Insulin resistance during androgen deprivation therapy in men with prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear. METHODS: The ADT & Metabolism Study was a single-center, 24-week, prospective observational study that enrolled ADT-naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non-ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks. RESULTS: At 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], -2.10 to 4.43; p = .47) or skeletal muscle (-3.2; 95% CI, -7.07 to 0.66; p = .10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non-ADT group. Men undergoing ADT gained 3.7 kg of fat mass. CONCLUSIONS: In men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short-term ADT.

The pace and prognosis of peripheral sensory loss in advanced age: association with gait speed and falls.

BACKGROUND: Peripheral sensory loss is considered one of many risk factors for gait impairments and falls in older adults, yet no prospective studies have examined changes in touch sensation in the foot over time and their relationship to mobility and falls. Therefore, we aimed to determine the prevalence and progression of peripheral sensory deficits in the feet of older adults, and whether sensory changes are associated with the slowing of gait and development of falls over 5 years. METHODS: Using baseline, and 18 and 60 month followup data from the Maintenance Of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Study in Boston, MA, we determined changes in the ability to detect stimulation of the great toe with Semmes Weinstein monofilaments in 351 older adults. We used covariate-adjusted repeated measures analysis of variance to determine relationships between sensory changes and gait speed or fall rates. RESULTS: Subjects whose sensory function was consistently impaired over 5 years had a significantly steeper decline in gait speed (- 0.23 m/s; 95% CI: -0.28 to - 0.18) compared to those with consistently intact sensory function (- 0.12 m/s; 95% CI: -0.15 to - 0.08) and those progressing from intact to impaired sensory function (- 0.13 m/s; - 0.16 to - 0.10). Compared to subjects with consistently intact sensation, those whose sensory function progressed to impairment during followup had the greatest risk of falls (adjusted risk ratio = 1.57 (95% confidence interval = 1.12 to 2.22). CONCLUSIONS: Our longitudinal results indicate that a progressive decline in peripheral touch sensation is a risk factor for mobility impairment and falls in older adults.

Long-term Tai Chi Training Is Associated With Better Dual-task Postural Control and Cognition in Aging Adults.

OBJECTIVE: Many activities within our daily lives require us to stand upright while concurrently performing a cognitive task (ie, dual tasking). The "costs" of dual tasking can present as a detriment to either task, or even both. Evidence supports that tai chi (TC), a mind-body exercise, improves both postural control and cognition. The purpose of this study was to (1) determine whether long-term TC training reduces dual-task costs to standing postural control, and (2) determine whether it characterizes the relationship between these costs and cognition in aging adults with and without long-term TC training. METHODS: Twenty-six TC experts (age 63 ± 8 y, TC experience 24 ± 11 y) and 60 controls (TC naïve: age 64 ± 8 y) were studied. Center-of-pressure sway speed and elliptical area were recorded during quiet and dual-task standing. In addition, postural sway speed and range were analyzed in the anterior-posterior and medial-lateral direction. Dual-task cost was calculated as the percent change in center-of-pressure outcomes from quiet to dual-task conditions. Cognition was assessed with the digit span (verbal memory), trail making test (working memory and task switching ability), category naming (semantic verbal fluency), and F-A-S test (phonemic verbal fluency). RESULTS: TC experts had significantly lower dual-task costs to postural control in elliptical area (16.1 vs 110.4%, 95% confidence interval [CI], -94.27 to -0.07) compared with TC-naïves. TC experts also performed better on the digit span (23.5 vs 19.2; 95% CI, 0.68 to 3.59), trail making test A (28.5 vs 32.6 s; 95% CI, -3.83 to -0.21), and category naming (46.2 vs 41.3, 95%, CI 0.80 to 4.09), compared with TC naïves. There was not a clear significant association between better cognitive functioning and lower dual-task costs for either groups. These group differences and associations were independent of age, body mass index, education, and physical activity level. CONCLUSIONS: These observations suggest cognitive-motor benefits from TC and the need for future controlled trials.

Sub-sensory vibratory noise augments the physiologic complexity of postural control in older adults.

