Eccentric exercise versus Usual-care with older cancer survivors: The impact on muscle and mobility- an exploratory pilot study

<p>Abstract</p> <p>Background</p> <p>Resistance exercise programs with high compliance are needed to counter impaired muscle and mobility in older cancer survivors. To date outcomes have focused on older prostate cancer survivors, though more heterogeneous groups of older survivors are in-need. The purpose of this exploratory pilot study is to examine whether resistance exercise via negative eccentrically-induced work (RENEW) improves muscle and mobility in a diverse sample of older cancer survivors.</p> <p>Methods</p> <p>A total of 40 individuals (25 female, 15 male) with a mean age of 74 (± 6) years who have survived (8.4 ± 8 years) since their cancer diagnosis (breast, prostate, colorectal and lymphoma) were assigned to a RENEW group or a non-exercise Usual-care group. RENEW was performed for 12 weeks and measures of muscle size, strength, power and mobility were made pre and post training.</p> <p>Results</p> <p>RENEW induced increases in quadriceps lean tissue average cross sectional area (Pre: 43.2 ± 10.8 cm²; Post: 44.9 ± 10.9 cm²), knee extension peak strength (Pre: 248.3 ± 10.8 N; Post: 275.4 ± 10.9 N), leg extension muscle power (Pre: 198.2 ± 74.7 W; Post 255.5 ± 87.3 W), six minute walk distance (Pre: 417.2 ± 127.1 m; Post 466.9 ± 125.1 m) and a decrease on the time to safely descend stairs (Pre: 6.8 ± 4.5 s; Post 5.4 ± 2.5 s). A significant (P < 0.05) group x time interaction was noted for the muscle size and mobility improvements.</p> <p>Conclusions</p> <p>This exploration of RENEW in a heterogeneous cohort of older cancer survivors demonstrates increases in muscle size, strength and power along with improved mobility. The efficacy of a high-force, low perceived exertion exercise suggests RENEW may be suited to older individuals who are survivors of cancer.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00335491">NCT00335491</a></p

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Four reasons to prefer Bayesian analyses over significance testing

Inference using significance testing and Bayes factors is compared and contrasted in five case studies based on real research. The first study illustrates that the methods will often agree, both in motivating researchers to conclude that H1 is supported better than H0, and the other way round, that H0 is better supported than H1. The next four, however, show that the methods will also often disagree. In these cases, the aim of the paper will be to motivate the sensible evidential conclusion, and then see which approach matches those intuitions. Specifically, it is shown that a high-powered non-significant result is consistent with no evidence for H0 over H1 worth mentioning, which a Bayes factor can show, and, conversely, that a low-powered non-significant result is consistent with substantial evidence for H0 over H1, again indicated by Bayesian analyses. The fourth study illustrates that a high-powered significant result may not amount to any evidence for H1 over H0, matching the Bayesian conclusion. Finally, the fifth study illustrates that different theories can be evidentially supported to different degrees by the same data; a fact that P-values cannot reflect but Bayes factors can. It is argued that appropriate conclusions match the Bayesian inferences, but not those based on significance testing, where they disagree

Community seroprevalence of SARS-CoV-2 in children and adolescents in England, 2019–2021

Objective: To understand community seroprevalence of SARS-CoV-2 in children and adolescents. This is vital to understanding the susceptibility of this cohort to COVID-19 and to inform public health policy for disease control such as immunisation. Design: We conducted a community-based cross-sectional seroprevalence study in participants aged 0–18 years old recruiting from seven regions in England between October 2019 and June 2021 and collecting extensive demographic and symptom data. Serum samples were tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins using Roche assays processed at UK Health Security Agency laboratories. Prevalence estimates were calculated for six time periods and were standardised by age group, ethnicity and National Health Service region. Results: Post-first wave (June–August 2020), the (anti-spike IgG) adjusted seroprevalence was 5.2%, varying from 0.9% (participants 10–14 years old) to 9.5% (participants 5–9 years old). By April–June 2021, this had increased to 19.9%, varying from 13.9% (participants 0–4 years old) to 32.7% (participants 15–18 years old). Minority ethnic groups had higher risk of SARS-CoV-2 seropositivity than white participants (OR 1.4, 95% CI 1.0 to 2.0), after adjusting for sex, age, region, time period, deprivation and urban/rural geography. In children <10 years, there were no symptoms or symptom clusters that reliably predicted seropositivity. Overall, 48% of seropositive participants with complete questionnaire data recalled no symptoms between February 2020 and their study visit. Conclusions: Approximately one-third of participants aged 15–18 years old had evidence of antibodies against SARS-CoV-2 prior to the introduction of widespread vaccination. These data demonstrate that ethnic background is independently associated with risk of SARS-CoV-2 infection in children. Trial registration number: NCT04061382

