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Benzodiazepines May Not Increase Dementia Risk
Benzodiazepine use by elderly adults is not causally related to an increased risk of dementia and cognitive decline, according to a prospective study published online ahead of print February 2 in BMJ.
The study included 3,434 individuals age 65 or older without dementia. For at least 10 years before enrollment in the study, all participants had been members of Group Health, an integrated health delivery system in the northwestern United States that maintains computerized pharmacy data, including names, drug doses, dates dispensed, and amounts dispensed of drugs used by its members.
Approximately 30% of participants had filled at least one prescription for a benzodiazepine in the 10 years before entering the study, and 3% of participants had used the drug within six months of study entry. The researchers categorized patients based on their level of benzodiazepine use, and patients in the highest-use category took at least 121 total standardized daily doses (TSDDs). The median level of use within that group was 375 TSDDs, equivalent to slightly more than a year of daily use.
In 2004, the study began continuous enrollment to replace participants who developed dementia, died, or dropped out. Participants were assessed for cognitive function at study entry and every two years afterward. All participants were followed until onset of dementia, disenrollment from Group Health, or their last study visit before September 30, 2012.
The researchers found no association between the use of benzodiazepines at the TSDD level defined as highest use and dementia (hazard ratio [HR], 1.07) or Alzheimer’s disease (HR, 0.95), compared with nonuse. “When we split the highest category of benzodiazepine use into two groups, the hazard ratio for dementia was 1.11 (0.78–1.58) for 121–364 TSDDs and 1.03 (0.73–1.44) for greater than or equal to 365 TSDDs. Findings for Alzheimer’s disease were similar,” said Shelly L. Gray, PharmD, Professor of Pharmacy at the University of Washington School of Pharmacy in Seattle, and her colleagues.
The authors found a slightly increased risk of dementia for study participants classified as low users (ie, those who took 1–30 TSDDs) or moderate users (ie, those who took 31–120 TSDDs) of benzodiazepine, when compared with nonusers. Low users of benzodiazepine were also at increased risk for Alzheimer’s disease (HR, 1.27).
“In conclusion, we found a slightly higher risk of dementia in people with the lowest benzodiazepine use, but no increased risk in those with the highest level of exposure. … Overall, our pattern of findings does not support the theory that cumulative benzodiazepine use at the levels observed in our population is causally related to an increased risk for dementia or cognitive decline. … Nonetheless, given the mixed evidence regarding benzodiazepines and risk of dementia and that these drugs are associated with many adverse events, health care providers are still advised to avoid benzodiazepines in older adults to prevent important adverse health outcomes, withdrawal, and dependence,” according to the researchers.
—Katie Wagner Lennon
Suggested Reading
Gray SL, Dublin S, Yu O, et al. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. BMJ. 2016 Feb 2;352:i90.
Benzodiazepine use by elderly adults is not causally related to an increased risk of dementia and cognitive decline, according to a prospective study published online ahead of print February 2 in BMJ.
The study included 3,434 individuals age 65 or older without dementia. For at least 10 years before enrollment in the study, all participants had been members of Group Health, an integrated health delivery system in the northwestern United States that maintains computerized pharmacy data, including names, drug doses, dates dispensed, and amounts dispensed of drugs used by its members.
Approximately 30% of participants had filled at least one prescription for a benzodiazepine in the 10 years before entering the study, and 3% of participants had used the drug within six months of study entry. The researchers categorized patients based on their level of benzodiazepine use, and patients in the highest-use category took at least 121 total standardized daily doses (TSDDs). The median level of use within that group was 375 TSDDs, equivalent to slightly more than a year of daily use.
In 2004, the study began continuous enrollment to replace participants who developed dementia, died, or dropped out. Participants were assessed for cognitive function at study entry and every two years afterward. All participants were followed until onset of dementia, disenrollment from Group Health, or their last study visit before September 30, 2012.
The researchers found no association between the use of benzodiazepines at the TSDD level defined as highest use and dementia (hazard ratio [HR], 1.07) or Alzheimer’s disease (HR, 0.95), compared with nonuse. “When we split the highest category of benzodiazepine use into two groups, the hazard ratio for dementia was 1.11 (0.78–1.58) for 121–364 TSDDs and 1.03 (0.73–1.44) for greater than or equal to 365 TSDDs. Findings for Alzheimer’s disease were similar,” said Shelly L. Gray, PharmD, Professor of Pharmacy at the University of Washington School of Pharmacy in Seattle, and her colleagues.
The authors found a slightly increased risk of dementia for study participants classified as low users (ie, those who took 1–30 TSDDs) or moderate users (ie, those who took 31–120 TSDDs) of benzodiazepine, when compared with nonusers. Low users of benzodiazepine were also at increased risk for Alzheimer’s disease (HR, 1.27).
“In conclusion, we found a slightly higher risk of dementia in people with the lowest benzodiazepine use, but no increased risk in those with the highest level of exposure. … Overall, our pattern of findings does not support the theory that cumulative benzodiazepine use at the levels observed in our population is causally related to an increased risk for dementia or cognitive decline. … Nonetheless, given the mixed evidence regarding benzodiazepines and risk of dementia and that these drugs are associated with many adverse events, health care providers are still advised to avoid benzodiazepines in older adults to prevent important adverse health outcomes, withdrawal, and dependence,” according to the researchers.
—Katie Wagner Lennon
Benzodiazepine use by elderly adults is not causally related to an increased risk of dementia and cognitive decline, according to a prospective study published online ahead of print February 2 in BMJ.
The study included 3,434 individuals age 65 or older without dementia. For at least 10 years before enrollment in the study, all participants had been members of Group Health, an integrated health delivery system in the northwestern United States that maintains computerized pharmacy data, including names, drug doses, dates dispensed, and amounts dispensed of drugs used by its members.
Approximately 30% of participants had filled at least one prescription for a benzodiazepine in the 10 years before entering the study, and 3% of participants had used the drug within six months of study entry. The researchers categorized patients based on their level of benzodiazepine use, and patients in the highest-use category took at least 121 total standardized daily doses (TSDDs). The median level of use within that group was 375 TSDDs, equivalent to slightly more than a year of daily use.
In 2004, the study began continuous enrollment to replace participants who developed dementia, died, or dropped out. Participants were assessed for cognitive function at study entry and every two years afterward. All participants were followed until onset of dementia, disenrollment from Group Health, or their last study visit before September 30, 2012.
The researchers found no association between the use of benzodiazepines at the TSDD level defined as highest use and dementia (hazard ratio [HR], 1.07) or Alzheimer’s disease (HR, 0.95), compared with nonuse. “When we split the highest category of benzodiazepine use into two groups, the hazard ratio for dementia was 1.11 (0.78–1.58) for 121–364 TSDDs and 1.03 (0.73–1.44) for greater than or equal to 365 TSDDs. Findings for Alzheimer’s disease were similar,” said Shelly L. Gray, PharmD, Professor of Pharmacy at the University of Washington School of Pharmacy in Seattle, and her colleagues.
The authors found a slightly increased risk of dementia for study participants classified as low users (ie, those who took 1–30 TSDDs) or moderate users (ie, those who took 31–120 TSDDs) of benzodiazepine, when compared with nonusers. Low users of benzodiazepine were also at increased risk for Alzheimer’s disease (HR, 1.27).
“In conclusion, we found a slightly higher risk of dementia in people with the lowest benzodiazepine use, but no increased risk in those with the highest level of exposure. … Overall, our pattern of findings does not support the theory that cumulative benzodiazepine use at the levels observed in our population is causally related to an increased risk for dementia or cognitive decline. … Nonetheless, given the mixed evidence regarding benzodiazepines and risk of dementia and that these drugs are associated with many adverse events, health care providers are still advised to avoid benzodiazepines in older adults to prevent important adverse health outcomes, withdrawal, and dependence,” according to the researchers.
—Katie Wagner Lennon
Suggested Reading
Gray SL, Dublin S, Yu O, et al. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. BMJ. 2016 Feb 2;352:i90.
Suggested Reading
Gray SL, Dublin S, Yu O, et al. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. BMJ. 2016 Feb 2;352:i90.
How Does Seafood Intake Correlate With Alzheimer’s Disease Pathology?
Among APOE ε4 carriers, moderate seafood consumption significantly correlates with lesser Alzheimer’s disease neuropathology, according to research published February 2 in JAMA. This association does not exist in people who do not carry the Alzheimer’s disease risk gene, however. In addition, seafood consumption correlates with higher brain levels of mercury, but these mercury levels do not correlate with brain neuropathology, researchers said.
Concerns About Mercury
Prior studies have found protective associations between seafood consumption and dementia, but mercury contamination in seafood has raised concerns. To study the association between seafood consumption, brain mercury level, and brain neuropathology in older adults, Martha Clare Morris, ScD, Director of Nutrition and Nutritional Epidemiology at Rush University Medical Center in Chicago, and colleagues conducted cross-sectional analyses of deceased participants in the Memory and Aging Project. The investigators included 286 participants from the clinical neuropathologic cohort study who had completed a dietary assessment, died between 2004 and 2013, and had a brain autopsy performed.
Mean age at death was 89.9, 67% of subjects were women, and average educational attainment was 14.6 years. Sixty-five participants (22.7%) had the APOE ε4 allele. The participants were residents of retirement communities and subsidized housing in Chicago.
Participants reported seafood intake by completing a food frequency questionnaire at a mean of 4.5 years before death. Mean seafood consumption in this cohort was 1.3 seafood meals per week in the lowest tertile and 2.7 seafood meals per week in the highest tertile.
Investigators assessed dementia-related pathologies, including Alzheimer’s disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. They measured tissue concentrations of mercury and selenium using instrumental neutron activation analyses in a subsample of 203 cases.
Pathologic Hallmarks
As in prior studies, seafood consumption did not correlate with Alzheimer’s disease outcomes in a linear way, and the investigators only presented findings where seafood was modeled as an indicator variable (ie, one or more meals per week vs less). After adjusting for age, sex, education, and total energy intake, eating one or more seafood meals per week was significantly associated with less Alzheimer’s disease pathology, including lower density of neuritic plaques and less severe and widespread neurofibrillary tangles in APOE ε4 carriers.
Brain mercury levels positively correlated with the number of seafood meals consumed per week, but levels did not correlate with neuropathology. “To our knowledge, this is the first study to report on the relationship between brain concentrations of mercury and brain neuropathology or diet,” said Dr. Morris and colleagues. “The finding of no deleterious correlations of mercury on the brain is supported by a number of case–control studies that found no difference between Alzheimer’s disease patients and controls in mercury concentrations in the brain, serum, or whole blood.”
Reassuring Data
That higher mercury levels do not correlate with dementia or Alzheimer’s disease pathology “is reassuring because ingested mercury accumulates in the body over decades, and brain levels hence result from exposure, which likely precedes any Alzheimer’s disease or dementia development,” said Edeltraut Kröger, PhD, and Robert Laforce Jr, MD, PhD, of Université Laval in Quebec City, Canada, in an accompanying editorial.
“Patients and their families may be hopeful that interventions such as seafood consumption may help reduce clinical manifestations of Alzheimer’s disease or dementia, and the report by Morris et al provides reassurance that seafood contamination with mercury is not related to increased brain pathology,” they said. “Eating fatty fish may continue to be considered potentially beneficial against cognitive decline in at least a proportion of older adults, a strategy that now generally should not be affected by concerns about mercury contamination in fish.”
Drs. Kröger and Laforce noted that large randomized clinical trials are needed before recommending dietary interventions, such as a Mediterranean-style diet, to improve cognitive health. In addition, relating brain pathology, including amyloid deposition, to clinical disease may be more complicated than previously thought. “Ultimately, proof of the brain pathological concepts of Alzheimer’s disease and other dementias will be based on data from clinical trials confirming that preventive or therapeutic interventions on these elements of brain neuropathology will reduce clinical manifestations of Alzheimer’s disease and other dementias,” they said.
