Susan London

SEATTLE — Oral cladribine reduced the annualized rate of relapse in patients with the relapsing-remitting form of multiple sclerosis by over half in a phase III trial presented at the annual meeting of the American Academy of Neurology.

Cladribine, an antineoplastic used primarily to treat hairy cell leukemia, has several properties relevant to the treatment of multiple sclerosis (MS): It produces a sustained reduction in numbers of CD4 and CD8 T cells and of B cells, decreases levels of proinflammatory chemokines, and crosses the blood-brain barrier, according to lead investigator Dr. Gavin Giovannoni, a neurologist at Barts and The London School of Medicine and Dentistry, London.

He and his coinvestigators enrolled patients who had definite, active relapsing-remitting MS and an Expanded Disability Status Scale (EDSS) score of 5.5 or less.

Of those patients, 433 received a lower total dose of cladribine (3.5 mg/kg), 456 received a higher total dose of cladribine (5.25 mg/kg), and 437 got a placebo. Medication was taken for only 4-5 days a month in 2-4 months a year.

“We were quite surprised,” Dr. Giovannoni said of the trial's results for the primary end point, the annualized relapse rate after 96 weeks of treatment. “Despite having a relatively low event rate in the placebo arm, there was a robust and highly significant impact on relapse rate in both [experimental] study arms.”

Specifically, in intention-to-treat analyses, annualized relapse rates were 0.14 and 0.15 in the lower- and higher-dose cladribine groups, respectively, compared with 0.33 in the placebo group. The differences corresponded to statistically significant 58% and 55% relative reductions.

Compared with their counterparts in the placebo group, patients in the lower- and higher-dose cladribine groups were significantly less likely to experience a relapse (relative risks, 0.52 and 0.54) or progression (hazard ratios, 0.67 and 0.69).

Dr. Giovannoni reported that he has received personal compensation from Merck-Serono.

The study was supported by Merck Serono S.A., Geneva, an affiliate of Merck KGaA, Darmstadt, Germany.

SEATTLE — Oral cladribine reduced the annualized rate of relapse in patients with the relapsing-remitting form of multiple sclerosis by over half in a phase III trial presented at the annual meeting of the American Academy of Neurology.

Cladribine, an antineoplastic used primarily to treat hairy cell leukemia, has several properties relevant to the treatment of multiple sclerosis (MS): It produces a sustained reduction in numbers of CD4 and CD8 T cells and of B cells, decreases levels of proinflammatory chemokines, and crosses the blood-brain barrier, according to lead investigator Dr. Gavin Giovannoni, a neurologist at Barts and The London School of Medicine and Dentistry, London.

He and his coinvestigators enrolled patients who had definite, active relapsing-remitting MS and an Expanded Disability Status Scale (EDSS) score of 5.5 or less.

Of those patients, 433 received a lower total dose of cladribine (3.5 mg/kg), 456 received a higher total dose of cladribine (5.25 mg/kg), and 437 got a placebo. Medication was taken for only 4-5 days a month in 2-4 months a year.

“We were quite surprised,” Dr. Giovannoni said of the trial's results for the primary end point, the annualized relapse rate after 96 weeks of treatment. “Despite having a relatively low event rate in the placebo arm, there was a robust and highly significant impact on relapse rate in both [experimental] study arms.”

Specifically, in intention-to-treat analyses, annualized relapse rates were 0.14 and 0.15 in the lower- and higher-dose cladribine groups, respectively, compared with 0.33 in the placebo group. The differences corresponded to statistically significant 58% and 55% relative reductions.

Compared with their counterparts in the placebo group, patients in the lower- and higher-dose cladribine groups were significantly less likely to experience a relapse (relative risks, 0.52 and 0.54) or progression (hazard ratios, 0.67 and 0.69).

Dr. Giovannoni reported that he has received personal compensation from Merck-Serono.

The study was supported by Merck Serono S.A., Geneva, an affiliate of Merck KGaA, Darmstadt, Germany.

SEATTLE — Oral cladribine reduced the annualized rate of relapse in patients with the relapsing-remitting form of multiple sclerosis by over half in a phase III trial presented at the annual meeting of the American Academy of Neurology.

Cladribine, an antineoplastic used primarily to treat hairy cell leukemia, has several properties relevant to the treatment of multiple sclerosis (MS): It produces a sustained reduction in numbers of CD4 and CD8 T cells and of B cells, decreases levels of proinflammatory chemokines, and crosses the blood-brain barrier, according to lead investigator Dr. Gavin Giovannoni, a neurologist at Barts and The London School of Medicine and Dentistry, London.

He and his coinvestigators enrolled patients who had definite, active relapsing-remitting MS and an Expanded Disability Status Scale (EDSS) score of 5.5 or less.

Of those patients, 433 received a lower total dose of cladribine (3.5 mg/kg), 456 received a higher total dose of cladribine (5.25 mg/kg), and 437 got a placebo. Medication was taken for only 4-5 days a month in 2-4 months a year.

“We were quite surprised,” Dr. Giovannoni said of the trial's results for the primary end point, the annualized relapse rate after 96 weeks of treatment. “Despite having a relatively low event rate in the placebo arm, there was a robust and highly significant impact on relapse rate in both [experimental] study arms.”

Specifically, in intention-to-treat analyses, annualized relapse rates were 0.14 and 0.15 in the lower- and higher-dose cladribine groups, respectively, compared with 0.33 in the placebo group. The differences corresponded to statistically significant 58% and 55% relative reductions.

Compared with their counterparts in the placebo group, patients in the lower- and higher-dose cladribine groups were significantly less likely to experience a relapse (relative risks, 0.52 and 0.54) or progression (hazard ratios, 0.67 and 0.69).

Dr. Giovannoni reported that he has received personal compensation from Merck-Serono.

The study was supported by Merck Serono S.A., Geneva, an affiliate of Merck KGaA, Darmstadt, Germany.

SEATTLE — Optimally controlling lipid and blood pressure levels can reduce the risk of stroke by up to 65% in patients at high risk, Dr. Pierre Amarenco reported at the annual meeting of the American Academy of Neurology.

The findings are based on a new analysis of data from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. The results of this trial, as well as the findings of a recent meta-analysis of stroke-prevention trials (Lancet Neurol. 2009;8:453-63), suggest that the risk of stroke falls steadily in direct proportion to declines in the level of low-density lipoprotein cholesterol (LDL-C).

To assess how much improvements in other cardiovascular risk factors add to risk reduction, Dr. Amarenco, a neurologist at the Denis Diderot University in Paris, and his colleagues further analyzed data from SPARCL.

The researchers assessed associations between lipid and blood pressure levels at 1 month after randomization and clinical outcomes after a mean follow-up of 4.9 years.

In SPARCL, 4,732 patients at high risk for stroke because of a previous stroke or transient ischemic attack were randomized in equal numbers to treatment with atorvastatin or placebo.

The trial's main results, previously reported, showed that patients in the atorvastatin group were significantly less likely to experience both stroke and major cardiovascular events. Patients whose reductions in LDL-C level exceeded the median overall reduction (16%) in the trial population were significantly less likely to experience a stroke (hazard ratio, 0.79) or a major cardiovascular event (hazard ratio, 0.76), compared with their counterparts.

The subset analysis by Dr. Amarenco and his associates went beyond these measures. They assessed associations between lipid and blood pressure levels at 1 month after randomization and clinical outcomes after a mean follow-up of 4.9 years.

For patients whose LDL-C reductions were above the median value, their risks of events also were significantly reduced if their levels of high-density lipoprotein cholesterol (HDL-C) exceeded the median value (47 mg/dL) or if their systolic BP levels were below the median value (138 mm Hg).

There also was a trend toward additional reductions in stroke and cardiovascular events for patients whose triglyceride levels were above the median reduction (15%), as well as for those whose diastolic BP was below the median value (80 mm Hg).

A final, exploratory analysis assessed the combined effects of optimal control of four measures, based on targets outlined in national guidelines: an LDL-C level of less than 70 mg/dL, an HDL-C level of more than 50 mg/dL, a triglyceride level of less than 150 mg/dL, and a BP of less than 120/80 mm Hg.

Optimal control was achieved for one measure by 24%, for two measures by 41%, for three by 19%, and for four by 2%.

“There was a dose-response relationship,” Dr. Amarenco observed. The hazard ratios for both stroke and major cardiovascular events decreased significantly as the number of optimally controlled measures increased.

Compared with trial participants who did not achieve optimal control of any measures, patients achieving optimal control of all four measures had a 65% relative reduction in the risk of stroke and a 75% relative reduction in the risk of major cardiovascular events.

Dr. Amarenco reported that he has received honoraria from Pfizer Inc. as a member of the steering committee and speaker fees. The SPARCL trial was sponsored by Pfizer Inc.

SEATTLE — Optimally controlling lipid and blood pressure levels can reduce the risk of stroke by up to 65% in patients at high risk, Dr. Pierre Amarenco reported at the annual meeting of the American Academy of Neurology.

The findings are based on a new analysis of data from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. The results of this trial, as well as the findings of a recent meta-analysis of stroke-prevention trials (Lancet Neurol. 2009;8:453-63), suggest that the risk of stroke falls steadily in direct proportion to declines in the level of low-density lipoprotein cholesterol (LDL-C).