BACKGROUND: Postural control requires numerous inputs interacting across multiple temporospatial scales. This organization, evidenced by the "complexity" contained within standing postural sway fluctuations, enables diverse system functionality. Age-related reduction of foot-sole somatosensation reduces standing postural sway complexity and diminishes the functionality of the postural control system. Sub-sensory vibrations applied to the foot soles reduce the speed and magnitude of sway and improve mobility in older adults. We thus hypothesized that these vibration-induced improvements to the functionality of the postural control system are associated with an increase in the standing postural sway complexity. METHOD: Twelve healthy older adults aged 74 ± 8 years completed three visits to test the effects of foot sole vibrations at 0 % (i.e., no vibration), 70 and 85 % of the sensory threshold. Postural sway was assessed during eyes-open and eyes-closed standing. The complexity of sway time-series was quantified using multiscale entropy. The timed up-and-go (TUG) was completed to assess mobility. RESULTS: When standing without vibration, participants with lower foot sole vibratory thresholds (better sensation) had greater mediolateral (ML) sway complexity (r (2) = 0.49, p < 0.001), and those with greater ML sway complexity had faster TUG times (better mobility) (r (2) = 0.38, p < 0.001). Foot sole vibrations at 70 and 85 % of sensory threshold increased ML sway complexity during eyes-open and eyes-closed standing (p < 0.0001). Importantly, these vibration-induced increases in complexity correlated with improvements in the TUG test of mobility (r (2) = 0.15 ~ 0.42, p < 0.001 ~ 0.03). CONCLUSIONS: Sub-sensory foot sole vibrations augment the postural control system functionality and such beneficial effects are reflected in an increase in the physiologic complexity of standing postural sway dynamics.

Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease.

BACKGROUND: Hospitalization, frequently complicated by delirium, can be a life-changing event for patients with Alzheimer disease (AD). OBJECTIVE: To determine risks for institutionalization, cognitive decline, or death associated with hospitalization and delirium in patients with AD. DESIGN: Prospective cohort enrolled between 1991 and 2006 into the Massachusetts Alzheimer's Disease Research Center (MADRC) patient registry. SETTING: Community-based. PARTICIPANTS: 771 persons aged 65 years or older with a clinical diagnosis of AD. MEASUREMENTS: Hospitalization, delirium, death, and institutionalization were identified through administrative databases. Cognitive decline was defined as a decrease of 4 or more points on the Blessed Information-Memory-Concentration test score. Multivariate analysis was used to calculate adjusted relative risks (RRs). RESULTS: Of 771 participants with AD, 367 (48%) were hospitalized and 194 (25%) developed delirium. Hospitalized patients who did not have delirium had an increased risk for death (adjusted RR, 4.7 [95% CI, 1.9 to 11.6]) and institutionalization (adjusted RR, 6.9 [CI, 4.0 to 11.7]). With delirium, risk for death (adjusted RR, 5.4 [CI, 2.3 to 12.5]) and institutionalization (adjusted RR, 9.3 [CI, 5.5 to 15.7]) increased further. With hospitalization and delirium, the adjusted RR for cognitive decline for patients with AD was 1.6 (CI, 1.2 to 2.3). Among hospitalized patients with AD, 21% of the incidences of cognitive decline, 15% of institutionalization, and 6% of deaths were associated with delirium. LIMITATIONS: Cognitive outcome was missing in 291 patients. Sensitivity analysis was performed to test the effect of missing data, and a composite outcome was used to decrease the effect of missing data. CONCLUSION: Approximately 1 in 8 hospitalized patients with AD who develop delirium will have at least 1 adverse outcome, including death, institutionalization, or cognitive decline, associated with delirium. Delirium prevention may represent an important strategy for reducing adverse outcomes in this population.

Gaining metabolic insight in older men undergoing androgen deprivation therapy for prostate cancer (the ADT & Metabolism Study): Protocol of a longitudinal, observational, cohort study.

Androgen deprivation therapy (ADT), a cornerstone of treatment for patients with locally advanced and metastatic prostate cancer, is associated with many adverse effects, including osteoporosis, sexual dysfunction, fatigue, and vasomotor symptoms. It is also associated with loss of muscle mass and increased adiposity. This change in body composition is likely the inciting event in the development of insulin resistance, an independent risk factor for diabetes mellitus and cardiovascular disease. Although the occurrence of insulin resistance during ADT has been reported, it remains unclear whether this insulin resistance is primarily hepatic or muscular. Similarly, the mechanisms that lead to insulin resistance also remain unknown. The ADT & Metabolism Study was designed to address these knowledge gaps, as the elucidation of the predominant site of insulin resistance will allow prevention strategies and the use of targeted, tissue-specific insulin-sensitizing agents in patients undergoing ADT. This prospective, mechanistic, single-center, 24-week, observational cohort study will enroll treatment-naïve adult men with prostate cancer about to undergo surgical or medical ADT for at least 24 weeks (ADT group; n = 50) and a control group of men who had undergone radical prostatectomy and are in remission (non-ADT group, n = 25). The primary outcome is to determine the site of insulin resistance (skeletal muscle or liver) using frequent sampling oral glucose tolerance test at baseline and 12 and 24 weeks after commencement of ADT (ADT group) or after enrollment in the study (non-ADT group). Secondary outcomes will assess changes in hepatic and intramyocellular fat (using magnetic resonance spectroscopy), inflammatory markers, adipokines, free fatty acids, and changes in body composition (assessed using dual-energy x-ray absorptiometry) and their correlation with the development of insulin resistance. Exploratory outcomes will include changes in muscle performance, physical function, physical activity, vitality, and sexual drive.

