Mary Ann Moon

A diet rich in certain foods such as nuts, fish, and vegetables and low in high-fat dairy foods and red meat appears to exert a preventative effect on the development of Alzheimer's disease, according to study findings.

“Our findings provide support for further exploration of food-combination–based dietary behavior for the prevention of this important public health problem,” wrote Yian Gu, Ph.D., of the Taub Institute for Research in Alzheimer's Disease and the Aging Brain at Columbia University, New York, and associates.

The researchers studied dietary data obtained by food frequency questionnaires in two multiethnic cohorts: elderly subjects participating in the 1992 and the 1999 Washington Heights–Inwood Columbia Aging Project (WHICAP). Their study included 2,148 individuals who underwent serial batteries of neuropsychological tests, assessments of social and occupational function, and specific testing for cognitive deficits and dementia.

During an average follow-up of about 4 years, 253 of these subjects developed Alzheimer's disease. Subjects were diagnosed for dementia using the criteria developed by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer Disease and Related Disorders Association. Some of the patients may have had stroke in addition to Alzheimer's.

The investigators calculated dietary patterns based on variations in the content of seven key nutrients that have been most consistently related to dementia risk in the literature. Only one dietary pattern was found to be strongly associated with AD prevention: a diet rich in omega-3 polyunsaturated fatty acids, omega-6 polyunsaturated fatty acids, vitamin E, and folate and poor in saturated fatty acids and vitamin B₁₂.

This pattern correlated with high intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous and dark leafy green vegetables and low intakes of high-fat dairy foods, such as butter, red meats, and organ meats, Dr. Gu and colleagues said (Arch. Neurol. 2010 April 12 [doi:10.1001/archneurol.2010.84]).

The protective effect of such a diet did not change after the data were adjusted to account for age, level of education, ethnicity, and sex. Further analysis adjusting for smoking status, body mass index, caloric intake, comorbidities, and apolipoprotein E genotype only slightly attenuated the results.

This study was funded by the National Institute on Aging. No conflicts of interest were reported.

Dark greens, such as spinach, and poultry were protective in the study.

Source Elenathewise/Fotolia.com

A diet rich in certain foods such as nuts, fish, and vegetables and low in high-fat dairy foods and red meat appears to exert a preventative effect on the development of Alzheimer's disease, according to study findings.

“Our findings provide support for further exploration of food-combination–based dietary behavior for the prevention of this important public health problem,” wrote Yian Gu, Ph.D., of the Taub Institute for Research in Alzheimer's Disease and the Aging Brain at Columbia University, New York, and associates.

The researchers studied dietary data obtained by food frequency questionnaires in two multiethnic cohorts: elderly subjects participating in the 1992 and the 1999 Washington Heights–Inwood Columbia Aging Project (WHICAP). Their study included 2,148 individuals who underwent serial batteries of neuropsychological tests, assessments of social and occupational function, and specific testing for cognitive deficits and dementia.

During an average follow-up of about 4 years, 253 of these subjects developed Alzheimer's disease. Subjects were diagnosed for dementia using the criteria developed by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer Disease and Related Disorders Association. Some of the patients may have had stroke in addition to Alzheimer's.

The investigators calculated dietary patterns based on variations in the content of seven key nutrients that have been most consistently related to dementia risk in the literature. Only one dietary pattern was found to be strongly associated with AD prevention: a diet rich in omega-3 polyunsaturated fatty acids, omega-6 polyunsaturated fatty acids, vitamin E, and folate and poor in saturated fatty acids and vitamin B₁₂.

This pattern correlated with high intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous and dark leafy green vegetables and low intakes of high-fat dairy foods, such as butter, red meats, and organ meats, Dr. Gu and colleagues said (Arch. Neurol. 2010 April 12 [doi:10.1001/archneurol.2010.84]).

The protective effect of such a diet did not change after the data were adjusted to account for age, level of education, ethnicity, and sex. Further analysis adjusting for smoking status, body mass index, caloric intake, comorbidities, and apolipoprotein E genotype only slightly attenuated the results.

This study was funded by the National Institute on Aging. No conflicts of interest were reported.

Dark greens, such as spinach, and poultry were protective in the study.

Source Elenathewise/Fotolia.com

A diet rich in certain foods such as nuts, fish, and vegetables and low in high-fat dairy foods and red meat appears to exert a preventative effect on the development of Alzheimer's disease, according to study findings.

“Our findings provide support for further exploration of food-combination–based dietary behavior for the prevention of this important public health problem,” wrote Yian Gu, Ph.D., of the Taub Institute for Research in Alzheimer's Disease and the Aging Brain at Columbia University, New York, and associates.

The researchers studied dietary data obtained by food frequency questionnaires in two multiethnic cohorts: elderly subjects participating in the 1992 and the 1999 Washington Heights–Inwood Columbia Aging Project (WHICAP). Their study included 2,148 individuals who underwent serial batteries of neuropsychological tests, assessments of social and occupational function, and specific testing for cognitive deficits and dementia.

During an average follow-up of about 4 years, 253 of these subjects developed Alzheimer's disease. Subjects were diagnosed for dementia using the criteria developed by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer Disease and Related Disorders Association. Some of the patients may have had stroke in addition to Alzheimer's.

The investigators calculated dietary patterns based on variations in the content of seven key nutrients that have been most consistently related to dementia risk in the literature. Only one dietary pattern was found to be strongly associated with AD prevention: a diet rich in omega-3 polyunsaturated fatty acids, omega-6 polyunsaturated fatty acids, vitamin E, and folate and poor in saturated fatty acids and vitamin B₁₂.

This pattern correlated with high intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous and dark leafy green vegetables and low intakes of high-fat dairy foods, such as butter, red meats, and organ meats, Dr. Gu and colleagues said (Arch. Neurol. 2010 April 12 [doi:10.1001/archneurol.2010.84]).

The protective effect of such a diet did not change after the data were adjusted to account for age, level of education, ethnicity, and sex. Further analysis adjusting for smoking status, body mass index, caloric intake, comorbidities, and apolipoprotein E genotype only slightly attenuated the results.

This study was funded by the National Institute on Aging. No conflicts of interest were reported.

Dark greens, such as spinach, and poultry were protective in the study.

Source Elenathewise/Fotolia.com

Indoor tanning is an addictive behavior for a substantial portion of adolescents and young adults, findings from a new study suggest.

Any efforts to reduce skin cancer risk must address the addictive nature of indoor tanning for these members of the population, said Catherine E. Mosher, Ph.D., of the department of psychiatry and behavioral sciences, Memorial Sloan-Kettering Cancer Center, New York, and Sharon Danoff-Burg, Ph.D., of the department of psychology at the State University of New York, Albany.

They studied the self-reported indoor tanning habits of more than 400 students at a state university in the northeastern United States. The students completed anonymous questionnaires that also detailed their substance use. They also completed the Beck Depression Inventory and the Beck Anxiety Inventory, and addictive behavior was assessed using two measures to identify substance-related disorders.

Nearly 40% of the 237 students who used indoor tanning met modified Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria for addiction to the behavior (Arch. Dermatol. 2010;146:412-7).

Students in this subgroup were more likely to report the recent use of two or more controlled substances (excluding alcohol), compared with those who occasionally or never used indoor tanning. A total of 42% of those who qualified as addicted to indoor tanning reported this level of substance use, compared with only 16% of the subjects who never used indoor tanning and 17% of those who occasionally did.

Students who met the criteria for addiction to indoor tanning also were approximately two times more likely to report symptoms of anxiety or depression than students who were not addicted to indoor tanning.

Taken together with the results of previous studies, these findings “suggest that individuals who use drugs may be more likely to develop dependence on indoor tanning because of a similar addictive process.

Disclosures: The study was funded in part by the National Cancer Institute. No conflicts of interest were reported.

Indoor tanning is an addictive behavior for a substantial portion of adolescents and young adults, findings from a new study suggest.

Any efforts to reduce skin cancer risk must address the addictive nature of indoor tanning for these members of the population, said Catherine E. Mosher, Ph.D., of the department of psychiatry and behavioral sciences, Memorial Sloan-Kettering Cancer Center, New York, and Sharon Danoff-Burg, Ph.D., of the department of psychology at the State University of New York, Albany.

They studied the self-reported indoor tanning habits of more than 400 students at a state university in the northeastern United States. The students completed anonymous questionnaires that also detailed their substance use. They also completed the Beck Depression Inventory and the Beck Anxiety Inventory, and addictive behavior was assessed using two measures to identify substance-related disorders.

Nearly 40% of the 237 students who used indoor tanning met modified Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria for addiction to the behavior (Arch. Dermatol. 2010;146:412-7).

Students in this subgroup were more likely to report the recent use of two or more controlled substances (excluding alcohol), compared with those who occasionally or never used indoor tanning. A total of 42% of those who qualified as addicted to indoor tanning reported this level of substance use, compared with only 16% of the subjects who never used indoor tanning and 17% of those who occasionally did.

Students who met the criteria for addiction to indoor tanning also were approximately two times more likely to report symptoms of anxiety or depression than students who were not addicted to indoor tanning.

Taken together with the results of previous studies, these findings “suggest that individuals who use drugs may be more likely to develop dependence on indoor tanning because of a similar addictive process.

Disclosures: The study was funded in part by the National Cancer Institute. No conflicts of interest were reported.

Indoor tanning is an addictive behavior for a substantial portion of adolescents and young adults, findings from a new study suggest.

