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Summary Glioblastoma (GBM) is an aggressive cancer with a very poor prognosis. Generally viewed as weakly immunogenic, GBM responds poorly to current immunotherapies. To understand this problem more clearly we used a combination of natural killer (NK) cell functional assays together with gene and protein expression profiling to define the NK cell response to GBM and explore immunosuppression in the GBM microenvironment. In addition, we used transcriptome data from patient cohorts to classify GBM according to immunological profiles. We show that glioma stem‐like cells, a source of post‐treatment tumour recurrence, express multiple immunomodulatory cell surface molecules and are targeted in preference to normal neural progenitor cells by natural killer (NK) cells ex vivo. In contrast, GBM‐infiltrating NK cells express reduced levels of activation receptors within the tumour microenvironment, with hallmarks of transforming growth factor (TGF)‐β‐mediated inhibition. This NK cell inhibition is accompanied by expression of multiple immune checkpoint molecules on T cells. Single‐cell transcriptomics demonstrated that both tumour and haematopoietic‐derived cells in GBM express multiple, diverse mediators of immune evasion. Despite this, immunome analysis across a patient cohort identifies a spectrum of immunological activity in GBM, with active immunity marked by co‐expression of immune effector molecules and feedback inhibitory mechanisms. Our data show that GBM is recognized by the immune system but that anti‐tumour immunity is restrained by multiple immunosuppressive pathways, some of which operate in the healthy brain. The presence of immune activity in a subset of patients suggests that these patients will more probably benefit from combination immunotherapies directed against multiple immunosuppressive pathways., Our manuscript challenges the current paradigm that Glioblastoma (GBM) is a poor candidate for immunotherapy, therefore impacting on clinical approaches. We identify NK cells as a target for immunosuppression in GBM, with multiple suppressive pathways within GBM human tumours. We also identify a group of GBM patients with higher immunological activity, who will benefit from immunotherapies that target these immunosuppressive pathways.

Objectives\ud Sacral nerve stimulation (SNS) may provide long-term symptom relief to patients suffering from chronic constipation. Patients are currently selected for SNS using a 2-week peripheral nerve evaluation (PNE) comprising stimulation by temporary leads. However, only 40% of test responders receive long-term benefit from treatment meaning that healthcare costs per successfully treated patient are too high. The primary objective was to assess tined-lead testing to predict benefit from SNS for chronic constipation.\ud Patients and methods\ud A randomized double-blind sham-controlled cross-over design evaluated enhanced PNE (ePNE) using tined quadripolar electrode leads over 6 weeks. The design differentiated between patients with discriminate and indiscriminate responses to testing. A score improvement of 25% or more was considered to be a positive response within a stimulation period. The primary outcome was the proportion of patients showing a reduction of at least 0.5 in constipation symptom score at 6 months.\ud Results\ud A total of 45 patients were randomized, of whom 29 (64.4%) were test-phase responders. Of these, 27 were implanted providing permanent SNS. During ePNE, seven (18%) were discriminate responders, 22 (56%) were indiscriminate responders and 10 (26%) were nonresponders. Six patients were withdrawn during the test phase because of infection or noncompliance. At 6 months, there was no significant difference in primary outcome between discriminate and indiscriminate responders (60 vs. 57%, P=0.76). The study was terminated prematurely because of a persistent infection rate of 10 (22%) during ePNE of which nine (20%) were severe.\ud Conclusion\ud ePNE is a poor predictor of treatment response at 6 months. This suggests a strong and persistent placebo response during both SNS PNE and treatment. An extended 6-week PNE poses a high risk of infection.

Objective Little is known about legal needs in the context of life-limiting illness, particularly the need for advice concerning legal arrangements, rights and entitlements. This UK-based multiagency stakeholder engagement exercise scoped legal needs associated with life-limiting illness and identified support structures, gaps and opportunities for practice improvement.Method and analysis Snowball sampling generated a stakeholder group from a wide range of regional and national organisations involved in care of people with life-limiting illness, spanning health, social care, legal support, advice, charities, prison services as well as patient and carer representatives. A coproduced survey of three open questions generated qualitative data, interpreted by thematic analysis.Results Stakeholders reported a broad spectrum of problems and needs raising legal issues, with no consistency of definition. A classification is proposed, identifying matters concerning rights and entitlements of patients/carers in day-to-day life and decisions around care, both immediate and in the future, as well as professional responsibilities in delivering personalised care. The support structures identified were predominantly online literature, although there was some availability of remote and face-to-face services. Limited awareness of the issues, variable service configuration, fragmentation of care and inequitable access were identified as barriers to support. Stakeholders recognised the need for education and closer multiagency working.Conclusions ‘Legal needs’ incorporate wide-ranging issues, but there is inconsistency in perceptions among stakeholders. Practice is variable, risking unmet need. Opportunities for improvement include more formal integration of social welfare legal services in the health context, generating clearer pathways for assessment and management.