Provider adherence to training components from the Trial to Reduce Antimicrobial use In Nursing home residents with Alzheimer's disease and other Dementias (TRAIN-AD) intervention.

Background: The Trial to Reduce Antimicrobial use In Nursing home residents with Alzheimer's disease and other Dementias (TRAIN-AD) was a cluster randomized clinical trial evaluating a multicomponent program to improve infection management among residents with advanced dementia. This report examines facility and provider characteristics associated with greater adherence to training components of the TRAIN-AD intervention. Methods: Logistic regression was used to identify facility and provider characteristics associated with: 1. Training seminar attendance, 2. Online course completion, and 3. Overall adherence, defined as participation in neither seminar nor course, either seminar or course, or both seminar and course. Results: Among 380 participating providers (nurses, N = 298; prescribing providers, N = 82) almost all (93%) participated in at least one training activity. Being a nurse was associated with higher likelihood of any seminar attendance (adjusted odds ratio (AOR) 5.37; 95% confidence interval (CI), 2.80-10.90). Providers who were in facilities when implementation begun (AOR, 3.01; 95% CI, 1.34-6.78) and in facilities with better quality ratings (AOR, 2.70; 95% CI, 1.59-4.57) were more likely to complete the online course. Prevalent participation (AOR, 2.01; 95% CI, 1.02-3.96) and higher facility quality (AOR, 2.44; 95% CI, 1.27-4.66) were also significantly associated with greater adherence to either seminar or online course. Conclusion: TRAIN-AD demonstrates feasibility in achieving high participation among nursing home providers in intervention training activities. Findings also suggest opportunities to maximize adherence, such as enhancing training efforts in lower quality facilities and targeting of providers who join the facility after implementation start-up.

A proinflammatory diet is associated with increased odds of frailty after 12-year follow-up in a cohort of adults.

BACKGROUND: Frailty occurs in 10-15% of community-living older adults and inflammation is a key determinant of frailty. Though diet is a modulator of inflammation, there are few prospective studies elucidating the role of diet-associated inflammation on frailty onset. OBJECTIVES: We sought to determine whether a proinflammatory diet was associated with increased odds of frailty in adults from the Framingham Heart Study (FHS). DESIGN AND METHODS: This study was nested in a prospective cohort that included individuals without frailty. Diet was assessed in 1998-2001 using a valid FFQ, and frailty was measured in 2011-2014. FFQ-derived energy-adjusted dietary inflammatory index (E-DII®) scores were computed, with higher E-DII scores indicating a more proinflammatory diet. Frailty was defined as fulfilling ≥3 of 5 Fried Phenotype criteria. Information on potential mediators, serum IL-6 and C-reactive protein was obtained in 1998-2001. Logistic regression estimated ORs and 95% CIs for E-DII (as continuous and in quartiles) and frailty onset adjusting for relevant confounders. RESULTS: Of 1701 individuals without frailty at baseline (mean ± SD age: 58 ± 8 y; range: 33-81 y; 55% female), 224 developed frailty (13% incidence) over ∼12 y. The mean ± SD E-DII score was -1.95 ± 2.20; range: -6.71 to +5.40. After adjusting for relevant confounders, a 1-unit higher E-DII score was associated with 16% increased odds of developing frailty (95% CI: 1.07, 1.25). In categorical analyses, participants in the highest (proinflammatory) compared with lowest quartile of E-DII had >2-fold increased odds of frailty (ORquartile4vs.1: 2.22; 95% CI: 1.37, 3.60; P-trend < 0.01). IL-6 and C-reactive protein were not major contributors in the pathway. CONCLUSIONS: In this cohort of middle-aged and older adults, a proinflammatory diet was associated with increased odds of frailty over ∼12 y of follow-up. Trials designed to increase consumption of anti-inflammatory foods for frailty prevention are warranted.

Factors Associated With Antimicrobial Use in Nursing Home Residents With Advanced Dementia.