To assess how much improvements in other cardiovascular risk factors add to risk reduction, Dr. Amarenco, a neurologist at the Denis Diderot University in Paris, and his colleagues further analyzed data from SPARCL.

The researchers assessed associations between lipid and blood pressure levels at 1 month after randomization and clinical outcomes after a mean follow-up of 4.9 years.

In SPARCL, 4,732 patients at high risk for stroke because of a previous stroke or transient ischemic attack were randomized in equal numbers to treatment with atorvastatin or placebo.

The trial's main results, previously reported, showed that patients in the atorvastatin group were significantly less likely to experience both stroke and major cardiovascular events. Patients whose reductions in LDL-C level exceeded the median overall reduction (16%) in the trial population were significantly less likely to experience a stroke (hazard ratio, 0.79) or a major cardiovascular event (hazard ratio, 0.76), compared with their counterparts.

The subset analysis by Dr. Amarenco and his associates went beyond these measures. They assessed associations between lipid and blood pressure levels at 1 month after randomization and clinical outcomes after a mean follow-up of 4.9 years.

For patients whose LDL-C reductions were above the median value, their risks of events also were significantly reduced if their levels of high-density lipoprotein cholesterol (HDL-C) exceeded the median value (47 mg/dL) or if their systolic BP levels were below the median value (138 mm Hg).

There also was a trend toward additional reductions in stroke and cardiovascular events for patients whose triglyceride levels were above the median reduction (15%), as well as for those whose diastolic BP was below the median value (80 mm Hg).

A final, exploratory analysis assessed the combined effects of optimal control of four measures, based on targets outlined in national guidelines: an LDL-C level of less than 70 mg/dL, an HDL-C level of more than 50 mg/dL, a triglyceride level of less than 150 mg/dL, and a BP of less than 120/80 mm Hg.

Optimal control was achieved for one measure by 24%, for two measures by 41%, for three by 19%, and for four by 2%.

“There was a dose-response relationship,” Dr. Amarenco observed. The hazard ratios for both stroke and major cardiovascular events decreased significantly as the number of optimally controlled measures increased.

Compared with trial participants who did not achieve optimal control of any measures, patients achieving optimal control of all four measures had a 65% relative reduction in the risk of stroke and a 75% relative reduction in the risk of major cardiovascular events.

Dr. Amarenco reported that he has received honoraria from Pfizer Inc. as a member of the steering committee and speaker fees. The SPARCL trial was sponsored by Pfizer Inc.

SEATTLE — Optimally controlling lipid and blood pressure levels can reduce the risk of stroke by up to 65% in patients at high risk, Dr. Pierre Amarenco reported at the annual meeting of the American Academy of Neurology.

The findings are based on a new analysis of data from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. The results of this trial, as well as the findings of a recent meta-analysis of stroke-prevention trials (Lancet Neurol. 2009;8:453-63), suggest that the risk of stroke falls steadily in direct proportion to declines in the level of low-density lipoprotein cholesterol (LDL-C).

To assess how much improvements in other cardiovascular risk factors add to risk reduction, Dr. Amarenco, a neurologist at the Denis Diderot University in Paris, and his colleagues further analyzed data from SPARCL.

The researchers assessed associations between lipid and blood pressure levels at 1 month after randomization and clinical outcomes after a mean follow-up of 4.9 years.

In SPARCL, 4,732 patients at high risk for stroke because of a previous stroke or transient ischemic attack were randomized in equal numbers to treatment with atorvastatin or placebo.

The trial's main results, previously reported, showed that patients in the atorvastatin group were significantly less likely to experience both stroke and major cardiovascular events. Patients whose reductions in LDL-C level exceeded the median overall reduction (16%) in the trial population were significantly less likely to experience a stroke (hazard ratio, 0.79) or a major cardiovascular event (hazard ratio, 0.76), compared with their counterparts.

The subset analysis by Dr. Amarenco and his associates went beyond these measures. They assessed associations between lipid and blood pressure levels at 1 month after randomization and clinical outcomes after a mean follow-up of 4.9 years.

For patients whose LDL-C reductions were above the median value, their risks of events also were significantly reduced if their levels of high-density lipoprotein cholesterol (HDL-C) exceeded the median value (47 mg/dL) or if their systolic BP levels were below the median value (138 mm Hg).

There also was a trend toward additional reductions in stroke and cardiovascular events for patients whose triglyceride levels were above the median reduction (15%), as well as for those whose diastolic BP was below the median value (80 mm Hg).

A final, exploratory analysis assessed the combined effects of optimal control of four measures, based on targets outlined in national guidelines: an LDL-C level of less than 70 mg/dL, an HDL-C level of more than 50 mg/dL, a triglyceride level of less than 150 mg/dL, and a BP of less than 120/80 mm Hg.

Optimal control was achieved for one measure by 24%, for two measures by 41%, for three by 19%, and for four by 2%.

“There was a dose-response relationship,” Dr. Amarenco observed. The hazard ratios for both stroke and major cardiovascular events decreased significantly as the number of optimally controlled measures increased.

Compared with trial participants who did not achieve optimal control of any measures, patients achieving optimal control of all four measures had a 65% relative reduction in the risk of stroke and a 75% relative reduction in the risk of major cardiovascular events.

Dr. Amarenco reported that he has received honoraria from Pfizer Inc. as a member of the steering committee and speaker fees. The SPARCL trial was sponsored by Pfizer Inc.

SAN FRANCISCO — Older women who smoke have an elevated risk of colorectal cancer, but they have a particularly high risk of cancers containing certain molecular features, a large prospective study has found.

Former and current smokers were much more likely than never smokers to develop colorectal cancers associated with a CpG island methylator phenotype and/or a BRAF mutation in the analysis of data and tissue samples from 37,399 women enrolled in the Iowa Women's Health Study.

“Existing observational data support a positive association between cigarette smoking and incident colorectal cancer,” lead author Dr. David Limsui said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology. “However, the molecular mechanisms underlying cigarette smoking-induced colorectal carcinogenesis remain incompletely defined.”

Studies have implicated hypermethylation of CpG islands, genome regions rich in CpG dinucleotides, noted Dr. Limsui, of the Mayo Clinic in Rochester, Minn. Patients having widespread methylation in these regions are said to have a CpG island methylator phenotype (CIMP). This phenotype has been associated with mutation of BRAF, a gene involved in cell signaling and cell growth.

Dr. Limsui and his coinvestigators analyzed data and tissue samples from women who were aged 55–69 years at baseline, had never had cancer, and reported their smoking status; 4% of the women developed colorectal cancer during a follow-up of 18 years.

Never smokers contributed 68% of 603,671 person-years of follow-up, former smokers contributed 19%, and current smokers contributed 13%.

The investigator assessed formalin-fixed, paraffin-embedded tumor specimens, available for 555 women with cancer, for CIMP status and the presence of BRAF mutation.

In a multivariate analysis among the entire cohort adjusted for potential confounders (age, body mass index, waist-to-hip ratio, physical activity, alcohol consumption, hormone replacement therapy use, and dietary factors), former and current smokers had 1.15 and 1.25 times the risk of any colorectal cancer, compared with never smokers.

The findings were similar when cumulative smoking was considered. Specifically, relative to their never-smoking peers, women having 1–19, 20–39, and 40 or more pack-years of exposure had 1.13, 1.11, and 1.38 times the risk, respectively, of any colorectal cancer.

The risk of CIMP-negative cancer did not vary by smoking status or exposure, but the risk of CIMP-positive cancer did. Compared with never smokers, former and current smokers had 1.21 and 1.85 times the risk of CIMP-positive cancer, respectively—increases that were more striking than those for colorectal cancer generally, Dr. Limsui commented.

The risk for CIMP-positive cancer among women with 1–19, 20–39, and 40 or more pack-years of smoking exposure was 1.32, 1.24, and 1.79, respectively, compared with never smokers.

Similarly, the risk of cancer without BRAF mutation did not vary by smoking status or exposure, but the risk of BRAF-mutated cancer did, he said. Compared with never smokers, former and current smokers had relative risk of 1.36 and 1.89—values again higher than those for colorectal cancer generally.

The relative risk for BRAF-mutated cancer among women with 1–19, 20–39, and 40 or more pack-years of smoking exposure was 1.58, 1.24, and 1.90, compared with never smokers.

Dr. Limsui reported that he had no conflicts of interest in association with the study.

SAN FRANCISCO — Older women who smoke have an elevated risk of colorectal cancer, but they have a particularly high risk of cancers containing certain molecular features, a large prospective study has found.

Former and current smokers were much more likely than never smokers to develop colorectal cancers associated with a CpG island methylator phenotype and/or a BRAF mutation in the analysis of data and tissue samples from 37,399 women enrolled in the Iowa Women's Health Study.

“Existing observational data support a positive association between cigarette smoking and incident colorectal cancer,” lead author Dr. David Limsui said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology. “However, the molecular mechanisms underlying cigarette smoking-induced colorectal carcinogenesis remain incompletely defined.”

Studies have implicated hypermethylation of CpG islands, genome regions rich in CpG dinucleotides, noted Dr. Limsui, of the Mayo Clinic in Rochester, Minn. Patients having widespread methylation in these regions are said to have a CpG island methylator phenotype (CIMP). This phenotype has been associated with mutation of BRAF, a gene involved in cell signaling and cell growth.

