Modifiable pre-treatment factors are associated with quality of life in women with gynaecological cancers at diagnosis and one year later: Results from the HORIZONS UK national cohort study.

OBJECTIVE: Personalised care requires the identification of modifiable risk factors so that interventions can be implemented rapidly following a gynaecological cancer diagnosis. Our objective was to determine what pre-treatment factors are associated with quality of life (QOL) at baseline (pre-treatment) and 12 months. METHODS: 1222 women with a confirmed diagnosis of endometrial, ovarian, cervical or vulvar cancer from 82 UK NHS hospitals agreed to complete questionnaires at baseline, three and 12 months. Questionnaires included measures of QOL, health, lifestyle, support and self-management. The primary outcome measure was QOL as measured by Quality of Life in Adult Cancer Survivors (QLACS). Sites provided clinical data at baseline, six and 12 months. Linear regression models were constructed to examine the association between baseline characteristics and QOL outcomes. RESULTS: QOL declined between baseline and 3 months, followed by an improvement at 12 months. Baseline (pre-treatment) factors associated with worse QOL at both baseline and 12 months were depression, anxiety, living in a more deprived area and comorbidities which limit daily activities, whereas higher self-efficacy and age of 50+ years were associated with better QOL. CONCLUSIONS: Depression, anxiety and self-efficacy are modifiable risk factors that can impact on QOL. Screening for these, and assessment of whether comorbidities limit daily activities, should be incorporated in a holistic needs assessment and interventions to improve self-efficacy should be made available. Care can then be personalised from the outset to enable all women with a gynaecological cancer the opportunity to have the best QOL.

A peer-delivered intervention to reduce harm and improve the well-being of homeless people with problem substance use: the SHARPS feasibility mixed-methods study.

BACKGROUND: For people experiencing homelessness and problem substance use, access to appropriate services can be challenging. There is evidence that development of trusting relationships with non-judgemental staff can facilitate service engagement. Peer-delivered approaches show particular promise, but the evidence base is still developing. This study tested the feasibility and acceptability of a peer-delivered intervention, through 'Peer Navigators', to support people who are homeless with problem substance use to address a range of health and social issues. OBJECTIVES: The study objectives were to design and implement a peer-delivered, relational intervention to reduce harms and improve health/well-being, quality of life and social functioning for people experiencing homelessness and problem substance use, and to conduct a concurrent process evaluation to inform a future randomised controlled trial. DESIGN: A mixed-methods feasibility study with concurrent process evaluation was conducted, involving qualitative interviews [staff interviews (one time point), n = 12; Peer Navigator interviews (three or four time points), n = 15; intervention participant interviews: first time point, n = 24, and second time point, n = 10], observations and quantitative outcome measures. SETTING: The intervention was delivered in three outreach services for people who are homeless in Scotland, and three Salvation Army hostels in England; there were two standard care settings: an outreach service in Scotland and a hostel in England. PARTICIPANTS: Participants were people experiencing homelessness and problem substance use (n = 68) (intervention). INTERVENTION: This was a peer-delivered, relational intervention drawing on principles of psychologically informed environments, with Peer Navigators providing practical and emotional support. MAIN OUTCOME MEASURES: Outcomes relating to participants' substance use, participants' physical and mental health needs, and the quality of Peer Navigator relationships were measured via a 'holistic health check', with six questionnaires completed at two time points: a specially created sociodemographic, health and housing status questionnaire; the Patient Health Questionnaire-9 items plus the Generalised Anxiety Disorder-7; the Maudsley Addiction Profile; the Substance Use Recovery Evaluator; the RAND Corporation Short Form survey-36 items; and the Consultation and Relational Empathy Measure. RESULTS: The Supporting Harm Reduction through Peer Support (SHARPS) study was found to be acceptable to, and feasible for, intervention participants, staff and Peer Navigators. Among participants, there was reduced drug use and an increase in the number of prescriptions for opioid substitution therapy. There were reductions in risky injecting practice and risky sexual behaviour. Participants reported improvements to service engagement and felt more equipped to access services on their own. The lived experience of the Peer Navigators was highlighted as particularly helpful, enabling the development of trusting, authentic and meaningful relationships. The relationship with the Peer Navigator was measured as excellent at baseline and follow-up. Some challenges were experienced in relation to the 'fit' of the intervention within some settings and will inform future studies. LIMITATIONS: Some participants did not complete the outcome measures, or did not complete both sets, meaning that we do not have baseline and/or follow-up data for all. The standard care data sample sizes make comparison between settings limited. CONCLUSIONS: A randomised controlled trial is recommended to assess the effectiveness of the Peer Navigator intervention. FUTURE WORK: A definitive cluster randomised controlled trial should particularly consider setting selection, outcomes and quantitative data collection instruments. TRIAL REGISTRATION: This trial is registered as ISRCTN15900054. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 14. See the NIHR Journals Library website for further project information.