OBJECTIVES: Widespread antimicrobial misuse among nursing home (NH) residents with advanced dementia raises concerns regarding the emergence of multidrug-resistant organisms and avoidable treatment burden in this vulnerable population. The objective of this report was to identify facility and resident level characteristics associated with receipt of antimicrobials in this population. DESIGN: Cross-sectional analysis of baseline data from the Trial to Reduce Antimicrobial use in Nursing home residents with Alzheimer's disease and other Dementias (TRAIN-AD). SETTING AND PARTICIPANTS: Twenty-eight Boston area NHs, 430 long stay NH residents with advanced dementia. MEASURES: The outcome was the proportion of residents who received any antimicrobials during the 2 months prior to the start of TRAIN-AD determined by chart review. Multivariable logistic regression was used to identify resident and facility characteristics associated with this outcome. RESULTS: A total of 13.7% of NH residents with advanced dementia received antimicrobials in the 2 months prior to the start of TRAIN-AD. Residents in facilities with the following characteristics were significantly more likely to receive antimicrobials: having a full time nurse practitioner/physician assistant on staff [adjusted odds ratio (aOR) 3.02; 95% confidence interval (CI), 1.54, 5.94], fewer existing infectious disease practices (eg, antimicrobial stewardship programs, established algorithms for infection management) (aOR, 2.35; 95% CI 1.14, 4.84), and having fewer residents with severely cognitively impaired residents (aOR 1.96; 95% CI 1.12, 3.40). No resident characteristics were independently associated with receipt of antimicrobials. CONCLUSIONS AND IMPLICATIONS: Facility-level characteristics are associated with the receipt of antimicrobials among residents with advanced dementia. Implementation of more intense infectious disease practices and targeting the prescribing practices of nurse practitioners/physician assistants may be critical targets for interventions aimed at reducing antimicrobial use in this population.

Beyond the Health Deficit Count: Examining Deficit Patterns in a Deficit-Accumulation Frailty Index.

BACKGROUND/OBJECTIVES: Exploring deficit patterns among frail people may reveal subgroups of different prognostic importance. DESIGN: Analysis of National Health and Aging Trends Study. SETTING: Community. PARTICIPANTS: Community dwelling older adults with mild to moderate frailty (deficit-accumulation frailty index (FI) of 0.25-0.40) (n = 1821). MEASUREMENTS: Latent class analysis identified distinct clinical subgroups based on comorbidity (range: 0-10), National Health and Aging Trends Study dementia classification, and short physical performance battery (SPPB) (range: 0-12). Survival analyses compared 5-year mortality by subgroups. RESULTS: Three latent classes existed: Class 1 (n = 831, mean FI = 0.30) had 2.7% probable dementia, high comorbidities (mean = 3.6), and low physical impairment (SPPB mean = 9.9); Class 2 (n = 734, mean FI = 0.32) had 6.9% probable dementia, low comorbidities (mean = 2.8), and moderate physical impairment (SPPB mean = 6.2); Class 3 (n = 256, mean FI = 0.34) had 20.7% probable dementia, low comorbidities (mean = 2.4), and high physical impairment (SPPB mean = 2.0). Compared to Class 1, Classes 2 and 3 experienced higher 5-year mortality (C2: 1.28 (95% confidence intervals (CI) = 1.00-1.62); C3: 1.87 (95% CI = 1.29-2.73)). CONCLUSION: Deficit patterns among the mild-to-moderately frail provide additional prognostic information and highlight opportunities for preventive interventions.

The Trial to Reduce Antimicrobial Use in Nursing Home Residents With Alzheimer Disease and Other Dementias (TRAIN-AD): A Cluster Randomized Clinical Trial.

Importance: Antimicrobials are extensively prescribed to nursing home residents with advanced dementia, often without evidence of infection or consideration of the goals of care. Objective: To test the effectiveness of a multicomponent intervention to improve the management of suspected urinary tract infections (UTIs) and lower respiratory infections (LRIs) for nursing home residents with advanced dementia. Design, Setting, and Participants: A cluster randomized clinical trial of 28 Boston-area nursing homes (14 per arm) and 426 residents with advanced dementia (intervention arm, 199 residents; control arm, 227 residents) was conducted from August 1, 2017, to April 30, 2020. Interventions: The intervention content integrated best practices from infectious diseases and palliative care for management of suspected UTIs and LRIs in residents with advanced dementia. Components targeting nursing home practitioners (physicians, physician assistants, nurse practitioners, and nurses) included an in-person seminar, an online course, management algorithms (posters, pocket cards), communication tips (pocket cards), and feedback reports on prescribing of antimicrobials. The residents' health care proxies received a booklet about infections in advanced dementia. Nursing homes in the control arm continued routine care. Main Outcomes and Measures: The primary outcome was antimicrobial treatment courses for suspected UTIs or LRIs per person-year. Outcomes were measured for as many as 12 months. Secondary outcomes were antimicrobial courses for suspected UTIs and LRIs when minimal criteria for treatment were absent per person-year and burdensome procedures used to manage these episodes (bladder catherization, chest radiography, venous blood sampling, or hospital transfer) per person-year. Results: The intervention arm had 199 residents (mean [SD] age, 87.7 [8.0] years; 163 [81.9%] women; 36 [18.1%] men), of which 163 (81.9%) were White and 27 (13.6%) were Black. The control arm had 227 residents (mean [SD] age, 85.3 [8.6] years; 190 [83.7%] women; 37 [16.3%] men), of which 200 (88.1%) were White and 22 (9.7%) were Black. There was a 33% (nonsignificant) reduction in antimicrobial treatment courses for suspected UTIs or LRIs per person-year in the intervention vs control arm (adjusted marginal rate difference, -0.27 [95% CI, -0.71 to 0.17]). This reduction was primarily attributable to reduced antimicrobial use for LRIs. The following secondary outcomes did not differ significantly between arms: antimicrobials initiated when minimal criteria were absent, bladder catheterizations, venous blood sampling, and hospital transfers. Chest radiography use was significantly lower in the intervention arm (adjusted marginal rate difference, -0.56 [95% CI, -1.10 to -0.03]). In-person or online training was completed by 88% of the targeted nursing home practitioners. Conclusions and Relevance: This cluster randomized clinical trial found that despite high adherence to the training, a multicomponent intervention promoting goal-directed care for suspected UTIs and LRIs did not significantly reduce antimicrobial use among nursing home residents with advanced dementia. Trial Registration: ClinicalTrials.gov Identifier: NCT03244917.