The study cohort was very old and largely non-Hispanic white, and the findings might not apply to younger adults or other racial or ethnic groups, the investigators said. The results also cannot be generalized to populations with higher seafood consumption or mercury exposure.
Suggested Reading
Kröger E, Laforce R Jr. Fish consumption, brain mercury, and neuropathology in patients with Alzheimer disease and dementia. JAMA. 2016;315(5):465-466.
Morris MC, Brockman J, Schneider JA, et al. Association of seafood consumption, brain mercury level, and APOE ε4 status with brain neuropathology in older adults. JAMA. 2016;315(5):489-497.
Among APOE ε4 carriers, moderate seafood consumption significantly correlates with lesser Alzheimer’s disease neuropathology, according to research published February 2 in JAMA. This association does not exist in people who do not carry the Alzheimer’s disease risk gene, however. In addition, seafood consumption correlates with higher brain levels of mercury, but these mercury levels do not correlate with brain neuropathology, researchers said.
Concerns About Mercury
Prior studies have found protective associations between seafood consumption and dementia, but mercury contamination in seafood has raised concerns. To study the association between seafood consumption, brain mercury level, and brain neuropathology in older adults, Martha Clare Morris, ScD, Director of Nutrition and Nutritional Epidemiology at Rush University Medical Center in Chicago, and colleagues conducted cross-sectional analyses of deceased participants in the Memory and Aging Project. The investigators included 286 participants from the clinical neuropathologic cohort study who had completed a dietary assessment, died between 2004 and 2013, and had a brain autopsy performed.
Mean age at death was 89.9, 67% of subjects were women, and average educational attainment was 14.6 years. Sixty-five participants (22.7%) had the APOE ε4 allele. The participants were residents of retirement communities and subsidized housing in Chicago.
Participants reported seafood intake by completing a food frequency questionnaire at a mean of 4.5 years before death. Mean seafood consumption in this cohort was 1.3 seafood meals per week in the lowest tertile and 2.7 seafood meals per week in the highest tertile.
Investigators assessed dementia-related pathologies, including Alzheimer’s disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. They measured tissue concentrations of mercury and selenium using instrumental neutron activation analyses in a subsample of 203 cases.
Pathologic Hallmarks
As in prior studies, seafood consumption did not correlate with Alzheimer’s disease outcomes in a linear way, and the investigators only presented findings where seafood was modeled as an indicator variable (ie, one or more meals per week vs less). After adjusting for age, sex, education, and total energy intake, eating one or more seafood meals per week was significantly associated with less Alzheimer’s disease pathology, including lower density of neuritic plaques and less severe and widespread neurofibrillary tangles in APOE ε4 carriers.
Brain mercury levels positively correlated with the number of seafood meals consumed per week, but levels did not correlate with neuropathology. “To our knowledge, this is the first study to report on the relationship between brain concentrations of mercury and brain neuropathology or diet,” said Dr. Morris and colleagues. “The finding of no deleterious correlations of mercury on the brain is supported by a number of case–control studies that found no difference between Alzheimer’s disease patients and controls in mercury concentrations in the brain, serum, or whole blood.”
Reassuring Data
That higher mercury levels do not correlate with dementia or Alzheimer’s disease pathology “is reassuring because ingested mercury accumulates in the body over decades, and brain levels hence result from exposure, which likely precedes any Alzheimer’s disease or dementia development,” said Edeltraut Kröger, PhD, and Robert Laforce Jr, MD, PhD, of Université Laval in Quebec City, Canada, in an accompanying editorial.
“Patients and their families may be hopeful that interventions such as seafood consumption may help reduce clinical manifestations of Alzheimer’s disease or dementia, and the report by Morris et al provides reassurance that seafood contamination with mercury is not related to increased brain pathology,” they said. “Eating fatty fish may continue to be considered potentially beneficial against cognitive decline in at least a proportion of older adults, a strategy that now generally should not be affected by concerns about mercury contamination in fish.”
Drs. Kröger and Laforce noted that large randomized clinical trials are needed before recommending dietary interventions, such as a Mediterranean-style diet, to improve cognitive health. In addition, relating brain pathology, including amyloid deposition, to clinical disease may be more complicated than previously thought. “Ultimately, proof of the brain pathological concepts of Alzheimer’s disease and other dementias will be based on data from clinical trials confirming that preventive or therapeutic interventions on these elements of brain neuropathology will reduce clinical manifestations of Alzheimer’s disease and other dementias,” they said.
The study cohort was very old and largely non-Hispanic white, and the findings might not apply to younger adults or other racial or ethnic groups, the investigators said. The results also cannot be generalized to populations with higher seafood consumption or mercury exposure.
Among APOE ε4 carriers, moderate seafood consumption significantly correlates with lesser Alzheimer’s disease neuropathology, according to research published February 2 in JAMA. This association does not exist in people who do not carry the Alzheimer’s disease risk gene, however. In addition, seafood consumption correlates with higher brain levels of mercury, but these mercury levels do not correlate with brain neuropathology, researchers said.
Concerns About Mercury
Prior studies have found protective associations between seafood consumption and dementia, but mercury contamination in seafood has raised concerns. To study the association between seafood consumption, brain mercury level, and brain neuropathology in older adults, Martha Clare Morris, ScD, Director of Nutrition and Nutritional Epidemiology at Rush University Medical Center in Chicago, and colleagues conducted cross-sectional analyses of deceased participants in the Memory and Aging Project. The investigators included 286 participants from the clinical neuropathologic cohort study who had completed a dietary assessment, died between 2004 and 2013, and had a brain autopsy performed.
Mean age at death was 89.9, 67% of subjects were women, and average educational attainment was 14.6 years. Sixty-five participants (22.7%) had the APOE ε4 allele. The participants were residents of retirement communities and subsidized housing in Chicago.
Participants reported seafood intake by completing a food frequency questionnaire at a mean of 4.5 years before death. Mean seafood consumption in this cohort was 1.3 seafood meals per week in the lowest tertile and 2.7 seafood meals per week in the highest tertile.
Investigators assessed dementia-related pathologies, including Alzheimer’s disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. They measured tissue concentrations of mercury and selenium using instrumental neutron activation analyses in a subsample of 203 cases.
Pathologic Hallmarks
As in prior studies, seafood consumption did not correlate with Alzheimer’s disease outcomes in a linear way, and the investigators only presented findings where seafood was modeled as an indicator variable (ie, one or more meals per week vs less). After adjusting for age, sex, education, and total energy intake, eating one or more seafood meals per week was significantly associated with less Alzheimer’s disease pathology, including lower density of neuritic plaques and less severe and widespread neurofibrillary tangles in APOE ε4 carriers.
Brain mercury levels positively correlated with the number of seafood meals consumed per week, but levels did not correlate with neuropathology. “To our knowledge, this is the first study to report on the relationship between brain concentrations of mercury and brain neuropathology or diet,” said Dr. Morris and colleagues. “The finding of no deleterious correlations of mercury on the brain is supported by a number of case–control studies that found no difference between Alzheimer’s disease patients and controls in mercury concentrations in the brain, serum, or whole blood.”
Reassuring Data
That higher mercury levels do not correlate with dementia or Alzheimer’s disease pathology “is reassuring because ingested mercury accumulates in the body over decades, and brain levels hence result from exposure, which likely precedes any Alzheimer’s disease or dementia development,” said Edeltraut Kröger, PhD, and Robert Laforce Jr, MD, PhD, of Université Laval in Quebec City, Canada, in an accompanying editorial.
“Patients and their families may be hopeful that interventions such as seafood consumption may help reduce clinical manifestations of Alzheimer’s disease or dementia, and the report by Morris et al provides reassurance that seafood contamination with mercury is not related to increased brain pathology,” they said. “Eating fatty fish may continue to be considered potentially beneficial against cognitive decline in at least a proportion of older adults, a strategy that now generally should not be affected by concerns about mercury contamination in fish.”
Drs. Kröger and Laforce noted that large randomized clinical trials are needed before recommending dietary interventions, such as a Mediterranean-style diet, to improve cognitive health. In addition, relating brain pathology, including amyloid deposition, to clinical disease may be more complicated than previously thought. “Ultimately, proof of the brain pathological concepts of Alzheimer’s disease and other dementias will be based on data from clinical trials confirming that preventive or therapeutic interventions on these elements of brain neuropathology will reduce clinical manifestations of Alzheimer’s disease and other dementias,” they said.
The study cohort was very old and largely non-Hispanic white, and the findings might not apply to younger adults or other racial or ethnic groups, the investigators said. The results also cannot be generalized to populations with higher seafood consumption or mercury exposure.
Suggested Reading
Kröger E, Laforce R Jr. Fish consumption, brain mercury, and neuropathology in patients with Alzheimer disease and dementia. JAMA. 2016;315(5):465-466.
Morris MC, Brockman J, Schneider JA, et al. Association of seafood consumption, brain mercury level, and APOE ε4 status with brain neuropathology in older adults. JAMA. 2016;315(5):489-497.
Suggested Reading
Kröger E, Laforce R Jr. Fish consumption, brain mercury, and neuropathology in patients with Alzheimer disease and dementia. JAMA. 2016;315(5):465-466.
Morris MC, Brockman J, Schneider JA, et al. Association of seafood consumption, brain mercury level, and APOE ε4 status with brain neuropathology in older adults. JAMA. 2016;315(5):489-497.
Natalizumab May Increase Risk of JCV Seroconversion
Patients with multiple sclerosis (MS) who receive natalizumab may have as much as a 10-fold greater risk of seroconversion to John Cunningham virus (JCV)-positive status, according to a study published online January 27 in Neurology Neuroimmunology & Neuroinflammation.
“An increase in the levels of anti-JCV antibodies could signify an increased risk of progressive multifocal leukoencephalopathy (PML),” said the study’s senior author, Heinz Wiendl, MD, Professor of Neurology at the University of Münster in Germany.
Dr. Wiendl and colleagues performed a longitudinal analysis of 525 German patients with MS and 711 French patients with MS, all of whom were treated with natalizumab, to assess whether the therapy influenced JCV seroconversion or JCV index value (ie, the level of anti-JCV antibody titers). An independent contractor processed and analyzed sera samples with the second-generation enzyme-linked immunosorbent assay kit STRATIFY JCV DxSelect.
Seroconversion and Increasing Index Value
Of the 525 German patients, 296 (56.4%) were JCV-negative throughout the observation period, and 171 were JCV-positive (32.6%). Forty-three patients changed from being JCV-negative to JCV-positive (8.2%), and 15 patients changed from being JCV-positive to JCV-negative (2.9%). When the authors used JCV serostatus to determine seroconversion, the longitudinal assessment started out with 339 initially JCV-negative patients. The serostatus of 43 of these initially JCV-negative patients changed to JCV-positive, which is a rate of 12.7% in 14.8 months (10.3% per year).
Of the 711 French patients, 243 initially were JCV-negative. The serostatus of 20 (8.2%) of these latter patients changed to JCV-positive in their first year of treatment, and 21 (8.6%) of the patients became JCV-positive in their second year of treatment. In all, the serostatus of 41 of 243 patients (16.9%) changed to JCV-positive in the first two years of natalizumab treatment (8.5% per year).
In addition, JCV index values changed in 525 patients during the observation period. The proportion of patients with an index value less than 0.4 was reduced by 20 patients (ie, from 65.1% to 61.3%), and the group of patients with low risk (ie, values between 0.4 and 0.9) was reduced by one patient to 7.8%. The patient groups with medium (ie, 0.9–1.5) and high risk (ie, greater than 1.5) increased by seven patients from 4.6% to 5.9% and by 14 patients from 22.3% to 25%, respectively.Furthermore, 161 of 201 JCV-positive patients (80%) had stable JCV index values over time. The remaining 40 patients (20%) had fluctuations of more than 30% in 14.8 months. Six of these patients (3%) had decreasing index values, and 34 (17%) had increasing index values (mean, 200.8%). Overall, the index value of all JCV-positive patients increased by an average of 15.9% in 14.8 months (12.9% per year).
