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.

International consensus is needed on a core outcome set to advance the evidence of best practice in cancer prehabilitation services and research.

Prehabilitation aims to optimise patients' physical and psychological status before treatment. The types of outcomes measured to assess the impact of prehabilitation interventions vary across clinical research and service evaluation, limiting the ability to compare between studies and services and to pool data. An international workshop involving academic and clinical experts in cancer prehabilitation was convened in May 2022 at Sheffield Hallam University's Advanced Wellbeing Research Centre, England. The workshop substantiated calls for a core outcome set to advance knowledge and understanding of best practice in cancer prehabilitation and to develop national and international databases to assess outcomes at a population level.

Moving through cancer: Setting the agenda to make exercise standard in oncology practice.

LAY SUMMARY: International evidence-based guidelines support the prescription of exercise for all individuals living with and beyond cancer. This article describes the agenda of the newly formed Moving Through Cancer initiative, which has a primary objective of making exercise standard practice in oncology by 2029.

An in vitro toolbox to accelerate anti-malarial drug discovery and development.

BACKGROUND: Modelling and simulation are being increasingly utilized to support the discovery and development of new anti-malarial drugs. These approaches require reliable in vitro data for physicochemical properties, permeability, binding, intrinsic clearance and cytochrome P450 inhibition. This work was conducted to generate an in vitro data toolbox using standardized methods for a set of 45 anti-malarial drugs and to assess changes in physicochemical properties in relation to changing target product and candidate profiles. METHODS: Ionization constants were determined by potentiometric titration and partition coefficients were measured using a shake-flask method. Solubility was assessed in biorelevant media and permeability coefficients and efflux ratios were determined using Caco-2 cell monolayers. Binding to plasma and media proteins was measured using either ultracentrifugation or rapid equilibrium dialysis. Metabolic stability and cytochrome P450 inhibition were assessed using human liver microsomes. Sample analysis was conducted by LC-MS/MS. RESULTS: Both solubility and fraction unbound decreased, and permeability and unbound intrinsic clearance increased, with increasing Log D7.4. In general, development compounds were somewhat more lipophilic than legacy drugs. For many compounds, permeability and protein binding were challenging to assess and both required the use of experimental conditions that minimized the impact of non-specific binding. Intrinsic clearance in human liver microsomes was varied across the data set and several compounds exhibited no measurable substrate loss under the conditions used. Inhibition of cytochrome P450 enzymes was minimal for most compounds. CONCLUSIONS: This is the first data set to describe in vitro properties for 45 legacy and development anti-malarial drugs. The studies identified several practical methodological issues common to many of the more lipophilic compounds and highlighted areas which require more work to customize experimental conditions for compounds being designed to meet the new target product profiles. The dataset will be a valuable tool for malaria researchers aiming to develop PBPK models for the prediction of human PK properties and/or drug-drug interactions. Furthermore, generation of this comprehensive data set within a single laboratory allows direct comparison of properties across a large dataset and evaluation of changing property trends that have occurred over time with changing target product and candidate profiles.

The effectiveness of home versus community-based weight control programmes initiated soon after breast cancer diagnosis: a randomised controlled trial.

BACKGROUND: Breast cancer diagnosis may be a teachable moment for lifestyle behaviour change and to prevent adjuvant therapy associated weight gain. We assessed the acceptability and effectiveness of two weight control programmes initiated soon after breast cancer diagnosis to reduce weight amongst overweight or obese women and prevent gains in normal-weight women. METHODS: Overweight or obese (n = 243) and normal weight (n = 166) women were randomised to a three-month unsupervised home (home), a supervised community weight control programme (community) or to standard written advice (control). Primary end points were change in weight and body fat at 12 months. Secondary end points included change in insulin, cardiovascular risk markers, quality of life and cost-effectiveness of the programmes. RESULTS: Forty-three percent of eligible women were recruited. Both programmes reduced weight and body fat: home vs. control mean (95% CI); weight -2.3 (-3.5, -1.0) kg, body fat -1.6 (-2.6, -0.7) kg, community vs. control; weight -2.4 (-3.6, -1.1) kg, body fat -1.4 (-2.4, -0.5) kg (all p < 0.001). The community group increased physical activity, reduced insulin, cardiovascular disease risk markers, increased QOL and was cost-effective. CONCLUSIONS: The programmes were equally effective for weight control, but the community programme had additional benefits. CLINICAL TRIAL REGISTRATION: ISRCTN68576140.

