis of women in the current study with severe disease, defined as requiring hospitalization, identified a nonsignificant trend for lower birth weight, compared with controls (3,013 g vs. 3,219 g), and lower gestational age (37.9 weeks vs. 38.7 weeks).

The combined outcome of term low birth weight, preterm birth, and abruption was significantly more common among the severe H1N1 cases than controls after study site, age, race, multiples, primiparity, medical conditions, and smoking were controlled for (31.4% vs. 15.7%; OR, 2.45). In addition, more than 30% of women in the severe group had complications, compared with only 15% in the control group, Dr. Naresh said.

The researchers also looked at the influence of early antiviral administration, which has been reported to be associated with fewer maternal ICU admissions and fewer deaths (JAMA 2010;303:1517-25).

Gestational age at delivery was 1 week earlier among the 27 women receiving oseltamivir (Tamiflu) more than 48 hours after symptom onset compared with the 52 women receiving it in less than 48 hours, as recommended by the manufacturer (37.6 weeks vs. 38.6 weeks).

"It’s not clear how clinically significant that is, but it’s interesting nonetheless," Dr. Naresh said.

Birth weights among the delayed- and early-treatment groups were similar at 3,007 g and 3,160 g.

All cases of H1N1 infection were significantly more likely than controls to be black (27% vs. 19%), and to have prepregnancy diabetes (4% vs. 1%), seizure disorder (3.4% vs. 0.8%), and asthma (17% vs. 9%). The average age of the cohort was 28 years.

Limitations of the study are that some of the controls may have had influenza since many were untested and data on specific neonatal outcomes associated with ICU admission were limited.

Dr. Naresh said future steps include a small-for-gestational-age analysis and an evaluation of the role of socioeconomic status and of differences among the three sites: the University of Pittsburgh Medical Center, the University of Colorado at Denver, and the University of Washington Medical Center in Seattle.

Dr. Naresh and her coauthors reported no relevant financial disclosures.

CHICAGO – H1N1 influenza infection during the 2009 pandemic did not impact pregnancy outcomes in a retrospective cohort study of 887 women.

Subtle differences were observed, however, among women with severe infection or delayed treatment, Dr. Amber Naresh reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

She presented a retrospective cohort study performed at three tertiary care medical centers of all inpatient and outpatient cases of pregnant women with laboratory-confirmed 2009 H1N1 influenza. For each case, five pregnant women who tested negative for H1N1 influenza or were untested were randomly chosen from each site’s database and matched by estimated date of confinement and site.

Based on a preliminary analysis, the 147 H1N1 cases and 740 controls had nearly identical birth weights (average 3,208 g vs. 3,219 g) and gestational ages at delivery (average 38.5 vs. 38.7 weeks).

After the investigators controlled for study site, age, race, multiples, primiparity, medical conditions, and smoking, the cases and controls also had similar rates of the following:

• Term low birth weight (5.6% vs. 3.6%; odds ratio, 1.45).

• Preterm delivery less than 37 weeks’ gestation (13.3% vs. 11.6%; OR, 1.10).

• Premature rupture of membranes (1.7% vs. 2.6%; OR, 0.61).

• Abruption (0.9% vs. 1.2%; OR, 0.49).

• Cesarean section (27.5% vs. 30%; OR, 0.82).

• Induction (36% vs. 39%; OR, 0.83).

• Fetal anomalies (4.7% vs. 4.9%; OR, 1.24).

• Hypertensive disorders of pregnancy (14.3% vs. 13.2%; OR, 0.98).

• Neonatal ICU admission (13% vs. 11%; OR, 1.21).

"There did not appear to be any significant differences in pregnancy outcomes between cases and controls," said Dr. Naresh of Magee-Women’s Hospital of the University of Pittsburgh.

Pregnancy outcomes also did not differ when stratified by trimester, although more infections occurred in the second trimester, followed by the third and first trimesters, she said.

Previous case series have suggested an increased rate of preterm delivery, reaching 30% in an early report of H1N1 influenza in pregnancy and 60% among critically ill women. A recent study also reported lower birth weights among 16 women with proven H1N1 infection, compared with 25 women with influenzalike illness (Am. J. Obstet. Gynecol. 2011;204[suppl. 1]:S58-63), she said.

A subgroup analysis of women in the current study with severe disease, defined as requiring hospitalization, identified a nonsignificant trend for lower birth weight, compared with controls (3,013 g vs. 3,219 g), and lower gestational age (37.9 weeks vs. 38.7 weeks).

The combined outcome of term low birth weight, preterm birth, and abruption was significantly more common among the severe H1N1 cases than controls after study site, age, race, multiples, primiparity, medical conditions, and smoking were controlled for (31.4% vs. 15.7%; OR, 2.45). In addition, more than 30% of women in the severe group had complications, compared with only 15% in the control group, Dr. Naresh said.

The researchers also looked at the influence of early antiviral administration, which has been reported to be associated with fewer maternal ICU admissions and fewer deaths (JAMA 2010;303:1517-25).

Gestational age at delivery was 1 week earlier among the 27 women receiving oseltamivir (Tamiflu) more than 48 hours after symptom onset compared with the 52 women receiving it in less than 48 hours, as recommended by the manufacturer (37.6 weeks vs. 38.6 weeks).

"It’s not clear how clinically significant that is, but it’s interesting nonetheless," Dr. Naresh said.

Birth weights among the delayed- and early-treatment groups were similar at 3,007 g and 3,160 g.

All cases of H1N1 infection were significantly more likely than controls to be black (27% vs. 19%), and to have prepregnancy diabetes (4% vs. 1%), seizure disorder (3.4% vs. 0.8%), and asthma (17% vs. 9%). The average age of the cohort was 28 years.

Limitations of the study are that some of the controls may have had influenza since many were untested and data on specific neonatal outcomes associated with ICU admission were limited.

