A systematic review of rehabilitation and exercise recommendations in oncology guidelines.

Guidelines promote high quality cancer care. Rehabilitation recommendations in oncology guidelines have not been characterized and may provide insight to improve integration of rehabilitation into oncology care. This report was developed as a part of the World Health Organization (WHO) Rehabilitation 2030 initiative to identify rehabilitation-specific recommendations in guidelines for oncology care. A systematic review of guidelines was conducted. Only guidelines published in English, for adults with cancer, providing recommendations for rehabilitation referral and assessment or interventions between 2009 and 2019 were included. 13840 articles were identified. After duplicates and applied filters, 4897 articles were screened. 69 guidelines were identified with rehabilitation-specific recommendations. Thirty-seven of the 69 guidelines endorsed referral to rehabilitation services but provided no specific recommendations regarding assessment or interventions. Thirty-two of the 69 guidelines met the full inclusion criteria and were assessed using the AGREE II tool. Twenty-one of these guidelines achieved an AGREE II quality score of ≥ 45 and were fully extracted. Guidelines exclusive to pharmacologic interventions and complementary and alternative interventions were excluded. Findings identify guidelines that recommend rehabilitation services across many cancer types and for various consequences of cancer treatment signifying that rehabilitation is a recognized component of oncology care. However, these findings are at odds with clinical reports of low rehabilitation utilization rates suggesting that guideline recommendations may be overlooked. Considering that functional morbidity negatively affects a majority of cancer survivors, improving guideline concordant rehabilitative care could have substantial impact on function and quality of life among cancer survivors.

Exercise to Prevent Accelerated Vascular Aging in People Living With HIV.

Given advances in antiretroviral therapy, the mortality rate for HIV infection has dropped considerably over recent decades. However, people living with HIV (PLWH) experience longer life spans coupled with persistent immune activation despite viral suppression and potential toxicity from long-term antiretroviral therapy use. Consequently, PLWH face a cardiovascular disease (CVD) risk more than twice that of the general population, making it the leading cause of death among this group. Here, we briefly review the epidemiology of CVD in PLWH highlighting disparities at the intersections of sex and gender, age, race/ethnicity, and the contributions of social determinants of health and psychosocial stress to increased CVD risk among individuals with marginalized identities. We then overview the pathophysiology of HIV and discuss the primary factors implicated as contributors to CVD risk among PLWH on antiretroviral therapy. Subsequently, we highlight the functional evidence of premature vascular dysfunction as an early pathophysiological determinant of CVD risk among PLWH, discuss several mechanisms underlying premature vascular dysfunction in PLWH, and synthesize current research on the pathophysiological mechanisms underlying accelerated vascular aging in PLWH, focusing on immune activation, chronic inflammation, and oxidative stress. We consider understudied aspects such as HIV-related changes to the gut microbiome and psychosocial stress, which may serve as mechanisms through which exercise can abrogate accelerated vascular aging. Emphasizing the significance of exercise, we review various modalities and their impacts on vascular health, proposing a holistic approach to managing CVD risks in PLWH. The discussion extends to critical future study areas related to vascular aging, CVD, and the efficacy of exercise interventions, with a call for more inclusive research that considers the diversity of the PLWH population.

Exercise is medicine in oncology: Engaging clinicians to help patients move through cancer.

Multiple organizations around the world have issued evidence-based exercise guidance for patients with cancer and cancer survivors. Recently, the American College of Sports Medicine has updated its exercise guidance for cancer prevention as well as for the prevention and treatment of a variety of cancer health-related outcomes (eg, fatigue, anxiety, depression, function, and quality of life). Despite these guidelines, the majority of people living with and beyond cancer are not regularly physically active. Among the reasons for this is a lack of clarity on the part of those who work in oncology clinical settings of their role in assessing, advising, and referring patients to exercise. The authors propose using the American College of Sports Medicine's Exercise Is Medicine initiative to address this practice gap. The simple proposal is for clinicians to assess, advise, and refer patients to either home-based or community-based exercise or for further evaluation and intervention in outpatient rehabilitation. To do this will require care coordination with appropriate professionals as well as change in the behaviors of clinicians, patients, and those who deliver the rehabilitation and exercise programming. Behavior change is one of many challenges to enacting the proposed practice changes. Other implementation challenges include capacity for triage and referral, the need for a program registry, costs and compensation, and workforce development. In conclusion, there is a call to action for key stakeholders to create the infrastructure and cultural adaptations needed so that all people living with and beyond cancer can be as active as is possible for them.

Telerehabilitation consultations with a physiotherapist for chronic knee pain versus in-person consultations in Australia: the PEAK non-inferiority randomised controlled trial.