Smoking, alcohol consumption, diet and physical activity following stoma formation surgery, stoma-related concerns, and desire for lifestyle advice: a United Kingdom survey.

BACKGROUND: Adherence to smoking, alcohol consumption, diet and physical activity (PA) guidelines may improve outcomes for people with a stoma. A better understanding of these behaviours following stoma formation surgery and their experiences and attitudes towards receiving lifestyle advice, could help identify specific gaps and inform interventions going forward. The aim of this study was to describe changes in current lifestyle following stoma formation and to explore concerns, desire for lifestyle information, advice and support among people who have or have had a stoma. METHODS: A sample of adults who currently had or in the past had a stoma for treatment for any medical condition was recruited online through relevant charities and companies, and invited to complete a cross-sectional, online survey. Consenting participants (n = 425) provided demographic information and completed brief, validated questionnaires about their lifestyle, alongside questions around their concerns regarding permanent stoma and experiences of lifestyle information and advice. Responses were summarised using descriptive statistics, and associations between reported concerns about stoma and changes in health behaviours were explored. RESULTS: Most respondents (93%) still had a stoma at the time of completing the survey. The majority (80%) had not consumed at least 5 portions of fruit and vegetables on the previous day and 20% reported they had not participated in at least 30 min of physical activity on any day in the previous week. Most respondents were non-smokers (84%) and did not exceed recommendations for alcohol intake (60%). Most (56%) felt their PA had decreased following stoma formation. Frequencies of concerns about a permanent stoma were high, and appeared to be associated with reported decreases in PA. Of those reporting nausea, 40% felt their diet had worsened since having their stoma. A large proportion of respondents had not received PA (42%) or dietary (30%) advice, and of these > 90% would have liked guidance. CONCLUSIONS: Few respondents to this survey were eating the recommended amount of fruit and vegetables, and most reported a decrease in their PA following stoma surgery. Lifestyle advice would be welcomed by this population, which professionals should take into account when addressing stoma- related concerns.

Research priorities about stoma-related quality of life from the perspective of people with a stoma: A pilot survey.

BACKGROUND: There is a recognized need to include patients in setting research priorities. Research priorities identified by people with a stoma are rarely elicited. OBJECTIVES: To improve the quality of life of people with a stoma through use of evidence-based practice based on research priorities set by patients. DESIGN AND METHODS: Online pilot survey publicized in 2016 via United Kingdom stoma charities. People ranked nine stoma-related quality of life topics in order of research priority. PARTICIPANTS: People 16 years of age and over who currently have or have had a stoma for treatment for any medical condition. ANALYSIS: Distributions of the priority scores for each of the nine research topics were examined. Group differences were explored using either the Mann-Whitney U-test or the Kruskal-Wallis test depending on the number of groups. RESULTS: In total, 225 people completed the survey. The most important research priority was pouch leak problems and stoma bag/appliance problems followed by hernia risk. There were statistically significant differences in ranking research priorities between males and females, age, underlying disease that led to a stoma, stoma type and length of time with a stoma. CONCLUSION: People with a stoma are willing to engage in and set research priorities. The results should contribute towards future research about setting the research agenda for the study of stoma-related concerns that impact quality of life.

A shift to placing parents in charge: Does it improve weight gain in youth with anorexia?