Dr. Limsui and his coinvestigators analyzed data and tissue samples from women who were aged 55–69 years at baseline, had never had cancer, and reported their smoking status; 4% of the women developed colorectal cancer during a follow-up of 18 years.

Never smokers contributed 68% of 603,671 person-years of follow-up, former smokers contributed 19%, and current smokers contributed 13%.

The investigator assessed formalin-fixed, paraffin-embedded tumor specimens, available for 555 women with cancer, for CIMP status and the presence of BRAF mutation.

In a multivariate analysis among the entire cohort adjusted for potential confounders (age, body mass index, waist-to-hip ratio, physical activity, alcohol consumption, hormone replacement therapy use, and dietary factors), former and current smokers had 1.15 and 1.25 times the risk of any colorectal cancer, compared with never smokers.

The findings were similar when cumulative smoking was considered. Specifically, relative to their never-smoking peers, women having 1–19, 20–39, and 40 or more pack-years of exposure had 1.13, 1.11, and 1.38 times the risk, respectively, of any colorectal cancer.

The risk of CIMP-negative cancer did not vary by smoking status or exposure, but the risk of CIMP-positive cancer did. Compared with never smokers, former and current smokers had 1.21 and 1.85 times the risk of CIMP-positive cancer, respectively—increases that were more striking than those for colorectal cancer generally, Dr. Limsui commented.

The risk for CIMP-positive cancer among women with 1–19, 20–39, and 40 or more pack-years of smoking exposure was 1.32, 1.24, and 1.79, respectively, compared with never smokers.

Similarly, the risk of cancer without BRAF mutation did not vary by smoking status or exposure, but the risk of BRAF-mutated cancer did, he said. Compared with never smokers, former and current smokers had relative risk of 1.36 and 1.89—values again higher than those for colorectal cancer generally.

The relative risk for BRAF-mutated cancer among women with 1–19, 20–39, and 40 or more pack-years of smoking exposure was 1.58, 1.24, and 1.90, compared with never smokers.

Dr. Limsui reported that he had no conflicts of interest in association with the study.

SAN FRANCISCO — Older women who smoke have an elevated risk of colorectal cancer, but they have a particularly high risk of cancers containing certain molecular features, a large prospective study has found.

Former and current smokers were much more likely than never smokers to develop colorectal cancers associated with a CpG island methylator phenotype and/or a BRAF mutation in the analysis of data and tissue samples from 37,399 women enrolled in the Iowa Women's Health Study.

“Existing observational data support a positive association between cigarette smoking and incident colorectal cancer,” lead author Dr. David Limsui said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology. “However, the molecular mechanisms underlying cigarette smoking-induced colorectal carcinogenesis remain incompletely defined.”

Studies have implicated hypermethylation of CpG islands, genome regions rich in CpG dinucleotides, noted Dr. Limsui, of the Mayo Clinic in Rochester, Minn. Patients having widespread methylation in these regions are said to have a CpG island methylator phenotype (CIMP). This phenotype has been associated with mutation of BRAF, a gene involved in cell signaling and cell growth.

Dr. Limsui and his coinvestigators analyzed data and tissue samples from women who were aged 55–69 years at baseline, had never had cancer, and reported their smoking status; 4% of the women developed colorectal cancer during a follow-up of 18 years.

Never smokers contributed 68% of 603,671 person-years of follow-up, former smokers contributed 19%, and current smokers contributed 13%.

The investigator assessed formalin-fixed, paraffin-embedded tumor specimens, available for 555 women with cancer, for CIMP status and the presence of BRAF mutation.

In a multivariate analysis among the entire cohort adjusted for potential confounders (age, body mass index, waist-to-hip ratio, physical activity, alcohol consumption, hormone replacement therapy use, and dietary factors), former and current smokers had 1.15 and 1.25 times the risk of any colorectal cancer, compared with never smokers.

The findings were similar when cumulative smoking was considered. Specifically, relative to their never-smoking peers, women having 1–19, 20–39, and 40 or more pack-years of exposure had 1.13, 1.11, and 1.38 times the risk, respectively, of any colorectal cancer.

The risk of CIMP-negative cancer did not vary by smoking status or exposure, but the risk of CIMP-positive cancer did. Compared with never smokers, former and current smokers had 1.21 and 1.85 times the risk of CIMP-positive cancer, respectively—increases that were more striking than those for colorectal cancer generally, Dr. Limsui commented.

The risk for CIMP-positive cancer among women with 1–19, 20–39, and 40 or more pack-years of smoking exposure was 1.32, 1.24, and 1.79, respectively, compared with never smokers.

Similarly, the risk of cancer without BRAF mutation did not vary by smoking status or exposure, but the risk of BRAF-mutated cancer did, he said. Compared with never smokers, former and current smokers had relative risk of 1.36 and 1.89—values again higher than those for colorectal cancer generally.

The relative risk for BRAF-mutated cancer among women with 1–19, 20–39, and 40 or more pack-years of smoking exposure was 1.58, 1.24, and 1.90, compared with never smokers.

Dr. Limsui reported that he had no conflicts of interest in association with the study.

SAN FRANCISCO — Confocal laser endomicroscopy accurately classifies lesions found during colonoscopy according to their malignant potential, the results of a prospective cohort study show.

“Confocal laser endomicroscopy is a promising tool for in vivo microscopic imaging of mucosal lesions during ongoing endoscopy,” said Dr. Anna Buchner, a gastroenterologist at the Mayo Clinic in Jacksonville, Fla.

“It may allow us to classify neoplastic and benign lesions in real time during colonoscopy, thus reducing the time and risk of procedures, with fewer polypectomies performed,” she said, reporting the results of the prospective study among patients undergoing surveillance colonoscopy.

Confocal laser endomicroscopy allows a clinician to look at living tissue in an area of interest, as if the tissue were under a microscope, while the endoscope is still in the patient. Mucosa can be inspected at a magnification of up to 1,000 times, much greater than the 100 times permitted by zoom endoscopy and the 30 times permitted by normal endoscopy.

The Cellvizio GI system used in the study had a confocal laser probe that can be passed through any endoscope, a laser scanning unit that acquires up to 12 images per second, and control and acquisition software that permit real-time image reconstruction.

Lesions were identified by high-resolution colonoscopy, and imaged by confocal laser endomicroscopy after administration of intravenous fluorescein contrast. They were then removed by polypectomy and examined histopathologically, Dr. Buchner reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

In the pilot part of the study, the confocal images were analyzed without the observers being blinded to the colonoscopic appearance and histopathology findings. This enabled investigators to develop key image features for distinguishing between hyperplastic and neoplastic lesions. Imaging was performed in six patients, with examination of a total of 10 normal sites, 10 hyperplastic lesions, and 10 neoplastic lesions.

Hyperplastic lesions typically had regular crypts with round or stellate-shaped crypt openings, Dr. Buchner reported. In contrast, neoplastic lesions typically had elongated, tubular crypt openings, a reduction in the number of goblet cells, increased and irregular vasculature, and dramatic variation in cell size.

Then the confocal images were analyzed by an investigator blinded to colonoscopic appearance and histopathology findings, to assess the accuracy of the confocal diagnosis relative to the gold standard of the histopathologic diagnosis.

For classification of lesions as neoplastic, confocal laser endomicroscopy had a sensitivity of 86%, a specificity of 93%, and an overall accuracy of 89%, according to Dr. Buchner. The positive predictive value was 95%, and the negative predictive value was 80%.

“The use of this method has the potential to avoid polypectomies of nonneoplastic polyps,” Dr. Buchner said.

She said she had no conflicts of interest relevant to the study, which was funded by a grant from the American Society for Gastrointestinal Endoscopy.

SAN FRANCISCO — Confocal laser endomicroscopy accurately classifies lesions found during colonoscopy according to their malignant potential, the results of a prospective cohort study show.

“Confocal laser endomicroscopy is a promising tool for in vivo microscopic imaging of mucosal lesions during ongoing endoscopy,” said Dr. Anna Buchner, a gastroenterologist at the Mayo Clinic in Jacksonville, Fla.

“It may allow us to classify neoplastic and benign lesions in real time during colonoscopy, thus reducing the time and risk of procedures, with fewer polypectomies performed,” she said, reporting the results of the prospective study among patients undergoing surveillance colonoscopy.

Confocal laser endomicroscopy allows a clinician to look at living tissue in an area of interest, as if the tissue were under a microscope, while the endoscope is still in the patient. Mucosa can be inspected at a magnification of up to 1,000 times, much greater than the 100 times permitted by zoom endoscopy and the 30 times permitted by normal endoscopy.

The Cellvizio GI system used in the study had a confocal laser probe that can be passed through any endoscope, a laser scanning unit that acquires up to 12 images per second, and control and acquisition software that permit real-time image reconstruction.

Lesions were identified by high-resolution colonoscopy, and imaged by confocal laser endomicroscopy after administration of intravenous fluorescein contrast. They were then removed by polypectomy and examined histopathologically, Dr. Buchner reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

In the pilot part of the study, the confocal images were analyzed without the observers being blinded to the colonoscopic appearance and histopathology findings. This enabled investigators to develop key image features for distinguishing between hyperplastic and neoplastic lesions. Imaging was performed in six patients, with examination of a total of 10 normal sites, 10 hyperplastic lesions, and 10 neoplastic lesions.

