Can proactive support prevent unscheduled care? A controlled observational retrospective cohort study in cancer patients in Scotland.

INTRODUCTION: Preventative spend is a global health and social care strategy. Improving Cancer Journeys (ICJ) is a proactive, holistic, multidisciplinary project consistent with this agenda, currently being rolled out across Scotland and parts of UK. ICJ helps people with cancer access whatever support they need to mitigate their most pressing concerns. This study hypothesised that ICJ service users should subsequently use less unscheduled care than matched cohorts not using ICJ. METHODS: Retrospective observational cohort study using linked national datasets. N = 1,214 ICJ users in Glasgow were matched for age, sex, deprivation, cancer type, stage, and diagnosis year to two control groups: 1. Cancer patients from Glasgow before ICJ (pre-2014), 2. Cancer patients from rest of Scotland during study period (2014-2018). Cancer registrations were linked for 12-month baseline and study periods to: NHS24 calls, A&E admissions, inpatient hospital admissions, unscheduled care, number & cost of psychotropic prescriptions. Per-person mean service uses were compared between groups. RESULTS: There was a significant increase in NHS24 calls in the ICJ group (0.36 per person vs. -0.03 or 0.35), more and longer A&E attendances in ICJ (0.37 per person vs. 0.19 or 0.26; 2.19 h per person vs. 0.81-0.92 h), more and longer hospital admissions in ICJ (4.25 vs. 2.59 or 2.53; 12.05 days vs. 8.37 or 8.64), more care pathways involving more steps in ICJ (0.77 spells vs. 0.39 or 0.57; 1.88 steps vs. 1.56 or 1.21), more psychotropic drug prescriptions and higher costs in ICJ (1.88 prescription vs. 1.56 or 1.21; £9.51 vs. £9.57 or £6.95) in comparison to both control groups. DISCUSSION: ICJ users sourced significantly more unscheduled care than matched cohorts. These findings were consistent with much of the comparable literature examining the impact of non-health interventions on subsequent health spend. They also add to the growing evidence showing that ICJ reached its intended target, those with the greatest need. Together these findings raise the possibility that those choosing to use ICJ may also be self-identifying as a cohort of people more likely to use unscheduled care in future. This needs to be tested prospectively, because this understanding would be very helpful for health and social care planners in all countries where proactive holistic services exist.

Holistic needs assessment in outpatient cancer care: a randomised controlled trial.

DESIGN: Analyst blinded, parallel, multi-centre, randomised controlled trial (RCT). PARTICIPANTS: People with confirmed diagnoses of cancer (head and neck, skin or colorectal) attending follow-up consultation 3 months post-treatment between 2015 and 2020. INTERVENTION: Holistic needs assessment (HNA) or care as usual during consultation. OBJECTIVE: To establish whether incorporating HNA into consultations would increase patient participation, shared decision making and postconsultation self-efficacy. OUTCOME MEASURES: Patient participation in the consultations examined was measured using (a) dialogue ratio (DR) and (b) the proportion of consultation initiated by patient. Shared decision making was measured with CollaboRATE and self-efficacy with Lorig Scale. Consultations were audio recorded and timed. RANDOMISATION: Block randomisation. BLINDING: Audio recording analyst was blinded to study group. RESULTS: 147 patients were randomised: 74 control versus 73 intervention. OUTCOME: No statistically significant differences were found between groups for DR, patient initiative, self-efficacy or shared decision making. Consultations were on average 1 min 46 s longer in the HNA group (respectively, 17 m 25 s vs 15 min 39 s). CONCLUSION: HNA did not change the amount of conversation initiated by the patient or the level of dialogue within the consultation. HNA did not change patient sense of collaboration or feelings of self-efficacy afterwards. HNA group raised more concerns and proportionally more emotional concerns, although their consultations took longer than treatment as usual. IMPLICATIONS FOR PRACTICE: This is the first RCT to test HNA in medically led outpatient settings. Results showed no difference in the way the consultations were structured or received. There is wider evidence to support the roll out of HNA as part of a proactive, multidisciplinary process, but this study did not support medical colleagues facilitating it. TRIAL REGISTRATION NUMBER: NCT02274701.