Background Visual field defects are a common consequence of stroke, and compensatory eye movement strategies have been identified as the most promising rehabilitation option. There has been a move toward compensatory telerehabilitation options, such as the Durham Reading and Exploration (DREX) training app, which significantly improves visual exploration, reading, and self-reported quality of life. Objective This study details an iterative process of liaising with stroke survivors, carers, and health care professionals to identify barriers and facilitators to using rehabilitation tools, as well as elements of good practice in telerehabilitation, with a focus on how the DREX package can be maximized. Methods Survey data from 75 stroke survivors informed 12 semistructured engagement activities (7 focus groups and 5 interviews) with 32 stroke survivors, 10 carers, and 24 occupational therapists. Results Thematic analysis identified key themes within the data. Themes identified problems associated with poststroke health care from both patients’ and occupational therapists’ perspectives that need to be addressed to improve uptake of this rehabilitation tool and telerehabilitation options generally. This included identifying additional materials or assistance that were required to boost the impact of training packages. The acute rehabilitation setting was an identified barrier, and perceptions of technology were considered a barrier by some but a facilitator by others. In addition, 4 key features of telerehabilitation were identified: additional materials, the importance of goal setting, repetition, and feedback. Conclusions The data were used to try to overcome some barriers to the DREX training and are further discussed as considerations for telerehabilitation in general moving forward.

BACKGROUND Visual field defects are a common consequence of stroke, and compensatory eye movement strategies have been identified as the most promising rehabilitation option. There has been a move toward compensatory telerehabilitation options, such as the Durham Reading and Exploration (DREX) training app, which significantly improves visual exploration, reading, and self-reported quality of life. OBJECTIVE This study details an iterative process of liaising with stroke survivors, carers, and health care professionals to identify barriers and facilitators to using rehabilitation tools, as well as elements of good practice in telerehabilitation, with a focus on how the DREX package can be maximized. METHODS Survey data from 75 stroke survivors informed 12 semistructured engagement activities (7 focus groups and 5 interviews) with 32 stroke survivors, 10 carers, and 24 occupational therapists. RESULTS Thematic analysis identified key themes within the data. Themes identified problems associated with poststroke health care from both patients’ and occupational therapists’ perspectives that need to be addressed to improve uptake of this rehabilitation tool and telerehabilitation options generally. This included identifying additional materials or assistance that were required to boost the impact of training packages. The acute rehabilitation setting was an identified barrier, and perceptions of technology were considered a barrier by some but a facilitator by others. In addition, 4 key features of telerehabilitation were identified: additional materials, the importance of goal setting, repetition, and feedback. CONCLUSIONS The data were used to try to overcome some barriers to the DREX training and are further discussed as considerations for telerehabilitation in general moving forward.

Background Life-limiting illness generates an array of challenges for patients and carers but little is known about legal issues. There is no definition of legal issues in this context and limited integration of care across health, social, advice, legal and charitable sectors although all contribute to holistic care. Aims The Legal Needs of Adults towards End of Life (LeNA) project investigated the scope and scale of legal needs from a range of perspectives, the support structures available and professional education needs with a view to shaping national policy. Methods Sept 2017 – June 2018: systematic literature review and national stakeholder engagement exercise across health, social, charitable, advice and legal services: definition of legal needs, available support and gaps. May 2018 – March 2019: semi-structured interviews (24 patient/carer) and questionnaires (124 patient/carer/staff) to evaluate experience of legal needs. Sept 2018 – Jan 2019: four inter-professional workshops to consider educational needs through a taster session and focus groups (6). Results Legal needs are very broad and practice highly variable. The project has developed a classification relating to patient/carer rights and professional responsibilities. This could direct future policy. Patients and carers struggle with unmet needs, uncertain of how to access help and unwilling to plan for the future in the context of active concerns. Some support structures already exist but the project identified a number of barriers and consideration needs to be given to accessibility and suitability of these. There is significant enthusiasm for widely inter-professional education in this area, using an interactive group structure. Conclusions Legal needs are poorly defined in palliative care, resulting in variability in practice and unmet need. This is an area for improvement and follow-on research is planned at national policy level. Together with novel education, this will support better assessment and integrated care around legal needs towards end of life.

This paper contributes to the international literature examining design of inpatient settings for mental health care. Theoretically, it elaborates the connections between conceptual frameworks from different strands of literature relating to therapeutic landscapes, social control and the social construction of risk. It does so through a discussion of the substantive example of research to evaluate the design of a purpose-built inpatient psychiatric health care facility, opened in 2010 as part of the National Health Service (NHS) in England. Findings are reported from interviews or discussion groups with staff, patients, and their family and friends. This paper demonstrates a strong, and often critical awareness among members of staff and other participants about how responsibilities for risk governance of ‘persons’ are exercised through ‘technical safety’ measures and the implications for therapeutic settings. Our participants often emphasised how responsibility for technical safety was being invested in the physical infrastructure of certain ‘places’ within the hospital where risks are seen to be ‘located’. This illuminates how the spatial dimensions of social constructions of risk are incorporated into understandings about therapeutic landscapes. There were also more subtle implications, partly relating to ‘Panopticist’ theories about how the institution uses technical safety to supervise its own mechanisms, through the observation of staff behaviour as well as patients and visitors. Furthermore, staff seemed to feel that in relying on technical safety measures they were, to a degree, divesting themselves of human responsibility for risks they are required to manage. However, their critical assessment showed their concerns about how this might conflict with a more therapeutic approach and they contemplated ways that they might be able to engage more effectively with patients without the imposition of technical safety measures. These findings advance our thinking about the construction of therapeutic landscapes in theory and in practice.

