Neurology

From the University of Nebraska, Lincoln (Mr. Puckett and Dr. Ryherd), University of Nebraska Medical Center, Omaha (Dr. Manley), and the University of Nebraska, Omaha (Dr. Ryan).

ABSTRACT

Objective: This study evaluated relationships between physical characteristics of nursing home residences and quality-of-care measures.

Design: This was a cross-sectional ecologic study. The dependent variables were 5 Centers for Medicare & Medicaid Services (CMS) Nursing Home Compare database long-stay quality measures (QMs) during 2019: percentage of residents who displayed depressive symptoms, percentage of residents who were physically restrained, percentage of residents who experienced 1 or more falls resulting in injury, percentage of residents who received antipsychotic medication, and percentage of residents who received anti-anxiety medication. The independent variables were 4 residence characteristics: ownership type, size, occupancy, and region within the United States. We explored how different types of each residence characteristic compare for each QM.

Setting, participants, and measurements: Quality measure values from 15,420 CMS-supported nursing homes across the United States averaged over the 4 quarters of 2019 reporting were used. Welch’s analysis of variance was performed to examine whether the mean QM values for groups within each residential characteristic were statistically different.

Results: Publicly owned and low-occupancy residences had the highest mean QM values, indicating the poorest performance. Nonprofit and high-occupancy residences generally had the lowest (ie, best) mean QM values. There were significant differences in mean QM values among nursing home sizes and regions.

Conclusion: This study suggests that residence characteristics are related to 5 nursing home QMs. Results suggest that physical characteristics may be related to overall quality of life in nursing homes.

Keywords: quality of care, quality measures, residence characteristics, Alzheimer’s disease and related dementias.

More than 55 million people worldwide are living with Alzheimer’s disease and related dementias (ADRD).¹ With the aging of the Baby Boomer population, this number is expected to rise to more than 78 million worldwide by 2030.¹ Given the growing number of cognitively impaired older adults, there is an increased need for residences designed for the specialized care of this population. Although there are dozens of living options for the elderly, and although most specialized establishments have the resources to meet the immediate needs of their residents, many facilities lack universal design features that support a high quality of life for someone with ADRD or mild cognitive impairment. Previous research has shown relationships between behavioral and psychological symptoms of dementia (BPSD) and environmental characteristics such as acoustics, lighting, and indoor air temperature.^2,3 Physical behaviors of BPSD, including aggression and wandering, and psychological symptoms, such as depression, anxiety, and delusions, put residents at risk of injury.⁴ Additionally, BPSD is correlated with caregiver burden and stress.^5-8 Patients with dementia may also experience a lower stress threshold, changes in perception of space, and decreased short-term memory, creating environmental difficulties for those with ADRD⁹ that lead them to exhibit BPSD due to poor environmental design. Thus, there is a need to learn more about design features that minimize BPSD and promote a high quality of life for those with ADRD.¹⁰

Although research has shown relationships between physical environmental characteristics and BPSD, in this work we study relationships between possible BPSD indicators and 4 residence-level characteristics: ownership type, size, occupancy, and region in the United States (determined by location of the Centers for Medicare & Medicaid Services [CMS] regional offices). We analyzed data from the CMS Nursing Home Compare database for the year 2019.¹¹ This database publishes quarterly data and star ratings for quality-of-care measures (QMs), staffing levels, and health inspections for every nursing home supported by CMS. Previous research has investigated the accuracy of QM reporting for resident falls, the impact of residential characteristics on administration of antipsychotic medication, the influence of profit status on resident outcomes and quality of care, and the effect of nursing home size on quality of life.^12-16 Additionally, research suggests that residential characteristics such as size and location could be associated with infection control in nursing homes.¹⁷

Certain QMs, such as psychotropic drug administration, resident falls, and physical restraint, provide indicators of agitation, disorientation, or aggression, which are often signals of BPSD episodes. We hypothesized that residence types are associated with different QM scores, which could indicate different occurrences of BPSD. We selected 5 QMs for long-stay residents that could potentially be used as indicators of BPSD. Short-stay resident data were not included in this work to control for BPSD that could be a result of sheer unfamiliarity with the environment and confusion from being in a new home.

Methods

Design and Data Collection

This was a cross-sectional ecologic study aimed at exploring relationships between aggregate residential characteristics and QMs. Data were retrieved from the 2019 annual archives found in the CMS provider data catalog on nursing homes, including rehabilitation services.¹¹ The dataset provides general residence information, such as ownership, number of beds, number of residents, and location, as well as residence quality metrics, such as QMs, staffing data, and inspection data. Residence characteristics and 4-quarter averages of QMs were retrieved and used as cross-sectional data. The data used are from 15,420 residences across the United States. Nursing homes located in Guam, the US Pacific Territories, Puerto Rico, and the US Virgin Islands, while supported by CMS and included in the dataset, were excluded from the study due to a severe absence of QM data.

Dependent Variables

We investigated 5 QMs that were averaged across the 4 quarters of 2019. The QMs used as dependent variables were percentage of residents who displayed depressive symptoms (depression), percentage of residents who were physically restrained (restraint), percentage of residents who experienced 1 or more falls resulting in a major injury (falls), percentage of residents who received antipsychotic medication (antipsychotic medication), and percentage of residents who received anti-anxiety or hypnotic medication (anti-anxiety medication).

A total of 2471 QM values were unreported across the 5 QM analyzed: 501 residences did not report depression data; 479 did not report restraint data; 477 did not report falls data; 508 did not report antipsychotic medication data; and 506 did not report anti-anxiety medication data. A residence with a missing QM value was excluded from that respective analysis.

To assess the relationships among the different QMs, a Pearson correlation coefficient r was computed for each unique pair of QMs (Figure). All QMs studied were found to be very weakly or weakly correlated with one another using the Evans classification for very weak and weak correlations (r < 0.20 and 0.20 < r < 0.39, respectively).¹⁸

Independent Variables

A total of 15,420 residences were included in the study. Seventy-nine residences did not report occupancy data, however, so those residences were excluded from the occupancy analyses. We categorized the ownership of each nursing home as for-profit, nonprofit, or public. We categorized nursing home size, based on quartiles of the size distribution, as large (> 127 beds), medium (64 to 126 beds), and small (< 64 beds). This method for categorizing the residential characteristics was similar to that used in previous work.¹⁹ Similarly, we categorized nursing home occupancy as high (> 92% occupancy), medium (73% to 91% occupancy), and low (< 73% occupancy) based on quartiles of the occupancy distribution. For the regional analysis, we grouped states together based on the CMS regional offices: Atlanta, Georgia; Boston, Massachusetts; Chicago, Illinois; Dallas, Texas; Denver, Colorado; Kansas City, Missouri; New York, New York; Philadelphia, Pennsylvania; San Francisco, California; and Seattle, Washington.²⁰

Analyses

We used Levene’s test to determine whether variances among the residential groups were equal for each QM, using an a priori α = 0.05. For all 20 tests conducted (4 residential characteristics for all 5 QMs), the resulting F-statistics were significant, indicating that the assumption of homogeneity of variance was not met.

We therefore used Welch’s analysis of variance (ANOVA) to evaluate whether the groups within each residential characteristic were the same on their QM means. For example, we tested whether for-profit, nonprofit, and public residences had significantly different mean depression rates. For statistically significant differences, a Games-Howell post-hoc test was conducted to test the difference between all unique pairwise comparisons. An a priori α = 0.05 was used for both Welch’s ANOVA and post-hoc testing. All analyses were conducted in RStudio Version 1.2.5033 (Posit Software, PBC).

 

 

Results

Mean Differences

Mean QM scores for the 5 QMs investigated, grouped by residential characteristic for the 2019 year of reporting, are shown in Table 1. It should be noted that the number of residences that reported occupancy data (n = 15,341) does not equal the total number of residences included in the study (N = 15,420) because 79 residences did not report occupancy data. For all QMs reported in Table 1, lower scores are better. Table 2 and Table 3 show results from pairwise comparisons of mean differences for the different residential characteristic and QM groupings. Mean differences and 95% CI are presented along with an indication of statistical significance (when applicable).

Ownership

Nonprofit residences had significantly lower (ie, better) mean scores than for-profit and public residences for 3 QMs: resident depression, antipsychotic medication use, and anti-anxiety medication use. For-profit and public residences did not significantly differ in their mean values for these QMs. For-profit residences had a significantly lower mean score for resident falls than both nonprofit and public residences, but no significant difference existed between scores for nonprofit and public residence falls. There were no statistically significant differences between mean restraint scores among the ownership types.

Size

Large (ie, high-capacity) residences had a significantly higher mean depression score than both medium and small residences, but there was not a significant difference between medium and small residences. Large residences had the significantly lowest mean score for resident falls, and medium residences scored significantly lower than small residences. Medium residences had a significantly higher mean score for anti-anxiety medication use than both small and large residences, but there was no significant difference between small and large residences. There were no statistically significant differences between mean scores for restraint and antipsychotic medication use among the nursing home sizes.

Occupancy

The mean scores for 4 out of the 5 QMs exhibited similar relationships with occupancy rates: resident depression, falls, and antipsychotic and anti-anxiety medication use. Low-occupancy residences consistently scored significantly higher than both medium- and high-occupancy residences, and medium-occupancy residences consistently scored significantly higher than high-occupancy residences. On average, high-occupancy (≥ 92%) residences reported better QM scores than low-occupancy (< 73%) and medium-occupancy (73% to 91%) residences for all the QMs studied except physical restraint, which yielded no significant results. These findings indicate a possible inverse relationship between building occupancy rate and these 4 QMs.

Region

Pairwise comparisons of mean QM scores by region are shown in Table 3. The Chicago region had a significantly higher mean depression score than all other regions, while the San Francisco region’s score was significantly lower than all other regions, except Atlanta and Boston. The Kansas City region had a significantly higher mean score for resident falls than all other regions, with the exception of Denver, and the San Francisco region scored significantly lower than all other regions in falls. The Boston region had a significantly higher mean score for administering antipsychotic medication than all other regions, except for Kansas City and Seattle, and the New York and San Francisco regions both had significantly lower scores than all other regions except for each other. The Atlanta region reported a significantly higher mean score for administering antianxiety medication than all other regions, and the Seattle region’s score for anti-anxiety medication use was significantly lower than all other regions except for San Francisco.

 

 

Discussion

This study presented mean percentages for 5 QMs reported in the Nursing Home Compare database for the year 2019: depression, restraint, falls, antipsychotic medication use, and anti-anxiety medication use. We investigated these scores by 4 residential characteristics: ownership type, size, occupancy, and region. In general, publicly owned and low-occupancy residences had the highest scores, and thus the poorest performances, for the 5 chosen QMs during 2019. Nonprofit and high-occupancy residences generally had the lowest (ie, better) scores, and this result agrees with previous findings on long-stay nursing home residents.²¹ One possible explanation for better performance by high-occupancy buildings could be that increased social interaction is beneficial to nursing home residents as compared with low-occupancy buildings, where less social interaction is probable. It is difficult to draw conclusions regarding nursing home size and region; however, there are significant differences among sizes for 3 out of the 5 QMs and significant differences among regions for all 5 QMs. The analyses suggest that residence-level characteristics are related to QM scores. Although reported QMs are not a direct representation of resident quality of life, this work agrees with previous research that residential characteristics have some impact on the lives of nursing home residents.^13-17 Improvements in QM reporting and changes in quality improvement goals since the formation of Nursing Home Compare exist, suggesting that nursing homes’ awareness of their reporting duties may impact quality of care or reporting tendencies.^21,22 Future research should consider investigating the impacts of the COVID-19 pandemic on quality-reporting trends and QM scores.

Other physical characteristics of nursing homes, such as noise, lighting levels, and air quality, may also have an impact on QMs and possibly nursing home residents themselves. This type of data exploration could be included in future research. Additionally, future research could include a similar analysis over a longer period, rather than the 1-year period examined here, to investigate which types of residences consistently have high or low scores or how different types of residences have evolved over the years, particularly considering the impact of the COVID-19 pandemic. Information such as staffing levels, building renovations, and inspection data could be accounted for in future studies. Different QMs could also be investigated to better understand the influence of residential characteristics on quality of care.

Conclusion

This study suggests that residence-level characteristics are related to 5 reported nursing home QMs. Overall, nonprofit and high-occupancy residences had the lowest QM scores, indicating the highest performance. Although the results do not necessarily suggest that residence-level characteristics impact individual nursing home residents’ quality of life, they suggest that physical characteristics affect overall quality of life in nursing homes. Future research is needed to determine the specific physical characteristics of these residences that affect QM scores.

Corresponding author: Brian J. Puckett, puckett.brian@huskers.unl.edu.

Disclosures: None reported.

From the University of Nebraska, Lincoln (Mr. Puckett and Dr. Ryherd), University of Nebraska Medical Center, Omaha (Dr. Manley), and the University of Nebraska, Omaha (Dr. Ryan).

ABSTRACT

Objective: This study evaluated relationships between physical characteristics of nursing home residences and quality-of-care measures.

Design: This was a cross-sectional ecologic study. The dependent variables were 5 Centers for Medicare & Medicaid Services (CMS) Nursing Home Compare database long-stay quality measures (QMs) during 2019: percentage of residents who displayed depressive symptoms, percentage of residents who were physically restrained, percentage of residents who experienced 1 or more falls resulting in injury, percentage of residents who received antipsychotic medication, and percentage of residents who received anti-anxiety medication. The independent variables were 4 residence characteristics: ownership type, size, occupancy, and region within the United States. We explored how different types of each residence characteristic compare for each QM.

Setting, participants, and measurements: Quality measure values from 15,420 CMS-supported nursing homes across the United States averaged over the 4 quarters of 2019 reporting were used. Welch’s analysis of variance was performed to examine whether the mean QM values for groups within each residential characteristic were statistically different.

Results: Publicly owned and low-occupancy residences had the highest mean QM values, indicating the poorest performance. Nonprofit and high-occupancy residences generally had the lowest (ie, best) mean QM values. There were significant differences in mean QM values among nursing home sizes and regions.

Conclusion: This study suggests that residence characteristics are related to 5 nursing home QMs. Results suggest that physical characteristics may be related to overall quality of life in nursing homes.

Keywords: quality of care, quality measures, residence characteristics, Alzheimer’s disease and related dementias.

More than 55 million people worldwide are living with Alzheimer’s disease and related dementias (ADRD).¹ With the aging of the Baby Boomer population, this number is expected to rise to more than 78 million worldwide by 2030.¹ Given the growing number of cognitively impaired older adults, there is an increased need for residences designed for the specialized care of this population. Although there are dozens of living options for the elderly, and although most specialized establishments have the resources to meet the immediate needs of their residents, many facilities lack universal design features that support a high quality of life for someone with ADRD or mild cognitive impairment. Previous research has shown relationships between behavioral and psychological symptoms of dementia (BPSD) and environmental characteristics such as acoustics, lighting, and indoor air temperature.^2,3 Physical behaviors of BPSD, including aggression and wandering, and psychological symptoms, such as depression, anxiety, and delusions, put residents at risk of injury.⁴ Additionally, BPSD is correlated with caregiver burden and stress.^5-8 Patients with dementia may also experience a lower stress threshold, changes in perception of space, and decreased short-term memory, creating environmental difficulties for those with ADRD⁹ that lead them to exhibit BPSD due to poor environmental design. Thus, there is a need to learn more about design features that minimize BPSD and promote a high quality of life for those with ADRD.¹⁰

Although research has shown relationships between physical environmental characteristics and BPSD, in this work we study relationships between possible BPSD indicators and 4 residence-level characteristics: ownership type, size, occupancy, and region in the United States (determined by location of the Centers for Medicare & Medicaid Services [CMS] regional offices). We analyzed data from the CMS Nursing Home Compare database for the year 2019.¹¹ This database publishes quarterly data and star ratings for quality-of-care measures (QMs), staffing levels, and health inspections for every nursing home supported by CMS. Previous research has investigated the accuracy of QM reporting for resident falls, the impact of residential characteristics on administration of antipsychotic medication, the influence of profit status on resident outcomes and quality of care, and the effect of nursing home size on quality of life.^12-16 Additionally, research suggests that residential characteristics such as size and location could be associated with infection control in nursing homes.¹⁷

Certain QMs, such as psychotropic drug administration, resident falls, and physical restraint, provide indicators of agitation, disorientation, or aggression, which are often signals of BPSD episodes. We hypothesized that residence types are associated with different QM scores, which could indicate different occurrences of BPSD. We selected 5 QMs for long-stay residents that could potentially be used as indicators of BPSD. Short-stay resident data were not included in this work to control for BPSD that could be a result of sheer unfamiliarity with the environment and confusion from being in a new home.

