Showing papers by "Jack M. Guralnik published in 2022"

Cost-effectiveness of a physical activity and behaviour maintenance programme on functional mobility decline in older adults: an economic evaluation of the REACT (Retirement in Action) trial

Abstract: Mobility limitations in older populations have a substantial impact on health outcomes, quality of life, and social care costs. The Retirement in Action (REACT) randomised controlled trial assessed a 12-month community-based group physical activity and behaviour maintenance intervention to help prevent decline in physical functioning in older adults at increased risk of mobility limitation. We aimed to do an economic evaluation of the REACT trial to investigate whether the intervention is cost-effective.In this health economic evaluation, we did cost-effectiveness and cost-utility analyses of the REACT programme versus standard care on the basis of resource use, primary outcome, and health-related quality-of-life data measured in the REACT trial. We also developed a decision analytic Markov model that forecasts the mobility of recipients beyond the 24-month follow-up of the trial and translated this into future costs and potential benefit to health-related quality of life using the National Health Service and Personal Social Services perspective. Participants completed questionnaire booklets at baseline, and at 6, 12, and 24 months after randomisation, which included a resource use questionnaire and the EQ-5D-5L and 36-item short-form survey (SF-36) health-related quality-of-life instruments. The cost of delivering the intervention was estimated by identifying key resources, such as REACT session leader time, time of an individual to coordinate the programme, and venue hire. EQ-5D-5L and SF-36 responses were converted to preference-based utility values, which were used to estimate quality-adjusted life-years (QALYs) over the 24-month trial follow-up using the area-under-the-curve method. We used generalised linear models to examine the effect of the REACT programme on costs and QALYs and adjust for baseline covariates. Costs and QALYs beyond 12 months were discounted at 3·5% per year. This is a pre-planned analysis of the REACT trial; the trial itself is registered with ISRCTN (ISRCTN45627165).The 12-month REACT programme was estimated to cost £622 per recipient to deliver. The most substantial cost components are the REACT session leader time (£309 per participant), venue hire (£109), and the REACT coordinator time (£80). The base-case analysis of the trial-based economic evaluation showed that reductions in health and social care usage due to the REACT programme could offset the REACT delivery costs (£3943 in the intervention group vs £4043 in the control group; difference: -£103 [95% CI -£695 to £489]) with a health benefit of 0·04 QALYs (0·009-0·071; 1·354 QALYs in the intervention group vs 1·314 QALYs in the control group) within the 24-month timeframe of the trial.The REACT programme could be considered a cost-effective approach for improving the health-related quality of life of older adults at risk of mobility limitations.National Institute for Health Research Public Health Research Programme.

Comparison of supine and seated orthostatic hypotension assessments and their association with falls and orthostatic symptoms

Abstract: Orthostatic hypotension (OH) based on a change from seated‐to‐standing blood pressure (BP) is often used interchangeably with supine‐to‐standing BP.

Long‐term sex differences in all‐cause and infection‐specific mortality post hip fracture

Abstract: Mortality rates among men are double that of women in the first 2 years after hip fracture and may be related to more infections. Research has only examined differences in short‐term mortality after hip fracture. Thus, the objective was to determine if long‐term all‐cause mortality and infection‐specific mortality rates are higher in men compared to women.

Effect of Telmisartan on Walking Performance in Patients With Lower Extremity Peripheral Artery Disease: The TELEX Randomized Clinical Trial.