Although there has been a shift toward treatment in the home and the community, in the UK, inpatient facilities are still important in modern mental health care. 'Informal carers', including family members, often play an essential role, not only in providing care in the community but also in care of patients during periods of hospitalisation. UK National Health Service policies increasingly consider the position of these carers as 'partners' in the care process, but relatively little attention has been paid to their position within the hospital settings where treatment is provided for inpatients. This paper contributes to geographical work on carers experiences, by reporting how this issue emerged through a study focused on perceptions of a newly built hospital, compared with the inpatient facilities it replaced. We draw on qualitative research findings from discussion groups and interviews with informal carers. The material considered here focused especially on carers' views of aspects of the hospital environment that were important for wellbeing of carers and the people they look after. The carers' views were supplemented by relevant material drawn from other interviews from our wider study, which included service users and members of hospital staff. These accounts revealed how informal carers experienced the hospital environment; we interpret our findings through a conceptual framework that emphasises carers' experiences of a 'journey' along a 'caring pathway' to and through the hospital space. This perspective allows us to make a connection between three bodies of literature. The first relates to phenomenological interpretations of one's environmental perception, formed as one moves through the world. The second derives from the literature concerning 'permeability' of hospital institutions. Bringing these ideas together provides an innovative, dynamic perspective on a third strand of literature from health geography that examines hospitals as 'therapeutic landscapes'. The analysis helps to explore the extent to which carers in this study were positioned as 'outsiders' in the hospital space.

Improving the care of the dying is regarded as a national priority and current guidelines stipulate the need to provide holistic palliative care. Despite this, many dying patients and carers report low levels of comfort and satisfaction with care. Reasons include poor coordination of care, variability in communication and crisis-driven interventions. Integrated care pathways aim to support care coordination and open communication with patients and carers. One example is the Liverpool Care Pathway (LCP). Using the LCP entails assessment of eligibility criteria which requires skills, knowledge and clinical judgement about its timing. This can be problematic, and little is known about actual uptake, characteristics of assessed patients and reasons for inclusion/exclusion. A comprehensive systematic review was conducted for papers published between January 1990 and July 2012 providing information on LCP uptake. 17 papers met inclusion criteria. A total of 18 052 patients were placed on the LCP, in a variety of inpatient and primary care settings, and cancer and non-cancer diagnoses. 47.4% of dying patients identified were placed on the LCP. Although the LCP is widely recommended, it is only used for around half of dying patients. Reasons may include lack of knowledge, high staff turnover and concerns about applicability particularly for unpredictable dying trajectories. The proportion of patients who meet the eligibility criteria and the reasons surrounding low uptake remain unclear. Research is urgently required to further quantify the variable use of the LCP, and to investigate whether alternative approaches should be developed for non-cancer groups.

Aims: Diagnosis of heart failure in older people in long-term care is challenging because of co-morbidities, cognitive deficit, polypharmacy, immobility, and poor access to services. This study aimed to ascertain heart failure prevalence and clinical management in this population. Methods and results: A total of 405 residents, aged 65–100 years, in 33 UK care facilities were prospectively enrolled between April 2009 and June 2010. The presence of heart failure was determined using European Society of Cardiology guidelines, modified where necessary for immobility. Evaluation of symptoms and signs, functional capacity, and quality of life, portable on-site echocardiography, and medical record review were completed in 399 cases. The point prevalence of heart failure was 22.8% [n = 91, 95% confidence interval (CI) 18.8–27.2%]; of these, 62.7% (n = 57, 95% CI 59.6–66.5%) had heart failure with preserved ejection fraction and 37.3% had left ventricular systolic dysfunction (n = 34, 95% CI 34.8–40.5%). A total of 76% (n = 61) of previous diagnoses of heart failure were not confirmed, and up to 90% (n = 82) of study cases were new. No symptoms or signs were reliable predictors of heart failure. Conclusion: Heart failure was diagnosed in almost a quarter of residents: the prevalence was substantially higher than in other populations. The majority of heart failure cases were undiagnosed, while three-quarters of previously recorded cases were misdiagnosed. Common symptoms and signs appear to have little clinical utility in this population. Early, accurate differential diagnosis is key to the effective management of heart failure; this may be failing in long-term care facilities.

Objectives Communication and planning for heart failure (HF) care near the end of life is known to be complex. Little is known about how the patient experience of palliative assessment and communication needs change over time, and how this might inform management. Our aim was to explore experiences of giving or receiving a prognosis and advanced palliative care planning (ACP) for those with HF. Methods We carried out a longitudinal grounded theory study, employing in-depth interviews with 14 clinicians (primary and secondary care) and observations of clinic and home appointments, followed by a series of interviews with 13 patients with HF and 9 carers. Results Overall, the majority of participants rejected notions of HF as a terminal illness in favour of a focus on day-to-day management and maintenance, despite obvious deterioration in disease stage and needs over time. Clinicians revealed frustration about the uncertain nature of HF prognosis, leading to difficulties in planning. Others highlighted the need to deliver problem-based, individualised care but felt constrained sometimes by the lack of multidisciplinary ACP. Patients reported an absence of prognostic discussions with clinicians. Conclusions This is the first study exploring the experiences of prognostic communication at all stages of HF. Findings raise questions regarding the pragmatic utility of the concept of HF as a terminal illness and have implications for future HF care pathway development. Findings support the incorporation of a problem-based approach to management, which recognises the importance of everyday functioning for patients and carers as well as the opportunity for ACP.