Methods

Design and Data Collection

This was a cross-sectional ecologic study aimed at exploring relationships between aggregate residential characteristics and QMs. Data were retrieved from the 2019 annual archives found in the CMS provider data catalog on nursing homes, including rehabilitation services.¹¹ The dataset provides general residence information, such as ownership, number of beds, number of residents, and location, as well as residence quality metrics, such as QMs, staffing data, and inspection data. Residence characteristics and 4-quarter averages of QMs were retrieved and used as cross-sectional data. The data used are from 15,420 residences across the United States. Nursing homes located in Guam, the US Pacific Territories, Puerto Rico, and the US Virgin Islands, while supported by CMS and included in the dataset, were excluded from the study due to a severe absence of QM data.

Dependent Variables

We investigated 5 QMs that were averaged across the 4 quarters of 2019. The QMs used as dependent variables were percentage of residents who displayed depressive symptoms (depression), percentage of residents who were physically restrained (restraint), percentage of residents who experienced 1 or more falls resulting in a major injury (falls), percentage of residents who received antipsychotic medication (antipsychotic medication), and percentage of residents who received anti-anxiety or hypnotic medication (anti-anxiety medication).

A total of 2471 QM values were unreported across the 5 QM analyzed: 501 residences did not report depression data; 479 did not report restraint data; 477 did not report falls data; 508 did not report antipsychotic medication data; and 506 did not report anti-anxiety medication data. A residence with a missing QM value was excluded from that respective analysis.

To assess the relationships among the different QMs, a Pearson correlation coefficient r was computed for each unique pair of QMs (Figure). All QMs studied were found to be very weakly or weakly correlated with one another using the Evans classification for very weak and weak correlations (r < 0.20 and 0.20 < r < 0.39, respectively).¹⁸

Independent Variables

A total of 15,420 residences were included in the study. Seventy-nine residences did not report occupancy data, however, so those residences were excluded from the occupancy analyses. We categorized the ownership of each nursing home as for-profit, nonprofit, or public. We categorized nursing home size, based on quartiles of the size distribution, as large (> 127 beds), medium (64 to 126 beds), and small (< 64 beds). This method for categorizing the residential characteristics was similar to that used in previous work.¹⁹ Similarly, we categorized nursing home occupancy as high (> 92% occupancy), medium (73% to 91% occupancy), and low (< 73% occupancy) based on quartiles of the occupancy distribution. For the regional analysis, we grouped states together based on the CMS regional offices: Atlanta, Georgia; Boston, Massachusetts; Chicago, Illinois; Dallas, Texas; Denver, Colorado; Kansas City, Missouri; New York, New York; Philadelphia, Pennsylvania; San Francisco, California; and Seattle, Washington.²⁰

Analyses

We used Levene’s test to determine whether variances among the residential groups were equal for each QM, using an a priori α = 0.05. For all 20 tests conducted (4 residential characteristics for all 5 QMs), the resulting F-statistics were significant, indicating that the assumption of homogeneity of variance was not met.

We therefore used Welch’s analysis of variance (ANOVA) to evaluate whether the groups within each residential characteristic were the same on their QM means. For example, we tested whether for-profit, nonprofit, and public residences had significantly different mean depression rates. For statistically significant differences, a Games-Howell post-hoc test was conducted to test the difference between all unique pairwise comparisons. An a priori α = 0.05 was used for both Welch’s ANOVA and post-hoc testing. All analyses were conducted in RStudio Version 1.2.5033 (Posit Software, PBC).

 

 

Results

Mean Differences

Mean QM scores for the 5 QMs investigated, grouped by residential characteristic for the 2019 year of reporting, are shown in Table 1. It should be noted that the number of residences that reported occupancy data (n = 15,341) does not equal the total number of residences included in the study (N = 15,420) because 79 residences did not report occupancy data. For all QMs reported in Table 1, lower scores are better. Table 2 and Table 3 show results from pairwise comparisons of mean differences for the different residential characteristic and QM groupings. Mean differences and 95% CI are presented along with an indication of statistical significance (when applicable).

Ownership

Nonprofit residences had significantly lower (ie, better) mean scores than for-profit and public residences for 3 QMs: resident depression, antipsychotic medication use, and anti-anxiety medication use. For-profit and public residences did not significantly differ in their mean values for these QMs. For-profit residences had a significantly lower mean score for resident falls than both nonprofit and public residences, but no significant difference existed between scores for nonprofit and public residence falls. There were no statistically significant differences between mean restraint scores among the ownership types.

Size

Large (ie, high-capacity) residences had a significantly higher mean depression score than both medium and small residences, but there was not a significant difference between medium and small residences. Large residences had the significantly lowest mean score for resident falls, and medium residences scored significantly lower than small residences. Medium residences had a significantly higher mean score for anti-anxiety medication use than both small and large residences, but there was no significant difference between small and large residences. There were no statistically significant differences between mean scores for restraint and antipsychotic medication use among the nursing home sizes.

Occupancy

The mean scores for 4 out of the 5 QMs exhibited similar relationships with occupancy rates: resident depression, falls, and antipsychotic and anti-anxiety medication use. Low-occupancy residences consistently scored significantly higher than both medium- and high-occupancy residences, and medium-occupancy residences consistently scored significantly higher than high-occupancy residences. On average, high-occupancy (≥ 92%) residences reported better QM scores than low-occupancy (< 73%) and medium-occupancy (73% to 91%) residences for all the QMs studied except physical restraint, which yielded no significant results. These findings indicate a possible inverse relationship between building occupancy rate and these 4 QMs.

Region

Pairwise comparisons of mean QM scores by region are shown in Table 3. The Chicago region had a significantly higher mean depression score than all other regions, while the San Francisco region’s score was significantly lower than all other regions, except Atlanta and Boston. The Kansas City region had a significantly higher mean score for resident falls than all other regions, with the exception of Denver, and the San Francisco region scored significantly lower than all other regions in falls. The Boston region had a significantly higher mean score for administering antipsychotic medication than all other regions, except for Kansas City and Seattle, and the New York and San Francisco regions both had significantly lower scores than all other regions except for each other. The Atlanta region reported a significantly higher mean score for administering antianxiety medication than all other regions, and the Seattle region’s score for anti-anxiety medication use was significantly lower than all other regions except for San Francisco.

 

 

Discussion

This study presented mean percentages for 5 QMs reported in the Nursing Home Compare database for the year 2019: depression, restraint, falls, antipsychotic medication use, and anti-anxiety medication use. We investigated these scores by 4 residential characteristics: ownership type, size, occupancy, and region. In general, publicly owned and low-occupancy residences had the highest scores, and thus the poorest performances, for the 5 chosen QMs during 2019. Nonprofit and high-occupancy residences generally had the lowest (ie, better) scores, and this result agrees with previous findings on long-stay nursing home residents.²¹ One possible explanation for better performance by high-occupancy buildings could be that increased social interaction is beneficial to nursing home residents as compared with low-occupancy buildings, where less social interaction is probable. It is difficult to draw conclusions regarding nursing home size and region; however, there are significant differences among sizes for 3 out of the 5 QMs and significant differences among regions for all 5 QMs. The analyses suggest that residence-level characteristics are related to QM scores. Although reported QMs are not a direct representation of resident quality of life, this work agrees with previous research that residential characteristics have some impact on the lives of nursing home residents.^13-17 Improvements in QM reporting and changes in quality improvement goals since the formation of Nursing Home Compare exist, suggesting that nursing homes’ awareness of their reporting duties may impact quality of care or reporting tendencies.^21,22 Future research should consider investigating the impacts of the COVID-19 pandemic on quality-reporting trends and QM scores.

Other physical characteristics of nursing homes, such as noise, lighting levels, and air quality, may also have an impact on QMs and possibly nursing home residents themselves. This type of data exploration could be included in future research. Additionally, future research could include a similar analysis over a longer period, rather than the 1-year period examined here, to investigate which types of residences consistently have high or low scores or how different types of residences have evolved over the years, particularly considering the impact of the COVID-19 pandemic. Information such as staffing levels, building renovations, and inspection data could be accounted for in future studies. Different QMs could also be investigated to better understand the influence of residential characteristics on quality of care.

Conclusion

This study suggests that residence-level characteristics are related to 5 reported nursing home QMs. Overall, nonprofit and high-occupancy residences had the lowest QM scores, indicating the highest performance. Although the results do not necessarily suggest that residence-level characteristics impact individual nursing home residents’ quality of life, they suggest that physical characteristics affect overall quality of life in nursing homes. Future research is needed to determine the specific physical characteristics of these residences that affect QM scores.

Corresponding author: Brian J. Puckett, puckett.brian@huskers.unl.edu.

Disclosures: None reported.

From the University of Nebraska, Lincoln (Mr. Puckett and Dr. Ryherd), University of Nebraska Medical Center, Omaha (Dr. Manley), and the University of Nebraska, Omaha (Dr. Ryan).

ABSTRACT

Objective: This study evaluated relationships between physical characteristics of nursing home residences and quality-of-care measures.

Design: This was a cross-sectional ecologic study. The dependent variables were 5 Centers for Medicare & Medicaid Services (CMS) Nursing Home Compare database long-stay quality measures (QMs) during 2019: percentage of residents who displayed depressive symptoms, percentage of residents who were physically restrained, percentage of residents who experienced 1 or more falls resulting in injury, percentage of residents who received antipsychotic medication, and percentage of residents who received anti-anxiety medication. The independent variables were 4 residence characteristics: ownership type, size, occupancy, and region within the United States. We explored how different types of each residence characteristic compare for each QM.

Setting, participants, and measurements: Quality measure values from 15,420 CMS-supported nursing homes across the United States averaged over the 4 quarters of 2019 reporting were used. Welch’s analysis of variance was performed to examine whether the mean QM values for groups within each residential characteristic were statistically different.

Results: Publicly owned and low-occupancy residences had the highest mean QM values, indicating the poorest performance. Nonprofit and high-occupancy residences generally had the lowest (ie, best) mean QM values. There were significant differences in mean QM values among nursing home sizes and regions.

Conclusion: This study suggests that residence characteristics are related to 5 nursing home QMs. Results suggest that physical characteristics may be related to overall quality of life in nursing homes.

Keywords: quality of care, quality measures, residence characteristics, Alzheimer’s disease and related dementias.

More than 55 million people worldwide are living with Alzheimer’s disease and related dementias (ADRD).¹ With the aging of the Baby Boomer population, this number is expected to rise to more than 78 million worldwide by 2030.¹ Given the growing number of cognitively impaired older adults, there is an increased need for residences designed for the specialized care of this population. Although there are dozens of living options for the elderly, and although most specialized establishments have the resources to meet the immediate needs of their residents, many facilities lack universal design features that support a high quality of life for someone with ADRD or mild cognitive impairment. Previous research has shown relationships between behavioral and psychological symptoms of dementia (BPSD) and environmental characteristics such as acoustics, lighting, and indoor air temperature.^2,3 Physical behaviors of BPSD, including aggression and wandering, and psychological symptoms, such as depression, anxiety, and delusions, put residents at risk of injury.⁴ Additionally, BPSD is correlated with caregiver burden and stress.^5-8 Patients with dementia may also experience a lower stress threshold, changes in perception of space, and decreased short-term memory, creating environmental difficulties for those with ADRD⁹ that lead them to exhibit BPSD due to poor environmental design. Thus, there is a need to learn more about design features that minimize BPSD and promote a high quality of life for those with ADRD.¹⁰

Although research has shown relationships between physical environmental characteristics and BPSD, in this work we study relationships between possible BPSD indicators and 4 residence-level characteristics: ownership type, size, occupancy, and region in the United States (determined by location of the Centers for Medicare & Medicaid Services [CMS] regional offices). We analyzed data from the CMS Nursing Home Compare database for the year 2019.¹¹ This database publishes quarterly data and star ratings for quality-of-care measures (QMs), staffing levels, and health inspections for every nursing home supported by CMS. Previous research has investigated the accuracy of QM reporting for resident falls, the impact of residential characteristics on administration of antipsychotic medication, the influence of profit status on resident outcomes and quality of care, and the effect of nursing home size on quality of life.^12-16 Additionally, research suggests that residential characteristics such as size and location could be associated with infection control in nursing homes.¹⁷

Certain QMs, such as psychotropic drug administration, resident falls, and physical restraint, provide indicators of agitation, disorientation, or aggression, which are often signals of BPSD episodes. We hypothesized that residence types are associated with different QM scores, which could indicate different occurrences of BPSD. We selected 5 QMs for long-stay residents that could potentially be used as indicators of BPSD. Short-stay resident data were not included in this work to control for BPSD that could be a result of sheer unfamiliarity with the environment and confusion from being in a new home.

Methods

Design and Data Collection

This was a cross-sectional ecologic study aimed at exploring relationships between aggregate residential characteristics and QMs. Data were retrieved from the 2019 annual archives found in the CMS provider data catalog on nursing homes, including rehabilitation services.¹¹ The dataset provides general residence information, such as ownership, number of beds, number of residents, and location, as well as residence quality metrics, such as QMs, staffing data, and inspection data. Residence characteristics and 4-quarter averages of QMs were retrieved and used as cross-sectional data. The data used are from 15,420 residences across the United States. Nursing homes located in Guam, the US Pacific Territories, Puerto Rico, and the US Virgin Islands, while supported by CMS and included in the dataset, were excluded from the study due to a severe absence of QM data.

Dependent Variables

We investigated 5 QMs that were averaged across the 4 quarters of 2019. The QMs used as dependent variables were percentage of residents who displayed depressive symptoms (depression), percentage of residents who were physically restrained (restraint), percentage of residents who experienced 1 or more falls resulting in a major injury (falls), percentage of residents who received antipsychotic medication (antipsychotic medication), and percentage of residents who received anti-anxiety or hypnotic medication (anti-anxiety medication).

A total of 2471 QM values were unreported across the 5 QM analyzed: 501 residences did not report depression data; 479 did not report restraint data; 477 did not report falls data; 508 did not report antipsychotic medication data; and 506 did not report anti-anxiety medication data. A residence with a missing QM value was excluded from that respective analysis.

To assess the relationships among the different QMs, a Pearson correlation coefficient r was computed for each unique pair of QMs (Figure). All QMs studied were found to be very weakly or weakly correlated with one another using the Evans classification for very weak and weak correlations (r < 0.20 and 0.20 < r < 0.39, respectively).¹⁸

Independent Variables

A total of 15,420 residences were included in the study. Seventy-nine residences did not report occupancy data, however, so those residences were excluded from the occupancy analyses. We categorized the ownership of each nursing home as for-profit, nonprofit, or public. We categorized nursing home size, based on quartiles of the size distribution, as large (> 127 beds), medium (64 to 126 beds), and small (< 64 beds). This method for categorizing the residential characteristics was similar to that used in previous work.¹⁹ Similarly, we categorized nursing home occupancy as high (> 92% occupancy), medium (73% to 91% occupancy), and low (< 73% occupancy) based on quartiles of the occupancy distribution. For the regional analysis, we grouped states together based on the CMS regional offices: Atlanta, Georgia; Boston, Massachusetts; Chicago, Illinois; Dallas, Texas; Denver, Colorado; Kansas City, Missouri; New York, New York; Philadelphia, Pennsylvania; San Francisco, California; and Seattle, Washington.²⁰

Analyses

We used Levene’s test to determine whether variances among the residential groups were equal for each QM, using an a priori α = 0.05. For all 20 tests conducted (4 residential characteristics for all 5 QMs), the resulting F-statistics were significant, indicating that the assumption of homogeneity of variance was not met.