People who are homeless have worse physical and mental health, and higher rates of drug/alcohol (substance) use, than the general population. For people experiencing these challenges, completely stopping the use of substances can be difficult. Harm reduction services can be useful in reducing risks. Approaches delivered by people who have had similar experiences (peers) are also promising. Some research has highlighted the importance of trusting relationships with service staff. More research is needed on how all of these should work with people who are homeless and who use substances. This study consisted of four 'Peer Navigators' providing practical and emotional support to a group of people who are homeless and use substances to help improve their quality of life and health. The Peer Navigators had similar past experiences. The Peer Navigators were hired, and worked with around 15 'participants' each, for 2­12 months. They were based in third-sector homelessness residential and outreach services in Scotland and England. The Peer Navigators developed relationships with participants. They worked with (and often accompanied) them to access services, such as substance use treatment, health care, housing and welfare/benefits. The Peer Navigators had access to a small budget to pay for essentials, including food and bus fares. The relationship between the Peer Navigators and participants was most important, so the Peer Navigators spent time getting to know and listening to them. The aim was to understand if this intervention could be delivered to individuals experiencing these challenges. This study was not designed to know if the intervention worked; a larger study is needed for that. Despite some challenges, the participants were able to make positive changes to their lives, and they valued working with their Peer Navigator. The Peer Navigators enjoyed their roles and staff generally supported the intervention. The next step is to conduct more research to assess if this intervention can make a difference.

Assessing the feasibility, acceptability and accessibility of a peer-delivered intervention to reduce harm and improve the well-being of people who experience homelessness with problem substance use: the SHARPS study.

BACKGROUND: For people experiencing homelessness and problem substance use, access to appropriate services can be challenging. There is evidence that the development of trusting relationships with non-judgemental staff can facilitate service engagement. Peer-delivered approaches show particular promise, but the evidence base is still developing. METHODS: The study used mixed methods to assess the feasibility, acceptability and accessibility of a peer-delivered, relational intervention to reduce harms and improve health/well-being, quality of life and social functioning, for people experiencing homelessness and problem substance use. Four Peer Navigators were employed to support individuals (n = 68 total, intervention participants). They were based in outreach services and hostels in Scotland and England. Qualitative interviews were conducted with intervention participants, Peer Navigators and staff in services, and observations were conducted in all settings. Quantitative outcomes relating to participants' substance use, physical and mental health, and quality of the Peer Navigator relationship, were measured via a 'holistic health check' with six questionnaires completed at two time-points. RESULTS: The intervention was found to be acceptable to, and feasible and accessible for, participants, Peer Navigators, and service staff. Participants reported improvements to service engagement, and feeling more equipped to access services independently. The lived experience of the Peer Navigators was highlighted as particularly helpful, enabling trusting, authentic, and meaningful relationships to be developed. Some challenges were experienced in relation to the 'fit' of the intervention within some settings. Among participants there were reductions in drug use and risky injecting practices. There were increases in the number of participants receiving opioid substitution therapy. Overall, the intervention was positively received, with collective recognition that the intervention was unique and highly valuable. While most of the measures chosen for the holistic health check were found to be suitable for this population, they should be streamlined to avoid duplication and participant burden. CONCLUSIONS: The study established that a peer-delivered, relational harm reduction intervention is acceptable to, and feasible and accessible for, people experiencing homelessness and problem substance use. While the study was not outcomes-focused, participants did experience a range of positive outcomes. A full randomised controlled trial is now required to assess intervention effectiveness. TRIAL REGISTRATION: Study registered with ISRCTN: 15900054.

Understanding the support needs of family members of people undergoing chemotherapy: A longitudinal qualitative study.