BACKGROUND: Telerehabilitation whether perceived as less effective than in-person care for musculoskeletal problems. We aimed to determine if physiotherapy video conferencing consultations were non-inferior to in-person consultations for chronic knee pain. METHODS: In this non-inferiority randomised controlled trial, we recruited primary care physiotherapists from 27 Australian clinics. Using computer-generated blocks, participants with chronic knee pain consistent with osteoarthritis were randomly assigned (1:1, stratified by physiotherapist and clinic) in-person or telerehabilitation (ie, video conferencing) physiotherapist consultations. Participants and physiotherapists were unmasked to group assignment. Both groups had five consultations over 3 months for strengthening, physical activity, and education. Primary outcomes were knee pain (on a numerical rating scale of 0-10) and physical function (using the Western Ontario and McMaster Universities osteoarthritis index of 0-68) at 3 months after randomisation. Primary analysis was by modified intention-to-treat using all available data. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12619001240134. FINDINGS: Between Dec 10, 2019, and June 17, 2022, 394 adults were enrolled, with 204 allocated to in-person care and 190 to telerehabilitation. 15 primary care physiotherapists were recruited. At 3 months, 383 (97%) participants provided information for primary outcomes and both groups reported improved pain (mean change 2·98, SD 2·23 for in-person care and 3·14, 1·87 for telerehabilitation) and function (10·20, 11·63 and 10·75, 9·62, respectively). Telerehabilitation was non-inferior for pain (mean difference 0·16, 95% CI -0·26 to 0·57) and function (1·65, -0·23 to 3·53). The number of participants reporting adverse events was similar between groups (40 [21%] for in-person care and 35 [19%] for telerehabilitation) and none were serious. INTERPRETATION: Telerehabilitation with a physiotherapist is non-inferior to in-person care for chronic knee pain. FUNDING: National Health and Medical Research Council.

Effectiveness and cost-effectiveness of an individualised, progressive walking and education intervention for the prevention of low back pain recurrence in Australia (WalkBack): a randomised controlled trial.

BACKGROUND: Recurrence of low back pain is common and a substantial contributor to the disease and economic burden of low back pain. Exercise is recommended to prevent recurrence, but the effectiveness and cost-effectiveness of an accessible and low-cost intervention, such as walking, is yet to be established. We aimed to investigate the clinical effectiveness and cost-effectiveness of an individualised, progressive walking and education intervention to prevent the recurrence of low back pain. METHODS: WalkBack was a two-armed, randomised controlled trial, which recruited adults (aged 18 years or older) from across Australia who had recently recovered from an episode of non-specific low back pain that was not attributed to a specific diagnosis, and which lasted for at least 24 h. Participants were randomly assigned to an individualised, progressive walking and education intervention facilitated by six sessions with a physiotherapist across 6 months or to a no treatment control group (1:1). The randomisation schedule comprised randomly permuted blocks of 4, 6, and 8 and was stratified by history of more than two previous episodes of low back pain and referral method. Physiotherapists and participants were not masked to allocation. Participants were followed for a minimum of 12 months and a maximum of 36 months, depending on the date of enrolment. The primary outcome was days to the first recurrence of an activity-limiting episode of low back pain, collected in the intention-to-treat population via monthly self-report. Cost-effectiveness was evaluated from the societal perspective and expressed as incremental cost per quality-adjusted life-year (QALY) gained. The trial was prospectively registered (ACTRN12619001134112). FINDINGS: Between Sept 23, 2019, and June 10, 2022, 3206 potential participants were screened for eligibility, 2505 (78%) were excluded, and 701 were randomly assigned (351 to the intervention group and 350 to the no treatment control group). Most participants were female (565 [81%] of 701) and the mean age of participants was 54 years (SD 12). The intervention was effective in preventing an episode of activity-limiting low back pain (hazard ratio 0·72 [95% CI 0·60-0·85], p=0·0002). The median days to a recurrence was 208 days (95% CI 149-295) in the intervention group and 112 days (89-140) in the control group. The incremental cost per QALY gained was AU$7802, giving a 94% probability that the intervention was cost-effective at a willingness-to-pay threshold of $28 000. Although the total number of participants experiencing at least one adverse event over 12 months was similar between the intervention and control groups (183 [52%] of 351 and 190 [54%] of 350, respectively, p=0·60), there was a greater number of adverse events related to the lower extremities in the intervention group than in the control group (100 in the intervention group and 54 in the control group). INTERPRETATION: An individualised, progressive walking and education intervention significantly reduced low back pain recurrence. This accessible, scalable, and safe intervention could affect how low back pain is managed. FUNDING: National Health and Medical Research Council, Australia.

