6-minute Walk Research Articles

Ab. No. 149 Therapeutic Effects of Yoga On Gait Variables, Walking Capacity, Balance, Lower Extremity Strength, and Flexibility in Ambulatory Children With Cerebral Palsy

Introduction: The purpose is to explore the effects of Yoga on gait variables, walking capacity, balance, and lower extremity strength and flexibility in ambulatory children with cerebral palsy. Children with cerebral palsy have limited access to skill-based movement programs that combine therapeutic principles of movement rehabilitation with community involvement, the need for activity-grounded therapeutics in cerebral palsy is the need of the hour. Rehabilitation typically focuses on range of motion exercises to prevent and delay contractures, flexibility exercises to increase range of motion, progressive resistance exercises to enhance strength, and varied interventions to improve posture, balance, and the acquisition of functional skills. Thus, the therapeutic movement that improves motor control and imitates social interaction. Methods: Twenty-one children with the potential to participate and corresponding to the inclusion criteria were recruited in the study. The mean average age group of the participants was 8.97 years with 5 girls and 16 boys. Children with cerebral palsy with Gross Motor Function Classification I–III were divided into a control group and an experimental group. Throughout 12 weeks, the control group received conventional physiotherapy treatment while the experimental group an additional one-hour yoga sessions three times each week. The Walking capacity (6 Minute Walk Test), Balance (Pediatric Balance Scale), Muscle strength (Manual Muscle Test Score), and Flexibility (rotational profile using goniometric measurements) were administered before, and after the interventions in each group. Wilcoxon signed-rank test was used to evaluate thedata. Results: Statistically significant differences were found in the walking capacity (p < 0.004), dynamic balance (p 0.002), Strength (p 0.007), and flexibility (p 0.007). Conclusion: Yoga can be used as an adjunct to conventional physiotherapy interventions. Implications: An improvement in walking capacity, and balance leads to increased mobility and improved functional activities of the children with cerebral palsy. As yoga was an additional therapy, this showed better engagement in therapy as it improved the zeal to attend the therapy. These further improved the quality of life as children could engage amongsttheir typically developing peers.

Clinical study on the safety and feasibility of AiWalker-K for lower limbs exercise rehabilitation in children with cerebral palsy.

Robotic-assisted gait training (RAGT) devices are effective for children with cerebral palsy (CP). Many RAGT devices have been created and put into clinical rehabilitation treatment. Therefore, we aimed to investigate the safety and feasibility of a new RAGT for children with CP. This study is a cross-over design with 23 subjects randomly divided into two groups. The occurrence of adverse events and changes in heart rate and blood pressure were recorded during each AiWalker-K training. Additionally, Gross Motor Function Measure-88 (GMFM-88), Pediatric Balance Scale (PBS), 6 Minutes Walking Test (6MWT), Physiological Cost Index, and Edinburgh Visual Gait Score (EVGS) were used to assess treatment, period, carry-over, and follow-up effects in this study. Adverse events included joint pain, skin pain, and injury. Heart rate and blood pressure were higher with the AiWalker-K compared to the rest (P < 0.05), but remained within safe ranges. After combined treatment with AiWalker-K and routine rehabilitation treatment, significant improvements in 6MWT, GMFM-88 D and E, PBS, and EVGS were observed compared to routine rehabilitation treatment alone (P < 0.05). Under the guidance of experienced medical personnel, AiWalker-K can be used for rehabilitation in children with CP.

Evaluation of the HEAL™ing Mental Health program: A prospective cohort study of short-term changes from a physical activity and lifestyle education program for people with mental health disorders living in rural Australia.

This study aimed to evaluate short-term outcomes of the HEAL™ing Mental Health program, an 8-week intervention for change in functional, behavioural and physiological health and wellbeing designed for people living with mental health conditions in rural or regional areas of Australia. A prospective cohort study was completed, reporting on 19 items (pre-program) and 15 (post-participation change), organised across seven domains. Participants took part in an Accredited Exercise Physiologist/Nurse led supervised group exercise (60 minutes) and healthy lifestyle education program (60 minutes). Separate linear mixed models with restricted maximum likelihood were used to examine the primary research question considering the effect of the program on: walking (min/week); planned, incidental and total physical activity (min/week); sitting time; active days; fruit and vegetable intake; body mass index; waist circumference; blood pressure; 6 minute walk distance; 30 second sit-to-stand; psychological distress symptoms; and stage of behaviour change. There were 99 participants (31 males, 68 females) out of 117 participants completed more than 50% of program sessions. Twelve of 15 measures achieved their desired target change and a statistically significant change toward the desired outcome was reported for 14 of 15 measures. Positive results were obtained for participants completing more than 50% of sessions, suggesting that HEAL™ ing Mental Health program is effective to increase physical activity and healthy lifestyle choices in individuals who self-report a mental health disorder.