Abstract: Importance Patients with lower extremity peripheral artery disease (PAD) have reduced lower extremity perfusion, impaired lower extremity skeletal muscle function, and poor walking performance. Telmisartan (an angiotensin receptor blocker) has properties that reverse these abnormalities. Objective To determine whether telmisartan improves 6-minute walk distance, compared with placebo, in patients with lower extremity PAD at 6-month follow-up. Design, Setting, and Participants Double-blind, randomized clinical trial conducted at 2 US sites and involving 114 participants. Enrollment occurred between December 28, 2015, and November 9, 2021. Final follow-up occurred on May 6, 2022. Interventions The trial randomized patients using a 2 × 2 factorial design to compare the effects of telmisartan plus supervised exercise vs telmisartan alone and supervised exercise alone and to compare telmisartan alone vs placebo. Participants with PAD were randomized to 1 of 4 groups: telmisartan plus exercise (n = 30), telmisartan plus attention control (n = 29), placebo plus exercise (n = 28), or placebo plus attention control (n = 27) for 6 months. The originally planned sample size was 240 participants. Due to slower than anticipated enrollment, the primary comparison was changed to the 2 combined telmisartan groups vs the 2 combined placebo groups and the target sample size was changed to 112 participants. Main Outcomes and Measures The primary outcome was the 6-month change in 6-minute walk distance (minimum clinically important difference, 8-20 m). The secondary outcomes were maximal treadmill walking distance; Walking Impairment Questionnaire scores for distance, speed, and stair climbing; and the 36-Item Short-Form Health Survey physical functioning score. The results were adjusted for study site, baseline 6-minute walk distance, randomization to exercise vs attention control, sex, and history of heart failure at baseline. Results Of the 114 randomized patients (mean age, 67.3 [SD, 9.9] years; 46 were women [40.4%]; and 81 were Black individuals [71.1%]), 105 (92%) completed 6-month follow-up. At 6-month follow-up, telmisartan did not significantly improve 6-minute walk distance (from a mean of 341.6 m to 343.0 m; within-group change: 1.32 m) compared with placebo (from a mean of 352.3 m to 364.8 m; within-group change: 12.5 m) and the adjusted between-group difference was -16.8 m (95% CI, -35.9 m to 2.2 m; P = .08). Compared with placebo, telmisartan did not significantly improve any of the 5 secondary outcomes. The most common serious adverse event was hospitalization for PAD (ie, lower extremity revascularization, amputation, or gangrene). Three participants (5.1%) in the telmisartan group and 2 participants (3.6%) in the placebo group were hospitalized for PAD. Conclusions and Relevance Among patients with PAD, telmisartan did not improve 6-minute walk distance at 6-month follow-up compared with placebo. These results do not support telmisartan for improving walking performance in patients with PAD. Trial Registration ClinicalTrials.gov Identifier: NCT02593110.

Traumatic Brain Injury and Risk of Long-Term Nursing Home Entry among Older Adults: An Analysis of Medicare Administrative Claims Data.

Abstract: Traumatic brain injury (TBI) is a leading cause of injury-related disability among older adults and there is increasing interest in post-discharge management as this population grows. We evaluated the association between TBI and long-term nursing home (NH) entry among a nationally representative sample of older adults. We identified 207,355 adults aged ≥ 65 years who were diagnosed with either a TBI, non-TBI trauma, or were uninjured between January 2008 and June 2015 from a 5% sample of Medicare beneficiaries. NH entry was operationalized as the first NH admission that resulted in a stay ≥100 days. Time to NH entry was calculated as the difference between the NH entry date and the index date (the date of TBI, non-TBI trauma, or inpatient/outpatient visit in the uninjured group). We used cause specific Cox proportional hazards models with stabilized inverse probability of exposure weights to model time to NH entry as a function of injury in the presence of death as a competing risk and generated hazard ratios (HR) and 95% confidence intervals (CI). After excluding beneficiaries living in a NH at index, there were 60,600 TBI, 63,762 non-TBI trauma, and 69,893 uninjured beneficiaries in the sample. In weighted models, beneficiaries with TBI entered NHs at higher rates relative to the non-TBI trauma (HR 1.15; 95% CI 1.10, 1.20) and uninjured (HR 1.67; 95% CI 1.60, 1.74) groups. Future research should focus on interventions to retain older adult TBI survivors within the community.