Progressive Resistance Training or Neuromuscular Exercise for Hip Osteoarthritis : A Multicenter Cluster Randomized Controlled Trial.

BACKGROUND: Exercise is recommended as first-line treatment for patients with hip osteoarthritis (OA). However, randomized controlled trials providing evidence for the optimal exercise type are lacking. OBJECTIVE: To investigate whether progressive resistance training (PRT) is superior to neuromuscular exercise (NEMEX) for improving functional performance in patients with hip OA. DESIGN: Multicenter, cluster-randomized, controlled, parallel-group, assessor-blinded, superiority trial. (ClinicalTrials.gov: NCT04714047). SETTING: Hospitals and physiotherapy clinics. PARTICIPANTS: 160 participants with clinically diagnosed hip OA were enrolled from 18 January 2021 to 28 April 2023 and randomly assigned to PRT (n = 82) or NEMEX (n = 78). INTERVENTION: Twelve weeks of PRT or NEMEX with 2 supervised 60-minute group sessions each week. The PRT intervention consisted of 5 high-intensity resistance training exercises targeting muscles at the hip and knee joints. The NEMEX intervention included 10 exercises and emphasized sensorimotor control and functional stability. MEASUREMENTS: The primary outcome was change in the 30-second chair stand test (30s-CST). Key secondary outcomes were changes in scores on the pain and hip-related quality of life (QoL) subscales of the Hip Disability and Osteoarthritis Outcome Score (HOOS). RESULTS: The mean changes from baseline to 12-week follow-up in the 30s-CST were 1.5 (95% CI, 0.9 to 2.1) chair stands with PRT and 1.5 (CI, 0.9 to 2.1) chair stands with NEMEX (difference, 0.0 [CI, -0.8 to 0.8] chair stands). For the HOOS pain subscale, mean changes were 8.6 (CI, 5.3 to 11.8) points with PRT and 9.3 (CI, 5.9 to 12.6) points with NEMEX (difference, -0.7 [CI, -5.3 to 4.0] points). For the HOOS QoL subscale, mean changes were 8.0 (CI, 4.3 to 11.7) points with PRT and 5.7 (CI, 1.9 to 9.5) points with NEMEX (difference, 2.3 [CI, -3.0 to 7.6] points). LIMITATION: Participants and physiotherapists were not blinded. CONCLUSION: In patients with hip OA, PRT is not superior to NEMEX for improving functional performance, hip pain, or hip-related QoL. PRIMARY FUNDING SOURCE: Independent Research Fund Denmark.

Primary cilia in satellite cells are the mechanical sensors for muscle hypertrophy.

Skeletal muscle atrophy is commonly associated with aging, immobilization, muscle unloading, and congenital myopathies. Generation of mature muscle cells from skeletal muscle satellite cells (SCs) is pivotal in repairing muscle tissue. Exercise therapy promotes muscle hypertrophy and strength. Primary cilium is implicated as the mechanical sensor in some mammalian cells, but its role in skeletal muscle cells remains vague. To determine mechanical sensors for exercise-induced muscle hypertrophy, we established three SC-specific cilium dysfunctional mouse models-Myogenic factor 5 (Myf5)-Arf-like Protein 3 (Arl3)-/-, Paired box protein Pax-7 (Pax7)-Intraflagellar transport protein 88 homolog (Ift88)-/-, and Pax7-Arl3-/--by specifically deleting a ciliary protein ARL3 in MYF5-expressing SCs, or IFT88 in PAX7-expressing SCs, or ARL3 in PAX7-expressing SCs, respectively. We show that the Myf5-Arl3-/- mice develop grossly the same as WT mice. Intriguingly, mechanical stimulation-induced muscle hypertrophy or myoblast differentiation is abrogated in Myf5-Arl3-/- and Pax7-Arl3-/- mice or primary isolated Myf5-Arl3-/- and Pax7-Ift88-/- myoblasts, likely due to defective cilia-mediated Hedgehog (Hh) signaling. Collectively, we demonstrate SC cilia serve as mechanical sensors and promote exercise-induced muscle hypertrophy via Hh signaling pathway.

Early hybrid cardiac rehabilitation in congenital heart disease: the QUALIREHAB trial.