Increased Index May Not Indicate Imminent PML
The high rate of seroconversion that the investigators observed “clearly supports the facilitation by treatment with natalizumab,” said Dr. Wiendl. “Our observed seroconversion of 8% to 10% per year and the rise in seroprevalence of 5% to 6% in 15 to 24 months is at least eight to 10 times as much as would be expected by age.” The study results imply that not every patient with MS is susceptible to JCV seroconversion by treatment, but natalizumab might facilitate seroconversion in patients who are susceptible.
No research has examined the influence of other MS treatments on JCV index values, and the investigators thus cannot be certain that natalizumab treatment caused the increase in index values observed in the study. But because there was no correlation between age and index value in JCV-positive patients, it is valid to speculate that natalizumab treatment induces rising JCV index values.
“If the hypothesis that treatment with natalizumab is associated with enhanced JCV seroconversion and higher index values is proven, it would also be important to determine whether cessation of natalizumab therapy (or perhaps prolonged infusion intervals) could lead to lower JCV index values as well,” Dr. Wiendl continued. The association “does not diminish [natalizumab’s] clinical efficacy, but calls for more elaborate strategies for PML risk stratification according to current scientific developments, also regarding patients with prior use of immunosuppressants, where the JCV index is not helpful.
“It is important that people with MS taking natalizumab speak with their doctor before making any changes to their treatment,” Dr. Wiendl added. “Still, this study shows anti-JCV antibodies may serve as a useful biomarker…. The results of this study underscore the need for frequent monitoring of anti-JCV antibodies in people who are being treated with natalizumab for MS.”
JCV serology, however, should not be the only PML risk biomarker to stratify patients treated with natalizumab, said Dr. Wiendl. Neurologists should explore and potentially apply additional biomarkers such as CD62L in peripheral blood or IgM bands in CSF. Together, all of these biomarkers may provide more accurate information about patients’ PML risk and help reduce the incidence of PML.
The investigators’ data extend earlier paired, longitudinal studies in various countries of patients treated with natalizumab who had similarly high rates of conversion and a rise in titers, said Adil Javed, MD, PhD, Associate Professor of Neurology, and Anthony T. Reder, MD, Professor of Neurology, both at the University of Chicago, in an accompanying editorial. Although the JCV index appears to be a valid serum marker of risk for PML, “risk is relative,” they said. “Despite a higher JCV replication state, an increase in JCV-antibody index does not necessarily mean that PML infection is imminent…. Schwab et al extend growing observations that JCV-antibody index values need to be monitored and that seroconversion or rising JCV-antibody titers alter the risk of PML in patients treated with natalizumab.”
—Erik Greb
Suggested Reading
Schwab N, Schneider-Hohendorf T, Pignolet B, et al. Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):e195.
Javed A, Reder AT. Rising JCV-Ab index during natalizumab therapy for MS: Inauspicious for a highly efficacious drug. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):e199.
Patients with multiple sclerosis (MS) who receive natalizumab may have as much as a 10-fold greater risk of seroconversion to John Cunningham virus (JCV)-positive status, according to a study published online January 27 in Neurology Neuroimmunology & Neuroinflammation.
“An increase in the levels of anti-JCV antibodies could signify an increased risk of progressive multifocal leukoencephalopathy (PML),” said the study’s senior author, Heinz Wiendl, MD, Professor of Neurology at the University of Münster in Germany.
Dr. Wiendl and colleagues performed a longitudinal analysis of 525 German patients with MS and 711 French patients with MS, all of whom were treated with natalizumab, to assess whether the therapy influenced JCV seroconversion or JCV index value (ie, the level of anti-JCV antibody titers). An independent contractor processed and analyzed sera samples with the second-generation enzyme-linked immunosorbent assay kit STRATIFY JCV DxSelect.
Seroconversion and Increasing Index Value
Of the 525 German patients, 296 (56.4%) were JCV-negative throughout the observation period, and 171 were JCV-positive (32.6%). Forty-three patients changed from being JCV-negative to JCV-positive (8.2%), and 15 patients changed from being JCV-positive to JCV-negative (2.9%). When the authors used JCV serostatus to determine seroconversion, the longitudinal assessment started out with 339 initially JCV-negative patients. The serostatus of 43 of these initially JCV-negative patients changed to JCV-positive, which is a rate of 12.7% in 14.8 months (10.3% per year).
Of the 711 French patients, 243 initially were JCV-negative. The serostatus of 20 (8.2%) of these latter patients changed to JCV-positive in their first year of treatment, and 21 (8.6%) of the patients became JCV-positive in their second year of treatment. In all, the serostatus of 41 of 243 patients (16.9%) changed to JCV-positive in the first two years of natalizumab treatment (8.5% per year).
In addition, JCV index values changed in 525 patients during the observation period. The proportion of patients with an index value less than 0.4 was reduced by 20 patients (ie, from 65.1% to 61.3%), and the group of patients with low risk (ie, values between 0.4 and 0.9) was reduced by one patient to 7.8%. The patient groups with medium (ie, 0.9–1.5) and high risk (ie, greater than 1.5) increased by seven patients from 4.6% to 5.9% and by 14 patients from 22.3% to 25%, respectively.Furthermore, 161 of 201 JCV-positive patients (80%) had stable JCV index values over time. The remaining 40 patients (20%) had fluctuations of more than 30% in 14.8 months. Six of these patients (3%) had decreasing index values, and 34 (17%) had increasing index values (mean, 200.8%). Overall, the index value of all JCV-positive patients increased by an average of 15.9% in 14.8 months (12.9% per year).
Increased Index May Not Indicate Imminent PML
The high rate of seroconversion that the investigators observed “clearly supports the facilitation by treatment with natalizumab,” said Dr. Wiendl. “Our observed seroconversion of 8% to 10% per year and the rise in seroprevalence of 5% to 6% in 15 to 24 months is at least eight to 10 times as much as would be expected by age.” The study results imply that not every patient with MS is susceptible to JCV seroconversion by treatment, but natalizumab might facilitate seroconversion in patients who are susceptible.
No research has examined the influence of other MS treatments on JCV index values, and the investigators thus cannot be certain that natalizumab treatment caused the increase in index values observed in the study. But because there was no correlation between age and index value in JCV-positive patients, it is valid to speculate that natalizumab treatment induces rising JCV index values.
“If the hypothesis that treatment with natalizumab is associated with enhanced JCV seroconversion and higher index values is proven, it would also be important to determine whether cessation of natalizumab therapy (or perhaps prolonged infusion intervals) could lead to lower JCV index values as well,” Dr. Wiendl continued. The association “does not diminish [natalizumab’s] clinical efficacy, but calls for more elaborate strategies for PML risk stratification according to current scientific developments, also regarding patients with prior use of immunosuppressants, where the JCV index is not helpful.
“It is important that people with MS taking natalizumab speak with their doctor before making any changes to their treatment,” Dr. Wiendl added. “Still, this study shows anti-JCV antibodies may serve as a useful biomarker…. The results of this study underscore the need for frequent monitoring of anti-JCV antibodies in people who are being treated with natalizumab for MS.”
JCV serology, however, should not be the only PML risk biomarker to stratify patients treated with natalizumab, said Dr. Wiendl. Neurologists should explore and potentially apply additional biomarkers such as CD62L in peripheral blood or IgM bands in CSF. Together, all of these biomarkers may provide more accurate information about patients’ PML risk and help reduce the incidence of PML.
The investigators’ data extend earlier paired, longitudinal studies in various countries of patients treated with natalizumab who had similarly high rates of conversion and a rise in titers, said Adil Javed, MD, PhD, Associate Professor of Neurology, and Anthony T. Reder, MD, Professor of Neurology, both at the University of Chicago, in an accompanying editorial. Although the JCV index appears to be a valid serum marker of risk for PML, “risk is relative,” they said. “Despite a higher JCV replication state, an increase in JCV-antibody index does not necessarily mean that PML infection is imminent…. Schwab et al extend growing observations that JCV-antibody index values need to be monitored and that seroconversion or rising JCV-antibody titers alter the risk of PML in patients treated with natalizumab.”
—Erik Greb
Patients with multiple sclerosis (MS) who receive natalizumab may have as much as a 10-fold greater risk of seroconversion to John Cunningham virus (JCV)-positive status, according to a study published online January 27 in Neurology Neuroimmunology & Neuroinflammation.
“An increase in the levels of anti-JCV antibodies could signify an increased risk of progressive multifocal leukoencephalopathy (PML),” said the study’s senior author, Heinz Wiendl, MD, Professor of Neurology at the University of Münster in Germany.
Dr. Wiendl and colleagues performed a longitudinal analysis of 525 German patients with MS and 711 French patients with MS, all of whom were treated with natalizumab, to assess whether the therapy influenced JCV seroconversion or JCV index value (ie, the level of anti-JCV antibody titers). An independent contractor processed and analyzed sera samples with the second-generation enzyme-linked immunosorbent assay kit STRATIFY JCV DxSelect.
Seroconversion and Increasing Index Value
Of the 525 German patients, 296 (56.4%) were JCV-negative throughout the observation period, and 171 were JCV-positive (32.6%). Forty-three patients changed from being JCV-negative to JCV-positive (8.2%), and 15 patients changed from being JCV-positive to JCV-negative (2.9%). When the authors used JCV serostatus to determine seroconversion, the longitudinal assessment started out with 339 initially JCV-negative patients. The serostatus of 43 of these initially JCV-negative patients changed to JCV-positive, which is a rate of 12.7% in 14.8 months (10.3% per year).
Of the 711 French patients, 243 initially were JCV-negative. The serostatus of 20 (8.2%) of these latter patients changed to JCV-positive in their first year of treatment, and 21 (8.6%) of the patients became JCV-positive in their second year of treatment. In all, the serostatus of 41 of 243 patients (16.9%) changed to JCV-positive in the first two years of natalizumab treatment (8.5% per year).
In addition, JCV index values changed in 525 patients during the observation period. The proportion of patients with an index value less than 0.4 was reduced by 20 patients (ie, from 65.1% to 61.3%), and the group of patients with low risk (ie, values between 0.4 and 0.9) was reduced by one patient to 7.8%. The patient groups with medium (ie, 0.9–1.5) and high risk (ie, greater than 1.5) increased by seven patients from 4.6% to 5.9% and by 14 patients from 22.3% to 25%, respectively.Furthermore, 161 of 201 JCV-positive patients (80%) had stable JCV index values over time. The remaining 40 patients (20%) had fluctuations of more than 30% in 14.8 months. Six of these patients (3%) had decreasing index values, and 34 (17%) had increasing index values (mean, 200.8%). Overall, the index value of all JCV-positive patients increased by an average of 15.9% in 14.8 months (12.9% per year).
Increased Index May Not Indicate Imminent PML
The high rate of seroconversion that the investigators observed “clearly supports the facilitation by treatment with natalizumab,” said Dr. Wiendl. “Our observed seroconversion of 8% to 10% per year and the rise in seroprevalence of 5% to 6% in 15 to 24 months is at least eight to 10 times as much as would be expected by age.” The study results imply that not every patient with MS is susceptible to JCV seroconversion by treatment, but natalizumab might facilitate seroconversion in patients who are susceptible.
No research has examined the influence of other MS treatments on JCV index values, and the investigators thus cannot be certain that natalizumab treatment caused the increase in index values observed in the study. But because there was no correlation between age and index value in JCV-positive patients, it is valid to speculate that natalizumab treatment induces rising JCV index values.
“If the hypothesis that treatment with natalizumab is associated with enhanced JCV seroconversion and higher index values is proven, it would also be important to determine whether cessation of natalizumab therapy (or perhaps prolonged infusion intervals) could lead to lower JCV index values as well,” Dr. Wiendl continued. The association “does not diminish [natalizumab’s] clinical efficacy, but calls for more elaborate strategies for PML risk stratification according to current scientific developments, also regarding patients with prior use of immunosuppressants, where the JCV index is not helpful.
