Balancing Benefit and Harm of Intensive Blood Pressure Lowering Based on Individual Outcome Profile Analysis.

BACKGROUND: Intensive blood pressure lowering prevents major adverse cardiovascular events, but some patients experience serious adverse events. Examining benefit-harm profiles may be more informative than analyzing major adverse cardiovascular events and serious adverse events separately. METHODS: We analyzed data from the Systolic Blood Pressure Intervention Trial (n = 9361), comparing intensive treatment (systolic blood pressure target <120 mm Hg) to standard treatment (<140 mm Hg). A 4-year hierarchical outcome profile was defined for each participant: 1) alive with neither major adverse cardiovascular events nor serious adverse events (most desirable); 2) alive with serious adverse events only; 3) alive with major adverse cardiovascular events only; 4) alive with both events; and 5) deceased (least desirable). We compared 4-year outcome profiles between the treatment groups in the entire population and by frailty subgroups defined using physical frailty phenotype (non-frail, pre-frail, and frail). RESULTS: The proportion who died were lower with intensive treatment than standard treatment (5% vs 6%). A higher proportion of the intensive treatment group was alive with serious adverse events and no major adverse cardiovascular events (36% vs 33%), and a lower proportion were alive with both events (6% vs 5%) than the standard treatment group. The outcome profiles were more favorable among those with physical frailty phenotype who were treated with intensive treatment vs standard treatment, but outcome profiles were similar between the treatment groups among non-frail or pre-frail participants. CONCLUSIONS: This post hoc proof-of-concept analysis demonstrates the utility of the outcome profile analysis that simultaneously examines the benefit and harm of the treatment.

Claims-Based Frailty Index as a Measure of Dementia Severity in Medicare Claims Data.

BACKGROUND: Dementia severity is unavailable in administrative claims data. We examined whether a claims-based frailty index (CFI) can measure dementia severity in Medicare claims. METHODS: This cross-sectional study included the National Health and Aging Trends Study Round 5 participants with possible or probable dementia whose Medicare claims were available. We estimated the Functional Assessment Staging Test (FAST) scale (range: 3 [mild cognitive impairment] to 7 [severe dementia]) using information from the survey. We calculated CFI (range: 0-1, higher scores indicating greater frailty) using Medicare claims 12 months prior to the participants' interview date. We examined C-statistics to evaluate the ability of the CFI in identifying moderate-to-severe dementia (FAST stage 5-7) and determined the optimal CFI cut-point that maximized both sensitivity and specificity. RESULTS: Of the 814 participants with possible or probable dementia and measurable CFI, 686 (72.2%) patients were ≥75 years old, 448 (50.8%) were female, and 244 (25.9%) had FAST stage 5-7. The C-statistic of CFI to identify FAST stage 5-7 was 0.78 (95% confidence interval: 0.72-0.83), with a CFI cut-point of 0.280, achieving the maximum sensitivity of 76.9% and specificity of 62.8%. Participants with CFI ≥0.280 had a higher prevalence of disability (19.4% vs 58.3%) and dementia medication use (6.0% vs 22.8%) and higher risk of mortality (10.7% vs 26.3%) and nursing home admission (4.5% vs 10.6%) over 2 years than those with CFI <0.280. CONCLUSIONS: Our study suggests that CFI can be useful in identifying moderate-to-severe dementia from administrative claims among older adults with dementia.

Post-Acute Care Rehabilitation Services and Outcomes in Skilled Nursing Facilities Before and During the COVID-19 Pandemic.

This cohort study evaluates changes in rehabilitation services provided by skilled nursing facilities during the COVID-19 pandemic.

Development and validation of the fall-related injury risk in nursing homes (INJURE-NH) prediction tool.