Dr. Naresh said future steps include a small-for-gestational-age analysis and an evaluation of the role of socioeconomic status and of differences among the three sites: the University of Pittsburgh Medical Center, the University of Colorado at Denver, and the University of Washington Medical Center in Seattle.

Dr. Naresh and her coauthors reported no relevant financial disclosures.

KANSAS CITY, MO. – Seventeen percent of American children and adolescents are obese, and an increasing number of them are landing in operating rooms for related issues. They bring to the table particular perioperative concerns.

Dr. Moises Auron of the Cleveland Clinic offered an example during a talk on pediatric perioperative management at the meeting: A 15-year-old African American with a body mass index of 60 kg/m

For this high-risk patient, he said, cardiovascular concerns top the list, because obese children and adolescents are predisposed to hypertension at roughly a threefold higher risk than nonobese children. As a result, they can develop left ventricular hypertrophy that can produce a hypertrophic cardiomyopathy–like scenario, as well as diastolic dysfunction that also can predispose them to develop heart failure.

Childhood obesity is typically defined as a BMI at or above the 95th percentile for age and sex, while morbid obesity, as in the above patient, is a BMI that exceeds the 99th percentile.

Three times as many U.S. youth are obese now as were just one generation ago, the most recent data from the Centers for Disease Control and Prevention suggest.

In addition, one in seven low-income, preschool-aged children is obese.

“Unfortunately, we are seeing more and more and more of these cases,” said Dr. Auron, a pediatric hospitalist with the Center for Pediatric Hospital Medicine at the Cleveland Clinic.

Obese patients may require surgery not only for a variety of common ailments such as tonsillitis, but also for obesity-related conditions such as slipped capital femoral epiphysis, Blount's disease, cholelithiasis, and polycystic ovary syndrome.

In addition, they present with comorbid conditions such as insulin resistance, hypertension, and idiopathic intracranial hypertension.

In the examination of these patients, Dr. Auron suggests that the history include any symptoms of sleep apnea or hypoventilation, such as falling asleep while watching television or when talking with friends, and poor tolerance to exercise, including breathlessness and asthma, because these may in fact represent symptoms of left ventricular dysfunction.

Documentation of recent weight loss or gain, as well as a careful history of current medications – especially herbs or special mixtures taken to lose weight – is paramount. Weight loss may be associated with malnutrition, while the use of common herbs can interfere with anesthesia or hemostasis and even be associated with tachycardia, hypertension, or dysrhythmias.

“Garlic and ginger are very good antiplatelet agents,” Dr. Auron said. “It's like taking baby aspirin, but it's not good if you're having surgery. You can bleed to death.

“Medications that contain ephedra can trigger a severe sympathetic response, including hypertensive crises and tachyarrhythmias.”

Other perioperative considerations to be wary of in the morbidly obese pediatric patient are diabetes/insulin resistance; gastroesophageal reflux; and nonalcoholic fatty liver disease (NAFLD), including its progressive form, nonalcoholic steatohepatitis (NASH).

“When they develop NASH, it can evolve to cirrhosis, horribly,” Dr. Auron said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association. “It's even worse than alcoholic cirrhosis or viral hepatitis cirrhosis. I'm not sure why this is, but it causes substantial morbidity in the obese population who develops it,” he noted.

The prevalence of NAFLD and NASH varies by setting. Among 41 morbidly obese adolescents aged 13-19 years undergoing gastric bypass surgery, 83% had NAFLD and 20% had NASH. Mean fasting glucose level was significantly higher in those with NASH, although the prevalence of the metabolic syndrome was not (Gastroenterol. Hepatol. 2006;4:226-32).

A second study, however, recently reported that fatty liver disease, independent of visceral fat and intramyocellular lipid content, plays a central role in the pathogenesis of insulin resistance in obese adolescents (Diabetes Care 2010; 33:1817-22).

Dr. Auron said he recommends echocardiography for hypertensive patients, although he noted that there is not a lot of evidence, even in the adult literature, to support an echocardiogram for every patient. The one exception is patients with cardiomegaly on x-ray; echocardiography is recommended for this patient group (Circulation 2009;120:86-95).

Preoperative fasting should follow the same rules as for nonobese patients, albeit perhaps a bit more fasting would not lead obese patients astray, he said, tongue in cheek.

Dr. Auron reported no relevant financial relationships.

A careful history of current meds – especially herbs or special mixtures taken to lose weight – is paramount.

Source DR. AURON

KANSAS CITY, MO. – Seventeen percent of American children and adolescents are obese, and an increasing number of them are landing in operating rooms for related issues. They bring to the table particular perioperative concerns.

Dr. Moises Auron of the Cleveland Clinic offered an example during a talk on pediatric perioperative management at the meeting: A 15-year-old African American with a body mass index of 60 kg/m

For this high-risk patient, he said, cardiovascular concerns top the list, because obese children and adolescents are predisposed to hypertension at roughly a threefold higher risk than nonobese children. As a result, they can develop left ventricular hypertrophy that can produce a hypertrophic cardiomyopathy–like scenario, as well as diastolic dysfunction that also can predispose them to develop heart failure.

Childhood obesity is typically defined as a BMI at or above the 95th percentile for age and sex, while morbid obesity, as in the above patient, is a BMI that exceeds the 99th percentile.

Three times as many U.S. youth are obese now as were just one generation ago, the most recent data from the Centers for Disease Control and Prevention suggest.

In addition, one in seven low-income, preschool-aged children is obese.

“Unfortunately, we are seeing more and more and more of these cases,” said Dr. Auron, a pediatric hospitalist with the Center for Pediatric Hospital Medicine at the Cleveland Clinic.

Obese patients may require surgery not only for a variety of common ailments such as tonsillitis, but also for obesity-related conditions such as slipped capital femoral epiphysis, Blount's disease, cholelithiasis, and polycystic ovary syndrome.