Family-based treatment (FBT) has emerged as a promising approach for medically stable youth with anorexia nervosa (AN). While there is evidence that therapists embrace the core principles of FBT, most face barriers in implementing the model with fidelity. Little research has been conducted to determine whether adhering to the core methods of placing parents in charge are sufficient in restoring weight in youth with AN. This study involved a chart review of youth under 16 years of age, treated by a Canadian tertiary care health centre-based eating disorders team (EDT). The purpose was to compare the weight gain of youth treated before and after the team was trained in FBT and shifted to empowering parents to be in charge of weight gain. As predicted, youth who participated in family sessions adhering to the 'parents in charge' approach (PIC, N=32) made greater gains in percentage of ideal body weight (%IBW) and were more likely to reach body weights within a healthy range as compared with youth (N=14) who participated in a 'non-specific therapy' (NST) involving expert driven psycho-educational family sessions. Youth whose parents were placed in charge of weight gain were also significantly less likely to be hospitalized on the psychiatry unit for weight restoration, had significantly shorter mean duration of stays on this unit, and required tube-feeding less frequently than youth who participated in NST. Collectively, the results suggest that placing parents in charge of refeeding promotes efficient weight gain, while decreasing the need for more intensive intervention.

Synthesis and antimalarial evaluation of amide and urea derivatives based on the thiaplakortone A natural product scaffold.

A series of amide (8­32, 40­45) and urea (33, 34, 36­39) analogues based on the thiaplakortone A natural product scaffold were synthesised and screened for in vitro antimalarial activity against chloroquine-sensitive (3D7) and chloroquine- and mefloquine-resistant (Dd2) Plasmodium falciparum parasite lines. Several analogues displayed potent inhibition of P. falciparum growth (IC50 <500 nM) and good selectivity for P. falciparum versus human neonatal foreskin fibroblast cells (selectivity index >100). Two of these compounds, 8 and 33, exhibited good aqueous solubility and metabolic stability, and when administered subcutaneously to mice (32 mg kg(-1)), plasma concentrations remained above 0.2 µM for at least 8 h. Both 8 and 33 were well tolerated in mice after subcutaneous administration of 32 mg kg(-1) twice daily for 4 days. Using this regimen blood stage P. berghei was suppressed by 52% for 8 and 26% for 33, relative to the vehicle control.

Treatment-related cardiovascular late effects and exercise training countermeasures in testicular germ cell cancer survivorship.

BACKGROUND: Treatment of testicular germ cell cancer constitutes a major success story in modern oncology. Today, the vast majority of patients are cured by a therapeutic strategy using one or more highly effective components including surgery (orchiectomy), radiotherapy and/or chemotherapy. However, the excellent cancer-specific survival comes at considerable costs, as individuals with a history of germ cell cancer experience serious long-term complications, including markedly increased risk of cardiovascular morbidities and premature cardiovascular death. The factors responsible, as well as their mode of action, are not fully understood and there is a lack of knowledge concerning optimal evidence-based long-term follow-up strategies. RESULTS: Here, we present the growing body of evidence suggesting that germ cell cancer patients as a consequence of the different treatment components, are subjected to toxicities, which individually, and synergistically, can cause physiological impairments leading to sub-clinical or clinical cardiovascular disorders (i.e. the 'multiple-hit hypothesis'). Furthermore, we discuss the efficacy and utility of structured exercise training to ameliorate treatment-induced cardiovascular dysfunction to prevent premature onset of clinical cardiovascular disease in germ cell cancer survivors, with a view towards highlighting future directions of exercise-based survivorship research in the germ cell cancer setting. CONCLUSION: As exercise training may have the potential to ameliorate and/or reverse long-term cardiovascular disease sequelae in germ cell cancer survivors, a strong rationale exists for the promotion of exercise oncology research in this setting, in order to provide exercise recommendations for optimal germ cell cancer survivorship.

Opportunities and Implications of Pasture-Based Lamb Fattening to Enhance the Long-Chain Fatty Acid Composition in Meat.

Health-conscious consumers following dietary fat recommendations require meat that is low in saturated fat with preferably high levels of long-chain omega-3 fatty acids. This review summarizes the influence of dietary lipids from red meat on human health and examines the potential to enhance lipid composition through pasture-feeding. The role of fatty acids in plant and ruminant metabolism is discussed to highlight the complexity of ruminal digestion when trying to enhance fatty acids in meat. Generally, ruminants that consume pasture diets have been shown to produce a more desirable fatty acid composition than those fed grain and offer potential to be further enhanced by using specific plant species. Elevated polyunsaturated fat content in meat, however, tends to increase susceptibility to oxidation, which influences other meat quality characteristics including shelf-life and color. The use of specific plant species may mitigate these negative effects due to vitamin E or other antioxidants in these plants, which protect polyunsaturated fats from oxidation. When assessing the potential of plants as a natural dietary fat source, consideration must be given to environmental influences on plant fatty acid composition to ensure consistent production of meat products with high nutritive value under a range of management practices. This review also explores the potential impact of climate change on plant fatty acid composition, and the potential implications of this for meat quality.

