An app with brief behavioural support to promote physical activity after a cancer diagnosis (APPROACH): study protocol for a pilot randomised controlled trial.

BACKGROUND: There are multiple health benefits from participating in physical activity after a cancer diagnosis, but many people living with and beyond cancer (LWBC) are not meeting physical activity guidelines. App-based interventions offer a promising platform for intervention delivery. This trial aims to pilot a theory-driven, app-based intervention that promotes brisk walking among people living with and beyond cancer. The primary aim is to investigate the feasibility and acceptability of study procedures before conducting a larger randomised controlled trial (RCT). METHODS: This is an individually randomised, two-armed pilot RCT. Patients with localised or metastatic breast, prostate, or colorectal cancer, who are aged 16 years or over, will be recruited from a single hospital site in South Yorkshire in the UK. The intervention includes an app designed to encourage brisk walking (Active 10) supplemented with habit-based behavioural support in the form of two brief telephone/video calls, an information leaflet, and walking planners. The primary outcomes will be feasibility and acceptability of the study procedures. Demographic and medical characteristics will be collected at baseline, through self-report and hospital records. Secondary outcomes for the pilot (assessed at 0 and 3 months) will be accelerometer measured and self-reported physical activity, body mass index (BMI) and waist circumference, and patient-reported outcomes of quality of life, fatigue, sleep, anxiety, depression, self-efficacy, and habit strength for walking. Qualitative interviews will explore experiences of participating or reasons for declining to participate. Parameters for the intended primary outcome measure (accelerometer measured average daily minutes of brisk walking (≥ 100 steps/min)) will inform a sample size calculation for the future RCT and a preliminary economic evaluation will be conducted. DISCUSSION: This pilot study will inform the design of a larger RCT to investigate the efficacy and cost-effectiveness of this intervention in people LWBC. TRIAL REGISTRATION: ISRCTN registry, ISRCTN18063498 . Registered 16 April 2021.

Metabolic syndrome and cardiovascular disease after haematopoietic cell transplantation (HCT) in adults: an EBMT cross-sectional non-interventional study.

Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p < 0.001, OR 3.69, 95% CI 2.09-6.54, p < 0.001), and, as expected, MetS and CVE were age-related. Unexpectedly, CVE were associated with occurrence of second malignancy. Screening for and management of MetS should be integrated within routine HCT long-term follow-up care for both allogeneic and autologous HCT survivors. Further research is warranted, including randomised controlled trials of interventional strategies and mechanistic studies of cardiovascular risk in HCT survivors.

Systematic review of the use of translated patient-reported outcome measures in cancer trials.

BACKGROUND: Patient-reported outcomes (PROs) are used in clinical trials to assess the effectiveness and tolerability of interventions. Inclusion of participants from different ethnic backgrounds is essential for generalisability of cancer trial results. PRO data collection should include appropriately translated patient-reported outcome measures (PROMs) to minimise missing data and sample attrition. METHODS: Protocols and/or publications from cancer clinical trials using a PRO endpoint and registered on the National Institute for Health Research Portfolio were systematically reviewed for information on recruitment, inclusion of ethnicity data, and use of appropriately translated PROMs. Semi-structured interviews were conducted with key stakeholders to explore barriers and facilitators for optimal PRO trial design, diverse recruitment and reporting, and use of appropriately translated PROMs. RESULTS: Eighty-four trials met the inclusion criteria, only 14 (17%) (n = 4754) reported ethnic group data, and ethnic group recruitment was low, 611 (13%). Although 8 (57%) studies were multi-centred and multi-national, none reported using translated PROMs, although available for 7 (88%) of the studies. Interviews with 44 international stakeholders identified a number of perceived barriers to ethnically diverse recruitment including diverse participant engagement, relevance of ethnicity to research question, prominence of PROs, and need to minimise investigator burden. Stakeholders had differing opinions on the use of translated PROMs, the impact of trial designs, and recruitment strategies on diverse recruitment. Facilitators of inclusive research were described and examples of good practice identified. CONCLUSIONS: Greater transparency is required when PROs are used as primary or secondary outcomes in clinical trials. Protocols and publications should demonstrate that recruitment was accessible to diverse populations and facilitated by trial design, recruitment strategies, and appropriate PROM usage. The use of translated PROMs should be made explicit when used in cancer clinical trials.

Current Practice in Vitamin D Management in Allogeneic Hematopoietic Stem Cell Transplantation: A Survey by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation.