BACKGROUND: Existing models to predict fall-related injuries (FRI) in nursing homes (NH) focus on hip fractures, yet hip fractures comprise less than half of all FRIs. We developed and validated a series of models to predict the absolute risk of FRIs in NH residents. METHODS: Retrospective cohort study of long-stay US NH residents (≥100 days in the same facility) between January 1, 2016 and December 31, 2017 (n = 733,427) using Medicare claims and Minimum Data Set v3.0 clinical assessments. Predictors of FRIs were selected through LASSO logistic regression in a 2/3 random derivation sample and tested in a 1/3 validation sample. Sub-distribution hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated for 6-month and 2-year follow-up. Discrimination was evaluated via C-statistic, and calibration compared the predicted rate of FRI to the observed rate. To develop a parsimonious clinical tool, we calculated a score using the five strongest predictors in the Fine-Gray model. Model performance was repeated in the validation sample. RESULTS: Mean (Q1, Q3) age was 85.0 (77.5, 90.6) years and 69.6% were women. Within 2 years of follow-up, 43,976 (6.0%) residents experienced ≥1 FRI. Seventy predictors were included in the model. The discrimination of the 2-year prediction model was good (C-index = 0.70), and the calibration was excellent. Calibration and discrimination of the 6-month model were similar (C-index = 0.71). In the clinical tool to predict 2-year risk, the five characteristics included independence in activities of daily living (ADLs) (HR 2.27; 95% CI 2.14-2.41) and a history of non-hip fracture (HR 2.02; 95% CI 1.94-2.12). Performance results were similar in the validation sample. CONCLUSIONS: We developed and validated a series of risk prediction models that can identify NH residents at greatest risk for FRI. In NH, these models should help target preventive strategies.

The age-related contribution of cognitive function to dual-task gait in middle-aged adults in Spain: observations from a population-based study.

BACKGROUND: Poor dual-task gait performance is associated with a risk of falls and cognitive decline in adults aged 65 years or older. When and why dual-task gait performance begins to deteriorate is unknown. This study aimed to characterise the relationships between age, dual-task gait, and cognitive function in middle age (ie, aged 40-64 years). METHODS: We conducted a secondary analysis of data from community-dwelling adults aged 40-64 years that took part in the Barcelona Brain Health Initiative (BBHI) study, an ongoing longitudinal cohort study in Barcelona, Spain. Participants were eligible for inclusion if they were able to walk independently without assistance and had completed assessments of both gait and cognition at the time of analysis and ineligble if they could not understand the study protocol, had any clinically diagnosed neurological or psychiatric diseases, were cognitively impaired, or had lower-extremity pain, osteoarthritis, or rheumatoid arthritis that could cause abnormal gait. Stride time and stride time variability were measured under single-task (ie, walking only) and dual-task (ie, walking while performing serial subtractions) conditions. Dual-task cost (DTC; the percentage increase in the gait outcomes from single-task to dual-task conditions) to each gait outcome was calculated and used as the primary measure in analyses. Global cognitive function and composite scores of five cognitive domains were derived from neuropsychological testing. We used locally estimated scatterplot smoothing to characterise the relationship between age and dual-task gait, and structural equation modelling to establish whether cognitive function mediated the association between observed biological age and dual tasks. FINDINGS: 996 people were recruited to the BBHI study between May 5, 2018, and July 7, 2020, of which 640 participants completed gait and cognitive assessments during this time (mean 24 days [SD 34] between first and second visit) and were included in our analysis (342 men and 298 women). Non-linear associations were observed between age and dual-task performance. Starting at 54 years, the DTC to stride time (ß=0·27 [95% CI 0·11 to 0·36]; p<0·0001) and stride time variability (0·24 [0·08 to 0·32]; p=0·0006) increased with advancing age. In individuals aged 54 years or older, decreased global cognitive function correlated with increased DTC to stride time (ß=-0·27 [-0·38 to -0·11]; p=0·0006) and increased DTC to stride time variability (ß=-0·19 [-0·28 to -0·08]; p=0·0002). INTERPRETATION: Dual-task gait performance begins to deteriorate in the sixth decade of life and, after this point, interindividual variance in cognition explains a substantial portion of dual-task performance. FUNDING: La Caixa Foundation, Institut Guttmann, and Fundació Abertis.