Abstract 11123: Effects of Home-Based Ischemic Leg Symptom-Inducing Exercise on Simultaneous Improvement in Treadmill Walking Distance and Patient Reported Outcomes and in Peripheral Artery Disease: The LITE Randomized Clinical Trial

Abstract: Introduction: An optimal exercise intervention for individuals with peripheral artery disease (PAD) should improve both objective measures of walking and patient reported outcomes (PROs). This study evaluated whether home-based walking exercise conducted at a pace that induced ischemic leg symptoms (high intensity) improved both treadmill walking distance and related PROs more often than walking exercise conducted at a pace that did not induce ischemic leg symptoms (low intensity) and a non-exercise control group (control), respectively. Methods: Post-hoc analysis of PAD patients who participated in the 12-month LITE Trial and were assessed at 12 months follow-up. The LITE Trial randomized people with PAD into home-based high intensity exercise, low intensity exercise, or control. Objective measures of walking were pain-free treadmill walking distance (PFWD) and maximal treadmill walking distance (MWD). PROs related to physical functioning consisted of Walking Impairment Questionnaire (WIQ) and the Short Form-36 (SF-36) physical function score. Participants were categorized into one of four groups at 12-month follow-up: 1) improved both treadmill outcome and PRO, 2) improved treadmill outcome but not PRO, 3) improved PRO but not treadmill outcome; and 4) improved neither treadmill outcome or PRO. Improvement was defined as follow-up score minus baseline >0. Results: Of the 305 people with PAD randomized, 186 (61% Black, 46% female) had data for both treadmill testing and at least one PRO available at baseline and 12-month follow-up (age, sex, race). Participants randomized to high intensity exercise were significantly more likely to improve both MWD and WIQ distance and speed (Table), as well as both PFWD and WIQ speed, compared to the other groups. Conclusions: To improve both treadmill outcomes and PROs, patients with PAD should be encouraged to walk for exercise at a pace inducing ischemic leg symptoms, and not at a pace without ischemic leg symptoms.

A group-based exercise and behavioural maintenance intervention for adults over 65 years with mobility limitations: the REACT RCT

Abstract: Mobility limitation in older age reduces quality of life, generates substantial health- and social-care costs, and increases mortality. The REtirement in ACTion (REACT) trial aimed to establish whether or not a community-based active ageing intervention could prevent decline in physical functioning in older adults already at increased risk of mobility limitation. A multicentre, pragmatic, two-arm, parallel-group randomised controlled trial with parallel process and health economic evaluations. Urban and semi-rural locations across three sites in England. Physically frail or pre-frail older adults (aged ≥ 65 years; Short Physical Performance Battery score of 4–9). Recruitment was primarily via 35 primary care practices. Participants were randomly assigned to receive brief advice (three healthy ageing education sessions) or a 12-month, group-based, multimodal exercise and behavioural maintenance programme delivered in fitness and community centres. Randomisation was stratified by site and used a minimisation algorithm to balance age, sex and Short Physical Performance Battery score. Data collection and analyses were blinded. The primary outcome was change in lower limb physical function (Short Physical Performance Battery score) at 24 months, analysed using an intention-to-treat analysis. The economic evaluation adopted the NHS and Personal Social Services perspective. Between June 2016 and October 2017, 777 participants (mean age 77.6 years, standard deviation 6.8 years; 66% female; mean Short Physical Performance Battery score 7.37, standard deviation 1.56) were randomised to the intervention arm (n = 410) or the control arm (n = 367). Data collection was completed in October 2019. Primary outcome data at 24 months were provided by 628 (80.8%) participants. At the 24-month follow-up, the Short Physical Performance Battery score was significantly greater in the intervention arm (mean 8.08, standard deviation 2.87) than in the control arm (mean 7.59, standard deviation 2.61), with an adjusted mean difference of 0.49 (95% confidence interval 0.06 to 0.92). The difference in lower limb function between intervention and control participants was clinically meaningful at both 12 and 24 months. Self-reported physical activity significantly increased in the intervention arm compared with the control arm, but this change was not observed in device-based physical activity data collected during the trial. One adverse event was related to the intervention. Attrition rates were low (19% at 24 months) and adherence was high. Engagement with the REACT intervention was associated with positive changes in exercise competence, relatedness and enjoyment and perceived physical, social and mental well-being benefits. The intervention plus usual care was cost-effective compared with care alone over the 2 years of REACT; the price year was 2019. In the base-case scenario, the intervention saved £103 per participant, with a quality-adjusted life-year gain of 0.04 (95% confidence interval 0.006 to 0.074) within the 2-year trial window. Lifetime horizon modelling estimated that further cost savings and quality-adjusted life-year gains were accrued up to 15 years post randomisation. A relatively low-resource, 1-year multimodal exercise and behavioural maintenance intervention can help older adults to retain physical functioning over a 24-month period. The results indicate that the well-established trajectory of declining physical functioning in older age is modifiable. Participants were not blinded to study arm allocation. However, the primary outcome was independently assessed by blinded data collectors. The secondary outcome analyses were exploratory, with no adjustment for multiple testing, and should be interpreted accordingly. Following refinements guided by the process evaluation findings, the REACT intervention is suitable for large-scale implementation. Further research will optimise implementation of REACT at scale. This trial is registered as ISRCTN45627165. This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 10, No. 14. See the NIHR Journals Library website for further project information.