Longitudinal analysis of physical function in older adults: the effects of physical inactivity and exercise training

Lack of exercise contributes to systemic inflammation and is a major cause of chronic disease. The long-term impact of initiating and sustaining exercise in late life, as opposed to sustaining a sedentary lifestyle, on whole-body health measures such as physical performance is not well known. This is an exploratory study to compare changes in physical performance among older adults initiating exercise late in life versus inactive older adults. Data from two observational cohorts were included in this analysis, representing two activity groups. The Active group cohort comprises older adults (n = 318; age 72.5 ± 7.2 years) enrolled in a supervised exercise program, “Gerofit.” The inactive group comprises older adults (n = 146; age 74.5 ± 5.5 years) from the Italian study “Act on Ageing” (AOA) who self-reported being inactive. Participants in both groups completed physical performance battery at baseline and 1-year including: 6-min walk test, 30-s chair stand, and timed up-and-go. Two-sample t-tests measured differences between Gerofit and AOA at baseline and 1-year across all measures. Significant between-group effects were seen for all performance measures (ps = 0.001). The AOA group declined across all measures from baseline to 1 year (range −18% to −24% change). The Gerofit group experienced significant gains in function for all measures (range +10% to +31% change). Older adults who initiated routine, sustained exercise were protected from age-related declines in physical performance, while those who remained sedentary suffered cumulative deficits across strength, aerobic endurance, and mobility. Interventions to reduce sedentary behaviors and increase physical activity are both important to promote multi-system, whole-body health

Contribution of Social Isolation, Restraint, and Hindlimb Unloading to Changes in Hemodynamic Parameters and Motion Activity in Rats

The most accepted animal model for simulation of the physiological and morphological consequences of microgravity on the cardiovascular system is one of head-down hindlimb unloading. Experimental conditions surrounding this model include not only head-down tilting of rats, but also social and restraint stresses that have their own influences on cardiovascular system function. Here, we studied levels of spontaneous locomotor activity, blood pressure, and heart rate during 14 days under the following experimental conditions: cage control, social isolation in standard rat housing, social isolation in special cages for hindlimb unloading, horizontal attachment (restraint), and head-down hindlimb unloading. General activity and hemodynamic parameters were continuously monitored in conscious rats by telemetry. Heart rate and blood pressure were both evaluated during treadmill running to reveal cardiovascular deconditioning development as a result of unloading. The main findings of our work are that: social isolation and restraint induced persistent physical inactivity, while unloading in rats resulted in initial inactivity followed by normalization and increased locomotion after one week. Moreover, 14 days of hindlimb unloading showed significant elevation of blood pressure and slight elevation of heart rate. Hemodynamic changes in isolated and restrained rats largely reproduced the trends observed during unloading. Finally, we detected no augmentation of tachycardia during moderate exercise in rats after 14 days of unloading. Thus, we concluded that both social isolation and restraint, as an integral part of the model conditions, contribute essentially to cardiovascular reactions during head-down hindlimb unloading, compared to the little changes in the hydrostatic gradient

Lifestyle interventions are feasible in patients with colorectal cancer with potential short-term health benefits:a systematic review