We therefore used Welch’s analysis of variance (ANOVA) to evaluate whether the groups within each residential characteristic were the same on their QM means. For example, we tested whether for-profit, nonprofit, and public residences had significantly different mean depression rates. For statistically significant differences, a Games-Howell post-hoc test was conducted to test the difference between all unique pairwise comparisons. An a priori α = 0.05 was used for both Welch’s ANOVA and post-hoc testing. All analyses were conducted in RStudio Version 1.2.5033 (Posit Software, PBC).

 

 

Results

Mean Differences

Mean QM scores for the 5 QMs investigated, grouped by residential characteristic for the 2019 year of reporting, are shown in Table 1. It should be noted that the number of residences that reported occupancy data (n = 15,341) does not equal the total number of residences included in the study (N = 15,420) because 79 residences did not report occupancy data. For all QMs reported in Table 1, lower scores are better. Table 2 and Table 3 show results from pairwise comparisons of mean differences for the different residential characteristic and QM groupings. Mean differences and 95% CI are presented along with an indication of statistical significance (when applicable).

Ownership

Nonprofit residences had significantly lower (ie, better) mean scores than for-profit and public residences for 3 QMs: resident depression, antipsychotic medication use, and anti-anxiety medication use. For-profit and public residences did not significantly differ in their mean values for these QMs. For-profit residences had a significantly lower mean score for resident falls than both nonprofit and public residences, but no significant difference existed between scores for nonprofit and public residence falls. There were no statistically significant differences between mean restraint scores among the ownership types.

Size

Large (ie, high-capacity) residences had a significantly higher mean depression score than both medium and small residences, but there was not a significant difference between medium and small residences. Large residences had the significantly lowest mean score for resident falls, and medium residences scored significantly lower than small residences. Medium residences had a significantly higher mean score for anti-anxiety medication use than both small and large residences, but there was no significant difference between small and large residences. There were no statistically significant differences between mean scores for restraint and antipsychotic medication use among the nursing home sizes.

Occupancy

The mean scores for 4 out of the 5 QMs exhibited similar relationships with occupancy rates: resident depression, falls, and antipsychotic and anti-anxiety medication use. Low-occupancy residences consistently scored significantly higher than both medium- and high-occupancy residences, and medium-occupancy residences consistently scored significantly higher than high-occupancy residences. On average, high-occupancy (≥ 92%) residences reported better QM scores than low-occupancy (< 73%) and medium-occupancy (73% to 91%) residences for all the QMs studied except physical restraint, which yielded no significant results. These findings indicate a possible inverse relationship between building occupancy rate and these 4 QMs.

Region

Pairwise comparisons of mean QM scores by region are shown in Table 3. The Chicago region had a significantly higher mean depression score than all other regions, while the San Francisco region’s score was significantly lower than all other regions, except Atlanta and Boston. The Kansas City region had a significantly higher mean score for resident falls than all other regions, with the exception of Denver, and the San Francisco region scored significantly lower than all other regions in falls. The Boston region had a significantly higher mean score for administering antipsychotic medication than all other regions, except for Kansas City and Seattle, and the New York and San Francisco regions both had significantly lower scores than all other regions except for each other. The Atlanta region reported a significantly higher mean score for administering antianxiety medication than all other regions, and the Seattle region’s score for anti-anxiety medication use was significantly lower than all other regions except for San Francisco.

 

 

Discussion

This study presented mean percentages for 5 QMs reported in the Nursing Home Compare database for the year 2019: depression, restraint, falls, antipsychotic medication use, and anti-anxiety medication use. We investigated these scores by 4 residential characteristics: ownership type, size, occupancy, and region. In general, publicly owned and low-occupancy residences had the highest scores, and thus the poorest performances, for the 5 chosen QMs during 2019. Nonprofit and high-occupancy residences generally had the lowest (ie, better) scores, and this result agrees with previous findings on long-stay nursing home residents.²¹ One possible explanation for better performance by high-occupancy buildings could be that increased social interaction is beneficial to nursing home residents as compared with low-occupancy buildings, where less social interaction is probable. It is difficult to draw conclusions regarding nursing home size and region; however, there are significant differences among sizes for 3 out of the 5 QMs and significant differences among regions for all 5 QMs. The analyses suggest that residence-level characteristics are related to QM scores. Although reported QMs are not a direct representation of resident quality of life, this work agrees with previous research that residential characteristics have some impact on the lives of nursing home residents.^13-17 Improvements in QM reporting and changes in quality improvement goals since the formation of Nursing Home Compare exist, suggesting that nursing homes’ awareness of their reporting duties may impact quality of care or reporting tendencies.^21,22 Future research should consider investigating the impacts of the COVID-19 pandemic on quality-reporting trends and QM scores.

Other physical characteristics of nursing homes, such as noise, lighting levels, and air quality, may also have an impact on QMs and possibly nursing home residents themselves. This type of data exploration could be included in future research. Additionally, future research could include a similar analysis over a longer period, rather than the 1-year period examined here, to investigate which types of residences consistently have high or low scores or how different types of residences have evolved over the years, particularly considering the impact of the COVID-19 pandemic. Information such as staffing levels, building renovations, and inspection data could be accounted for in future studies. Different QMs could also be investigated to better understand the influence of residential characteristics on quality of care.

Conclusion

This study suggests that residence-level characteristics are related to 5 reported nursing home QMs. Overall, nonprofit and high-occupancy residences had the lowest QM scores, indicating the highest performance. Although the results do not necessarily suggest that residence-level characteristics impact individual nursing home residents’ quality of life, they suggest that physical characteristics affect overall quality of life in nursing homes. Future research is needed to determine the specific physical characteristics of these residences that affect QM scores.

Corresponding author: Brian J. Puckett, puckett.brian@huskers.unl.edu.

Disclosures: None reported.

Study 1 Overview (Menon et al)

Objective: To determine whether a 0.25 mg/kg dose of intravenous tenecteplase is noninferior to intravenous alteplase 0.9 mg/kg for patients with acute ischemic stroke eligible for thrombolytic therapy.

Design: Multicenter, parallel-group, open-label randomized controlled trial.

Setting and participants: The trial was conducted at 22 primary and comprehensive stroke centers across Canada. A primary stroke center was defined as a hospital capable of offering intravenous thrombolysis to patients with acute ischemic stroke, while a comprehensive stroke center was able to offer thrombectomy services in addition. The involved centers also participated in Canadian quality improvement registries (either Quality Improvement and Clinical Research [QuiCR] or Optimizing Patient Treatment in Major Ischemic Stroke with EVT [OPTIMISE]) that track patient outcomes. Patients were eligible for inclusion if they were aged 18 years or older, had a diagnosis of acute ischemic stroke, presented within 4.5 hours of symptom onset, and were eligible for thrombolysis according to Canadian guidelines.

Patients were randomized in a 1:1 fashion to either intravenous tenecteplase (0.25 mg/kg single dose, maximum of 25 mg) or intravenous alteplase (0.9 mg/kg total dose to a maximum of 90 mg, delivered as a bolus followed by a continuous infusion). A total of 1600 patients were enrolled, with 816 randomly assigned to the tenecteplase arm and 784 to the alteplase arm; 1577 patients were included in the intention-to-treat (ITT) analysis (n = 806 tenecteplase; n = 771 alteplase). The median age of enrollees was 74 years, and 52.1% of the ITT population were men.

Main outcome measures: In the ITT population, the primary outcome measure was a modified Rankin score (mRS) of 0 or 1 at 90 to 120 days post treatment. Safety outcomes included symptomatic intracerebral hemorrhage, orolingual angioedema, extracranial bleeding that required blood transfusion (all within 24 hours of thrombolytic administration), and all-cause mortality at 90 days. The noninferiority threshold for intravenous tenecteplase was set as the lower 95% CI of the difference between the tenecteplase and alteplase groups in the proportion of patients who met the primary outcome exceeding –5%.

Main results: The primary outcome of mRS of either 0 or 1 at 90 to 120 days of treatment occurred in 296 (36.9%) of the 802 patients assigned to tenecteplase and 266 (34.8%) of the 765 patients assigned to alteplase (unadjusted risk difference, 2.1%; 95% CI, –2.6 to 6.9). The prespecified noninferiority threshold was met. There were no significant differences between the groups in rates of intracerebral hemorrhage at 24 hours or 90-day all-cause mortality.

Conclusion: Intravenous tenecteplase is a reasonable alternative to alteplase for patients eligible for thrombolytic therapy.

Study 2 Overview (Wang et al)

Objective: To determine whether tenecteplase (dose 0.25 mg/kg) is noninferior to alteplase in patients with acute ischemic stroke who are within 4.5 hours of symptom onset and eligible for thrombolytic therapy but either refused or were ineligible for endovascular thrombectomy.

Design: Multicenter, prospective, open-label, randomized, controlled noninferiority trial.

Setting and participants: This trial was conducted at 53 centers across China and included patients 18 years of age or older who were within 4.5 hours of symptom onset and were thrombolytic eligible, had a mRS ≤ 1 at enrollment, and had a National Institutes of Health Stroke Scale score between 5 and 25. Eligible participants were randomized 1:1 to either tenecteplase 0.25 mg/kg (maximum dose 25 mg) or alteplase 0.9 mg/kg (maximum dose 90 mg, administered as a bolus followed by infusion). During the enrollment period (June 12, 2021, to May 29, 2022), a total of 1430 participants were enrolled, and, of those, 716 were randomly assigned to tenecteplase and 714 to alteplase. Six patients assigned to tenecteplase and 7 assigned to alteplase did not receive drugs. At 90 days, 5 in the tenecteplase group and 11 in the alteplase group were lost to follow up.

Main outcome measures: The primary efficacy outcome was a mRS of 0 or 1 at 90 days. The primary safety outcome was intracranial hemorrhage within 36 hours. Safety outcomes included parenchymal hematoma 2, as defined by the European Cooperative Acute Stroke Study III; any intracranial or significant hemorrhage, as defined by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria; and death from all causes at 90 days. Noninferiority for tenecteplase would be declared if the lower 97.5% 1-sided CI for the relative risk (RR) for the primary outcome did not cross 0.937.

Main results: In the modified ITT population, the primary outcome occurred in 439 (62%) of the tenecteplase group and 405 (68%) of the alteplase group (RR, 1.07; 95% CI, 0.98-1.16). This met the prespecified margin for noninferiority. Intracranial hemorrhage within 36 hours was experienced by 15 (2%) patients in the tenecteplase group and 13 (2%) in the alteplase group (RR, 1.18; 95% CI, 0.56-2.50). Death at 90 days occurred in 46 (7%) patients in the tenecteplase group and 35 (5%) in the alteplase group (RR, 1.31; 95% CI, 0.86-2.01).

Conclusion: Tenecteplase was noninferior to alteplase in patients with acute ischemic stroke who met criteria for thrombolysis and either refused or were ineligible for endovascular thrombectomy.

Commentary

Alteplase has been FDA-approved for managing acute ischemic stroke since 1996 and has demonstrated positive effects on functional outcomes. Drawbacks of alteplase therapy, however, include bleeding risk as well as cumbersome administration of a bolus dose followed by a 60-minute infusion. In recent years, the question of whether or not tenecteplase could replace alteplase as the preferred thrombolytic for acute ischemic stroke has garnered much attention. Several features of tenecteplase make it an attractive option, including increased fibrin specificity, a longer half-life, and ease of administration as a single, rapid bolus dose. In phase 2 trials that compared tenecteplase 0.25 mg/kg with alteplase, findings suggested the potential for early neurological improvement as well as improved outcomes at 90 days. While the role of tenecteplase in acute myocardial infarction has been well established due to ease of use and a favorable adverse-effect profile,¹ there is much less evidence from phase 3 randomized controlled clinical trials to secure the role of tenecteplase in acute ischemic stroke.²

Menon et al attempted to close this gap in the literature by conducting a randomized controlled clinical trial (AcT) comparing tenecteplase to alteplase in a Canadian patient population. The trial's patient population mirrors that of real-world data from global registries in terms of age, sex, and baseline stroke severity. In addition, the eligibility window of 4.5 hours from symptom onset as well as the inclusion and exclusion criteria for therapy are common to those utilized in other countries, making the findings generalizable. There were some limitations to the study, however, including the impact of COVID-19 on recruitment efforts as well as limitations of research infrastructure and staffing, which may have limited enrollment efforts at primary stroke centers. Nonetheless, the authors concluded that their results provide evidence that tenecteplase is comparable to alteplase, with similar functional and safety outcomes.

TRACE-2 focused on an Asian patient population and provided follow up to the dose-ranging TRACE-1 phase 2 trial. TRACE-1 showed that tenecteplase 0.25 mg/kg had a similar safety profile to alteplase 0.9 mg/kg in Chinese patients presenting with acute ischemic stroke. TRACE-2 sought to establish noninferiority of tenecteplase and excluded patients who were ineligible for or refused thrombectomy. Interestingly, the tenecteplase arm, as the authors point out, had numerically greater mortality as well as intracranial hemorrhage, but these differences were not statistically significant between the treatment groups at 90 days. The TRACE-2 results parallel those of AcT, and although there were differences in ethnicity between the 2 trials, the authors cite this as evidence that the results are consistent and provide evidence for the role of tenecteplase in the management of acute ischemic stroke. Limitations of this trial include potential bias from its open-label design, as well as exclusion of patients with more severe strokes eligible for thrombectomy, which may limit generalizability to patients with more disabling strokes who could have a higher risk of intracranial hemorrhage.

Application for Clinical Practice and System Implementation

Across the country, many organizations have adopted the off-label use of tenecteplase for managing fibrinolytic-eligible acute ischemic stroke patients. In most cases, the impetus for change is the ease of dosing and administration of tenecteplase compared to alteplase, while the inclusion and exclusion criteria and overall management remain the same. Timely administration of therapy in stroke is critical. This, along with other time constraints in stroke workflows, the weight-based calculation of alteplase doses, and alteplase’s administration method may lead to medication errors when using this agent to treat patients with acute stroke. The rapid, single-dose administration of tenecteplase removes many barriers that hospitals face when patients may need to be treated and then transferred to another site for further care. Without the worry to “drip and ship,” the completion of administration may allow for timely patient transfer and eliminate the need for monitoring of an infusion during transfer. For some organizations, there may be a potential for drug cost-savings as well as improved metrics, such as door-to-needle time, but the overall effects of switching from alteplase to tenecteplase remain to be seen. Currently, tenecteplase is included in stroke guidelines as a “reasonable choice,” though with a low level of evidence.³ However, these 2 studies support the role of tenecteplase in acute ischemic stroke treatment and may provide a foundation for further studies to establish the role of tenecteplase in the acute ischemic stroke population.

Practice Points

• Tenecteplase may be considered as an alternative to alteplase for acute ischemic stroke for patients who meet eligibility criteria for thrombolytics; this recommendation is included in the most recent stroke guidelines, although tenecteplase has not been demonstrated to be superior to alteplase.
• The ease of administration of tenecteplase as a single intravenous bolus dose represents a benefit compared to alteplase; it is an off-label use, however, and further studies are needed to establish the superiority of tenecteplase in terms of functional and safety outcomes.

– Carol Heunisch, PharmD, BCPS, BCCP
Pharmacy Department, NorthShore–Edward-Elmhurst Health, Evanston, IL

Study 1 Overview (Menon et al)

Objective: To determine whether a 0.25 mg/kg dose of intravenous tenecteplase is noninferior to intravenous alteplase 0.9 mg/kg for patients with acute ischemic stroke eligible for thrombolytic therapy.

Design: Multicenter, parallel-group, open-label randomized controlled trial.

Setting and participants: The trial was conducted at 22 primary and comprehensive stroke centers across Canada. A primary stroke center was defined as a hospital capable of offering intravenous thrombolysis to patients with acute ischemic stroke, while a comprehensive stroke center was able to offer thrombectomy services in addition. The involved centers also participated in Canadian quality improvement registries (either Quality Improvement and Clinical Research [QuiCR] or Optimizing Patient Treatment in Major Ischemic Stroke with EVT [OPTIMISE]) that track patient outcomes. Patients were eligible for inclusion if they were aged 18 years or older, had a diagnosis of acute ischemic stroke, presented within 4.5 hours of symptom onset, and were eligible for thrombolysis according to Canadian guidelines.