Ocean acidification increases copper toxicity to the early life history stages of the polychaete Arenicola marina in artificial seawater.

The speciation and therefore bioavailability of the common pollutant copper is predicted to increase within the pH range anticipated under near-future ocean acidification (OA), hence the potential exists for copper toxicity to marine organisms to also increase. We investigated the impact of OA (seawater pH values of 7.77 (pCO2 1400 µatm) and 7.47 (pCO2 3000 µatm)) upon copper toxicity responses in early life history stages of the polychaete Arenicola marina and found both synergistic and additive toxicity effects of combined exposures depending on life history stage. The toxicity of copper on sperm DNA damage and early larval survivorship was synergistically increased under OA conditions. Larval survival was reduced by 24% when exposed to both OA and copper combined compared to single OA or copper exposures. Sperm motility was negatively affected by both OA and copper singularly with additive toxicity effects of the two stressors when combined. Fertilization success was also negatively affected by both OA and copper individually, but no additive effects when exposed as combined stressors were present for this stage. These findings add to the growing body of evidence that OA will act to increase the toxicity of copper to marine organisms, which has clear implications for coastal benthic ecosystems suffering chronic metal pollution as pCO2 levels rise and drive a reduction in seawater pH.

Establishment of clinical exercise physiology as a regulated healthcare profession in the UK: a progress report.

In 2021, a 'call to action' was published to highlight the need for professional regulation of clinical exercise physiologists to be established within UK healthcare systems to ensure patient safety and align training and regulation with other health professions. This manuscript provides a progress report on the actions that Clinical Exercise Physiology UK (CEP-UK) has undertaken over the past 4 years, during which time clinical exercise physiologists have implemented regulation and gained formal recognition as healthcare professionals in the UK. An overview of the consultation process involved in creating a regulated health profession, notably the development of policies and procedures for both individual registration and institutional master's degree (MSc) accreditation is outlined. Additionally, the process for developing an industry-recognised scope of practice, a university MSc-level curriculum framework, the Academy for Healthcare Science Practitioner standards of proficiency and Continuing Professional Development opportunities is included. We outline the significant activities and milestones undertaken by CEP-UK and provide insight and clarity for other health professionals to understand the training and registration process for a clinical exercise physiologist in the UK. Finally, we include short, medium and long-term objectives for the future advocacy development of this workforce in the UK.

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer.

INTRODUCTION: Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS: More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS: The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS: With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.

Multidimensional rehabilitation programmes for adult cancer survivors.

BACKGROUND: Multidimensional rehabilitation programmes (MDRPs) have developed in response to the growing number of people living with and surviving cancer. MDRPs comprise a physical component and a psychosocial component. Studies of the effectiveness of these programmes have not been reviewed and synthesised. OBJECTIVES: To conduct a systematic review of studies examining the effectiveness of MDRPs in terms of maintaining or improving the physical and psychosocial well-being of adult cancer survivors. SEARCH METHODS: We conducted electronic searches in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsychINFO up to February 2012. SELECTION CRITERIA: Selection criteria focused on randomised controlled trials (RCTs) of multidimensional interventions for adult cancer survivors. Interventions had to include a physical component and a psychosocial component and to have been carried out on two or more occasions following completion of primary cancer treatment. Outcomes had to be assessed using validated measures of physical health and psychosocial well-being. Non-English language papers were included. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected trials, rated their methodological quality and extracted relevant data. Although meta-analyses of primary and secondary endpoints were planned there was a high level of study heterogeneity and only one common outcome measure (SF-36) could be statistically synthesised. In addition, we conducted a narrative analysis of interventions, particularly in terms of inspecting and identifying intervention components, grouping or categorising interventions and examining potential common links and outcomes. MAIN RESULTS: Twelve RCTs (comprising 1669 participants) met the eligibility criteria. We judged five studies to have a moderate risk of bias and assessed the remaining seven as having a high risk of bias. It was possible to include SF-36 physical health component scores from five studies in a meta-analysis. Participating in a MDRP was associated with an increase in SF-36 physical health component scores (mean difference (MD) 2.22, 95% confidence interval (CI) 0.12 to 4.31, P = 0.04). The findings from the narrative analysis suggested that MDRPs with a single domain or outcome focus appeared to be more successful than programmes with multiple aims. In addition, programmes that comprised participants with different types of cancer compared to cancer site-specific programmes were more likely to show positive improvements in physical outcomes. The most effective mode of service delivery appeared to be face-to-face contact supplemented with at least one follow-up telephone call. There was no evidence to indicate that MDRPs which lasted longer than six months improved outcomes beyond the level attained at six months. In addition, there was no evidence to suggest that services were more effective if they were delivered by a particular type of health professional. AUTHORS' CONCLUSIONS: There is some evidence to support the effectiveness of brief, focused MDRPs for cancer survivors. Rigorous and methodologically sound clinical trials that include an economic analysis are required.