A mobile app for delirium screening.

OBJECTIVE: The objective of this study is to describe the algorithm and technical implementation of a mobile app that uses adaptive testing to assess an efficient mobile app for the diagnosis of delirium. MATERIALS AND METHODS: The app was used as part of a NIH-funded project to assess the feasibility, effectiveness, administration time, and costs of the 2-step delirium identification protocol when performed by physicians and nurses, and certified nursing assistants (CNA). The cohort included 535 hospitalized patients aged 79.7 (SD = 6.6) years enrolled at 2 different sites. Each patient was assessed on 2 consecutive days by the research associate who performed the reference delirium assessment. Thereafter, physicians, nurses, and CNAs performed adaptive delirium assessments using the app. Qualitative data to assess the experience of administering the 2-step protocol, and the app usability were also collected and analyzed from 50 physicians, 189 nurses, and 83 CNAs. We used extensible hypertext markup language (XHTML) and JavaScript to develop the app for the iOS-based iPad. The App was linked to Research Electronic Data Capture (REDCap), a relational database system, via a REDCap application programming interface (API) that sent and received data from/to the app. The data from REDCap were sent to the Statistical Analysis System for statistical analysis. RESULTS: The app graphical interface was successfully implemented by XHTML and JavaScript. The API facilitated the instant updating and retrieval of delirium status data between REDCap and the app. Clinicians performed 881 delirium assessments using the app for 535 patients. The transmission of data between the app and the REDCap system showed no errors. Qualitative data indicated that the users were enthusiastic about using the app with no negative comments, 82% positive comments, and 18% suggestions of improvement. Delirium administration time for the 2-step protocol showed similar total time between nurses and physicians (103.9 vs 106.5 seconds). Weekly enrollment reports of the app data were generated for study tracking purposes, and the data are being used for statistical analyses for publications. DISCUSSION: The app developed using iOS could be easily converted to other operating systems such as Android and could be linked to other relational databases beside REDCap, such as electronic health records to facilitate better data retrieval and updating of patient's delirium status. CONCLUSION: Our app operationalizes an adaptive 2-step delirium screening protocol. Its algorithm and cross-plat formed code of XHTML and JavaScript can be easily exported to other operating systems and hardware platforms, thus enabling wider use of the efficient delirium screening protocol that we have developed. The app is currently implemented as a research tool, but with adaptation could be implemented in the clinical setting to facilitate widespread delirium screening in hospitalized older adults.

Covariate-constrained randomization for cluster randomized trials in the long-term care setting: Application to the TRAIN-AD trial.