Patients were randomized in a 1:1 fashion to either intravenous tenecteplase (0.25 mg/kg single dose, maximum of 25 mg) or intravenous alteplase (0.9 mg/kg total dose to a maximum of 90 mg, delivered as a bolus followed by a continuous infusion). A total of 1600 patients were enrolled, with 816 randomly assigned to the tenecteplase arm and 784 to the alteplase arm; 1577 patients were included in the intention-to-treat (ITT) analysis (n = 806 tenecteplase; n = 771 alteplase). The median age of enrollees was 74 years, and 52.1% of the ITT population were men.

Main outcome measures: In the ITT population, the primary outcome measure was a modified Rankin score (mRS) of 0 or 1 at 90 to 120 days post treatment. Safety outcomes included symptomatic intracerebral hemorrhage, orolingual angioedema, extracranial bleeding that required blood transfusion (all within 24 hours of thrombolytic administration), and all-cause mortality at 90 days. The noninferiority threshold for intravenous tenecteplase was set as the lower 95% CI of the difference between the tenecteplase and alteplase groups in the proportion of patients who met the primary outcome exceeding –5%.

Main results: The primary outcome of mRS of either 0 or 1 at 90 to 120 days of treatment occurred in 296 (36.9%) of the 802 patients assigned to tenecteplase and 266 (34.8%) of the 765 patients assigned to alteplase (unadjusted risk difference, 2.1%; 95% CI, –2.6 to 6.9). The prespecified noninferiority threshold was met. There were no significant differences between the groups in rates of intracerebral hemorrhage at 24 hours or 90-day all-cause mortality.

Conclusion: Intravenous tenecteplase is a reasonable alternative to alteplase for patients eligible for thrombolytic therapy.

Study 2 Overview (Wang et al)

Objective: To determine whether tenecteplase (dose 0.25 mg/kg) is noninferior to alteplase in patients with acute ischemic stroke who are within 4.5 hours of symptom onset and eligible for thrombolytic therapy but either refused or were ineligible for endovascular thrombectomy.

Design: Multicenter, prospective, open-label, randomized, controlled noninferiority trial.

Setting and participants: This trial was conducted at 53 centers across China and included patients 18 years of age or older who were within 4.5 hours of symptom onset and were thrombolytic eligible, had a mRS ≤ 1 at enrollment, and had a National Institutes of Health Stroke Scale score between 5 and 25. Eligible participants were randomized 1:1 to either tenecteplase 0.25 mg/kg (maximum dose 25 mg) or alteplase 0.9 mg/kg (maximum dose 90 mg, administered as a bolus followed by infusion). During the enrollment period (June 12, 2021, to May 29, 2022), a total of 1430 participants were enrolled, and, of those, 716 were randomly assigned to tenecteplase and 714 to alteplase. Six patients assigned to tenecteplase and 7 assigned to alteplase did not receive drugs. At 90 days, 5 in the tenecteplase group and 11 in the alteplase group were lost to follow up.

Main outcome measures: The primary efficacy outcome was a mRS of 0 or 1 at 90 days. The primary safety outcome was intracranial hemorrhage within 36 hours. Safety outcomes included parenchymal hematoma 2, as defined by the European Cooperative Acute Stroke Study III; any intracranial or significant hemorrhage, as defined by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria; and death from all causes at 90 days. Noninferiority for tenecteplase would be declared if the lower 97.5% 1-sided CI for the relative risk (RR) for the primary outcome did not cross 0.937.

Main results: In the modified ITT population, the primary outcome occurred in 439 (62%) of the tenecteplase group and 405 (68%) of the alteplase group (RR, 1.07; 95% CI, 0.98-1.16). This met the prespecified margin for noninferiority. Intracranial hemorrhage within 36 hours was experienced by 15 (2%) patients in the tenecteplase group and 13 (2%) in the alteplase group (RR, 1.18; 95% CI, 0.56-2.50). Death at 90 days occurred in 46 (7%) patients in the tenecteplase group and 35 (5%) in the alteplase group (RR, 1.31; 95% CI, 0.86-2.01).

Conclusion: Tenecteplase was noninferior to alteplase in patients with acute ischemic stroke who met criteria for thrombolysis and either refused or were ineligible for endovascular thrombectomy.

Commentary

Alteplase has been FDA-approved for managing acute ischemic stroke since 1996 and has demonstrated positive effects on functional outcomes. Drawbacks of alteplase therapy, however, include bleeding risk as well as cumbersome administration of a bolus dose followed by a 60-minute infusion. In recent years, the question of whether or not tenecteplase could replace alteplase as the preferred thrombolytic for acute ischemic stroke has garnered much attention. Several features of tenecteplase make it an attractive option, including increased fibrin specificity, a longer half-life, and ease of administration as a single, rapid bolus dose. In phase 2 trials that compared tenecteplase 0.25 mg/kg with alteplase, findings suggested the potential for early neurological improvement as well as improved outcomes at 90 days. While the role of tenecteplase in acute myocardial infarction has been well established due to ease of use and a favorable adverse-effect profile,¹ there is much less evidence from phase 3 randomized controlled clinical trials to secure the role of tenecteplase in acute ischemic stroke.²

Menon et al attempted to close this gap in the literature by conducting a randomized controlled clinical trial (AcT) comparing tenecteplase to alteplase in a Canadian patient population. The trial's patient population mirrors that of real-world data from global registries in terms of age, sex, and baseline stroke severity. In addition, the eligibility window of 4.5 hours from symptom onset as well as the inclusion and exclusion criteria for therapy are common to those utilized in other countries, making the findings generalizable. There were some limitations to the study, however, including the impact of COVID-19 on recruitment efforts as well as limitations of research infrastructure and staffing, which may have limited enrollment efforts at primary stroke centers. Nonetheless, the authors concluded that their results provide evidence that tenecteplase is comparable to alteplase, with similar functional and safety outcomes.

TRACE-2 focused on an Asian patient population and provided follow up to the dose-ranging TRACE-1 phase 2 trial. TRACE-1 showed that tenecteplase 0.25 mg/kg had a similar safety profile to alteplase 0.9 mg/kg in Chinese patients presenting with acute ischemic stroke. TRACE-2 sought to establish noninferiority of tenecteplase and excluded patients who were ineligible for or refused thrombectomy. Interestingly, the tenecteplase arm, as the authors point out, had numerically greater mortality as well as intracranial hemorrhage, but these differences were not statistically significant between the treatment groups at 90 days. The TRACE-2 results parallel those of AcT, and although there were differences in ethnicity between the 2 trials, the authors cite this as evidence that the results are consistent and provide evidence for the role of tenecteplase in the management of acute ischemic stroke. Limitations of this trial include potential bias from its open-label design, as well as exclusion of patients with more severe strokes eligible for thrombectomy, which may limit generalizability to patients with more disabling strokes who could have a higher risk of intracranial hemorrhage.

Application for Clinical Practice and System Implementation

Across the country, many organizations have adopted the off-label use of tenecteplase for managing fibrinolytic-eligible acute ischemic stroke patients. In most cases, the impetus for change is the ease of dosing and administration of tenecteplase compared to alteplase, while the inclusion and exclusion criteria and overall management remain the same. Timely administration of therapy in stroke is critical. This, along with other time constraints in stroke workflows, the weight-based calculation of alteplase doses, and alteplase’s administration method may lead to medication errors when using this agent to treat patients with acute stroke. The rapid, single-dose administration of tenecteplase removes many barriers that hospitals face when patients may need to be treated and then transferred to another site for further care. Without the worry to “drip and ship,” the completion of administration may allow for timely patient transfer and eliminate the need for monitoring of an infusion during transfer. For some organizations, there may be a potential for drug cost-savings as well as improved metrics, such as door-to-needle time, but the overall effects of switching from alteplase to tenecteplase remain to be seen. Currently, tenecteplase is included in stroke guidelines as a “reasonable choice,” though with a low level of evidence.³ However, these 2 studies support the role of tenecteplase in acute ischemic stroke treatment and may provide a foundation for further studies to establish the role of tenecteplase in the acute ischemic stroke population.

Practice Points

• Tenecteplase may be considered as an alternative to alteplase for acute ischemic stroke for patients who meet eligibility criteria for thrombolytics; this recommendation is included in the most recent stroke guidelines, although tenecteplase has not been demonstrated to be superior to alteplase.
• The ease of administration of tenecteplase as a single intravenous bolus dose represents a benefit compared to alteplase; it is an off-label use, however, and further studies are needed to establish the superiority of tenecteplase in terms of functional and safety outcomes.

– Carol Heunisch, PharmD, BCPS, BCCP
Pharmacy Department, NorthShore–Edward-Elmhurst Health, Evanston, IL

Study 1 Overview (Menon et al)

Objective: To determine whether a 0.25 mg/kg dose of intravenous tenecteplase is noninferior to intravenous alteplase 0.9 mg/kg for patients with acute ischemic stroke eligible for thrombolytic therapy.

Design: Multicenter, parallel-group, open-label randomized controlled trial.

Setting and participants: The trial was conducted at 22 primary and comprehensive stroke centers across Canada. A primary stroke center was defined as a hospital capable of offering intravenous thrombolysis to patients with acute ischemic stroke, while a comprehensive stroke center was able to offer thrombectomy services in addition. The involved centers also participated in Canadian quality improvement registries (either Quality Improvement and Clinical Research [QuiCR] or Optimizing Patient Treatment in Major Ischemic Stroke with EVT [OPTIMISE]) that track patient outcomes. Patients were eligible for inclusion if they were aged 18 years or older, had a diagnosis of acute ischemic stroke, presented within 4.5 hours of symptom onset, and were eligible for thrombolysis according to Canadian guidelines.

Patients were randomized in a 1:1 fashion to either intravenous tenecteplase (0.25 mg/kg single dose, maximum of 25 mg) or intravenous alteplase (0.9 mg/kg total dose to a maximum of 90 mg, delivered as a bolus followed by a continuous infusion). A total of 1600 patients were enrolled, with 816 randomly assigned to the tenecteplase arm and 784 to the alteplase arm; 1577 patients were included in the intention-to-treat (ITT) analysis (n = 806 tenecteplase; n = 771 alteplase). The median age of enrollees was 74 years, and 52.1% of the ITT population were men.

Main outcome measures: In the ITT population, the primary outcome measure was a modified Rankin score (mRS) of 0 or 1 at 90 to 120 days post treatment. Safety outcomes included symptomatic intracerebral hemorrhage, orolingual angioedema, extracranial bleeding that required blood transfusion (all within 24 hours of thrombolytic administration), and all-cause mortality at 90 days. The noninferiority threshold for intravenous tenecteplase was set as the lower 95% CI of the difference between the tenecteplase and alteplase groups in the proportion of patients who met the primary outcome exceeding –5%.

Main results: The primary outcome of mRS of either 0 or 1 at 90 to 120 days of treatment occurred in 296 (36.9%) of the 802 patients assigned to tenecteplase and 266 (34.8%) of the 765 patients assigned to alteplase (unadjusted risk difference, 2.1%; 95% CI, –2.6 to 6.9). The prespecified noninferiority threshold was met. There were no significant differences between the groups in rates of intracerebral hemorrhage at 24 hours or 90-day all-cause mortality.

Conclusion: Intravenous tenecteplase is a reasonable alternative to alteplase for patients eligible for thrombolytic therapy.

Study 2 Overview (Wang et al)

Objective: To determine whether tenecteplase (dose 0.25 mg/kg) is noninferior to alteplase in patients with acute ischemic stroke who are within 4.5 hours of symptom onset and eligible for thrombolytic therapy but either refused or were ineligible for endovascular thrombectomy.

Design: Multicenter, prospective, open-label, randomized, controlled noninferiority trial.

Setting and participants: This trial was conducted at 53 centers across China and included patients 18 years of age or older who were within 4.5 hours of symptom onset and were thrombolytic eligible, had a mRS ≤ 1 at enrollment, and had a National Institutes of Health Stroke Scale score between 5 and 25. Eligible participants were randomized 1:1 to either tenecteplase 0.25 mg/kg (maximum dose 25 mg) or alteplase 0.9 mg/kg (maximum dose 90 mg, administered as a bolus followed by infusion). During the enrollment period (June 12, 2021, to May 29, 2022), a total of 1430 participants were enrolled, and, of those, 716 were randomly assigned to tenecteplase and 714 to alteplase. Six patients assigned to tenecteplase and 7 assigned to alteplase did not receive drugs. At 90 days, 5 in the tenecteplase group and 11 in the alteplase group were lost to follow up.

Main outcome measures: The primary efficacy outcome was a mRS of 0 or 1 at 90 days. The primary safety outcome was intracranial hemorrhage within 36 hours. Safety outcomes included parenchymal hematoma 2, as defined by the European Cooperative Acute Stroke Study III; any intracranial or significant hemorrhage, as defined by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria; and death from all causes at 90 days. Noninferiority for tenecteplase would be declared if the lower 97.5% 1-sided CI for the relative risk (RR) for the primary outcome did not cross 0.937.

Main results: In the modified ITT population, the primary outcome occurred in 439 (62%) of the tenecteplase group and 405 (68%) of the alteplase group (RR, 1.07; 95% CI, 0.98-1.16). This met the prespecified margin for noninferiority. Intracranial hemorrhage within 36 hours was experienced by 15 (2%) patients in the tenecteplase group and 13 (2%) in the alteplase group (RR, 1.18; 95% CI, 0.56-2.50). Death at 90 days occurred in 46 (7%) patients in the tenecteplase group and 35 (5%) in the alteplase group (RR, 1.31; 95% CI, 0.86-2.01).

Conclusion: Tenecteplase was noninferior to alteplase in patients with acute ischemic stroke who met criteria for thrombolysis and either refused or were ineligible for endovascular thrombectomy.

Commentary

Alteplase has been FDA-approved for managing acute ischemic stroke since 1996 and has demonstrated positive effects on functional outcomes. Drawbacks of alteplase therapy, however, include bleeding risk as well as cumbersome administration of a bolus dose followed by a 60-minute infusion. In recent years, the question of whether or not tenecteplase could replace alteplase as the preferred thrombolytic for acute ischemic stroke has garnered much attention. Several features of tenecteplase make it an attractive option, including increased fibrin specificity, a longer half-life, and ease of administration as a single, rapid bolus dose. In phase 2 trials that compared tenecteplase 0.25 mg/kg with alteplase, findings suggested the potential for early neurological improvement as well as improved outcomes at 90 days. While the role of tenecteplase in acute myocardial infarction has been well established due to ease of use and a favorable adverse-effect profile,¹ there is much less evidence from phase 3 randomized controlled clinical trials to secure the role of tenecteplase in acute ischemic stroke.²

Menon et al attempted to close this gap in the literature by conducting a randomized controlled clinical trial (AcT) comparing tenecteplase to alteplase in a Canadian patient population. The trial's patient population mirrors that of real-world data from global registries in terms of age, sex, and baseline stroke severity. In addition, the eligibility window of 4.5 hours from symptom onset as well as the inclusion and exclusion criteria for therapy are common to those utilized in other countries, making the findings generalizable. There were some limitations to the study, however, including the impact of COVID-19 on recruitment efforts as well as limitations of research infrastructure and staffing, which may have limited enrollment efforts at primary stroke centers. Nonetheless, the authors concluded that their results provide evidence that tenecteplase is comparable to alteplase, with similar functional and safety outcomes.

TRACE-2 focused on an Asian patient population and provided follow up to the dose-ranging TRACE-1 phase 2 trial. TRACE-1 showed that tenecteplase 0.25 mg/kg had a similar safety profile to alteplase 0.9 mg/kg in Chinese patients presenting with acute ischemic stroke. TRACE-2 sought to establish noninferiority of tenecteplase and excluded patients who were ineligible for or refused thrombectomy. Interestingly, the tenecteplase arm, as the authors point out, had numerically greater mortality as well as intracranial hemorrhage, but these differences were not statistically significant between the treatment groups at 90 days. The TRACE-2 results parallel those of AcT, and although there were differences in ethnicity between the 2 trials, the authors cite this as evidence that the results are consistent and provide evidence for the role of tenecteplase in the management of acute ischemic stroke. Limitations of this trial include potential bias from its open-label design, as well as exclusion of patients with more severe strokes eligible for thrombectomy, which may limit generalizability to patients with more disabling strokes who could have a higher risk of intracranial hemorrhage.