Men's perspectives of caring for a female partner with cancer: A longitudinal narrative study.

Increasing evidence on men's involvement in informal, unpaid care has not transferred to the research literature around men's experiences. The aim was to explore the perspectives of men who are caring for a female partner with cancer over 1 year. Longitudinal narrative interviews (n = 22) were conducted with eight men in the UK from 2018 to 2019. Participants were aged from 32 to 76 years old, were all white British and in heterosexual relationships with women diagnosed with a range of cancer types. Interviews were transcribed and then analysed using a structural and performance approach to narrative analysis. We present, across four scenes, a process of change, transition and emotion management as the men were launched into a role that came with new responsibilities and expectations. Our study advances knowledge by highlighting the way that men perform and reflect on their negotiation with masculine discourses while supporting their partner, with implications for policy, research and practice.

Meeting psychosocial needs to improve health: a prospective cohort study.

BACKGROUND: Cancer impacts on patients and their families across a range of different domains. For that reason, optimal cancer care has moved away from a disease-centric focus to a more holistic approach in order to proactively support people with their individual needs and concerns. While international policy clearly advocates this agenda, implementation into routine care is limited. Therefore, relevant interventions that measurably improve patient outcomes are essential to understand if this ideal is to become routine multidisciplinary practice. The aim of this study was to analyse the impact of a proactive, holistic, community-based intervention on health-related quality of life in a cohort of people diagnosed with cancer. Secondary aim was to explore the relationship between changes in health status and: cancer type, cancer stage, number of concerns expressed and change in severity of concerns pre and post intervention. METHOD: Prospective observational cohort study. A convenience sample of 437 individuals were referred to the service 'Improving the Cancer Journey (ICJ) in the UK. Each completed the Euroqol EQ-5D-3 L and visual analogue scale (VAS) and a Holistic Needs Assessment (HNA) during initial visit to the service and again at follow-up review, median 84 days later. Change between scores was tested with paired t-tests and relationships between variables with multiple regression models with heteroscedasticity-consistent standard errors. RESULTS: Participants were White British with median age between 50 and 64 years. Cancer type and stage were varied. EQ-5D utility scores improved at follow-up by 0.121 [0.0891-0.153], p < .001, and VAS scores improved by 7.81 [5.88-9.74], p < .001. The strongest predictor of change was a decrease in severity of concerns. Cancer stage 'palliative care' contributed to a reduction in health status. CONCLUSION: This study is the first to show that a holistic community intervention dedicated to supporting the individual concerns of participants had both a statistically significant and clinically meaningful impact on participants' health-related quality of life. The mean change in EQ-5D scores was more than the 'minimally important clinical difference' described in the literature. This is important because while quality of life has multiple determinants, this study has shown for the first time that it is possible to capture a clinically meaningful improvement as a function of reducing someone's personally identified concerns.

A J curve of interprofessional change: co-locating non-health partners in an oncology unit.

BACKGROUND: Internationally, clinicians face increased demand, pressure on resources and unmet patient needs. A community social support service was co-located within cancer clinics in Glasgow, Scotland to help address some of these needs. AIM: To analyse the impact of the service on clinical staff and to propose an explanatory theory of change. METHOD: Qualitative exploratory design, using thematic analysis of semistructured interviews with 8 nurse specialists and 2 medical oncologists from lung, breast, head and neck, and gastrointestinal oncology teams in Glasgow in 2018-2019. FINDINGS: Four themes captured this process: 'The conversation', 'A better experience', 'Freedom to focus' and 'Working hand in hand'. CONCLUSION: Together, these four themes explained the process of effective interprofessional working. This process would have been predicted by the J-curve literature on diffusion of innovations. Linking J-curve theory to this successful process provides new understanding that could prove essential for clinical teams who are implementing change within their practice.

The implementation and impact of Holistic Needs Assessments for people affected by cancer: A systematic review and thematic synthesis of the literature.