BACKGROUND AND AIMS: Cardiopulmonary fitness in congenital heart disease (CHD) decreases faster than in the general population resulting in impaired health-related quality of life (HRQoL). As the standard of care seems insufficient to encourage and maintain fitness, an early hybrid cardiac rehabilitation programme could improve HRQoL in CHD. METHODS: The QUALIREHAB multicentre, randomized, controlled trial evaluated and implemented a 12-week centre- and home-based hybrid cardiac rehabilitation programme, including multidisciplinary care and physical activity sessions. Adolescent and young adult CHD patients with impaired cardiopulmonary fitness were randomly assigned to either the intervention (i.e. cardiac rehabilitation) or the standard of care. The primary outcome was the change in HRQoL from baseline to 12-month follow-up in an intention-to-treat analysis. The secondary outcomes were the change in cardiovascular parameters, cardiopulmonary fitness, and mental health. RESULTS: The expected number of 142 patients was enroled in the study (mean age 17.4 ± 3.4 years, 52% female). Patients assigned to the intervention had a significant positive change in HRQoL total score [mean difference 3.8; 95% confidence interval (CI) 0.2; 7.3; P = .038; effect size 0.34], body mass index [mean difference -0.7 kg/m2 (95% CI -1.3; -0.1); P = .022; effect size 0.41], level of physical activity [mean difference 2.5 (95% CI 0.1; 5); P = .044; effect size 0.39], and disease knowledge [mean difference 2.7 (95% CI 0.8; 4.6); P = .007; effect size 0.51]. The per-protocol analysis confirmed these results with a higher magnitude of differences. Acceptability, safety, and short-time effect of the intervention were good to excellent. CONCLUSIONS: This early hybrid cardiac rehabilitation programme improved HRQoL, body mass index, physical activity, and disease knowledge, in youth with CHD, opening up the possibility for the QUALIREHAB programme to be rolled out to the adult population of CHD and non-congenital cardiac disease.

Exercise therapy for chronic symptomatic peripheral artery disease.

All guidelines worldwide strongly recommend exercise as a pillar of the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended for clinicians to promote and assist for the set-up of comprehensive exercise programmes to best advice in patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are narratively described based on the current best evidence. The document ends by highlighting disparities in access to supervised exercise programmes across Europe and the series of gaps for evidence requiring further research.

Conserved mammalian muscle mechanics during eccentric contractions.

Skeletal muscle has a broad range of biomechanical functions, including power generation and energy absorption. These roles are underpinned by the force-velocity relationship, which comprises two distinct components: a concentric and an eccentric force-velocity relationship. The concentric component has been extensively studied across a wide range of muscles with different muscle properties. However, to date, little progress has been made in accurately characterising the eccentric force-velocity relationship in mammalian muscle with varying muscle properties. Consequently, mathematical models of this muscle behaviour are based on a poorly understood phenomenon. Here, we present a comprehensive assessment of the concentric force-velocity and eccentric force-velocity relationships of four mammalian muscles (soleus, extensor digitorum longus, diaphragm and digastric) with varying biomechanical functions, spanning three orders of magnitude in body mass (mouse, rat and rabbits). The force-velocity relationship was characterised using a hyperbolic-linear equation for the concentric component a hyperbolic equation for the eccentric component, at the same time as measuring the rate of force development in the two phases of force development in relation to eccentric lengthening velocity. We demonstrate that, despite differences in the curvature and plateau height of the eccentric force-velocity relationship, the rates of relative force development were consistent for the two phases of the force-time response during isovelocity lengthening ramps, in relation to lengthening velocity, in the four muscles studied. Our data support the hypothesis that this relationship depends on cross-bridge and titin activation. Hill-type musculoskeletal models of the eccentric force-velocity relationship for mammalian muscles should incorporate this biphasic force response. KEY POINTS: The capacity of skeletal muscle to generate mechanical work and absorb energy is underpinned by the force-velocity relationship. Despite identification of the lengthening (eccentric) force-velocity relationship over 80 years ago, no comprehensive study has been undertaken to characterise this relationship in skeletal muscle. We show that the biphasic force response seen during active muscle lengthening is conserved over three orders of magnitude of mammalian skeletal muscle mass. Using mice with a small deletion in titin, we show that part of this biphasic force profile in response to muscle lengthening is reliant on normal titin activation. The rate of force development during muscle stretch may be a more reliable way to describe the forces experienced during eccentric muscle contractions compared to the traditional hyperbolic curve fitting, and functions as a novel predictor of force-velocity characteristics that may be used to better inform hill-type musculoskeletal models and assess pathophysiological remodelling.

Increasing Activity After Stroke: A Randomized Controlled Trial of High-Intensity Walking and Step Activity Intervention.

