Digital Remote Monitoring Using an mHealth Solution for Survivors of Cancer: Protocol for a Pilot Observational Study.

BACKGROUND: Healthy lifestyle interventions have a positive impact on multiple disease trajectories, including cancer-related outcomes. Specifically, appropriate habitual physical activity, adequate sleep, and a regular wholesome diet are of paramount importance for the wellness and supportive care of survivors of cancer. Mobile health (mHealth) apps have the potential to support novel tailored lifestyle interventions. OBJECTIVE: This observational pilot study aims to assess the feasibility of mHealth multidimensional longitudinal monitoring in survivors of cancer. The primary objective is to test the compliance (user engagement) with the monitoring solution. Secondary objectives include recording clinically relevant subjective and objective measures collected through the digital solution. METHODS: This is a monocentric pilot study taking place in Bangor, Wales, United Kingdom. We plan to enroll up to 100 adult survivors of cancer not receiving toxic anticancer treatment, who will provide self-reported behavioral data recorded via a dedicated app and validated questionnaires and objective data automatically collected by a paired smartwatch over 16 weeks. The participants will continue with their normal routine surveillance care for their cancer. The primary end point is feasibility (eg, mHealth monitoring acceptability). Composite secondary end points include clinically relevant patient-reported outcome measures (eg, the Edmonton Symptom Assessment System score) and objective physiological measures (eg, step counts). This trial received a favorable ethical review in May 2023 (Integrated Research Application System 301068). RESULTS: This study is part of an array of pilots within a European Union funded project, entitled "GATEKEEPER," conducted at different sites across Europe and covering various chronic diseases. Study accrual is anticipated to commence in January 2024 and continue until June 2024. It is hypothesized that mHealth monitoring will be feasible in survivors of cancer; specifically, at least 50% (50/100) of the participants will engage with the app at least once a week in 8 of the 16 study weeks. CONCLUSIONS: In a population with potentially complex clinical needs, this pilot study will test the feasibility of multidimensional remote monitoring of patient-reported outcomes and physiological parameters. Satisfactory compliance with the use of the app and smartwatch, whether confirmed or infirmed through this study, will be propaedeutic to the development of innovative mHealth interventions in survivors of cancer. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52957.

The development and internal pilot trial of a digital physical activity and emotional well-being intervention (Kidney BEAM) for people with chronic kidney disease.

This trial assessed the feasibility and acceptability of Kidney BEAM, a physical activity and emotional well-being self-management digital health intervention (DHI) for people with chronic kidney disease (CKD), which offers live and on-demand physical activity sessions, educational blogs and videos, and peer support. In this mixed-methods, multicentre randomised waitlist-controlled internal pilot, adults with established CKD were recruited from five NHS hospitals and randomised 1:1 to Kidney BEAM or waitlist control. Feasibility outcomes were based upon a priori progression criteria. Acceptability was primarily explored via individual semi-structured interviews (n = 15). Of 763 individuals screened, n = 519 (68%, 95% CI 65 to 71%) were eligible. Of those eligible, n = 303 (58%, 95% CI 54-63%) did not respond to an invitation to participate by the end of the pilot period. Of the 216 responders, 50 (23%, 95% CI 18-29%) consented. Of the 42 randomised, n = 22 (10 (45%) male; 49 ± 16 years; 14 (64%) White British) were allocated to Kidney BEAM and n = 20 (12 (55%) male; 56 ± 11 years; 15 (68%) White British) to the waitlist control group. Overall, n = 15 (30%, 95% CI 18-45%) withdrew during the pilot phase. Participants completed a median of 14 (IQR 5-21) sessions. At baseline, 90-100% of outcome data (patient reported outcome measures and a remotely conducted physical function test) were completed and 62-83% completed at 12 weeks follow-up. Interview data revealed that remote trial procedures were acceptable. Participants' reported that Kidney BEAM increased their opportunity and motivation to be physically active, however, lack of time remained an ongoing barrier to engagement with the DHI. An randomised controlled trial of Kidney BEAM is feasible and acceptable, with adaptations to increase recruitment, retention and engagement.Trial registration NCT04872933. Date of first registration 05/05/2021.

Evaluating the effect of a digital health intervention to enhance physical activity in people with chronic kidney disease (Kidney BEAM): a multicentre, randomised controlled trial in the UK.