Hyperplastic lesions typically had regular crypts with round or stellate-shaped crypt openings, Dr. Buchner reported. In contrast, neoplastic lesions typically had elongated, tubular crypt openings, a reduction in the number of goblet cells, increased and irregular vasculature, and dramatic variation in cell size.

Then the confocal images were analyzed by an investigator blinded to colonoscopic appearance and histopathology findings, to assess the accuracy of the confocal diagnosis relative to the gold standard of the histopathologic diagnosis.

For classification of lesions as neoplastic, confocal laser endomicroscopy had a sensitivity of 86%, a specificity of 93%, and an overall accuracy of 89%, according to Dr. Buchner. The positive predictive value was 95%, and the negative predictive value was 80%.

“The use of this method has the potential to avoid polypectomies of nonneoplastic polyps,” Dr. Buchner said.

She said she had no conflicts of interest relevant to the study, which was funded by a grant from the American Society for Gastrointestinal Endoscopy.

SAN FRANCISCO — Confocal laser endomicroscopy accurately classifies lesions found during colonoscopy according to their malignant potential, the results of a prospective cohort study show.

“Confocal laser endomicroscopy is a promising tool for in vivo microscopic imaging of mucosal lesions during ongoing endoscopy,” said Dr. Anna Buchner, a gastroenterologist at the Mayo Clinic in Jacksonville, Fla.

“It may allow us to classify neoplastic and benign lesions in real time during colonoscopy, thus reducing the time and risk of procedures, with fewer polypectomies performed,” she said, reporting the results of the prospective study among patients undergoing surveillance colonoscopy.

Confocal laser endomicroscopy allows a clinician to look at living tissue in an area of interest, as if the tissue were under a microscope, while the endoscope is still in the patient. Mucosa can be inspected at a magnification of up to 1,000 times, much greater than the 100 times permitted by zoom endoscopy and the 30 times permitted by normal endoscopy.

The Cellvizio GI system used in the study had a confocal laser probe that can be passed through any endoscope, a laser scanning unit that acquires up to 12 images per second, and control and acquisition software that permit real-time image reconstruction.

Lesions were identified by high-resolution colonoscopy, and imaged by confocal laser endomicroscopy after administration of intravenous fluorescein contrast. They were then removed by polypectomy and examined histopathologically, Dr. Buchner reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

In the pilot part of the study, the confocal images were analyzed without the observers being blinded to the colonoscopic appearance and histopathology findings. This enabled investigators to develop key image features for distinguishing between hyperplastic and neoplastic lesions. Imaging was performed in six patients, with examination of a total of 10 normal sites, 10 hyperplastic lesions, and 10 neoplastic lesions.

Hyperplastic lesions typically had regular crypts with round or stellate-shaped crypt openings, Dr. Buchner reported. In contrast, neoplastic lesions typically had elongated, tubular crypt openings, a reduction in the number of goblet cells, increased and irregular vasculature, and dramatic variation in cell size.

Then the confocal images were analyzed by an investigator blinded to colonoscopic appearance and histopathology findings, to assess the accuracy of the confocal diagnosis relative to the gold standard of the histopathologic diagnosis.

For classification of lesions as neoplastic, confocal laser endomicroscopy had a sensitivity of 86%, a specificity of 93%, and an overall accuracy of 89%, according to Dr. Buchner. The positive predictive value was 95%, and the negative predictive value was 80%.

“The use of this method has the potential to avoid polypectomies of nonneoplastic polyps,” Dr. Buchner said.

She said she had no conflicts of interest relevant to the study, which was funded by a grant from the American Society for Gastrointestinal Endoscopy.

SEATTLE — States vary widely as to whether they legally require physicians to report patients whose driving may be impaired because of seizures, and whether they provide reporting physicians any legal protection, a new study shows.

Physicians across specialties often encounter patients with seizure disorders and they may be unsure of their legal obligation to report such patients to the state's department of motor vehicles, said Dr. Michael C. Harlow, a forensic psychiatrist at the University of South Dakota, Sioux Falls.

Dr. Harlow and his colleagues searched legal and medical databases in an effort to identify statutory and case law in all 50 states and the District of Columbia regarding physician reporting of driving-impaired seizure patients.

All states allow physicians to report patients who are impaired to drive because of seizures, but only six of them—California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania—mandate it, Dr. Harlow said at the annual meeting of the American Academy of Psychiatry and the Law.

About half of the states do not provide relevant legal protections to reporting physicians, a fact that may discourage some physicians from reporting, Dr. Harlow noted.

Only 22 states legally protect physicians from disciplinary action for breaking physician-patient confidentiality in order to report a driving-impaired seizure patient.

And only 26 states provide reporting physicians with liability immunity from third parties if the reported patient has a motor vehicle accident that results in injuries or death.

“What is interesting is that some of the states that have mandatory reporting don't provide full legal protection to the physician doing the reporting,” Dr. Harlow commented. “So that puts the physician in a quandary.”

For example, although the state of New Jersey requires physicians to report driving-impaired seizure patients, it does not protect the physician for breach of confidentiality under that circumstance.

There also is a variety of definitions as to what activates a reporting statute, Dr. Harlow observed. Some of the six states specify seizures, whereas others use a broader definition of a medical condition that can cause loss of consciousness, such as diabetes or cardiovascular disease.

There also is marked variation in the penalties for failure to report in these states, Dr. Harlow noted.

Three of those states have no penalties, two have civil penalties, and one—Nevada—classifies failure to report as a misdemeanor offense.

In other words, physicians could face criminal charges.

Whether physicians follow these state statutes is another question. Data from California suggest that many physicians do not report patients with seizures despite the state's stringent statute.

And in legal cases testing the issue, California courts have thus far drawn distinctions based on the nature of the physician's relationship with the patient, he noted.

“If you are a physician treating a patient for a broken arm and realize that they have a neurologic condition, but you are not their neurologist and you don't report them, and they go off and [have an accident], then you are not liable,” Dr. Harlow explained.

However, if “you are the treating neurologist, then you would have a problem potentially under the law,” he added.

Dr. Harlow reported that he had no conflicts of interest in association with the study.

SEATTLE — States vary widely as to whether they legally require physicians to report patients whose driving may be impaired because of seizures, and whether they provide reporting physicians any legal protection, a new study shows.

Physicians across specialties often encounter patients with seizure disorders and they may be unsure of their legal obligation to report such patients to the state's department of motor vehicles, said Dr. Michael C. Harlow, a forensic psychiatrist at the University of South Dakota, Sioux Falls.

Dr. Harlow and his colleagues searched legal and medical databases in an effort to identify statutory and case law in all 50 states and the District of Columbia regarding physician reporting of driving-impaired seizure patients.

All states allow physicians to report patients who are impaired to drive because of seizures, but only six of them—California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania—mandate it, Dr. Harlow said at the annual meeting of the American Academy of Psychiatry and the Law.

About half of the states do not provide relevant legal protections to reporting physicians, a fact that may discourage some physicians from reporting, Dr. Harlow noted.

Only 22 states legally protect physicians from disciplinary action for breaking physician-patient confidentiality in order to report a driving-impaired seizure patient.

And only 26 states provide reporting physicians with liability immunity from third parties if the reported patient has a motor vehicle accident that results in injuries or death.

“What is interesting is that some of the states that have mandatory reporting don't provide full legal protection to the physician doing the reporting,” Dr. Harlow commented. “So that puts the physician in a quandary.”

For example, although the state of New Jersey requires physicians to report driving-impaired seizure patients, it does not protect the physician for breach of confidentiality under that circumstance.

There also is a variety of definitions as to what activates a reporting statute, Dr. Harlow observed. Some of the six states specify seizures, whereas others use a broader definition of a medical condition that can cause loss of consciousness, such as diabetes or cardiovascular disease.

There also is marked variation in the penalties for failure to report in these states, Dr. Harlow noted.

Three of those states have no penalties, two have civil penalties, and one—Nevada—classifies failure to report as a misdemeanor offense.

In other words, physicians could face criminal charges.

Whether physicians follow these state statutes is another question. Data from California suggest that many physicians do not report patients with seizures despite the state's stringent statute.

And in legal cases testing the issue, California courts have thus far drawn distinctions based on the nature of the physician's relationship with the patient, he noted.

“If you are a physician treating a patient for a broken arm and realize that they have a neurologic condition, but you are not their neurologist and you don't report them, and they go off and [have an accident], then you are not liable,” Dr. Harlow explained.

However, if “you are the treating neurologist, then you would have a problem potentially under the law,” he added.

Dr. Harlow reported that he had no conflicts of interest in association with the study.

SEATTLE — States vary widely as to whether they legally require physicians to report patients whose driving may be impaired because of seizures, and whether they provide reporting physicians any legal protection, a new study shows.

Physicians across specialties often encounter patients with seizure disorders and they may be unsure of their legal obligation to report such patients to the state's department of motor vehicles, said Dr. Michael C. Harlow, a forensic psychiatrist at the University of South Dakota, Sioux Falls.

Dr. Harlow and his colleagues searched legal and medical databases in an effort to identify statutory and case law in all 50 states and the District of Columbia regarding physician reporting of driving-impaired seizure patients.

All states allow physicians to report patients who are impaired to drive because of seizures, but only six of them—California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania—mandate it, Dr. Harlow said at the annual meeting of the American Academy of Psychiatry and the Law.

About half of the states do not provide relevant legal protections to reporting physicians, a fact that may discourage some physicians from reporting, Dr. Harlow noted.