Physical Functional Impairment and the Risk of Incident Mild Cognitive Impairment in an Observational Study of World Trade Center Responders

Abstract: Background and Objectives Posttraumatic stress disorder (PTSD) has been linked to increased risk of cognitive dysfunction and physical functional impairment (PFI). The objective of this prospective cohort study was to examine whether PFI was associated with increased risk of incident mild cognitive impairment (MCI) among World Trade Center (WTC) responders with PTSD. We hypothesized that responders with PTSD would have an elevated risk of incident MCI and that PFI would mediate this increase. Methods We examined responder participants in the WTC Aging Study whose baseline physical assessments were completed by May 2016–April 2017 and were followed up at least once before December 2019. Those without complete demographic, medical, or behavioral data were excluded. PFI was assessed using measures of upper body strength (maximal handgrip strength [HGS]) and lower extremity physical functioning (Short Physical Performance Battery). PTSD was rated using a diagnostic interview and symptom checklist; MCI and dementia were assessed using the Montreal Cognitive Assessment and diagnosed using the National Institute on Aging–Alzheimer's Association criteria. Group differences and longitudinal comparisons were examined. Cox proportional hazards models were evaluated from time to incident MCI and conversion to dementia. A mediation analysis examined whether PFI mediated associations between PTSD and MCI. Results Within the sample of 2,687 WTC responders, 324 (12.06%, 95% CI = [10.83–13.29]) had lower extremity PFI. Responders with lower extremity PFI were older, had lower education and higher body mass, and were at a higher risk of pulmonary embolisms and PTSD. Responders with lower extremity PFI demonstrated lower baseline cognition and had increased hazards of MCI (multivariable-adjusted hazards ratio [aHR] = 1.55 [95% CI 1.21–1.98]); those with MCI converted to dementia more rapidly than those without PFI (2.73 [1.38–5.39] p = 0.004). In addition, each standard deviation decrease in HGS was associated with increased hazards of developing MCI (aHR = 1.35 [95% CI 1.10–1.66]). A mediation model suggested PFI played an intermediary role in the relationship between PTSD and MCI. Discussion WTC responders with PFI demonstrated worse cognitive and behavioral outcomes, and PFI played an intermediary role in the relationship between PTSD and incident MCI, suggesting that PFI may be an early indicator of MCI in responders with PTSD. Regular monitoring of PFI should be considered among PTSD populations.