Predictors of Response to Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer: A Prospective Cohort Study

Introduction: Lung cancer carries the highest cancer-related mortality rates worldwide. Despite all recent advances, the mortality from lung cancer is still rising. A better understanding of the risk factors may help us predict responses to chemotherapy for better management. Aim: To evaluate predictors of response to chemotherapy in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Materials and Methods: This was a prospective cohort study conducted in the Department of Pulmonary Medicine at Government Medical College and Hospital, Chandigarh, India. A total of 60 confirmed cases of advanced (stage IIIB and IV) NSCLC patients were enrolled consecutively for a duration of two years. Baseline clinical parameters, routine blood tests, spirometry, exercise capacity using the 6 Minute Walk Test Distance (6MWTD), and Computed Tomography (CT)-based tumour size were recorded. Certain pre-defined patient, disease, and therapy-related factors (age, gender, dyspnoea, baseline blood tests, tumour size, histology, etc.) were evaluated for their possible role as predictors of treatment response in advanced NSCLC patients. A positive response was defined if the response to chemotherapy was Complete Response (CR) or Partial Response (PR), and a negative response if the response was Progressive Disease (PD) or Stable Disease (SD) as per revised RECIST (Response evaluation criteria in solid tumors) 1.1 criteria. Variables between the two groups were compared using the Mann-Whitney U test and Chi-square test. To find out the factors that may predict response to treatment, univariate and multivariate logistic regression analysis were used. Results: Out of a total of 60 confirmed cases of NSCLC patients, only 40 patients were able to complete the four cycles of chemotherapy. The mean age of the patients was 58.5±9.6 years. There were a total of 35 males (87.5%) and five females (12.5%) in the study. Out of 40 patients, 27 (67.5%) had squamous cell carcinoma and 13 (32.5%) had adenocarcinoma. On univariate analysis, Neutrophil-Lymphocyte Ratio (NLR) had a statistically significant association with tumour response (p&lt;0.001). On multivariate analysis, advanced age (p=0.05) and high (&gt;3.81) NLR (p=0.002) were found as independent predictors of poor response to chemotherapy. Conclusion: Pre-treatment high NLR and advanced age are significant factors for a poor response to chemotherapy treatment in advanced NSCLC patients.

Six Minutes Walking Test as Assessment in Determining Fitness to Work After Spinal Tuberculosis Post Stabilization and Comprehensive Rehabilitation: A Case Report

Introduction: Spinal tuberculosis is the most common extrapulmonary skeletal form of tuberculosis that can lead to neuromuscular deficit. Neuromuscular deficit may include paraplegia in both legs, inability to perform daily activities, and an increased risk of loss of occupation. Case Presentation: A 37-year-old male presented with a chief complaint of weakness in both legs and was unable to stand properly unassisted. This patient was diagnosed with spinal tuberculosis, confirmed by MRI. The rehabilitation program was designed for 6 months, focusing on the preservation of cardiorespiratory endurance and planning a return to work. Evaluation of physical fitness and working ability was carried out using the 6-Minute Walking Test (6MWT) and Work Ability Index (WAI) questionnaires to determine whether the patient was fit to work. Six months after the rehabilitation program, the patient showed moderate physical fitness and a WAI score of 37 indicating fitness to work. Conclusion: Complications of spinal tuberculosis can cause disability in daily activities and result in loss of occupation. In this case, after six months of a comprehensive rehabilitation program and evaluation of fitness capacity, the patient can return to work but still needs more support of his work ability than before the illness.

PHYSICAL RESERVE MEASURES AS PREDICTORS OF RESILIENCE IN OLDER ADULTS UNDERGOING TOTAL KNEE REPLACEMENT

Abstract Measures of physical reserve have been shown to predict resilience following surgery in older adults. The objective of this study was to evaluate the utility of gait speed, hand grip strength, and 3-minute walk distance to predict resilience in older adults scheduled for total knee arthroplasty (TKA), in whom preoperative gait and mobility may be limited by pain or reduced range of motion. We conducted an interim analysis of data from PRIME-KNEE, an ongoing prospective study following participants age ≥60 years undergoing TKA recruited from Duke hospitals. We determined the change in self-reported Lower Extremity Physical Activities of Daily Living (LE PADL) score from pre-surgery baseline to 4 months following TKA in 133 participants (mean age = 72, 59% female). Gait speed, hand grip, and 3-minute walk were collected at baseline. A total of 110 (83%) participants exhibited “resilience,” defined dichotomously as any improvement in LE PADL score (occurred in 38 participants) or return to a non-disabled state (occurred in 72 participants). Logistic regression analysis adjusted for age and sex revealed that 3-minute walk distance was significantly associated with resilience at 4 months (OR=1.012 [CI 1.002-1.022]) with an area under the curve of 0.634. The presentation will review the implications of these results and present findings with an updated sample, as well as discuss the need for other predictive measures, such as provocative tests (i.e., tests that measure response to an experimental stressor) and biomarkers.

GAIT PARAMETERS IN OLDER BREAST CANCER SURVIVORS WITH PERSISTENT CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY

Abstract Chemotherapy-induced peripheral neuropathy (CIPN) results from chemotherapy for breast cancer treatment. CIPN symptoms persist causing significant loss of functional abilities and increased risk of falls. This study aimed to assess the spatiotemporal gait parameters in breast cancer survivors with CIPIN using an IMU system. We hypothesized that spatiotemporal gait parameters will differ between patients with persistent CIPN as compared to normative values. Thirty-two women who completed taxane-based chemotherapy for breast cancer and who have symptomatic neuropathy &amp;gt;6 months following completion of chemotherapy. Gait was assessed using seven Inertial Measurement Unit (IMU) sensors positioned at the sacrum, upper and lower leg, and foot. Participants completed a 2-minute walk at a comfortable walking pace. The outcome variables assessed included gait speed, single limb support, stride length, gait cycle time, stance percent, swing percent, double support percent, and cadence. Mean age 65(10) years, gait speed was 0.95(0.2) meters/second, single limb support 37.9(2.2) % of gait cycle, stride length 1.1(0.2) meters, gait cycle time 1.2(0.1) seconds, stance percent 62.1(2.2)% GC, swing percent 37.9(2.2)% GC, double support percent 23.9(4.3)% GC, and cadence 104.6(12.3) steps/min. Gait parameters assessed in this study showed an excellent test-retest reliability (r &amp;gt;0.86; ICC &amp;gt; 0.90). This is the first study to assess gait parameters in older breast cancer survivors with CIPN. Breast cancer survivors with CIPN showed reductions in all gait parameters. Reduced gait speed and stride length are critical indicators of fall risk for women with CIPN. Our study confirmed differences in spatiotemporal parameters between patients with persistent CIPN.

