Legal Issues in Life-Limiting Illness: Can Cross-Agency, Interprofessional Education Support Integration of Care?

Legal issues are prevalent in life-limiting illness, relating to social welfare needs as well as delivery of legally compliant care. Yet the broad range of agencies delivering care is fragmented, risking unmet needs. This mixed-methods research explored the potential of cross-agency, interprofessional education to raise awareness and understanding of legal needs in this context and promote closer service integration. Four identical workshops, run in north-east England, brought together 99 participants from health, social, legal, advice, charitable, public and private sectors. Participants were overwhelmingly positive about the value of learning together with 97% wanting more sessions. Learning priorities included greater awareness of services and referral routes as well as areas of law relating to advance care planning and mental capacity. Interprofessional education, spanning the breadth of relevant agencies and supported by national strategy, was identified as a route to integrating services.

Qualitative investigation of patient and carer experiences of everyday legal needs towards end of life.

BACKGROUND: Legal issues are common in chronic illness. These include matters of daily life, such as problems with employment, finances and housing, where rights or entitlements are prescribed by law. They also include planning ahead, for example, making a Lasting Power of Attorney. However, the nature, impact and management of legal needs in the context of end of life care are not known. This study investigated these from the perspectives of patients and carers. METHODS: Patients, with estimated prognosis 12 months or less, and carers were recruited from two sites: day services within an urban hospice and primary care in an area of deprivation in North-East England. Semi-structured interviews explored the nature and impact of legal issues, access to appropriate support and unmet needs. Thematic analysis of data was undertaken. RESULTS: Twenty-seven interviews were conducted with 14 patients (10/14 hospice) and 13 carers (7/13 hospice). Five were patient-carer dyads. All participants had experienced problems raising legal issues, which generated significant practical and psychological challenges. All had struggled to access support for social welfare legal issues, describing not knowing what, who, or when to ask for help. All participants accessed some support, however routes, timing and issues addressed were variable. Facilitators included serendipitous triggers and informed healthcare professionals who offered support directly, or signposted elsewhere. A range of professionals and organisations provided support; resolution of issues conferred substantial benefit. The majority of participants identified unresolved legal issues, predominantly related to planning ahead. The challenge of facing increased dependency and death proved a key barrier to this; informed and compassionate healthcare professionals were important enablers. CONCLUSION: Everyday legal needs are a common and distressing consequence of life-limiting illness, affecting patients and carers alike. This study identified inconsistent approaches but practical and psychological benefit when needs were met. Healthcare professionals were central to meeting social welfare legal needs and facilitating effective planning, with important roles as 'critical noticers', trusted intermediaries and compassionate communicators. Increased awareness, clearer pathways to support and closer service integration are needed to meet legal needs as a component of holistic care.

Maximizing Telerehabilitation for Patients With Visual Loss After Stroke: Interview and Focus Group Study With Stroke Survivors, Carers, and Occupational Therapists.

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.

Legal needs of adults with life-limiting illness: what are they and how are they managed? A qualitative multiagency stakeholder exercise.

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.

What were the impacts of the Committee on Safety of Medicines warning and publication of the NICE guidelines on trends in child and adolescent antidepressant prescribing in primary care? A population based study.

OBJECTIVES: To assess the impact of both the Committee on Safety of Medicines (CSM) warning (December 2003) and the National Institute for Health and Care Excellence (NICE) guidance (September 2005) on antidepressant prescription rates in children and adolescents within the UK primary care service. SETTING: Population based study of primary care antidepressant prescribing using the Clinical Practice Research Datalink (CPRD). PARTICIPANTS: Under-18s presenting to primary care with a depressive disorder or related diagnostic code recorded in the CPRD. PRIMARY OUTCOME MEASURE: Antidepressant prescription rates per month per 100 000 depressed 4-17 year olds. RESULTS: Following the CSM warning, the prior trend towards increased prescribing rates for selective serotonin reuptake inhibitors (SSRIs) in children was significantly reversed (ß for change in trend -12.34 (95% CI -18.67 to -6.00, p<0.001)). However, after the publication of the NICE guidelines the prior trend towards increased prescribing resumed for those SSRIs mentioned as potential treatments in the guidance (fluoxetine, citalopram and sertraline) (ß for change in trend 11.52 (95% CI 5.32 to 17.73, p<0.001)). Prescribing of other SSRIs and tricyclics remained low. CONCLUSIONS: Despite a strong emphasis on psychosocial interventions for child and adolescent depression, it may be that the NICE guidelines inadvertently encouraged further antidepressant prescribing, at least for those SSRIs cited. Although the guidelines gave cautions and caveats for the use of antidepressants, practitioners may have interpreted these recommendations as endorsing their use in young people with depression and related conditions. However, more accurate prevalence trend estimates for depression in this age group, and information on the use of psychosocial interventions would be needed to rule out other reasons underlying this increase in prescribing.