BACKGROUND: Physical inactivity in people with chronic stroke profoundly affects daily function and increases recurrent stroke risk and mortality, making physical activity improvements an important target of intervention. We compared the effects of a high-intensity walking intervention (FAST), a step activity monitoring behavioral intervention (SAM), or a combined intervention (FAST+SAM) on physical activity (ie, steps/day). We hypothesized the combined intervention would yield the greatest increase in steps/day. METHODS: This assessor-blinded multisite randomized controlled trial was conducted at 4 university/hospital-based laboratories. Participants were 21 to 85 years old, walking without physical assistance following a single, unilateral noncerebellar stroke of ≥6 months duration, and randomly assigned to FAST, SAM, or FAST+SAM for 12 weeks (2-3 sessions/week). FAST training consisted of walking-related activities at 70% to 80% heart rate reserve, while SAM received daily feedback and goal setting of walking activity (steps/day). Assessors and study statistician were masked to group assignment. The a priori-determined primary outcome and end point was a comparison of the change in steps/day between the 3 intervention groups from pre- to post-intervention. Adverse events were tracked after randomization. All randomized participants were included in the intent-to-treat analysis. RESULTS: Participants were enrolled from July 18, 2016, to November 16, 2021. Of 2385 participants initially screened, 250 participants were randomized (mean [SE] age, 63 [0.80] years; 116 females/134 males), with 89 assigned to FAST, 81 to SAM, and 80 to FAST+SAM. Steps/day significantly increased in both the SAM (mean [SE], 1542 [267; 95% CI, 1014-2069] P<0.001) and FAST+SAM group (1307 [280; 95% CI, 752-1861] P<0.001) but not in the FAST group (406 [238; 95% CI, -63 to 876] P=0.09). There were no deaths or serious study-related adverse events. CONCLUSIONS: Only individuals with chronic stroke who completed a step activity monitoring behavioral intervention with skilled coaching and goal progression demonstrated improvements in physical activity (steps/day). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02835313.

Effect of Exercise Training on Prognosis in Community-acquired Pneumonia: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effect of standard care (SoC) combined with supervised in-bed cycling (Bed-Cycle) or booklet exercises (Book-Exe) versus SoC in community-acquired pneumonia (CAP). METHODS: In this randomized controlled trial, 186 patients with CAP were assigned to SoC (n = 62), Bed-Cycle (n = 61), or Book-Exe (n = 63). Primary outcome length of stay (LOS) was analyzed with analysis of covariance. Secondary outcomes, 90-day readmission, and 180-day mortality were analyzed with Cox proportional hazard regression and readmission days with negative-binominal regression. RESULTS: LOS was -2% (95% CI: -24 to 25) and -1% (95% CI: -22 to 27) for Bed-Cycle and Book-Exe, compared with SoC. Ninety-day readmission was 35.6% for SoC, 27.6% for Bed-Cycle, and 21.3% for Book-Exe. Adjusted hazard ratio (aHR) for 90-day readmission was 0.63 (95% CI: .33-1.21) and 0.54 (95% CI: .27-1.08) for Bed-Cycle and Book-Exe compared with SoC. aHR for 90-day readmission for combined exercise was 0.59 (95% CI: .33-1.03) compared with SoC. aHR for 180-day mortality was 0.84 (95% CI: .27-2.60) and 0.82 (95% CI: .26-2.55) for Bed-Cycle and Book-Exe compared with SoC. Number of readmission days was 226 for SoC, 161 for Bed-Cycle, and 179 for Book-Exe. Incidence rate ratio for readmission days was 0.73 (95% CI: .48-1.10) and 0.77 (95% CI: .51-1.15) for Bed-Cycle and Book-Exe compared with SoC. CONCLUSIONS: Although supervised exercise training during admission with CAP did not reduce LOS or mortality, this trial suggests its potential to reduce readmission risk and number of readmission days. CLINICAL TRIALS REGISTRATION: NCT04094636.

Acute Intermittent Hypoxia With High-Intensity Gait Training in Chronic Stroke: A Phase II Randomized Crossover Trial.