“It is important that people with MS taking natalizumab speak with their doctor before making any changes to their treatment,” Dr. Wiendl added. “Still, this study shows anti-JCV antibodies may serve as a useful biomarker…. The results of this study underscore the need for frequent monitoring of anti-JCV antibodies in people who are being treated with natalizumab for MS.”
JCV serology, however, should not be the only PML risk biomarker to stratify patients treated with natalizumab, said Dr. Wiendl. Neurologists should explore and potentially apply additional biomarkers such as CD62L in peripheral blood or IgM bands in CSF. Together, all of these biomarkers may provide more accurate information about patients’ PML risk and help reduce the incidence of PML.
The investigators’ data extend earlier paired, longitudinal studies in various countries of patients treated with natalizumab who had similarly high rates of conversion and a rise in titers, said Adil Javed, MD, PhD, Associate Professor of Neurology, and Anthony T. Reder, MD, Professor of Neurology, both at the University of Chicago, in an accompanying editorial. Although the JCV index appears to be a valid serum marker of risk for PML, “risk is relative,” they said. “Despite a higher JCV replication state, an increase in JCV-antibody index does not necessarily mean that PML infection is imminent…. Schwab et al extend growing observations that JCV-antibody index values need to be monitored and that seroconversion or rising JCV-antibody titers alter the risk of PML in patients treated with natalizumab.”
—Erik Greb
Suggested Reading
Schwab N, Schneider-Hohendorf T, Pignolet B, et al. Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):e195.
Javed A, Reder AT. Rising JCV-Ab index during natalizumab therapy for MS: Inauspicious for a highly efficacious drug. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):e199.
Suggested Reading
Schwab N, Schneider-Hohendorf T, Pignolet B, et al. Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):e195.
Javed A, Reder AT. Rising JCV-Ab index during natalizumab therapy for MS: Inauspicious for a highly efficacious drug. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):e199.
Slower Resolution of Emotional Distress May Contribute to Hyperarousal
Restless REM sleep may interfere with the overnight resolution of emotional distress, which in turn may promote the development of chronic hyperarousal, according to research published online ahead of print February 8 in Proceedings of the National Academy of Sciences. These findings suggest that REM sleep's role in regulating emotions is clinically relevant in insomnia and other disorders.
Prior research has identified hyperarousal as a key factor in the cause of chronic insomnia, but the mechanisms underlying hyperarousal are not well understood. "Given the role of REM sleep in emotion regulation, we hypothesized that restless REM sleep could interfere with the overnight resolution of emotional distress, thus contributing to accumulation of arousal," said Rick Wassing, MSc, a doctoral student at the Netherlands Institute for Neuroscience in Amsterdam, and colleagues.
To test their hypothesis, the investigators had 1,199 participants in the Netherlands Sleep Registry complete online questionnaires on insomnia severity, hyperarousal, self-conscious emotional distress, and thoughtlike rather than dreamlike nocturnal mentation. The investigators had assessed 32 people with polysomnography to validate thoughtlike nocturnal mentation as a specific proxy for restless REM sleep (ie, REM sleep with a high number of phasic events, including arousals and eye movements). Participants had an average age of 52.1, and approximately 74% of participants were female.
Using multiple regression analyses and structural equation modeling, the investigators found that insomnia severity was associated with how often emotional distress lasted overnight, but not with how often distress resolved within a day. Insomnia severity also was associated with nocturnal mentation and hyperarousal.
Distress that lasted overnight was associated with higher hyperarousal ratings, whereas short-lasting distress was not associated with hyperarousal. Adjusting for major life events and the possible presence of other disorders only had a marginal effect on the results.
"Most importantly, the present findings show that the overnight resolution of distress from shame is compromised in people with insomnia; that this deficit contributes to hyperarousal; and that this deficit seems, in part, to be due to a process that is reflected in a high density of arousals and eye movements in REM sleep and concomitant thoughtlike nocturnal mentation," the investigators said.
—Jake Remaly
Suggested Reading
Wassing R, Benjamins JS, Dekker K, et al. Slow dissolving of emotional distress contributes to hyperarousal. Proc Natl Acad Sci U S A. 2016 Feb 8 [Epub ahead of print].
Restless REM sleep may interfere with the overnight resolution of emotional distress, which in turn may promote the development of chronic hyperarousal, according to research published online ahead of print February 8 in Proceedings of the National Academy of Sciences. These findings suggest that REM sleep's role in regulating emotions is clinically relevant in insomnia and other disorders.
Prior research has identified hyperarousal as a key factor in the cause of chronic insomnia, but the mechanisms underlying hyperarousal are not well understood. "Given the role of REM sleep in emotion regulation, we hypothesized that restless REM sleep could interfere with the overnight resolution of emotional distress, thus contributing to accumulation of arousal," said Rick Wassing, MSc, a doctoral student at the Netherlands Institute for Neuroscience in Amsterdam, and colleagues.
To test their hypothesis, the investigators had 1,199 participants in the Netherlands Sleep Registry complete online questionnaires on insomnia severity, hyperarousal, self-conscious emotional distress, and thoughtlike rather than dreamlike nocturnal mentation. The investigators had assessed 32 people with polysomnography to validate thoughtlike nocturnal mentation as a specific proxy for restless REM sleep (ie, REM sleep with a high number of phasic events, including arousals and eye movements). Participants had an average age of 52.1, and approximately 74% of participants were female.
Using multiple regression analyses and structural equation modeling, the investigators found that insomnia severity was associated with how often emotional distress lasted overnight, but not with how often distress resolved within a day. Insomnia severity also was associated with nocturnal mentation and hyperarousal.
Distress that lasted overnight was associated with higher hyperarousal ratings, whereas short-lasting distress was not associated with hyperarousal. Adjusting for major life events and the possible presence of other disorders only had a marginal effect on the results.
"Most importantly, the present findings show that the overnight resolution of distress from shame is compromised in people with insomnia; that this deficit contributes to hyperarousal; and that this deficit seems, in part, to be due to a process that is reflected in a high density of arousals and eye movements in REM sleep and concomitant thoughtlike nocturnal mentation," the investigators said.
—Jake Remaly
Restless REM sleep may interfere with the overnight resolution of emotional distress, which in turn may promote the development of chronic hyperarousal, according to research published online ahead of print February 8 in Proceedings of the National Academy of Sciences. These findings suggest that REM sleep's role in regulating emotions is clinically relevant in insomnia and other disorders.
Prior research has identified hyperarousal as a key factor in the cause of chronic insomnia, but the mechanisms underlying hyperarousal are not well understood. "Given the role of REM sleep in emotion regulation, we hypothesized that restless REM sleep could interfere with the overnight resolution of emotional distress, thus contributing to accumulation of arousal," said Rick Wassing, MSc, a doctoral student at the Netherlands Institute for Neuroscience in Amsterdam, and colleagues.
To test their hypothesis, the investigators had 1,199 participants in the Netherlands Sleep Registry complete online questionnaires on insomnia severity, hyperarousal, self-conscious emotional distress, and thoughtlike rather than dreamlike nocturnal mentation. The investigators had assessed 32 people with polysomnography to validate thoughtlike nocturnal mentation as a specific proxy for restless REM sleep (ie, REM sleep with a high number of phasic events, including arousals and eye movements). Participants had an average age of 52.1, and approximately 74% of participants were female.
Using multiple regression analyses and structural equation modeling, the investigators found that insomnia severity was associated with how often emotional distress lasted overnight, but not with how often distress resolved within a day. Insomnia severity also was associated with nocturnal mentation and hyperarousal.
Distress that lasted overnight was associated with higher hyperarousal ratings, whereas short-lasting distress was not associated with hyperarousal. Adjusting for major life events and the possible presence of other disorders only had a marginal effect on the results.
"Most importantly, the present findings show that the overnight resolution of distress from shame is compromised in people with insomnia; that this deficit contributes to hyperarousal; and that this deficit seems, in part, to be due to a process that is reflected in a high density of arousals and eye movements in REM sleep and concomitant thoughtlike nocturnal mentation," the investigators said.
—Jake Remaly
Suggested Reading
Wassing R, Benjamins JS, Dekker K, et al. Slow dissolving of emotional distress contributes to hyperarousal. Proc Natl Acad Sci U S A. 2016 Feb 8 [Epub ahead of print].
Suggested Reading
Wassing R, Benjamins JS, Dekker K, et al. Slow dissolving of emotional distress contributes to hyperarousal. Proc Natl Acad Sci U S A. 2016 Feb 8 [Epub ahead of print].
Effects of Low-Literacy Asthma Action Plans on Provider Counseling
Clinical question: Can physician counseling for asthma care be improved by using low-literacy asthma action plans?
Background: Although asthma action plans are recommended for all children with asthma and have been associated with improved medication adherence, written asthma action plans are given to fewer than half of patients with asthma. Children with asthma whose parents have low health literacy have worse asthma-related outcomes; most asthma action plans do not use principles of health literacy. Researchers sought to investigate if asthma counseling was improved when providers were given a low-literacy asthma action plan versus a standard plan to structure their counseling.
Study design: Randomized controlled trial.
Setting: Two large, academic medical centers.
Synopsis: The study enrolled 126 physicians, of which 119 were randomized, with 61 counseling based on the low-literacy asthma action plan and 58 counseling based on a standard asthma action plan. There were no significant differences between the two groups of physicians in terms of age, gender, frequency in providing asthma care, confidence in asthma counseling, or training category (resident, fellow, attending).
These physicians counseled research assistants acting in the role of parents of children with moderate persistent asthma. The children were on a regimen of daily orally inhaled fluticasone and montelukast by mouth and as-needed albuterol. The low-literacy plan used photographs of medications, pictograms, and colors to delineate asthma severity and was prepopulated with the patient’s regimen. The standard plan was from the American Academy of Allergy, Asthma & Immunology (AAAAI); it required the physician to write in the names and doses of the patient’s medications and had no photos or pictograms. Counseling sessions were recorded and coded for content.
Using health literacy principles, the authors valued plain-language descriptions (e.g., “ribs show when breathing”) over jargon (e.g., “respiratory distress”) and specific times (e.g., “morning and night”) over times-per-day dosing (e.g., “two times a day”).
Physicians using the low-literacy plan were much more likely to use specific time of day rather than doses per day (odds ratio = 27.5; 95% CI, 6.1–123.4), much more likely to mention spacers (odds ratio = 6; 95% CI, 2.8–15), and much more likely to use plain-language descriptors of respiratory distress (odds ratio = 33; 95% CI, 7.4–147.5). These differences were present regardless of physicians’ stated comfort with asthma counseling or experience level. There was no significant difference in duration of counseling between the two plans. Physicians stated a preference for the low-literacy plan.
Bottom line: Use of low-literacy asthma action plans improves the quality of physician counseling for asthma.
Citation: Yin HS, Gupta RS, Tomopoulos S, et al. A low-literacy asthma action plan to improve provider asthma counseling: a randomized study. Pediatrics. 2016;137(1):1-11. doi:10.1542/peds.2015-0468.
Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and assistant professor of pediatrics at Thomas Jefferson Medical College in Philadelphia.
Clinical question: Can physician counseling for asthma care be improved by using low-literacy asthma action plans?
Background: Although asthma action plans are recommended for all children with asthma and have been associated with improved medication adherence, written asthma action plans are given to fewer than half of patients with asthma. Children with asthma whose parents have low health literacy have worse asthma-related outcomes; most asthma action plans do not use principles of health literacy. Researchers sought to investigate if asthma counseling was improved when providers were given a low-literacy asthma action plan versus a standard plan to structure their counseling.
Study design: Randomized controlled trial.
Setting: Two large, academic medical centers.