A randomized double-blinded sham-controlled cross-over trial of tined-lead sacral nerve stimulation testing for chronic constipation.

OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Should heart failure be regarded as a terminal illness requiring palliative care? A study of heart failure patients', carers' and clinicians' understanding of heart failure prognosis and its management.

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.

Low-volume versus high-volume initiated trans-anal irrigation therapy in adults with chronic constipation: study protocol for a randomised controlled trial.

BACKGROUND: Constipation is common in adults and up to 20% of the population report this symptom. Chronic constipation (CC), usually defined as more than 6 months of symptoms, is less common but results in 0.5 million UK GP consultations per annum. The effect of symptoms on measured quality of life (QOL) is significant, and CC consumes significant health care resources. In the UK, it is estimated that 10% of district nursing time is spent on constipation. Trans-anal irrigation therapy has become a widely used treatment despite a lack of robust efficacy data to support its use. The long-term outcome of treatment is also unclear. A randomised comparison of two different methods of irrigation (high- and low-volume) will provide valuable evidence of superiority of one system over the other, as well as providing efficacy data for the treatment as a whole. METHODS: Participants will be recruited based on predetermined eligibility criteria. Following informed consent, they will be randomised to either high-volume (HV) or low-volume (LV) irrigation and undergo standardised radiological and physiological investigations. Following training, they will commence home irrigation with the allocated device. Data will be collected at 1, 3, 6 and 12 months according to a standardised outcomes framework. The primary outcome is PAC-QOL, measured at 3 months. The study is powered to detect a 10% difference in outcome between systems at 3 months; this means that 300 patients will need to be recruited. DISCUSSION: This study will be the first randomised comparison of two different methods of trans-anal irrigation. It will also be the largest prospective study of CC patients treated with irrigation. It will provide evidence for the effectiveness of irrigation in the treatment of CC, as well as the comparative effectiveness of the two methods. This will enable more cost-effective and evidence-based use of irrigation. Also, the results will be combined with the other studies in the CapaCiTY programme to generate an evidence-based treatment algorithm for CC in adults. TRIAL REGISTRATION: ISRCTN, identifier: ISRCTN11093872 . Registered on 11 November 2015. Trial not retrospectively registered. Protocol version 3 (22 January 2016).

Narrow band imaging optical diagnosis of small colorectal polyps in routine clinical practice: the Detect Inspect Characterise Resect and Discard 2 (DISCARD 2) study.

BACKGROUND: Accurate optical characterisation and removal of small adenomas (<10 mm) at colonoscopy would allow hyperplastic polyps to be left in situ and surveillance intervals to be determined without the need for histopathology. Although accurate in specialist practice the performance of narrow band imaging (NBI), colonoscopy in routine clinical practice is poorly understood. METHODS: NBI-assisted optical diagnosis was compared with reference standard histopathological findings in a prospective, blinded study, which recruited adults undergoing routine colonoscopy in six general hospitals in the UK. Participating colonoscopists (N=28) were trained using the NBI International Colorectal Endoscopic (NICE) classification (relating to colour, vessel structure and surface pattern). By comparing the optical and histological findings in patients with only small polyps, test sensitivity was determined at the patient level using two thresholds: presence of adenoma and need for surveillance. Accuracy of identifying adenomatous polyps <10 mm was compared at the polyp level using hierarchical models, allowing determinants of accuracy to be explored. FINDINGS: Of 1688 patients recruited, 722 (42.8%) had polyps <10 mm with 567 (78.5%) having only polyps <10 mm. Test sensitivity (presence of adenoma, N=499 patients) by NBI optical diagnosis was 83.4% (95% CI 79.6% to 86.9%), significantly less than the 95% sensitivity (p<0.001) this study was powered to detect. Test sensitivity (need for surveillance) was 73.0% (95% CI 66.5% to 79.9%). Analysed at the polyp level, test sensitivity (presence of adenoma, N=1620 polyps) was 76.1% (95% CI 72.8% to 79.1%). In fully adjusted analyses, test sensitivity was 99.4% (95% CI 98.2% to 99.8%) if two or more NICE adenoma characteristics were identified. Neither colonoscopist expertise, confidence in diagnosis nor use of high definition colonoscopy independently improved test accuracy. INTERPRETATION: This large multicentre study demonstrates that NBI optical diagnosis cannot currently be recommended for application in routine clinical practice. Further work is required to evaluate whether variation in test accuracy is related to polyp characteristics or colonoscopist training. TRIAL REGISTRATION NUMBER: The study was registered with clinicaltrials.gov (NCT01603927).