Any efforts to reduce skin cancer risk must address the addictive nature of indoor tanning for these members of the population, said Catherine E. Mosher, Ph.D., of the department of psychiatry and behavioral sciences, Memorial Sloan-Kettering Cancer Center, New York, and Sharon Danoff-Burg, Ph.D., of the department of psychology at the State University of New York, Albany.

They studied the self-reported indoor tanning habits of more than 400 students at a state university in the northeastern United States. The students completed anonymous questionnaires that also detailed their substance use. They also completed the Beck Depression Inventory and the Beck Anxiety Inventory, and addictive behavior was assessed using two measures to identify substance-related disorders.

Nearly 40% of the 237 students who used indoor tanning met modified Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria for addiction to the behavior (Arch. Dermatol. 2010;146:412-7).

Students in this subgroup were more likely to report the recent use of two or more controlled substances (excluding alcohol), compared with those who occasionally or never used indoor tanning. A total of 42% of those who qualified as addicted to indoor tanning reported this level of substance use, compared with only 16% of the subjects who never used indoor tanning and 17% of those who occasionally did.

Students who met the criteria for addiction to indoor tanning also were approximately two times more likely to report symptoms of anxiety or depression than students who were not addicted to indoor tanning.

Taken together with the results of previous studies, these findings “suggest that individuals who use drugs may be more likely to develop dependence on indoor tanning because of a similar addictive process.

Disclosures: The study was funded in part by the National Cancer Institute. No conflicts of interest were reported.

The link between anticonvulsant agents and suicidal acts or violent death—first revealed in a Food and Drug Administration meta-analysis in 2008—appears to have been confirmed for four of the drugs: gabapentin, lamotrigine, oxcarbazepine, and tiagabine, according to a new report.

In what investigators described as the first study to directly compare suicide risks with different anticonvulsants given in routine care, “increased risk for suicidal acts beginning within the first 14 days of treatment initiation” was found, reported Dr. Elisabetta Patorno of Brigham and Women's Hospital, Boston, and her associates. This finding opens the possibility that anticonvulsants “could induce [adverse] behavioral effects prior to the achievement of their full therapeutic effectiveness,” they wrote.

The investigators noted that in the FDA meta-analysis, the number of events was small and largely confined to cases of suicidal ideation only. This “prevented definitive conclusions about the safety of individual agents.”

In addition, in many of the studies included in the meta-analysis, the anticonvulsant agents were used as adjunctive treatment, “further complicating the assessment of their individual effect.

“Thus, the FDA meta-analysis could not provide patients or clinicians with clear guidelines on risk for specific agents or patient subgroups,” Dr. Patorno and her colleagues noted.

They addressed these issues by conducting a cohort study using a data from 297,620 new prescriptions for anticonvulsant drugs in 17 states between 2001 and 2006 The risks of attempted or completed suicidal acts or violent deaths were compared between patients aged 15 and older who had initiated treatment with one of two reference anticonvulsants (topiramate or carbamazepine) and patients who had initiated treatment with any of 13 other anticonvulsants.

The study subjects were to be followed for 180 days or until they discontinued or switched medications, had a study outcome, or discontinued the study for other reasons. Mean follow-up turned out to be 91 days.

There were 801 attempted suicides, 26 completed suicides, and 41 violent deaths within 180 days of initiating anticonvulsant therapy. Compared with subjects initiating use of topiramate or carbamazepine, those starting on gabapentin, lamotrigine, oxcarbazepine, and tiagabine were at significantly increased risk for these events, the investigators said (JAMA 2010;303:1401-9).

A further analysis of the data showed that new users of gabapentin had an excess of 5.6 cases of attempted or completed suicide per 1,000 person-years, new users of oxcarbazepine had an excess of 10 cases per 1,000 person-years, and new users of tiagabine had an excess of 14.1 cases per 1,000 person-years, compared with new users of topiramate.

“These findings are compatible with the results of the FDA meta-analysis, which found similarly increased risks of suicidal behavior or ideation for all anticonvulsant drugs compared with placebo,” Dr. Patorno and her associates said.

They cautioned that their study was exploratory in nature, and so could only suggest rather than definitively establish a causal relationship between these drugs and suicidal behavior. “There is no clear understanding of a possible mechanism of action that could lead to suicidal behavior in patients taking these medications,” the researchers added.

Gabapentin and lamotrigine have been linked to behavioral problems such as aggression and hyperactivity, particularly in children and adults who have learning disabilities or cognitive impairment. Tiagabine has been reported to cause nervousness and depressive mood in some patients. And oxcarbazepine is thought to have a stimulant effect on psychomotor functioning in some, they said.

Disclosures: This study was funded by the HealthCore Fellowship in Pharmacoepidemiology and the Pharmacoepidemiology Research and Training Fund of the Harvard School of Public Health. Dr. Patorno reported no financial conflicts of interest.

The link between anticonvulsant agents and suicidal acts or violent death—first revealed in a Food and Drug Administration meta-analysis in 2008—appears to have been confirmed for four of the drugs: gabapentin, lamotrigine, oxcarbazepine, and tiagabine, according to a new report.

In what investigators described as the first study to directly compare suicide risks with different anticonvulsants given in routine care, “increased risk for suicidal acts beginning within the first 14 days of treatment initiation” was found, reported Dr. Elisabetta Patorno of Brigham and Women's Hospital, Boston, and her associates. This finding opens the possibility that anticonvulsants “could induce [adverse] behavioral effects prior to the achievement of their full therapeutic effectiveness,” they wrote.

The investigators noted that in the FDA meta-analysis, the number of events was small and largely confined to cases of suicidal ideation only. This “prevented definitive conclusions about the safety of individual agents.”

In addition, in many of the studies included in the meta-analysis, the anticonvulsant agents were used as adjunctive treatment, “further complicating the assessment of their individual effect.

“Thus, the FDA meta-analysis could not provide patients or clinicians with clear guidelines on risk for specific agents or patient subgroups,” Dr. Patorno and her colleagues noted.

They addressed these issues by conducting a cohort study using a data from 297,620 new prescriptions for anticonvulsant drugs in 17 states between 2001 and 2006 The risks of attempted or completed suicidal acts or violent deaths were compared between patients aged 15 and older who had initiated treatment with one of two reference anticonvulsants (topiramate or carbamazepine) and patients who had initiated treatment with any of 13 other anticonvulsants.

The study subjects were to be followed for 180 days or until they discontinued or switched medications, had a study outcome, or discontinued the study for other reasons. Mean follow-up turned out to be 91 days.

There were 801 attempted suicides, 26 completed suicides, and 41 violent deaths within 180 days of initiating anticonvulsant therapy. Compared with subjects initiating use of topiramate or carbamazepine, those starting on gabapentin, lamotrigine, oxcarbazepine, and tiagabine were at significantly increased risk for these events, the investigators said (JAMA 2010;303:1401-9).

A further analysis of the data showed that new users of gabapentin had an excess of 5.6 cases of attempted or completed suicide per 1,000 person-years, new users of oxcarbazepine had an excess of 10 cases per 1,000 person-years, and new users of tiagabine had an excess of 14.1 cases per 1,000 person-years, compared with new users of topiramate.

“These findings are compatible with the results of the FDA meta-analysis, which found similarly increased risks of suicidal behavior or ideation for all anticonvulsant drugs compared with placebo,” Dr. Patorno and her associates said.

They cautioned that their study was exploratory in nature, and so could only suggest rather than definitively establish a causal relationship between these drugs and suicidal behavior. “There is no clear understanding of a possible mechanism of action that could lead to suicidal behavior in patients taking these medications,” the researchers added.

Gabapentin and lamotrigine have been linked to behavioral problems such as aggression and hyperactivity, particularly in children and adults who have learning disabilities or cognitive impairment. Tiagabine has been reported to cause nervousness and depressive mood in some patients. And oxcarbazepine is thought to have a stimulant effect on psychomotor functioning in some, they said.

Disclosures: This study was funded by the HealthCore Fellowship in Pharmacoepidemiology and the Pharmacoepidemiology Research and Training Fund of the Harvard School of Public Health. Dr. Patorno reported no financial conflicts of interest.

The link between anticonvulsant agents and suicidal acts or violent death—first revealed in a Food and Drug Administration meta-analysis in 2008—appears to have been confirmed for four of the drugs: gabapentin, lamotrigine, oxcarbazepine, and tiagabine, according to a new report.

In what investigators described as the first study to directly compare suicide risks with different anticonvulsants given in routine care, “increased risk for suicidal acts beginning within the first 14 days of treatment initiation” was found, reported Dr. Elisabetta Patorno of Brigham and Women's Hospital, Boston, and her associates. This finding opens the possibility that anticonvulsants “could induce [adverse] behavioral effects prior to the achievement of their full therapeutic effectiveness,” they wrote.

The investigators noted that in the FDA meta-analysis, the number of events was small and largely confined to cases of suicidal ideation only. This “prevented definitive conclusions about the safety of individual agents.”

In addition, in many of the studies included in the meta-analysis, the anticonvulsant agents were used as adjunctive treatment, “further complicating the assessment of their individual effect.

“Thus, the FDA meta-analysis could not provide patients or clinicians with clear guidelines on risk for specific agents or patient subgroups,” Dr. Patorno and her colleagues noted.