Differences In Nursing Home Staff COVID-19 Testing Rates And Odds Of Vaccination Across Work Shifts.

COVID-19 vaccination and regular testing of nursing home staff have been critical interventions for mitigating COVID-19 outbreaks in US nursing homes. Although implementation of testing has largely been left to nursing home organizations to coordinate, vaccination occurred through a combination of state, federal, and organization efforts. Little research has focused on structural variation in these processes. We examined whether one structural factor, the primary shift worked by staff, was associated with differences in COVID-19 testing rates and odds of vaccination, using staff-level data from a multistate sample of 294 nursing homes. In facility fixed effects analyses, we found that night-shift staff had the lowest testing rates and lowest odds of vaccination, whereas day-shift staff had the highest testing rates and odds of vaccination. These findings highlight the need to coordinate resources and communication evenly across shifts when implementing large-scale processes in nursing homes and other organizations with shift-based workforces.

Brain activity during dual-task standing in older adults.

BACKGROUND: In older adults, the extent to which performing a cognitive task when standing diminishes postural control is predictive of future falls and cognitive decline. The neurophysiology of such "dual-tasking" and its effect on postural control (i.e., dual-task cost) in older adults are poorly understood. The purpose of this study was to use electroencephalography (EEG) to examine the effects of dual-tasking when standing on brain activity in older adults. We hypothesized that compared to single-task "quiet" standing, dual-task standing would decrease alpha power, which has been linked to decreased motor inhibition, as well as increase the ratio of theta to beta power, which has been linked to increased attentional control. METHODS: Thirty older adults without overt disease completed four separate visits. Postural sway together with EEG (32-channels) were recorded during trials of standing with and without a concurrent verbalized serial subtraction dual-task. Postural control was measured by average sway area, velocity, and path length. EEG metrics included absolute alpha-, theta-, and beta-band powers as well as theta/beta power ratio, within six demarcated regions-of-interest: the left and right anterior, central, and posterior regions of the brain. RESULTS: Most EEG metrics demonstrated moderate-to-high between-day test-retest reliability (intra-class correlation coefficients > 0.70). Compared with quiet standing, dual-tasking decreased alpha-band power particularly in the central regions bilaterally (p = 0.002) and increased theta/beta power ratio in the anterior regions bilaterally (p < 0.001). A greater increase in theta/beta ratio from quiet standing to dual-tasking in numerous demarcated brain regions correlated with greater dual-task cost (i.e., absolute increase, indicative of worse performance) to postural sway metrics (r = 0.45-0.56, p < 0.01). Lastly, participants who exhibited greater alpha power during dual-tasking in the anterior-right (r = 0.52, p < 0.01) and central-right (r = 0.48, p < 0.01) regions had greater postural sway velocity during dual-tasking. CONCLUSION: In healthy older adults, alpha power and theta/beta power ratio change with dual-task standing. The change in theta/beta power ratio in particular may be related to the ability to regulate standing postural control when simultaneously performing unrelated, attention-demanding cognitive tasks. Modulation of brain oscillatory activity might therefore be a novel target to minimize dual-task cost in older adults.

Osteoporosis Medications Prevent Subsequent Fracture in Frail Older Adults.