In addition, they present with comorbid conditions such as insulin resistance, hypertension, and idiopathic intracranial hypertension.

In the examination of these patients, Dr. Auron suggests that the history include any symptoms of sleep apnea or hypoventilation, such as falling asleep while watching television or when talking with friends, and poor tolerance to exercise, including breathlessness and asthma, because these may in fact represent symptoms of left ventricular dysfunction.

Documentation of recent weight loss or gain, as well as a careful history of current medications – especially herbs or special mixtures taken to lose weight – is paramount. Weight loss may be associated with malnutrition, while the use of common herbs can interfere with anesthesia or hemostasis and even be associated with tachycardia, hypertension, or dysrhythmias.

“Garlic and ginger are very good antiplatelet agents,” Dr. Auron said. “It's like taking baby aspirin, but it's not good if you're having surgery. You can bleed to death.

“Medications that contain ephedra can trigger a severe sympathetic response, including hypertensive crises and tachyarrhythmias.”

Other perioperative considerations to be wary of in the morbidly obese pediatric patient are diabetes/insulin resistance; gastroesophageal reflux; and nonalcoholic fatty liver disease (NAFLD), including its progressive form, nonalcoholic steatohepatitis (NASH).

“When they develop NASH, it can evolve to cirrhosis, horribly,” Dr. Auron said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association. “It's even worse than alcoholic cirrhosis or viral hepatitis cirrhosis. I'm not sure why this is, but it causes substantial morbidity in the obese population who develops it,” he noted.

The prevalence of NAFLD and NASH varies by setting. Among 41 morbidly obese adolescents aged 13-19 years undergoing gastric bypass surgery, 83% had NAFLD and 20% had NASH. Mean fasting glucose level was significantly higher in those with NASH, although the prevalence of the metabolic syndrome was not (Gastroenterol. Hepatol. 2006;4:226-32).

A second study, however, recently reported that fatty liver disease, independent of visceral fat and intramyocellular lipid content, plays a central role in the pathogenesis of insulin resistance in obese adolescents (Diabetes Care 2010; 33:1817-22).

Dr. Auron said he recommends echocardiography for hypertensive patients, although he noted that there is not a lot of evidence, even in the adult literature, to support an echocardiogram for every patient. The one exception is patients with cardiomegaly on x-ray; echocardiography is recommended for this patient group (Circulation 2009;120:86-95).

Preoperative fasting should follow the same rules as for nonobese patients, albeit perhaps a bit more fasting would not lead obese patients astray, he said, tongue in cheek.

Dr. Auron reported no relevant financial relationships.

A careful history of current meds – especially herbs or special mixtures taken to lose weight – is paramount.

Source DR. AURON

KANSAS CITY, MO. – Seventeen percent of American children and adolescents are obese, and an increasing number of them are landing in operating rooms for related issues. They bring to the table particular perioperative concerns.

Dr. Moises Auron of the Cleveland Clinic offered an example during a talk on pediatric perioperative management at the meeting: A 15-year-old African American with a body mass index of 60 kg/m

For this high-risk patient, he said, cardiovascular concerns top the list, because obese children and adolescents are predisposed to hypertension at roughly a threefold higher risk than nonobese children. As a result, they can develop left ventricular hypertrophy that can produce a hypertrophic cardiomyopathy–like scenario, as well as diastolic dysfunction that also can predispose them to develop heart failure.

Childhood obesity is typically defined as a BMI at or above the 95th percentile for age and sex, while morbid obesity, as in the above patient, is a BMI that exceeds the 99th percentile.

Three times as many U.S. youth are obese now as were just one generation ago, the most recent data from the Centers for Disease Control and Prevention suggest.

In addition, one in seven low-income, preschool-aged children is obese.

“Unfortunately, we are seeing more and more and more of these cases,” said Dr. Auron, a pediatric hospitalist with the Center for Pediatric Hospital Medicine at the Cleveland Clinic.

Obese patients may require surgery not only for a variety of common ailments such as tonsillitis, but also for obesity-related conditions such as slipped capital femoral epiphysis, Blount's disease, cholelithiasis, and polycystic ovary syndrome.

In addition, they present with comorbid conditions such as insulin resistance, hypertension, and idiopathic intracranial hypertension.

In the examination of these patients, Dr. Auron suggests that the history include any symptoms of sleep apnea or hypoventilation, such as falling asleep while watching television or when talking with friends, and poor tolerance to exercise, including breathlessness and asthma, because these may in fact represent symptoms of left ventricular dysfunction.

Documentation of recent weight loss or gain, as well as a careful history of current medications – especially herbs or special mixtures taken to lose weight – is paramount. Weight loss may be associated with malnutrition, while the use of common herbs can interfere with anesthesia or hemostasis and even be associated with tachycardia, hypertension, or dysrhythmias.

“Garlic and ginger are very good antiplatelet agents,” Dr. Auron said. “It's like taking baby aspirin, but it's not good if you're having surgery. You can bleed to death.

“Medications that contain ephedra can trigger a severe sympathetic response, including hypertensive crises and tachyarrhythmias.”

Other perioperative considerations to be wary of in the morbidly obese pediatric patient are diabetes/insulin resistance; gastroesophageal reflux; and nonalcoholic fatty liver disease (NAFLD), including its progressive form, nonalcoholic steatohepatitis (NASH).

“When they develop NASH, it can evolve to cirrhosis, horribly,” Dr. Auron said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association. “It's even worse than alcoholic cirrhosis or viral hepatitis cirrhosis. I'm not sure why this is, but it causes substantial morbidity in the obese population who develops it,” he noted.

The prevalence of NAFLD and NASH varies by setting. Among 41 morbidly obese adolescents aged 13-19 years undergoing gastric bypass surgery, 83% had NAFLD and 20% had NASH. Mean fasting glucose level was significantly higher in those with NASH, although the prevalence of the metabolic syndrome was not (Gastroenterol. Hepatol. 2006;4:226-32).