Only 22 states legally protect physicians from disciplinary action for breaking physician-patient confidentiality in order to report a driving-impaired seizure patient.

And only 26 states provide reporting physicians with liability immunity from third parties if the reported patient has a motor vehicle accident that results in injuries or death.

“What is interesting is that some of the states that have mandatory reporting don't provide full legal protection to the physician doing the reporting,” Dr. Harlow commented. “So that puts the physician in a quandary.”

For example, although the state of New Jersey requires physicians to report driving-impaired seizure patients, it does not protect the physician for breach of confidentiality under that circumstance.

There also is a variety of definitions as to what activates a reporting statute, Dr. Harlow observed. Some of the six states specify seizures, whereas others use a broader definition of a medical condition that can cause loss of consciousness, such as diabetes or cardiovascular disease.

There also is marked variation in the penalties for failure to report in these states, Dr. Harlow noted.

Three of those states have no penalties, two have civil penalties, and one—Nevada—classifies failure to report as a misdemeanor offense.

In other words, physicians could face criminal charges.

Whether physicians follow these state statutes is another question. Data from California suggest that many physicians do not report patients with seizures despite the state's stringent statute.

And in legal cases testing the issue, California courts have thus far drawn distinctions based on the nature of the physician's relationship with the patient, he noted.

“If you are a physician treating a patient for a broken arm and realize that they have a neurologic condition, but you are not their neurologist and you don't report them, and they go off and [have an accident], then you are not liable,” Dr. Harlow explained.

However, if “you are the treating neurologist, then you would have a problem potentially under the law,” he added.

Dr. Harlow reported that he had no conflicts of interest in association with the study.

SEATTLE — States vary widely as to whether they legally require physicians to report patients whose driving may be impaired because of seizures, and whether they provide reporting physicians any legal protection, a new study shows.

Physicians across specialties often encounter patients with seizure disorders, and they may be unsure of their legal obligation to report such patients to the state's department of motor vehicles, said Dr. Michael C. Harlow, a forensic psychiatrist at the University of South Dakota, Sioux Falls.

For the study, Dr. Harlow and his colleagues searched legal and medical databases to identify statutory and case law in all 50 states and the District of Columbia regarding physician reporting of driving-impaired seizure patients.

All states allow physicians to report patients who are impaired to drive because of seizures, but only six of them—California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania—mandate it, Dr. Harlow said at the annual meeting of the American Academy of Psychiatry and the Law.

About half of states do not provide relevant legal protections to reporting physicians, a fact that may discourage some physicians from reporting, Dr. Harlow noted.

Only 22 states legally protect physicians from disciplinary action for breaking physician-patient confidentiality in order to report a driving-impaired seizure patient.

And only 26 states provide reporting physicians with liability immunity from third parties if the reported patient has a motor vehicle accident that results in injuries or death.

“What is interesting is that some of the states that have mandatory reporting don't provide full legal protection to the physician doing the reporting,” Dr. Harlow commented. “So that puts the physician in a quandary.”

For example, although New Jersey requires physicians to report driving-impaired seizure patients, it does not offer protection for the physician for breach of confidentiality under that circumstance.

There also are a variety of definitions as to what activates a reporting statute, Dr. Harlow observed. Some of the six states specify seizures, whereas others use a broader definition of a medical condition that can cause loss of consciousness, such as diabetes or cardiovascular disease.

There also is marked variation in the penalties for failure to report in these states, Dr. Harlow noted. Three of them have no penalties, two have civil penalties, and one—Nevada—classifies failure to report as a misdemeanor offense, meaning physicians could face criminal charges.

Whether physicians follow these state statutes is another question. Data from California suggest that many physicians do not report patients with seizures despite the state's stringent statute, Dr. Harlow said.

And in legal cases testing the issue, California courts have thus far drawn distinctions based on the nature of the physician's relationship with the patient, he noted.

“If you are a physician treating a patient for a broken arm and realize that they have a neurologic condition, but you are not their neurologist and you don't report them, and they go off and [have an accident], you are not liable,” he explained. However, if “you are the treating neurologist, then you would have a problem potentially under the law.”

Dr. Harlow reported that he had no conflicts of interest in association with the study.

SEATTLE — States vary widely as to whether they legally require physicians to report patients whose driving may be impaired because of seizures, and whether they provide reporting physicians any legal protection, a new study shows.

Physicians across specialties often encounter patients with seizure disorders, and they may be unsure of their legal obligation to report such patients to the state's department of motor vehicles, said Dr. Michael C. Harlow, a forensic psychiatrist at the University of South Dakota, Sioux Falls.

For the study, Dr. Harlow and his colleagues searched legal and medical databases to identify statutory and case law in all 50 states and the District of Columbia regarding physician reporting of driving-impaired seizure patients.

All states allow physicians to report patients who are impaired to drive because of seizures, but only six of them—California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania—mandate it, Dr. Harlow said at the annual meeting of the American Academy of Psychiatry and the Law.

About half of states do not provide relevant legal protections to reporting physicians, a fact that may discourage some physicians from reporting, Dr. Harlow noted.

Only 22 states legally protect physicians from disciplinary action for breaking physician-patient confidentiality in order to report a driving-impaired seizure patient.

And only 26 states provide reporting physicians with liability immunity from third parties if the reported patient has a motor vehicle accident that results in injuries or death.

“What is interesting is that some of the states that have mandatory reporting don't provide full legal protection to the physician doing the reporting,” Dr. Harlow commented. “So that puts the physician in a quandary.”

For example, although New Jersey requires physicians to report driving-impaired seizure patients, it does not offer protection for the physician for breach of confidentiality under that circumstance.

There also are a variety of definitions as to what activates a reporting statute, Dr. Harlow observed. Some of the six states specify seizures, whereas others use a broader definition of a medical condition that can cause loss of consciousness, such as diabetes or cardiovascular disease.

There also is marked variation in the penalties for failure to report in these states, Dr. Harlow noted. Three of them have no penalties, two have civil penalties, and one—Nevada—classifies failure to report as a misdemeanor offense, meaning physicians could face criminal charges.

Whether physicians follow these state statutes is another question. Data from California suggest that many physicians do not report patients with seizures despite the state's stringent statute, Dr. Harlow said.

And in legal cases testing the issue, California courts have thus far drawn distinctions based on the nature of the physician's relationship with the patient, he noted.

“If you are a physician treating a patient for a broken arm and realize that they have a neurologic condition, but you are not their neurologist and you don't report them, and they go off and [have an accident], you are not liable,” he explained. However, if “you are the treating neurologist, then you would have a problem potentially under the law.”

Dr. Harlow reported that he had no conflicts of interest in association with the study.

SEATTLE — States vary widely as to whether they legally require physicians to report patients whose driving may be impaired because of seizures, and whether they provide reporting physicians any legal protection, a new study shows.

Physicians across specialties often encounter patients with seizure disorders, and they may be unsure of their legal obligation to report such patients to the state's department of motor vehicles, said Dr. Michael C. Harlow, a forensic psychiatrist at the University of South Dakota, Sioux Falls.

For the study, Dr. Harlow and his colleagues searched legal and medical databases to identify statutory and case law in all 50 states and the District of Columbia regarding physician reporting of driving-impaired seizure patients.

All states allow physicians to report patients who are impaired to drive because of seizures, but only six of them—California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania—mandate it, Dr. Harlow said at the annual meeting of the American Academy of Psychiatry and the Law.

About half of states do not provide relevant legal protections to reporting physicians, a fact that may discourage some physicians from reporting, Dr. Harlow noted.

Only 22 states legally protect physicians from disciplinary action for breaking physician-patient confidentiality in order to report a driving-impaired seizure patient.

And only 26 states provide reporting physicians with liability immunity from third parties if the reported patient has a motor vehicle accident that results in injuries or death.

“What is interesting is that some of the states that have mandatory reporting don't provide full legal protection to the physician doing the reporting,” Dr. Harlow commented. “So that puts the physician in a quandary.”

For example, although New Jersey requires physicians to report driving-impaired seizure patients, it does not offer protection for the physician for breach of confidentiality under that circumstance.

There also are a variety of definitions as to what activates a reporting statute, Dr. Harlow observed. Some of the six states specify seizures, whereas others use a broader definition of a medical condition that can cause loss of consciousness, such as diabetes or cardiovascular disease.

There also is marked variation in the penalties for failure to report in these states, Dr. Harlow noted. Three of them have no penalties, two have civil penalties, and one—Nevada—classifies failure to report as a misdemeanor offense, meaning physicians could face criminal charges.

Whether physicians follow these state statutes is another question. Data from California suggest that many physicians do not report patients with seizures despite the state's stringent statute, Dr. Harlow said.

And in legal cases testing the issue, California courts have thus far drawn distinctions based on the nature of the physician's relationship with the patient, he noted.

“If you are a physician treating a patient for a broken arm and realize that they have a neurologic condition, but you are not their neurologist and you don't report them, and they go off and [have an accident], you are not liable,” he explained. However, if “you are the treating neurologist, then you would have a problem potentially under the law.”

Dr. Harlow reported that he had no conflicts of interest in association with the study.

SAN FRANCISCO — Most patients with colorectal cancer have an immune response to the flu vaccine regardless of whether they are receiving chemotherapy and which drug regimen is used, according to the first study to look at the issue specifically in this population.