Discordance of patient-reported outcome measures with objectively assessed walking decline in peripheral artery disease

ObjectiveAmong people with peripheral artery disease (PAD), perceived change in walking difficulty over time, compared with people without PAD, is unclear. Among people reporting no change in walking difficulty over time, differences in objectively measured change in walking performance between people with and without PAD are unknown. MethodsA total of 1289 participants were included. Eight hundred seventy-four participants with PAD (aged 71.1 ± 9.1 years) were identified from noninvasive vascular laboratories and 415 without PAD (aged 69.9 ± 7.6 years) were identified from people with normal vascular laboratory testing or general medical practices in Chicago. The Walking Impairment Questionnaire and 6-minute walk were completed at baseline and 1-year follow-up. The Walking Impairment Questionnaire assessed perceived difficulty walking due to symptoms in the calves or buttocks on a Likert scale (range, 0-4). Symptom change was determined by comparing difficulty reported at 1-year follow-up to difficulty reported at baseline. ResultsAt 1-year follow-up, 31.9% of participants with and 20.6% of participants without PAD reported walking difficulty that was improved (P < .01), whereas 41.2% vs 55%, respectively, reported walking difficulty that was unchanged (P < .01). Among all reporting no change in walking difficulty, participants with PAD declined in 6-minute walk, whereas participants without PAD improved (−10 vs +15 meters; mean difference, −25; 95% confidence interval, −38 to −13; P < .01). ConclusionsMost people with PAD reported improvement or no change in walking difficulty from calf or buttock symptoms at one-year follow-up. Among all participants who perceived stable walking ability, those with PAD had significant greater declines in objectively measured walking performance, compared with people without PAD.

Post-Exercise Carbohydrate Intake in the Early Postoperative Phase Following Primary Total Hip and Knee Arthroplasties – A Randomized Controlled Trial

The aim of this study was to investigate whether post exercise carbohydrate intake improves training effect in the first postoperative days, in patients who have had a primary total knee or hip arthroplasty. Subjects were primary total hip (THA) (n=18), and total knee arthroplasties (TKA)(n=25) patients randomized to consume 30 g maltodextrin or placebo within 15 minutes after each training session as a supplement to the standard diet. The outcome measures were six minute walk test (6-MWT), number of completed training sessions, training intensity, and duration. There was no difference in the 6-MWT, number of completed training sessions, training intensity and duration between the intervention vs control group. When stratified for operation procedure, THA patients in the intervention group trained longer (26.7 ± 5.8 vs 15.2 ± 4.1 min, P = 0.017), and at an overall higher intensity (scale 1-5) (2.4 ± 1.0 vs 1.75 ± 0.8, P = 0.021) and during the training sessions with the physiotherapist (2.5 ± 1.1 vs and 1.8 ± 0.9, P = 0.044) compared with controls. In contrary, the duration of self-training was longer in the TKA control group compared with the intervention group (19.7 ± 7.0 vs 13.8 ± 3.3 min, P = 0.021). In conclusion, minor positive effects of maltodextrin were observed after hip arthroplasties, while minor negative effects of maltodextrin were observed after knee arthroplasties. It is unknown whether these findings are due to the low dose of maltodextrin, small number of study participants, differences in overall nutritional status, or lack of effect.

Assessing the robustness of muscle strength and physical performance measures in women older than 40 years: a test-retest reliability study.

This study investigated the test-retest reliability and minimal detectable change (MDC) of muscle strength and physical performance tests in women older than 40 years. A total of 113 women, aged 58 ± 11 years (82% postmenopausal women), with a body mass index of 28.5 ± 5.8 kg/m 2 , participated in this study. One-repetition maximum (1RM) tests were conducted for seven strength exercises: 45° leg press, bench press, leg extension, pec deck, wide-grip lateral pull-down, leg curl, and seated cable row, with a retest after 48 hours. Timed Up and Go (TUG), 6-minute walk, and 30-second sit-to-stand tests were performed on the same day and retested after 72 hours. The tests and retests were administered by the same evaluators. Relative reliability (consistency of participant rank between test-retest) was assessed using the intraclass correlation coefficient for consistency and agreement, and absolute reliability (precision of score) was assessed using the MDC based on the standard error of prediction. The 1RM and performance tests exhibited excellent reliability: 45° leg press (consistency, 0.99; agreement, 0.98), bench press (consistency, 0.96; agreement, 0.96), leg extension (consistency, 0.93; agreement, 0.91), pec deck (consistency, 0.90; agreement, 0.88), wide-grip lateral pull-down (consistency, 0.91; agreement, 0.89), leg curl (consistency, 0.84; agreement, 0.83), seated cable row (consistency, 0.92; agreement, 0.94), TUG (consistency, 0.87; agreement, 0.87), 6-minute walk (consistency, 0.96; agreement, 0.95), and 30-second sit to stand (consistency, 0.85; agreement, 0.80). These tests showed meaningful MDC values, particularly for the 1RM test performed on the machine and the 30-second sit-to-stand test: 45° leg press, 22.2 kg (15%); bench press, 4.9 kg (19%); leg extension, 9.2 kg (35%); pec deck, 8.8 kg (44%); wide-grip lateral pull-down, 9.4 kg (31%); leg curl, 9.2 kg (51%); seated cable row, 11.4 kg (29%); TUG, 1.4 seconds (20%); 6-minute walk, 50.9 m (10%); and 30-second sit to stand, 4.6 reps (30%). Although the muscle strength and physical performance tests demonstrate excellent relative reliability in women older than 40 years, they exhibit low absolute reliability, particularly the 1RM test performed on the machine and the 30-second sit-to-stand test. Therefore, although these tests show good consistency in the positioning of women within the group after repeated measures, their precision measure is relatively low (high fluctuation). Changes in these tests that are smaller than the MDC may not indicate real changes in women at middle age and older.