Little has been reported on strategies to ensure key covariate balance in cluster randomized trials in the nursing home setting. Facilities vary widely on key characteristics, small numbers may be randomized, and staggered enrollment is often necessary. A covariate-constrained algorithm was used to randomize facilities in the Trial to Reduce Antimicrobial use In Nursing home residents with Alzheimer's Disease and other Dementias (TRAIN-AD), an ongoing trial in Boston-area facilities (14 facilities/arm). Publicly available 2015 LTCfocus.org data were leveraged to inform the distribution of key facility-level covariates. The algorithm was applied in waves (2-8 facilities/wave) June 2017-March 2019. To examine the algorithm's general performance, simulations calculated an imbalance score (minimum 0) for similar trial designs. The algorithm provided good balance for profit status (Arm 1, 7 facilities; Arm 2, 6 facilities). Arm 2 was allocated more nursing homes with the number of severely cognitive impaired residents above the median (Arm 1, 7 facilities; Arm 2, 10 facilities), resulting in an imbalance in total number of residents enrolled (Arm 1, 196 residents; Arm 2, 228 residents). Facilities with number of black residents above the median were balanced (7 facilities/arm), while the numbers of black residents enrolled differed slightly between arms (Arm 1, 26 residents (13%); Arm 2, 22 residents (10%)). Simulations showed the median imbalance for TRAIN-AD's original randomization scheme (score = 3), was similar to the observed imbalance (score = 4). Covariate-constrained randomization flexibly accommodates logistical complexities of cluster trials in the nursing home setting, where LTCfocus.org is a valuable source of baseline data. TRIAL REGISTRATION NUMBER AND TRIAL REGISTER: ClinicalTrials.gov Identifier: NCT03244917.

Diminished Locomotor Control Is Associated With Reduced Neurovascular Coupling in Older Adults.

BACKGROUND: Walking, especially while dual-tasking, requires functional activation of cognitive brain regions and their connected neural networks. This study examined the relationship between neurovascular coupling (NVC), as measured by the change in cerebral blood flow in response to performing a cognitive executive task, and dual-task walking performance. METHODS: Seventy community-dwelling older adults aged 84 ± 5 years within the Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly (MOBILIZE) Boston Study were divided into LOW (n = 35) and HIGH (n = 35) NVC. NVC was quantified by transcranial Doppler ultrasound and stratified by the median change in cerebral blood flow velocity of the middle cerebral artery induced by the performance of the n-back task of executive function. Walking metrics included walking speed, step width, stride length, stride time, stride time variability, and double-support time from single- and dual-task walking conditions, as well as the "cost" of dual-tasking. RESULTS: During both single- and dual-task walking, older adults with LOW NVC displayed narrower step width (p = .02 and p = .02), shorter stride length (p = .01 and p = .02), and longer double-support time (p = .03 and p = .002) when compared with the HIGH group. During single-task walking only, LOW NVC was also linked to slower walking speed (p = .02). These associations were independent of age, height, hypertension, atrial fibrillation, and assistive device. The LOW and HIGH NVC groups did not differ in dual-task costs to walking performance. CONCLUSION: In older adults, diminished capacity to regulate cerebral blood flow in response to an executive function task is linked to worse walking performance under both single- and dual-task conditions, but not necessarily dual-task costs.

Concordance Between Proxy Level of Care Preference and Advance Directives Among Nursing Home Residents With Advanced Dementia: A Cluster Randomized Clinical Trial.

CONTEXT: Care consistent with goals is the desired outcome of advance care planning (ACP). OBJECTIVES: The objectives of this study were to examine concordance between advance directives and proxy care preferences among nursing home residents with advanced dementia and to determine the impact of an ACP video on concordance. METHODS: Data were from Educational Video to Improve Nursing home Care in End-stage dementia, a cluster randomized clinical trial conducted in 64 Boston-area facilities (32/arm) from 2013 to 2017. Participants included advanced dementia residents and their proxies (N = 328 dyads). At the baseline and quarterly (up to 12 months), proxies stated their preferred level of care for the resident (comfort, basic, or intensive) and advance directives for specific treatments (resuscitation, hospitalization, tube-feeding, intravenous hydration, antibiotics) were abstracted from the charts. At the baseline, proxies in intervention facilities viewed an ACP video. Their care preferences after viewing it were shared via a written communication with the primary care team. At each assessment, concordance between directives and proxy preferences was determined. RESULTS: Among the residents (mean age, 86.6 years; 19.5% male), the most prevalent directive was DNR (89.3%) and foregoing antibiotics was least common (parenteral, 8.2%; any type, 4.0%). Concordance between directives and each level of care preference was as follows: comfort, 7%; basic, 49%; and intensive, 58%. When comfort care was preferred, concordance was higher in intervention versus control facilities (10.8% vs. 2.5%; adjusted odds ratio, 2.48; 95% CI, 1.01-6.09). CONCLUSION: Better alignment between preferences for comfort-focused care and advance directives is needed in advanced dementia. An ACP video may help achieve that goal.

The trial to reduce antimicrobial use in nursing home residents with Alzheimer's disease and other dementias: study protocol for a cluster randomized controlled trial.