Beyond its impact on bone health, numerous studies have investigated the immune-regulatory properties of vitamin D and shown how its deficiency can affect outcomes in allogeneic hematopoietic stem cell transplantation (HSCT), particularly in acute or chronic graft-versus-host disease. This survey, carried out by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT), describes the current clinical practice discrepancies across the EBMT HSCT programs. We therefore recommend the development of evidence-based guidelines to standardize evaluation criteria and to harmonize the management of vitamin D deficiency in patients undergoing allogeneic HSCT.

Late treatment effects following bone marrow transplant: Efficacy of implementing international guidelines.

An increasing cohort of haematopoietic cell transplantation (HCT) survivors has raised awareness of long-term and late effects. Updated recommendations for HCT late effects screening were published in 2012 [Majhail et al. Biology of Blood and Marrow Transplantation, 18 (2012):348]. We aimed to assess the clinical efficacy of a dedicated screening clinic to identify problems in HCT survivors using the international guidelines. Clinic letters and test results of the first 59 consecutive patients attending the screening clinic were evaluated. 30 females and 29 males (mean age of 49 years, range 22-74) were included. The mean time since transplant was 6 years (0.5-18). 49/65 transplants were allogeneic. Primary indications for HCT were myeloid (56%), lymphoid (37%), solid tumour (5%) and auto-immune diseases (2%). 134 complications were reported (mean 2, range 0-8), with 114 documented further actions/referrals. The most commonly reported concerns were pain 18/59 (31%), fatigue 14/59 (24%), sexual function 14/59 (24%) and sleep disturbance 11/59 (19%). Second primary malignancies were recorded in five cases. Implementation and audit of the international late effect screening guidelines confirm the need for systematic long-term physical and psychological screening and care, thus ensuring timely and efficient identification of problems and the opportunity to minimise morbidity effects and optimise health.

Provision of long-term monitoring and late effects services following adult allogeneic haematopoietic stem cell transplant: a survey of UK NHS-based programmes.

Despite international guidelines, optimal delivery models of late effects (LE) services for HSCT patients are unclear from the clinical, organizational and economic viewpoints. To scope current LE service delivery models within the UK NHS (National Health Service), in 2014, we surveyed the 27 adult allogeneic HSCT centres using a 30-question online tool, achieving a 100% response rate. Most LE services were led and delivered by senior physicians (>80% centres). Follow-up was usually provided in a dedicated allograft or LE clinic for the first year (>90% centres), but thereafter attrition meant that only ~50% of patients were followed after 5 years. Most centres (69%) had a standard operating procedure for long-term monitoring but access to a LE Multi-Disciplinary Team was rare (19% centres). Access to medical specialities necessary for LE management was good, but specialist interest in long-term HSCT complications was uncommon. Some screening (endocrinopathy, cardiovascular) was near universal, but other areas were more limited (mammography, cervical smears). Funding of extra staff and investigations were the most commonly perceived barriers to implementation of LE services. This survey shows variation in the long-term follow-up of allogeneic HSCT survivors within the UK NHS and further work is warranted to optimize effective, sustainable and affordable models of LE service delivery among this group.

Metabolic syndrome and cardiovascular disease following hematopoietic cell transplantation: screening and preventive practice recommendations from CIBMTR and EBMT.

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.

Endocrine, metabolic, nutritional and body composition abnormalities are common in advanced intensively-treated (transplanted) multiple myeloma.

Modern treatment strategies have increased life expectancy in multiple myeloma, but little is known about the endocrine, metabolic and nutritional status of long-term survivors. We performed endocrine, metabolic, bone, body composition and nutritional evaluations in 32 patients with intensively-treated, advanced but stable, myeloma a median duration of 6 years from diagnosis and three lines of intensive treatment, including at least one haematopoietic SCT procedure. All patients were off active treatment. There was a high prevalence of endocrine dysfunction: hypothyroidism (9%), hypogonadism (65% males) and elevated prolactin (19%). Adrenocortical function was preserved despite large cumulative corticosteroid pretreatment. Biochemical markers were consistent with postmenopausal status in all females and infertility in males. Nutritionally, 59% were vitamin D insufficient/deficient, reduced serum folate in 25% and vitamin B12 in 6%. Total body DEXA scanning confirmed 'sarcopenic-obesity' in 65%, but reduced bone density was seen in a minority. We conclude that potentially correctable endocrine, metabolic and nutritional abnormalities are prevalent in heavily-treated patients with stable multiple myeloma. Preservation of bone supports the efficacy of bisphosphonate treatment from diagnosis, but sarcopenic-obesity may contribute to frailty. Ultimately, multi-system screening and appropriate interventions may optimise quality of long-term survival and further studies are warranted.