BACKGROUND: Remote digital health interventions to enhance physical activity provide a potential solution to improve the sedentary behaviour, physical inactivity, and poor health-related quality of life that are typical of chronic conditions, particularly for people with chronic kidney disease. However, there is a need for high-quality evidence to support implementation in clinical practice. The Kidney BEAM trial evaluated the clinical effect of a 12-week physical activity digital health intervention on health-related quality of life. METHODS: In a single-blind, randomised controlled trial conducted at 11 centres in the UK, adult participants (aged ≥18 years) with chronic kidney disease were recruited and randomly assigned (1:1) to the Kidney BEAM physical activity digital health intervention or a waiting list control group. Randomisation was performed with a web-based system, in randomly permuted blocks of six. Outcome assessors were masked to treatment allocation. The primary outcome was the difference in the Kidney Disease Quality of Life Short Form version 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between baseline and 12 weeks. The trial was powered to detect a clinically meaningful difference of 3 arbitrary units (AU) in KDQoL-SF1.3 MCS. Outcomes were analysed by an intention-to-treat approach using an analysis of covariance model, with baseline measures and age as covariates. The trial was registered with ClinicalTrials.gov, NCT04872933. FINDINGS: Between May 6, 2021, and Oct 30, 2022, 1102 individuals were assessed for eligibility, of whom 340 participants were enrolled and randomly assigned to the Kidney BEAM intervention group (n=173) or the waiting list control group (n=167). 268 participants completed the trial (112 in the Kidney BEAM group and 156 in the waiting list control group). All 340 randomly assigned participants were included in the intention-to treat population. At 12 weeks, there was a significant improvement in KDQoL-SF.13 MCS score in the Kidney BEAM group (from mean 44·6 AU [SD 10·8] at baseline to 47·0 AU [10·6] at 12 weeks) compared with the waiting list control group (from 46·1 AU [10·5] to 45·0 AU [10·1]; between-group difference of 3·1 AU [95% CI 1·8-4·4]; p<0·0001). INTERPRETATION: The Kidney BEAM physical activity platform is an efficacious digital health intervention to improve mental health-related quality of life in patients with chronic kidney disease. These findings could facilitate the incorporation of remote digital health interventions into clinical practice and offer a potential intervention worthy of investigation in other chronic conditions. FUNDING: Kidney Research UK.

Achieving consensus on psychosocial and physical rehabilitation management for people living with kidney disease.

Background: People living with chronic kidney disease (CKD) need to be able to live well with their condition. The provision of psychosocial interventions (psychological, psychiatric and social care) and physical rehabilitation management is variable across England, as well as the rest of the UK. There is a need for clear recommendations for standards of psychosocial and physical rehabilitation care for people living with CKD, and guidance for the commissioning and measurement of these services. The National Health Service (NHS) England Renal Services Transformation Programme (RSTP) supported a programme of work and modified Delphi process to address the management of psychosocial and physical rehabilitation care as part of a larger body of work to formulate a comprehensive commissioning toolkit for renal care services across England. We sought to achieve expert consensus regarding the psychosocial and physical rehabilitation management of people living with CKD in England and the rest of the UK. Methods: A Delphi consensus method was used to gather and refine expert opinions of senior members of the kidney multi-disciplinary team (MDT) and other key stakeholders in the UK. An agreement was sought on 16 statements reflecting aspects of psychosocial and physical rehabilitation management for people living with CKD. Results: Twenty-six expert practitioners and other key stakeholders, including lived experience representatives, participated in the process. The consensus (>80% affirmative votes) amongst the respondents for all 16 statements was high. Nine recommendation statements were discussed and refined further to be included in the final iteration of the 'Systems' section of the NHS England RSTP commissioning toolkit. These priority recommendations reflect pragmatic solutions that can be implemented in renal care and include recommendations for a holistic wellbeing assessment for all people living with CKD who are approaching dialysis, or who are at listing for kidney transplantation, which includes the use of validated measurement tools to assess the need for further intervention in psychosocial and physical rehabilitation management. It is recommended that the scores from these measurement tools be included in the NHS England Renal Data Dashboard. There was also a recommendation for referral as appropriate to NHS Talking Therapies, psychology, counselling or psychotherapy, social work or liaison psychiatry for those with identified psychosocial needs. The use of digital resources was recommended to be used in addition to face-to-face care to provide physical rehabilitation, and all healthcare professionals should be educated to recognize psychosocial and physical rehabilitation needs and refer/sign-post people with CKD to appropriate services. Conclusion: There was high consensus amongst senior members of the kidney MDT and other key stakeholders, including those with lived experience, in the UK on all aspects of the psychosocial and physical rehabilitation management of people living with CKD. The results of this process will be used by NHS England to inform the 'Systems' section of the commissioning toolkit and data dashboard and to inform the National Standards of Care for people living with CKD.