Abstract 11480: Telmisartan to Improve Walking Performance in People With Lower Extremity Peripheral Artery Disease: The Telex Randomized Clinical Trial

Abstract: BACKGROUND. People with lower extremity peripheral artery disease (PAD) have reduced lower extremity perfusion, impaired lower extremity skeletal muscle function, and poor walking performance. Telmisartan, an angiotensin receptor blocker (ARB), has properties that reverse these abnormalities. This randomized clinical trial tested whether telmisartan improved six-minute walk distance, compared to placebo, in people with PAD at 6-month follow-up. METHODS. This multi-centered randomized clinical trial was designed as a 2 x 2 factorial design, comparing the effects of telmisartan plus supervised exercise therapy (SET) to telmisartan alone and SET alone, respectively and comparing telmisartan alone to placebo. PAD participants were randomized to one of four groups: telmisartan+SET (N=30), telmisartan + attention control (N=29), placebo + SET (N=28), or placebo+ attention control (N=27) for six months. Due to slower than anticipated enrollment, the primary comparison was changed to a comparison of the two telmisartan groups combined to the two placebo groups combined. The primary outcome was 6-month change in 6-minute walk distance. Secondary outcomes were maximal treadmill walking distance, the Walking Impairment Questionnaire distance, speed, and stair climbing scores, and the short-form 36 physical functioning score. Results adjusted for site, baseline six-minute walk distance, randomization to SET vs. attention control, and group differences in the prevalence of sex and heart failure at baseline. RESULTS. Of 114 randomized patients (mean [SD] age, 67.3 [9.9] years, 46 (40.4%) female, 81 (71.1%) Black), 105 (92%) completed 6-month follow-up. See the Table for results. CONCLUSIONS. These results do not support telmisartan for improving objectively measured walking performance or patient reported outcomes in patients with PAD.

Effects of Walking Exercise at a Pace With Versus Without Ischemic Leg Symptoms on Functional Performance Measures in People With Lower Extremity Peripheral Artery Disease: The LITE Randomized Clinical Trial

Abstract: Background In people with peripheral artery disease, post hoc analyses of the LITE (Low Intensity Exercise Intervention in Peripheral Artery Disease) randomized trial were conducted to evaluate the effects of walking exercise at a pace inducing ischemic leg symptoms on walking velocity and the Short Physical Performance Battery, compared with walking exercise without ischemic leg symptoms and compared with a nonexercising control group. Methods and Results Participants with peripheral artery disease were randomized to: home‐based walking exercise that induced ischemic leg symptoms; home‐based walking exercise conducted without ischemic leg symptoms; or a nonexercising control group for 12 months. Outcomes were change of walking velocity over 4 m and change of the Short Physical Performance Battery (0–12, with 12=best) at 6‐ and 12‐month follow‐up. A total of 264 participants (48% women, 61% Black race) were included. Compared with walking exercise without ischemic symptoms, walking exercise that induced ischemic symptoms improved change in usual‐paced walking velocity over 4 m at 6‐month (0.056 m/s [95% CI, 0.019–0.094 m/s]; P<0.01) and 12‐month follow‐up (0.084 m/s [95% CI, 0.049–0.120 m/s]; P<0.01), change in fast‐paced of walking velocity over 4 m at 6‐month follow‐up (P=0.03), and change in the Short Physical Performance Battery at 12‐month follow‐up (0.821 [95% CI, 0.309–1.334]; P<0.01). Compared with control, walking exercise at a pace inducing ischemic symptoms improved change in usual‐paced walking velocity over 4 m at 6‐month follow‐up (0.066 m/s [95% CI, 0.021–0.111 m/s]; P<0.01). Conclusions In people with peripheral artery disease, those who walked for exercise at a comfortable pace without ischemic leg symptoms slowed their walking speed during daily life and worsened the Short Physical Performance Battery score, a potentially harmful effect, compared with people who walked for exercise at a pace inducing ischemic leg symptoms. Compared with a control group who did not exercise, home‐based walking exercise at a pace inducing ischemic leg symptoms significantly improved change of walking velocity over 4 m at 6‐month follow‐up, but this benefit did not persist at 12‐month follow‐up. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02538900.