OBJECTIVE: Globally, cancer services herald the use of Holistic Needs Assessments (HNA). Implementation is, however, heterogeneous. There is a need to understand what effect implementation variation has on patient experience, outcomes and service demand. This is the first study to examine whether the way in which HNA is implemented, impacts on patient outcomes. METHODS: MEDLINE, AMED, CINAHL, PsycINFO and the Psychological and Behavioural Sciences Collection were searched (June 2000-June 2018). Search strategy included international HNA tools and synonyms for "needs." An overview of quality was obtained through application of the Mixed Methods Appraisal Tool. Key themes were identified through thematic synthesis. RESULTS: Twenty studies were included (RCTs [n = 4], service evaluations [n = 8] and feasibility studies [n = 8]). Implementation approaches and assessor actions were identified and through thematic synthesis were defined as detecting, discussing/dealing, directing and downstream care. The way in which HNA is implemented is more important to understanding outcomes than what is implemented. CONCLUSION: There is a need to conceptualise HNA as a means and not an end in itself. Pursuers of HNA-led outcomes must understand and strengthen connections between assessment and outcomes. The conceptual framework can assist development of more insightful measures of both process and outcomes.

A qualitative study on the perceived impact of using an integrated community-based supportive cancer service.

OBJECTIVE: "Improving the Cancer Journey" (ICJ) is an original, community-based, multidisciplinary service offering holistic support to people diagnosed with cancer in Scotland. It is the first service of its kind in the UK. The aim of this qualitative study was to explore the experiences of people who have used this service. METHOD: Twenty service users were purposively sampled to capture a diverse range of age, sex, cancer types, and deprivation status. Semi-structured interviews explored their experiences of using ICJ. Interviews were transcribed verbatim and thematically analysed. RESULTS: Thirteen women and seven men (mean age 58 years) were interviewed. Three themes were identified: "one person, one place," "routes to unexpected support" and "safety net." CONCLUSION: Improving the Cancer Journey was perceived to be beneficial because it met the holistic needs of the ICJ service users. By helping people address concerns earlier rather than later, it prevented problems becoming unmanageable. Having an accessible expert to guide and support them through a range of services provided reassurance and created the space to self-manage at a time of distress. These original findings are internationally relevant because there is little evidence on the impact of holistic support services from the patient perspective.

Proactive community support tailored to holistic needs: A cohort study.

BACKGROUND: It is increasingly internationally recognized that a cancer diagnosis impacts on people practically and financially as well as physically and psychologically. It is less clear what to do about this. This study introduces an original community service designed to mitigate this wider impact. Nonclinical "link officers" use holistic needs assessment (HNA) to help newly diagnosed people identify and quantify the severity of their physical, psychological, practical, financial, and social concerns. A care plan is then agreed, usually involving community interventions from partner agencies. Following intervention, assessment is repeated. The primary aim of this study was to establish whether there was a significant difference between initial assessment and follow-up, postintervention. Secondary aim was to identify potential predictors of increased levels of concern at baseline and follow-up. METHOD: Pre- and postintervention observational cohort study. Paired t test examined the difference in mean (SD) concern severity between baseline and follow-up. Multiple linear regression models were computed to hypothesize potential predictors of initial concern severity and severity change. RESULTS: The service saw 2413 people 2014-2017. Participants identified average 5.5 (4.7) concerns, financial concerns being most frequent. Mean severity at baseline was 7.12 (out of 10) (2.50), reducing to 3.83 (3.49) post-treatment, paired t(4454) = 64.68, P < 0.0001, reduction of 3.31 (95% CI 3.21-3.41). Factors associated with higher initial concern included unemployment and caring responsibilities. Unemployment was also associated with a smaller reduction of concern severity at follow-up. CONCLUSION: Patient level of concern went from a level associated with specialist referral to a much more manageable level. This original finding is internationally significant because it extends Khera et al's (2017) "provocative idea" that all patients should be screened for financial problems to show that they can be helped with all their concerns. This article describes a successful, transferable model of community care.

Protocol for a mixed methods longitudinal enquiry into the impact of a community based supportive service for people affected by cancer.