Synopsis: The study enrolled 126 physicians, of which 119 were randomized, with 61 counseling based on the low-literacy asthma action plan and 58 counseling based on a standard asthma action plan. There were no significant differences between the two groups of physicians in terms of age, gender, frequency in providing asthma care, confidence in asthma counseling, or training category (resident, fellow, attending).
These physicians counseled research assistants acting in the role of parents of children with moderate persistent asthma. The children were on a regimen of daily orally inhaled fluticasone and montelukast by mouth and as-needed albuterol. The low-literacy plan used photographs of medications, pictograms, and colors to delineate asthma severity and was prepopulated with the patient’s regimen. The standard plan was from the American Academy of Allergy, Asthma & Immunology (AAAAI); it required the physician to write in the names and doses of the patient’s medications and had no photos or pictograms. Counseling sessions were recorded and coded for content.
Using health literacy principles, the authors valued plain-language descriptions (e.g., “ribs show when breathing”) over jargon (e.g., “respiratory distress”) and specific times (e.g., “morning and night”) over times-per-day dosing (e.g., “two times a day”).
Physicians using the low-literacy plan were much more likely to use specific time of day rather than doses per day (odds ratio = 27.5; 95% CI, 6.1–123.4), much more likely to mention spacers (odds ratio = 6; 95% CI, 2.8–15), and much more likely to use plain-language descriptors of respiratory distress (odds ratio = 33; 95% CI, 7.4–147.5). These differences were present regardless of physicians’ stated comfort with asthma counseling or experience level. There was no significant difference in duration of counseling between the two plans. Physicians stated a preference for the low-literacy plan.
Bottom line: Use of low-literacy asthma action plans improves the quality of physician counseling for asthma.
Citation: Yin HS, Gupta RS, Tomopoulos S, et al. A low-literacy asthma action plan to improve provider asthma counseling: a randomized study. Pediatrics. 2016;137(1):1-11. doi:10.1542/peds.2015-0468.
Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and assistant professor of pediatrics at Thomas Jefferson Medical College in Philadelphia.
Clinical question: Can physician counseling for asthma care be improved by using low-literacy asthma action plans?
Background: Although asthma action plans are recommended for all children with asthma and have been associated with improved medication adherence, written asthma action plans are given to fewer than half of patients with asthma. Children with asthma whose parents have low health literacy have worse asthma-related outcomes; most asthma action plans do not use principles of health literacy. Researchers sought to investigate if asthma counseling was improved when providers were given a low-literacy asthma action plan versus a standard plan to structure their counseling.
Study design: Randomized controlled trial.
Setting: Two large, academic medical centers.
Synopsis: The study enrolled 126 physicians, of which 119 were randomized, with 61 counseling based on the low-literacy asthma action plan and 58 counseling based on a standard asthma action plan. There were no significant differences between the two groups of physicians in terms of age, gender, frequency in providing asthma care, confidence in asthma counseling, or training category (resident, fellow, attending).
These physicians counseled research assistants acting in the role of parents of children with moderate persistent asthma. The children were on a regimen of daily orally inhaled fluticasone and montelukast by mouth and as-needed albuterol. The low-literacy plan used photographs of medications, pictograms, and colors to delineate asthma severity and was prepopulated with the patient’s regimen. The standard plan was from the American Academy of Allergy, Asthma & Immunology (AAAAI); it required the physician to write in the names and doses of the patient’s medications and had no photos or pictograms. Counseling sessions were recorded and coded for content.
Using health literacy principles, the authors valued plain-language descriptions (e.g., “ribs show when breathing”) over jargon (e.g., “respiratory distress”) and specific times (e.g., “morning and night”) over times-per-day dosing (e.g., “two times a day”).
Physicians using the low-literacy plan were much more likely to use specific time of day rather than doses per day (odds ratio = 27.5; 95% CI, 6.1–123.4), much more likely to mention spacers (odds ratio = 6; 95% CI, 2.8–15), and much more likely to use plain-language descriptors of respiratory distress (odds ratio = 33; 95% CI, 7.4–147.5). These differences were present regardless of physicians’ stated comfort with asthma counseling or experience level. There was no significant difference in duration of counseling between the two plans. Physicians stated a preference for the low-literacy plan.
Bottom line: Use of low-literacy asthma action plans improves the quality of physician counseling for asthma.
Citation: Yin HS, Gupta RS, Tomopoulos S, et al. A low-literacy asthma action plan to improve provider asthma counseling: a randomized study. Pediatrics. 2016;137(1):1-11. doi:10.1542/peds.2015-0468.
Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and assistant professor of pediatrics at Thomas Jefferson Medical College in Philadelphia.
Electronic Screen Exposure Is Associated With Migraine in Young Adults
Too much time in front of electronic screens can increase the risk of headaches and migraine in young adults, according to research published online ahead of print December 2, 2015, in Cephalalgia.
Previous studies have observed associations between screen time exposure and headaches in children between ages 10 and 12 and adolescents. Data also have found an association between screen time exposure and low-back and shoulder pain in adolescents. “This [information] had led to speculation that the high amount of screen time exposure among students of higher education institutions may be correlated with the high prevalence of headache and migraine observed in this population,” said Ilaria Montagni, PhD, a research fellow at the University of Bordeaux in Talence, France.
Dr. Montagni and her coinvestigators studied 4,927 individuals in France, all of whom were age 18 or older and part of the Internet-based Students Health Research Enterprise (i-Share) project cohort, which is an ongoing, prospective, population-based study of students at French-speaking universities and institutions of higher education. The mean age of the students was 20.8, and 75.5% were female.
Subjects completed self-reported surveys on the average amount of time they spend in front of screens during the following five activities: computer or tablet work, playing video games on a computer or tablet, Internet surfing on a computer or tablet, watching videos on a computer or tablet, and using a smartphone. All questions were scored using a five-point scale. A score of 0 indicated never, 1 indicated less than 30 minutes, 2 indicated 30 minutes to two hours, 3 indicated four to eight hours, and 5 indicated eight hours or more. Scores from the surveys were divided into quartiles of very low, low, high, and very high screen-time exposure.
Surveys also asked if participants had experienced any headaches that had lasted several hours in the previous 12 months. Participants who answered negatively were classified as “no headache,” while those who answered positively were asked a series of follow-up questions related to symptom type and severity, sensitivity to light or sound, nausea, vomiting, and disruption of daily routines. To establish a classification of migraine, the investigators used the “probable migraine” category of the International Classification of Headache Disorders, third edition. With these data, the investigators used multinomial logistic regression models to calculate odds ratios of any relationship between screen time exposure and the presence and severity of headaches.
Of the 4,927 participants, 2,773 (56.3%) reported no headaches. In all, 710 (14.4%) participants reported a nonmigraine headache, 791 (16.1%) reported migraine without aura, and 653 (13.3%) reported migraine with aura. In comparisons against very low screen time exposure, very high exposure increased the likelihood of having migraine by 37%, which resulted in a statistically significant 50% greater odds for migraine without aura, but not for migraine with aura.
“Students reporting very high screen time exposure were more likely to be male, to be older, to have higher BMI, and to consume cannabis [and] were also more likely to report nonmigraine headache or migraine,” the authors noted. Furthermore, higher exposure to screens was a significant indicator of recurrent headaches in adolescent males, and the same indicator was seen in adolescent females who spent more time on the computer and in front of the TV.
—Deepak Chitnis
Suggested Reading
Montagni I, Guichard E, Carpenet C, et al. Screen time exposure and reporting of headaches in young adults: A cross-sectional study. Cephalalgia. 2015 Dec 2 [Epub ahead of print].
Too much time in front of electronic screens can increase the risk of headaches and migraine in young adults, according to research published online ahead of print December 2, 2015, in Cephalalgia.
Previous studies have observed associations between screen time exposure and headaches in children between ages 10 and 12 and adolescents. Data also have found an association between screen time exposure and low-back and shoulder pain in adolescents. “This [information] had led to speculation that the high amount of screen time exposure among students of higher education institutions may be correlated with the high prevalence of headache and migraine observed in this population,” said Ilaria Montagni, PhD, a research fellow at the University of Bordeaux in Talence, France.
Dr. Montagni and her coinvestigators studied 4,927 individuals in France, all of whom were age 18 or older and part of the Internet-based Students Health Research Enterprise (i-Share) project cohort, which is an ongoing, prospective, population-based study of students at French-speaking universities and institutions of higher education. The mean age of the students was 20.8, and 75.5% were female.
Subjects completed self-reported surveys on the average amount of time they spend in front of screens during the following five activities: computer or tablet work, playing video games on a computer or tablet, Internet surfing on a computer or tablet, watching videos on a computer or tablet, and using a smartphone. All questions were scored using a five-point scale. A score of 0 indicated never, 1 indicated less than 30 minutes, 2 indicated 30 minutes to two hours, 3 indicated four to eight hours, and 5 indicated eight hours or more. Scores from the surveys were divided into quartiles of very low, low, high, and very high screen-time exposure.
Surveys also asked if participants had experienced any headaches that had lasted several hours in the previous 12 months. Participants who answered negatively were classified as “no headache,” while those who answered positively were asked a series of follow-up questions related to symptom type and severity, sensitivity to light or sound, nausea, vomiting, and disruption of daily routines. To establish a classification of migraine, the investigators used the “probable migraine” category of the International Classification of Headache Disorders, third edition. With these data, the investigators used multinomial logistic regression models to calculate odds ratios of any relationship between screen time exposure and the presence and severity of headaches.
Of the 4,927 participants, 2,773 (56.3%) reported no headaches. In all, 710 (14.4%) participants reported a nonmigraine headache, 791 (16.1%) reported migraine without aura, and 653 (13.3%) reported migraine with aura. In comparisons against very low screen time exposure, very high exposure increased the likelihood of having migraine by 37%, which resulted in a statistically significant 50% greater odds for migraine without aura, but not for migraine with aura.
“Students reporting very high screen time exposure were more likely to be male, to be older, to have higher BMI, and to consume cannabis [and] were also more likely to report nonmigraine headache or migraine,” the authors noted. Furthermore, higher exposure to screens was a significant indicator of recurrent headaches in adolescent males, and the same indicator was seen in adolescent females who spent more time on the computer and in front of the TV.
—Deepak Chitnis
Too much time in front of electronic screens can increase the risk of headaches and migraine in young adults, according to research published online ahead of print December 2, 2015, in Cephalalgia.
Previous studies have observed associations between screen time exposure and headaches in children between ages 10 and 12 and adolescents. Data also have found an association between screen time exposure and low-back and shoulder pain in adolescents. “This [information] had led to speculation that the high amount of screen time exposure among students of higher education institutions may be correlated with the high prevalence of headache and migraine observed in this population,” said Ilaria Montagni, PhD, a research fellow at the University of Bordeaux in Talence, France.
Dr. Montagni and her coinvestigators studied 4,927 individuals in France, all of whom were age 18 or older and part of the Internet-based Students Health Research Enterprise (i-Share) project cohort, which is an ongoing, prospective, population-based study of students at French-speaking universities and institutions of higher education. The mean age of the students was 20.8, and 75.5% were female.
Subjects completed self-reported surveys on the average amount of time they spend in front of screens during the following five activities: computer or tablet work, playing video games on a computer or tablet, Internet surfing on a computer or tablet, watching videos on a computer or tablet, and using a smartphone. All questions were scored using a five-point scale. A score of 0 indicated never, 1 indicated less than 30 minutes, 2 indicated 30 minutes to two hours, 3 indicated four to eight hours, and 5 indicated eight hours or more. Scores from the surveys were divided into quartiles of very low, low, high, and very high screen-time exposure.
Surveys also asked if participants had experienced any headaches that had lasted several hours in the previous 12 months. Participants who answered negatively were classified as “no headache,” while those who answered positively were asked a series of follow-up questions related to symptom type and severity, sensitivity to light or sound, nausea, vomiting, and disruption of daily routines. To establish a classification of migraine, the investigators used the “probable migraine” category of the International Classification of Headache Disorders, third edition. With these data, the investigators used multinomial logistic regression models to calculate odds ratios of any relationship between screen time exposure and the presence and severity of headaches.