Purpose: Lifestyle interventions have been proposed to improve cancer survivorship in patients with colorectal cancer (CRC), but with treatment pathways becoming increasingly multi-modal and prolonged, opportunities for interventions may be limited. This systematic review assessed the evidence for the feasibility of performing lifestyle interventions in CRC patients and evaluated any short- and long-term health benefits. Methods: Using PRISMA Guidelines, selected keywords identified randomised controlled studies (RCTs) of lifestyle interventions [smoking, alcohol, physical activity (PA) and diet/excess body weight] in CRC patients. These electronic databases were searched in June 2015: Dynamed, Cochrane Database, OVID MEDLINE, OVID EMBASE, and PEDro. Results: Fourteen RCTs were identified: PA RCTs (n = 10) consisted mainly of telephone-prompted walking or cycling interventions of varied durations, predominately in adjuvant setting; dietary/excess weight interventions RCTs (n = 4) focused on low-fat and/or high-fibre diets within a multi-modal lifestyle intervention. There were no reported RCTs in smoking or alcohol cessation/reduction. PA and/or dietary/excess weight interventions reported variable recruitment rates, but good adherence and retention/follow-up rates, leading to short-term improvements in dietary quality, physical, psychological and quality-of-life parameters. Only one study assessed long-term follow-up, finding significantly improved cancer-specific survival after dietary intervention. Conclusions: This is the first systematic review on lifestyle interventions in patients with CRC finding these interventions to be feasible with improvements in short-term health. Future work should focus on defining the optimal type of intervention (type, duration, timing and intensity) that not only leads to improved short-term outcomes but also assesses long-term survival

Statistical inference and the replication crisis

The replication crisis has prompted many to call for statistical reform within the psychological sciences. Here we examine issues within Frequentist statistics that may have led to the replication crisis, and we examine the alternative—Bayesian statistics—that many have suggested as a replacement. The Frequentist approach and the Bayesian approach offer radically different perspectives on evidence and inference with the Frequentist approach prioritising error control and the Bayesian approach offering a formal method for quantifying the relative strength of evidence for hypotheses. We suggest that rather than mere statistical reform, what is needed is a better understanding of the different modes of statistical inference and a better understanding of how statistical inference relates to scientific inference

Temporal Expression of Chemokines Dictates the Hepatic Inflammatory Infiltrate in a Murine Model of Schistosomiasis

Schistosomiasis continues to be an important cause of parasitic morbidity and mortality world-wide. Determining the molecular mechanisms regulating the development of granulomas and fibrosis will be essential for understanding how schistosome antigens interact with the host environment. We report here the first whole genome microarray analysis of the murine liver during the progression of Schistosoma japonicum egg-induced granuloma formation and hepatic fibrosis. Our results reveal a distinct temporal relationship between the expression of chemokine subsets and the recruitment of cells to the infected liver. Genes up-regulated earlier in the response included T- and B-cell chemoattractants, reflecting the early recruitment of these cells illustrated by flow cytometry. The later phases of the response corresponded with peak recruitment of eosinophils, neutrophils, macrophages and myofibroblasts/hepatic stellate cells (HSCs) and the expression of chemokines with activity for these cells including CCL11 (eotaxin 1), members of the Monocyte-chemoattractant protein family (CCL7, CCL8, CCL12) and the Hepatic Stellate Cell/Fibrocyte chemoattractant CXCL1. Peak expression of macrophage chemoattractants (CCL6, CXCL14) and markers of alternatively activated macrophages (e.g. Retnla) during this later phase provides further evidence of a role for these cells in schistosome-induced pathology. Additionally, we demonstrate that CCL7 immunolocalises to the fibrotic zone of granulomas. Furthermore, striking up-regulation of neutrophil markers and the localisation of neutrophils and the neutrophil chemokine S100A8 to fibrotic areas suggest the involvement of neutrophils in S. japonicum-induced hepatic fibrosis. These results further our understanding of the immunopathogenic and, especially, chemokine signalling pathways that regulate the development of S. japonicum-induced granulomas and fibrosis and may provide correlative insight into the pathogenesis of other chronic inflammatory diseases of the liver where fibrosis is a common feature

Magnetic Resonance Imaging in Huntington's Disease.

Magnetic resonance imaging (MRI) is a noninvasive technique used routinely to image the body in both clinical and research settings. Through the manipulation of radio waves and static field gradients, MRI uses the principle of nuclear magnetic resonance to produce images with high spatial resolution, appropriate for the investigation of brain structure and function