They addressed these issues by conducting a cohort study using a data from 297,620 new prescriptions for anticonvulsant drugs in 17 states between 2001 and 2006 The risks of attempted or completed suicidal acts or violent deaths were compared between patients aged 15 and older who had initiated treatment with one of two reference anticonvulsants (topiramate or carbamazepine) and patients who had initiated treatment with any of 13 other anticonvulsants.

The study subjects were to be followed for 180 days or until they discontinued or switched medications, had a study outcome, or discontinued the study for other reasons. Mean follow-up turned out to be 91 days.

There were 801 attempted suicides, 26 completed suicides, and 41 violent deaths within 180 days of initiating anticonvulsant therapy. Compared with subjects initiating use of topiramate or carbamazepine, those starting on gabapentin, lamotrigine, oxcarbazepine, and tiagabine were at significantly increased risk for these events, the investigators said (JAMA 2010;303:1401-9).

A further analysis of the data showed that new users of gabapentin had an excess of 5.6 cases of attempted or completed suicide per 1,000 person-years, new users of oxcarbazepine had an excess of 10 cases per 1,000 person-years, and new users of tiagabine had an excess of 14.1 cases per 1,000 person-years, compared with new users of topiramate.

“These findings are compatible with the results of the FDA meta-analysis, which found similarly increased risks of suicidal behavior or ideation for all anticonvulsant drugs compared with placebo,” Dr. Patorno and her associates said.

They cautioned that their study was exploratory in nature, and so could only suggest rather than definitively establish a causal relationship between these drugs and suicidal behavior. “There is no clear understanding of a possible mechanism of action that could lead to suicidal behavior in patients taking these medications,” the researchers added.

Gabapentin and lamotrigine have been linked to behavioral problems such as aggression and hyperactivity, particularly in children and adults who have learning disabilities or cognitive impairment. Tiagabine has been reported to cause nervousness and depressive mood in some patients. And oxcarbazepine is thought to have a stimulant effect on psychomotor functioning in some, they said.

Disclosures: This study was funded by the HealthCore Fellowship in Pharmacoepidemiology and the Pharmacoepidemiology Research and Training Fund of the Harvard School of Public Health. Dr. Patorno reported no financial conflicts of interest.

Real-time polymerase chain reaction assays of dried blood spots are not sensitive enough to reliably identify cytomegalovirus infection in newborns, according to a recent report.

Two such methods missed approximately two-thirds of the CMV infections in a prospective cohort study of 20,448 newborns, said Dr. Suresh B. Boppana of the University of Alabama at Birmingham and associates (JAMA 2010;303:1375-82).

“These results have major public health implications because they indicate that such methods, as currently performed, will not be suitable for the mass screening of newborns for congenital CMV infection,” the investigators noted.

Traditional isolation of CMV from cultured saliva or urine samples is the standard method of identifying the congenital infection, but it is not amenable to mass screening. Experts had been hopeful that PCR technology would prove sensitive and specific at identifying occult CMV infection, since “bit does not require tissue culture facilities and is amenable to automation with the screening of large numbers of specimens at low cost,” Dr. Boppana and colleagues said.

Dried blood spots already are collected routinely for newborn metabolic screening, and there has been “considerable” enthusiasm for using PCR assays for CMV on such samples, Bbut their diagnostic accuracy hads never been directly compared with that of standard tissue culture methods.

The researchers compared standard saliva culturing with dried blood spot sampling in infants born at seven U.S. medical centers in 2007-2008. Two different PCR techniques, a single-primer and a double-primer assay, were assessed.

A total of 92 infants (0.45%) were found to have congenital CMV infection.

Saliva screening correctly identified 91 of the 92 affected newborns (99%). In contrast, single-primer blood spot PCR identified only 17 of the 60 infants (28%) who were tested by that method and double-primer blood spot PCR detected only 11 of the 32 infants (34%) who were tested by that method.

The sensitivity and specificity of the single-primer blood spot PCR were 28% and 99.9%. The sensitivity and specificity of the double-primer blood spot PCR were 34% and 99.9%.

“Our data indicate that as many as 80% of infants with congenital CMV infections could be missed” with the dried blood spot real-time PCR assays, Dr. Boppana and associates said. This failure probably was due to an absence of detectable CMV DNA in the peripheral blood of most newborns with congenital CMV.

Disclosures: This study was supported by the National Institute on Deafness and Other Communication Disorders. No financial conflicts were reported.

Traditional isolation from saliva (above) is not amenable to mass screening.

Source Courtesy CDC/Dr. Haraszti

Real-time polymerase chain reaction assays of dried blood spots are not sensitive enough to reliably identify cytomegalovirus infection in newborns, according to a recent report.

Two such methods missed approximately two-thirds of the CMV infections in a prospective cohort study of 20,448 newborns, said Dr. Suresh B. Boppana of the University of Alabama at Birmingham and associates (JAMA 2010;303:1375-82).

“These results have major public health implications because they indicate that such methods, as currently performed, will not be suitable for the mass screening of newborns for congenital CMV infection,” the investigators noted.

Traditional isolation of CMV from cultured saliva or urine samples is the standard method of identifying the congenital infection, but it is not amenable to mass screening. Experts had been hopeful that PCR technology would prove sensitive and specific at identifying occult CMV infection, since “bit does not require tissue culture facilities and is amenable to automation with the screening of large numbers of specimens at low cost,” Dr. Boppana and colleagues said.

Dried blood spots already are collected routinely for newborn metabolic screening, and there has been “considerable” enthusiasm for using PCR assays for CMV on such samples, Bbut their diagnostic accuracy hads never been directly compared with that of standard tissue culture methods.

The researchers compared standard saliva culturing with dried blood spot sampling in infants born at seven U.S. medical centers in 2007-2008. Two different PCR techniques, a single-primer and a double-primer assay, were assessed.

A total of 92 infants (0.45%) were found to have congenital CMV infection.

Saliva screening correctly identified 91 of the 92 affected newborns (99%). In contrast, single-primer blood spot PCR identified only 17 of the 60 infants (28%) who were tested by that method and double-primer blood spot PCR detected only 11 of the 32 infants (34%) who were tested by that method.

The sensitivity and specificity of the single-primer blood spot PCR were 28% and 99.9%. The sensitivity and specificity of the double-primer blood spot PCR were 34% and 99.9%.

“Our data indicate that as many as 80% of infants with congenital CMV infections could be missed” with the dried blood spot real-time PCR assays, Dr. Boppana and associates said. This failure probably was due to an absence of detectable CMV DNA in the peripheral blood of most newborns with congenital CMV.

Disclosures: This study was supported by the National Institute on Deafness and Other Communication Disorders. No financial conflicts were reported.

Traditional isolation from saliva (above) is not amenable to mass screening.

Source Courtesy CDC/Dr. Haraszti

Real-time polymerase chain reaction assays of dried blood spots are not sensitive enough to reliably identify cytomegalovirus infection in newborns, according to a recent report.

Two such methods missed approximately two-thirds of the CMV infections in a prospective cohort study of 20,448 newborns, said Dr. Suresh B. Boppana of the University of Alabama at Birmingham and associates (JAMA 2010;303:1375-82).

“These results have major public health implications because they indicate that such methods, as currently performed, will not be suitable for the mass screening of newborns for congenital CMV infection,” the investigators noted.

Traditional isolation of CMV from cultured saliva or urine samples is the standard method of identifying the congenital infection, but it is not amenable to mass screening. Experts had been hopeful that PCR technology would prove sensitive and specific at identifying occult CMV infection, since “bit does not require tissue culture facilities and is amenable to automation with the screening of large numbers of specimens at low cost,” Dr. Boppana and colleagues said.

Dried blood spots already are collected routinely for newborn metabolic screening, and there has been “considerable” enthusiasm for using PCR assays for CMV on such samples, Bbut their diagnostic accuracy hads never been directly compared with that of standard tissue culture methods.

The researchers compared standard saliva culturing with dried blood spot sampling in infants born at seven U.S. medical centers in 2007-2008. Two different PCR techniques, a single-primer and a double-primer assay, were assessed.

A total of 92 infants (0.45%) were found to have congenital CMV infection.

Saliva screening correctly identified 91 of the 92 affected newborns (99%). In contrast, single-primer blood spot PCR identified only 17 of the 60 infants (28%) who were tested by that method and double-primer blood spot PCR detected only 11 of the 32 infants (34%) who were tested by that method.

The sensitivity and specificity of the single-primer blood spot PCR were 28% and 99.9%. The sensitivity and specificity of the double-primer blood spot PCR were 34% and 99.9%.

“Our data indicate that as many as 80% of infants with congenital CMV infections could be missed” with the dried blood spot real-time PCR assays, Dr. Boppana and associates said. This failure probably was due to an absence of detectable CMV DNA in the peripheral blood of most newborns with congenital CMV.

Disclosures: This study was supported by the National Institute on Deafness and Other Communication Disorders. No financial conflicts were reported.

Traditional isolation from saliva (above) is not amenable to mass screening.

Source Courtesy CDC/Dr. Haraszti

The link between anticonvulsant agents and suicidal acts or violent death–first revealed in a Food and Drug Administration meta-analysis in 2008–appears to have been confirmed for four of the drugs: gabapentin, lamotrigine, oxcarbazepine, and tiagabine, according to a report in JAMA.

In what investigators described as the first study to directly compare suicide risks with different anticonvulsants given in routine care, “increased risk for suicidal acts beginning within the first 14 days of treatment initiation” were found, reported Dr. Elisabetta Patorno of Brigham and Women's Hospital, Boston, and her associates. This finding opens the possibility that anticonvulsants “could induce [adverse] behavioral effects prior to the achievement of their full therapeutic effectiveness,” they wrote.