Comparison of a single session of tDCS on cerebellum vs. motor cortex in stroke patients: a randomized sham-controlled trial

Objective The purpose of this study was to determine whether a single session of trans-cranial direct current stimulation (tDCS) of the cerebellum and M1 has any advantages over one another or sham stimulation in terms of balance, gait and lower limb function. Methods A total of 66 patients who had experienced their first ever stroke were recruited into three groups for this double-blinded, parallel, randomized, sham-controlled trial: cerebellar stimulation group (CbSG), M1 stimulation group (MSG) and sham stimulation group (SSG). A single session of anodal tDCS with an intensity of 2 mA for a duration of 20 min was administered in addition to gait and balance training based on virtual reality using an Xbox 360 with Kinect. Balance, gait, cognition and risk of fall were assessed using outcome measures before intervention (T0), immediately after intervention (T1) and an hour after intervention (T2). Results Across group analysis of all outcome measures showed statistically non-significant results (p > .05) except for Six Minute Walk Test (p value T0 = .003, p value T1 = .025, p value T2 = .016). The training effect difference showed a significant difference in balance, gait and cognition, as well as cerebral and cerebellar stimulation, in comparison to sham stimulation (p < .05). The risk of falls remained unaffected by any stimulation (p > .05). Conclusions In addition to Xbox Kinect-based rehabilitation training, a single session of anodal tDCS to the M1 or cerebellum may be beneficial for improving lower limb function, balance and gait performance.

Effects of Lower Extremity Functional Training (LIFT) on Gross Motor Function and Gait in Children with Spastic Cerebral Palsy

Background: Children with spastic cerebral palsy face challenges in mobility due to impairments in gross motor function and gait. Lower Extremity Functional Training (LIFT) is posited as a potential intervention to ameliorate these difficulties. Objective: This study aimed to evaluate the effectiveness of LIFT on enhancing gross motor function and gait in children with spastic cerebral palsy. Methods: Employing a Randomized Controlled Trial design, the study recruited 22 participants and allocated them into intervention and control groups. Over six weeks, the intervention group received LIFT along with baseline treatment, while the control group received only baseline treatment. Outcomes were measured using the 2-minute Walk Test, Single Leg Stance Test, and Gross Motor Function Measure (GMFM). Results: Post-intervention, the intervention group exhibited a statistically significant improvement in the Single Leg Stance Test (p=0.032). However, no significant differences were observed in the 2 Minute Walk Test (p=0.448) and GMFM (p=0.289) between the intervention and control groups. Within-group comparisons showed significant improvements from pre- to post-intervention in both the Single Leg Stance Test (p=0.006) and the 2 Minute Walk Test (p=0.012) for the intervention group, and in the 2 Minute Walk Test (p=0.003) and GMFM (p=0.004) for the control group. Conclusion: While LIFT resulted in significant within-group improvements in single-leg balance, it did not demonstrate a significant advantage over baseline treatment alone in improving overall gait and gross motor function in children with spastic cerebral palsy. Further research with larger sample sizes and longer intervention durations may be necessary to ascertain the full impact of LIFT in this population.

Effect of the COVID-19 pandemic on crowding aversion in public transport and transport mode choice: The case of Santiago, Chile

Mode choice modeling has shown a significant crowding effect over travel time perception. But the recent COVID-19 pandemic and the related sanitary measures have changed perceptions of overcrowding on the mode choice. This study aims to quantify these changes through a hybrid discrete choice model using data collected through a revealed preferences survey applied in two time periods in Santiago, Chile. Although the overcrowding aversion was included in the choice model as a latent variable, that had a significant effect on the mode choice of people only for the set of responses belonging to the first time period, which implies a reduction of the initial pandemic impact. Results also show that women and people younger than 35 years old have higher levels of crowding aversion. By analyzing the disutility generated by each alternative mode, it is determined that the bicycle is preferred over the car for trips of distances less than 4 km. In the same way, for trips of less than 3 km, the walk has a preference over public transport. Regarding the marginal rates of substitution between travel and walking time in public transport, for trips of 30 min with an overcrowding level of 6 pax/m2, women over 35 years are willing to trade 2 min of travel for 1 min of walking. When comparing the rates obtained in a pre-pandemic study, it is obtained that for trips of less than 9 min, people in the pandemic have more preferences for walking over spending time inside public transport.

Outcomes Associated With Translating Evidence-Based Research Into Practice: The Physical Activity for Lifelong Success Program.