BACKGROUND: Studies in individuals with chronic stroke indicate high-intensity training (HIT) focused on walking improves locomotor function, which may be due to repeated activation of locomotor circuits and serotonin-dependent modulation of motor output. Separate studies in animals and individuals with spinal cord injury suggest acute intermittent hypoxia (AIH) can augment the effects of locomotor interventions through similar serotonin-dependent mechanisms, although no studies have coupled AIH with HIT in individuals poststroke. The goal of this study was to evaluate the safety and efficacy of AIH+HIT versus HIT alone in individuals with chronic stroke. METHODS: This phase II double-blind randomized, crossover trial recruited individuals between 18 and 85 years old, >6 months poststroke, and self-selected speeds <1.0 m/s. Participants received up to 15 sessions of AIH for 30 minutes using 15 cycles of hypoxia (60-90 seconds; 8%-9% O2) and normoxia (30-60 seconds; 21% O2), followed by 1 hour of HIT targeting >75% heart rate reserve. The control condition received normoxia for 30 minutes before HIT. Following the first training phase, participants performed the second phase >1 month later. The primary outcomes were self-selected speed and fastest speed, a 6-minute walk test, and peak treadmill speed. A 3-way mixed-model ANOVA assessed the effects of time, training, and order of interventions. RESULTS: Of 55 individuals screened, 35 were randomized to AIH+HIT or normoxia+HIT first, and 28 individuals completed both interventions, revealing greater gains in self-selected speeds (0.14 [0.08-0.18] versus 0.05 [0.01-0.10] m/s), fastest speed (0.16 [0.10-0.21] versus 0.06 [0.02-0.10] m/s), and peak treadmill speed (0.21 [0.14-0.29] versus 0.11 [0.06-0.16] m/s) following AIH+HIT versus normoxia+HIT (P<0.01) with no order effects. Greater gains in spatiotemporal symmetry were observed with AIH+HIT, with worse outcomes for those prescribed serotonin-mediated antidepressant medications. CONCLUSIONS: AIH+HIT resulted in greater gains in locomotor function than normoxia+HIT. Subsequent phase III trials should further evaluate the efficacy of this intervention. REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT04472442.

Cardioprotective effect of intradialytic exercise on left atrial mechanics.

Left atrial (LA) function plays a pivotal role in cardiac performance by modulating left ventricular (LV) function. Impairments in LV function are commonly reported during hemodialysis (HD), but available data describing changes in LA function are limited. There is growing evidence of the cardioprotective effect of intradialytic exercise (IDE) on LV function, but studies analyzing its effect on LA function are scarce. Our aim was to evaluate whether IDE can limit the severity of HD-induced impairment in LA myocardial function. In this prospective, open-label, two-center randomized crossover trial, 56 stable individuals receiving HD participated in 2 HD sessions in random order: standard HD and a session incorporating 30 min of aerobic exercise. LA and LV global longitudinal strains (GLSs) were obtained before and at peak stress of HD (i.e., 30 min before the HD ending). IDE totally eradicated the decline in LA reservoir strain observed during HD (estimated difference: 3.1%, 95% confidence interval: 0.4/5.8, P = 0.02), whereas it did not affect the other components of LA mechanics. A similar result favoring IDE intervention was also demonstrated on GLS changes over the HD procedure (P < 0.001). Between-session differences of changes in GLS and LA reservoir strain were correlated (r = -0.32, P = 0.03). The cardioprotective effect of IDE disappeared in patients with LA enlargement (i.e., LA volume index >34 mL/m2). In conclusion, even a short duration of IDE at moderate intensity is effective in preventing HD-associated decline in LA reservoir function. Further research is needed to explore the long-term benefits of IDE on LA function.NEW & NOTEWORTHY A single bout of intradialytic exercise (IDE) at moderate intensity can prevent the hemodialysis-associated decline in left atrial (LA) function. This was partially explained by the relative preservation of left ventricular systolic function with IDE. Benefits of IDE on LA function were lost in patients with LA dilation. Further studies are needed to explore the mechanisms behind IDE-induced cardioprotection and evaluate the clinical impacts of the repetitive cardioprotective effects of IDE on LA function.

Short-term learning of the vestibulo-ocular reflex induced by a custom interactive computer game.

Retinal image slip during head rotation drives motor learning in the rotational vestibulo-ocular reflex (VOR) and forms the basis of gaze-stability exercises that treat vestibular dysfunction. Clinical exercises, however, are unengaging, cannot easily be titrated to the level of impairment, and provide neither direct feedback nor tracking of the patient's adherence, performance, and progress. To address this, we have developed a custom application for VOR training based on an interactive computer game. In this study, we tested the ability of this game to induce VOR learning in individuals with normal vestibular function, and we compared the efficacy of single-step and incremental learning protocols. Eighteen participants played the game twice on different days. All participants tolerated the game and were able to complete both sessions. The game scenario incorporated a series of brief head rotations, similar to active head impulses, that were paired with a dynamic acuity task and with a visual-vestibular mismatch (VVM) intended to increase VOR gain (single-step: 300 successful trials at ×1.5 viewing; incremental: 100 trials each of ×1.13, ×1.33, and ×1.5 viewing). Overall, VOR gain increased by 15 ± 4.7% (mean ± 95% CI, P < 0.001). Gains increased similarly for active and passive head rotations, and, contrary to our hypothesis, there was little effect of the learning strategy. This study shows that an interactive computer game provides robust VOR training and has the potential to deliver effective, engaging, and trackable gaze-stability exercises to patients with a range of vestibular dysfunctions.NEW & NOTEWORTHY This study demonstrates the feasibility and efficacy of a customized computer game to induce motor learning in the high-frequency rotational vestibulo-ocular reflex. It provides a physiological basis for the deployment of this technology to clinical vestibular rehabilitation.