Application for Clinical Practice and System Implementation

Across the country, many organizations have adopted the off-label use of tenecteplase for managing fibrinolytic-eligible acute ischemic stroke patients. In most cases, the impetus for change is the ease of dosing and administration of tenecteplase compared to alteplase, while the inclusion and exclusion criteria and overall management remain the same. Timely administration of therapy in stroke is critical. This, along with other time constraints in stroke workflows, the weight-based calculation of alteplase doses, and alteplase’s administration method may lead to medication errors when using this agent to treat patients with acute stroke. The rapid, single-dose administration of tenecteplase removes many barriers that hospitals face when patients may need to be treated and then transferred to another site for further care. Without the worry to “drip and ship,” the completion of administration may allow for timely patient transfer and eliminate the need for monitoring of an infusion during transfer. For some organizations, there may be a potential for drug cost-savings as well as improved metrics, such as door-to-needle time, but the overall effects of switching from alteplase to tenecteplase remain to be seen. Currently, tenecteplase is included in stroke guidelines as a “reasonable choice,” though with a low level of evidence.³ However, these 2 studies support the role of tenecteplase in acute ischemic stroke treatment and may provide a foundation for further studies to establish the role of tenecteplase in the acute ischemic stroke population.

Practice Points

• Tenecteplase may be considered as an alternative to alteplase for acute ischemic stroke for patients who meet eligibility criteria for thrombolytics; this recommendation is included in the most recent stroke guidelines, although tenecteplase has not been demonstrated to be superior to alteplase.
• The ease of administration of tenecteplase as a single intravenous bolus dose represents a benefit compared to alteplase; it is an off-label use, however, and further studies are needed to establish the superiority of tenecteplase in terms of functional and safety outcomes.

– Carol Heunisch, PharmD, BCPS, BCCP
Pharmacy Department, NorthShore–Edward-Elmhurst Health, Evanston, IL

Both tooth loss and diabetes can lead to accelerated cognitive decline in older adults, most specifically in those 65-74 years of age, new findings suggest.

The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.

“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.

Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”

Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.

The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.

The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.  
 

Diabetes, edentulism, and cognitive decline

The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.

They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.

Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”

The condition of having no teeth is known as edentulism.

The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).

Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).

In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).

Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).

“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
 

Study limitations: Better data needed

The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.

“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.

Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.

Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”

The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Both tooth loss and diabetes can lead to accelerated cognitive decline in older adults, most specifically in those 65-74 years of age, new findings suggest.

The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.

“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.

Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”

Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.

The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.

The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.  
 

Diabetes, edentulism, and cognitive decline

The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.

They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.

Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”

The condition of having no teeth is known as edentulism.

The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).

Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).

In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).

Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).

“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
 

Study limitations: Better data needed

The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.

“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.

Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.

Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”

The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Both tooth loss and diabetes can lead to accelerated cognitive decline in older adults, most specifically in those 65-74 years of age, new findings suggest.

The data come from a 12-year follow-up of older adults in a nationally representative U.S. survey.

“From a clinical perspective, our study demonstrates the importance of improving access to dental health care and integrating primary dental and medical care. Health care professionals and family caregivers should pay close attention to the cognitive status of diabetic older adults with poor oral health status,” lead author Bei Wu, PhD, of New York University, said in an interview. Dr. Wu is the Dean’s Professor in Global Health and codirector of the NYU Aging Incubator.

Moreover, said Dr. Wu: “For individuals with both poor oral health and diabetes, regular dental visits should be encouraged in addition to adherence to the diabetes self-care protocol.”

Diabetes has long been recognized as a risk factor for cognitive decline, but the findings have been inconsistent for different age groups. Tooth loss has also been linked to cognitive decline and dementia, as well as diabetes.

The mechanisms aren’t entirely clear, but “co-occurring diabetes and poor oral health may increase the risk for dementia, possibly via the potentially interrelated pathways of chronic inflammation and cardiovascular risk factors,” Dr. Wu said.

The new study, published in the Journal of Dental Research, is the first to examine the relationships between all three conditions by age group.  
 

Diabetes, edentulism, and cognitive decline

The data came from a total of 9,948 participants in the Health and Retirement Study (HRS) from 2006 to 2018. At baseline, 5,440 participants were aged 65-74 years, 3,300 were aged 75-84, and 1,208 were aged 85 years or older.

They were assessed every 2 years using the 35-point Telephone Survey for Cognitive Status, which included tests of immediate and delayed word recall, repeated subtracting by 7, counting backward from 20, naming objects, and naming the president and vice president of the U.S. As might be expected, the youngest group scored the highest, averaging 23 points, while the oldest group scored lowest, at 18.5 points.

Participants were also asked if they had ever been told by a doctor that they have diabetes. Another question was: “Have you lost all of your upper and lower natural permanent teeth?”

The condition of having no teeth is known as edentulism.

The percentages of participants who reported having both diabetes and edentulism were 6.0%, 6.7%, and 5.0% for those aged 65-74 years, 75-84 years, and 85 years or older, respectively. The proportions with neither of those conditions were 63.5%, 60.4%, and 58.3% in those three age groups, respectively (P < .001).

Compared with their counterparts with neither diabetes nor edentulism at baseline, older adults with both conditions aged 65-74 years (P < .001) and aged 75-84 years had worse cognitive function (P < .001).

In terms of the rate of cognitive decline, compared with those with neither condition from the same age cohort, older adults aged 65-74 years with both conditions declined at a higher rate (P < .001).

Having diabetes alone led to accelerated cognitive decline in older adults aged 65-74 years (P < .001). Having edentulism alone led to accelerated decline in older adults aged 65-74 years (P < .001) and older adults aged 75-84 years (P < 0.01).

“Our study finds the co-occurrence of diabetes and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65-74 years,” say Wu and colleagues.
 

Study limitations: Better data needed

The study has several limitations, most of them due to the data source. For example, while the HRS collects detailed information on cognitive status, edentulism is its only measure of oral health. There were no data on whether individuals had replacements such as dentures or implants that would affect their ability to eat, which could influence other health factors.

“I have made repeated appeals for federal funding to collect more oral health-related information in large national surveys,” Dr. Wu told this news organization.

Similarly, assessments of diabetes status such as hemoglobin A1c were only available for small subsets and not sufficient to demonstrate statistical significance, she explained.

Dr. Wu suggested that both oral health and cognitive screening might be included in the “Welcome to Medicare” preventive visit. In addition, “Oral hygiene practice should also be highlighted to improve cognitive health. Developing dental care interventions and programs are needed for reducing the societal cost of dementia.”

The study was partially supported by the National Institutes of Health. The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Urine drug testing can be valuable for monitoring patients undergoing treatment with buprenorphine for opioid use disorder (OUD). However, some patients alter their test results by adding buprenorphine directly to their urine sample to imply adherence, a new study shows.

In the study, nearly 2% of all urine drug test specimens analyzed were suggestive of spiking and nearly 8% of patients had at least one specimen that was possibly spiked.

“I anticipate a much-needed increase” in the number of people gaining access to buprenorphine therapy, given elimination of the X waiver, first author Jarratt D. Pytell, MD, with University of Colorado at Denver, Aurora, said in a statement.

“New prescribers of buprenorphine will need to learn how to conduct the increasingly complex initiation of treatment and then gauge whether it is successful or not,” added Dr. Pytell, a general internist and addiction medicine specialist.

“Spiking suggests that treatment is not working – especially in patients continuing illicit drug use. Detecting spiking allows clinicians to adjust or intensify the treatment plan,” Dr. Pytell said in an interview.

The study was published online in JAMA Psychiatry.
 

A sign of elevated patient risk

In a cross-sectional study using Millennium Health’s proprietary urine drug test (UDT) database, researchers analyzed 507,735 urine specimens from 58,476 OUD patients collected between January 2017 and April 2022.

A total of 9546 (1.9%) specimens from 4,550 patients (7.6%) were suggestive of spiking.

UDT specimens suggestive of spiking had two times the odds of being positive for other opioids (fentanyl or heroin), compared with opioid negative samples.

UDT specimens obtained from primary care clinics, from patients aged 35-44 years, and from patients living in the South Atlantic region of the United States were also more likely to be suggestive of buprenorphine spiking.

“Our study demonstrated that a buprenorphine to norbuprenorphine ratio of less than 0.02 indicates the possibility of spiking,” Dr. Pytell said in an interview.

“Nevertheless, it is important to note that this cutoff is not a definitive standard and further controlled studies are necessary to determine its predictive value for spiking. But recognizing possible spiking is very important since it demonstrates a point of elevated risk for the patient and the treatment approach should be reconsidered,” Dr. Pytell said.

“At Millennium Health, we have been tracking the enormity of the drug use crisis. This study suggests that spiking is an important patient safety issue, and it is not uncommon,” study coauthor Eric Dawson, PharmD, vice president of clinical affairs, Millennium Health, said in a statement.

“Detection of spiking requires definitive drug testing. Immunoassay-based, point-of-care tests cannot detect spiking because they are generally incapable of quantitative analysis and differentiating buprenorphine from norbuprenorphine,” Dr. Dawson said.
 

Best practices?

“We need to develop best practices specific for this situation where a patient has added buprenorphine to the urine drug test specimen,” said Dr. Pytell.

“As with all unexpected findings, it is crucial for clinicians to approach this finding in a nonjudgmental manner and work with the patient to understand what might have motivated them to alter their urine specimen,” he added.

Dr. Pytell said a common reaction for clinicians might be to discontinue treatment. However, this is actually a time to try and engage with the patient.

“Clinicians should work collaboratively with patients to identify potential reasons for spiking and determine what changes may need to be made to better support the patient’s recovery,” Dr. Pytell said.

“This could include more frequent monitoring or referral to a higher level of care. In addition, clinicians should be aware that patients who engage in spiking may be experiencing other challenges that impact their ability to adhere to treatment, such as inadequate housing, mental health issues, or financial strain. Addressing these underlying issues may help patients overcome barriers to treatment adherence and reduce the likelihood of future spiking,” Dr. Pytell said.

This study was supported by Millennium Health. The authors have no relevant disclosures.

A version of this article first appeared on Medscape.com.

Urine drug testing can be valuable for monitoring patients undergoing treatment with buprenorphine for opioid use disorder (OUD). However, some patients alter their test results by adding buprenorphine directly to their urine sample to imply adherence, a new study shows.

In the study, nearly 2% of all urine drug test specimens analyzed were suggestive of spiking and nearly 8% of patients had at least one specimen that was possibly spiked.

“I anticipate a much-needed increase” in the number of people gaining access to buprenorphine therapy, given elimination of the X waiver, first author Jarratt D. Pytell, MD, with University of Colorado at Denver, Aurora, said in a statement.

“New prescribers of buprenorphine will need to learn how to conduct the increasingly complex initiation of treatment and then gauge whether it is successful or not,” added Dr. Pytell, a general internist and addiction medicine specialist.

“Spiking suggests that treatment is not working – especially in patients continuing illicit drug use. Detecting spiking allows clinicians to adjust or intensify the treatment plan,” Dr. Pytell said in an interview.

The study was published online in JAMA Psychiatry.
 

A sign of elevated patient risk

In a cross-sectional study using Millennium Health’s proprietary urine drug test (UDT) database, researchers analyzed 507,735 urine specimens from 58,476 OUD patients collected between January 2017 and April 2022.

A total of 9546 (1.9%) specimens from 4,550 patients (7.6%) were suggestive of spiking.

UDT specimens suggestive of spiking had two times the odds of being positive for other opioids (fentanyl or heroin), compared with opioid negative samples.

UDT specimens obtained from primary care clinics, from patients aged 35-44 years, and from patients living in the South Atlantic region of the United States were also more likely to be suggestive of buprenorphine spiking.

“Our study demonstrated that a buprenorphine to norbuprenorphine ratio of less than 0.02 indicates the possibility of spiking,” Dr. Pytell said in an interview.

“Nevertheless, it is important to note that this cutoff is not a definitive standard and further controlled studies are necessary to determine its predictive value for spiking. But recognizing possible spiking is very important since it demonstrates a point of elevated risk for the patient and the treatment approach should be reconsidered,” Dr. Pytell said.

“At Millennium Health, we have been tracking the enormity of the drug use crisis. This study suggests that spiking is an important patient safety issue, and it is not uncommon,” study coauthor Eric Dawson, PharmD, vice president of clinical affairs, Millennium Health, said in a statement.

“Detection of spiking requires definitive drug testing. Immunoassay-based, point-of-care tests cannot detect spiking because they are generally incapable of quantitative analysis and differentiating buprenorphine from norbuprenorphine,” Dr. Dawson said.
 

Best practices?

“We need to develop best practices specific for this situation where a patient has added buprenorphine to the urine drug test specimen,” said Dr. Pytell.

“As with all unexpected findings, it is crucial for clinicians to approach this finding in a nonjudgmental manner and work with the patient to understand what might have motivated them to alter their urine specimen,” he added.

Dr. Pytell said a common reaction for clinicians might be to discontinue treatment. However, this is actually a time to try and engage with the patient.

“Clinicians should work collaboratively with patients to identify potential reasons for spiking and determine what changes may need to be made to better support the patient’s recovery,” Dr. Pytell said.

“This could include more frequent monitoring or referral to a higher level of care. In addition, clinicians should be aware that patients who engage in spiking may be experiencing other challenges that impact their ability to adhere to treatment, such as inadequate housing, mental health issues, or financial strain. Addressing these underlying issues may help patients overcome barriers to treatment adherence and reduce the likelihood of future spiking,” Dr. Pytell said.

This study was supported by Millennium Health. The authors have no relevant disclosures.

A version of this article first appeared on Medscape.com.

Urine drug testing can be valuable for monitoring patients undergoing treatment with buprenorphine for opioid use disorder (OUD). However, some patients alter their test results by adding buprenorphine directly to their urine sample to imply adherence, a new study shows.

In the study, nearly 2% of all urine drug test specimens analyzed were suggestive of spiking and nearly 8% of patients had at least one specimen that was possibly spiked.

“I anticipate a much-needed increase” in the number of people gaining access to buprenorphine therapy, given elimination of the X waiver, first author Jarratt D. Pytell, MD, with University of Colorado at Denver, Aurora, said in a statement.

“New prescribers of buprenorphine will need to learn how to conduct the increasingly complex initiation of treatment and then gauge whether it is successful or not,” added Dr. Pytell, a general internist and addiction medicine specialist.

“Spiking suggests that treatment is not working – especially in patients continuing illicit drug use. Detecting spiking allows clinicians to adjust or intensify the treatment plan,” Dr. Pytell said in an interview.

The study was published online in JAMA Psychiatry.
 

A sign of elevated patient risk

In a cross-sectional study using Millennium Health’s proprietary urine drug test (UDT) database, researchers analyzed 507,735 urine specimens from 58,476 OUD patients collected between January 2017 and April 2022.

A total of 9546 (1.9%) specimens from 4,550 patients (7.6%) were suggestive of spiking.

UDT specimens suggestive of spiking had two times the odds of being positive for other opioids (fentanyl or heroin), compared with opioid negative samples.

UDT specimens obtained from primary care clinics, from patients aged 35-44 years, and from patients living in the South Atlantic region of the United States were also more likely to be suggestive of buprenorphine spiking.

“Our study demonstrated that a buprenorphine to norbuprenorphine ratio of less than 0.02 indicates the possibility of spiking,” Dr. Pytell said in an interview.

“Nevertheless, it is important to note that this cutoff is not a definitive standard and further controlled studies are necessary to determine its predictive value for spiking. But recognizing possible spiking is very important since it demonstrates a point of elevated risk for the patient and the treatment approach should be reconsidered,” Dr. Pytell said.

“At Millennium Health, we have been tracking the enormity of the drug use crisis. This study suggests that spiking is an important patient safety issue, and it is not uncommon,” study coauthor Eric Dawson, PharmD, vice president of clinical affairs, Millennium Health, said in a statement.