Few programs assess for outcomes once translated into practice. The Physical Activity for Lifelong Success program was developed as a center-based public health intervention and shown to improve walking speed and distance among older adults with type 2 diabetes. We adapted the program for community-based delivery by lay leaders to physically inactive older adults. We followed the Replicating Effective Programs framework to identify community stakeholders, adapt, implement, and evaluate fidelity of delivery in community settings, and plan for maintenance and evolution. Sixteen community sites enrolled 184 adults (mean age 73.5y, 85% female, 93% White) in 21 workshops. Baseline and postworkshop measures assessed participants' health-related quality of life, physical function, and physical fitness. Data were analyzed using Fisher exact tests, Student t test, and paired linear regression with fixed effects. Fidelity testing indicated leader training was sufficient to maintain key elements with delivery. Data from 122 participants showed improvements in chair stands (P < .001), arm curls (P < .001), 2-minute step test (P < .001), sit-and-reach (P = .001), 8-foot up-and-go (P < .001), and 10-m walk (P < .001). Adaptation of Physical Activity for Lifelong Success for implementation by community organizations for physically inactive older adults demonstrates that fidelity and effectiveness can be maintained after program translation.

The level of physical activity among ambulant stroke survivors at one year: a cross sectional study in a tertiary center in Malaysia

Background &amp; Objective: Despite the importance of physical activity, there is lack of evidence measuring the level of activity performed by the stroke survivors. This study aims to determine the level of physical activity amongst ambulant stroke patients in a tertiary centre in Malaysia and to investigate the factors that may impact their physical activity. Methods: A cross-sectional study was conducted on ambulant stroke participants at one year post stroke. International Physical Activity Questionnaire (IPAQ) was used to measure the level of physical activity, and 6 Minute Walk Test (6MWT) was recorded to assess the participants functional walking distance and endurance. The participants were categorised into low, moderate, or high physical activity levels. Age-matched healthy controls were recruited form community. Factors including presence of depression were tested in relation to physical activity. P-value of &lt;0.05 was considered statically significant in all statistical analyses. Results: There were 45 stroke patients and 30 controls recruited in this study. Participants in the stroke group has significantly lower level of physical activity compared to the control group, especially in the high physical activity level (p&lt;0.001); 55.6% reported having moderate, 31.1% low and 13.3% high physical activity level respectively. No significant factors were found to be associated with the physical activity. Only depression was found to have a weak negative correlation with level of physical activity (p=0.003). Conclusion: Stroke survivors have lower level of physical activity at one year post stroke despite having mild physical impairments. Rehabilitation strategies to promote physical activities should be implemented early to take advantage on the benefits of cardiovascular fitness as secondary prevention of stroke.

Identifying Geriatric Syndromes in Adults with Sickle Cell Disease Using the Sickle Cell Disease Functional Assessment (SCD-FA): The Sickle Cell Disease Functional Assessment Validation and Refinement (SILVR) Study

Introduction As people with sickle cell disease (SCD) age, they experience accelerated functional decline. Since historically survival for SCD has been limited to middle age, geriatric syndromes in adults with SCD remains understudied. Chronological age does not accurately represent a person's health status; thus, valid functional measures for adults with SCD are required. Geriatric assessments are commonly used to measure function in older adults in the general population. We previously demonstrated feasibility, safety, and acceptability of a geriatric assessment battery called the Sickle Cell Disease Functional Assessment (SCD-FA) in adults with SCD. The SCD-FA includes physical performance test and surveys evaluating multiple health domains. The purpose of this study was to evaluate the construct validity of the SCD-FA. Methods We enrolled younger (age 18-39) and older (age ≥ 40 years) adults with SCD in a single center prospective study. We assessed construct validity of each SCD-FA measure by determining known-group validity. Specifically, we evaluated whether the SCD-FA could distinguish between participants known to differ based on the following: age (&amp;lt; 40 vs ≥ 40), SCD genotype non-severe (HbSC/HbSβ +-thalassemia) vs severe (HbSS/HbSβ 0-thalassemia), and dependence in Activities of Daily Living/Instrumental Activities of Daily Living (no ADL/IADL deficit vs ≥ 1 ADL/IADL deficits). We used Student's t-tests and Wilcoxon rank sum test to gauge significant differences between groups. Results We performed the SCD-FA in 111 adults with SCD at steady state, with 93 (84%) having complete data. Most participants (58%) were female. The mean age of all participants was 44 ± 14 (range 19-82 years), with most (56%) age ≥ 40 years. The mean age for younger adults (18-39 years) was 30 ± 5.8 and 54 ± 9.3 for older adults (≥ 40 years). When evaluating SCD-FA measures by age, older adults had lower scores on PROMIS Physical Function (younger 52 ± 6.9 vs older 46 ± 8.4; p&amp;lt;0.001). Although there was no difference in number of falls by age, there were several participants with ≥ 1 fall (15%) or near fall (36%) in the last 6 months. Older adults had higher scores on the Social Support Survey (implying better support) (younger 69 ± 30 vs older 80 ± 20; p&amp;lt; 0.05). Older adults had more non-SCD comorbidities (younger 0.5 ± 0.7 vs older 1.7 ± 1.7; p&amp;lt;0.001), with no younger adults with ≥ 3 comorbidities vs. 33% of older adults with ≥ 3 comorbidities, more SCD conditions (younger 2.0 ± 1.5 vs older 2.7 ± 1.7; p&amp;lt; 0.05), and more reports of fair or poor hearing (0% younger vs 8% older; p = 0.01). Older adults took more prescribed medications (younger 3.9 ± 2.4 vs older 6.3 ± 3.9; p = 0.001) and were more likely to meet criteria for polypharmacy (defined as ≥ 5 prescribed medications) with 30% of younger adults vs 64% of older adults (Figure). Most participants (64%) had HbSS/HbSβ 0 (severe genotype) and 36% had HbSC/HbSβ + (non-severe genotype). When comparing groups by genotype, participants with severe genotypeshad a lower body mass index (severe25 ± 5.8 vs non-severe 31 ± 8.4 kg/m2; p &amp;lt; 0.005) and fewer non-SCD comorbidities (severe 0.75 ± 1.0 vs non-severe 1.9 ± 1.8; p&amp;lt; 0.005). There was no difference in physical performance, falls, psychological state, SCD conditions, and number of medications by genotypes. Of all participants, 34% reported dependence in ≥ 1 ADL/IADL. When comparing groups by ADL/IADL dependence, those who were dependent in ≥ 1 ADL/IADL had worse physical performance for all measures (gait speed, grip strength, 6-minute walk, Timed Up and Go test, and 30-Second Chair Stands). ADL/IADL dependent participants had more falls, higher PHQ-9 scores, lower MiniCog scores, more non-SCD comorbidities, and were more likely to report fair or poor vision. There was no difference in reported hearing deficits. (Table) Conclusion The SCD-FA was able to distinguish between known-groups by age and ADL/IADL dependence and identify deficits in adults with SCD such as falls, polypharmacy, comorbidities, and sensory deficits. Geriatric syndromes did increase with age in adults with SCD and were more common than in the general population (34% ADL dependent SCD participants vs 15% of middle-aged U.S. adults). Therefore, there is a need for early initiation of interventions to improve function and quality of life. We are currently adapting geriatric interventions for older adults with SCD. In future studies we will assess the predictive validity of the SCD-FA.