BACKGROUND: Globally, cancer rates are increasing. In Scotland, it is estimated that 2 in 5 people will develop cancer in their lifetime. Therefore, this is crucial time to provide personalised care and support to individuals affected by cancer. In response to this a community based supportive cancer service was launched in Glasgow, Scotland. The aim of this service is to proactively provide those affected by cancer with an assessment of their needs and personalised support where needed. To our knowledge, there is no other service like this in the United Kingdom. METHODS: The aim of this study is to understand if and how the service impacts upon the experiences and outcomes of people living with and affected by cancer. The study uses a sequential mixed methods design across a 5 year time point. Data gathering includes questionnaires, interviews, observations and reflective diaries. Participants include people affected by cancer who have used the service, a comparative sample who have not used the service, individuals who deliver the service and wider stakeholders. Outcomes include measures of patient activation, quality of life, health status, and social support. Data collection occurs at baseline, 2.5 years and 4 years with data from observations and reflective diaries supplemented throughout. DISCUSSION: This study evaluates an innovative community based cancer service. It focuses on impact and process issues relevant to a) the individuals in receipt of the service, b) the service providers, and c) the wider culture. As the programme evolves overtime, the research has been designed to draw out learning from the programme in order to support future commissioning both within Scotland and across the UK.

Evaluating holistic needs assessment in outpatient cancer care--a randomised controlled trial: the study protocol.

INTRODUCTION: People living with and beyond cancer are vulnerable to a number of physical, functional and psychological issues. Undertaking a holistic needs assessment (HNA) is one way to support a structured discussion of patients' needs within a clinical consultation. However, there is little evidence on how HNA impacts on the dynamics of the clinical consultation. This study aims to establish (1) how HNA affects the type of conversation that goes on during a clinical consultation and (2) how these putative changes impact on shared decision-making and self-efficacy. METHODS AND ANALYSIS: The study is hosted by 10 outpatient oncology clinics in the West of Scotland and South West England. Participants are patients with a diagnosis of head and neck, breast, urological, gynaecological and colorectal cancer who have received treatment for their cancer. Patients are randomised to an intervention or control group. The control group entails standard care--routine consultation between the patient and clinician. In the intervention group, the patient completes a holistic needs assessment prior to consultation. The completed assessment is then given to the clinician where it informs a discussion based on the patient's needs and concerns as identified by them. The primary outcome measure is patient participation, as determined by dialogue ratio (DR) and preponderance of initiative (PI) within the consultation. The secondary outcome measures are shared decision-making and self-efficacy. It is hypothesised that HNA will be associated with greater patient participation within the consultation, and that shared decision-making and feelings of self-efficacy will increase as a function of the intervention. ETHICS AND DISSEMINATION: This study has been given a favourable opinion by the West of Scotland Research Ethics Committee and NHS Research & Development. Study findings will be disseminated through peer-reviewed publications and conference attendance. TRAIL REGISTRATION NUMBER: Clinical Trials.gov NCT02274701.

The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models.

Dysregulation of PI3K/PTEN pathway components, resulting in hyperactivated PI3K signaling, is frequently observed in various cancers and correlates with tumor growth and survival. Resistance to a variety of anticancer therapies, including receptor tyrosine kinase (RTK) inhibitors and chemotherapeutic agents, has been attributed to the absence or attenuation of downregulating signals along the PI3K/PTEN pathway. Thus, PI3K inhibitors have therapeutic potential as single agents and in combination with other therapies for a variety of cancer indications. XL147 (SAR245408) is a potent and highly selective inhibitor of class I PI3Ks (α, ß, γ, and δ). Moreover, broad kinase selectivity profiling of >130 protein kinases revealed that XL147 is highly selective for class I PI3Ks over other kinases. In cellular assays, XL147 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 in multiple tumor cell lines with diverse genetic alterations affecting the PI3K pathway. In a panel of tumor cell lines, XL147 inhibits proliferation with a wide range of potencies, with evidence of an impact of genotype on sensitivity. In mouse xenograft models, oral administration of XL147 results in dose-dependent inhibition of phosphorylation of AKT, p70S6K, and S6 with a duration of action of at least 24 hours. Repeat-dose administration of XL147 results in significant tumor growth inhibition in multiple human xenograft models in nude mice. Administration of XL147 in combination with chemotherapeutic agents results in antitumor activity in xenograft models that is enhanced over that observed with the corresponding single agents.