Holistic needs assessment in advanced, intensively treated multiple myeloma patients.

PURPOSE: It is recommended that patients with multiple myeloma should be assessed for unmet holistic needs at key times in their disease trajectory. The aim of this exploratory study was to characterise the holistic needs of advanced, intensively treated multiple myeloma using a structured assessment tool. METHODS: Patients with multiple myeloma who had undergone a haematopoietic stem cell transplantation and subsequent treatment for at least one episode of progressive disease but were in stable plateau phase were included in the study. Patients' holistic needs were assessed using the self-reporting tool, Sheffield Profile for Assessment and Referral for Care (SPARC). RESULTS: Thirty-two patients with a median age of 60 years at assessment and a median of 5.5 years from diagnosis were recruited. Using the SPARC, half of the patients reported tiredness as 'quite a bit/very much,' while one third complained that daytime somnolence and insomnia were 'quite a bit/very much.' Forty-four percent of patients reported pain. One third of patients were bothered and distressed by the side effects from their treatment and were worried about long-term effects of their treatment. Thirty-one percent of patients felt that the effect of their condition had an impact on their sexual life, and 40 % were worried about the effect that their illness was having on their family or other people. CONCLUSION: This is the first study to use a self-reported holistic needs assessment tool in multiple myeloma. A multidimensional structured questionnaire like the SPARC could provide a useful first step in the effective delivery of supportive and palliative care for patients with multiple myeloma.

Gender differences in self-reported late effects, quality of life and satisfaction with clinic in survivors of lymphoma.

OBJECTIVES: Gender differences in perceived vulnerability to late effects and views about follow-up among cancer survivors have received little attention. As lymphoma affects both genders similarly, we compared the consequences of cancer (late effects, perceived vulnerability and quality of life (health-related quality of life (HRQoL)), and satisfaction with clinic visits between genders. METHODS: A cohort of 115 younger adults (18-45 years, >5 years disease-free survival), who had been treated for lymphoma participated. Questionnaires (n = 91) were completed before and after (n = 62) routine consultant-led appointments. Survivors (n = 24) without appointments were recruited by post. Questionnaires included HRQoL, late effects, perceived vulnerability, issues survivors wanted to discuss and reported discussing in clinic, time waiting in clinic and consultation satisfaction. RESULTS: There were no gender differences in number of self-reported late effects or perceived vulnerability. Men with more late effects reported worse psychological HRQoL (r = 0.50, p<0.001). While men wanted to discuss more topics than they did, women were able to discuss the topics they wanted (ANOVA, p = 0.01). Multiple regression analyses showed a shorter wait in clinic (r = -0.46, p = 0.009) and discussing more topics (r = 0.34, p = 0.06) explained 30.6% of the variance in consultation satisfaction for men. CONCLUSIONS: Issues surrounding follow-up provision are increasingly important given the length of survival in young adults following treatment for lymphoma. Men may experience poor psychological well-being due to distress about unanswered concerns. Consideration of their concerns should be prioritised, given that satisfaction and ultimately continued attendance at clinic and HRQoL may be dependent on the extent to which follow-up meets survivors' expectations.

Follow-up care for cancer survivors: views of the younger adult.

BACKGROUND: Since the launch of the National Cancer Survivorship Initiative, there has been a surge of interest surrounding the value and organisation of long-term follow-up care after cancer treatment. We report the views of 309 adult cancer survivors (aged 18-45 years) on provision of follow-up and preferences for care. METHODS: A total of 207 survivors completed questionnaires before and after routine consultant-led follow-up appointments and 102 were recruited by post. Measures of health status (including late effects, perceived vulnerability to late effects and quality of life), reasons for attending follow-up (clinical and supportive), issues to be discussed at follow-up and preferences for different models of care were assessed. RESULTS: In all, 59% of the survivors reported experiencing one or more cancer-related health problems. Survivors rated clinical reasons for attending follow-up more highly than supportive reasons (P<0.001), although nutritional advice and counselling were considered useful (60 and 47%, respectively). Those still receiving scheduled follow-up appointments did not discuss the range of issues intended with 'late effects' and 'fertility', which were particularly under-discussed. Hospital rather than GP follow-up was more highly rated. CONCLUSION: Survivors value the clinical reassurance currently provided by consultant-led care. However, supportive needs are not systematically addressed. Multi-disciplinary services are recommended to meet supportive needs in addition to clinical care.