The investigators noted that in the FDA meta-analysis, the number of events was small and largely confined to cases of suicidal ideation only. This “prevented definitive conclusions about the safety of individual agents.”

In addition, in many of the studies included in the meta-analysis, the anticonvulsant agents were used as adjunctive treatment, “further complicating the assessment of their individual effect.

“Thus, the FDA meta-analysis could not provide patients or clinicians with clear guidelines on risk for specific agents or patient subgroups,” Dr. Patorno and her colleagues noted.

They addressed these issues by conducting a cohort study using a database that included 297,620 new prescriptions for anticonvulsant drugs in 17 states between 2001 and 2006. The risk of attempted or completed suicidal acts or violent deaths were compared between patients aged 15 and older who had initiated treatment with one of two reference anticonvulsants (topiramate or carbamazepine) and patients who had initiated treatment with any of 13 other anticonvulsants.

The study subjects were to be followed for 180 days or until they discontinued or switched medications, had a study outcome, or discontinued the study for other reasons. Mean follow-up turned out to be 91 days. There were 801 attempted suicides, 26 completed suicides, and 41 violent deaths within 180 days of initiating anticonvulsant therapy.

Compared with subjects initiating use of topiramate or carbamazepine, those starting on gabapentin, lamotrigine, oxcarbazepine, and tiagabine were at significantly increased risk for these events, the investigators said (JAMA 2010;303:1401–9).

A further analysis of the data showed that new users of gabapentin had an excess of 5.6 cases of attempted or completed suicide per 1,000 person-years, new users of oxcarbazepine had an excess of 10 cases per 1,000 person-years, and new users of tiagabine had an excess of 14.1 cases per 1,000 person-years, compared with new users of topiramate.

This study was funded by the HealthCore Fellowship in Pharmacoepidemiology and the Pharmacoepidemiology Research and Training Fund of the Harvard School of Public Health. Dr. Patorno reported no financial conflicts of interest.

The link between anticonvulsant agents and suicidal acts or violent death–first revealed in a Food and Drug Administration meta-analysis in 2008–appears to have been confirmed for four of the drugs: gabapentin, lamotrigine, oxcarbazepine, and tiagabine, according to a report in JAMA.

In what investigators described as the first study to directly compare suicide risks with different anticonvulsants given in routine care, “increased risk for suicidal acts beginning within the first 14 days of treatment initiation” were found, reported Dr. Elisabetta Patorno of Brigham and Women's Hospital, Boston, and her associates. This finding opens the possibility that anticonvulsants “could induce [adverse] behavioral effects prior to the achievement of their full therapeutic effectiveness,” they wrote.

The investigators noted that in the FDA meta-analysis, the number of events was small and largely confined to cases of suicidal ideation only. This “prevented definitive conclusions about the safety of individual agents.”

In addition, in many of the studies included in the meta-analysis, the anticonvulsant agents were used as adjunctive treatment, “further complicating the assessment of their individual effect.

“Thus, the FDA meta-analysis could not provide patients or clinicians with clear guidelines on risk for specific agents or patient subgroups,” Dr. Patorno and her colleagues noted.

They addressed these issues by conducting a cohort study using a database that included 297,620 new prescriptions for anticonvulsant drugs in 17 states between 2001 and 2006. The risk of attempted or completed suicidal acts or violent deaths were compared between patients aged 15 and older who had initiated treatment with one of two reference anticonvulsants (topiramate or carbamazepine) and patients who had initiated treatment with any of 13 other anticonvulsants.

The study subjects were to be followed for 180 days or until they discontinued or switched medications, had a study outcome, or discontinued the study for other reasons. Mean follow-up turned out to be 91 days. There were 801 attempted suicides, 26 completed suicides, and 41 violent deaths within 180 days of initiating anticonvulsant therapy.

Compared with subjects initiating use of topiramate or carbamazepine, those starting on gabapentin, lamotrigine, oxcarbazepine, and tiagabine were at significantly increased risk for these events, the investigators said (JAMA 2010;303:1401–9).

A further analysis of the data showed that new users of gabapentin had an excess of 5.6 cases of attempted or completed suicide per 1,000 person-years, new users of oxcarbazepine had an excess of 10 cases per 1,000 person-years, and new users of tiagabine had an excess of 14.1 cases per 1,000 person-years, compared with new users of topiramate.

This study was funded by the HealthCore Fellowship in Pharmacoepidemiology and the Pharmacoepidemiology Research and Training Fund of the Harvard School of Public Health. Dr. Patorno reported no financial conflicts of interest.

The link between anticonvulsant agents and suicidal acts or violent death–first revealed in a Food and Drug Administration meta-analysis in 2008–appears to have been confirmed for four of the drugs: gabapentin, lamotrigine, oxcarbazepine, and tiagabine, according to a report in JAMA.

In what investigators described as the first study to directly compare suicide risks with different anticonvulsants given in routine care, “increased risk for suicidal acts beginning within the first 14 days of treatment initiation” were found, reported Dr. Elisabetta Patorno of Brigham and Women's Hospital, Boston, and her associates. This finding opens the possibility that anticonvulsants “could induce [adverse] behavioral effects prior to the achievement of their full therapeutic effectiveness,” they wrote.

The investigators noted that in the FDA meta-analysis, the number of events was small and largely confined to cases of suicidal ideation only. This “prevented definitive conclusions about the safety of individual agents.”

In addition, in many of the studies included in the meta-analysis, the anticonvulsant agents were used as adjunctive treatment, “further complicating the assessment of their individual effect.

“Thus, the FDA meta-analysis could not provide patients or clinicians with clear guidelines on risk for specific agents or patient subgroups,” Dr. Patorno and her colleagues noted.

They addressed these issues by conducting a cohort study using a database that included 297,620 new prescriptions for anticonvulsant drugs in 17 states between 2001 and 2006. The risk of attempted or completed suicidal acts or violent deaths were compared between patients aged 15 and older who had initiated treatment with one of two reference anticonvulsants (topiramate or carbamazepine) and patients who had initiated treatment with any of 13 other anticonvulsants.

The study subjects were to be followed for 180 days or until they discontinued or switched medications, had a study outcome, or discontinued the study for other reasons. Mean follow-up turned out to be 91 days. There were 801 attempted suicides, 26 completed suicides, and 41 violent deaths within 180 days of initiating anticonvulsant therapy.

Compared with subjects initiating use of topiramate or carbamazepine, those starting on gabapentin, lamotrigine, oxcarbazepine, and tiagabine were at significantly increased risk for these events, the investigators said (JAMA 2010;303:1401–9).

A further analysis of the data showed that new users of gabapentin had an excess of 5.6 cases of attempted or completed suicide per 1,000 person-years, new users of oxcarbazepine had an excess of 10 cases per 1,000 person-years, and new users of tiagabine had an excess of 14.1 cases per 1,000 person-years, compared with new users of topiramate.

This study was funded by the HealthCore Fellowship in Pharmacoepidemiology and the Pharmacoepidemiology Research and Training Fund of the Harvard School of Public Health. Dr. Patorno reported no financial conflicts of interest.

Major Finding: At 9 months, 66% of paroxysmal atrial fibrillation patients who received radiofrequency catheter ablation were free of treatment failure vs. 16% of patients who received drug therapy.

Data Source: A randomized, multicenter trial of 167 patients with symptomatic paroxysmal atrial fibrillation who did not respond to drug treatment.

Disclosures: Funding and ablation catheters provided by Biosense Webster. Dr. Wilber and several of the coinvestigators reported having financial ties to Biosense Webster and other device makers.

In patients with paroxysmal atrial fibrillation that fails to respond to the first course of drug therapy, radiofrequency catheter ablation is superior to a different antiarrhythmic agent, according to a prospective, multicenter study.

The procedure was better than antiarrhythmic drug treatment, reducing the risk of recurrent arrhythmia and producing clinically meaningful improvements in symptoms and quality of life, said Dr. David J. Wilber of Loyola University, Maywood, Ill., and his associates.

Several studies have compared catheter ablation with drug therapy, but in small populations at a single or a few medical centers.

In their study, Dr. Wilber and his colleagues assessed 167 patients at 19 centers in the United States, Europe, Canada, and Latin America. The patients had not responded to one medication for frequently symptomatic atrial fibrillation and had not received other treatments. After randomization, 106 patients were assigned to undergo catheter ablation and 61 were given a different antiarrhythmic agent (including dofetilide, flecainide, propafenone, sotalol, or quinidine).

The patients were followed for about 1 year. The trial was halted when an interim analysis showed the clear superiority of catheter ablation, with 66% of that group showing an early treatment response that persisted during follow-up vs. 16% of the drug therapy group.

By the end of the trial, “70% of patients treated by catheter ablation remained free of symptomatic recurrent atrial arrhythmia vs. 19% of patients treated with drug therapy,” the researchers said (JAMA 2010;303:333–40). Of the 47 patients who failed to respond to the second course of drug therapy, 36 subsequently underwent ablation.

Major treatment-related adverse events occurred in five patients (4.9%) in the ablation group (one pericardial effusion, one case of pulmonary edema, one case of pneumonia, one vascular complication, and one case of heart failure). In the drug therapy group, five patients (8.8%) had life-threatening arrhythmias and disabling drug intolerance.