Of the 4,927 participants, 2,773 (56.3%) reported no headaches. In all, 710 (14.4%) participants reported a nonmigraine headache, 791 (16.1%) reported migraine without aura, and 653 (13.3%) reported migraine with aura. In comparisons against very low screen time exposure, very high exposure increased the likelihood of having migraine by 37%, which resulted in a statistically significant 50% greater odds for migraine without aura, but not for migraine with aura.
“Students reporting very high screen time exposure were more likely to be male, to be older, to have higher BMI, and to consume cannabis [and] were also more likely to report nonmigraine headache or migraine,” the authors noted. Furthermore, higher exposure to screens was a significant indicator of recurrent headaches in adolescent males, and the same indicator was seen in adolescent females who spent more time on the computer and in front of the TV.
—Deepak Chitnis
Suggested Reading
Montagni I, Guichard E, Carpenet C, et al. Screen time exposure and reporting of headaches in young adults: A cross-sectional study. Cephalalgia. 2015 Dec 2 [Epub ahead of print].
Suggested Reading
Montagni I, Guichard E, Carpenet C, et al. Screen time exposure and reporting of headaches in young adults: A cross-sectional study. Cephalalgia. 2015 Dec 2 [Epub ahead of print].
Hepatitis C May Increase Risk of Parkinson’s Disease
Hepatitis C infection may increase the risk of Parkinson’s disease, according to a nationwide population-based study published online ahead of print December 23, 2015, in Neurology. Researchers analyzed 10 years of data from the Taiwan National Health Insurance Research Database, which included 49,967 patients with viral hepatitis—35,619 with hepatitis B infection, 10,286 with hepatitis C, and 4,062 with both—and 199,868 noninfected controls.
Individuals with hepatitis C infection had a 29% greater incidence of Parkinson’s disease after adjustment for confounders such as sex, age, heart disease, stroke, and head injury. The researchers found no significant associations between hepatitis B or coinfection and Parkinson’s disease risk.
Age was the most common risk factor for Parkinson’s disease across all cohorts, and in the control group, comorbidities such as hyperlipidemia, hypertension, ischemic heart disease, diabetes, and head injury all were associated with a significant increase in the risk of Parkinson’s disease. Among individuals with hepatitis C infection, however, only ischemic heart disease and head injury remained significantly associated with Parkinson’s disease risk.
The possibility of an association between hepatitis C infection and Parkinson’s disease has emerged recently, with evidence showing that the virus is neurotropic and can replicate in the CNS, reported Hsin-Hsi Tsai, MD, a neurologist at the National Taiwan University Hospital in Taipei, and coauthors.
“Parkinsonism is rarely a described feature in patients with hepatitis C virus. However, a recent study has discovered that hepatitis C virus can induce dopaminergic neuron death, suggesting a possible association between hepatitis C virus infection and” Parkinson’s disease, said the authors.
The study also showed that the association between hepatitis C infection and Parkinson’s disease was more significant in individuals younger than 65, who had a 61% greater risk of developing the neurodegenerative disease.
“Some of the risk factors for hepatitis C virus infection, such as illicit drug use and associated behaviors, may be confounding factors in this age group,” said the authors. They pointed out, however, that in Taiwan, use of IV drugs was not known to be a risk factor for infection. Commenting on a possible mechanism for the association between hepatitis C infection and Parkinson’s disease, Dr. Tsai and associates suggested that the hepatitis C virus could be a possible viral candidate for triggering the neuroinflammation that is a characteristic feature of Parkinson’s disease.
“An earlier imaging study that involved using magnetic resonance spectroscopy to investigate the cerebral effect of hepatitis C virus showed that chronic hepatitis C virus infection was associated with elevated choline/creatinine ratios, a biomarker indicating inflammatory and infective conditions, in the basal ganglia and white matter,” they said.
—Bianca Nogrady
Suggested Reading
Tsai HH, Liou HH, Muo CH, et al. Hepatitis C virus infection as a risk factor for Parkinson disease: A nationwide cohort study. Neurology. 2015 Dec 23 [Epub ahead of print].
Hepatitis C infection may increase the risk of Parkinson’s disease, according to a nationwide population-based study published online ahead of print December 23, 2015, in Neurology. Researchers analyzed 10 years of data from the Taiwan National Health Insurance Research Database, which included 49,967 patients with viral hepatitis—35,619 with hepatitis B infection, 10,286 with hepatitis C, and 4,062 with both—and 199,868 noninfected controls.
Individuals with hepatitis C infection had a 29% greater incidence of Parkinson’s disease after adjustment for confounders such as sex, age, heart disease, stroke, and head injury. The researchers found no significant associations between hepatitis B or coinfection and Parkinson’s disease risk.
Age was the most common risk factor for Parkinson’s disease across all cohorts, and in the control group, comorbidities such as hyperlipidemia, hypertension, ischemic heart disease, diabetes, and head injury all were associated with a significant increase in the risk of Parkinson’s disease. Among individuals with hepatitis C infection, however, only ischemic heart disease and head injury remained significantly associated with Parkinson’s disease risk.
The possibility of an association between hepatitis C infection and Parkinson’s disease has emerged recently, with evidence showing that the virus is neurotropic and can replicate in the CNS, reported Hsin-Hsi Tsai, MD, a neurologist at the National Taiwan University Hospital in Taipei, and coauthors.
“Parkinsonism is rarely a described feature in patients with hepatitis C virus. However, a recent study has discovered that hepatitis C virus can induce dopaminergic neuron death, suggesting a possible association between hepatitis C virus infection and” Parkinson’s disease, said the authors.
The study also showed that the association between hepatitis C infection and Parkinson’s disease was more significant in individuals younger than 65, who had a 61% greater risk of developing the neurodegenerative disease.
“Some of the risk factors for hepatitis C virus infection, such as illicit drug use and associated behaviors, may be confounding factors in this age group,” said the authors. They pointed out, however, that in Taiwan, use of IV drugs was not known to be a risk factor for infection. Commenting on a possible mechanism for the association between hepatitis C infection and Parkinson’s disease, Dr. Tsai and associates suggested that the hepatitis C virus could be a possible viral candidate for triggering the neuroinflammation that is a characteristic feature of Parkinson’s disease.
“An earlier imaging study that involved using magnetic resonance spectroscopy to investigate the cerebral effect of hepatitis C virus showed that chronic hepatitis C virus infection was associated with elevated choline/creatinine ratios, a biomarker indicating inflammatory and infective conditions, in the basal ganglia and white matter,” they said.
—Bianca Nogrady
Hepatitis C infection may increase the risk of Parkinson’s disease, according to a nationwide population-based study published online ahead of print December 23, 2015, in Neurology. Researchers analyzed 10 years of data from the Taiwan National Health Insurance Research Database, which included 49,967 patients with viral hepatitis—35,619 with hepatitis B infection, 10,286 with hepatitis C, and 4,062 with both—and 199,868 noninfected controls.
Individuals with hepatitis C infection had a 29% greater incidence of Parkinson’s disease after adjustment for confounders such as sex, age, heart disease, stroke, and head injury. The researchers found no significant associations between hepatitis B or coinfection and Parkinson’s disease risk.
Age was the most common risk factor for Parkinson’s disease across all cohorts, and in the control group, comorbidities such as hyperlipidemia, hypertension, ischemic heart disease, diabetes, and head injury all were associated with a significant increase in the risk of Parkinson’s disease. Among individuals with hepatitis C infection, however, only ischemic heart disease and head injury remained significantly associated with Parkinson’s disease risk.
The possibility of an association between hepatitis C infection and Parkinson’s disease has emerged recently, with evidence showing that the virus is neurotropic and can replicate in the CNS, reported Hsin-Hsi Tsai, MD, a neurologist at the National Taiwan University Hospital in Taipei, and coauthors.
“Parkinsonism is rarely a described feature in patients with hepatitis C virus. However, a recent study has discovered that hepatitis C virus can induce dopaminergic neuron death, suggesting a possible association between hepatitis C virus infection and” Parkinson’s disease, said the authors.
The study also showed that the association between hepatitis C infection and Parkinson’s disease was more significant in individuals younger than 65, who had a 61% greater risk of developing the neurodegenerative disease.
“Some of the risk factors for hepatitis C virus infection, such as illicit drug use and associated behaviors, may be confounding factors in this age group,” said the authors. They pointed out, however, that in Taiwan, use of IV drugs was not known to be a risk factor for infection. Commenting on a possible mechanism for the association between hepatitis C infection and Parkinson’s disease, Dr. Tsai and associates suggested that the hepatitis C virus could be a possible viral candidate for triggering the neuroinflammation that is a characteristic feature of Parkinson’s disease.
“An earlier imaging study that involved using magnetic resonance spectroscopy to investigate the cerebral effect of hepatitis C virus showed that chronic hepatitis C virus infection was associated with elevated choline/creatinine ratios, a biomarker indicating inflammatory and infective conditions, in the basal ganglia and white matter,” they said.
—Bianca Nogrady
Suggested Reading
Tsai HH, Liou HH, Muo CH, et al. Hepatitis C virus infection as a risk factor for Parkinson disease: A nationwide cohort study. Neurology. 2015 Dec 23 [Epub ahead of print].
Suggested Reading
Tsai HH, Liou HH, Muo CH, et al. Hepatitis C virus infection as a risk factor for Parkinson disease: A nationwide cohort study. Neurology. 2015 Dec 23 [Epub ahead of print].
High Urate Concentration May Protect Men Against Parkinson’s Disease
Men with a high plasma urate concentration have a decreased risk of developing Parkinson’s disease, independent of potential risk factors such as age, smoking, and caffeine intake, according to research published online ahead of print January 13 in Neurology. Plasma urate concentration appears to have no association with risk of Parkinson’s disease among women, however. For men, urate could protect against Parkinson’s disease risk or slow the progression of preclinical Parkinson’s disease, according to the authors.
“Our findings, together with previous observations that urate can be elevated by administration of its precursor inosine, which is generally safe and tolerable, in early Parkinson’s disease, provide strong evidence supporting the design of a randomized trial of urate elevation in patients with early Parkinson’s disease or pre-Parkinson syndrome,” said Xiang Gao, MD, PhD, Director of the Nutritional Epidemiology Laboratory at Pennsylvania State University in University Park.
Dr. Gao and colleagues examined blood samples for more than 90,000 men and women who participated in the Health Professionals Follow-up Study, the Nurses’ Health Study, or the Cancer Prevention Study II Nutrition. The researchers confirmed cases of Parkinson’s disease based on a detailed questionnaire that the treating neurologist or internists completed, or through a movement disorder specialist’s review of medical records. Only patients with definite or probable Parkinson’s disease were included in the analysis. Between one and six controls were selected randomly for each case. The investigators used questionnaires to collect data on potential confounders, including age, smoking status, height, weight, chronic diseases, and consumption of caffeinated coffee and alcohol.
Dr. Gao’s group identified 388 new incident cases of Parkinson’s disease since blood collection and matched them with 1,267 controls. Higher baseline urate concentrations were associated with lower risk of Parkinson’s disease in men, but not in women. The multivariate-adjusted risk ratios of Parkinson’s disease, comparing the highest and lowest quartiles of urate, were 0.63 in men and 1.04 in women. Adjusting the data for cardiovascular factors, including history of cardiovascular disease and diabetes, did not affect the results.
The researchers pooled the results of their study with those of three previous investigations that included 325 patients with Parkinson’s disease. The pooled risk ratios comparing the highest and lowest categories of urate were 0.63 in men and 0.89 in women.
Animal and human studies suggest that urate is a neuroprotective agent, noted the authors. Their own previous research indicates that urate may slow disease progression during the preclinical stage of Parkinson’s disease.