Understanding barriers to exercise implementation 5-year post-breast cancer diagnosis: a large-scale qualitative study.

Due to the amount of literature supporting exercise participation after cancer diagnosis, there has been recent interest in barriers to exercise engagement among cancer patients. However, little is known regarding reasons why people choose to disengage and how this disengagement occurs over time. This study aimed to qualitatively study the perceived barriers to exercise implementation, 5-year post-breast cancer diagnosis. Eighty-three female breast cancer survivors participated in a one-to-one semi-structured interview, regarding their experience of exercise over the past 5 years following their original participation in a group-based structured exercise intervention after diagnosis (41 from intervention and 42 from original control group). The data were analysed using inductive thematic analysis. The findings included three main themes and several subthemes regarding the women's perceived barriers: psychological barriers (lack of motivation, fears, dislike of gym, not being the 'sporty type'), physical barriers (the ageing process, cancer treatment and other physical co-morbidities, fatigue and weight gain) and contextual and environmental barriers (employment, traditional female care-giving roles, proximity/access to facilities, seasonal weather). The findings add inductive support to the current survivor health research advocating the use of activity immediately after diagnosis, as well as the need for tailored activity programmes in order to overcome potential obstacles.

Impact, Ramifications and Taking Back Control: A Qualitative Study of Male Survivors of Childhood Sexual Abuse.

There is increasing recognition of the occurrence and frequency of male childhood sexual abuse (MCSA). Quantitative and qualitative research has demonstrated a number of adverse outcomes associated with MCSA in terms of mental health, physical health and difficulties in behavioural, social or interrelationship functioning. The present study gives voice to male survivors of childhood sexual abuse by exploring themes around the impact of MCSA over the course of their life. Interpretative phenomenological analysis (IPA) of semi-structured interviews with nine male survivors of childhood sexual abuse identified a single overarching theme of control and six related superordinate themes of: (i) responsibility, blame and shame; (ii) development of knowledge about sex and abuse; (iii) avoidance of coping with abuse; (iv) effects on relationships as adults; (v) disclosure of abuse to others; and (vi) gaining a sense of meaning of the abuse. The findings showed that being sexually abused defines and controls a person's life, and that despite the difficulties experienced by victims to move past the abuse, some experienced a degree of personal growth. The findings illustrate the way in which individuals can create meaning around their abuse experiences and take back control.

Looking back: a review of policy implications for exercise oncology.

The evidence to support the benefits of exercise for people living with and beyond cancer is robust. Still, exercise oncology interventions in the United States are only eligible for coverage by third-party payers within the restrictions of cancer rehabilitation settings. Without expanded coverage, access will remain highly inequitable, tending toward the most well-resourced. This article describes the pathway to third-party coverage for 3 programs that address a chronic disease and utilize exercise professionals: the Diabetes Prevention Program, Supervised Exercise Training for Peripheral Artery Disease, and Cancer Rehabilitation. Lessons learned will be applied toward expanding third-party coverage for exercise oncology programming.