Improving the care of cancer patients: holistic needs assessment.

This discussion paper presents a review of holistic needs assessments (HNAs) in the care of patients with cancer. HNAs entail a structured review of patient needs as articulated by the patient. This discussion then leads to a care plan grounded in issues pertinent to that patient. Despite policy guidance advocating its use, there are barriers to overcome in order to integrate HNAs into routine care. This article discusses what role communication skills and clinician confidence may have on the use of HNAs in practice, and suggests a strategy to support HNAs becoming the norm.

Characterization of the activity of the PI3K/mTOR inhibitor XL765 (SAR245409) in tumor models with diverse genetic alterations affecting the PI3K pathway.

Activation of the PI3K (phosphoinositide 3-kinase) pathway is a frequent occurrence in human tumors and is thought to promote growth, survival, and resistance to diverse therapies. Here, we report pharmacologic characterization of the pyridopyrimidinone derivative XL765 (SAR245409), a potent and highly selective pan inhibitor of class I PI3Ks (α, ß, γ, and δ) with activity against mTOR. Broad kinase selectivity profiling of >130 protein kinases revealed that XL765 is highly selective for class I PI3Ks and mTOR over other kinases. In cellular assays, XL765 inhibits the formation of PIP(3) in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 phosphorylation in multiple tumor cell lines with different genetic alterations affecting the PI3K pathway. In a panel of tumor cell lines, XL765 inhibits proliferation with a wide range of potencies, with evidence of an impact of genotype on sensitivity. In mouse xenograft models, oral administration of XL765 results in dose-dependent inhibition of phosphorylation of AKT, p70S6K, and S6 with a duration of action of approximately 24 hours. Repeat dose administration of XL765 results in significant tumor growth inhibition in multiple human xenograft models in nude mice that is associated with antiproliferative, antiangiogenic, and proapoptotic effects.

Discovery of XL413, a potent and selective CDC7 inhibitor.

CDC7 is a serine/threonine kinase that has been shown to be required for the initiation and maintenance of DNA replication. Up-regulation of CDC7 is detected in multiple tumor cell lines, with inhibition of CDC7 resulting in cell cycle arrest. In this paper, we disclose the discovery of a potent and selective CDC7 inhibitor, XL413 (14), which was advanced into Phase 1 clinical trials. Starting from advanced lead 3, described in a preceding communication, we optimized the CDC7 potency and selectivity to demonstrate in vitro CDC7 dependent cell cycle arrest and in vivo tumor growth inhibition in a Colo-205 xenograft model.

Markers of bone destruction and formation and periodontitis in type 1 diabetes mellitus.

AIM: To determine plasma concentrations of bone metabolism markers in type 1 diabetes mellitus patients and non-diabetic and to evaluate the influence of periodontitis on biomarkers of bone formation in these patient groups. METHODS: Plasma concentrations of receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide of type 1 collagen and osteocalcin were measured in type 1 diabetes mellitus patients (n=63) and non-diabetics (n=38) who were also subdivided on the basis of their periodontal status. RESULTS: Diabetics had significantly lower osteocalcin concentrations, lower RANKL to OPG ratios and higher OPG concentrations (as shown by other researchers) than non-diabetics. The ratio of RANKL to OPG was altered by the periodontal status. Osteocalcin had a negative correlation and OPG a positive correlation with the percentage of glycated haemoglobin in the blood. CONCLUSION: Because, osteocalcin, a biomarker of bone formation, is lower in patients with periodontitis and in patients with type 1 diabetes mellitus with and without periodontitis than in non-diabetics without periodontitis, this might indicate that diabetics are less able to replace bone lost during active bursts of periodontitis and explain the greater severity of disease seen in studies of patients with diabetes.