“These data strongly support the use of catheter ablation in patients with paroxysmal AF” who do not respond to initial antiarrhythmic drug therapy, Dr. Wilber and his associates wrote.

Major Finding: At 9 months, 66% of paroxysmal atrial fibrillation patients who received radiofrequency catheter ablation were free of treatment failure vs. 16% of patients who received drug therapy.

Data Source: A randomized, multicenter trial of 167 patients with symptomatic paroxysmal atrial fibrillation who did not respond to drug treatment.

Disclosures: Funding and ablation catheters provided by Biosense Webster. Dr. Wilber and several of the coinvestigators reported having financial ties to Biosense Webster and other device makers.

In patients with paroxysmal atrial fibrillation that fails to respond to the first course of drug therapy, radiofrequency catheter ablation is superior to a different antiarrhythmic agent, according to a prospective, multicenter study.

The procedure was better than antiarrhythmic drug treatment, reducing the risk of recurrent arrhythmia and producing clinically meaningful improvements in symptoms and quality of life, said Dr. David J. Wilber of Loyola University, Maywood, Ill., and his associates.

Several studies have compared catheter ablation with drug therapy, but in small populations at a single or a few medical centers.

In their study, Dr. Wilber and his colleagues assessed 167 patients at 19 centers in the United States, Europe, Canada, and Latin America. The patients had not responded to one medication for frequently symptomatic atrial fibrillation and had not received other treatments. After randomization, 106 patients were assigned to undergo catheter ablation and 61 were given a different antiarrhythmic agent (including dofetilide, flecainide, propafenone, sotalol, or quinidine).

The patients were followed for about 1 year. The trial was halted when an interim analysis showed the clear superiority of catheter ablation, with 66% of that group showing an early treatment response that persisted during follow-up vs. 16% of the drug therapy group.

By the end of the trial, “70% of patients treated by catheter ablation remained free of symptomatic recurrent atrial arrhythmia vs. 19% of patients treated with drug therapy,” the researchers said (JAMA 2010;303:333–40). Of the 47 patients who failed to respond to the second course of drug therapy, 36 subsequently underwent ablation.

Major treatment-related adverse events occurred in five patients (4.9%) in the ablation group (one pericardial effusion, one case of pulmonary edema, one case of pneumonia, one vascular complication, and one case of heart failure). In the drug therapy group, five patients (8.8%) had life-threatening arrhythmias and disabling drug intolerance.

“These data strongly support the use of catheter ablation in patients with paroxysmal AF” who do not respond to initial antiarrhythmic drug therapy, Dr. Wilber and his associates wrote.

Major Finding: At 9 months, 66% of paroxysmal atrial fibrillation patients who received radiofrequency catheter ablation were free of treatment failure vs. 16% of patients who received drug therapy.

Data Source: A randomized, multicenter trial of 167 patients with symptomatic paroxysmal atrial fibrillation who did not respond to drug treatment.

Disclosures: Funding and ablation catheters provided by Biosense Webster. Dr. Wilber and several of the coinvestigators reported having financial ties to Biosense Webster and other device makers.

In patients with paroxysmal atrial fibrillation that fails to respond to the first course of drug therapy, radiofrequency catheter ablation is superior to a different antiarrhythmic agent, according to a prospective, multicenter study.

The procedure was better than antiarrhythmic drug treatment, reducing the risk of recurrent arrhythmia and producing clinically meaningful improvements in symptoms and quality of life, said Dr. David J. Wilber of Loyola University, Maywood, Ill., and his associates.

Several studies have compared catheter ablation with drug therapy, but in small populations at a single or a few medical centers.

In their study, Dr. Wilber and his colleagues assessed 167 patients at 19 centers in the United States, Europe, Canada, and Latin America. The patients had not responded to one medication for frequently symptomatic atrial fibrillation and had not received other treatments. After randomization, 106 patients were assigned to undergo catheter ablation and 61 were given a different antiarrhythmic agent (including dofetilide, flecainide, propafenone, sotalol, or quinidine).

The patients were followed for about 1 year. The trial was halted when an interim analysis showed the clear superiority of catheter ablation, with 66% of that group showing an early treatment response that persisted during follow-up vs. 16% of the drug therapy group.

By the end of the trial, “70% of patients treated by catheter ablation remained free of symptomatic recurrent atrial arrhythmia vs. 19% of patients treated with drug therapy,” the researchers said (JAMA 2010;303:333–40). Of the 47 patients who failed to respond to the second course of drug therapy, 36 subsequently underwent ablation.

Major treatment-related adverse events occurred in five patients (4.9%) in the ablation group (one pericardial effusion, one case of pulmonary edema, one case of pneumonia, one vascular complication, and one case of heart failure). In the drug therapy group, five patients (8.8%) had life-threatening arrhythmias and disabling drug intolerance.

“These data strongly support the use of catheter ablation in patients with paroxysmal AF” who do not respond to initial antiarrhythmic drug therapy, Dr. Wilber and his associates wrote.

Major Finding: A dose-response relationship was seen between younger onset age of cannabis use and greater risk of psychosis-related outcomes in sibling pairs.

Data Source: Prospective, sibling pair analysis of 3,081 adults born between 1981 and 1984.

Disclosures: None of the investigators had any financial conflicts of interest to report.

The use of cannabis at a younger age is associated with psychosis symptoms in early adulthood, according to an Australian study.

This is the first study to show the association in a subgroup of sibling pairs, “reducing the likelihood that the association was due to unmeasured shared genetic and/or environmental influences,” said Dr. John McGrath of the Queensland Brain Institute, Wacol, Australia, and his colleagues. The study also demonstrated a dose-response relationship between younger age at first use and higher risk of psychosis-related outcomes, they noted.

The researchers examined the link using data from a birth cohort of more than 7,000 mother-infant pairs who were first studied in 1981–1984 and followed 5, 14, and 21 years later.

The study comprised 3,801 of these infants and their close-in-age siblings. The latest follow-up occurred when they were aged 18–23 years. At that time, about 18% of the subjects said they had been using marijuana for 3 or fewer years, 16% said they had been using it for 4–5 years, and 14% said they had been using it for 6 or more years.

At final follow-up, 65 of these subjects had received diagnoses of nonaffective psychosis because they met the criteria for schizophrenia (53 subjects), persistent delusional disorder (3), or acute transient psychotic disorders (9). Another 233 subjects reported at least one visual or auditory hallucination.

Only subjects with the longest duration since first cannabis use (those who started using marijuana at age 15 years or younger) were at significantly increased risk for developing symptoms of nonaffective psychosis in young adulthood. Those who started using marijuana at that age were twice as likely to receive such a diagnosis than were subjects who said they had never used marijuana, the researchers said (Arch. Gen. Psychiatry 2010 March 1 [doi:10.1001/archgenpsychiatry.2010.6]).

Compared with subjects who did not use cannabis, those who used it at a younger age were 4 times more likely to score in the top quartile on the 21-item Peters et al. Delusional Inventory (PDI) and to report hallucinations on the CIDI.

Moreover, the longer the interval since first cannabis use, the higher the risk of these adverse psychosis-related outcomes. In a subsample of 218 sibling pairs, there was a significant association between earlier first use of cannabis and higher scores on the PDI. For every additional year since first exposure to marijuana, the sibling with the younger age at first use scored one item higher than the other sibling, the researchers said.

This study was not designed to determine causality.

Those who began marijuana use at age 15 or younger had double the risk of psychosis.

Source ©ron hilton/iStockphoto.com

Major Finding: A dose-response relationship was seen between younger onset age of cannabis use and greater risk of psychosis-related outcomes in sibling pairs.

Data Source: Prospective, sibling pair analysis of 3,081 adults born between 1981 and 1984.

Disclosures: None of the investigators had any financial conflicts of interest to report.

The use of cannabis at a younger age is associated with psychosis symptoms in early adulthood, according to an Australian study.

This is the first study to show the association in a subgroup of sibling pairs, “reducing the likelihood that the association was due to unmeasured shared genetic and/or environmental influences,” said Dr. John McGrath of the Queensland Brain Institute, Wacol, Australia, and his colleagues. The study also demonstrated a dose-response relationship between younger age at first use and higher risk of psychosis-related outcomes, they noted.

The researchers examined the link using data from a birth cohort of more than 7,000 mother-infant pairs who were first studied in 1981–1984 and followed 5, 14, and 21 years later.

The study comprised 3,801 of these infants and their close-in-age siblings. The latest follow-up occurred when they were aged 18–23 years. At that time, about 18% of the subjects said they had been using marijuana for 3 or fewer years, 16% said they had been using it for 4–5 years, and 14% said they had been using it for 6 or more years.

At final follow-up, 65 of these subjects had received diagnoses of nonaffective psychosis because they met the criteria for schizophrenia (53 subjects), persistent delusional disorder (3), or acute transient psychotic disorders (9). Another 233 subjects reported at least one visual or auditory hallucination.

Only subjects with the longest duration since first cannabis use (those who started using marijuana at age 15 years or younger) were at significantly increased risk for developing symptoms of nonaffective psychosis in young adulthood. Those who started using marijuana at that age were twice as likely to receive such a diagnosis than were subjects who said they had never used marijuana, the researchers said (Arch. Gen. Psychiatry 2010 March 1 [doi:10.1001/archgenpsychiatry.2010.6]).

Compared with subjects who did not use cannabis, those who used it at a younger age were 4 times more likely to score in the top quartile on the 21-item Peters et al. Delusional Inventory (PDI) and to report hallucinations on the CIDI.