Dr. Ajithkumar Puthillath, a senior fellow in oncology at the Roswell Park Cancer Institute in Buffalo, New York, and his colleagues conducted their study during the 2006–2007 flu season, enrolling outpatients with colorectal cancer who received the trivalent flu vaccine (Fluzone), which was designed to protect against the H1N1, H3N2, and B/Malaysia strains of the virus.

The 85 patients studied had a median age of 61 years. Slightly more than half were male (56%), and had metastatic disease (57%). Sixty-eight percent of the patients received cytotoxic chemotherapy within a month before and for up to 3 months after vaccination, he reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Overall, 71% of the patient population had an immune response to the vaccine, with no significant difference between those who received chemotherapy and those who did not (69% vs. 74%), Dr. Puthillath reported.

“The take-home message is that in colorectal cancer patients, especially in the community, flu vaccination should be offered to all patients irrespective of age and irrespective of chemotherapy use,” said Dr. Puthillath, who reported that he had no conflicts of interest in association with the study.

SAN FRANCISCO — Most patients with colorectal cancer have an immune response to the flu vaccine regardless of whether they are receiving chemotherapy and which drug regimen is used, according to the first study to look at the issue specifically in this population.

Dr. Ajithkumar Puthillath, a senior fellow in oncology at the Roswell Park Cancer Institute in Buffalo, New York, and his colleagues conducted their study during the 2006–2007 flu season, enrolling outpatients with colorectal cancer who received the trivalent flu vaccine (Fluzone), which was designed to protect against the H1N1, H3N2, and B/Malaysia strains of the virus.

The 85 patients studied had a median age of 61 years. Slightly more than half were male (56%), and had metastatic disease (57%). Sixty-eight percent of the patients received cytotoxic chemotherapy within a month before and for up to 3 months after vaccination, he reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Overall, 71% of the patient population had an immune response to the vaccine, with no significant difference between those who received chemotherapy and those who did not (69% vs. 74%), Dr. Puthillath reported.

“The take-home message is that in colorectal cancer patients, especially in the community, flu vaccination should be offered to all patients irrespective of age and irrespective of chemotherapy use,” said Dr. Puthillath, who reported that he had no conflicts of interest in association with the study.

SAN FRANCISCO — Most patients with colorectal cancer have an immune response to the flu vaccine regardless of whether they are receiving chemotherapy and which drug regimen is used, according to the first study to look at the issue specifically in this population.

Dr. Ajithkumar Puthillath, a senior fellow in oncology at the Roswell Park Cancer Institute in Buffalo, New York, and his colleagues conducted their study during the 2006–2007 flu season, enrolling outpatients with colorectal cancer who received the trivalent flu vaccine (Fluzone), which was designed to protect against the H1N1, H3N2, and B/Malaysia strains of the virus.

The 85 patients studied had a median age of 61 years. Slightly more than half were male (56%), and had metastatic disease (57%). Sixty-eight percent of the patients received cytotoxic chemotherapy within a month before and for up to 3 months after vaccination, he reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Overall, 71% of the patient population had an immune response to the vaccine, with no significant difference between those who received chemotherapy and those who did not (69% vs. 74%), Dr. Puthillath reported.

“The take-home message is that in colorectal cancer patients, especially in the community, flu vaccination should be offered to all patients irrespective of age and irrespective of chemotherapy use,” said Dr. Puthillath, who reported that he had no conflicts of interest in association with the study.

SEATTLE — Most children with epilepsy who become seizure free with antiepileptic drug therapy are able to stop taking the drugs without developing intractable seizures, according to findings from a population-based cohort study.

Dr. Katherine C. Nickels said that about a third of children with epilepsy experience a recurrence after becoming seizure free on antiepileptic drugs (AEDs) and stopping therapy. More than half of those who resume AEDs are rapidly able to regain seizure control.

To put the findings in perspective, she noted the 20% rate of intractable seizures is similar to that seen among children with a new diagnosis of epilepsy.

“Children who achieve seizure freedom on antiseizure medications can be considered for antiseizure medication withdrawal without high risk of intractable epilepsy,” Dr. Nickels reported at the annual meeting of the American Epilepsy Society. Dr. Nickels said she had no disclosures to report in association with the study.

“Antiepileptic medications may have serious side effects, including cognitive slowing, weight change, fatigue, and hepatotoxicity,” she said.

Children who become seizure free while taking AEDs are often weaned off of them, but there is a concern that seizures will recur and—most worrisome—that they will be intractable when they do.

“The current data regarding the risk of recurrence of seizures as well as the risk of intractable seizures following medication withdrawal varies widely from one study to the next,” said Dr. Nickels, a pediatric neurologist at the Mayo Clinic, Rochester, Minn. Moreover, “many of them are not population based.”

Using data from the Rochester Epidemiology Project, she and her coinvestigators reviewed the medical charts of all children aged 1 month to 16 years who received a new diagnosis of epilepsy while living in Olmsted County during 1990-2000 and had follow-up of at least 5 years after their first seizure. To be included in the study, children were required to have had two or more unprovoked seizures in the absence of any progressive neurologic disorder and to be receiving AEDs daily.

The investigators focused on the group who became seizure free and discontinued their AEDs. They reviewed the medical charts of these children through their last follow-up to assess seizure recurrence (defined as occurrence of at least one seizure) and the development of intractable seizures (defined as occurrence of at least one seizure every 3 months during the last year of follow-up and failure of at least two AEDs to control the seizures at maximum tolerated doses).

A total of 152 children fit the study criteria. Some 56 (37%) became seizure free and were weaned off of the drugs. Their mean duration of seizure freedom while on treatment had been 2.3 years.

After a mean follow-up of 8 years, 20 (36%) of this group had a recurrence of seizures. Among these children, 15 restarted AEDs, 4 remained off AEDs with rare or no additional seizures, and 1 died of sudden unexpected death in epilepsy.

After a mean follow-up of 5.7 years in the 15 children who restarted AEDs, 10 again became seizure free within 2 years, whereas 5 never did. Of those five children, three—5% of the total stopping AEDs or 20% of the total restarting them—had intractable seizures.

An analysis of the time until seizures recurred among the children with this outcome showed that 55% had their recurrence within 1 year of stopping AEDs, said Dr. Nickels. But 20% had their recurrence more than 5 years after stopping.

Finally, an analysis of the time until regaining freedom from seizures among the 15 children who had a recurrence and restarted AEDs showed that 8 became seizure free within 1 year and another 2 achieved this status within 2 years. The remaining five children never regained freedom from seizures.

SEATTLE — Most children with epilepsy who become seizure free with antiepileptic drug therapy are able to stop taking the drugs without developing intractable seizures, according to findings from a population-based cohort study.

Dr. Katherine C. Nickels said that about a third of children with epilepsy experience a recurrence after becoming seizure free on antiepileptic drugs (AEDs) and stopping therapy. More than half of those who resume AEDs are rapidly able to regain seizure control.

To put the findings in perspective, she noted the 20% rate of intractable seizures is similar to that seen among children with a new diagnosis of epilepsy.

“Children who achieve seizure freedom on antiseizure medications can be considered for antiseizure medication withdrawal without high risk of intractable epilepsy,” Dr. Nickels reported at the annual meeting of the American Epilepsy Society. Dr. Nickels said she had no disclosures to report in association with the study.

“Antiepileptic medications may have serious side effects, including cognitive slowing, weight change, fatigue, and hepatotoxicity,” she said.

Children who become seizure free while taking AEDs are often weaned off of them, but there is a concern that seizures will recur and—most worrisome—that they will be intractable when they do.

“The current data regarding the risk of recurrence of seizures as well as the risk of intractable seizures following medication withdrawal varies widely from one study to the next,” said Dr. Nickels, a pediatric neurologist at the Mayo Clinic, Rochester, Minn. Moreover, “many of them are not population based.”

Using data from the Rochester Epidemiology Project, she and her coinvestigators reviewed the medical charts of all children aged 1 month to 16 years who received a new diagnosis of epilepsy while living in Olmsted County during 1990-2000 and had follow-up of at least 5 years after their first seizure. To be included in the study, children were required to have had two or more unprovoked seizures in the absence of any progressive neurologic disorder and to be receiving AEDs daily.

The investigators focused on the group who became seizure free and discontinued their AEDs. They reviewed the medical charts of these children through their last follow-up to assess seizure recurrence (defined as occurrence of at least one seizure) and the development of intractable seizures (defined as occurrence of at least one seizure every 3 months during the last year of follow-up and failure of at least two AEDs to control the seizures at maximum tolerated doses).

A total of 152 children fit the study criteria. Some 56 (37%) became seizure free and were weaned off of the drugs. Their mean duration of seizure freedom while on treatment had been 2.3 years.

After a mean follow-up of 8 years, 20 (36%) of this group had a recurrence of seizures. Among these children, 15 restarted AEDs, 4 remained off AEDs with rare or no additional seizures, and 1 died of sudden unexpected death in epilepsy.

After a mean follow-up of 5.7 years in the 15 children who restarted AEDs, 10 again became seizure free within 2 years, whereas 5 never did. Of those five children, three—5% of the total stopping AEDs or 20% of the total restarting them—had intractable seizures.

An analysis of the time until seizures recurred among the children with this outcome showed that 55% had their recurrence within 1 year of stopping AEDs, said Dr. Nickels. But 20% had their recurrence more than 5 years after stopping.