Prospective Identification of Variables As Outcomes for Treatment (PIVOT): A Phase II Clinical Trial of Hydroxyurea for Children and Adults with HbSC Disease

Introduction: HbSC is a common form of sickle cell disease especially prevalent in West Africa. Despite experiencing similar clinical events as those with sickle cell anemia (HbSS or HbSβ 0 thalassemia), individuals with HbSC disease have received much less attention because disease complications occur less frequently and often manifest later in life. Retrospective reports suggest that hydroxyurea might benefit people living with HbSC disease, but rigorous prospective data are unavailable to describe potential treatment benefits, long-term safety, and appropriate study endpoints. We designed a Phase II clinical trial of hydroxyurea for children and adults with HbSC disease with the following aims: 1) to measure possible laboratory toxicities of hydroxyurea; 2) to assess the clinical effects of hydroxyurea on sickle-related clinical and laboratory parameters; and 3) to identify study endpoints that are suitable for a future definitive Phase III trial of hydroxyurea for HbSC disease. Methods: Prospective Identification of Variables as Outcomes for Treatment (PIVOT, Trial ID PACTR202108893981080) is a double-blind, randomized, placebo-controlled Phase II trial of hydroxyurea. Inclusion criteria included people with HbSC disease, age 5 to 50 years, receiving care at Korle Bu Teaching Hospital, Accra, Ghana. Exclusion criteria included treatment with hydroxyurea or other disease-modifying treatment or participation in a therapeutic trial in the previous 6 months, hospitalization &amp;gt;10 times in the past 12 months, pregnancy, severe chronic kidney disease or other underlying illness making participation ill-advised, previous myelosuppressive therapy or stem cell transplant, or inability to take hydroxyurea. After written informed consent, participants underwent initial screening for 2 months before randomization to placebo or hydroxyurea (donated by Addmedica, Inc, Paris) with a goal of treating ~100 participants in each arm for one year. Randomization is stratified by age and sex to ensure equal numbers of children and adults with balanced baseline characteristics in each arm. The primary study outcome is cumulative hematological toxicities after 12 months of treatment. Here we report the baseline characteristics of the enrolled cohort. Results: From April 2022 to June 2023, a total of 243 patients with HbSC disease (123 children, 120 adults) consented and began screening (Figure); after ~10% screen failures, 217 (112 children, 105 adults) were eligible for randomization. The average age (mean ± SD) at enrollment was 21.9 ± 14.6 years and 47% were female. Baseline medical history documented that almost all study participants (93%) reported previous hospitalization, while 87% had previous vaso-occlusive events, 78% had malaria, 21% reported transfusion, and 1 patient had a stroke. Baseline labs included hemoglobin = 11.0 ± 1.3 g/dL, HbF = 1.8 ± 1.5 %, ANC = 3.7 ± 1.8 x 10 9/L, and platelets 269 ± 115 x 10 9/L. Additional baseline laboratory studies include whole blood viscosity, ektacytometry, and point-of-sickling. Baseline assessment revealed a palpable spleen in 6 children (5%) and 1 adult (1%), but abdominal ultrasonography documented splenic tissue in 97% of children and 83% of adults with an average volume of 116 ± 71 mL (range 13 - 354 mL) and 222 ± 165 mL (range 4 - 707 mL), respectively. TCD examinations on children revealed an average maximum time-averaged mean velocity of 111 ± 19 cm/sec with 98% normal exams, 1% conditional, 0% abnormal, and 1% inadequate. Retinopathy was identified in 46% of children and 85% of adults, including both proliferative and non-proliferative findings. Near Infrared Spectrometry (NIRS), 6-minute walk, and Quality of Life were also collected. Discussion: Individuals with HbSC endure a substantial number of life-altering clinical complications and early mortality. Better treatments for this large group of people are desperately needed, and hydroxyurea is an obvious choice due to its low cost and ease of oral administration. Better understanding of the rate and severity of disease manifestations across the age span is needed to more completely understand the best time to treat this group to mitigate complications. Now fully enrolled, PIVOT will provide invaluable insights into the effects and potential benefits of hydroxyurea on clinical and laboratory outcomes among people living with HbSC disease.