Moreover, the longer the interval since first cannabis use, the higher the risk of these adverse psychosis-related outcomes. In a subsample of 218 sibling pairs, there was a significant association between earlier first use of cannabis and higher scores on the PDI. For every additional year since first exposure to marijuana, the sibling with the younger age at first use scored one item higher than the other sibling, the researchers said.

This study was not designed to determine causality.

Those who began marijuana use at age 15 or younger had double the risk of psychosis.

Source ©ron hilton/iStockphoto.com

Major Finding: A dose-response relationship was seen between younger onset age of cannabis use and greater risk of psychosis-related outcomes in sibling pairs.

Data Source: Prospective, sibling pair analysis of 3,081 adults born between 1981 and 1984.

Disclosures: None of the investigators had any financial conflicts of interest to report.

The use of cannabis at a younger age is associated with psychosis symptoms in early adulthood, according to an Australian study.

This is the first study to show the association in a subgroup of sibling pairs, “reducing the likelihood that the association was due to unmeasured shared genetic and/or environmental influences,” said Dr. John McGrath of the Queensland Brain Institute, Wacol, Australia, and his colleagues. The study also demonstrated a dose-response relationship between younger age at first use and higher risk of psychosis-related outcomes, they noted.

The researchers examined the link using data from a birth cohort of more than 7,000 mother-infant pairs who were first studied in 1981–1984 and followed 5, 14, and 21 years later.

The study comprised 3,801 of these infants and their close-in-age siblings. The latest follow-up occurred when they were aged 18–23 years. At that time, about 18% of the subjects said they had been using marijuana for 3 or fewer years, 16% said they had been using it for 4–5 years, and 14% said they had been using it for 6 or more years.

At final follow-up, 65 of these subjects had received diagnoses of nonaffective psychosis because they met the criteria for schizophrenia (53 subjects), persistent delusional disorder (3), or acute transient psychotic disorders (9). Another 233 subjects reported at least one visual or auditory hallucination.

Only subjects with the longest duration since first cannabis use (those who started using marijuana at age 15 years or younger) were at significantly increased risk for developing symptoms of nonaffective psychosis in young adulthood. Those who started using marijuana at that age were twice as likely to receive such a diagnosis than were subjects who said they had never used marijuana, the researchers said (Arch. Gen. Psychiatry 2010 March 1 [doi:10.1001/archgenpsychiatry.2010.6]).

Compared with subjects who did not use cannabis, those who used it at a younger age were 4 times more likely to score in the top quartile on the 21-item Peters et al. Delusional Inventory (PDI) and to report hallucinations on the CIDI.

Moreover, the longer the interval since first cannabis use, the higher the risk of these adverse psychosis-related outcomes. In a subsample of 218 sibling pairs, there was a significant association between earlier first use of cannabis and higher scores on the PDI. For every additional year since first exposure to marijuana, the sibling with the younger age at first use scored one item higher than the other sibling, the researchers said.

This study was not designed to determine causality.

Those who began marijuana use at age 15 or younger had double the risk of psychosis.

Source ©ron hilton/iStockphoto.com

Gastric banding allowed extremely obese adolescents to achieve a more substantial and durable weight loss than did an intensive lifestyle modification program, in a clinical trial with 50 adolescents.

Dr. Paul E. O'Brien of the Centre for Obesity Research and Education at Monash University, Melbourne, and his associates compared the two approaches in adolescents aged 14–18 years with a body mass index above 35 kg/m

The patients were randomly assigned to undergo laparoscopic adjustable gastric binding with follow-up education and guidance or to an intensive nonsurgical intervention program. The program focused on reduced energy intake, increased physical activity (with structured exercise for at least 30 minutes per day), and behavior modification. Subjects received 6 weeks of instruction from a personal trainer and met with a physician, a dietitian, or an exercise consultant every 6 weeks (JAMA 2010;303:519-26).

Of the 25 patients in the surgery group, 24 (96%) completed the full 2 years of follow-up, compared with 18 of the 25 patients in the lifestyle group (72%).

In the surgery group, 21 patients (84%) achieved the primary outcome measure of a loss of at least 50% of excess weight, compared with only 3 (12%) of those in the lifestyle group. At 2 years, the surgery group had lost a mean of 35 kg, or a mean loss of 28% of total body weight. Patients in the lifestyle group lost a mean of 3 kg, or a mean loss of 3% of total body weight, Dr. O'Brien and his colleagues reported.

Metabolic syndrome, present at baseline in 9 surgery patients and 10 lifestyle patients, resolved in all of the surgery patients and in 6 of the lifestyle patients. Similarly, insulin resistance resolved in all patients in the surgery group but persisted in three patients in the lifestyle group.

There were no operative or postoperative complications, and the rates of adverse events were similar between the two groups. Seven patients in the surgery group (28%) required revisional procedures, a finding that the researchers said was not surprising because such revisions are “intrinsic to the gastric banding procedure.”

In an editorial, Dr. Edward H. Livingston, of the University of Texas Southwestern Medical Center, Dallas, said that the 28% rate of revisional procedures is important because the investigators “are among the most experienced group in the world with these operations, suggesting that these complication rates will probably be higher in actual community practice” (JAMA 2010;303:559-60).

Disclosures: The study was supported in part by Allergan, which provided the gastric bands. Dr. O'Brien reported no potential conflicts of interest; one of his associates is a consultant for Allergan and other pharmaceutical firms. Dr. Livingston reported no potential conflicts of interest.

Gastric banding allowed extremely obese adolescents to achieve a more substantial and durable weight loss than did an intensive lifestyle modification program, in a clinical trial with 50 adolescents.

Dr. Paul E. O'Brien of the Centre for Obesity Research and Education at Monash University, Melbourne, and his associates compared the two approaches in adolescents aged 14–18 years with a body mass index above 35 kg/m

The patients were randomly assigned to undergo laparoscopic adjustable gastric binding with follow-up education and guidance or to an intensive nonsurgical intervention program. The program focused on reduced energy intake, increased physical activity (with structured exercise for at least 30 minutes per day), and behavior modification. Subjects received 6 weeks of instruction from a personal trainer and met with a physician, a dietitian, or an exercise consultant every 6 weeks (JAMA 2010;303:519-26).

Of the 25 patients in the surgery group, 24 (96%) completed the full 2 years of follow-up, compared with 18 of the 25 patients in the lifestyle group (72%).

In the surgery group, 21 patients (84%) achieved the primary outcome measure of a loss of at least 50% of excess weight, compared with only 3 (12%) of those in the lifestyle group. At 2 years, the surgery group had lost a mean of 35 kg, or a mean loss of 28% of total body weight. Patients in the lifestyle group lost a mean of 3 kg, or a mean loss of 3% of total body weight, Dr. O'Brien and his colleagues reported.

Metabolic syndrome, present at baseline in 9 surgery patients and 10 lifestyle patients, resolved in all of the surgery patients and in 6 of the lifestyle patients. Similarly, insulin resistance resolved in all patients in the surgery group but persisted in three patients in the lifestyle group.

There were no operative or postoperative complications, and the rates of adverse events were similar between the two groups. Seven patients in the surgery group (28%) required revisional procedures, a finding that the researchers said was not surprising because such revisions are “intrinsic to the gastric banding procedure.”

In an editorial, Dr. Edward H. Livingston, of the University of Texas Southwestern Medical Center, Dallas, said that the 28% rate of revisional procedures is important because the investigators “are among the most experienced group in the world with these operations, suggesting that these complication rates will probably be higher in actual community practice” (JAMA 2010;303:559-60).

Disclosures: The study was supported in part by Allergan, which provided the gastric bands. Dr. O'Brien reported no potential conflicts of interest; one of his associates is a consultant for Allergan and other pharmaceutical firms. Dr. Livingston reported no potential conflicts of interest.

Gastric banding allowed extremely obese adolescents to achieve a more substantial and durable weight loss than did an intensive lifestyle modification program, in a clinical trial with 50 adolescents.

Dr. Paul E. O'Brien of the Centre for Obesity Research and Education at Monash University, Melbourne, and his associates compared the two approaches in adolescents aged 14–18 years with a body mass index above 35 kg/m

The patients were randomly assigned to undergo laparoscopic adjustable gastric binding with follow-up education and guidance or to an intensive nonsurgical intervention program. The program focused on reduced energy intake, increased physical activity (with structured exercise for at least 30 minutes per day), and behavior modification. Subjects received 6 weeks of instruction from a personal trainer and met with a physician, a dietitian, or an exercise consultant every 6 weeks (JAMA 2010;303:519-26).

Of the 25 patients in the surgery group, 24 (96%) completed the full 2 years of follow-up, compared with 18 of the 25 patients in the lifestyle group (72%).

In the surgery group, 21 patients (84%) achieved the primary outcome measure of a loss of at least 50% of excess weight, compared with only 3 (12%) of those in the lifestyle group. At 2 years, the surgery group had lost a mean of 35 kg, or a mean loss of 28% of total body weight. Patients in the lifestyle group lost a mean of 3 kg, or a mean loss of 3% of total body weight, Dr. O'Brien and his colleagues reported.

Metabolic syndrome, present at baseline in 9 surgery patients and 10 lifestyle patients, resolved in all of the surgery patients and in 6 of the lifestyle patients. Similarly, insulin resistance resolved in all patients in the surgery group but persisted in three patients in the lifestyle group.