“Detection of spiking requires definitive drug testing. Immunoassay-based, point-of-care tests cannot detect spiking because they are generally incapable of quantitative analysis and differentiating buprenorphine from norbuprenorphine,” Dr. Dawson said.
 

Best practices?

“We need to develop best practices specific for this situation where a patient has added buprenorphine to the urine drug test specimen,” said Dr. Pytell.

“As with all unexpected findings, it is crucial for clinicians to approach this finding in a nonjudgmental manner and work with the patient to understand what might have motivated them to alter their urine specimen,” he added.

Dr. Pytell said a common reaction for clinicians might be to discontinue treatment. However, this is actually a time to try and engage with the patient.

“Clinicians should work collaboratively with patients to identify potential reasons for spiking and determine what changes may need to be made to better support the patient’s recovery,” Dr. Pytell said.

“This could include more frequent monitoring or referral to a higher level of care. In addition, clinicians should be aware that patients who engage in spiking may be experiencing other challenges that impact their ability to adhere to treatment, such as inadequate housing, mental health issues, or financial strain. Addressing these underlying issues may help patients overcome barriers to treatment adherence and reduce the likelihood of future spiking,” Dr. Pytell said.

This study was supported by Millennium Health. The authors have no relevant disclosures.

A version of this article first appeared on Medscape.com.

People with epilepsy have a twofold increased risk for death, compared with their counterparts without the condition, irrespective of comorbidities or disease severity, new research shows.

“To our knowledge, this is the only study that has assessed the cause-specific mortality risk among people with epilepsy according to age and disease course,” investigators led by Seo-Young Lee, MD, PhD, of Kangwon National University, Chuncheon, South Korea, write. “Understanding cause-specific mortality risk, particularly the risk of external causes, is important because they are mostly preventable.”

The findings were published online  in Neurology.
 

Higher mortality risk

For the study, researchers analyzed data from the National Health Insurance Service database in Korea from 2006 to 2017 and vital statistics from Statistics Korea from 2008 to 2017.

The study population included 138,998 patients with newly treated epilepsy, with an average at diagnosis of 48.6 years.

Over 665,928 person years of follow-up (mean follow-up, 4.79 years), 20.095 patients died.

People with epilepsy had more than twice the risk for death, compared with the overall population (standardized mortality ratio, 2.25; 95% confidence interval, 2.22-2.28). Mortality was highest in children aged 4 years or younger and was higher in the first year after diagnosis and in women at all age points.

People with epilepsy had a higher mortality risk, compared with the general public, regardless of how many anti-seizure medications they were taking. Those taking only one medication had a 156% higher risk for death (SMR, 1.56; 95% CI, 1.53-1.60), compared with 493% higher risk in those taking four or more medications (SMR, 4.93; 95% CI, 4.76-5.10).

Where patients lived also played a role in mortality risk. Living in a rural area was associated with a 247% higher risk for death, compared with people without epilepsy who lived in the same area (SMR, 2.47; 95% CI, 2.41-2.53), and the risk was 203% higher risk among those living in urban centers (SMR, 2.03; 95% CI, 1.98-2.09).

Although people with comorbidities had higher mortality rates, even those without any other health conditions had a 161% higher risk for death, compared with people without epilepsy (SMR, 1.61; 95% CI, 1.50-1.72).
 

Causes of death

The most frequent causes of death were malignant neoplasm and cerebrovascular disease, which researchers noted are thought to be underlying causes of epilepsy.

Among external causes of death, suicide was the most common cause (2.6%). The suicide rate was highest among younger patients and gradually decreased with age.

Deaths tied directly to epilepsy, transport accidents, or falls were lower in this study than had been previously reported, which may be due to adequate seizure control or because the number of older people with epilepsy and comorbidities is higher in Korea than that reported in other countries.

“To reduce mortality in people with epilepsy, comprehensive efforts [are needed], including a national policy against stigma of epilepsy and clinicians’ total management such as risk stratification, education about injury prevention, and monitoring for suicidal ideation with psychological intervention, as well as active control of seizures,” the authors write.
 

Generalizable findings

Joseph Sirven, MD, professor of neurology at Mayo Clinic Florida, Jacksonville, said that although the study included only Korean patients, the findings are applicable to other counties.

That researchers found patients with epilepsy were more than twice as likely to die prematurely, compared with the general population wasn’t particularly surprising, Dr. Sirven said.

“What struck me the most was the fact that even patients who were on a single drug and seemingly well controlled also had excess mortality reported,” Dr. Sirven said. “That these risks occur should be part of what we tell all patients with epilepsy so that they can better arm themselves with information and help to address some of the risks that this study showed.”

Another important finding is the risk for suicide in patients with epilepsy, especially those who are newly diagnosed, he said.

“When we treat a patient with epilepsy, it should not just be about seizures, but we need to inquire about the psychiatric comorbidities and more importantly manage them in a comprehensive manner,” Dr. Sirven said.

The study was funded by Soonchunhyang University Research Fund and the Korea Health Technology R&D Project. The study authors and Dr. Sirven report no relevant financial conflicts.

A version of this article first appeared on Medscape.com.

People with epilepsy have a twofold increased risk for death, compared with their counterparts without the condition, irrespective of comorbidities or disease severity, new research shows.

“To our knowledge, this is the only study that has assessed the cause-specific mortality risk among people with epilepsy according to age and disease course,” investigators led by Seo-Young Lee, MD, PhD, of Kangwon National University, Chuncheon, South Korea, write. “Understanding cause-specific mortality risk, particularly the risk of external causes, is important because they are mostly preventable.”

The findings were published online  in Neurology.
 

Higher mortality risk

For the study, researchers analyzed data from the National Health Insurance Service database in Korea from 2006 to 2017 and vital statistics from Statistics Korea from 2008 to 2017.

The study population included 138,998 patients with newly treated epilepsy, with an average at diagnosis of 48.6 years.

Over 665,928 person years of follow-up (mean follow-up, 4.79 years), 20.095 patients died.

People with epilepsy had more than twice the risk for death, compared with the overall population (standardized mortality ratio, 2.25; 95% confidence interval, 2.22-2.28). Mortality was highest in children aged 4 years or younger and was higher in the first year after diagnosis and in women at all age points.

People with epilepsy had a higher mortality risk, compared with the general public, regardless of how many anti-seizure medications they were taking. Those taking only one medication had a 156% higher risk for death (SMR, 1.56; 95% CI, 1.53-1.60), compared with 493% higher risk in those taking four or more medications (SMR, 4.93; 95% CI, 4.76-5.10).

Where patients lived also played a role in mortality risk. Living in a rural area was associated with a 247% higher risk for death, compared with people without epilepsy who lived in the same area (SMR, 2.47; 95% CI, 2.41-2.53), and the risk was 203% higher risk among those living in urban centers (SMR, 2.03; 95% CI, 1.98-2.09).

Although people with comorbidities had higher mortality rates, even those without any other health conditions had a 161% higher risk for death, compared with people without epilepsy (SMR, 1.61; 95% CI, 1.50-1.72).
 

Causes of death

The most frequent causes of death were malignant neoplasm and cerebrovascular disease, which researchers noted are thought to be underlying causes of epilepsy.

Among external causes of death, suicide was the most common cause (2.6%). The suicide rate was highest among younger patients and gradually decreased with age.

Deaths tied directly to epilepsy, transport accidents, or falls were lower in this study than had been previously reported, which may be due to adequate seizure control or because the number of older people with epilepsy and comorbidities is higher in Korea than that reported in other countries.

“To reduce mortality in people with epilepsy, comprehensive efforts [are needed], including a national policy against stigma of epilepsy and clinicians’ total management such as risk stratification, education about injury prevention, and monitoring for suicidal ideation with psychological intervention, as well as active control of seizures,” the authors write.
 

Generalizable findings

Joseph Sirven, MD, professor of neurology at Mayo Clinic Florida, Jacksonville, said that although the study included only Korean patients, the findings are applicable to other counties.

That researchers found patients with epilepsy were more than twice as likely to die prematurely, compared with the general population wasn’t particularly surprising, Dr. Sirven said.

“What struck me the most was the fact that even patients who were on a single drug and seemingly well controlled also had excess mortality reported,” Dr. Sirven said. “That these risks occur should be part of what we tell all patients with epilepsy so that they can better arm themselves with information and help to address some of the risks that this study showed.”

Another important finding is the risk for suicide in patients with epilepsy, especially those who are newly diagnosed, he said.

“When we treat a patient with epilepsy, it should not just be about seizures, but we need to inquire about the psychiatric comorbidities and more importantly manage them in a comprehensive manner,” Dr. Sirven said.

The study was funded by Soonchunhyang University Research Fund and the Korea Health Technology R&D Project. The study authors and Dr. Sirven report no relevant financial conflicts.

A version of this article first appeared on Medscape.com.

People with epilepsy have a twofold increased risk for death, compared with their counterparts without the condition, irrespective of comorbidities or disease severity, new research shows.

“To our knowledge, this is the only study that has assessed the cause-specific mortality risk among people with epilepsy according to age and disease course,” investigators led by Seo-Young Lee, MD, PhD, of Kangwon National University, Chuncheon, South Korea, write. “Understanding cause-specific mortality risk, particularly the risk of external causes, is important because they are mostly preventable.”

The findings were published online  in Neurology.
 

Higher mortality risk

For the study, researchers analyzed data from the National Health Insurance Service database in Korea from 2006 to 2017 and vital statistics from Statistics Korea from 2008 to 2017.

The study population included 138,998 patients with newly treated epilepsy, with an average at diagnosis of 48.6 years.

Over 665,928 person years of follow-up (mean follow-up, 4.79 years), 20.095 patients died.

People with epilepsy had more than twice the risk for death, compared with the overall population (standardized mortality ratio, 2.25; 95% confidence interval, 2.22-2.28). Mortality was highest in children aged 4 years or younger and was higher in the first year after diagnosis and in women at all age points.

People with epilepsy had a higher mortality risk, compared with the general public, regardless of how many anti-seizure medications they were taking. Those taking only one medication had a 156% higher risk for death (SMR, 1.56; 95% CI, 1.53-1.60), compared with 493% higher risk in those taking four or more medications (SMR, 4.93; 95% CI, 4.76-5.10).

Where patients lived also played a role in mortality risk. Living in a rural area was associated with a 247% higher risk for death, compared with people without epilepsy who lived in the same area (SMR, 2.47; 95% CI, 2.41-2.53), and the risk was 203% higher risk among those living in urban centers (SMR, 2.03; 95% CI, 1.98-2.09).

Although people with comorbidities had higher mortality rates, even those without any other health conditions had a 161% higher risk for death, compared with people without epilepsy (SMR, 1.61; 95% CI, 1.50-1.72).
 

Causes of death

The most frequent causes of death were malignant neoplasm and cerebrovascular disease, which researchers noted are thought to be underlying causes of epilepsy.

Among external causes of death, suicide was the most common cause (2.6%). The suicide rate was highest among younger patients and gradually decreased with age.

Deaths tied directly to epilepsy, transport accidents, or falls were lower in this study than had been previously reported, which may be due to adequate seizure control or because the number of older people with epilepsy and comorbidities is higher in Korea than that reported in other countries.

“To reduce mortality in people with epilepsy, comprehensive efforts [are needed], including a national policy against stigma of epilepsy and clinicians’ total management such as risk stratification, education about injury prevention, and monitoring for suicidal ideation with psychological intervention, as well as active control of seizures,” the authors write.
 

Generalizable findings

Joseph Sirven, MD, professor of neurology at Mayo Clinic Florida, Jacksonville, said that although the study included only Korean patients, the findings are applicable to other counties.

That researchers found patients with epilepsy were more than twice as likely to die prematurely, compared with the general population wasn’t particularly surprising, Dr. Sirven said.

“What struck me the most was the fact that even patients who were on a single drug and seemingly well controlled also had excess mortality reported,” Dr. Sirven said. “That these risks occur should be part of what we tell all patients with epilepsy so that they can better arm themselves with information and help to address some of the risks that this study showed.”

Another important finding is the risk for suicide in patients with epilepsy, especially those who are newly diagnosed, he said.

“When we treat a patient with epilepsy, it should not just be about seizures, but we need to inquire about the psychiatric comorbidities and more importantly manage them in a comprehensive manner,” Dr. Sirven said.

The study was funded by Soonchunhyang University Research Fund and the Korea Health Technology R&D Project. The study authors and Dr. Sirven report no relevant financial conflicts.

A version of this article first appeared on Medscape.com.

Restless legs syndrome (RLS) is associated with an elevated risk of dementia among older adults, suggesting the disorder may be a risk factor for dementia or a very early noncognitive sign of dementia, researchers say.

In a large population-based cohort study, adults with RLS were significantly more likely to develop dementia over more than a decade than were their peers without RLS.

If confirmed in future studies, “regular check-ups for cognitive decline in older patients with RLS may facilitate earlier detection and intervention for those with dementia risk,” wrote investigators led by Eosu Kim, MD, PhD, with Yonsei University, Seoul, Republic of Korea.

The study was published online in Alzheimer’s Research and Therapy.
 

Sleep disorders and dementia

RLS is associated with poor sleep, depression/anxiety, poor diet, microvasculopathy, and hypoxia – all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia has been unclear.

The researchers compared risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) among 2,501 adults with newly diagnosed RLS and 9,977 matched control persons participating in the Korean National Health Insurance Service–Elderly Cohort, a nationwide population-based cohort of adults aged 60 and older.

The mean age of the cohort was 73 years; most of the participants were women (65%). Among all 12,478 participants, 874 (7%) developed all-cause dementia during follow-up – 475 (54%) developed AD, and 194 (22%) developed VaD.

The incidence of all-cause dementia was significantly higher among the RLS group than among the control group (10.4% vs. 6.2%). Incidence rates of AD and VaD (5.6% and 2.6%, respectively) were also higher in the RLS group than in the control group (3.4% and 1.3%, respectively).

In Cox regression analysis, RLS was significantly associated with an increased risk of all-cause dementia (adjusted hazard ratio [aHR], 1.46; 95% confidence interval [CI], 1.24-1.72), AD (aHR 1.38; 95% CI, 1.11-1.72) and VaD (aHR, 1.81; 95% CI, 1.30-2.53).

The researchers noted that RLS may precede deterioration of cognitive function, leading to dementia, and they suggest that RLS could be regarded as a “newly identified” risk factor or prodromal sign of dementia.
 

Modifiable risk factor

Reached for comment, Thanh Dang-Vu, MD, PhD, professor and research chair in sleep, neuroimaging, and cognitive health at Concordia University in Montreal, said there is now “increasing literature that shows sleep as a modifiable risk factor for cognitive decline.

“Previous evidence indicates that both sleep apnea and insomnia disorder increase the risk for cognitive decline and possibly dementia. Here the study adds to this body of evidence linking sleep disorders to dementia, suggesting that RLS should also be considered as a sleep-related risk factor,” Dr. Dang-Vu told this news organization.

“More evidence is needed, though, as here, all diagnoses were based on national health insurance diagnostic codes, and it is likely there were missed diagnoses for RLS but also for other sleep disorders, as there was no systematic screening for them,” Dr. Dang-Vu cautioned.

Support for the study was provided by the Ministry of Health and Welfare, the Korean government, and Yonsei University. Dr. Kim and Dr. Dang-Vu reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Restless legs syndrome (RLS) is associated with an elevated risk of dementia among older adults, suggesting the disorder may be a risk factor for dementia or a very early noncognitive sign of dementia, researchers say.

In a large population-based cohort study, adults with RLS were significantly more likely to develop dementia over more than a decade than were their peers without RLS.

If confirmed in future studies, “regular check-ups for cognitive decline in older patients with RLS may facilitate earlier detection and intervention for those with dementia risk,” wrote investigators led by Eosu Kim, MD, PhD, with Yonsei University, Seoul, Republic of Korea.

The study was published online in Alzheimer’s Research and Therapy.
 

Sleep disorders and dementia

RLS is associated with poor sleep, depression/anxiety, poor diet, microvasculopathy, and hypoxia – all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia has been unclear.