A second study, however, recently reported that fatty liver disease, independent of visceral fat and intramyocellular lipid content, plays a central role in the pathogenesis of insulin resistance in obese adolescents (Diabetes Care 2010; 33:1817-22).

Dr. Auron said he recommends echocardiography for hypertensive patients, although he noted that there is not a lot of evidence, even in the adult literature, to support an echocardiogram for every patient. The one exception is patients with cardiomegaly on x-ray; echocardiography is recommended for this patient group (Circulation 2009;120:86-95).

Preoperative fasting should follow the same rules as for nonobese patients, albeit perhaps a bit more fasting would not lead obese patients astray, he said, tongue in cheek.

Dr. Auron reported no relevant financial relationships.

A careful history of current meds – especially herbs or special mixtures taken to lose weight – is paramount.

Source DR. AURON

Major Finding: Receipt of any flu vaccination was significantly associated with higher infant birth weight (3,178 gram vs. 2,903 grams) and longer gestational age (38.3 weeks vs. 36.8 weeks; both P less than .0001).

Data Source: Preliminary analysis of 1,641 women delivering at Duke University Hospital during the 2009-2010 influenza season.

Disclosures: The study was funded by the 2010 American College of Obstetricians and Gynecologists/Merck & Co. Research Award on Immunization. Dr. Fortner and her colleagues reported no relevant financial disclosures.

CHICAGO – Influenza vaccination appears to improve neonatal outcomes, but coverage remains inadequate among pregnant women.

Among 1,641 evaluable women delivering at Duke University Medical Center, Durham, N.C., during the 2009-2010 influenza season, receipt of any flu vaccination was significantly associated with higher infant birth weight (3,178 g vs. 2,903 g) and longer gestational age (38.3 weeks vs. 36.8 weeks; both P values less than .0001).

Women who received at least one flu vaccine also were significantly less likely to require an antepartum visit or hospital admission than were those who did not (39% vs. 44%; P = .005).

“This information supports prior accumulating data that receipt of a flu vaccine improves not only maternal outcomes, but also birth outcomes,” Dr. Kimberly Fortner said at the meeting.

In all, 44% of women in the preliminary analysis received both vaccines in compliance with recommendations, far higher than historical influenza vaccination rates of 12%-34% and comparable to other reports from the season. Another 7% elected no vaccine at all, and 24% of the population had no documented receipt of vaccine in obstetrical records or other electronic medical records.

Uptake of seasonal influenza vaccine was 58% vs. 55% for the 2009 H1N1 influenza vaccine, which is unique among published prior literature. Even though rates were nearly equal, 24% of women elected to receive only one of the two recommended vaccines, resulting in inadequate coverage, said Dr. Fortner of the Translational Medicine Institute at Duke.

The researchers hypothesized that pregnant women may have had inappropriate or inadequate vaccination during the 2009-2010 flu season due to issues of vaccine distribution, sensationalism of the H1N1 influenza pandemic, and recommendations by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices that pregnant women receive both the seasonal and H1N1 influenza monovalent vaccines.

The earlier women went in for prenatal care, however, the more likely they were to receive a vaccine, she said.

Mean gestational age at first prenatal visit was significantly lower at 14.8 weeks among women who received the vaccine, compared with 18.6 weeks for women who did not receive any vaccine and 21.2 weeks for those with unknown vaccine status (P less than .0001).

Black women and those with public insurance or no insurance were significantly less likely to receive any vaccine.

In multivariate analysis that adjusted for maternal age, black race, less than a high school education, Medicaid or no insurance, and medical comorbidities, receipt of any influenza vaccine during that season was significantly associated with an estimated 133.7-g increase in birth weight (P = .0003).

The vaccine gives pregnant women a greater chance of having a heavier baby who is born closer to term.

Source ©Availablelight/istockphoto.com

Major Finding: Receipt of any flu vaccination was significantly associated with higher infant birth weight (3,178 gram vs. 2,903 grams) and longer gestational age (38.3 weeks vs. 36.8 weeks; both P less than .0001).

Data Source: Preliminary analysis of 1,641 women delivering at Duke University Hospital during the 2009-2010 influenza season.

Disclosures: The study was funded by the 2010 American College of Obstetricians and Gynecologists/Merck & Co. Research Award on Immunization. Dr. Fortner and her colleagues reported no relevant financial disclosures.

CHICAGO – Influenza vaccination appears to improve neonatal outcomes, but coverage remains inadequate among pregnant women.

Among 1,641 evaluable women delivering at Duke University Medical Center, Durham, N.C., during the 2009-2010 influenza season, receipt of any flu vaccination was significantly associated with higher infant birth weight (3,178 g vs. 2,903 g) and longer gestational age (38.3 weeks vs. 36.8 weeks; both P values less than .0001).

Women who received at least one flu vaccine also were significantly less likely to require an antepartum visit or hospital admission than were those who did not (39% vs. 44%; P = .005).

“This information supports prior accumulating data that receipt of a flu vaccine improves not only maternal outcomes, but also birth outcomes,” Dr. Kimberly Fortner said at the meeting.

In all, 44% of women in the preliminary analysis received both vaccines in compliance with recommendations, far higher than historical influenza vaccination rates of 12%-34% and comparable to other reports from the season. Another 7% elected no vaccine at all, and 24% of the population had no documented receipt of vaccine in obstetrical records or other electronic medical records.

Uptake of seasonal influenza vaccine was 58% vs. 55% for the 2009 H1N1 influenza vaccine, which is unique among published prior literature. Even though rates were nearly equal, 24% of women elected to receive only one of the two recommended vaccines, resulting in inadequate coverage, said Dr. Fortner of the Translational Medicine Institute at Duke.