The strengths of the current study include its prospective design, large sample size, and availability of information on covariates that may confound the potential association between serum urate and Parkinson’s disease risk, according to the authors. The study was based on a single measure of plasma urate, however, and did not account for within-person variability in urate levels. In addition, the results may be difficult to generalize because the majority of participants were Caucasian and had high educational attainment and socioeconomic status.
—Erik Greb
Suggested Reading
Gao X, O’Reilly ÉJ, Schwarzschild MA, Ascherio A. Prospective study of plasma urate and risk of Parkinson disease in men and women. Neurology. 2016 Jan 13 [Epub ahead of print].
Men with a high plasma urate concentration have a decreased risk of developing Parkinson’s disease, independent of potential risk factors such as age, smoking, and caffeine intake, according to research published online ahead of print January 13 in Neurology. Plasma urate concentration appears to have no association with risk of Parkinson’s disease among women, however. For men, urate could protect against Parkinson’s disease risk or slow the progression of preclinical Parkinson’s disease, according to the authors.
“Our findings, together with previous observations that urate can be elevated by administration of its precursor inosine, which is generally safe and tolerable, in early Parkinson’s disease, provide strong evidence supporting the design of a randomized trial of urate elevation in patients with early Parkinson’s disease or pre-Parkinson syndrome,” said Xiang Gao, MD, PhD, Director of the Nutritional Epidemiology Laboratory at Pennsylvania State University in University Park.
Dr. Gao and colleagues examined blood samples for more than 90,000 men and women who participated in the Health Professionals Follow-up Study, the Nurses’ Health Study, or the Cancer Prevention Study II Nutrition. The researchers confirmed cases of Parkinson’s disease based on a detailed questionnaire that the treating neurologist or internists completed, or through a movement disorder specialist’s review of medical records. Only patients with definite or probable Parkinson’s disease were included in the analysis. Between one and six controls were selected randomly for each case. The investigators used questionnaires to collect data on potential confounders, including age, smoking status, height, weight, chronic diseases, and consumption of caffeinated coffee and alcohol.
Dr. Gao’s group identified 388 new incident cases of Parkinson’s disease since blood collection and matched them with 1,267 controls. Higher baseline urate concentrations were associated with lower risk of Parkinson’s disease in men, but not in women. The multivariate-adjusted risk ratios of Parkinson’s disease, comparing the highest and lowest quartiles of urate, were 0.63 in men and 1.04 in women. Adjusting the data for cardiovascular factors, including history of cardiovascular disease and diabetes, did not affect the results.
The researchers pooled the results of their study with those of three previous investigations that included 325 patients with Parkinson’s disease. The pooled risk ratios comparing the highest and lowest categories of urate were 0.63 in men and 0.89 in women.
Animal and human studies suggest that urate is a neuroprotective agent, noted the authors. Their own previous research indicates that urate may slow disease progression during the preclinical stage of Parkinson’s disease.
The strengths of the current study include its prospective design, large sample size, and availability of information on covariates that may confound the potential association between serum urate and Parkinson’s disease risk, according to the authors. The study was based on a single measure of plasma urate, however, and did not account for within-person variability in urate levels. In addition, the results may be difficult to generalize because the majority of participants were Caucasian and had high educational attainment and socioeconomic status.
—Erik Greb
Men with a high plasma urate concentration have a decreased risk of developing Parkinson’s disease, independent of potential risk factors such as age, smoking, and caffeine intake, according to research published online ahead of print January 13 in Neurology. Plasma urate concentration appears to have no association with risk of Parkinson’s disease among women, however. For men, urate could protect against Parkinson’s disease risk or slow the progression of preclinical Parkinson’s disease, according to the authors.
“Our findings, together with previous observations that urate can be elevated by administration of its precursor inosine, which is generally safe and tolerable, in early Parkinson’s disease, provide strong evidence supporting the design of a randomized trial of urate elevation in patients with early Parkinson’s disease or pre-Parkinson syndrome,” said Xiang Gao, MD, PhD, Director of the Nutritional Epidemiology Laboratory at Pennsylvania State University in University Park.
Dr. Gao and colleagues examined blood samples for more than 90,000 men and women who participated in the Health Professionals Follow-up Study, the Nurses’ Health Study, or the Cancer Prevention Study II Nutrition. The researchers confirmed cases of Parkinson’s disease based on a detailed questionnaire that the treating neurologist or internists completed, or through a movement disorder specialist’s review of medical records. Only patients with definite or probable Parkinson’s disease were included in the analysis. Between one and six controls were selected randomly for each case. The investigators used questionnaires to collect data on potential confounders, including age, smoking status, height, weight, chronic diseases, and consumption of caffeinated coffee and alcohol.
Dr. Gao’s group identified 388 new incident cases of Parkinson’s disease since blood collection and matched them with 1,267 controls. Higher baseline urate concentrations were associated with lower risk of Parkinson’s disease in men, but not in women. The multivariate-adjusted risk ratios of Parkinson’s disease, comparing the highest and lowest quartiles of urate, were 0.63 in men and 1.04 in women. Adjusting the data for cardiovascular factors, including history of cardiovascular disease and diabetes, did not affect the results.
The researchers pooled the results of their study with those of three previous investigations that included 325 patients with Parkinson’s disease. The pooled risk ratios comparing the highest and lowest categories of urate were 0.63 in men and 0.89 in women.
Animal and human studies suggest that urate is a neuroprotective agent, noted the authors. Their own previous research indicates that urate may slow disease progression during the preclinical stage of Parkinson’s disease.
The strengths of the current study include its prospective design, large sample size, and availability of information on covariates that may confound the potential association between serum urate and Parkinson’s disease risk, according to the authors. The study was based on a single measure of plasma urate, however, and did not account for within-person variability in urate levels. In addition, the results may be difficult to generalize because the majority of participants were Caucasian and had high educational attainment and socioeconomic status.
—Erik Greb
Suggested Reading
Gao X, O’Reilly ÉJ, Schwarzschild MA, Ascherio A. Prospective study of plasma urate and risk of Parkinson disease in men and women. Neurology. 2016 Jan 13 [Epub ahead of print].
Suggested Reading
Gao X, O’Reilly ÉJ, Schwarzschild MA, Ascherio A. Prospective study of plasma urate and risk of Parkinson disease in men and women. Neurology. 2016 Jan 13 [Epub ahead of print].
Mortality Risk Is High After NOAC-Related Intracerebral Hemorrhage
Intracerebral hemorrhage related to non–vitamin-K antagonist oral anticoagulants (NOACs) is associated with a high risk of mortality and frequently involves hematoma expansion, according to a study published online ahead of print December 14, 2015, in JAMA Neurology.
The characteristics and natural history of acute-phase NOAC-associated ICH “are largely unknown,” and there are no prospective data concerning hematoma expansion or the effectiveness of prothrombin complex concentrate in limiting that expansion by reversing anticoagulation. Nevertheless, current recommendations suggest that clinicians consider administering prothrombin complex concentrate to this patient population, said Jan C. Purrucker, MD, neurology intern at Heidelberg University in Germany, and his associates.
To characterize the clinical and radiologic course, management, and outcome of NOAC-associated ICH in routine clinical practice, Dr. Purrucker and associates performed the ICH substudy of the Registry of Acute Stroke Under New Oral Anticoagulants (RASUNOA). This is a prospective registry involving 38 neurology departments with certified stroke units across Germany. For their substudy, the investigators examined 61 adults with a mean age of 76 (range, 46 to 97) who were taking NOACs (ie, apixaban, dabigatran etexilate, or rivaroxaban) and had moderate to severe neurologic deficit and a median hematoma volume of 10.8 mL at presentation. Thirty-five of these patients (57%) were treated with prothrombin complex concentrate.
The mortality rate was 16% (10 patients) during the acute inpatient stay and 28% (17 patients) at three months. Overall, 65% of the survivors had an unfavorable outcome. Substantial hematoma expansion, defined as a 33% or greater relative increase or a 6-mL or greater absolute increase in ICH volume, occurred in 38% of patients. “This proportion was within the range reported for vitamin-K antagonist–associated intracerebral hemorrhage (36% to 56%) and is higher, compared with that related to ICH in patients not receiving anticoagulation (12% to 26%),” said the investigators.
Larger hematoma volume at baseline (odds ratio [OR], 2.37) and intraventricular extension at baseline (OR, 8.13) strongly correlated with adverse outcomes. In contrast, prothrombin complex concentrate failed to limit lesion expansion or avert adverse outcomes. This failure might result from the fact that patients given the treatment tended to have more severe initial neurologic deficits and more unfavorable hematoma location than did those who were not given prothrombin complex concentrate. “Our study design, the limited sample size, and the potential for confounding by indication do not allow any [firm] conclusions regarding a potential association between prothrombin complex concentrate treatment and outcome,” the authors concluded.
—Mary Ann Moon
Suggested Reading
Purrucker JC, Haas K, Rizos T, et al. Early clinical and radiological course, management, and outcome of intracerebral hemorrhage related to new oral anticoagulants. JAMA Neurol. 2015 Dec 14 [Epub ahead of print].
Intracerebral hemorrhage related to non–vitamin-K antagonist oral anticoagulants (NOACs) is associated with a high risk of mortality and frequently involves hematoma expansion, according to a study published online ahead of print December 14, 2015, in JAMA Neurology.
The characteristics and natural history of acute-phase NOAC-associated ICH “are largely unknown,” and there are no prospective data concerning hematoma expansion or the effectiveness of prothrombin complex concentrate in limiting that expansion by reversing anticoagulation. Nevertheless, current recommendations suggest that clinicians consider administering prothrombin complex concentrate to this patient population, said Jan C. Purrucker, MD, neurology intern at Heidelberg University in Germany, and his associates.
To characterize the clinical and radiologic course, management, and outcome of NOAC-associated ICH in routine clinical practice, Dr. Purrucker and associates performed the ICH substudy of the Registry of Acute Stroke Under New Oral Anticoagulants (RASUNOA). This is a prospective registry involving 38 neurology departments with certified stroke units across Germany. For their substudy, the investigators examined 61 adults with a mean age of 76 (range, 46 to 97) who were taking NOACs (ie, apixaban, dabigatran etexilate, or rivaroxaban) and had moderate to severe neurologic deficit and a median hematoma volume of 10.8 mL at presentation. Thirty-five of these patients (57%) were treated with prothrombin complex concentrate.
The mortality rate was 16% (10 patients) during the acute inpatient stay and 28% (17 patients) at three months. Overall, 65% of the survivors had an unfavorable outcome. Substantial hematoma expansion, defined as a 33% or greater relative increase or a 6-mL or greater absolute increase in ICH volume, occurred in 38% of patients. “This proportion was within the range reported for vitamin-K antagonist–associated intracerebral hemorrhage (36% to 56%) and is higher, compared with that related to ICH in patients not receiving anticoagulation (12% to 26%),” said the investigators.
Larger hematoma volume at baseline (odds ratio [OR], 2.37) and intraventricular extension at baseline (OR, 8.13) strongly correlated with adverse outcomes. In contrast, prothrombin complex concentrate failed to limit lesion expansion or avert adverse outcomes. This failure might result from the fact that patients given the treatment tended to have more severe initial neurologic deficits and more unfavorable hematoma location than did those who were not given prothrombin complex concentrate. “Our study design, the limited sample size, and the potential for confounding by indication do not allow any [firm] conclusions regarding a potential association between prothrombin complex concentrate treatment and outcome,” the authors concluded.
—Mary Ann Moon
Intracerebral hemorrhage related to non–vitamin-K antagonist oral anticoagulants (NOACs) is associated with a high risk of mortality and frequently involves hematoma expansion, according to a study published online ahead of print December 14, 2015, in JAMA Neurology.