The researchers compared risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) among 2,501 adults with newly diagnosed RLS and 9,977 matched control persons participating in the Korean National Health Insurance Service–Elderly Cohort, a nationwide population-based cohort of adults aged 60 and older.

The mean age of the cohort was 73 years; most of the participants were women (65%). Among all 12,478 participants, 874 (7%) developed all-cause dementia during follow-up – 475 (54%) developed AD, and 194 (22%) developed VaD.

The incidence of all-cause dementia was significantly higher among the RLS group than among the control group (10.4% vs. 6.2%). Incidence rates of AD and VaD (5.6% and 2.6%, respectively) were also higher in the RLS group than in the control group (3.4% and 1.3%, respectively).

In Cox regression analysis, RLS was significantly associated with an increased risk of all-cause dementia (adjusted hazard ratio [aHR], 1.46; 95% confidence interval [CI], 1.24-1.72), AD (aHR 1.38; 95% CI, 1.11-1.72) and VaD (aHR, 1.81; 95% CI, 1.30-2.53).

The researchers noted that RLS may precede deterioration of cognitive function, leading to dementia, and they suggest that RLS could be regarded as a “newly identified” risk factor or prodromal sign of dementia.
 

Modifiable risk factor

Reached for comment, Thanh Dang-Vu, MD, PhD, professor and research chair in sleep, neuroimaging, and cognitive health at Concordia University in Montreal, said there is now “increasing literature that shows sleep as a modifiable risk factor for cognitive decline.

“Previous evidence indicates that both sleep apnea and insomnia disorder increase the risk for cognitive decline and possibly dementia. Here the study adds to this body of evidence linking sleep disorders to dementia, suggesting that RLS should also be considered as a sleep-related risk factor,” Dr. Dang-Vu told this news organization.

“More evidence is needed, though, as here, all diagnoses were based on national health insurance diagnostic codes, and it is likely there were missed diagnoses for RLS but also for other sleep disorders, as there was no systematic screening for them,” Dr. Dang-Vu cautioned.

Support for the study was provided by the Ministry of Health and Welfare, the Korean government, and Yonsei University. Dr. Kim and Dr. Dang-Vu reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Restless legs syndrome (RLS) is associated with an elevated risk of dementia among older adults, suggesting the disorder may be a risk factor for dementia or a very early noncognitive sign of dementia, researchers say.

In a large population-based cohort study, adults with RLS were significantly more likely to develop dementia over more than a decade than were their peers without RLS.

If confirmed in future studies, “regular check-ups for cognitive decline in older patients with RLS may facilitate earlier detection and intervention for those with dementia risk,” wrote investigators led by Eosu Kim, MD, PhD, with Yonsei University, Seoul, Republic of Korea.

The study was published online in Alzheimer’s Research and Therapy.
 

Sleep disorders and dementia

RLS is associated with poor sleep, depression/anxiety, poor diet, microvasculopathy, and hypoxia – all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia has been unclear.

The researchers compared risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) among 2,501 adults with newly diagnosed RLS and 9,977 matched control persons participating in the Korean National Health Insurance Service–Elderly Cohort, a nationwide population-based cohort of adults aged 60 and older.

The mean age of the cohort was 73 years; most of the participants were women (65%). Among all 12,478 participants, 874 (7%) developed all-cause dementia during follow-up – 475 (54%) developed AD, and 194 (22%) developed VaD.

The incidence of all-cause dementia was significantly higher among the RLS group than among the control group (10.4% vs. 6.2%). Incidence rates of AD and VaD (5.6% and 2.6%, respectively) were also higher in the RLS group than in the control group (3.4% and 1.3%, respectively).

In Cox regression analysis, RLS was significantly associated with an increased risk of all-cause dementia (adjusted hazard ratio [aHR], 1.46; 95% confidence interval [CI], 1.24-1.72), AD (aHR 1.38; 95% CI, 1.11-1.72) and VaD (aHR, 1.81; 95% CI, 1.30-2.53).

The researchers noted that RLS may precede deterioration of cognitive function, leading to dementia, and they suggest that RLS could be regarded as a “newly identified” risk factor or prodromal sign of dementia.
 

Modifiable risk factor

Reached for comment, Thanh Dang-Vu, MD, PhD, professor and research chair in sleep, neuroimaging, and cognitive health at Concordia University in Montreal, said there is now “increasing literature that shows sleep as a modifiable risk factor for cognitive decline.

“Previous evidence indicates that both sleep apnea and insomnia disorder increase the risk for cognitive decline and possibly dementia. Here the study adds to this body of evidence linking sleep disorders to dementia, suggesting that RLS should also be considered as a sleep-related risk factor,” Dr. Dang-Vu told this news organization.

“More evidence is needed, though, as here, all diagnoses were based on national health insurance diagnostic codes, and it is likely there were missed diagnoses for RLS but also for other sleep disorders, as there was no systematic screening for them,” Dr. Dang-Vu cautioned.

Support for the study was provided by the Ministry of Health and Welfare, the Korean government, and Yonsei University. Dr. Kim and Dr. Dang-Vu reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

When I read the news that Bruce Willis had disclosed his diagnosis of frontotemporal dementia (FTD), I was reminded that all of us are at risk for spending our final epoch lost in a neurologic swamp. What is remarkable about the swamp that we call FTD is that it’s a somewhat rare and unusual type of dementia. We tend to characterize dementia as the erosion of memory, but FTD is more characterized by the loss of control over emotions and other cognitive functions. What›s especially tragic for performers like Mr. Willis is the loss of the verbal fluency required for delivering one’s lines.

Frontotemporal dementia

To this casual observer, Bruce Willis was an almost invincible force, vigorous, vital, one of the “immortals.” Alas, with his FTD diagnosis, we know that even a die-hard like Mr. Willis, now only 67 years of age, may have to endure years of progressive decline. If the disease follows its typical path, that will probably include slowly disconnecting and progressively losing emotional judgment and control as well as losing a reasonable understanding of what or why any of it is happening. He may also experience a progressive deterioration of the control of bodily functions and general health.

Most people with dementia lose their neurocognitive abilities through a number of different pathways, all of which result in brain shrinkage, disconnection, evident neuropathology, neurobehavioral expressions of loss, and forms of befuddlement. Alzheimer’s disease leads the list as the most common form of dementia, but vascular dementias; dementia with Lewy bodies; “mixed” dementias; dementias associated with Parkinson’s, Huntington’s, or other diseases; dementia rising from alcoholic or other brain poisoning, HIV, Lyme disease, or a host of other brain infections; or from traumatic encephalopathy (chronic or more current) may present at any active neurology clinic. These are what you might think of as your “grandpa’s dementia” – the common types often associated with old age.

FTD is a particularly interesting variant for several reasons. First, it usually arises in relatively young individuals, with initial symptoms emerging in one’s 50s or 60s. In most cases, there is no genetic and, with rare exception, any other explanation of origin – except that old medical standby, bad luck.

Second, FTD has little initial impact on a patient’s broader memory and associated cognitive abilities. The patient will stumble to come up with that next word and ultimately slow down their speech as their brain struggles with verbal fluency; they will struggle with translating their feelings and emotions into fast and appropriate actions expressed in their mind and their physical body while their memory will appear intact.

In all other dementias, cognitive losses can be profound, whereas social and emotional control and voluble speech production are generally better sustained. Imagine the impact that these struggles in verbal fluency and in emotional calibration and response must have for an established actor. By all reports, Mr. Willis vigorously pursued the work that he loved right up until the time of his dementia diagnosis, even as his colleagues would almost certainly have seen that he was struggling. Sadly, a lack of that type of self-awareness is an expected consequence of FTD.
 

The salience network and von Economo neurons

Third and most intriguing to a neuroscientific nerd like me is that patients with FTD experience an initial loss of a special population of cortical neurons located within the salience network in our brains, called the von Economo neurons. That salience network is designed to quickly read and evaluate our complex thoughts and emotions and via those Economo neurons, initiate appropriate neurologic and physical responses.

We share this special von Economo machinery with great apes, whales, elephants, and a handful of other especially social mammalian species.

When we see or hear or otherwise sense something that induces fear, alarm, or a potential reward, the salience network in our brain acts as a kind of gatekeeper. First, it assesses the emergent or changing situation, then it rapidly initiates an emotional and physical response. As I sit with a patient in obvious distress in my office, my salience network turns on an empathetic alarm. My brain and body immediately adjust to initiate appropriately sympathetic reactions. The von Economo neurons – those very neurons that have substantially died off in a brain with FTD – are the linchpins in this fast-response emotion and complex body signal-informed system.

Controlled emotional response is at the heart of our humanity. It’s a sad day when we lose it.

In other neurologic clinical conditions marked by the loss of specific brain cells, different forms of “disuse atrophy” are partly the cause. We don’t know whether that’s the case for FTD. Scientists have shown that specific forms of computerized brain exercises can sharply increase activity levels in the salience network which is linked to improvements in the regulatory control of the autonomic nervous system – one of the key response-mediating targets of the network’s von Economo neurons.

Interestingly, superagers who sustain body and brain health into their 90s (and beyond) die with a full complement of von Economo neurons operating happily in a still-vigorous salience network.

This neuroscientist can foresee a day when we routinely assess the integrity of this important brain system and more reliably maintain its good health. Keeping those very special neurons alive would have probably allowed Mr. Willis to sustain himself on the soundstage and on the grander stage of life for a long time to come. Alas, like so many things in medicine, there is promise. But at this moment for this famous patient, our current medical science appears to be a day late, and a dollar short.

Dr. Merzenichis is professor emeritus at the University of California, San Francisco, and a Kavli Laureate in Neuroscience. He reported conflicts of interest with the National Institutes of Health, Stronger Brains, and Posit Science.
 

A version of this article first appeared on Medscape.com.

When I read the news that Bruce Willis had disclosed his diagnosis of frontotemporal dementia (FTD), I was reminded that all of us are at risk for spending our final epoch lost in a neurologic swamp. What is remarkable about the swamp that we call FTD is that it’s a somewhat rare and unusual type of dementia. We tend to characterize dementia as the erosion of memory, but FTD is more characterized by the loss of control over emotions and other cognitive functions. What›s especially tragic for performers like Mr. Willis is the loss of the verbal fluency required for delivering one’s lines.

Frontotemporal dementia

To this casual observer, Bruce Willis was an almost invincible force, vigorous, vital, one of the “immortals.” Alas, with his FTD diagnosis, we know that even a die-hard like Mr. Willis, now only 67 years of age, may have to endure years of progressive decline. If the disease follows its typical path, that will probably include slowly disconnecting and progressively losing emotional judgment and control as well as losing a reasonable understanding of what or why any of it is happening. He may also experience a progressive deterioration of the control of bodily functions and general health.

Most people with dementia lose their neurocognitive abilities through a number of different pathways, all of which result in brain shrinkage, disconnection, evident neuropathology, neurobehavioral expressions of loss, and forms of befuddlement. Alzheimer’s disease leads the list as the most common form of dementia, but vascular dementias; dementia with Lewy bodies; “mixed” dementias; dementias associated with Parkinson’s, Huntington’s, or other diseases; dementia rising from alcoholic or other brain poisoning, HIV, Lyme disease, or a host of other brain infections; or from traumatic encephalopathy (chronic or more current) may present at any active neurology clinic. These are what you might think of as your “grandpa’s dementia” – the common types often associated with old age.

FTD is a particularly interesting variant for several reasons. First, it usually arises in relatively young individuals, with initial symptoms emerging in one’s 50s or 60s. In most cases, there is no genetic and, with rare exception, any other explanation of origin – except that old medical standby, bad luck.

Second, FTD has little initial impact on a patient’s broader memory and associated cognitive abilities. The patient will stumble to come up with that next word and ultimately slow down their speech as their brain struggles with verbal fluency; they will struggle with translating their feelings and emotions into fast and appropriate actions expressed in their mind and their physical body while their memory will appear intact.

In all other dementias, cognitive losses can be profound, whereas social and emotional control and voluble speech production are generally better sustained. Imagine the impact that these struggles in verbal fluency and in emotional calibration and response must have for an established actor. By all reports, Mr. Willis vigorously pursued the work that he loved right up until the time of his dementia diagnosis, even as his colleagues would almost certainly have seen that he was struggling. Sadly, a lack of that type of self-awareness is an expected consequence of FTD.
 

The salience network and von Economo neurons

Third and most intriguing to a neuroscientific nerd like me is that patients with FTD experience an initial loss of a special population of cortical neurons located within the salience network in our brains, called the von Economo neurons. That salience network is designed to quickly read and evaluate our complex thoughts and emotions and via those Economo neurons, initiate appropriate neurologic and physical responses.

We share this special von Economo machinery with great apes, whales, elephants, and a handful of other especially social mammalian species.

When we see or hear or otherwise sense something that induces fear, alarm, or a potential reward, the salience network in our brain acts as a kind of gatekeeper. First, it assesses the emergent or changing situation, then it rapidly initiates an emotional and physical response. As I sit with a patient in obvious distress in my office, my salience network turns on an empathetic alarm. My brain and body immediately adjust to initiate appropriately sympathetic reactions. The von Economo neurons – those very neurons that have substantially died off in a brain with FTD – are the linchpins in this fast-response emotion and complex body signal-informed system.

Controlled emotional response is at the heart of our humanity. It’s a sad day when we lose it.

In other neurologic clinical conditions marked by the loss of specific brain cells, different forms of “disuse atrophy” are partly the cause. We don’t know whether that’s the case for FTD. Scientists have shown that specific forms of computerized brain exercises can sharply increase activity levels in the salience network which is linked to improvements in the regulatory control of the autonomic nervous system – one of the key response-mediating targets of the network’s von Economo neurons.

Interestingly, superagers who sustain body and brain health into their 90s (and beyond) die with a full complement of von Economo neurons operating happily in a still-vigorous salience network.

This neuroscientist can foresee a day when we routinely assess the integrity of this important brain system and more reliably maintain its good health. Keeping those very special neurons alive would have probably allowed Mr. Willis to sustain himself on the soundstage and on the grander stage of life for a long time to come. Alas, like so many things in medicine, there is promise. But at this moment for this famous patient, our current medical science appears to be a day late, and a dollar short.

Dr. Merzenichis is professor emeritus at the University of California, San Francisco, and a Kavli Laureate in Neuroscience. He reported conflicts of interest with the National Institutes of Health, Stronger Brains, and Posit Science.
 

A version of this article first appeared on Medscape.com.

When I read the news that Bruce Willis had disclosed his diagnosis of frontotemporal dementia (FTD), I was reminded that all of us are at risk for spending our final epoch lost in a neurologic swamp. What is remarkable about the swamp that we call FTD is that it’s a somewhat rare and unusual type of dementia. We tend to characterize dementia as the erosion of memory, but FTD is more characterized by the loss of control over emotions and other cognitive functions. What›s especially tragic for performers like Mr. Willis is the loss of the verbal fluency required for delivering one’s lines.

Frontotemporal dementia

To this casual observer, Bruce Willis was an almost invincible force, vigorous, vital, one of the “immortals.” Alas, with his FTD diagnosis, we know that even a die-hard like Mr. Willis, now only 67 years of age, may have to endure years of progressive decline. If the disease follows its typical path, that will probably include slowly disconnecting and progressively losing emotional judgment and control as well as losing a reasonable understanding of what or why any of it is happening. He may also experience a progressive deterioration of the control of bodily functions and general health.

Most people with dementia lose their neurocognitive abilities through a number of different pathways, all of which result in brain shrinkage, disconnection, evident neuropathology, neurobehavioral expressions of loss, and forms of befuddlement. Alzheimer’s disease leads the list as the most common form of dementia, but vascular dementias; dementia with Lewy bodies; “mixed” dementias; dementias associated with Parkinson’s, Huntington’s, or other diseases; dementia rising from alcoholic or other brain poisoning, HIV, Lyme disease, or a host of other brain infections; or from traumatic encephalopathy (chronic or more current) may present at any active neurology clinic. These are what you might think of as your “grandpa’s dementia” – the common types often associated with old age.