There were no operative or postoperative complications, and the rates of adverse events were similar between the two groups. Seven patients in the surgery group (28%) required revisional procedures, a finding that the researchers said was not surprising because such revisions are “intrinsic to the gastric banding procedure.”

In an editorial, Dr. Edward H. Livingston, of the University of Texas Southwestern Medical Center, Dallas, said that the 28% rate of revisional procedures is important because the investigators “are among the most experienced group in the world with these operations, suggesting that these complication rates will probably be higher in actual community practice” (JAMA 2010;303:559-60).

Disclosures: The study was supported in part by Allergan, which provided the gastric bands. Dr. O'Brien reported no potential conflicts of interest; one of his associates is a consultant for Allergan and other pharmaceutical firms. Dr. Livingston reported no potential conflicts of interest.

The link between anticonvulsant agents and suicidal acts or violent death—first revealed in a Food and Drug Administration meta-analysis in 2008—appears to have been confirmed for four of the drugs: gabapentin, lamotrigine, oxcarbazepine, and tiagabine, investigators reported.

In what they described as the first study to directly compare suicide risks with different anticonvulsants given in routine care, the investigators reported finding “increased risk for suicidal acts beginning within the first 14 days of treatment initiation.” The finding opens the possibility that anticonvulsants “could induce [adverse] behavioral effects prior to the achievement of their full therapeutic effectiveness,” reported Dr. Elisabetta Patorno of Brigham and Women's Hospital, Boston, and her associates (JAMA 2010;303:1401-9).

In the FDA meta-analysis, the number of events was small and largely confined to cases of suicidal ideation only. This “prevented definitive conclusions about the safety of individual agents,” the investigators said. In addition, the anticonvulsant agents were used as adjunctive treatment in many of the studies included in the meta-analysis, “further complicating the assessment of their individual effect. Thus, the FDA meta-analysis could not provide patients or clinicians with clear guidelines on risk for specific agents or patient subgroups,” Dr. Patorno and her colleagues noted.

They addressed these issues by conducting a cohort study using a database that included 297,620 new prescriptions for anticonvulsant drugs in 17 states between 2001 and 2006. The risk of attempted or completed suicidal acts or violent deaths was compared between patients aged 15 and older who had initiated treatment with one of two reference anticonvulsants (topiramate or carbamazepine) and patients who had initiated treatment with any of 13 other anticonvulsants. The study subjects were to be followed for 180 days or until they discontinued or switched medications, had a study outcome, or discontinued the study for other reasons. The mean follow-up turned out to be 91 days.

There were 801 attempted suicides, 26 completed suicides, and 41 violent deaths within 180 days of initiating anticonvulsant therapy.

Compared with subjects initiating use of topiramate or carbamazepine, those starting on gabapentin, lamotrigine, oxcarbazepine, and tiagabine were at significantly increased risk for these events, the investigators said.

A further analysis of the data showed that new users of gabapentin had an excess of 5.6 cases of attempted or completed suicide per 1,000 person-years, new users of oxcarbazepine had an excess of 10 cases per 1,000 person-years, and new users of tiagabine had an excess of 14.1 cases per 1,000 person-years, compared with new users of topiramate.

“These findings are compatible with the results of the FDA meta-analysis, which found similarly increased risks of suicidal behavior or ideation for all anticonvulsant drugs compared with placebo,” Dr. Patorno and her associates said.

They cautioned that their study was exploratory in nature, and so could only suggest rather than definitively establish a causal relationship between these drugs and suicidal behavior. “There is no clear understanding of a possible mechanism of action that could lead to suicidal behavior in patients taking these medications,” the researchers added.

Gabapentin and lamotrigine have been linked to behavioral problems such as aggression and hyperactivity, particularly in children and adults who have learning disabilities or cognitive impairment. Tiagabine has been reported to cause nervousness and depressive mood in some patients. And oxcarbazepine is thought to have a stimulant effect on psychomotor functioning in some, they said.

Disclosures: The study was funded by the HealthCore Fellowship in Pharmacoepidemiology and the Pharmacoepidemiology Research and Training Fund of the Harvard School of Public Health. Dr. Patorno reported no financial conflicts of interest.

The link between anticonvulsant agents and suicidal acts or violent death—first revealed in a Food and Drug Administration meta-analysis in 2008—appears to have been confirmed for four of the drugs: gabapentin, lamotrigine, oxcarbazepine, and tiagabine, investigators reported.

In what they described as the first study to directly compare suicide risks with different anticonvulsants given in routine care, the investigators reported finding “increased risk for suicidal acts beginning within the first 14 days of treatment initiation.” The finding opens the possibility that anticonvulsants “could induce [adverse] behavioral effects prior to the achievement of their full therapeutic effectiveness,” reported Dr. Elisabetta Patorno of Brigham and Women's Hospital, Boston, and her associates (JAMA 2010;303:1401-9).

In the FDA meta-analysis, the number of events was small and largely confined to cases of suicidal ideation only. This “prevented definitive conclusions about the safety of individual agents,” the investigators said. In addition, the anticonvulsant agents were used as adjunctive treatment in many of the studies included in the meta-analysis, “further complicating the assessment of their individual effect. Thus, the FDA meta-analysis could not provide patients or clinicians with clear guidelines on risk for specific agents or patient subgroups,” Dr. Patorno and her colleagues noted.

They addressed these issues by conducting a cohort study using a database that included 297,620 new prescriptions for anticonvulsant drugs in 17 states between 2001 and 2006. The risk of attempted or completed suicidal acts or violent deaths was compared between patients aged 15 and older who had initiated treatment with one of two reference anticonvulsants (topiramate or carbamazepine) and patients who had initiated treatment with any of 13 other anticonvulsants. The study subjects were to be followed for 180 days or until they discontinued or switched medications, had a study outcome, or discontinued the study for other reasons. The mean follow-up turned out to be 91 days.

There were 801 attempted suicides, 26 completed suicides, and 41 violent deaths within 180 days of initiating anticonvulsant therapy.

Compared with subjects initiating use of topiramate or carbamazepine, those starting on gabapentin, lamotrigine, oxcarbazepine, and tiagabine were at significantly increased risk for these events, the investigators said.

A further analysis of the data showed that new users of gabapentin had an excess of 5.6 cases of attempted or completed suicide per 1,000 person-years, new users of oxcarbazepine had an excess of 10 cases per 1,000 person-years, and new users of tiagabine had an excess of 14.1 cases per 1,000 person-years, compared with new users of topiramate.

“These findings are compatible with the results of the FDA meta-analysis, which found similarly increased risks of suicidal behavior or ideation for all anticonvulsant drugs compared with placebo,” Dr. Patorno and her associates said.

They cautioned that their study was exploratory in nature, and so could only suggest rather than definitively establish a causal relationship between these drugs and suicidal behavior. “There is no clear understanding of a possible mechanism of action that could lead to suicidal behavior in patients taking these medications,” the researchers added.

Gabapentin and lamotrigine have been linked to behavioral problems such as aggression and hyperactivity, particularly in children and adults who have learning disabilities or cognitive impairment. Tiagabine has been reported to cause nervousness and depressive mood in some patients. And oxcarbazepine is thought to have a stimulant effect on psychomotor functioning in some, they said.

Disclosures: The study was funded by the HealthCore Fellowship in Pharmacoepidemiology and the Pharmacoepidemiology Research and Training Fund of the Harvard School of Public Health. Dr. Patorno reported no financial conflicts of interest.

The link between anticonvulsant agents and suicidal acts or violent death—first revealed in a Food and Drug Administration meta-analysis in 2008—appears to have been confirmed for four of the drugs: gabapentin, lamotrigine, oxcarbazepine, and tiagabine, investigators reported.

In what they described as the first study to directly compare suicide risks with different anticonvulsants given in routine care, the investigators reported finding “increased risk for suicidal acts beginning within the first 14 days of treatment initiation.” The finding opens the possibility that anticonvulsants “could induce [adverse] behavioral effects prior to the achievement of their full therapeutic effectiveness,” reported Dr. Elisabetta Patorno of Brigham and Women's Hospital, Boston, and her associates (JAMA 2010;303:1401-9).

In the FDA meta-analysis, the number of events was small and largely confined to cases of suicidal ideation only. This “prevented definitive conclusions about the safety of individual agents,” the investigators said. In addition, the anticonvulsant agents were used as adjunctive treatment in many of the studies included in the meta-analysis, “further complicating the assessment of their individual effect. Thus, the FDA meta-analysis could not provide patients or clinicians with clear guidelines on risk for specific agents or patient subgroups,” Dr. Patorno and her colleagues noted.

They addressed these issues by conducting a cohort study using a database that included 297,620 new prescriptions for anticonvulsant drugs in 17 states between 2001 and 2006. The risk of attempted or completed suicidal acts or violent deaths was compared between patients aged 15 and older who had initiated treatment with one of two reference anticonvulsants (topiramate or carbamazepine) and patients who had initiated treatment with any of 13 other anticonvulsants. The study subjects were to be followed for 180 days or until they discontinued or switched medications, had a study outcome, or discontinued the study for other reasons. The mean follow-up turned out to be 91 days.

There were 801 attempted suicides, 26 completed suicides, and 41 violent deaths within 180 days of initiating anticonvulsant therapy.

Compared with subjects initiating use of topiramate or carbamazepine, those starting on gabapentin, lamotrigine, oxcarbazepine, and tiagabine were at significantly increased risk for these events, the investigators said.