Micro-RNA content of circulating extracellular vesicles in early rheumatoid arthritis as biomarkers and mediators of methotrexate efficacy.

OBJECTIVES: Extracellular vesicles (EVs) are abundant in body fluids, contributing to intercellular signalling by transferring cargo that includes microRNAs (miRs) - themselves implicated in pathobiology. For the first time we evaluated the potential of EV miRs to contribute diagnostic information in early RA, predict methotrexate (MTX) efficacy or shed light on the drug's mechanism of action. METHODS: 798 miRs isolated from serum-derived EVs of 46 patients with untreated RA, 23 with untreated polymyalgia rheumatica (PMR; inflammatory disease control group) and 12 in whom significant inflammatory disease had been excluded (non-inflammatory controls; NICs) were profiled (Nanostring); the same measurements were made for RA patients after 6 months' MTX treatment. Analyses took multiple testing into account. RESULTS: 28 EV miRs were robustly differentially expressed between early RA (but not PMR) patients and NICs after correction for age and sex, suggesting discriminatory value. Cross-validated partial least squared-discriminant analysis also indicated the predictive potential of a distinct baseline EV miR signature with respect to MTX-induced remission at 6 months. The change in expression of 13 miRs over the course of MTX treatment differed significantly between responders and non-responders, and four of those exhibiting increased relative abundance amongst responders have known roles in regulating the pathogenic potential of synovial fibroblasts, namely miR-212-3p, miR-338-5p, miR-410-3p, and miR-537. CONCLUSION: Our data highlight the potential of serum EV miRs as diagnostic and therapeutic biomarkers, highlighting a novel potential mechanism via which MTX may exert its therapeutic effect in early RA that warrants further investigation.

The effect of exercise on vascular health in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease. This increased risk cannot be fully explained by traditional risk factors such as hypertension. Endothelial dysfunction and arterial stiffness have been suggested as factors that explain some of the increased risk and are independently associated with important cardiovascular outcomes in patients with CKD. Studies in other disease populations have shown the positive effects of exercise on vascular dysfunction. The aim of this review was to determine whether exercise training interventions improve measures of vascular function and morphology in patients across the spectrum of CKD and which exercise training interventions are most efficacious. A systematic search of Medline, Embase, and the Cochrane Central Register identified 25 randomized controlled trials. Only randomized control trials using an exercise intervention with a nonexercising control group and at least one measure of vascular function or morphology were included. Participants were patients with nondialysis CKD or transplant patients or those requiring dialysis therapy. A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A meta-analysis was completed for pulse wave velocity, augmentation index, and measures of endothelium-dependent vasodilation. Data from 25 studies with 872 participants showed that exercise training reduced pulse wave velocity and augmentation index but had no effect on endothelium-dependent vasodilation. Subgroup analyses suggested that exercise interventions of at least moderate intensity were more likely to be effective. Limitations included the absence of observational studies or other interventions aimed at increasing habitual physical activity. Further studies are warranted to investigate which are the most effective exercise interventions.NEW & NOTEWORTHY A thorough systematic review and meta-analysis of the effects of exercise training on measures of vascular function in patients with chronic kidney disease, including arterial stiffness and endothelial function, were conducted. Subgroup analyses investigated how differences in exercise training, according to frequency, intensity, type, and timing, have an impact on the efficacy of the intervention.

Bio-impedance spectroscopy added to a fluid management protocol does not improve preservation of residual kidney function in incident hemodialysis patients in a randomized controlled trial.