Frailty is common in older adults with fractures. Osteoporosis medications reduce subsequent fracture, but limited data exist on medication efficacy in frail individuals. Our objective was to determine whether medications reduce the risk of subsequent fracture in frail, older adults. A retrospective cohort of Medicare fee-for-service beneficiaries was conducted (2014-2016). We included adults aged ≥65 years who were hospitalized with fractures without osteoporosis treatment. Pre-fracture frailty was defined using claims-based frailty index (≥0.2 = frail). Exposure to any osteoporosis treatment (oral or intravenous bisphosphonates, denosumab, and teriparatide) was ascertained using Part B and D claims and categorized according to the cumulative duration of exposure: none, 1-90 days, and >90 days. Subsequent fractures were ascertained from Part A or B claims. Cause-specific hazard models with time-varying exposure were fit to examine the association between treatment and fracture outcomes, controlling for relevant covariates. Among 29,904 patients hospitalized with fractures, 15,345 (51.3%) were frail, and 2148 (7.2%) received osteoporosis treatment (median treatment duration 183.0 days). Patients who received treatment were younger (80.2 versus 82.2 years), female (86.5% versus 73.0%), and less frail (0.20 versus 0.22) than patients without treatment. During follow-up, 5079 (17.0%) patients experienced a subsequent fracture. Treatment with osteoporosis medications for >90 days compared with no treatment reduced the risk of fracture (hazard ratio [HR] = 0.82; 95% confidence interval [CI] 0.68-1.00) overall. Results were similar in frail (HR = 0.85; 95% CI 0.65-1.12) and non-frail (HR = 0.80; 95% CI 0.61-1.04) patients but not significant. In conclusion, osteoporosis treatment >90 days was associated with similar trends in reduced risk of subsequent fracture in frail and non-frail persons. Treatment rates were very low, particularly among the frail. When weighing treatment options in frail older adults with hospitalized fractures, clinicians should be aware that drug therapy does not appear to lose its efficacy. © 2022 American Society for Bone and Mineral Research (ASBMR).

Arterial stiffness and contralateral differences in blood pressure: The Atherosclerosis Risk in Communities (ARIC) study.

A large interarm difference in brachial systolic blood pressure (SBP) (≥10 or ≥15 mmHg) is strongly associated with elevated cardiovascular events and mortality. Evidence demonstrating whether such contralateral differences in SBP occur in ankle blood pressure and its association with arterial stiffness is scarce. The aims of this study were to characterize arm and ankle contralateral SBP differences in a sample of community-dwelling older adults (5077), and to determine whether this difference is associated with arterial stiffness assessed by pulse wave velocity (PWV) between the heart and ankle (haPWV), femoral artery and ankle (faPWV), and brachial artery and ankle (baPWV) in the right and left sides. Prevalence of interarm SBP differences ≥10 and ≥15 mmHg was 5.1% and .7%, respectively; the corresponding prevalence for interankle SBP was 24.9% and 12.0%. Higher BMI and lower ankle-brachial index (ABI) were significantly correlated with greater interarm SBP differences. Increased age, higher BMI, lower ABI, and greater contralateral differences in haPWV, faPWV, and baPWV were significantly correlated to greater interankle SBP differences. Interankle SBP difference ≥15 mmHg was significantly associated with contralateral differences of >80 cm/s in haPWV (OR = 1.94 [95% CI = 1.52-2.49]), >165 cm/s in faPWV (OR = 1.64 [95% CI = 1.27-2.12]), and >240 cm/s in baPWV (OR = 2.43 [95% CI = 1.94-3.05]). The associations remained significant after adjustment for age, sex, race, BMI, smoking status, and ABI. Compared with interarm differences, interankle differences in SBP are common in older adults. The magnitude of interankle, but not interarm, differences in SBP is associated with various measures of arterial stiffness.

Network-Based Transcranial Direct Current Stimulation May Modulate Gait Variability in Young Healthy Adults.