A further analysis of the data showed that new users of gabapentin had an excess of 5.6 cases of attempted or completed suicide per 1,000 person-years, new users of oxcarbazepine had an excess of 10 cases per 1,000 person-years, and new users of tiagabine had an excess of 14.1 cases per 1,000 person-years, compared with new users of topiramate.

“These findings are compatible with the results of the FDA meta-analysis, which found similarly increased risks of suicidal behavior or ideation for all anticonvulsant drugs compared with placebo,” Dr. Patorno and her associates said.

They cautioned that their study was exploratory in nature, and so could only suggest rather than definitively establish a causal relationship between these drugs and suicidal behavior. “There is no clear understanding of a possible mechanism of action that could lead to suicidal behavior in patients taking these medications,” the researchers added.

Gabapentin and lamotrigine have been linked to behavioral problems such as aggression and hyperactivity, particularly in children and adults who have learning disabilities or cognitive impairment. Tiagabine has been reported to cause nervousness and depressive mood in some patients. And oxcarbazepine is thought to have a stimulant effect on psychomotor functioning in some, they said.

Disclosures: The study was funded by the HealthCore Fellowship in Pharmacoepidemiology and the Pharmacoepidemiology Research and Training Fund of the Harvard School of Public Health. Dr. Patorno reported no financial conflicts of interest.

In patients whose mild cognitive impairment affects executive function but not memory, the presence of hypertension signals an increased likelihood of progression to full dementia, according to data from almost 1,000 patients.

This subgroup comprises about one-third of all patients who have mild cognitive impairment. “Control of hypertension in this population could decrease by one-half the projected 50% 5-year rate of progression to dementia,” said Dr. Shahram Oveisgharan and Dr. Vladimir Hachinski of the University of Western Ontario, London.

Although some studies have found an association between late-life hypertension and the development of dementia, others have not. The investigators postulated that the cognitive domain of dysfunction, or the abilities that have been affected by the impairment, may be the crucial factor that determines the association between hypertension and cognitive deterioration.

“To our knowledge, this has not been addressed in previous studies,” Dr. Oveisgharan and Dr. Hachinski noted (Arch. Neurol. 2010;67:187-92).

They used data from a community-based longitudinal cohort study, the Canadian Study of Health and Aging (CSHA), to assess this association. More than 10,000 subjects aged 65 years and older underwent a battery of neuropsychological tests in the CSHA.

A total of 990 participants were diagnosed as having cognitive impairment without dementia and were followed for 5 years. Only people whose mild cognitive impairment (MCI) was not related to neurologic disorders, psychiatric illness, or substance abuse disorders were included in this study.

In the cohort as a whole, hypertension was not related to cognitive deterioration. Approximately 60% of participants with hypertension and 64% of those without hypertension progressed from mild cognitive impairment to dementia during follow-up, a difference that was not significant.

Hypertension, however, did predict progression to dementia in one subgroup of patients: those who had MCI with executive dysfunction alone. Approximately 58% of this subgroup who had hypertension progressed to dementia, compared with only 28% who did not have hypertension, the investigators said.

In contrast, the presence of hypertension did not predict progression to dementia in patients who had MCI with memory dysfunction alone or in patients who had MCI with both executive and memory dysfunction.

To rule out the possibility that a history of stroke could be influencing the findings for the subgroup of patients who had MCI with executive dysfunction alone, the researchers conducted a further analysis of the subgroup, excluding all stroke patients. Hypertension remained a significant predictor of progression to dementia, with 52% of the nonstroke hypertensive patients progressing to dementia, compared with only 19% of nonstroke nonhypertensive subjects.

This study was limited in that it was a secondary analysis of data amassed for another study, and thus “has the limitations of a post hoc analysis,” they noted. Moreover, cognitive status could not be determined in about 10% of the cohort who refused retesting, and it could only be estimated (from information on death certificates and in interviews with relatives) in another 30% who died during follow-up, Dr. Oveisgharan and Dr. Hachinski said.

Disclosures: This study was supported in part by a grant from the Alzheimer Association. Neither investigator reported a financial conflict of interest.

In patients whose mild cognitive impairment affects executive function but not memory, the presence of hypertension signals an increased likelihood of progression to full dementia, according to data from almost 1,000 patients.

This subgroup comprises about one-third of all patients who have mild cognitive impairment. “Control of hypertension in this population could decrease by one-half the projected 50% 5-year rate of progression to dementia,” said Dr. Shahram Oveisgharan and Dr. Vladimir Hachinski of the University of Western Ontario, London.

Although some studies have found an association between late-life hypertension and the development of dementia, others have not. The investigators postulated that the cognitive domain of dysfunction, or the abilities that have been affected by the impairment, may be the crucial factor that determines the association between hypertension and cognitive deterioration.

“To our knowledge, this has not been addressed in previous studies,” Dr. Oveisgharan and Dr. Hachinski noted (Arch. Neurol. 2010;67:187-92).

They used data from a community-based longitudinal cohort study, the Canadian Study of Health and Aging (CSHA), to assess this association. More than 10,000 subjects aged 65 years and older underwent a battery of neuropsychological tests in the CSHA.

A total of 990 participants were diagnosed as having cognitive impairment without dementia and were followed for 5 years. Only people whose mild cognitive impairment (MCI) was not related to neurologic disorders, psychiatric illness, or substance abuse disorders were included in this study.

In the cohort as a whole, hypertension was not related to cognitive deterioration. Approximately 60% of participants with hypertension and 64% of those without hypertension progressed from mild cognitive impairment to dementia during follow-up, a difference that was not significant.

Hypertension, however, did predict progression to dementia in one subgroup of patients: those who had MCI with executive dysfunction alone. Approximately 58% of this subgroup who had hypertension progressed to dementia, compared with only 28% who did not have hypertension, the investigators said.

In contrast, the presence of hypertension did not predict progression to dementia in patients who had MCI with memory dysfunction alone or in patients who had MCI with both executive and memory dysfunction.

To rule out the possibility that a history of stroke could be influencing the findings for the subgroup of patients who had MCI with executive dysfunction alone, the researchers conducted a further analysis of the subgroup, excluding all stroke patients. Hypertension remained a significant predictor of progression to dementia, with 52% of the nonstroke hypertensive patients progressing to dementia, compared with only 19% of nonstroke nonhypertensive subjects.

This study was limited in that it was a secondary analysis of data amassed for another study, and thus “has the limitations of a post hoc analysis,” they noted. Moreover, cognitive status could not be determined in about 10% of the cohort who refused retesting, and it could only be estimated (from information on death certificates and in interviews with relatives) in another 30% who died during follow-up, Dr. Oveisgharan and Dr. Hachinski said.

Disclosures: This study was supported in part by a grant from the Alzheimer Association. Neither investigator reported a financial conflict of interest.

In patients whose mild cognitive impairment affects executive function but not memory, the presence of hypertension signals an increased likelihood of progression to full dementia, according to data from almost 1,000 patients.

This subgroup comprises about one-third of all patients who have mild cognitive impairment. “Control of hypertension in this population could decrease by one-half the projected 50% 5-year rate of progression to dementia,” said Dr. Shahram Oveisgharan and Dr. Vladimir Hachinski of the University of Western Ontario, London.

Although some studies have found an association between late-life hypertension and the development of dementia, others have not. The investigators postulated that the cognitive domain of dysfunction, or the abilities that have been affected by the impairment, may be the crucial factor that determines the association between hypertension and cognitive deterioration.

“To our knowledge, this has not been addressed in previous studies,” Dr. Oveisgharan and Dr. Hachinski noted (Arch. Neurol. 2010;67:187-92).

They used data from a community-based longitudinal cohort study, the Canadian Study of Health and Aging (CSHA), to assess this association. More than 10,000 subjects aged 65 years and older underwent a battery of neuropsychological tests in the CSHA.

A total of 990 participants were diagnosed as having cognitive impairment without dementia and were followed for 5 years. Only people whose mild cognitive impairment (MCI) was not related to neurologic disorders, psychiatric illness, or substance abuse disorders were included in this study.

In the cohort as a whole, hypertension was not related to cognitive deterioration. Approximately 60% of participants with hypertension and 64% of those without hypertension progressed from mild cognitive impairment to dementia during follow-up, a difference that was not significant.

Hypertension, however, did predict progression to dementia in one subgroup of patients: those who had MCI with executive dysfunction alone. Approximately 58% of this subgroup who had hypertension progressed to dementia, compared with only 28% who did not have hypertension, the investigators said.

In contrast, the presence of hypertension did not predict progression to dementia in patients who had MCI with memory dysfunction alone or in patients who had MCI with both executive and memory dysfunction.

To rule out the possibility that a history of stroke could be influencing the findings for the subgroup of patients who had MCI with executive dysfunction alone, the researchers conducted a further analysis of the subgroup, excluding all stroke patients. Hypertension remained a significant predictor of progression to dementia, with 52% of the nonstroke hypertensive patients progressing to dementia, compared with only 19% of nonstroke nonhypertensive subjects.

This study was limited in that it was a secondary analysis of data amassed for another study, and thus “has the limitations of a post hoc analysis,” they noted. Moreover, cognitive status could not be determined in about 10% of the cohort who refused retesting, and it could only be estimated (from information on death certificates and in interviews with relatives) in another 30% who died during follow-up, Dr. Oveisgharan and Dr. Hachinski said.

Disclosures: This study was supported in part by a grant from the Alzheimer Association. Neither investigator reported a financial conflict of interest.