Avoiding excessive dialysis-associated volume depletion may help preserve residual kidney function (RKF). To establish whether knowledge of the estimated normally hydrated weight from bioimpedance measurements (BI-NHW) when setting the post-hemodialysis target weight (TW) might mitigate rate of loss of RKF, we undertook an open label, randomized controlled trial in incident patients receiving HD, with clinicians and patients blinded to bioimpedance readings in controls. A total of 439 patients with over 500 ml urine/day or residual GFR exceeding 3 ml/min/1.73m2 were recruited from 34 United Kingdom centers and randomized 1:1, stratified by center. Fluid assessments were made for up to 24 months using a standardized proforma in both groups, supplemented by availability of BI-NHW in the intervention group. Primary outcome was time to anuria, analyzed using competing-risk survival models adjusted for baseline characteristics, by intention to treat. Secondary outcomes included rate of RKF decline (mean urea and creatinine clearance), blood pressure and patient-reported outcomes. There were no group differences in cause-specific hazard rates of anuria (0.751; 95% confidence interval (0.459, 1.229)) or sub-distribution hazard rates (0.742 (0.453, 1.215)). RKF decline was markedly slower than anticipated, pooled linear rates in year 1: -0.178 (-0.196, -0.159)), year 2: -0.061 (-0.086, -0.036)) ml/min/1.73m2/month. Blood pressure and patient-reported outcomes did not differ by group. The mean difference agreement between TW and BI-NHW was similar for both groups, Bioimpedance: -0.04 kg; Control: -0.25 kg. Thus, use of a standardized clinical protocol for fluid assessment when setting TW is associated with excellent preservation of RKF. Hence, bioimpedance measurements are not necessary to achieve this.

Modeling the Effects of IL-1ß-mediated Inflammation During Ex Vivo Lung Perfusion Using a Split Human Donor Model.

BACKGROUND: The association between interleukin-1ß (IL-1ß) concentrations during ex vivo lung perfusion (EVLP) with donor organ quality and post-lung transplant outcome has been demonstrated in several studies. The mechanism underlying IL-1ß-mediated donor lung injury was investigated using a paired single-lung EVLP model. METHODS: Human lung pairs were dissected into individual lungs and perfused on identical separate EVLP circuits, with one lung from each pair receiving a bolus of IL-1ß. Fluorescently labeled human neutrophils isolated from a healthy volunteer were infused into both circuits and quantified in perfusate at regular timepoints. Perfusates and tissues were subsequently analyzed, with perfusates also used in functional assays. RESULTS: Neutrophil numbers were significantly lower in perfusate samples collected from the IL-1ß-stimulated lungs consistent with increased neutrophil adhesion ( P = 0.042). Stimulated lungs gained significantly more weight than controls ( P = 0.046), which correlated with soluble intercellular adhesion molecule-1 (R 2 = 0.71, P = 0.0043) and von-Willebrand factor (R 2 = 0.39, P = 0.040) in perfusate. RNA expression patterns for inflammatory genes were differentially regulated via IL-1ß. Blockade of IL-1ß significantly reduced neutrophil adhesion in vitro ( P = 0.025). CONCLUSION: These data illustrate the proinflammatory functions of IL-1ß in the context of EVLP, suggesting this pathway may be susceptible to therapeutic modulation before transplantation.

Feasibility of randomized controlled trials and long-term implementation of interventions: Insights from a qualitative process evaluation of the PEDAL trial.

Introduction: A multi-site randomized controlled trial was carried out between 2015 and 2019 to evaluate the impacts on quality of life of an intradialytic exercise programme for people living with chronic kidney disease. This included a qualitative process evaluation which gave valuable insights in relation to feasibility of the trial and of the intervention in the long-term. These can inform future clinical Trial design and evaluation studies. Methods: A constructivist phenomenological approach underpinned face-to-face, semi-structured interviews. Purposive recruitment ensured inclusion of participants in different arms of the PEDAL Trial, providers with different roles and trial team members from seven Renal Units in five study regions. Following ethical review, those willing took part in one interview in the Renal Unit. Audio-recorded interviews were transcribed (intelligent verbatim) and inductively thematically analyzed. Results: Participants (n = 65) (Intervention arm: 26% completed; 13% who did not; Usual care arm: 13%; 46% women; 54% men; mean age 60 year) and providers (n = 39) were interviewed (23% PEDAL Trial team members). Three themes emerged: (1) Implementing the Intervention; (2) Implementing the trial; and (3) Engagement of the clinical team. Explanatory theory named "the Ideal Scenario" was developed, illustrating complex interactions between different aspects of intervention and trial implementation with the clinical context. This describes characteristics likely to optimize trial feasibility and intervention sustainability in the long-term. Key aspects of this relate to careful integration of the trial within the clinical context to optimize promotion of the trial in the short-term and engagement and ownership in the long-term. Strong leadership in both the clinical and trial teams is crucial to ensure a proactive and empowering culture. Conclusion: Novel explanatory theory is proposed with relevance for Implementation Science. The "Ideal Scenario" is provided to guide trialists in pre-emptive and ongoing risk analysis relating to trial feasibility and long-term intervention implementation. Alternative study designs should be explored to minimize the research-to-practice gap and optimize the likelihood of informative findings and long-term implementation. These might include Realist Randomized Controlled Trials and Hybrid Effectiveness-Implementation studies.