Patients using intravenous drugs have particular physical healthcare needs.1 Drug-related death rates for patients using heroin and morphine have risen sharply recently.2 Nevertheless, drug overdoses are only one of many factors that contribute to the high mortality rate. Methadone or buprenorphine treatment reduces but does not eliminate the high mortality rate. Patients in this group also experience high morbidity rates.3 ### Infections O’Donnell and colleagues alert us to the high prevalence of skin and groin infections. Infections in this group are complex and wide ranging. Injecting manure and other materials used in heroin production produces predictable soft-tissue infections and abscesses, as well as the occasional exotic infection such as botulism, necrotising fasciitis, or tetanus. Other relatively more common but still serious infections include subacute bacterial endocarditis (SABE) and osteomyelitis, which may be difficult to diagnose, perhaps because it is not easy to think of the diagnoses in standard consultations. Infections not directly related to injecting, such as pneumonia, are also more common than the general population and likely to be caused by poor living conditions and poor nutrition. ### Hepatitis C This group represents the major cause of hepatitis C infection in the UK; the RCGP has done much to make GPs aware of the connection and arrange appropriate testing and follow-up. There may also be opportunities for primary care to be involved in hepatitis C treatment through new commissioning routes.4 ### Deep vein thrombosis Deep vein thrombosis (DVT) is common, and in addition to the acute dangers causes poor quality of life from chronically swollen and sometimes ulcerated legs.5 Pharmaceutical management of DVT poses particular …

Background Accurate optical characterisation and removal of small adenomas (

For many years, health professionals have debated about the term used to address service recipients, with discussion centring upon the terms ‘patient’ ‘client’ and ‘service user’. The current study assessed the preference of individuals referred to a psychological therapy service.

With reference to her own study of children with long-term conditions, Helen Close considers whether photography as a research method can be both valuable and ethical.

Background Trans-anal irrigation (TAI) is used widely to treat bowel dysfunction, although evidence for its use in adult chronic functional constipation remains unclear. Long-term outcome data are lacking, and the effectiveness of therapy in this patient group is not definitively known. Methods Evidence for effectiveness and safety was reviewed and the quality of studies was assessed. Primary research articles of patients with chronic functional constipation, treated with TAI as outpatients and published in English in indexed journals were eligible. Searching included major bibliographical databases and search terms: bowel dysfunction, defecation, constipation and irrigation. Fixed- and random-effect meta-analyses were performed. Results Seven eligible uncontrolled studies, including 254 patients, of retrospective or prospective design were identified. The definition of treatment response varied and was investigator-determined. The fixed-effect pooled response rate (the proportion of patients with a positive outcome based on investigator-reported response for each study) was 50.4 % (95 % CI: 44.3–56.5 %) but featured substantial heterogeneity (I2 = 67.1 %). A random-effects estimate was similar: 50.9 % (95 % CI: 39.4–62.3 %). Adverse events were inconsistently reported but were commonplace and minor. Conclusions The reported success rate of irrigation for functional constipation is about 50 %, comparable to or better than the response seen in trials of pharmacological therapies. TAI is a safe treatment benefitting some patients with functional constipation, which is a chronic refractory condition. However findings for TAI vary, possibly due to varying methodology and context. Well-designed prospective trials are required to improve the current weak evidence base.

Nausea and vomiting are common and distressing symptoms of advanced cancer for which there are currently no systematic and rigorous assessment tools. The advent of extended nurse prescribing gives nurses the opportunity to address these symptoms but puts the onus on them to provide a clear rationale for prescribing decisions. A care study is used to illustrate aspects of holistic management of these symptoms. An assessment tool described by Twycross and Back (1998) is suggested as a method for the nurse prescriber to manage nausea and vomiting in a rigorous, holistic manner. Recommendations are made regarding the development of an holistic assessment model and a flow chart to guide decisions regarding the management of terminally ill patients with nausea and vomiting.

We examine emotional reactions to changes to medical spaces of care, linked with past experiences. In this paper we draw on findings from a qualitative study of the transfer of psychiatric inpatient care from an old to a newly built facility. We show how the meanings attributed to 'therapeutic landscapes' from one's past can evoke emotions and memories, manifesting in ideas about nostalgia, solastalgia, salvage and abandonment, which can impinge on one's present therapeutic experience. We reflect on how consideration of these ideas might contribute to better future design of psychiatric inpatient facilities and the wellbeing of those using them.