FTD is a particularly interesting variant for several reasons. First, it usually arises in relatively young individuals, with initial symptoms emerging in one’s 50s or 60s. In most cases, there is no genetic and, with rare exception, any other explanation of origin – except that old medical standby, bad luck.

Second, FTD has little initial impact on a patient’s broader memory and associated cognitive abilities. The patient will stumble to come up with that next word and ultimately slow down their speech as their brain struggles with verbal fluency; they will struggle with translating their feelings and emotions into fast and appropriate actions expressed in their mind and their physical body while their memory will appear intact.

In all other dementias, cognitive losses can be profound, whereas social and emotional control and voluble speech production are generally better sustained. Imagine the impact that these struggles in verbal fluency and in emotional calibration and response must have for an established actor. By all reports, Mr. Willis vigorously pursued the work that he loved right up until the time of his dementia diagnosis, even as his colleagues would almost certainly have seen that he was struggling. Sadly, a lack of that type of self-awareness is an expected consequence of FTD.
 

The salience network and von Economo neurons

Third and most intriguing to a neuroscientific nerd like me is that patients with FTD experience an initial loss of a special population of cortical neurons located within the salience network in our brains, called the von Economo neurons. That salience network is designed to quickly read and evaluate our complex thoughts and emotions and via those Economo neurons, initiate appropriate neurologic and physical responses.

We share this special von Economo machinery with great apes, whales, elephants, and a handful of other especially social mammalian species.

When we see or hear or otherwise sense something that induces fear, alarm, or a potential reward, the salience network in our brain acts as a kind of gatekeeper. First, it assesses the emergent or changing situation, then it rapidly initiates an emotional and physical response. As I sit with a patient in obvious distress in my office, my salience network turns on an empathetic alarm. My brain and body immediately adjust to initiate appropriately sympathetic reactions. The von Economo neurons – those very neurons that have substantially died off in a brain with FTD – are the linchpins in this fast-response emotion and complex body signal-informed system.

Controlled emotional response is at the heart of our humanity. It’s a sad day when we lose it.

In other neurologic clinical conditions marked by the loss of specific brain cells, different forms of “disuse atrophy” are partly the cause. We don’t know whether that’s the case for FTD. Scientists have shown that specific forms of computerized brain exercises can sharply increase activity levels in the salience network which is linked to improvements in the regulatory control of the autonomic nervous system – one of the key response-mediating targets of the network’s von Economo neurons.

Interestingly, superagers who sustain body and brain health into their 90s (and beyond) die with a full complement of von Economo neurons operating happily in a still-vigorous salience network.

This neuroscientist can foresee a day when we routinely assess the integrity of this important brain system and more reliably maintain its good health. Keeping those very special neurons alive would have probably allowed Mr. Willis to sustain himself on the soundstage and on the grander stage of life for a long time to come. Alas, like so many things in medicine, there is promise. But at this moment for this famous patient, our current medical science appears to be a day late, and a dollar short.

Dr. Merzenichis is professor emeritus at the University of California, San Francisco, and a Kavli Laureate in Neuroscience. He reported conflicts of interest with the National Institutes of Health, Stronger Brains, and Posit Science.
 

A version of this article first appeared on Medscape.com.

Children with autism spectrum disorder (ASD) are significantly less likely to have vision screening at well visits for 3- to 5-year-olds than are typically developing children, researchers have found.

The report, by Kimberly Hoover, MD, of Thomas Jefferson University in Philadelphia, and colleagues, was published online in Pediatrics.

While 59.9% of children without ASD got vision screening in these visits, only 36.5% of children with ASD got the screening. Both screening rates miss the mark set by American Academy of Pediatrics guidelines.

The AAP recommends “annual instrument-based vision screening, if available, at well visits for children starting at age 12 months to 3 years, and direct visual acuity testing beginning at 4 years of age. However, in children with developmental delays, the AAP recommends instrument-based screening, such as photoscreening, as a useful alternative at any age.”
 

Racial, age disparities as well

Racial disparities were evident in the data as well. Of the children who had ASD, Black children had the lowest rates of screening (27.6%), while the rate for White children was 39.7%. The rate for other/multiracial children with ASD was 39.8%.

The lowest rates of screening occurred in the youngest children, at the 3-year visit.

The researchers analyzed data from 63,829 well-child visits between January 2016 and December 2019, collected from the large primary care database PEDSnet.
 

Photoscreening vs. acuity screening

The authors pointed out that children with ASD are less likely to complete a vision test, which can be problematic in a busy primary care office.

“Children with ASD were significantly less likely to have at least one completed vision screening (43.2%) compared with children without ASD (72.1%; P <. 01),” the authors wrote, “with only 6.9% of children with ASD having had two or more vision screenings compared with 22.3% of children without ASD.”

The researchers saw higher vision test completion rates with photoscreening, using a sophisticated camera, compared with acuity screening, which uses a wall chart and requires responses.

Less patient participation is required for photoscreening and it can be done in less than 2 minutes.

If ability to complete the vision tests is a concern, the authors wrote, photoscreening may be a better solution.
 

Photoscreening takes 90 seconds

“Photoscreening has high sensitivity in detecting ocular conditions in children with ASD and has an average screening time of 90 seconds, and [it has] been validated in both children with ASD and developmental delays,” the authors wrote.

Andrew Adesman, MD, chief of developmental and behavioral pediatrics at Cohen Children’s Medical Center in New Hyde Park, N.Y., said the authors of this study quantify the gap between need and reality for vision tests for those with ASD.

“Other studies have shown that children on the autism spectrum have more than three times greater risk of having eye disease or vision problems,” he said in an interview. “You’ve got a high-risk population in need of assessment and the likelihood of them getting an assessment is much reduced.”

He said in addition to attention problems in taking the test, vision screening may get lost in the plethora of concerns parents want to talk about in well-child visits.

“If you’re the parent of a child with developmental delays, language delays, poor social engagement, there are a multitude of things the visit could be focused on and it may be that vision screening possibly gets compromised or not done,” Dr. Adesman said.

That, he said, may be a focus area for improving the screening numbers.

Neither parents nor providers should forget that vision screening is important, despite the myriad other issues to address, he said. “They don’t have to take a long time.”

When it comes to vision problems and children, “the earlier they’re identified the better,” Dr. Adesman says, particularly to identify the need for eye muscle surgery or corrective lenses, the two major interventions for strabismus or refractive error.

“If those problems are significant and go untreated, there’s a risk of loss of vision in the affected eye,” he said.
 

Reimbursement concerns for photoscreening

This study strongly supports the use of routine photoscreening to help eliminate the vision screening gap in children with ASD, the authors wrote.

They noted, however, that would require insurance reimbursement for primary care practices to effectively use that screening.

The researchers advised, “Providers treating patients with race, ethnicity, region, or age categories that reduce the adjusted odds of photoscreening can take steps in their practices to address these disparities, particularly in children with ASD.”

The study authors and Dr. Adesman reported no relevant financial relationships.

Children with autism spectrum disorder (ASD) are significantly less likely to have vision screening at well visits for 3- to 5-year-olds than are typically developing children, researchers have found.

The report, by Kimberly Hoover, MD, of Thomas Jefferson University in Philadelphia, and colleagues, was published online in Pediatrics.

While 59.9% of children without ASD got vision screening in these visits, only 36.5% of children with ASD got the screening. Both screening rates miss the mark set by American Academy of Pediatrics guidelines.

The AAP recommends “annual instrument-based vision screening, if available, at well visits for children starting at age 12 months to 3 years, and direct visual acuity testing beginning at 4 years of age. However, in children with developmental delays, the AAP recommends instrument-based screening, such as photoscreening, as a useful alternative at any age.”
 

Racial, age disparities as well

Racial disparities were evident in the data as well. Of the children who had ASD, Black children had the lowest rates of screening (27.6%), while the rate for White children was 39.7%. The rate for other/multiracial children with ASD was 39.8%.

The lowest rates of screening occurred in the youngest children, at the 3-year visit.

The researchers analyzed data from 63,829 well-child visits between January 2016 and December 2019, collected from the large primary care database PEDSnet.
 

Photoscreening vs. acuity screening

The authors pointed out that children with ASD are less likely to complete a vision test, which can be problematic in a busy primary care office.

“Children with ASD were significantly less likely to have at least one completed vision screening (43.2%) compared with children without ASD (72.1%; P <. 01),” the authors wrote, “with only 6.9% of children with ASD having had two or more vision screenings compared with 22.3% of children without ASD.”

The researchers saw higher vision test completion rates with photoscreening, using a sophisticated camera, compared with acuity screening, which uses a wall chart and requires responses.

Less patient participation is required for photoscreening and it can be done in less than 2 minutes.

If ability to complete the vision tests is a concern, the authors wrote, photoscreening may be a better solution.
 

Photoscreening takes 90 seconds

“Photoscreening has high sensitivity in detecting ocular conditions in children with ASD and has an average screening time of 90 seconds, and [it has] been validated in both children with ASD and developmental delays,” the authors wrote.

Andrew Adesman, MD, chief of developmental and behavioral pediatrics at Cohen Children’s Medical Center in New Hyde Park, N.Y., said the authors of this study quantify the gap between need and reality for vision tests for those with ASD.

“Other studies have shown that children on the autism spectrum have more than three times greater risk of having eye disease or vision problems,” he said in an interview. “You’ve got a high-risk population in need of assessment and the likelihood of them getting an assessment is much reduced.”

He said in addition to attention problems in taking the test, vision screening may get lost in the plethora of concerns parents want to talk about in well-child visits.

“If you’re the parent of a child with developmental delays, language delays, poor social engagement, there are a multitude of things the visit could be focused on and it may be that vision screening possibly gets compromised or not done,” Dr. Adesman said.

That, he said, may be a focus area for improving the screening numbers.

Neither parents nor providers should forget that vision screening is important, despite the myriad other issues to address, he said. “They don’t have to take a long time.”

When it comes to vision problems and children, “the earlier they’re identified the better,” Dr. Adesman says, particularly to identify the need for eye muscle surgery or corrective lenses, the two major interventions for strabismus or refractive error.

“If those problems are significant and go untreated, there’s a risk of loss of vision in the affected eye,” he said.
 

Reimbursement concerns for photoscreening

This study strongly supports the use of routine photoscreening to help eliminate the vision screening gap in children with ASD, the authors wrote.

They noted, however, that would require insurance reimbursement for primary care practices to effectively use that screening.

The researchers advised, “Providers treating patients with race, ethnicity, region, or age categories that reduce the adjusted odds of photoscreening can take steps in their practices to address these disparities, particularly in children with ASD.”

The study authors and Dr. Adesman reported no relevant financial relationships.

Children with autism spectrum disorder (ASD) are significantly less likely to have vision screening at well visits for 3- to 5-year-olds than are typically developing children, researchers have found.

The report, by Kimberly Hoover, MD, of Thomas Jefferson University in Philadelphia, and colleagues, was published online in Pediatrics.

While 59.9% of children without ASD got vision screening in these visits, only 36.5% of children with ASD got the screening. Both screening rates miss the mark set by American Academy of Pediatrics guidelines.

The AAP recommends “annual instrument-based vision screening, if available, at well visits for children starting at age 12 months to 3 years, and direct visual acuity testing beginning at 4 years of age. However, in children with developmental delays, the AAP recommends instrument-based screening, such as photoscreening, as a useful alternative at any age.”
 

Racial, age disparities as well

Racial disparities were evident in the data as well. Of the children who had ASD, Black children had the lowest rates of screening (27.6%), while the rate for White children was 39.7%. The rate for other/multiracial children with ASD was 39.8%.

The lowest rates of screening occurred in the youngest children, at the 3-year visit.

The researchers analyzed data from 63,829 well-child visits between January 2016 and December 2019, collected from the large primary care database PEDSnet.
 

Photoscreening vs. acuity screening

The authors pointed out that children with ASD are less likely to complete a vision test, which can be problematic in a busy primary care office.

“Children with ASD were significantly less likely to have at least one completed vision screening (43.2%) compared with children without ASD (72.1%; P <. 01),” the authors wrote, “with only 6.9% of children with ASD having had two or more vision screenings compared with 22.3% of children without ASD.”

The researchers saw higher vision test completion rates with photoscreening, using a sophisticated camera, compared with acuity screening, which uses a wall chart and requires responses.

Less patient participation is required for photoscreening and it can be done in less than 2 minutes.

If ability to complete the vision tests is a concern, the authors wrote, photoscreening may be a better solution.
 

Photoscreening takes 90 seconds

“Photoscreening has high sensitivity in detecting ocular conditions in children with ASD and has an average screening time of 90 seconds, and [it has] been validated in both children with ASD and developmental delays,” the authors wrote.

Andrew Adesman, MD, chief of developmental and behavioral pediatrics at Cohen Children’s Medical Center in New Hyde Park, N.Y., said the authors of this study quantify the gap between need and reality for vision tests for those with ASD.

“Other studies have shown that children on the autism spectrum have more than three times greater risk of having eye disease or vision problems,” he said in an interview. “You’ve got a high-risk population in need of assessment and the likelihood of them getting an assessment is much reduced.”

He said in addition to attention problems in taking the test, vision screening may get lost in the plethora of concerns parents want to talk about in well-child visits.

“If you’re the parent of a child with developmental delays, language delays, poor social engagement, there are a multitude of things the visit could be focused on and it may be that vision screening possibly gets compromised or not done,” Dr. Adesman said.

That, he said, may be a focus area for improving the screening numbers.

Neither parents nor providers should forget that vision screening is important, despite the myriad other issues to address, he said. “They don’t have to take a long time.”

When it comes to vision problems and children, “the earlier they’re identified the better,” Dr. Adesman says, particularly to identify the need for eye muscle surgery or corrective lenses, the two major interventions for strabismus or refractive error.

“If those problems are significant and go untreated, there’s a risk of loss of vision in the affected eye,” he said.
 

Reimbursement concerns for photoscreening

This study strongly supports the use of routine photoscreening to help eliminate the vision screening gap in children with ASD, the authors wrote.

They noted, however, that would require insurance reimbursement for primary care practices to effectively use that screening.

The researchers advised, “Providers treating patients with race, ethnicity, region, or age categories that reduce the adjusted odds of photoscreening can take steps in their practices to address these disparities, particularly in children with ASD.”

The study authors and Dr. Adesman reported no relevant financial relationships.

A common chemical that is used in correction fluid, paint removers, gun cleaners, aerosol cleaning products, and dry cleaning may be the key culprit behind the dramatic increase in Parkinson’s disease (PD), researchers say.

An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).

Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”

“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”

The paper was published online in the Journal of Parkinson’s Disease.
 

Invisible, ubiquitous

TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.

“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.

In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”

Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.

TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.

“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.

He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”

Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”

To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.

“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.

TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.

Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”

Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.

The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.

People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”

They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”

Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.

The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.

Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.

All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.

The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.

They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
 

Recall bias?

Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”

Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”

Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”

In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.

These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.

Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
 

A version of this article first appeared on Medscape.com.

A common chemical that is used in correction fluid, paint removers, gun cleaners, aerosol cleaning products, and dry cleaning may be the key culprit behind the dramatic increase in Parkinson’s disease (PD), researchers say.

An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).

Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”

“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”

The paper was published online in the Journal of Parkinson’s Disease.
 

Invisible, ubiquitous

TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.

“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.

In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”

Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.

TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.

“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.

He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”

Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”

To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.

“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.

TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.

Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”

Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.

The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.

People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”

They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”

Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.

The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.

Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.

All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.

The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.

They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
 

Recall bias?

Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”

Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”

Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”

In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.

These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.

Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
 

A version of this article first appeared on Medscape.com.

A common chemical that is used in correction fluid, paint removers, gun cleaners, aerosol cleaning products, and dry cleaning may be the key culprit behind the dramatic increase in Parkinson’s disease (PD), researchers say.

An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).

Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”

“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”

The paper was published online in the Journal of Parkinson’s Disease.
 

Invisible, ubiquitous

TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.

“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.

In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”

Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.

TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.

“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.

He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”

Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”

To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.

“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.

TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.

Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”

Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.

The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.

People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”

They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”

Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.

The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.

Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.

All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.

The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.

They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
 

Recall bias?

Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”

Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”

Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”

In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.

These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.

Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
 

A version of this article first appeared on Medscape.com.

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.