The researchers hypothesized that pregnant women may have had inappropriate or inadequate vaccination during the 2009-2010 flu season due to issues of vaccine distribution, sensationalism of the H1N1 influenza pandemic, and recommendations by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices that pregnant women receive both the seasonal and H1N1 influenza monovalent vaccines.

The earlier women went in for prenatal care, however, the more likely they were to receive a vaccine, she said.

Mean gestational age at first prenatal visit was significantly lower at 14.8 weeks among women who received the vaccine, compared with 18.6 weeks for women who did not receive any vaccine and 21.2 weeks for those with unknown vaccine status (P less than .0001).

Black women and those with public insurance or no insurance were significantly less likely to receive any vaccine.

In multivariate analysis that adjusted for maternal age, black race, less than a high school education, Medicaid or no insurance, and medical comorbidities, receipt of any influenza vaccine during that season was significantly associated with an estimated 133.7-g increase in birth weight (P = .0003).

The vaccine gives pregnant women a greater chance of having a heavier baby who is born closer to term.

Source ©Availablelight/istockphoto.com

Major Finding: Receipt of any flu vaccination was significantly associated with higher infant birth weight (3,178 gram vs. 2,903 grams) and longer gestational age (38.3 weeks vs. 36.8 weeks; both P less than .0001).

Data Source: Preliminary analysis of 1,641 women delivering at Duke University Hospital during the 2009-2010 influenza season.

Disclosures: The study was funded by the 2010 American College of Obstetricians and Gynecologists/Merck & Co. Research Award on Immunization. Dr. Fortner and her colleagues reported no relevant financial disclosures.

CHICAGO – Influenza vaccination appears to improve neonatal outcomes, but coverage remains inadequate among pregnant women.

Among 1,641 evaluable women delivering at Duke University Medical Center, Durham, N.C., during the 2009-2010 influenza season, receipt of any flu vaccination was significantly associated with higher infant birth weight (3,178 g vs. 2,903 g) and longer gestational age (38.3 weeks vs. 36.8 weeks; both P values less than .0001).

Women who received at least one flu vaccine also were significantly less likely to require an antepartum visit or hospital admission than were those who did not (39% vs. 44%; P = .005).

“This information supports prior accumulating data that receipt of a flu vaccine improves not only maternal outcomes, but also birth outcomes,” Dr. Kimberly Fortner said at the meeting.

In all, 44% of women in the preliminary analysis received both vaccines in compliance with recommendations, far higher than historical influenza vaccination rates of 12%-34% and comparable to other reports from the season. Another 7% elected no vaccine at all, and 24% of the population had no documented receipt of vaccine in obstetrical records or other electronic medical records.

Uptake of seasonal influenza vaccine was 58% vs. 55% for the 2009 H1N1 influenza vaccine, which is unique among published prior literature. Even though rates were nearly equal, 24% of women elected to receive only one of the two recommended vaccines, resulting in inadequate coverage, said Dr. Fortner of the Translational Medicine Institute at Duke.

The researchers hypothesized that pregnant women may have had inappropriate or inadequate vaccination during the 2009-2010 flu season due to issues of vaccine distribution, sensationalism of the H1N1 influenza pandemic, and recommendations by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices that pregnant women receive both the seasonal and H1N1 influenza monovalent vaccines.

The earlier women went in for prenatal care, however, the more likely they were to receive a vaccine, she said.

Mean gestational age at first prenatal visit was significantly lower at 14.8 weeks among women who received the vaccine, compared with 18.6 weeks for women who did not receive any vaccine and 21.2 weeks for those with unknown vaccine status (P less than .0001).

Black women and those with public insurance or no insurance were significantly less likely to receive any vaccine.

In multivariate analysis that adjusted for maternal age, black race, less than a high school education, Medicaid or no insurance, and medical comorbidities, receipt of any influenza vaccine during that season was significantly associated with an estimated 133.7-g increase in birth weight (P = .0003).

The vaccine gives pregnant women a greater chance of having a heavier baby who is born closer to term.

Source ©Availablelight/istockphoto.com

CHICAGO – Pregnant women were significantly more likely to receive information on pertussis vaccination from their pediatrician than from their obstetrician in a survey of 314 women.

“Multiple opportunities exist for education of obstetricians and gynecologists to improve Tdap vaccination rates in the United States,” Dr. Rachel Gutkin said.

She reported on 314 pregnant women presenting to an academic perinatal center between March and June 2011 who answered an anonymous, multiple-choice questionnaire regarding their knowledge and opinions on vaccination in general, and Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis adsorbed) specifically. Overall, 218 (69%) of the women had heard about the Tdap booster vaccine, with 76 (24%) women learning about it at their pediatrician's office and 54 (17%) at their obstetrician's office. Just 8% of women learned about Tdap from the Internet, while 19% did so from friends or family, and 17% from TV or radio, said Dr. Gutkin, a resident in the department of obstetrics and gynecology at the University of California, Los Angeles. The remaining 15% learned of it from other sources.

The majority of respondents knew that pertussis is a significant health risk for children (76%) and newborns (86%), and 50% also thought it was a significant health risk for fetuses. When asked whether they would receive a Tdap vaccination during pregnancy to protect their newborn from whooping cough, 11% said they would if their doctor recommended it, 12% said yes if they knew it was safe, and 66% said they would if both conditions were true. Additionally, 11% said they would not receive Tdap during pregnancy under any circumstances, she said.

Women who discussed Tdap with their obstetrician were nearly five times more likely to be vaccinated than those who did not (odds ratio, 4.93). Only 13% of women who did not discuss Tdap with their ob.gyn. were vaccinated.

Although women were significantly more likely to discuss Tdap with their pediatrician, women were nearly three times more likely to be vaccinated if they were counseled by their ob.gyn. versus their pediatrician (OR, 2.9).