Finally, an analysis of the time until regaining freedom from seizures among the 15 children who had a recurrence and restarted AEDs showed that 8 became seizure free within 1 year and another 2 achieved this status within 2 years. The remaining five children never regained freedom from seizures.

SEATTLE — Most children with epilepsy who become seizure free with antiepileptic drug therapy are able to stop taking the drugs without developing intractable seizures, according to findings from a population-based cohort study.

Dr. Katherine C. Nickels said that about a third of children with epilepsy experience a recurrence after becoming seizure free on antiepileptic drugs (AEDs) and stopping therapy. More than half of those who resume AEDs are rapidly able to regain seizure control.

To put the findings in perspective, she noted the 20% rate of intractable seizures is similar to that seen among children with a new diagnosis of epilepsy.

“Children who achieve seizure freedom on antiseizure medications can be considered for antiseizure medication withdrawal without high risk of intractable epilepsy,” Dr. Nickels reported at the annual meeting of the American Epilepsy Society. Dr. Nickels said she had no disclosures to report in association with the study.

“Antiepileptic medications may have serious side effects, including cognitive slowing, weight change, fatigue, and hepatotoxicity,” she said.

Children who become seizure free while taking AEDs are often weaned off of them, but there is a concern that seizures will recur and—most worrisome—that they will be intractable when they do.

“The current data regarding the risk of recurrence of seizures as well as the risk of intractable seizures following medication withdrawal varies widely from one study to the next,” said Dr. Nickels, a pediatric neurologist at the Mayo Clinic, Rochester, Minn. Moreover, “many of them are not population based.”

Using data from the Rochester Epidemiology Project, she and her coinvestigators reviewed the medical charts of all children aged 1 month to 16 years who received a new diagnosis of epilepsy while living in Olmsted County during 1990-2000 and had follow-up of at least 5 years after their first seizure. To be included in the study, children were required to have had two or more unprovoked seizures in the absence of any progressive neurologic disorder and to be receiving AEDs daily.

The investigators focused on the group who became seizure free and discontinued their AEDs. They reviewed the medical charts of these children through their last follow-up to assess seizure recurrence (defined as occurrence of at least one seizure) and the development of intractable seizures (defined as occurrence of at least one seizure every 3 months during the last year of follow-up and failure of at least two AEDs to control the seizures at maximum tolerated doses).

A total of 152 children fit the study criteria. Some 56 (37%) became seizure free and were weaned off of the drugs. Their mean duration of seizure freedom while on treatment had been 2.3 years.

After a mean follow-up of 8 years, 20 (36%) of this group had a recurrence of seizures. Among these children, 15 restarted AEDs, 4 remained off AEDs with rare or no additional seizures, and 1 died of sudden unexpected death in epilepsy.

After a mean follow-up of 5.7 years in the 15 children who restarted AEDs, 10 again became seizure free within 2 years, whereas 5 never did. Of those five children, three—5% of the total stopping AEDs or 20% of the total restarting them—had intractable seizures.

An analysis of the time until seizures recurred among the children with this outcome showed that 55% had their recurrence within 1 year of stopping AEDs, said Dr. Nickels. But 20% had their recurrence more than 5 years after stopping.

Finally, an analysis of the time until regaining freedom from seizures among the 15 children who had a recurrence and restarted AEDs showed that 8 became seizure free within 1 year and another 2 achieved this status within 2 years. The remaining five children never regained freedom from seizures.

VANCOUVER, B.C. — Chronic kidney disease and heart failure often go hand in hand, and the treatment strategy is similar for both. But there are some finer points to treating patients who have both conditions, according to Dr. Michael Copland, a nephrologist at Vancouver General Hospital.

In patients with cardiorenal syndrome, cardiac and renal dysfunction synergistically amplify each other. The end result is a sharply elevated rate of cardiovascular events. In general, 44% of deaths among patients with chronic kidney disease are due to cardiovascular causes, Dr. Copland said at the annual Canadian Hospitalist Conference.

For patients with kidney disease and heart failure, focus on diet and lifestyle changes, and control of hypertension, diabetes, and lipids. “These are all very cardiovascular-sounding items, but each of these items carries with it a survival benefit in terms of kidney protection for this group of people,” he said.

Renoprotective measures include angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs). “We should be doing our best to get all of our patients on ACE inhibitors and ARBs if they have impaired renal function—particularly if they are diabetic, particularly if they have protein in their urine—because that … is associated with preservation of their renal function,” Dr. Copland said at the meeting, which was sponsored by the University of British Columbia.

Renal function should be monitored closely after starting these agents. “We will accept a 25% loss of renal function up front,” he noted, because this short-term trade-off is acceptable for the long-term gain in renal protection. But “if renal function continues to worsen, that's the one group of people in whom I would have to say I would abandon the therapy.”

Development of hyperkalemia is not a reason to discontinue ACE inhibitors and ARBs. “I add on other therapies for their hyperkalemia,” Dr. Copland said. Calcium resonium is typically preferred over sodium polystyrene, because the sodium in the latter will worsen heart failure.

In treating blood pressure, “our initial target would be 130/80 mm Hg, particularly for people who have protein in their urine,” he said. If they still have proteinuria at that target, “we would just keep going as low as they tolerate.”

Recent studies of epoetin alfa have found no cardiovascular benefit for patients with chronic kidney disease, and a trend toward an increased risk of death. “People do feel better, so they stay off of dialysis for longer. So from a cost point of view, which is not a clinical parameter, we use this therapy,” Dr. Copland said.

“Sometimes treating the heart failure actually treats the kidney disease,” he noted. For challenging patients who have both high cardiac output and volume overload, treatments include loop diuretics, nitrates, positive airway pressure, nesiritide, and possibly ultrafiltration, which may offer an alternative to diuresis.

Trials of ultrafiltration have had conflicting results, Dr. Copland said. In the largest one to date—the UNLOAD trial (Ultrafiltration vs. IV Diuretics for Patients Hospitalized for Acute Decompensated CHF)—patients given ultrafiltration had a greater weight loss than patients given diuretics, with a difference of 5 vs. 3 kg (J. Am. Coll. Cardiol. 2007;49:675–83). Subjective dyspnea scores did not differ. But at 90 days, patients given ultrafiltration were less likely to have been rehospitalized for heart failure (18% vs. 32%).

“The problem with all of these trials is that they excluded the sickest groups of people, so I think the jury is still a bit out,” he said.

Dr. Copland said that he sits on the advisory board of Baxter Healthcare.

'Sometimes treating the heart failure actually treats the kidney disease.' DR. COPLAND

VANCOUVER, B.C. — Chronic kidney disease and heart failure often go hand in hand, and the treatment strategy is similar for both. But there are some finer points to treating patients who have both conditions, according to Dr. Michael Copland, a nephrologist at Vancouver General Hospital.

In patients with cardiorenal syndrome, cardiac and renal dysfunction synergistically amplify each other. The end result is a sharply elevated rate of cardiovascular events. In general, 44% of deaths among patients with chronic kidney disease are due to cardiovascular causes, Dr. Copland said at the annual Canadian Hospitalist Conference.

For patients with kidney disease and heart failure, focus on diet and lifestyle changes, and control of hypertension, diabetes, and lipids. “These are all very cardiovascular-sounding items, but each of these items carries with it a survival benefit in terms of kidney protection for this group of people,” he said.

Renoprotective measures include angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs). “We should be doing our best to get all of our patients on ACE inhibitors and ARBs if they have impaired renal function—particularly if they are diabetic, particularly if they have protein in their urine—because that … is associated with preservation of their renal function,” Dr. Copland said at the meeting, which was sponsored by the University of British Columbia.

Renal function should be monitored closely after starting these agents. “We will accept a 25% loss of renal function up front,” he noted, because this short-term trade-off is acceptable for the long-term gain in renal protection. But “if renal function continues to worsen, that's the one group of people in whom I would have to say I would abandon the therapy.”

Development of hyperkalemia is not a reason to discontinue ACE inhibitors and ARBs. “I add on other therapies for their hyperkalemia,” Dr. Copland said. Calcium resonium is typically preferred over sodium polystyrene, because the sodium in the latter will worsen heart failure.

In treating blood pressure, “our initial target would be 130/80 mm Hg, particularly for people who have protein in their urine,” he said. If they still have proteinuria at that target, “we would just keep going as low as they tolerate.”

Recent studies of epoetin alfa have found no cardiovascular benefit for patients with chronic kidney disease, and a trend toward an increased risk of death. “People do feel better, so they stay off of dialysis for longer. So from a cost point of view, which is not a clinical parameter, we use this therapy,” Dr. Copland said.

“Sometimes treating the heart failure actually treats the kidney disease,” he noted. For challenging patients who have both high cardiac output and volume overload, treatments include loop diuretics, nitrates, positive airway pressure, nesiritide, and possibly ultrafiltration, which may offer an alternative to diuresis.

Trials of ultrafiltration have had conflicting results, Dr. Copland said. In the largest one to date—the UNLOAD trial (Ultrafiltration vs. IV Diuretics for Patients Hospitalized for Acute Decompensated CHF)—patients given ultrafiltration had a greater weight loss than patients given diuretics, with a difference of 5 vs. 3 kg (J. Am. Coll. Cardiol. 2007;49:675–83). Subjective dyspnea scores did not differ. But at 90 days, patients given ultrafiltration were less likely to have been rehospitalized for heart failure (18% vs. 32%).