BACKGROUND: Infections are common in nursing home (NH) residents with advanced dementia but are often managed inappropriately. Antimicrobials are extensively prescribed, but frequently with insufficient evidence to support a bacterial infection, promoting the emergence of multidrug-resistant organisms. Moreover, the benefits of antimicrobials remain unclear in these seriously ill residents for whom comfort is often the goal of care. Prior NH infection management interventions evaluated in randomized clinical trials (RCTs) did not consider patient preferences and lack evidence to support their effectiveness in 'real-world' practice. METHODS: This report presents the rationale and methodology of TRAIN-AD (Trial to reduce antimicrobial use in nursing home residents with Alzheimer's disease and other dementias), a parallel group, cluster RCT evaluating a multicomponent intervention to improve infection management for suspected urinary tract infections (UTIs) and lower respiratory tract infections (LRIs) among NH residents with advanced dementia. TRAIN-AD is being conducted in 28 facilities in the Boston, USA, area randomized in waves using minimization to achieve a balance on key characteristics (N = 14 facilities/arm). The involvement of the facilities includes a 3-month start-up period and a 24-month implementation/data collection phase. Residents are enrolled during the first 12 months of the 24-month implementation period and followed for up to 12 months. Individual consent is waived, thus almost all eligible residents are enrolled (target sample size, N = 410). The intervention integrates infectious disease and palliative care principles and includes provider training delivered through multiple modalities (in-person seminar, online course, management algorithms, and prescribing feedback) and an information booklet for families. Control facilities employ usual care. The primary outcome, abstracted from the residents' charts, is the number of antimicrobial courses prescribed for UTIs and LRIs per person-year alive. DISCUSSION: TRAIN-AD is the first cluster RCT testing a multicomponent intervention to improve infection management in NH residents with advanced dementia. Its findings will provide an evidence base to support the benefit of a program addressing the critical clinical and public health problem of antimicrobial misuse in these seriously ill residents. Moreover, its hybrid efficacy-effectiveness design will inform the future conduct of cluster RCTs evaluating nonpharmacological interventions in the complex NH setting in a way that is both internally valid and adaptable to the 'real-world'. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03244917 . Registered on 10 August 2017.

An Advance Care Planning Video Decision Support Tool for Nursing Home Residents With Advanced Dementia: A Cluster Randomized Clinical Trial.

Importance: Better advance care planning (ACP) can help promote goal-directed care in patients with advanced dementia. Objectives: To test whether an ACP video (vs usual care) has an effect on documented advance directives, level of care preferences, goals-of-care discussions, and burdensome treatments among nursing home residents with advanced dementia. Design, Setting, and Participants: The Educational Video to Improve Nursing home Care in End-stage dementia (EVINCE) trial was a cluster randomized clinical trial conducted between February 2013 and July 2017, at 64 Boston-area nursing homes (32 facilities per arm). A total of 402 residents with advanced dementia and their proxies (intervention arm, n = 212; control arm, n = 190) were assessed quarterly for 12 months. Interventions: A 12-minute ACP video for proxies with written communication of their preferred level of care (comfort, basic, or intensive) to the primary care team. Main Outcomes and Measures: The primary outcome was the proportion of residents with do-not-hospitalize (DNH) directives by 6 months. Secondary outcomes included preference for comfort care, documented directives to withhold tube-feeding and intravenous hydration, documented goals-of-care discussions, and burdensome treatments (hospital transfers, tube-feeding, or parenteral therapy) per 1000 resident-days. Exploratory analyses examined associations between trial arm and documented advance directives when comfort care was preferred. Results: The mean age of the 402 study residents was 86.7 years [range, 67-102 years]; 350 were white (87.1%) and 323 were female (80.3%), with DNH directives that by 6 months did not differ between arms (63% in both arms; adjusted odds ratio [AOR], 1.08; 95% CI, 0.69-1.69). Preferences for comfort care, directives to withhold intravenous hydration, and burdensome treatments did not differ between arms. Residents in intervention vs control facilities were more likely to have directives for no tube-feeding at 6 months (70.10% vs 61.90%; AOR, 1.79; 95% CI, 1.13-2.82) and all other time periods, and documented goals-of-care discussions at 3 months (16.10% vs 7.90%; AOR, 2.58; 95% CI, 1.20-5.54). When comfort care was preferred, residents in the intervention arm were more likely to have both DNH and no tube-feeding directives (72.20% vs 52.80%; AOR, 2.68; 95% CI, 2.68-5.85). Conclusions and Relevance: An ACP video did not have an effect on preferences, DNH status, or burdensome treatments among residents with advanced dementia, but did increase directives to withhold tube-feeding. When proxies preferred comfort care, advance directives of residents in the intervention arm were more likely to align with that preference. Trial Registration: clinicaltrials.gov Identifier: NCT01774799.

Association of Prognostic Estimates With Burdensome Interventions in Nursing Home Residents With Advanced Dementia.