Follow-up care for cancer survivors: the views of clinicians.

BACKGROUND: Evidence for the efficacy of late effects surveillance in adult cancer survivors is lacking and there is little agreement among clinicians on appropriate follow-up care. METHODS: We report the views of both cancer experts and general practitioners (GPs) on long-term follow-up provision for cancer survivors, focussing on the 18-45 years age group. A total of 421 cancer experts (36% haematologists, 33% oncologists, 18% surgeons, 10% nurses, 2% other) and 54 GPs responded to a structured online survey. Reasons for follow-up care (clinical or supportive); advantages and disadvantages of follow-up in primary care; current practice; and resources required for a quality follow-up service were assessed. RESULTS: Clinicians valued clinical reasons for follow-up more highly than supportive reasons (P<0.001). Learning more about late effects and checking for cancer recurrence were rated as the most important reasons for follow-up by cancer experts and GPs. A total of 85% of cancer specialists hold follow-up consultations alongside patients on active treatment. Cancer experts agreed that primary care follow-up would increase their availability for acute oncological care, but reduce information on late effects. The most important resource to provide a quality follow-up service was specialist nursing support (91%). CONCLUSIONS: Follow-up guidelines that include late effects surveillance are needed. Where and who should deliver this care requires further debate.

Follow-up care after childhood cancer: survivors' expectations and preferences for care.

AIMS: To describe (1) self-rated quality of life, late effects and perceived future vulnerability, (2) expectations before a follow-up appointment, subsequent satisfaction and preferences for different models of care and (3) differences between survivors in quality of life, perceived late effects, vulnerability, expectations regarding follow-up, information needs (topics they want to and did discuss) and preferences for different models of care depending on risk stratification among childhood cancer survivors. METHOD: One hundred and twelve of 141 survivors (18-45 years), diagnosed before 16 years and >5 years since diagnosis completed questionnaires before and after a follow-up appointment (or an abridged questionnaire if they did not attend an appointment within the study period). We collected data on physical (physical component score [PCS]) and mental (mental component score [MCS]) quality of life, late effects, future vulnerability and expectations about care (clinical: identification of late effects; supportive: employment, relationships). Medical information was extracted from case notes. RESULTS: MCS and PCS were comparable to population norms, but 55.5% of survivors reported > or =1 late effect (range 1-9). Clinical care was rated more highly than supportive care (p<0.001) especially in those with worse PCS (p=0.042). Supportive care was rated highly by survivors who reported more late effects (p=0.040), higher future vulnerability (p<0.001) and lower MCS (p=0.005), and by women (p=0.014). Regardless of risk stratification, consultant-led follow-up was valued higher than other models (nurse-led care, GP-led care or postal/telephone follow-up, p<0.001). CONCLUSION: Childhood cancer survivors are in favour of sustaining long-term follow-up care within the existing consultant-led model but this is not feasible given the increasing number of survivors. In the future we therefore need to develop alternative services which will provide the best medical care for each survivor's needs.

Prevalence and consequences of androgen deficiency in young male cancer survivors in a controlled cross-sectional study.

BACKGROUND: Testosterone replacement in hypogonadal males improves body composition, sexual function, and health-related quality of life. Male cancer survivors are at risk of androgen deficiency; however, when and in whom testosterone should be replaced remain unanswered questions. OBJECTIVE: The aim of our study was to define the prevalence of androgen deficiency in this patient group through assessment of testosterone levels and related measures. DESIGN: This was a cross-sectional, observational study of cases and controls. We recruited 176 cancer survivors and 213 controls, aged 25-45 yr. RESULTS: Of cancer survivors, 97% had received chemotherapy and 40% radiotherapy. Cancer survivors had lower total testosterone (tT) levels than controls (mean difference 2.67 nmol/liter; 95% confidence interval 1.58-3.76; P = 0.003), and 24 of 176 (13.6%; 95% confidence interval 9.3-19.5) had a tT less than 10 nmol/liter, which was less than 2.5% centile for controls. Cancer survivors had a greater fat mass, higher fasting insulin and glucose levels, increased fatigue, and reduced sexual function and health-related quality of life. In both cohorts, the tT correlated negatively with insulin levels and negatively with body fat mass; however, the difference in tT between them was independent of fat mass. We measured tT and SHBG and calculated bioavailable testosterone. The changes in calculated bioavailable testosterone were similar to tT. CONCLUSIONS: A significant proportion of young male cancer survivors had a frankly low tT associated with an increased fat mass and insulin level compared with controls. These factors would be predicted to improve in response to testosterone replacement therapy and provide a powerful argument for an interventional study of testosterone therapy in young male cancer survivors.