Effects of a combined exercise and dietary intervention on body composition, physical functioning and fatigue in patients with ovarian cancer: results of the PADOVA trial.

BACKGROUND: Guidelines recommend to include exercise and dietary advice in standard care for patients with cancer, based on evidence primarily derived from patients with breast cancer. Its applicability to patients with ovarian cancer is uncertain due to differences in patient characteristics and treatments. The PADOVA trial examined the effectiveness of a combined exercise and dietary intervention on fat-free mass (FFM), physical functioning, and fatigue. METHODS: In total, 81 patients with ovarian cancer were randomised to the exercise and dietary intervention (n = 40) or control (n = 41) group. Measurements were performed before chemotherapy, after chemotherapy, and 12 weeks later. FFM was assessed by bioelectrical impedance analysis, and physical functioning and fatigue were assessed using questionnaires. Intervention effects were assessed on an intention-to-treat basis using linear mixed models. RESULTS: FFM and physical functioning increased, and fatigue decreased significantly over time in both groups. No significant difference between the groups were found for FFM (ß = -0.5 kg; 95% CI = -3.2; 2.1), physical functioning (ß = 1.4; 95% CI = -5.4; 8.3) and fatigue (ß = 0.7; 95% CI = -1.5; 2.8). CONCLUSIONS: During treatment, both groups improved in FFM, physical functioning, and fatigue. The intervention group, however, did not demonstrate additional benefits compared to the control group. This highlights the need for caution when extrapolating findings from different cancer populations to patients with ovarian cancer.

Exercise in Octogenarians: How Much Is Too Little?

The global population is rapidly aging, with predictions of many more people living beyond 85 years. Age-related physiological adaptations predispose to decrements in physical function and functional capacity, the rate of which can be accelerated by chronic disease and prolonged physical inactivity. Decrements in physical function exacerbate the risk of chronic disease, disability, dependency, and frailty with advancing age. Regular exercise positively influences health status, physical function, and disease risk in adults of all ages. Herein, we review the role of structured exercise training in the oldest old on cardiorespiratory fitness and muscular strength and power, attributes critical for physical function, mobility, and independent living.

A Feasibility Study Investigating an Exercise Program in Metastatic Cancer Based on the Patient-Preferred Delivery Mode.

BACKGROUND: Feasibility of exercise in patients with metastatic cancer is still a challenge. This study aimed to determine the feasibility and preliminary efficacy of an exercise intervention based on a patient-preferred delivery mode in patients affected by metastatic cancer. MATERIALS AND METHODS: Forty-four patients with a confirmed diagnosis of metastatic cancer were recruited in a 3-month exercise program. Whereas the exercise program consisted of aerobic and resistance activities performed twice a week, the participants may choose the mode of delivery: home based, personal training, or group based. The primary endpoint was the feasibility, defined by recruitment rate, attendance, adherence, dropout rate, tolerability (comparing the session RPE with the target RPE), and safety (using the Common Terminology Criteria for Adverse Events, version 5.0). Secondary endpoints included cardiorespiratory fitness (six minutes walking test), muscle strength (handgrip strength test and isometric leg press test), flexibility (the back scratch and chair sit and reach tests), anthropometric parameters (body mass index and waist-hip ratio), quality of life (EORTC QLQ C-30 questionnaire), and amount of physical exercise (Godin's Shepard Leisure Time Exercise Questionnaire). Descriptive statistics, Student t test, and Wilcoxon signed rank test were used to analyze data. RESULTS: The study recruitment rate was 81%. Out of 44 recruited patients, 28 chose the personal training program, 16 chose the home-based program, and none chose the group-based program. Nine dropouts occurred (20%), 6 in the personal training program, and 3 in the home-based intervention. The median attendance rate was 92%, adherence was 88%, tolerability was 100%, and 9 nonsevere adverse events were registered during the exercise sessions. An increase in cardiorespiratory fitness (P < .001) and flexibility (P = .011 for chair sit and reach; P = .040 for back scratch) was observed at the end of the intervention, while no changes in anthropometric values and muscle strength were detected. Different quality-of-life domains were improved following the intervention, including physical (P = .002), emotional (P < .001), and role functioning (P = .018), fatigue (P = .030), and appetite loss (P = .005). CONCLUSION: A 3-month exercise program based on a patient-preferred delivery mode is feasible in patients with metastatic cancer and may improve physical function and quality of life. TRIAL REGISTRATION: NCT04226508.