The survey was conducted in California, which in 2010 experienced the largest outbreak of pertussis in 65 years, with 9,120 cases reported, including 10 deaths.

Still, almost one-quarter of women were not sure if vaccines in general are safe (22%). Roughly two-thirds were not sure if vaccines are safe in pregnancy (68%) and a full 10% were not sure if vaccines are effective in preventing illness, Dr. Gutkin said.

Women were significantly more likely to have discussed the influenza vaccine with their ob.gyn. than Tdap (47% vs. 19%), and to be vaccinated for influenza than pertussis (42% vs. 18%). Of note, women were three times more likely to receive Tdap if they had received a flu shot (OR, 3.68). “Discussion with their ob.gyn. was a significant factor in the acceptance of Tdap and influenza vaccines during pregnancy,” she said.

'Discussion with their ob.gyn. was a significant factor in the acceptance of Tdap … vaccines during pregnancy.'

Source DR. GUTKIN

CHICAGO – Pregnant women were significantly more likely to receive information on pertussis vaccination from their pediatrician than from their obstetrician in a survey of 314 women.

“Multiple opportunities exist for education of obstetricians and gynecologists to improve Tdap vaccination rates in the United States,” Dr. Rachel Gutkin said.

She reported on 314 pregnant women presenting to an academic perinatal center between March and June 2011 who answered an anonymous, multiple-choice questionnaire regarding their knowledge and opinions on vaccination in general, and Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis adsorbed) specifically. Overall, 218 (69%) of the women had heard about the Tdap booster vaccine, with 76 (24%) women learning about it at their pediatrician's office and 54 (17%) at their obstetrician's office. Just 8% of women learned about Tdap from the Internet, while 19% did so from friends or family, and 17% from TV or radio, said Dr. Gutkin, a resident in the department of obstetrics and gynecology at the University of California, Los Angeles. The remaining 15% learned of it from other sources.

The majority of respondents knew that pertussis is a significant health risk for children (76%) and newborns (86%), and 50% also thought it was a significant health risk for fetuses. When asked whether they would receive a Tdap vaccination during pregnancy to protect their newborn from whooping cough, 11% said they would if their doctor recommended it, 12% said yes if they knew it was safe, and 66% said they would if both conditions were true. Additionally, 11% said they would not receive Tdap during pregnancy under any circumstances, she said.

Women who discussed Tdap with their obstetrician were nearly five times more likely to be vaccinated than those who did not (odds ratio, 4.93). Only 13% of women who did not discuss Tdap with their ob.gyn. were vaccinated.

Although women were significantly more likely to discuss Tdap with their pediatrician, women were nearly three times more likely to be vaccinated if they were counseled by their ob.gyn. versus their pediatrician (OR, 2.9).

The survey was conducted in California, which in 2010 experienced the largest outbreak of pertussis in 65 years, with 9,120 cases reported, including 10 deaths.

Still, almost one-quarter of women were not sure if vaccines in general are safe (22%). Roughly two-thirds were not sure if vaccines are safe in pregnancy (68%) and a full 10% were not sure if vaccines are effective in preventing illness, Dr. Gutkin said.

Women were significantly more likely to have discussed the influenza vaccine with their ob.gyn. than Tdap (47% vs. 19%), and to be vaccinated for influenza than pertussis (42% vs. 18%). Of note, women were three times more likely to receive Tdap if they had received a flu shot (OR, 3.68). “Discussion with their ob.gyn. was a significant factor in the acceptance of Tdap and influenza vaccines during pregnancy,” she said.

'Discussion with their ob.gyn. was a significant factor in the acceptance of Tdap … vaccines during pregnancy.'

Source DR. GUTKIN

CHICAGO – Pregnant women were significantly more likely to receive information on pertussis vaccination from their pediatrician than from their obstetrician in a survey of 314 women.

“Multiple opportunities exist for education of obstetricians and gynecologists to improve Tdap vaccination rates in the United States,” Dr. Rachel Gutkin said.

She reported on 314 pregnant women presenting to an academic perinatal center between March and June 2011 who answered an anonymous, multiple-choice questionnaire regarding their knowledge and opinions on vaccination in general, and Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis adsorbed) specifically. Overall, 218 (69%) of the women had heard about the Tdap booster vaccine, with 76 (24%) women learning about it at their pediatrician's office and 54 (17%) at their obstetrician's office. Just 8% of women learned about Tdap from the Internet, while 19% did so from friends or family, and 17% from TV or radio, said Dr. Gutkin, a resident in the department of obstetrics and gynecology at the University of California, Los Angeles. The remaining 15% learned of it from other sources.

The majority of respondents knew that pertussis is a significant health risk for children (76%) and newborns (86%), and 50% also thought it was a significant health risk for fetuses. When asked whether they would receive a Tdap vaccination during pregnancy to protect their newborn from whooping cough, 11% said they would if their doctor recommended it, 12% said yes if they knew it was safe, and 66% said they would if both conditions were true. Additionally, 11% said they would not receive Tdap during pregnancy under any circumstances, she said.

Women who discussed Tdap with their obstetrician were nearly five times more likely to be vaccinated than those who did not (odds ratio, 4.93). Only 13% of women who did not discuss Tdap with their ob.gyn. were vaccinated.

Although women were significantly more likely to discuss Tdap with their pediatrician, women were nearly three times more likely to be vaccinated if they were counseled by their ob.gyn. versus their pediatrician (OR, 2.9).

The survey was conducted in California, which in 2010 experienced the largest outbreak of pertussis in 65 years, with 9,120 cases reported, including 10 deaths.

Still, almost one-quarter of women were not sure if vaccines in general are safe (22%). Roughly two-thirds were not sure if vaccines are safe in pregnancy (68%) and a full 10% were not sure if vaccines are effective in preventing illness, Dr. Gutkin said.