PURPOSE: Capture change in family members' experiences as they look after patients during chemotherapy, and understand variability in their needs for support. METHOD: Longitudinal digitally-recorded qualitative semi-structured interviews with family carers at the beginning, mid-point, and end of treatment. Twenty-five family members (17 women, 8 men), mean age 53, were interviewed. Fifteen participants were supporting a relative having chemotherapy with curative intent, and 10 a patient receiving palliative chemotherapy. They were recruited from two UK locations: a regional cancer centre in Southampton and a comprehensive cancer centre in London. Sixty-three interviews were conducted in total, and the data were analysed using Framework Analysis. RESULTS: Three themes were generated from the data: Changing lives, Changing roles; Confidence in caring, and Managing uncertainty. These captured family carers' evolving needs and sense of confidence in caregiving during chemotherapy. Carers reported considerable anxiety at the outset of treatment which persisted throughout. Anxiety was underpinned by fears of disease recurrence or progression and concerns about treatment outcomes. CONCLUSIONS: This study presents original fine-grained work that captures the changes over time in family carers' experiences of chemotherapy and their adaptation to caregiving. It provides fundamental evidence of the challenges that cancer carers face during patients' treatment; evidence that can be used as a basis for carer assessment and to build much-needed carer interventions. Oncology nurses should assess carers': ability to care; needs for information and support to prepare them for this; wellbeing over time; and, any support they may require to prevent them from becoming overburdened.

Supporting Harm Reduction through Peer Support (SHARPS): testing the feasibility and acceptability of a peer-delivered, relational intervention for people with problem substance use who are homeless, to improve health outcomes, quality of life and social functioning and reduce harms: study protocol.

BACKGROUND: While people who are homeless often experience poor mental and physical health and problem substance use, getting access to appropriate services can be challenging. The development of trusting relationships with non-judgemental staff can facilitate initial and sustained engagement with health and wider support services. Peer-delivered approaches seem to have particular promise, but there is limited evidence regarding peer interventions that are both acceptable to, and effective for, people who are homeless and using drugs and/or alcohol. In the proposed study, we will develop and test the use of a peer-to-peer relational intervention with people experiencing homelessness. Drawing on the concept of psychologically informed environments, it will focus on building trusting and supportive relationships and providing practical elements of support such as access to primary care, treatment and housing options. METHODS: A mixed-method feasibility study with concurrent process evaluation will be conducted to explore the feasibility and acceptability of a peer-delivered, relational intervention for people with problem substance use who are homeless. Peer Navigators will be based in homelessness outreach and residential services in Scotland and England. Peer Navigators will work with a small number of participants for up to 12 months providing both practical and emotional support. The sample size for the intervention is 60. Those receiving the intervention must be currently homeless or at risk of homelessness, over the age of 18 years and self-report alcohol/drug problems. A holistic health check will be conducted in the first few months of the intervention and repeated towards the end. Health checks will be conducted by a researcher in the service where the Peer Navigator is based. Semi-structured qualitative interviews with intervention participants and staff in both intervention and standard care settings, and all Peer Navigators, will be conducted to explore their experiences with the intervention. Non-participant observation will be conducted in intervention and standard care sites to document similarities and differences between care pathways. DISCUSSION: The SHARPS study will provide evidence regarding whether a peer-delivered harm reduction intervention is feasible and acceptable to people experiencing homelessness and problem substance use in order to develop a definitive trial. TRIAL REGISTRATION: SRCTN registry ISRCTN15900054, protocol version 1.3, March 12, 2018.

Follow-up care after treatment for prostate cancer: evaluation of a supported self-management and remote surveillance programme.

BACKGROUND: Alternative models of cancer follow-up care are needed to ameliorate pressure on services and better meet survivors' long-term needs. This paper reports an evaluation of a service improvement initiative for the follow-up care of prostate cancer patients based on remote monitoring and supported self-management. METHODS: This multi-centred, historically controlled study compared patient reported outcomes of men experiencing the new Programme with men experiencing a traditional clinic appointment model of follow-up care, who were recruited in the period immediately prior to the introduction of the Programme. Data were collected by self-completed questionnaires, with follow up measurement at four and eight months post-baseline. The primary outcome was men's unmet survivorship needs, measured by the Cancer Survivors' Unmet Needs Survey. Secondary outcomes included cancer specific quality of life, psychological wellbeing and satisfaction with care. The analysis was intention to treat. Regression analyses were conducted for outcomes at each time point separately, controlling for pre-defined clinical and demographic variables. All outcome analyses are presented in the paper. Costs were compared between the two groups. RESULTS: Six hundred and twenty-seven men (61%) were consented to take part in the study (293 in the Programme and 334 in the comparator group.) Regarding the primary measure of unmet survivorship needs, 25 of 26 comparisons favoured the Programme, of which 4 were statistically significant. For the secondary measures of activation for self-management, quality of life, psychological well-being and lifestyle, 20 of 32 comparisons favoured the Programme and 3 were statistically significant. There were 22 items on the satisfaction with care questionnaire and 13 were statistically significant. Per participant costs (British pounds, 2015) in the 8 month follow up period were slightly lower in the programme than in the comparator group (£289 versus £327). The Programme was acceptable to patients. CONCLUSION: The Programme is shown to be broadly comparable to traditional follow-up care in all respects, adding to evidence of the viability of such models.