Physical Rehabilitation for Older Patients Hospitalized for Heart Failure.

BACKGROUND: Older patients who are hospitalized for acute decompensated heart failure have high rates of physical frailty, poor quality of life, delayed recovery, and frequent rehospitalizations. Interventions to address physical frailty in this population are not well established. METHODS: We conducted a multicenter, randomized, controlled trial to evaluate a transitional, tailored, progressive rehabilitation intervention that included four physical-function domains (strength, balance, mobility, and endurance). The intervention was initiated during, or early after, hospitalization for heart failure and was continued after discharge for 36 outpatient sessions. The primary outcome was the score on the Short Physical Performance Battery (total scores range from 0 to 12, with lower scores indicating more severe physical dysfunction) at 3 months. The secondary outcome was the 6-month rate of rehospitalization for any cause. RESULTS: A total of 349 patients underwent randomization; 175 were assigned to the rehabilitation intervention and 174 to usual care (control). At baseline, patients in each group had markedly impaired physical function, and 97% were frail or prefrail; the mean number of coexisting conditions was five in each group. Patient retention in the intervention group was 82%, and adherence to the intervention sessions was 67%. After adjustment for baseline Short Physical Performance Battery score and other baseline characteristics, the least-squares mean (±SE) score on the Short Physical Performance Battery at 3 months was 8.3±0.2 in the intervention group and 6.9±0.2 in the control group (mean between-group difference, 1.5; 95% confidence interval [CI], 0.9 to 2.0; P<0.001). At 6 months, the rates of rehospitalization for any cause were 1.18 in the intervention group and 1.28 in the control group (rate ratio, 0.93; 95% CI, 0.66 to 1.19). There were 21 deaths (15 from cardiovascular causes) in the intervention group and 16 deaths (8 from cardiovascular causes) in the control group. The rates of death from any cause were 0.13 and 0.10, respectively (rate ratio, 1.17; 95% CI, 0.61 to 2.27). CONCLUSIONS: In a diverse population of older patients who were hospitalized for acute decompensated heart failure, an early, transitional, tailored, progressive rehabilitation intervention that included multiple physical-function domains resulted in greater improvement in physical function than usual care. (Funded by the National Institutes of Health and others; REHAB-HF ClinicalTrials.gov number, NCT02196038.).

Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined.

BACKGROUND: Weight regain after weight loss is a major problem in the treatment of persons with obesity. METHODS: In a randomized, head-to-head, placebo-controlled trial, we enrolled adults with obesity (body-mass index [the weight in kilograms divided by the square of the height in meters], 32 to 43) who did not have diabetes. After an 8-week low-calorie diet, participants were randomly assigned for 1 year to one of four strategies: a moderate-to-vigorous-intensity exercise program plus placebo (exercise group); treatment with liraglutide (3.0 mg per day) plus usual activity (liraglutide group); exercise program plus liraglutide therapy (combination group); or placebo plus usual activity (placebo group). End points with prespecified hypotheses were the change in body weight (primary end point) and the change in body-fat percentage (secondary end point) from randomization to the end of the treatment period in the intention-to-treat population. Prespecified metabolic health-related end points and safety were also assessed. RESULTS: After the 8-week low-calorie diet, 195 participants had a mean decrease in body weight of 13.1 kg. At 1 year, all the active-treatment strategies led to greater weight loss than placebo: difference in the exercise group, -4.1 kg (95% confidence interval [CI], -7.8 to -0.4; P = 0.03); in the liraglutide group, -6.8 kg (95% CI, -10.4 to -3.1; P<0.001); and in the combination group, -9.5 kg (95% CI, -13.1 to -5.9; P<0.001). The combination strategy led to greater weight loss than exercise (difference, -5.4 kg; 95% CI, -9.0 to -1.7; P = 0.004) but not liraglutide (-2.7 kg; 95% CI, -6.3 to 0.8; P = 0.13). The combination strategy decreased body-fat percentage by 3.9 percentage points, which was approximately twice the decrease in the exercise group (-1.7 percentage points; 95% CI, -3.2 to -0.2; P = 0.02) and the liraglutide group (-1.9 percentage points; 95% CI, -3.3 to -0.5; P = 0.009). Only the combination strategy was associated with improvements in the glycated hemoglobin level, insulin sensitivity, and cardiorespiratory fitness. Increased heart rate and cholelithiasis were observed more often in the liraglutide group than in the combination group. CONCLUSIONS: A strategy combining exercise and liraglutide therapy improved healthy weight loss maintenance more than either treatment alone. (Funded by the Novo Nordisk Foundation and others; EudraCT number, 2015-005585-32; ClinicalTrials.gov number, NCT04122716.).