High incidence of late effects found in Hodgkin's lymphoma survivors, following recall for breast cancer screening.

Assessment of late effects in a cohort of female Hodgkin's lymphoma patients treated with mantle radiotherapy, identified from the DoH breast cancer screening recall showed high mortality and frequent undiagnosed abnormalities in tissues affected by radiotherapy. With increasing age, this patient group may suffer premature cardiac and respiratory morbidity.

Direct correlation between diffusion of Loxosceles reclusa venom and extent of dermal inflammation.

OBJECTIVES: Envenomation by Loxosceles species (brown recluse) spiders results in large dermal inflammatory lesions. Venom-induced dermal inflammation occurs indirectly via soluble mediators of inflammation. This study aimed to explore whether the anatomic extent of dermonecrotic arachnidism is due to the cascade of soluble proinflammatory mediators elicited by venom deposited at the bite site, or due to diffusion of the venom per se. METHODS: Three New Zealand white rabbits received intradermal L. reclusa venom (3-microg) injections in the flank. At the time of maximum dermal inflammation (24 hr), paired 4-mm dermal biopsies were obtained in 2-cm intervals extending 0 to 12 cm from the inoculation site. Normal dermal tissue was obtained from the opposite flank to serve as a negative control. One biopsy sample from each interval was homogenized and assayed for myeloperoxidase (MPO) activity and for the presence of venom via an enzyme immunoassay (EIA). The other paired dermal biopsy was sectioned, and examined for the presence of polymorphonuclear neutrophils (PMNs) by microscopy. Lesional areas were measured using digital images imported into imaging software. RESULTS: Mean +/- SD lesional diameter 24 hours post inoculation measured 9.18 +/- 0.64 cm. Venom was detected in biopsies 0 to 10 cm from the injection site. As expected, the highest venom concentrations were measured at the inoculation site (4.28 +/- 3.9 ng/4 mm). In addition, PMNs and MPO were detected up to 8 and 10 cm from the inoculation site, respectively. Neither PMNs nor MPO was detected in tissue absent of venom (kappa = 0.88, p < 0.001). CONCLUSIONS: Loxosceles venom diffuses from the envenomation site. The extent of dermal inflammation mirrors the extent of Loxosceles venom diffusion. This observation implies that the venom itself defines the extent and magnitude of tissue injury following Loxosceles envenomation.

Risk factors for ankle fracture.

Ankle fractures are frequently observed in postmenopausal women although the pattern of incidence and risk factor profile suggest that ankle fracture may not be a typical osteoporotic fracture. The aims of this study were to determine the prevalence of osteopenia and vertebral fracture and to evaluate the diagnostic accuracy of dual-energy X-ray absorptiometry (DXA), anthropometry, lifestyle and reproductive factors in women who have sustained an ankle fracture. We studied 103 women aged 50-80 years (mean 63.2, 7.9 SD) with ankle fracture. These were compared with 375 women aged 50-86 years (mean 64.5, 9.1 SD) from a population-based cohort. Bone mineral density (BMD) at the lumbar spine (LS) and contralateral proximal femur (including femoral neck (FN), Ward's triangle (WT) and trochanteric region (TR)) was measured by DXA. Quantitative ultrasound (QUS) of the calcaneus and proximal digits was measured using three different devices. Radiographs of the thoracolumbar spine were taken (anteroposterior and lateral views). There were no significant differences in the prevalence of osteoporosis (T<-2.5 level) at the LS, FN and WT sites. The population-based cohort had lower TR BMD than the ankle fracture cohort. Age-and weight-adjusted Z-scores of FN BMD were significantly lower in the ankle fracture group. Age- and weight-adjusted Z-scores of QUS gave contradictory results. There were no differences in the receiver operating characteristics of DXA compared with QUS. Twenty-seven women (7%) of the population-based cohort and 10 women (10%) of the ankle fracture cohort were found to have prevalent vertebral fractures; these were not significantly different.