Trial in Progress: Investigating the Prognostic Significance of Malnutrition and Sarcopenia in Older Adults with Acute Myeloid Leukemia

Background and Significance: For older adults (≥60 years) newly diagnosed with acute myeloid leukemia (AML), tumor-specific and patient-specific factors have been used to predict treatment-related mortality (TRM) and determine suitability for intensive antileukemic therapy. Comprehensive Geriatric Assessment (CGA) is a tool designed to comprehensively evaluate health among older adults. CGA assesses multiple health domains including physical function, cognition, nutrition, mental health, polypharmacy, comorbidities, and social support but does not currently incorporate body imaging. Sarcopenia is defined as loss of muscle mass and strength. It can be measured objectively by CT, DEXA or Bioimpedance Analysis (BIA) in combination with tests of muscle strength. It has been proposed as a more accurate nutritional marker compared to BMI or serum markers. Nearly all older adults with AML receive a CT scan during their cancer evaluation. Therefore, there is an opportunity to leverage CT sarcopenia measures to improve risk prediction. Our study aims to (1) assess the burden of malnutrition and sarcopenia in older adults with newly diagnosed AML undergoing induction and (2) determine the prognostic impact of traditional markers of nutrition and novel sarcopenia measures on TRM. Study Design and Methods: This is a prospective, observational study of 82 newly diagnosed, older adult patients with AML undergoing induction treatment at the University of Chicago Comprehensive Cancer Center (NCT05458258). Key inclusion criteria include age ≥60 years and receipt of induction therapy for newly diagnosed AML. Key exclusion criteria include presence of a pacemaker or defibrillator. To assess Aim 1, newly diagnosed older adult patients with AML will be undergo a subjective global nutrition assessment and serum nutritional markers [prealbumin, albumin, CRP, ferritin]. Body composition (fat-mass, fat-free mass, lean mass) will be assessed using BIA and CT. Sarcopenia will be defined by the CT Skeletal Muscle Index (SMI) at L3 plus impairment on either maximal hand grip strength, 6-minute walk, Timed Up and Go test (TUG), the Short Physical Performance Battery (SPPB). Patients will also undergo an assessment of disability (instrumental activities of daily living (IADL) and activities of daily living (ADL) surveys), Short Physical Performance Battery [SPPB], and Montreal cognitive assessment [MOCA]) prior to starting induction. All measures will be repeated at the start of post-remission therapy. Results from both timepoints will be compared against healthy controls matched by age, sex and Charlson Comorbidity Index. Healthy control data will come from the Frailty, Activity, Body Composition, and Energy Expenditure (FACE) Aging dataset housed by the Department of Geriatrics at the University of Chicago, a 1-year longitudinal, observation study of frailty in older adults residing around the university. We will match 1 AML case to 1 control. In order to ensure that all subjects are matched, 2:1 propensity score matching will be used to generate matching controls for each case. To assess Aim 2, multivariable Cox proportional hazards regression models will be performed for each of those nutrition status and sarcopenia markers significant for TRM in univariate analysis. In multivariable analyses, we will control for age, European Leukemia Net 2022 risk stratification, ECOG PS, and CGA measures as covariates. A sample size of 82 patients will give us 80% power to detect a hazard ratio of 3.0 for TRM, the primary end point, for CT diagnosed sarcopenia using a Cox proportional hazards model with a 0.05 significance level and a 60-day mortality rate of 18%. We anticipate completion of enrollment within two years of study initiation. To date, 17 patients have been approached for consent with 11 patients enrolled. When complete, this trial will provide initial evidence necessary to recommend nutritional assessment as a part of the Comprehensive Geriatric Assessment in all older adult AML patients. Furthermore, it may provide evidence to support a future interventional study assessing the impact of improved nutritional status on TRM. Figure 1. NCT05458258 study schema.

Clinical Results of a Randomized Placebo Controlled Trial of Inhaled Mometasone to Promote Reduction in Vaso-Occlusive Events (IMPROVE-II)