Follow-up care after treatment for prostate cancer: protocol for an evaluation of a nurse-led supported self-management and remote surveillance programme.

BACKGROUND: As more men survive a diagnosis of prostate cancer, alternative models of follow-up care that address men's enduring unmet needs and are economical to deliver are needed. This paper describes the protocol for an ongoing evaluation of a nurse-led supported self-management and remote surveillance programme implemented within the secondary care setting. METHODS/DESIGN: The evaluation is taking place within a real clinical setting, comparing the outcomes of men enrolled in the Programme with the outcomes of a pre-service change cohort of men, using a repeated measures design. Men are followed up at four and 8 months post recruitment on a number of outcomes, including quality of life, unmet need, psychological wellbeing and activation for self-management. An embedded health economic analysis and qualitative evaluation of implementation processes are being undertaken. DISCUSSION: The evaluation will provide important information regarding the effectiveness, cost effectiveness and implementation of an integrated supported self-management follow-up care pathway within secondary care.

Vascular Endothelial Growth Factor-A165b Is Protective and Restores Endothelial Glycocalyx in Diabetic Nephropathy.

Diabetic nephropathy is the leading cause of ESRD in high-income countries and a growing problem across the world. Vascular endothelial growth factor-A (VEGF-A) is thought to be a critical mediator of vascular dysfunction in diabetic nephropathy, yet VEGF-A knockout and overexpression of angiogenic VEGF-A isoforms each worsen diabetic nephropathy. We examined the vasculoprotective effects of the VEGF-A isoform VEGF-A165b in diabetic nephropathy. Renal expression of VEGF-A165b mRNA was upregulated in diabetic individuals with well preserved kidney function, but not in those with progressive disease. Reproducing this VEGF-A165b upregulation in mouse podocytes in vivo prevented functional and histologic abnormalities in diabetic nephropathy. Biweekly systemic injections of recombinant human VEGF-A165b reduced features of diabetic nephropathy when initiated during early or advanced nephropathy in a model of type 1 diabetes and when initiated during early nephropathy in a model of type 2 diabetes. VEGF-A165b normalized glomerular permeability through phosphorylation of VEGF receptor 2 in glomerular endothelial cells, and reversed diabetes-induced damage to the glomerular endothelial glycocalyx. VEGF-A165b also improved the permeability function of isolated diabetic human glomeruli. These results show that VEGF-A165b acts via the endothelium to protect blood vessels and ameliorate diabetic nephropathy.

Multiple metabolic alterations exist in mutant PI3K cancers, but only glucose is essential as a nutrient source.

Targeting tumour metabolism is becoming a major new area of pharmaceutical endeavour. Consequently, a systematic search to define whether there are specific energy source dependencies in tumours, and how these might be dictated by upstream driving genetic mutations, is required. The PI3K-AKT-mTOR signalling pathway has a seminal role in regulating diverse cellular processes including cell proliferation and survival, but has also been associated with metabolic dysregulation. In this study, we sought to define how mutations within PI3KCA may affect the metabolic dependency of a cancer cell, using precisely engineered isogenic cell lines. Studies revealed gene expression signatures in PIK3CA mutant cells indicative of a consistent up-regulation of glycolysis. Interestingly, the genes up- and down-regulated varied between isogenic models suggesting that the primary node of regulation is not the same between models. Additional gene expression changes were also observed, suggesting that metabolic pathways other than glycolysis, such as glutaminolysis, were also affected. Nutrient dependency studies revealed that growth of PIK3CA mutant cells is highly dependent on glucose, whereas glutamine dependency is independent of PIK3CA status. In addition, the glucose dependency exhibited by PIK3CA mutant cells could not be overridden by supplementation with other nutrients. This specific dependence on glucose for growth was further illustrated by studies evaluating the effects of targeted disruption of the glycolytic pathway using siRNA and was also found to be present across a wider panel of cancer cell lines harbouring endogenous PIK3CA mutations. In conclusion, we have found that PIK3CA mutations lead to a shift towards a highly glycolytic phenotype, and that despite suggestions that cancer cells are adept at utilising alternative nutrient sources, PIK3CA mutant cells are not able to compensate for glucose withdrawal. Understanding the metabolic dependencies of PIK3CA mutant cancers will provide critical information for the design of effective therapies and tumour visualisation strategies.