The characteristics and natural history of acute-phase NOAC-associated ICH “are largely unknown,” and there are no prospective data concerning hematoma expansion or the effectiveness of prothrombin complex concentrate in limiting that expansion by reversing anticoagulation. Nevertheless, current recommendations suggest that clinicians consider administering prothrombin complex concentrate to this patient population, said Jan C. Purrucker, MD, neurology intern at Heidelberg University in Germany, and his associates.
To characterize the clinical and radiologic course, management, and outcome of NOAC-associated ICH in routine clinical practice, Dr. Purrucker and associates performed the ICH substudy of the Registry of Acute Stroke Under New Oral Anticoagulants (RASUNOA). This is a prospective registry involving 38 neurology departments with certified stroke units across Germany. For their substudy, the investigators examined 61 adults with a mean age of 76 (range, 46 to 97) who were taking NOACs (ie, apixaban, dabigatran etexilate, or rivaroxaban) and had moderate to severe neurologic deficit and a median hematoma volume of 10.8 mL at presentation. Thirty-five of these patients (57%) were treated with prothrombin complex concentrate.
The mortality rate was 16% (10 patients) during the acute inpatient stay and 28% (17 patients) at three months. Overall, 65% of the survivors had an unfavorable outcome. Substantial hematoma expansion, defined as a 33% or greater relative increase or a 6-mL or greater absolute increase in ICH volume, occurred in 38% of patients. “This proportion was within the range reported for vitamin-K antagonist–associated intracerebral hemorrhage (36% to 56%) and is higher, compared with that related to ICH in patients not receiving anticoagulation (12% to 26%),” said the investigators.
Larger hematoma volume at baseline (odds ratio [OR], 2.37) and intraventricular extension at baseline (OR, 8.13) strongly correlated with adverse outcomes. In contrast, prothrombin complex concentrate failed to limit lesion expansion or avert adverse outcomes. This failure might result from the fact that patients given the treatment tended to have more severe initial neurologic deficits and more unfavorable hematoma location than did those who were not given prothrombin complex concentrate. “Our study design, the limited sample size, and the potential for confounding by indication do not allow any [firm] conclusions regarding a potential association between prothrombin complex concentrate treatment and outcome,” the authors concluded.
—Mary Ann Moon
Suggested Reading
Purrucker JC, Haas K, Rizos T, et al. Early clinical and radiological course, management, and outcome of intracerebral hemorrhage related to new oral anticoagulants. JAMA Neurol. 2015 Dec 14 [Epub ahead of print].
Suggested Reading
Purrucker JC, Haas K, Rizos T, et al. Early clinical and radiological course, management, and outcome of intracerebral hemorrhage related to new oral anticoagulants. JAMA Neurol. 2015 Dec 14 [Epub ahead of print].
Global Screening Measures Poorly Predict Progression of Alzheimer’s Disease
Patients with Alzheimer’s disease who perform poorly on early cognitive tests may progress more rapidly than those with less baseline impairment, according to research published online ahead of print December 8, 2015, in American Journal of Alzheimer’s Disease & Other Dementias. Age also may predict rate of progression; younger patients may decline at a more rapid pace, said the authors.
No single test, including those routinely used as diagnostic tools, successfully predicted participants’ rate of decline, said Paul J. Massman, PhD, Associate Professor of Clinical Psychology at Baylor College of Medicine in Houston. “Tests that differed between the rapidly and slowly progressing groups tended to measure higher-order cognitive skills such as executive functioning, memory, and visuospatial construction,” said Dr. Massman. “This [result] indicates that a full neuropsychologic evaluation, rather than sole use of a global screening measure such as the Mini-Mental State Examination [MMSE] or Alzheimer’s Disease Assessment Scale–Cognitive [ADAS-Cog], may be useful for predicting future cognitive decline.”
Although the individual course of Alzheimer’s dementia is notoriously unpredictable, the ability to predict the rate of decline would help patients and caregivers, as well as medical staff, said the investigators. “Prediction of rate of decline among patients with [Alzheimer’s disease] may allow caregivers and physicians to make more informed decisions about future care of the patient.”
The team examined dementia progression over a period of two years in 110 patients with Alzheimer’s disease who were seen at the Baylor College of Medicine Alzheimer’s Disease and Memory Disorders Center. Of these participants, half had slow disease progression and half had rapid disease progression.
The group was assessed at baseline and at two years with 14 neuropsychologic tests, including the MMSE, Clinical Dementia Rating scale (CDR), ADAS-Cog, and the Instrumental Activities of Daily Living (IADL). Other tests measured overall intelligence, memory and verbal fluency, executive function, and physical function.
At baseline, fast progression was significantly associated with younger age (age 72 vs age 77). Sex, ADAS-Cog and MMSE scores, and APOE4 genetic status were not different between the groups. Functional status, as measured by IADL, was similar. The baseline CDR score, however, was significantly different. Approximately 48% of slow progressers had a score of 0.5, compared with 24% of rapid progressers. The lack of difference between the groups at baseline on the ADAS-Cog or MMSE “indicates that these global measures are not as useful for predicting rate of decline as are more specific measures of neuropsychologic functioning,” said the authors.
Many of the more specific tests accurately differentiated between the groups. The rapid progressers had significantly poorer scores on the Logical Memory, Verbal Series Attention Test, Controlled Oral Word Association Test verbal fluency, and block design in the Wechsler Adult Intelligence Scale. There were also persistent significant differences for the Boston Naming Test and Rey-Osterrieth Complex.
The investigators suggested that future research examine the predictive value of performance in tests that measure higher-order thinking skills “to determine whether the differences in the rate of progression observed in the current study occur throughout the course of the disease.”
—Michele G. Sullivan
Suggested Reading
Seidl JN, Massman PJ. Rapidly versus slowly progressing patients with Alzheimer’s disease: differences in baseline cognition. Am J Alzheimers Dis Other Demen. 2015 Dec 8 [Epub ahead of print].
Patients with Alzheimer’s disease who perform poorly on early cognitive tests may progress more rapidly than those with less baseline impairment, according to research published online ahead of print December 8, 2015, in American Journal of Alzheimer’s Disease & Other Dementias. Age also may predict rate of progression; younger patients may decline at a more rapid pace, said the authors.
No single test, including those routinely used as diagnostic tools, successfully predicted participants’ rate of decline, said Paul J. Massman, PhD, Associate Professor of Clinical Psychology at Baylor College of Medicine in Houston. “Tests that differed between the rapidly and slowly progressing groups tended to measure higher-order cognitive skills such as executive functioning, memory, and visuospatial construction,” said Dr. Massman. “This [result] indicates that a full neuropsychologic evaluation, rather than sole use of a global screening measure such as the Mini-Mental State Examination [MMSE] or Alzheimer’s Disease Assessment Scale–Cognitive [ADAS-Cog], may be useful for predicting future cognitive decline.”
Although the individual course of Alzheimer’s dementia is notoriously unpredictable, the ability to predict the rate of decline would help patients and caregivers, as well as medical staff, said the investigators. “Prediction of rate of decline among patients with [Alzheimer’s disease] may allow caregivers and physicians to make more informed decisions about future care of the patient.”
The team examined dementia progression over a period of two years in 110 patients with Alzheimer’s disease who were seen at the Baylor College of Medicine Alzheimer’s Disease and Memory Disorders Center. Of these participants, half had slow disease progression and half had rapid disease progression.
The group was assessed at baseline and at two years with 14 neuropsychologic tests, including the MMSE, Clinical Dementia Rating scale (CDR), ADAS-Cog, and the Instrumental Activities of Daily Living (IADL). Other tests measured overall intelligence, memory and verbal fluency, executive function, and physical function.
At baseline, fast progression was significantly associated with younger age (age 72 vs age 77). Sex, ADAS-Cog and MMSE scores, and APOE4 genetic status were not different between the groups. Functional status, as measured by IADL, was similar. The baseline CDR score, however, was significantly different. Approximately 48% of slow progressers had a score of 0.5, compared with 24% of rapid progressers. The lack of difference between the groups at baseline on the ADAS-Cog or MMSE “indicates that these global measures are not as useful for predicting rate of decline as are more specific measures of neuropsychologic functioning,” said the authors.
Many of the more specific tests accurately differentiated between the groups. The rapid progressers had significantly poorer scores on the Logical Memory, Verbal Series Attention Test, Controlled Oral Word Association Test verbal fluency, and block design in the Wechsler Adult Intelligence Scale. There were also persistent significant differences for the Boston Naming Test and Rey-Osterrieth Complex.
The investigators suggested that future research examine the predictive value of performance in tests that measure higher-order thinking skills “to determine whether the differences in the rate of progression observed in the current study occur throughout the course of the disease.”
—Michele G. Sullivan
Patients with Alzheimer’s disease who perform poorly on early cognitive tests may progress more rapidly than those with less baseline impairment, according to research published online ahead of print December 8, 2015, in American Journal of Alzheimer’s Disease & Other Dementias. Age also may predict rate of progression; younger patients may decline at a more rapid pace, said the authors.
No single test, including those routinely used as diagnostic tools, successfully predicted participants’ rate of decline, said Paul J. Massman, PhD, Associate Professor of Clinical Psychology at Baylor College of Medicine in Houston. “Tests that differed between the rapidly and slowly progressing groups tended to measure higher-order cognitive skills such as executive functioning, memory, and visuospatial construction,” said Dr. Massman. “This [result] indicates that a full neuropsychologic evaluation, rather than sole use of a global screening measure such as the Mini-Mental State Examination [MMSE] or Alzheimer’s Disease Assessment Scale–Cognitive [ADAS-Cog], may be useful for predicting future cognitive decline.”
Although the individual course of Alzheimer’s dementia is notoriously unpredictable, the ability to predict the rate of decline would help patients and caregivers, as well as medical staff, said the investigators. “Prediction of rate of decline among patients with [Alzheimer’s disease] may allow caregivers and physicians to make more informed decisions about future care of the patient.”
The team examined dementia progression over a period of two years in 110 patients with Alzheimer’s disease who were seen at the Baylor College of Medicine Alzheimer’s Disease and Memory Disorders Center. Of these participants, half had slow disease progression and half had rapid disease progression.
The group was assessed at baseline and at two years with 14 neuropsychologic tests, including the MMSE, Clinical Dementia Rating scale (CDR), ADAS-Cog, and the Instrumental Activities of Daily Living (IADL). Other tests measured overall intelligence, memory and verbal fluency, executive function, and physical function.
At baseline, fast progression was significantly associated with younger age (age 72 vs age 77). Sex, ADAS-Cog and MMSE scores, and APOE4 genetic status were not different between the groups. Functional status, as measured by IADL, was similar. The baseline CDR score, however, was significantly different. Approximately 48% of slow progressers had a score of 0.5, compared with 24% of rapid progressers. The lack of difference between the groups at baseline on the ADAS-Cog or MMSE “indicates that these global measures are not as useful for predicting rate of decline as are more specific measures of neuropsychologic functioning,” said the authors.
Many of the more specific tests accurately differentiated between the groups. The rapid progressers had significantly poorer scores on the Logical Memory, Verbal Series Attention Test, Controlled Oral Word Association Test verbal fluency, and block design in the Wechsler Adult Intelligence Scale. There were also persistent significant differences for the Boston Naming Test and Rey-Osterrieth Complex.
The investigators suggested that future research examine the predictive value of performance in tests that measure higher-order thinking skills “to determine whether the differences in the rate of progression observed in the current study occur throughout the course of the disease.”
—Michele G. Sullivan
Suggested Reading
Seidl JN, Massman PJ. Rapidly versus slowly progressing patients with Alzheimer’s disease: differences in baseline cognition. Am J Alzheimers Dis Other Demen. 2015 Dec 8 [Epub ahead of print].
Suggested Reading
Seidl JN, Massman PJ. Rapidly versus slowly progressing patients with Alzheimer’s disease: differences in baseline cognition. Am J Alzheimers Dis Other Demen. 2015 Dec 8 [Epub ahead of print].