Introduction: A subset of patients living with sickle cell disease (SCD) who do not meet diagnostic criteria for asthma exhibit episodic cough or wheeze (ECW), and this is associated with higher rates of vaso-occlusive pain crisis and acute chest syndrome. ECW may be caused by pulmonary inflammation from SCD. In the former IMPROVE trial, 54 patients with SCD and ECW were randomized to receive 16 weeks of placebo or mometasone furoate, an inhaled corticosteroid used to treat pulmonary inflammation. Treatment with mometasone was associated with significant reductions in daily pain, markers of hemolysis, and soluble vascular cell adhesion molecule (sVCAM) (a biomarker of disease severity in SCD) compared to placebo. The IMPROVE-II trial evaluated whether treatment with mometasone over a longer period could improve clinical and biological endpoints in non-asthmatic patients with SCD and ECW. We report here the clinical outcomes from the IMPROVE-II trial. Methods: We conducted a randomized, placebo-controlled, single-center interventional trial. Patients with SCD without asthma were randomized to receive either mometasone furoate 220 mcg or placebo inhaled powder for 48 weeks followed by a 4-week wash out. Key inclusion criteria included age &amp;gt; 18 years with SCD genotype HbSS/HbSβ0 at stable baseline who endorsed ECW. Patients were excluded if they had &amp;gt;15 emergency department (ED) visits for vaso-occlusive pain crisis in the past 12 months or if other treatments for SCD (i.e. hydroxyurea, L-glutamine) were being titrated. The primary outcome was the change in soluble vascular cell adhesion molecule (sVCAM) level with treatment. Clinical outcomes included ED visits and hospitalizations for any reason, and health care visits for acute chest syndrome, pneumonia, stroke, or transient ischemic attack, as well as daily pain (self-report 1-10 scale), and 6 Minute Walk. Adaptive covariate randomization was used to balance covariates including hydroxyurea use (yes/no), age, and previous rate of ED use. Results: A total of 80 patients were randomized and 77 received study treatment; 40 were assigned to mometasone and 37 to placebo (Figure 1). There were no significant differences between treatment groups in patient demographics (Table 1). Treatment with mometasone was associated with higher rates of acute care visits for vaso-occlusive crisis (4 (2/19) vs 1 (1/3) /patient year (50%(25%/75%), p&amp;lt;0.001), hospitalization for acute chest syndrome (mean 0.2 vs 0.1/patient year, p=0.05) and ED utilization (2 (1/5) vs 2 (1/4) /patient year (50%(25%/75%), p0.01). Laboratory outcomes including sVCAM are not yet resulted. Adverse events that were reported by more than 5% of patients are listed in Table 1; there was no difference between rates of adverse (&amp;lt;5%) events between mometasone and placebo. There were no deaths during the study. Conclusions: In individuals with SCD and ECW who do not have asthma, long-term treatment with inhaled corticosteroids did not improve clinical outcomes and may be harmful as they were associated with higher rates of acute care visits for pain crisis, ED visits, and acute chest syndrome. Further analyses of biological endpoints and clinical laboratory data are needed to fully elucidate the effects of inhaled corticosteroids in SCD.

Personalized Exercise Intervention for Older Adults with Sickle Cell Disease: The Sicklefit Study

Background Older adults with sickle cell disease (SCD) (defined as age ≥ 40 years) experience both SCD and age-related conditions such as recurrent pain episodes, avascular necrosis of the joints, and cardiopulmonary disease that can result in accelerated functional decline. Individuals with SCD experience vaso-occlusive events that lead to reduced oxygen delivery to organs such as bones, muscles, and lungs. Due to these unique risk factors, existing generic exercise programs may be too intense– and even detrimental– for older adults with SCD. Gerofit is a supervised exercise program designed for veterans age ≥ 65 years with chronic disease and/or impaired mobility that has been shown to improve physical function, mental health, quality of life, and survival. The purpose of the study is a pilot evaluation of the feasibility and safety of SickleFit, an exercise training program for older adults with SCD adapted from Gerofit. Methods SickleFit is a group exercise program held on Zoom 3 days a week and includes a safety check in, warm-up, cardio segment, strength training, flexibility, balance, and mindfulness. Our primary endpoint is feasibility measured by proportion of participants attending at least 50% of the sessions over 6 weeks. The secondary outcomes are safety and acceptability. We measured safety as the number of moderate or severe adverse events within 48 hours after each exercise session. Acceptability was measured as the proportion of participants reporting the intervention as satisfactory. Exploratory outcomes were changes in physical performance in a battery of physical assessments including: Usual Gait Speed, 6 Minute Walk Distance (6MWD), Plank duration, Timed Up-and-go (TUG), Seated Grip Strength, Weight, and Neck Circumference. Results Cohort 1 consisted of 2 male (aged 55 and 66 both with SS genotype) and 2 female participants (aged 43 and 53 with Beta + Thalassemia and SS genotype). All 4 participants met the feasibility endpoint of attending at least 50% of exercise sessions, with a mean attendance of 83%. The majority of absences were due to schedule conflicts (2), property maintenance (2), and general malaise (4). Over a third of the missed sessions were due to minor (2) or major (3) adverse events unrelated to the intervention (motor vehicle incident, work-related injury). There were no major or life-threatening adverse events as a result of the exercise intervention. Minor adverse events related to exercise were knee, shoulder, and back soreness and pain. All participants responded as either ‘Pleased’ (50%) or ‘Delighted’ (50%) with the program on the acceptability survey. In addition, all participants saw a positive increase in their performance of the Usual Gait Speed, TUG, 6MWD, and plank duration. Minor improvement in grip strength was seen in 3 participants, but a slight loss in grip strength occurred in one individual whom also lost the most weight. While no significant change occurred in the BMI of the participants, a reduction in neck circumference did occur. Conclusion In cohort 1, we found that the SickleFit exercise program is feasible, acceptable, and safe for older adults with SCD. Participants demonstrated improvements in Usual Gait Speed, TUG, 6MWD, and plank duration, among other physical metrics. Participants expressed satisfaction in the program and a desire to continue in the program, even after the program ended. Based on patient feedback, The Sicklefit program is being optimized further to better meet the needs of older adults with SCD. Optimizations include shortening of the cardio section for the initial weeks of the program, dedicating more time to discussing the biomechanics and form involved in the exercises, integration of more ground-based and vertical pulling patterns with resistance bands, and adding further diversity in the movement practices included in the sessions.