BACKGROUND: Compared to unipolar depression (UD), depressed mood in bipolar disorder (BD) has been associated with amplified negative mental imagery of the future ('flashforwards'). However, imagery characteristics during positive mood remain poorly explored. We hypothesise first, that unlike UD patients, the most significant positive images of BD patients will be 'flashforwards' (rather than past memories). Second, that BD patients will experience more frequent (and more 'powerful') positive imagery as compared to verbal thoughts and third, that behavioural activation scores will be predicted by imagery variables in the BD group. METHODS: BD (n=26) and UD (n=26) patients completed clinical and trait imagery measures followed by an Imagery Interview and a measure of behavioural activation. RESULTS: Compared to UD, BD patients reported more 'flashforwards' compared to past memories and rated their 'flashforwards' as more vivid, exciting and pleasurable. Only the BD group found positive imagery more 'powerful', (preoccupying, 'real' and compelling) as compared to verbal thoughts. Imagery-associated pleasure predicted levels of drive and reward responsiveness in the BD group. LIMITATIONS: A limitation in the study was the retrospective design. Moreover pathological and non-pathological periods of "positive" mood were not distinguished in the BD sample. CONCLUSIONS: This study reveals BD patients experience positive 'flashforward' imagery in positive mood, with more intense qualities than UD patients. This could contribute to the amplification of emotional states and goal directed behaviour leading into mania, and differentiate BD from UD.

Objectives To explore changes in healthcare professionals’ views about the diagnosis and management of heart failure since a study in 2003. Design Focus groups and a national online cross-sectional survey. Setting and participants Focus groups (n=8 with a total of 56 participants) were conducted in the North East of England using a phenomenological framework and purposive sampling, informing a UK online survey (n=514). Results 4 categories were identified as contributing to variations in the diagnosis and management of heart failure. Three previously known categories included: uncertainty about clinical practice, the value of clinical guidelines and tensions between individual and organisational practice. A new category concerned uncertainty about end-of-life care. Survey responses found that confidence varied among professional groups in diagnosing left ventricular systolic dysfunction (LVSD): 95% of cardiologists, 93% of general physicians, 66% of general practitioners (GPs) and 32% of heart failure nurses. For heart failure with preserved ejection fraction (HFpEF), confidence levels were much lower: 58% of cardiologists, 43% of general physicians, 7% of GPs and 6% of heart failure nurses. Only 5–35% of respondents used natriuretic peptides for LVSD or HFpEF. Confidence in interpreting test findings was fundamental to the use of all diagnostic tests. Clinical guidelines were reported to be helpful when diagnosing LVSD by 33% of nurses and 50–56% of other groups, but fell to 5–28% for HFpEF. Some GPs did not routinely initiate diuretics (23%), ACE-inhibitors (22%) or β-blockers (38%) for LVSD for reasons including historical teaching, perceived side effects and burden of monitoring. For end-of-life care, there was no consensus about responsibility for heart failure management. Conclusions Reported differences in the way heart failure is diagnosed and managed have changed little in the past decade. Variable access to diagnostic tests, modes of care delivery and non-uniform management approaches persist. The current National Health Service (NHS) context may not be conducive to addressing these issues.

Coping strategies used by hospitalized stroke patients: implications for continuity and management of care¶ This paper describes findings from an English study into the perceptions of multi-professional practice given by stroke patients, their informal carers and hospital staff. Unstructured interviews were conducted with nine stroke patients and eight informal carers. Case studies were developed from the interview data which formed the basis of a questionnaire designed to ascertain the aims of care for the case studies and the location of professional responsibility for meeting these aims. This was returned by 31 respondents from a range of professional backgrounds. The findings indicate that patients and carers sought out relationships with staff and other patients in order to gain information to help them understand their uncertain futures. Professional staff were reluctant to pass specific information on to patients as it might be misleading in each individual case. The uncertainty surrounding individual recovery means that supportive relationships initiated by patients and carers may need to be recognized and nurtured.

Objectives. This study examines cognitive behavioural assessments of auditory hallucinations (‘voices’) in people with psychoses. It aims to compare findings with previous work and validate the Assessment of Voices Schedule (Chadwick & Birchwood, 1994). Data were collected on appraisals of voices in relation to the self. It was hypothesized that self-appraisals may be a further factor in understanding the emotional impact of voices. Design. A replication study where data were collected from a new sample of participants and compared with a previous independent sample. Method. Voices of 30 patients with a diagnosis of schizophrenia were assessed using a semi-structured interview and questionnaires. Thought-chaining was used to assess appraisals of the voice in relation to the self. Results. Compared to the previous study, current participants were significantly less likely to believe in the omnipotence of their voices, to view their voices as omniscient and to have a positive affective response to benevolent voices. Similar numbers in this study construed their voices as malevolent, but fewer participants in this sample had benevolent voices. There were no significant differences between samples in behavioural responses to voices or in the affective responses to malevolent voices. The Assessment of Voices Schedule was found to have generally good test—retest and inter-rater reliability. Extremely negative self-appraisals were common, as were negative affective responses to the voice experience and low selfesteem. Conclusion. The implications of these findings for both cognitive behavioural models and therapy are discussed.