Purpose: Previous studies have linked gait variability to resting-state functional connectivity between the dorsal attention network (DAN) and the default network (DN) in the brain. The purpose of this study was to examine the effects of a novel transcranial direct current stimulation (tDCS) paradigm designed to simultaneously facilitate the excitability of the DAN and suppress the excitability of the DN (i.e., DAN+/DN-tDCS) on gait variability and other gait characteristics in young healthy adults. Methods: In this double-blinded randomized and sham-controlled study, 48 healthy adults aged 22 ± 2 years received one 20-min session of DAN+/DN-tDCS (n = 24) or no stimulation (the Sham group, n = 24). Immediately before and after stimulation, participants completed a gait assessment under three conditions: walking at self-selected speed (i.e., normal walking), walking as fast as possible (i.e., fast walking), and walking while counting backward (i.e., dual-task walking). Primary outcomes included gait stride time variability and gait stride length variability in normal walking conditions. Secondary outcomes include gait stride time and length variability in fast and dual-task conditions, and other gait metrics derived from the three walking conditions. Results: Compared to the Sham group, DAN+/DN-tDCS reduced stride length variability in normal and fast walking conditions, double-limb support time variability in fast and dual-task walking conditions, and step width variability in fast walking conditions. In contrast, DAN+/DN-tDCS did not alter average gait speed or the average value of any other gait metrics as compared to the sham group. Conclusion: In healthy young adults, a single exposure to tDCS designed to simultaneously modulate DAN and DN excitability reduced gait variability, yet did not alter gait speed or other average gait metrics, when tested just after stimulation. These results suggest that gait variability may be uniquely regulated by these spatially-distinct yet functionally-connected cortical networks. These results warrant additional research on the short- and longer-term effects of this type of network-based tDCS on the cortical control of walking in younger and older populations.

Transcranial Direct Current Stimulation May Reduce Prefrontal Recruitment During Dual Task Walking in Functionally Limited Older Adults - A Pilot Study.

Introduction: Transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (dlPFC) improves dual task walking in older adults, when tested just after stimulation. The acute effects of tDCS on the cortical physiology of walking, however, remains unknown. Methods: In a previous study, older adults with slow gait and executive dysfunction completed a dual task walking assessment before and after 20 min of tDCS targeting the left dlPFC or sham stimulation. In a subset of seven participants per group, functional near-infrared spectroscopy (fNIRS) was used to quantify left and right prefrontal recruitment defined as the oxygenated hemoglobin response to usual and dual task walking (ΔHbO2), as well as the absolute change in this metric from usual to dual task conditions (i.e., ΔHbO2 cost ). Paired t-tests examined pre- to post-stimulation differences in each fNIRS metric within each group. Results: The tDCS group exhibited pre- to post-stimulation reduction in left prefrontal ΔHbO2 cost (p = 0.03). This mitigation of dual task "cost" to prefrontal recruitment was induced primarily by a reduction in left prefrontal ΔHbO2 specifically within the dual task condition (p = 0.001), an effect that was observed in all seven participants within this group. Sham stimulation did not influence ΔHbO2 cost or ΔHbO2 in either walking condition (p > 0.35), and neither tDCS nor sham substantially influenced right prefrontal recruitment (p > 0.16). Discussion: This preliminary fNIRS data suggests that tDCS over the left dlPFC may modulate prefrontal recruitment, as reflected by a relative reduction in the oxygen consumption of this brain region in response to dual task walking.

COVID-19 Vaccine Uptake Among Nursing Home Staff via Statewide Policy: The Mississippi Vaccinate or Test Out Policy.

Objectives. To examine whether COVID-19 vaccine mandates that allow a test-out exemption for nursing home staff are associated with increased staff vaccination rates in nursing homes. Methods. Using the National Healthcare Safety Network data, we conducted analyses to test trends over time in statewide staff vaccination rates between June 1, 2021, and August 29, 2021, in Mississippi, 4 adjacent states, and the United States overall. Results. COVID-19 staff vaccination rates increased slowly following Mississippi enacting a vaccinate-or-test-out policy, achieving small, but statistically greater gains than most comparator states. Yet, staff vaccination rates in Mississippi remained well below the national average and similar numerically to surrounding states without mandates. Conclusions. Mississippi's COVID-19 vaccinate-or-test policy was ineffective in meaningfully increasing staff vaccination rates. For COVID-19 nursing home mandates to be effective while still balancing the staff turnover risks, facilities might consider a more stringent or hybrid approach (e.g., test-out option not offered to new staff). Public Health Implications. Statewide COVID-19 vaccine mandates, when given a test-out option, do not appear to be an effective strategy to meaningfully increase nursing home staff COVID-19 vaccination. (Am J Public Health. 2022;112(5):762-765. https://doi.org/10.2105/AJPH.2022.306800).