Importance: Prognostication in advanced dementia is challenging but may influence care. Objectives: To determine the accuracy of proxies' prognostic estimates for nursing home residents with advanced dementia, identify factors associated with those estimates, and examine the association between their estimates and use of burdensome interventions. Design, Setting, and Participants: Data were combined from 2 studies that prospectively followed 764 residents with advanced dementia and their proxies in Boston-area nursing homes for 12 months: (1) the Study of Pathogen Resistance and Exposure to Antimicrobials in Dementia, conducted from September 2009 to November 2012 (362 resident/proxy dyads; 35 facilities); and (2) the Educational Video to Improve nursing home Care in End-Stage Dementia, conducted from March 2013 to July 2017 (402 resident/proxy dyads; 62 facilities). Proxies were the residents' formally or informally designated medical decision makers. Main Outcomes and Measures: During quarterly telephone interviews, proxies stated whether they believed the resident would live less than 1 month, 1 to 6 months, 7 to 12 months, or more than 12 months. Prognostic estimates were compared with resident survival. Resident and proxy characteristics associated with proxy prognostic estimates were determined. The association between prognostic estimates and whether residents experienced any of the following was determined: hospital transfers, parenteral therapy, tube feeding, venipunctures, and bladder catheterizations. Results: The residents' mean (SD) age was 86.6 (7.3) years; 631 (82.6%) were women and 133 (17.4%) were men. Of the 764 residents, 310 (40.6%) died later than 12 months. Proxies estimated survival with moderate accuracy (C statistic, 0.67). When proxies perceived the resident would die within 6 months, they were more likely to report being asked (183 [7.2%] of 2526) vs not being asked (126 [5.0%] of 2526) about goals of care by nursing home clinicians (adjusted odds ratio [AOR], 1.94; 95% CI, 1.50-2.52). Residents were less likely to experience burdensome interventions when the proxy prognostic estimate was less than 6 months (89 [4.4%] of 2031) vs greater than 6 months (1008 [49.6%] of 2031) (AOR, 0.46; 95% CI, 0.34-0.62). Conclusions and Relevance: Proxies estimated the prognosis of nursing home residents with advanced dementia with moderate accuracy. Having been asked about their opinion about the goal of care was associated with the proxies' perception that the resident had less than 6 months to live and that perception was associated with a lower likelihood the resident experienced burdensome interventions.

High levels of an endothelial dysfunction marker (sVCAM-1) are associated with injurious and recurrent falls and mortality over a 5-year interval in an older population.

We investigated the association between elevated plasma concentrations of circulating soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and injurious falls and mortality over a 5-year period. We studied the prospective relationship between levels of circulating adhesion molecules and falls in 680 community-dwelling participants in the MOBILIZE Boston Study. The mean sVCAM-1 (±SD) concentration was 1192 ±â€¯428 ng/mL. Over 5-years of follow-up, 10.2% of participants died. The baseline sVCAM-1 (±SD) concentration was 1434 ±â€¯511 ng/mL in those who died vs. 1162 ±â€¯402 ng/mL in those who survived (P < 0.0001). sVCAM-1 level was associated with recurrent falls (P < 0.01); compared to the lowest quintile, the highest quintile of sVCAM-1 was associated with increased risk of injurious falls [multivariable adjusted Incidence Rate Ratio = 1.9, 95% CI (1.2-2.9), P = 0.009]. On survival analysis, the highest sVCAM-1 quintile was associated with the greatest mortality over 5 years (log-rank test, P < 0.0001). The adjusted hazard ratio was 2.4 [95% CI (2.1-2.7), P = 0.002]. High sVCAM-1 blood concentration was strongly associated with recurrent falls, injurious falls, and mortality in older adults.

Chronic Pain and Attention in Older Community-Dwelling Adults.

OBJECTIVES: To examine the cross-sectional relationship between chronic pain and complex attention in a population of community-living older adults. DESIGN: Prospective cross-sectional cohort study. SETTING: Population-based Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston Study II. PARTICIPANTS: Individuals aged 71 to 101 (N=354). MEASUREMENTS: Chronic pain was measured using the pain severity and interference subscales of the Brief Pain Inventory. Four subscales of the Test of Everyday Attention were used to measure domains of attention switching and selective, sustained, and divided attention. RESULTS: Before and after multivariable adjustment, pain severity was associated with poorer scores on measures of selective and sustained attention. Pain interference scores also were significantly inversely associated with selective attention. CONCLUSION: Chronic pain is associated with poorer performance in selective and sustained attention in community-dwelling older adults. Further research is needed to determine whether effective pain management could lead to better attentional performance in older adults. Older adults who live with chronic pain, often undertreated, are potentially at risk of cognitive difficulties and related functional consequences.