Introduction: This multicentre randomised controlled trial investigated whether a computed tomography (CT) scan of the axilla could more accurately assess whether the axillary lymph nodes were involved with malignancy in patients with newly diagnosed breast cancer and therefore influence surgical decision-making with regard to axillary surgery. Methods: Patients with newly diagnosed breast cancer (via screening and symptomatic routes) at two NHS Trusts in the North East of England were recruited and randomised in equal numbers. Both groups received routine diagnostic and surgical care (usual care). In addition, one group received a CT scan of their axilla on the same side as the breast cancer. Results: The study recruited 297 patients, of whom 291 contributed to findings. CT scan-guided care did not result in a change in the need for a second operation, with about 20% of both groups needing further surgery. Patients within the two groups were similar before treatment, had similar types and grade of cancer, experienced similar pattern complications and reported similar experiences of care. Conclusion: New diagnostic imaging technologies regularly enter NHS centres of excellence as research tools. It is important these are evaluated rigorously before becoming routine care. In patients newly diagnosed with breast cancer, CT-augmented diagnosis of cancer in the axilla was not found to improve surgical outcomes or patient experience.

Objective: Lithium users are offered routine renal monitoring but few studies have quantified the risk to renal health. The aim of this study was to assess the association between use of lithium carbonate and incidence of renal failure in patients with bipolar disorder. Methods: This was a retrospective cohort study using the General Practice Research Database (GPRD) and a nested validation study of lithium exposure and renal failure. A cohort of 6360 participants aged over 18 years had a first recorded diagnosis of bipolar disorder between January 1, 1990 and December 31, 2007. Data were examined from electronic primary care records from 418 general practices across the UK. The primary outcome was the hazard ratio for renal failure in participants exposed to lithium carbonate as compared with non-users of lithium, adjusting for age, gender, co-morbidities, and poly-pharmacy. Results: Ever use of lithium was associated with a hazard ratio for renal failure of 2.5 (95% confidence interval 1.6 to 4.0) adjusted for known renal risk factors. Absolute risk was age dependent, with patients of 50 years or older at particular risk of renal failure: Number Needed to Harm (NNH) was 44 (21 to 150). Conclusions: Lithium is associated with an increased risk of renal failure, particularly among the older age group. The absolute risk of renal failure associated with lithium use remains small.

This paper reports on research framed by theories of therapeutic landscapes and the ways that the social, physical and symbolic dimensions of landscapes relate to wellbeing and healing. We focus especially on the question of how attributes of therapeutic landscapes are constructed in different ways according to the variable perspectives of individuals and groups. Through an ethnographic case study in a psychiatric hospital in the North of England we explore the perceived significance for wellbeing of 'smoking spaces' (where tobacco smoking is practiced in ways that may, or may not be officially sanctioned). We interpret our findings in light of literature on how smoking spaces are linked to the socio-geographical power relations that determine how smoking is organised within the hospital and how this is understood by different groups using the hospital building. We draw on qualitative research findings from discussion groups, observations, and interviews with patients, carers and staff. These focused on their views about the building design and setting of the new psychiatric hospital in relation to their wellbeing, and issues relating to smoking spaces emerged as important for many participants. Creating and managing smoking spaces as a public health measure in psychiatric hospitals is shown to be a controversial issue involving conflicting aims for health and wellbeing of patients and staff. Our findings indicate that although from a physical health perspective, smoking is detrimental, the spaces in which patients and staff smoke have social and psychological significance, providing a forum for the creation of social capital and resistance to institutional control. While the findings relate to one case study setting, the paper illustrates issues of wider relevance and contributes to an international literature concerning the tensions between perceived psychological and psychosocial benefits of smoking vs. physical harm that smoking is likely to cause. We consider the implications for hospital design and the model of care.

Background: Older people in care-facilities may be less likely to access gold standard diagnosis and treatment for heart failure (HF) than non residents; little is understood about the factors that influence this variability. This study aimed to examine the experiences and expectations of clinicians, care-facility staff and residents in interpreting suspected symptoms of HF and deciding whether and how to intervene. Methods: This was a nested qualitative study using in-depth interviews with older residents with a diagnosis of heart failure (n=17), care-facility staff (n=8), HF nurses (n=3) and general practitioners (n=5). Results: Participants identified a lack of clear lines of responsibility in providing HF care in care-facilities. Many clinical staff expressed negative assumptions about the acceptability and utility of interventions, and inappropriately moderated residents’ access to HF diagnosis and treatment. Care-facility staff and residents welcomed intervention but experienced a lack of opportunity for dialogue about the balance of risks and benefits. Most residents wanted to be involved in healthcare decisions but physical, social and organisational barriers precluded this. An onsite HF service offered a potential solution and proved to be acceptable to residents and care-facility staff. Conclusions: HF diagnosis and management is of variable quality in long-term care. Conflicting expectations and a lack of co-ordinated responsibility for care, contribute to a culture of benign neglect that excludes the wishes and needs of residents. A greater focus on rights, responsibilities and co-ordination may improve healthcare quality for older people in care. Trial registration: ISRCTN: ISRCTN19781227