An experimental investigation of a simulated online intergenerational friendship.

Reducing ageism is a significant social issue. The current study involved a novel experimental examination of whether a one-time simulated online intergenerational friendship would reduce ageism. Undergraduate participants were randomly assigned to complete an interpersonal closeness exercise (the "fast friends" procedure, Aron et al., 1997; Lytle & Levy, 2015) with a confederate who used a script to answer the fast friends questions, during which they either did not reveal their age (control condition) or revealed being an older adult (age 65; experimental condition). Results indicate that experimental (vs. control) participants reported less ageism and more positive behavior (friendlier responses). These findings suggest that positive online intergenerational contact may help combat ageism. As intergenerational contact was limited before the COVID-19 pandemic and even more so during the pandemic, facilitating online intergenerational contact may be a particularly worthwhile ageism reduction strategy. Further implications of these findings and future directions are discussed.

Lineage switching of the cellular distribution of BRAFV600E in multisystem Langerhans cell histiocytosis.

Most children with high-risk Langerhans cell histiocytosis (LCH) have BRAFV600E mutation. BRAFV600E alleles are detectable in myeloid mononuclear cells at diagnosis but it is not known if the cellular distribution of mutation evolves over time. Here, the profiles of 16 patients with high-risk disease were analyzed. Two received conventional salvage chemotherapy, 4 patients on inhibitors were tracked at intervals of 3 to 6 years, and 10 patients, also given inhibitors, were analyzed more than 2 years after diagnosis. In contrast to the patients responding to salvage chemotherapy who completely cleared BRAFV600E within 6 months, children who received inhibitors maintained high BRAFV600E alleles in their blood. At diagnosis, mutation was detected predominantly in monocytes and myeloid dendritic cells. With time, mutation switched to the T-cell compartment, which accounted for most of the mutational burden in peripheral blood mononuclear cells, more than 2 years from diagnosis (median, 85.4%; range, 44.5%-100%). The highest level of mutation occurred in naïve CD4+ T cells (median, 51.2%; range, 3.8%-93.5%). This study reveals an unexpected lineage switch of BRAFV600E mutation in high-risk LCH, which may influence monitoring strategies for the potential withdrawal of inhibitor treatment and has new implications for the pathogenesis of neurodegeneration, which occurred in 4 patients.

Hypoxia alters posterior cingulate cortex metabolism during a memory task: A 1H fMRS study.

Environmental hypoxia (fraction of inspired oxygen (FIO2) ∼ 0.120) is known to trigger a global increase in cerebral blood flow (CBF). However, regionally, a heterogeneous response is reported, particularly within the posterior cingulate cortex (PCC) where decreased CBF is found after two hours of hypoxic exposure. Furthermore, hypoxia reverses task-evoked BOLD signals within the PCC, and other regions of the default mode network, suggesting a reversal of neurovascular coupling. An alternative explanation is that the neural architecture supporting cognitive tasks is reorganised. Therefore, to confirm if this previous result is neural or vascular in origin, a measure of neural activity that is not haemodynamic-dependant is required. To achieve this, we utilised functional magnetic resonance spectroscopy to probe the glutamate response to memory recall in the PCC during normoxia (FIO2 = 0.209) and after two hours of poikilocapnic hypoxia (FIO2 = 0.120). We also acquired ASL-based measures of CBF to confirm previous findings of reduced CBF within the PCC in hypoxia. Consistent with previous findings, hypoxia induced a reduction in CBF within the PCC and other regions of the default mode network. Under normoxic conditions, memory recall was associated with an 8% increase in PCC glutamate compared to rest (P = 0.019); a change which was not observed during hypoxia. However, exploratory analysis of other neurometabolites showed that PCC glucose was reduced during hypoxia compared to normoxia both at rest (P = 0.039) and during the task (P = 0.046). We conclude that hypoxia alters the activity-induced increase in glutamate, which may reflect a reduction in oxidative metabolism within the PCC. The reduction in glucose in hypoxia reflects continued metabolism, presumably by non-oxidative means, without replacement of glucose due to reduced CBF.