Women were significantly more likely to have discussed the influenza vaccine with their ob.gyn. than Tdap (47% vs. 19%), and to be vaccinated for influenza than pertussis (42% vs. 18%). Of note, women were three times more likely to receive Tdap if they had received a flu shot (OR, 3.68). “Discussion with their ob.gyn. was a significant factor in the acceptance of Tdap and influenza vaccines during pregnancy,” she said.

'Discussion with their ob.gyn. was a significant factor in the acceptance of Tdap … vaccines during pregnancy.'

Source DR. GUTKIN

PARIS – Intra-aortic counterpulsation balloon therapy during percutaneous coronary intervention did not reduce infarct size in patients with ST-elevation myocardial infarction without shock in the multicenter, international CRISP-AMI trial.

The findings do not, however, close the door on this widely used therapy, Dr. Manesh Patel said at the annual congress of the European Society of Cardiology.

"Clinicians should continue to be vigilant about identifying patients who are at risk for rapid deterioration or hypertension that may still benefit from support, as seen with the crossover in this trial," he said at the meeting.

In all, 8.5% of patients randomized to percutaneous coronary intervention (PCI) alone crossed over to rescue intra-aortic balloon counterpulsation (IABC) in the CRISP-AMI (Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction) study.

Among all 337 patients in the trial, mean infarct size was 42% of the left ventricle in patients randomized to IABC prior to PCI and continued for at least 12 hours and 37.5% in the PCI-alone group (P = .06), said Dr. Patel of the Duke Clinical Research Institute in Durham, N.C.

In patients with proximal left anterior descending and thrombolysis in myocardial infarction flow scores of 0 or 1, the mean infarct size was 46.7% of the left ventricle vs. 42.3%, respectively (P = .11).

Invited discussant Dr. Kurt Huber, director of the department of medicine, cardiology, and emergency medicine at Wilhelminenspital in Vienna, said, "I’m sure that this method is still important for certain patient groups."

He noted that American Heart Association guidelines recommend IABC for patients in cardiogenic shock, with a 1B recommendation.

Moreover, despite missing statistical significance, hard clinical end points were lower in the IABC arm, Dr. Huber said.

At 6 months, three patients in the IABC plus PCI group had died vs. nine in the PCI-alone group (P = .12).

An exploratory composite end point of time to death, shock, or new or worsening heart failure also favored the counterpulsation therapy plus PCI group over the PCI-alone group (8 events vs. 21 events, P = .03).

There was, however, a nonsignificant increase in side effects, particularly vascular complications, Dr. Huber said.

At 30 days, major vascular complications occurred in seven patients in the IABC plus PCI group vs. only two in the PCI-alone group (P = .09.). Major bleeding or transfusion occurred in five patients vs. three patients, respectively, Dr. Patel reported.

Dr. Huber said other studies are needed to define which patients might benefit from IABC. He highlighted the only other prospective trial of IACP, the TACTICS trial, in which IAPC failed to offer a survival benefit when added to fibrinolysis for patients with MI who were hemodynamically unstable, but suggested a possible benefit for patients with the most severe heart failure or hypertension (J. Thromb. Thrombolysis 2005;19:33-9).

Session comoderator Dr. Christodoulos Stefanadis of Athens University Medical School said in an interview that it is still acceptable to use IACP in both stable and unstable patients, but agreed that other studies are needed to resolve the issue.

"For many years, we believe that the use of the intra-aortic pump is an effective means to reduce infarct size and to reduce the mortality rate, especially in patients with cardiogenic shock," he said.

"In unstable patients, I personally believe that the use of the intra-aortic pump remains effective, but the question is what happens in stable patients without low blood pressure or shock."

At baseline, CRISP-AMI patients were hemodynamically stable, with a median systolic blood pressure of 130 mm Hg in the IABC plus PCI group and 135 mm Hg in the PCI-alone patients.

The time required to insert the intra-aortic balloon added just 9 minutes to the procedure, making it unlikely that this derailed the potential benefits of counterpulsation therapy, Dr. Patel said in an interview.

The results of CRISP-AMI were simultaneously published online by JAMA (2011 Aug. 30 [doi:10.1001/jama.2011.1280]).

Dr. Patel reported receiving grant funding and travel reimbursement from the study sponsor Maquet (formerly Datascope).

PARIS – Intra-aortic counterpulsation balloon therapy during percutaneous coronary intervention did not reduce infarct size in patients with ST-elevation myocardial infarction without shock in the multicenter, international CRISP-AMI trial.

The findings do not, however, close the door on this widely used therapy, Dr. Manesh Patel said at the annual congress of the European Society of Cardiology.

"Clinicians should continue to be vigilant about identifying patients who are at risk for rapid deterioration or hypertension that may still benefit from support, as seen with the crossover in this trial," he said at the meeting.

In all, 8.5% of patients randomized to percutaneous coronary intervention (PCI) alone crossed over to rescue intra-aortic balloon counterpulsation (IABC) in the CRISP-AMI (Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction) study.

Among all 337 patients in the trial, mean infarct size was 42% of the left ventricle in patients randomized to IABC prior to PCI and continued for at least 12 hours and 37.5% in the PCI-alone group (P = .06), said Dr. Patel of the Duke Clinical Research Institute in Durham, N.C.

In patients with proximal left anterior descending and thrombolysis in myocardial infarction flow scores of 0 or 1, the mean infarct size was 46.7% of the left ventricle vs. 42.3%, respectively (P = .11).

Invited discussant Dr. Kurt Huber, director of the department of medicine, cardiology, and emergency medicine at Wilhelminenspital in Vienna, said, "I’m sure that this method is still important for certain patient groups."

He noted that American Heart Association guidelines recommend IABC for patients in cardiogenic shock, with a 1B recommendation.

Moreover, despite missing statistical significance, hard clinical end points were lower in the IABC arm, Dr. Huber said.