Strategies associated with COVID-19 vaccine coverage among nursing home staff.

BACKGROUND: After the first of three COVID-19 vaccination clinics in U.S. nursing homes (NHs), the median vaccination coverage of staff was 37.5%, indicating the need to identify strategies to increase staff coverage. We aimed at comparing the facility-level activities, policies, incentives, and communication methods associated with higher staff COVID-19 vaccination coverage. METHODS: Design. Case-control analysis. SETTING: Nationally stratified random sample of 1338 U.S. NHs participating in the Pharmacy Partnership for Long-Term Care Program. PARTICIPANTS: Nursing home leadership. MEASUREMENT: During February 4-March 2, 2021, we surveyed NHs with low (<35%), medium (40%-60%), and high (>75%) staff vaccination coverage, to collect information on facility strategies used to encourage staff vaccination. Cases were respondents with medium and high vaccination coverage, whereas controls were respondents with low coverage. We used logistic regression modeling, adjusted for county and NH characteristics, to identify strategies associated with facility-level vaccination coverage. RESULTS: We obtained responses from 413 of 1338 NHs (30.9%). Compared with facilities with lower staff vaccination coverage, facilities with medium or high coverage were more likely to have designated frontline staff champions (medium: adjusted odds ratio [aOR] 3.6, 95% CI 1.3-10.3; high: aOR 2.9, 95% CI 1.1-7.7) and set vaccination goals (medium: aOR 2.4, 95% 1.0-5.5; high: aOR 3.7, 95% CI 1.6-8.3). NHs with high vaccination coverage were more likely to have given vaccinated staff rewards such as T-shirts compared with NHs with low coverage (aOR 3.8, 95% CI 1.3-11.0). Use of multiple strategies was associated with greater likelihood of facilities having medium or high vaccination coverage: For example, facilities that used ≥9 strategies were three times more likely to have high staff vaccination coverage than facilities using <6 strategies (aOR 3.3, 95% CI 1.2-8.9). CONCLUSIONS: Use of designated champions, setting targets, and use of non-monetary awards were associated with high NH staff COVID-19 vaccination coverage.

Intensive versus standard blood pressure control in type 2 diabetes: a restricted mean survival time analysis of a randomised controlled trial.

BACKGROUND: Restricted mean survival time analysis offers an intuitive and robust summary of treatment effect compared with HRs. OBJECTIVE: To examine the effect of intensive versus standard blood pressure (BP) control on death or cardiovascular events in type 2 diabetes. DESIGN: Secondary analysis of the Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial. SETTING: 77 sites in the USA and Canada. PARTICIPANTS: 4733 adults with type 2 diabetes at high risk for cardiovascular events. INTERVENTIONS: Systolic BP target <120 mm Hg (n=2371) versus <140 mm Hg (n=2362). MEASUREMENTS: Composite endpoint of death, non-fatal myocardial infarction or non-fatal stroke. RESULTS: The mean event-free survival time over 5 years (1825 days) was similar between intensive and standard BP control (1716 vs 1714 days; mean difference, 1.3 (95% CI -18.1 to 20.7) days). However, intensive BP treatment was more beneficial for those assigned to standard glycaemic control (1725 vs 1697 days; mean difference, 28.1 (95% CI 0.4 to 55.9) days), but not for those assigned to intensive glycaemic control (1706 vs 1731 days; mean difference, -25.2 (95% CI -52.3 to 1.9) days) (p=0.008 for interaction). In subgroup analysis, the mean event-free survival time difference between intensive and standard BP treatment was -76.0 (95% CI -131.8 to -20.3) days for those with cognitive impairment and 21.8 (95% CI -24.0 to 67.5) days for those with normal cognitive function (p=0.008 for interaction). The effect was not different by age, sex and baseline cardiovascular disease status. CONCLUSIONS: Intensive BP treatment may reduce death and cardiovascular events among patients with type 2 diabetes receiving standard glycaemic treatment and without cognitive impairment. TRIAL REGISTRATION NUMBER: NCT00000620; Post-results.