PD-1 and TIGIT blockade differentially affect tumour cell survival under hypoxia and glucose deprived conditions in oesophageal adenocarcinoma; implications for overcoming resistance to PD-1 blockade in hypoxic tumours.

Recent studies have demontrated that immune checkpoint receptors are expressed on the surface of oesophageal adenocarcinoma (OAC) cells and might confer a survival advantage. This study explores the role of PD-1 and TIGIT signalling in OAC cells in either promoting or inhibiting the survival of OAC cells under characteristic features of the tumour microenvironment including nutrient-deprivation and hypoxia. PD-1 and TIGIT are expressed in normal and pre-malignant oesophageal epithelial cells and this expression significantly decreases along the normal- Barrett's Oesophagus- OAC disease sequence. However, glucose-deprivation and hypoxia significantly upregulated PD-1 and TIGIT on the surface of OAC cells in vitro. PD-1 blockade decreased OAC cell proliferation under normoxia but enhanced proliferation and decreased cell death in OAC cells under hypoxia and glucose-deprivation. TIGIT blockade decreased proliferation and induced OAC cell death, an effect that was maintained under nutrient-deprivation and hypoxia. Basal respiration and glycolytic reserve were enhanced and GLUT1 was upregulated on the surface of a subpopulation of OAC cells following PD-1 blockade. In contrast, TIGIT blockade enhanced a glycolytic phenotype in OAC cells, yet decreased other metabolic parameters including oxidative phosphorylation and basal respiration. Interestingly, inhibition of oxidative phosphorylation significantly upregulated TIGIT expression and inhibition of oxidative phosphorylation and glycolysis significantly decreased PD-1 on the surface of a subpopulation of OAC cells in vitro. These findings suggest an immune-independent mechanism for PD-1 inhibitor resistance in hypoxic tumours and suggest that TIGIT might be a more effective therapeutic target in OAC compared with PD-1 for treating hypoxic tumours.

Pre-pandemic Ageism Toward Older Adults Predicts Behavioral Intentions During the COVID-19 Pandemic.

OBJECTIVES: During the coronavirus disease 2019 (COVID-19) pandemic, older adults have been disproportionately affected by high rates of health complications and mortality. Reactions toward older adults included a mix of prosocial behaviors and ageist responses, consistent with the history of positive and negative views and treatment of older adults in the United States. METHODS: In a two-part study (n = 113, Mage = 18.49, SD = 0.50; range 18-19), we examined whether pre-pandemic ageism among undergraduates predicts prosocial behavioral intentions toward older adults both specific to COVID-19 and in general. RESULTS: Pre-pandemic ageism toward older adults predicted less intentions to help older adults generally and specific to COVID-19. Whereas viewing older adults as incompetent predicted greater intentions to help specific to COVID-19. DISCUSSION: These results reflect the complexity of predicting helping behaviors and suggest that even supportive behaviors toward older adults during the COVID-19 pandemic may be rooted in negative ageist stereotypes. Implications and directions for future research are discussed.

An Examination of Intergenerational Contact Experiences Using 10,338 Journal Entries From 2,414 Young Adults.

BACKGROUND AND OBJECTIVES: With continued negative depictions of older adults and limitations on positive intergenerational contact, ageism is a significant social issue. Using a rich data set of journal entries, we examined sentiments, emotions, and optimal intergenerational contact conditions among volunteers in an intergenerational program. RESEARCH DESIGN AND METHODS: 10,338 journal entries were analyzed from 2,414 young adult volunteers from GlamourGals Foundation, Inc., a U.S. nonprofit, which aims to reduce isolation by facilitating intergenerational contact. Applying the PEACE (Positive Education about Aging and Contact Experiences) theoretical model, each sentence was coded using sentiment analysis, emotional analysis, and supervised learning methods across 5 optimal intergenerational contact conditions. RESULTS: Out of 74,475 sentences, participants reported predominantly positive sentiments (64.2% positive, 29% neutral, and 6.8% negative) and more positive emotions (e.g., joy) than negative emotions (e.g., disgust). Nearly all participants (98.2%) wrote at least a sentence that included at least 1 of the 5 optimal intergenerational contact conditions. Moreover, positive sentiment was present in higher percentages when more instances of optimal contact conditions were reported (54.4% for none, 71.6% for 1 category, 81.5% for 2, 83% for 3, 89.2% for 4, 98.4% for 5). DISCUSSION AND IMPLICATIONS: The present investigation applied a theoretical model to assess a long-standing community intergenerational program. Contact that provided one-to-one, cooperative, equal status interactions involving personal disclosure that was sanctioned by the program administrators was associated with positive sentiment. Future directions and implications are discussed.