At 6 months, three patients in the IABC plus PCI group had died vs. nine in the PCI-alone group (P = .12).

An exploratory composite end point of time to death, shock, or new or worsening heart failure also favored the counterpulsation therapy plus PCI group over the PCI-alone group (8 events vs. 21 events, P = .03).

There was, however, a nonsignificant increase in side effects, particularly vascular complications, Dr. Huber said.

At 30 days, major vascular complications occurred in seven patients in the IABC plus PCI group vs. only two in the PCI-alone group (P = .09.). Major bleeding or transfusion occurred in five patients vs. three patients, respectively, Dr. Patel reported.

Dr. Huber said other studies are needed to define which patients might benefit from IABC. He highlighted the only other prospective trial of IACP, the TACTICS trial, in which IAPC failed to offer a survival benefit when added to fibrinolysis for patients with MI who were hemodynamically unstable, but suggested a possible benefit for patients with the most severe heart failure or hypertension (J. Thromb. Thrombolysis 2005;19:33-9).

Session comoderator Dr. Christodoulos Stefanadis of Athens University Medical School said in an interview that it is still acceptable to use IACP in both stable and unstable patients, but agreed that other studies are needed to resolve the issue.

"For many years, we believe that the use of the intra-aortic pump is an effective means to reduce infarct size and to reduce the mortality rate, especially in patients with cardiogenic shock," he said.

"In unstable patients, I personally believe that the use of the intra-aortic pump remains effective, but the question is what happens in stable patients without low blood pressure or shock."

At baseline, CRISP-AMI patients were hemodynamically stable, with a median systolic blood pressure of 130 mm Hg in the IABC plus PCI group and 135 mm Hg in the PCI-alone patients.

The time required to insert the intra-aortic balloon added just 9 minutes to the procedure, making it unlikely that this derailed the potential benefits of counterpulsation therapy, Dr. Patel said in an interview.

The results of CRISP-AMI were simultaneously published online by JAMA (2011 Aug. 30 [doi:10.1001/jama.2011.1280]).

Dr. Patel reported receiving grant funding and travel reimbursement from the study sponsor Maquet (formerly Datascope).

PARIS – Intra-aortic counterpulsation balloon therapy during percutaneous coronary intervention did not reduce infarct size in patients with ST-elevation myocardial infarction without shock in the multicenter, international CRISP-AMI trial.

The findings do not, however, close the door on this widely used therapy, Dr. Manesh Patel said at the annual congress of the European Society of Cardiology.

"Clinicians should continue to be vigilant about identifying patients who are at risk for rapid deterioration or hypertension that may still benefit from support, as seen with the crossover in this trial," he said at the meeting.

In all, 8.5% of patients randomized to percutaneous coronary intervention (PCI) alone crossed over to rescue intra-aortic balloon counterpulsation (IABC) in the CRISP-AMI (Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction) study.

Among all 337 patients in the trial, mean infarct size was 42% of the left ventricle in patients randomized to IABC prior to PCI and continued for at least 12 hours and 37.5% in the PCI-alone group (P = .06), said Dr. Patel of the Duke Clinical Research Institute in Durham, N.C.

In patients with proximal left anterior descending and thrombolysis in myocardial infarction flow scores of 0 or 1, the mean infarct size was 46.7% of the left ventricle vs. 42.3%, respectively (P = .11).

Invited discussant Dr. Kurt Huber, director of the department of medicine, cardiology, and emergency medicine at Wilhelminenspital in Vienna, said, "I’m sure that this method is still important for certain patient groups."

He noted that American Heart Association guidelines recommend IABC for patients in cardiogenic shock, with a 1B recommendation.

Moreover, despite missing statistical significance, hard clinical end points were lower in the IABC arm, Dr. Huber said.

At 6 months, three patients in the IABC plus PCI group had died vs. nine in the PCI-alone group (P = .12).

An exploratory composite end point of time to death, shock, or new or worsening heart failure also favored the counterpulsation therapy plus PCI group over the PCI-alone group (8 events vs. 21 events, P = .03).

There was, however, a nonsignificant increase in side effects, particularly vascular complications, Dr. Huber said.

At 30 days, major vascular complications occurred in seven patients in the IABC plus PCI group vs. only two in the PCI-alone group (P = .09.). Major bleeding or transfusion occurred in five patients vs. three patients, respectively, Dr. Patel reported.

Dr. Huber said other studies are needed to define which patients might benefit from IABC. He highlighted the only other prospective trial of IACP, the TACTICS trial, in which IAPC failed to offer a survival benefit when added to fibrinolysis for patients with MI who were hemodynamically unstable, but suggested a possible benefit for patients with the most severe heart failure or hypertension (J. Thromb. Thrombolysis 2005;19:33-9).

Session comoderator Dr. Christodoulos Stefanadis of Athens University Medical School said in an interview that it is still acceptable to use IACP in both stable and unstable patients, but agreed that other studies are needed to resolve the issue.

"For many years, we believe that the use of the intra-aortic pump is an effective means to reduce infarct size and to reduce the mortality rate, especially in patients with cardiogenic shock," he said.

"In unstable patients, I personally believe that the use of the intra-aortic pump remains effective, but the question is what happens in stable patients without low blood pressure or shock."

At baseline, CRISP-AMI patients were hemodynamically stable, with a median systolic blood pressure of 130 mm Hg in the IABC plus PCI group and 135 mm Hg in the PCI-alone patients.

The time required to insert the intra-aortic balloon added just 9 minutes to the procedure, making it unlikely that this derailed the potential benefits of counterpulsation therapy, Dr. Patel said in an interview.

The results of CRISP-AMI were simultaneously published online by JAMA (2011 Aug. 30 [doi:10.1001/jama.2011.1280]).

Dr. Patel reported receiving grant funding and travel reimbursement from the study sponsor Maquet (formerly Datascope).