In this article the authors present the recent discovery of a novel method of supplementing written grounded theory memos with voice recording, the combination of which may provide significant analytical advantages over solely the traditional written method. Memo writing is an essential component of a grounded theory study, however it is often difficult to capture thoughts, feelings, and emerging theorising using written methods after a research interview. I found that many of these potentially valuable ideas were lost or misunderstood upon reading my subsequent written memo, and the feelings and context which influenced the emerging theory were not always clear. I turned to voice recording to enhance my grounded theory memos and soon discovered substantial additional benefits upon listening back. This novel method, the cognitively different ways in which human brains process verbal and written information, and the ultimate benefits I have enjoyed by combining writing and voice recording memos are presented. Keywords: Grounded Theory, Memos, Voice Recording, Memory, Cognition, Research Context, Interpretivism In this article the authors present research insights on extending the use of voice recording grounded theory based interviews, to supplement written memos with voice recording, and the additional layers of understanding and reflection that this method can provide. Grounded theory (GT; Glaser & Strauss, 1967) provides a framework for structuring

Background Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT). Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD) remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records. Methods 51,182 menopausal women were identified using the UK General Practice Research Database between 1995–2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs) were calculated for GORD and proton-pump inhibitor (PPI) use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy. Results In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen) were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18–1.89). Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03–1.74). Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01–2.22). Conclusions This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance.

In this issue of the Journal, two papers highlight the importance of sleep. The first reiterates the role of obstructive sleep apnoea in patients with hypertension and how continuous positive airway pressure (CPAP) therapy can improve blood pressure.1 The second, a qualitative study with patients and clinicians, restates the need for practitioners to be more aware of patients' concerns and the impact of the sleep problem on their lives.2 Sleep has been associated with health problems for a long time. Classically, sleep disturbances, particularly early morning awakening and an inability to get off to sleep, have been associated with anxiety and depression. The consequences of inadequate sleep have been associated with lack of concentration, daytime sleepiness, and impaired performance. Transport authorities have long recognised this through restrictions on heavy vehicle drivers and airline pilots. Closer to home, European Working Time Directives have restricted the amount of on-call allowed, leading to a radical shift in NHS work patterns. However, there can be confusion as to what constitutes a sleep problem. One approach is to consider two entities: first, sleep-disordered breathing including obstructive sleep apnoea, hyperventilation syndrome, upper airways resistance syndrome, and night-time Cheyne-Stokes breathing; and secondly, …

Introduction Colorectal cancer is preventable through polypectomy at colonoscopy. Most polyps are adenomas, with malignant potential, or hyperplastic with no malignant risk. Most adenomas are small (

Introduction Sacral nerve stimulation (SNS) can be an effective treatment for some patients with functional bowel disorders. The highly variable nerve stimulation waveforms generated by the re-usable “brown box” (model 3625, Medtronic US) SNS test stimulator have previously been reported. 1 Since 2013, the single-use digital test stimulator “Verify” (model 3531, Medtronic US) has been used in our trust. Within the UK most clinicians continue to use the brown box; Medtronic no longer manufacture model 3625 and it requires recalibration between patient use. We aimed to assess the Verify stimulator’s output waveform to quantify if this was as variable as the analogue precursor. Method A prospective output waveform assessment of 15 used Verify SNS test stimulators using a cross-calibrated oscilloscope (Tektronix model 2230) and a counter-timer (Black Star Apollo 100). Devices were successively loaded with the same AAAA batteries and connected to a constant simulated tissue load (993Ω) circuit with two output electrodes attached to the oscilloscope (Figure 1). The output waveform amplitude and pulse width were measured at clinically used settings and compared with the expected output values (amplitude by V = IR). Devices passed the calibration test if within tolerances of 10% and 20%. Results At clinical settings (14 Hz/210 µSec) the measured amplitude and pulse width did not vary significantly from expected at a programmed current of 0.2, 0.5, 1.0, 2.0 and 3.0 mAmp, and 100% of devices passed the calibration test (Table 1). 6 devices failed at 0.1milliAmps due to more variation at low energy settings. The variations in device frequency were too small to be measured with the counter-timer and therefore in the order of magnitude of × 10 –4 Hertz. Similarly, the pulse width times were just as accurate at 100, 210 and 400 µSec with the standard deviations 0.48, 0.93 and 0.69 µSec respectively. Conclusion At all clinically relevant settings 100% of the devices passed the calibration test. The failures at 0.1 mAmps are irrelevant (below therapeutic thresholds). Given these results, the lack of manufacturer support for the 3625 model, and its reported variability, we conclude that only the Verify testing device is fit for purpose in clinical practice. Disclosure of interest None Declared. Reference Etherson KJ, Davidson A, Yiannakou Y, Mason JM. Surgeons don’t forget to calibrate: Findings from SNS test stimulators. Gut 2013; 62 :A27-A8

Objective The contraceptive needs of illicit opioid users differ from non-drug users but are poorly understood. The aim of this study was to describe contraceptive use and pregnancy outcomes in opioid-using women, and to examine their association with a range of risk factors. Method This retrospective cohort study used UK general practice records, Treatment Outcomes Profile and National Drug Treatment Monitoring System data, and a nested data validation exercise. A cohort of 376 women aged 20–61 years were in active treatment for opioid addiction in October 2010 at two specialised primary care practices in North-East England. Outcomes were age-adjusted prevalence estimates for contraceptive use and pregnancy outcomes in users of illicit opioids. The association between lifestyle-related risk factors and contraception was explored. Results Drug-using women made lower use of planned (non-condom) contraception (24% vs 50%, p