MEDEX 2015: Prophylactic Effects of Positive Expiratory Pressure in Trekkers at Very High Altitude.

Purpose: Positive expiratory pressure (PEP) breathing has been shown to increase arterial oxygenation during acute hypoxic exposure but the underlying mechanisms and consequences on symptoms during prolonged high-altitude exposure remain to be elucidated. Methods: Twenty-four males (41 ± 16 years) were investigated, at sea level and at 5,085 m after 18 days of trekking from 570 m. Participants breathed through a face-mask with PEP = 0 cmH2O (PEP0, 0-45th min) and with PEP = 10 cmH2O (PEP10, 46-90th min). Arterial (SpO2), quadriceps and prefrontal (near infrared spectroscopy) oxygenation was measured continuously. Middle cerebral artery blood velocity (MCAv, transcranial Doppler), cardiac function (2D-echocardiography), extravascular lung water accumulation (UsLC, thoracic ultrasound lung comets) and acute mountain sickness (Lake Louise score, LLS) were assessed during PEP0 and PEP10. Results: At 5,085 m with PEP0, SpO2 was 78 ± 4%, UsLC was 8 ± 5 (a.u.) and the LLS was 2.3 ± 1.7 (all P < 0.05 versus sea level). At 5,085 m, PEP10 increased significantly SpO2 (+9 ± 5%), quadriceps (+2 ± 2%) and prefrontal cortex (+2 ± 2%) oxygenation (P < 0.05), and decreased significantly MCAv (-16 ± 14 cm.s-1) and cardiac output (-0.7 ± 1.2 L.min-1) together with a reduced stroke volume (-9 ± 15 mL, all P < 0.05) and no systemic hypotension. PEP10 decreased slightly the number of UsLC (-1.4 ± 2.7, P = 0.04) while the incidence of acute mountain sickness (LLS ≥ 3) fell from 42% with PEP0 to 25% after PEP10 (P = 0.043). Conclusion: PEP10 breathing improved arterial and tissue oxygenation and symptoms of acute mountain sickness after trekking to very high altitude, despite reduced cerebral perfusion and cardiac output. Further studies are required to establish whether PEP-breathing prophylactic mechanisms also occur in participants with more severe acute mountain sickness.

Randomized Trial-PrEscription of intraDialytic exercise to improve quAlity of Life in Patients Receiving Hemodialysis.

INTRODUCTION: Whether clinically implementable exercise interventions in people receiving hemodialysis (HD) therapy improve health-related quality of life (HRQoL) remains unknown. The PrEscription of intraDialytic exercise to improve quAlity of Life (PEDAL) study evaluated the clinical benefit and cost-effectiveness of a 6-month intradialytic exercise program. METHODS: In a multicenter, single-blinded, randomized, controlled trial, people receiving HD were randomly assigned to (i) intradialytic exercise training (exercise intervention group [EX]) and (ii) usual care (control group [CON]). Primary outcome was change in Kidney Disease Quality of Life Short-Form Physical Component Summary (KDQOL-SF 1.3 PCS) from baseline to 6 months. Cost-effectiveness was determined using health economic analysis; physiological impairment was evaluated by peak oxygen uptake; and harms were recorded. RESULTS: We randomized 379 participants; 335 and 243 patients (EX n = 127; CON n = 116) completed baseline and 6-month assessments, respectively. Mean difference in change PCS from baseline to 6 months between EX and CON was 2.4 (95% confidence interval [CI]: -0.1 to 4.8) arbitrary units (P = 0.055); no improvements were observed in peak oxygen uptake or secondary outcome measures. Participants in the intervention group had poor compliance (47%) and poor adherence (18%) to the exercise prescription. Cost of delivering intervention ranged from US$598 to US$1092 per participant per year. The number of participants with harms was similar between EX (n = 69) and CON (n = 56). A primary limitation was the lack of an attention CON. Many patients also withdrew from the study or were too unwell to complete all physiological outcome assessments. CONCLUSIONS: A 6-month intradialytic aerobic exercise program was not clinically beneficial in improving HRQoL as delivered to this cohort of deconditioned patients on HD.