Multitarget Transcranial Electrical Stimulation for Freezing of Gait: A Randomized Controlled Trial.

BACKGROUND: Treatments of freezing of gait (FOG) in Parkinson's disease are suboptimal. OBJECTIVE: The aim of this study was to evaluate the effects of multiple sessions of transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex and primary motor cortex (M1) on FOG. METHODS: Seventy-seven individuals with Parkinson's disease and FOG were enrolled in a double-blinded randomized trial. tDCS and sham interventions comprised 10 sessions over 2 weeks followed by five once-weekly sessions. FOG-provoking test performance (primary outcome), functional outcomes, and self-reported FOG severity were assessed. RESULTS: Primary analyses demonstrated no advantage for tDCS in the FOG-provoking test. In secondary analyses, tDCS, compared with sham, decreased self-reported FOG severity and increased daily living step counts. Among individuals with mild-to-moderate FOG severity, tDCS improved FOG-provoking test time and self-report of FOG. CONCLUSIONS: Multisession tDCS targeting the left dorsolateral prefrontal cortex and M1 did not improve laboratory-based FOG-provoking test performance. Improvements observed in participants with mild-to-moderate FOG severity warrant further investigation. © 2021 International Parkinson and Movement Disorder Society.

Targeted tDCS Mitigates Dual-Task Costs to Gait and Balance in Older Adults.

OBJECTIVE: Among older adults, the ability to stand or walk while performing cognitive tasks (ie, dual-tasking) requires coordinated activation of several brain networks. In this multicenter, double-blinded, randomized, and sham-controlled study, we examined the effects of modulating the excitability of the left dorsolateral prefrontal cortex (L-DLPFC) and the primary sensorimotor cortex (SM1) on dual-task performance "costs" to standing and walking. METHODS: Fifty-seven older adults without overt illness or disease completed 4 separate study visits during which they received 20 minutes of transcranial direct current stimulation (tDCS) optimized to facilitate the excitability of the L-DLPFC and SM1 simultaneously, or each region separately, or neither region (sham). Before and immediately after stimulation, participants completed a dual-task paradigm in which they were asked to stand and walk with and without concurrent performance of a serial-subtraction task. RESULTS: tDCS simultaneously targeting the L-DLPFC and SM1, as well as tDCS targeting the L-DLPFC alone, mitigated dual-task costs to standing and walking to a greater extent than tDCS targeting SM1 alone or sham (p < 0.02). Blinding efficacy was excellent and participant subjective belief in the type of stimulation received (real or sham) did not contribute to the observed functional benefits of tDCS. INTERPRETATION: These results demonstrate that in older adults, dual-task decrements may be amenable to change and implicate L-DPFC excitability as a modifiable component of the control system that enables dual-task standing and walking. tDCS may be used to improve resilience and the ability of older results to walk and stand under challenging conditions, potentially enhancing everyday functioning and reducing fall risks. ANN NEUROL 2021;90:428-439.

Impact of Gender on Transcatheter Aortic Valve Implantation Outcomes.