AIM: To undertake a randomised pilot study comparing biodegradable stents and endoscopic dilatation in patients with strictures. METHODS: This British multi-site study recruited seventeen symptomatic adult patients with refractory strictures. Patients were randomised using a multicentre, blinded assessor design, comparing a biodegradable stent (BS) with endoscopic dilatation (ED). The primary endpoint was the average dysphagia score during the first 6 mo. Secondary endpoints included repeat endoscopic procedures, quality of life, and adverse events. Secondary analysis included follow-up to 12 mo. Sensitivity analyses explored alternative estimation methods for dysphagia and multiple imputation of missing values. Nonparametric tests were used. RESULTS: Although both groups improved, the average dysphagia scores for patients receiving stents were higher after 6 mo: BS-ED 1.17 (95%CI: 0.63-1.78) P = 0.029. The finding was robust under different estimation methods. Use of additional endoscopic procedures and quality of life (QALY) estimates were similar for BS and ED patients at 6 and 12 mo. Concomitant use of gastrointestinal prescribed medication was greater in the stent group (BS 5.1, ED 2.0 prescriptions; P < 0.001), as were related adverse events (BS 1.4, ED 0.0 events; P = 0.024). Groups were comparable at baseline and findings were statistically significant but numbers were small due to under-recruitment. The oesophageal tract has somatic sensitivity and the process of the stent dissolving, possibly unevenly, might promote discomfort or reflux. CONCLUSION: Stenting was associated with greater dysphagia, co-medication and adverse events. Rigorously conducted and adequately powered trials are needed before widespread adoption of this technology.

Purpose: To explore changes in health care professionals' views about facilitators and barriers to the diagnosis and management of heart failure, since a previous study in 2003. Methods: Using a phenomenological framework, focus groups were conducted with primary care physicians/general practitioners (GPs) (n=39 in 8 groups), cardiologists (n=4), acute physicians (n=6) and heart failure nurses (n=7). Barriers and facilitators to diagnosis and treatment were explored. Derived themes informed a national survey of left ventricular systolic dysfunction (LVSD) and heart failure with preserved ejection fraction (HFpEF). Responses from 494 clinicians across the UK included GPs (50%), consultant cardiologists (20%), heart failure nurses (16%), and acute physicians (11%). Results: From focus groups, three categories contributed to variations in diagnosis and care: uncertainty about appropriate clinical practice; the utility of clinical guidelines; individual preferences and local organisational factors - these replicated 2003 findings. Two new categories were: uncertainty about end-of-life care; uncertain lines of responsibility for care from diagnosis to end-of-life. Of those involved with heart failure diagnosis, there was variability between groups in the use of diagnostic tests. When diagnosing LVSD, 97% of cardiologists, 91% of acute physicians and 41% of GPs used echocardiographic findings. For diagnosing HFpEF, echocardiography use was broadly similarly, but cardiologists also used ECGs (65%) and chest x-rays (64%) more than other groups. Only 5% to 35% of respondents valued natriuretic peptides for LVSD or HFpEF. Confidence with test interpretation underpinned decisions about diagnostic test usage. 96% of nurses and 52%-68% of other groups found clinical guidelines helpful when diagnosing LVSD compared with just 18%-35% for HFpEF. Some GPs did not routinely initiate diuretics (23%), ACEi (22%) or β blockers (38%), based on historical teaching, risk of side effects and the burden of monitoring. There was no consensus about who held responsibility for heart failure diagnosis, management and end-of -life care. Conclusions: Reasons for variability in heart failure diagnosis and management have changed little in the last decade. Issues of variable access to diagnostic tests, delivery of care and a lack of co-ordination persist. The current UK working environment may not to be conducive to greater ownership or engagement with these difficulties. The primary need may be for health services to promote coordinated care, responsibility and training.

Background Many older people in long-term care do not receive evidence-based diagnosis or management for heart failure; it is not known whether this can be achieved for this population. We initiated an onsite heart failure service, compared with ‘usual care’ with the aim of establishing the feasibility of accurate diagnosis and appropriate management. Methods A pilot randomised controlled trial which randomised residents from 33 care facilities in North-East England with left ventricular systolic dysfunction (LVSD) to usual care or an onsite heart failure service. The primary outcome was the optimum prescription of angiotensin-converting enzyme inhibitors and beta-adrenergic antagonists at 6 months. Results Of 399 echocardiographically-screened residents aged 65–100 years, 30 subjects with LVSD were eligible; 28 (93%) consented and were randomised (HF service: 16; routine care: 12). Groups were similar at baseline; six month follow-up was completed for 25 patients (89%); 3 (11%) patients died. Results for the primary outcome were not statistically significant but there was a consistent pattern of increased drug use and titration to optimum dose in the intervention group (21% compared to 0% receiving routine care, p=0.250). Hospitalisation rates, quality of life and mortality at 6 months were similar between groups. Conclusions This study demonstrated the feasibility of an on-site heart failure service for older long-term care populations. Optimisation of medication appeared possible without adversely affecting quality of life; this questions clinicians’ concerns about adverse effects in this group. This has international implications for managing such patients. These methods should be replicated in a large-scale study to quantify the scale of benefit. Trial registration ISRCTN19781227 http://www.controlled-trials.com/ISRCTN19781227