“The problem with all of these trials is that they excluded the sickest groups of people, so I think the jury is still a bit out,” he said.

Dr. Copland said that he sits on the advisory board of Baxter Healthcare.

'Sometimes treating the heart failure actually treats the kidney disease.' DR. COPLAND

VANCOUVER, B.C. — Chronic kidney disease and heart failure often go hand in hand, and the treatment strategy is similar for both. But there are some finer points to treating patients who have both conditions, according to Dr. Michael Copland, a nephrologist at Vancouver General Hospital.

In patients with cardiorenal syndrome, cardiac and renal dysfunction synergistically amplify each other. The end result is a sharply elevated rate of cardiovascular events. In general, 44% of deaths among patients with chronic kidney disease are due to cardiovascular causes, Dr. Copland said at the annual Canadian Hospitalist Conference.

For patients with kidney disease and heart failure, focus on diet and lifestyle changes, and control of hypertension, diabetes, and lipids. “These are all very cardiovascular-sounding items, but each of these items carries with it a survival benefit in terms of kidney protection for this group of people,” he said.

Renoprotective measures include angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs). “We should be doing our best to get all of our patients on ACE inhibitors and ARBs if they have impaired renal function—particularly if they are diabetic, particularly if they have protein in their urine—because that … is associated with preservation of their renal function,” Dr. Copland said at the meeting, which was sponsored by the University of British Columbia.

Renal function should be monitored closely after starting these agents. “We will accept a 25% loss of renal function up front,” he noted, because this short-term trade-off is acceptable for the long-term gain in renal protection. But “if renal function continues to worsen, that's the one group of people in whom I would have to say I would abandon the therapy.”

Development of hyperkalemia is not a reason to discontinue ACE inhibitors and ARBs. “I add on other therapies for their hyperkalemia,” Dr. Copland said. Calcium resonium is typically preferred over sodium polystyrene, because the sodium in the latter will worsen heart failure.

In treating blood pressure, “our initial target would be 130/80 mm Hg, particularly for people who have protein in their urine,” he said. If they still have proteinuria at that target, “we would just keep going as low as they tolerate.”

Recent studies of epoetin alfa have found no cardiovascular benefit for patients with chronic kidney disease, and a trend toward an increased risk of death. “People do feel better, so they stay off of dialysis for longer. So from a cost point of view, which is not a clinical parameter, we use this therapy,” Dr. Copland said.

“Sometimes treating the heart failure actually treats the kidney disease,” he noted. For challenging patients who have both high cardiac output and volume overload, treatments include loop diuretics, nitrates, positive airway pressure, nesiritide, and possibly ultrafiltration, which may offer an alternative to diuresis.

Trials of ultrafiltration have had conflicting results, Dr. Copland said. In the largest one to date—the UNLOAD trial (Ultrafiltration vs. IV Diuretics for Patients Hospitalized for Acute Decompensated CHF)—patients given ultrafiltration had a greater weight loss than patients given diuretics, with a difference of 5 vs. 3 kg (J. Am. Coll. Cardiol. 2007;49:675–83). Subjective dyspnea scores did not differ. But at 90 days, patients given ultrafiltration were less likely to have been rehospitalized for heart failure (18% vs. 32%).

“The problem with all of these trials is that they excluded the sickest groups of people, so I think the jury is still a bit out,” he said.

Dr. Copland said that he sits on the advisory board of Baxter Healthcare.

'Sometimes treating the heart failure actually treats the kidney disease.' DR. COPLAND

SEATTLE — Intravenous lorazepam is more effective than rectal diazepam in stopping status epilepticus in children who present to the emergency department with seizures that began at home, judging from findings from an English study.

The finding challenges earlier reports that suggested the two agents are equivalent for this indication, especially given the contention that it is easier to administer rectal drugs than to start an intravenous line outside the hospital.

Most of the existing data on optimal treatment come from hospital-based research, which “doesn't take into consideration the different time periods: what happens in the community, what happens on arrival into hospital, what happens after failure of first-line treatment in hospital,” Dr. Richard F. Chin said at the annual meeting of the American Epilepsy Society.

From May 2002 to April 2004, investigators in the ongoing North London Status Epilepticus in Childhood Surveillance Study prospectively collected population-based data at 22 North London hospitals about children who experienced community-onset convulsive status epilepticus.

During the study period, 240 episodes of community-onset convulsive status epilepticus were documented in 182 children, reported Dr. Chin, the study's lead investigator and a pediatric neurologist with the Institute of Child Health in London. The children had a median age of 3.2 years, and 52% were girls.

Overall, 2% percent of the episodes ended without any treatment. Another 61% were initially treated outside the hospital, and of these 22% were terminated before hospital arrival.

In multivariate analyses of the 203 episodes that were treated in the hospital, children were more than three times as likely to have termination of their seizures with first-line therapy in the emergency department if that therapy was intravenous lorazepam instead of rectal diazepam.

“That is very important because current guidelines, certainly within the [United Kingdom and other settings], suggest some degree of potential equivalence between a choice of rectal medication and [intravenous] medication,” he said. “Some people think there is a bit of concern getting IV access and administering medication. Certainly, there doesn't seem to be any basis for this within our setting.”

When first-line therapy failed, children were nearly nine times more likely to have seizure termination with second-line therapy if that therapy was intravenous phenytoin instead of rectal paraldehyde.

Dr. Chin had no relevant conflicts of interest to report.

SEATTLE — Intravenous lorazepam is more effective than rectal diazepam in stopping status epilepticus in children who present to the emergency department with seizures that began at home, judging from findings from an English study.

The finding challenges earlier reports that suggested the two agents are equivalent for this indication, especially given the contention that it is easier to administer rectal drugs than to start an intravenous line outside the hospital.

Most of the existing data on optimal treatment come from hospital-based research, which “doesn't take into consideration the different time periods: what happens in the community, what happens on arrival into hospital, what happens after failure of first-line treatment in hospital,” Dr. Richard F. Chin said at the annual meeting of the American Epilepsy Society.

From May 2002 to April 2004, investigators in the ongoing North London Status Epilepticus in Childhood Surveillance Study prospectively collected population-based data at 22 North London hospitals about children who experienced community-onset convulsive status epilepticus.

During the study period, 240 episodes of community-onset convulsive status epilepticus were documented in 182 children, reported Dr. Chin, the study's lead investigator and a pediatric neurologist with the Institute of Child Health in London. The children had a median age of 3.2 years, and 52% were girls.

Overall, 2% percent of the episodes ended without any treatment. Another 61% were initially treated outside the hospital, and of these 22% were terminated before hospital arrival.

In multivariate analyses of the 203 episodes that were treated in the hospital, children were more than three times as likely to have termination of their seizures with first-line therapy in the emergency department if that therapy was intravenous lorazepam instead of rectal diazepam.

“That is very important because current guidelines, certainly within the [United Kingdom and other settings], suggest some degree of potential equivalence between a choice of rectal medication and [intravenous] medication,” he said. “Some people think there is a bit of concern getting IV access and administering medication. Certainly, there doesn't seem to be any basis for this within our setting.”

When first-line therapy failed, children were nearly nine times more likely to have seizure termination with second-line therapy if that therapy was intravenous phenytoin instead of rectal paraldehyde.

Dr. Chin had no relevant conflicts of interest to report.

SEATTLE — Intravenous lorazepam is more effective than rectal diazepam in stopping status epilepticus in children who present to the emergency department with seizures that began at home, judging from findings from an English study.

The finding challenges earlier reports that suggested the two agents are equivalent for this indication, especially given the contention that it is easier to administer rectal drugs than to start an intravenous line outside the hospital.

Most of the existing data on optimal treatment come from hospital-based research, which “doesn't take into consideration the different time periods: what happens in the community, what happens on arrival into hospital, what happens after failure of first-line treatment in hospital,” Dr. Richard F. Chin said at the annual meeting of the American Epilepsy Society.

From May 2002 to April 2004, investigators in the ongoing North London Status Epilepticus in Childhood Surveillance Study prospectively collected population-based data at 22 North London hospitals about children who experienced community-onset convulsive status epilepticus.

During the study period, 240 episodes of community-onset convulsive status epilepticus were documented in 182 children, reported Dr. Chin, the study's lead investigator and a pediatric neurologist with the Institute of Child Health in London. The children had a median age of 3.2 years, and 52% were girls.

Overall, 2% percent of the episodes ended without any treatment. Another 61% were initially treated outside the hospital, and of these 22% were terminated before hospital arrival.

In multivariate analyses of the 203 episodes that were treated in the hospital, children were more than three times as likely to have termination of their seizures with first-line therapy in the emergency department if that therapy was intravenous lorazepam instead of rectal diazepam.

“That is very important because current guidelines, certainly within the [United Kingdom and other settings], suggest some degree of potential equivalence between a choice of rectal medication and [intravenous] medication,” he said. “Some people think there is a bit of concern getting IV access and administering medication. Certainly, there doesn't seem to be any basis for this within our setting.”

When first-line therapy failed, children were nearly nine times more likely to have seizure termination with second-line therapy if that therapy was intravenous phenytoin instead of rectal paraldehyde.

Dr. Chin had no relevant conflicts of interest to report.