Previous studies indicate that women who underwentwho underwent transcatheter aortic valve implantation (TAVI) have poorer 30-day outcomes compared with men. However, the effect of gender as a prognostic factor for long-term outcomes following TAVI remains unclear. Between 2008 and 2018, all patients (n = 683) who underwent TAVI in 2 centres in Melbourne, Australia were prospectively included in a registry. The primary end-point was long-term mortality. The secondary end points were Valve Academic Research Consortium-2 (VARC-2) in-hospital complications and mortality at 30-days and 1-year. Of 683 patients, 328 (48%) were women. Women had a higher mean STS-PROM score (5.2 ± 3.1 vs 4.6 ± 3.5, p < 0.001) but less co-morbidities than men. Women had a significantly higher in-hospital bleeding rates (3.3% vs 1.0%, Odds Ratio 4.21, 95% confidence interval [CI] 1.16 to15.25, p = 0.027) and higher 30-day mortality (2.4% vs 0.3%, hazard ratio [HR] 8.75, 95% CI 1.09 to 69.6, p = 0.040) than men. Other VARC-2 outcomes were similar between genders. Overall mortality rate was 36% (246) over a median follow up of 2.7 (interquartile rang [IQR] 1.7 to 4.2) years. Median time to death was 5.3 (95% CI 4.7 to 5.7) years. One-year mortality was similar between genders (8.3% vs 7.8%), as was long-term mortality (HR = 0.91, 95% CI 0.71 to 1.17, p = 0.38). On multivariable analysis, female gender was an independent predictor for 1-year mortality (HR = 2.33, 95% CI 1.11 to 4.92, p = 0.026), but not long-term mortality (HR = 0.78, 95% CI 0.54 to 1.14, p = 0.20). In the women only cohort, STS-PROM was the only independent predictor of long-term mortality (HR 1.88, 95% CI 1.42 to 2.48, p < 0.001). In conclusion, women had higher rates of peri-procedural major bleeding and 30-day mortality following TAVI. However, long-term outcomes were similar between genders.

Using Wearable Sensors and Machine Learning to Automatically Detect Freezing of Gait during a FOG-Provoking Test.

Freezing of gait (FOG) is a debilitating motor phenomenon that is common among individuals with advanced Parkinson's disease. Objective and sensitive measures are needed to better quantify FOG. The present work addresses this need by leveraging wearable devices and machine-learning methods to develop and evaluate automated detection of FOG and quantification of its severity. Seventy-one subjects with FOG completed a FOG-provoking test while wearing three wearable sensors (lower back and each ankle). Subjects were videotaped before (OFF state) and after (ON state) they took their antiparkinsonian medications. Annotations of the videos provided the "ground-truth" for FOG detection. A leave-one-patient-out validation process with a training set of 57 subjects resulted in 84.1% sensitivity, 83.4% specificity, and 85.0% accuracy for FOG detection. Similar results were seen in an independent test set (data from 14 other subjects). Two derived outcomes, percent time frozen and number of FOG episodes, were associated with self-report of FOG. Bother derived-metrics were higher in the OFF state than in the ON state and in the most challenging level of the FOG-provoking test, compared to the least challenging level. These results suggest that this automated machine-learning approach can objectively assess FOG and that its outcomes are responsive to therapeutic interventions.

Self-Reported Head Trauma Predicts Poor Dual Task Gait in Retired National Football League Players.

OBJECTIVE: Symptomatic head trauma associated with American-style football (ASF) has been linked to brain pathology, along with physical and mental distress in later life. However, the longer-term effects of such trauma on objective metrics of cognitive-motor function remain poorly understood. We hypothesized that ASF-related symptomatic head trauma would predict worse gait performance, particularly during dual task conditions (ie, walking while performing an additional cognitive task), in later life. METHODS: Sixty-six retired professional ASF players aged 29 to 75 years completed a health and wellness questionnaire. They also completed a validated smartphone-based assessment in their own homes, during which gait was monitored while they walked normally and while they performed a verbalized serial-subtraction cognitive task. RESULTS: Participants who reported more symptomatic head trauma, defined as the total number of impacts to the head or neck followed by concussion-related symptoms, exhibited greater dual task cost (ie, percentage increase) to stride time variability (ie, the coefficient of variation of mean stride time). Those who reported ≥1 hit followed by loss of consciousness, compared to those who did not, also exhibited greater dual task costs to this metric. Relationships between reported trauma and dual task costs were independent of age, body mass index, National Football League career duration, and history of musculoskeletal surgery. Symptomatic head trauma was not correlated with average stride times in either walking condition. INTERPRETATION: Remote, smartphone-based assessments of dual task walking may be utilized to capture meaningful data sensitive to the long-term impact of symptomatic head trauma in former professional ASF players and other contact sport athletes. ANN NEUROL 2020;87:75-83.