Trans-anal irrigation therapy to treat adult chronic functional constipation: systematic review and meta-analysis.

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 (I(2) = 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.

Risk of Ischaemic Heart Disease in Patients with Inflammatory Bowel Disease: Cohort Study Using the General Practice Research Database.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) demonstrate an inflammatory response which bears some similarities to that seen in ischaemic heart disease (IHD). The nature of the association of IBD with IHD is uncertain. We aimed to define the extent and direction of that association. DESIGN: This retrospective cohort study examined records from patients aged ≥ 15 years with IBD from 1987-2009 (n = 19163) who were age and gender matched with patients without IBD (n = 75735) using the General Practice Research Database. The primary outcome was the hazard ratio for IHD. RESULTS: A higher proportion of IBD patients had a recorded diagnosis of IHD ever, 2220 (11.6%) compared with 6504 (8.6%) of controls. However, the majority (4494, 51.5%) developed IHD prior to IBD diagnosis (1404 (63.2%) of IBD cases and 3090 (47.5%) of controls). There was increased IHD incidence in the first year after IBD diagnosis. Mean age at IHD diagnosis was statistically similar across all IBD groups apart from for those with Ulcerative Colitis (UC) who were slightly younger at diagnosis of angina compared to controls (64.5y vs. 67.0y, p = 0.008) and coronary heart disease (65.7y vs.67.9y, p = 0.015). Of those developing IHD following IBD diagnosis, UC patients were at higher risk of IHD (unadjusted HR 1.3 (95% CI 1.1-1.5), p<0.001) or MI (unadjusted HR 1.4 (95% CI 1.1-1.6), p = 0.004). CONCLUSION: Although IHD prevalence was higher in IBD patients, most IHD diagnoses predated the diagnosis of IBD. This implies a more complex relationship than previously proposed between the inflammatory responses associated with IHD and IBD, and alternative models should be considered.

'Therapeutic landscapes' and the importance of nostalgia, solastalgia, salvage and abandonment for psychiatric hospital design.

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.

Contraceptive use and pregnancy outcomes among opioid drug-using women: a retrospective cohort study.

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<0.001), had more frequent pregnancy terminations (0.46 vs. 0.025, p = 0.004) and higher annual incidence of chlamydia (1.1% vs. 0.33%, p<0.001), when compared with age-matched population data. Specifically, there was low use of oral contraceptives (4% vs. 25%, p<0.001), IUCD (1% vs. 6%, p<0.001), and sterilisation (7% vs. 6%, p = 0.053), but higher rates of injectable contraceptives (6% vs. 3%, p = 0.003). A total of 64% of children aged <16 years born to this group did not live with their mother. No individual risk factor (such as sex-working) significantly explained the lower use or type of non-condom contraception. CONCLUSIONS: This is the first study to describe planned contraceptive use among drug-users, as well as the association with a range of risk factors and pregnancy outcomes. The low uptake of planned contraception, set against high rates of terminations and sexually transmitted disease demonstrates the urgent clinical need to improve contraceptive services, informed by qualitative work to explore the values and beliefs influencing low contraceptive uptake.

Mental imagery in bipolar affective disorder versus unipolar depression: investigating cognitions at times of 'positive' mood.

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.

Barriers to accurate diagnosis and effective management of heart failure have not changed in the past 10 years: a qualitative study and national survey.

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 ß-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.

Renal failure in lithium-treated bipolar disorder: a retrospective cohort study.

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.

Biodegradable stent or balloon dilatation for benign oesophageal stricture: pilot randomised controlled trial.

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.

Spaces for smoking in a psychiatric hospital: social capital, resistance to control, and significance for 'therapeutic landscapes'.

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.

Structural basis of high-order oligomerization of the cullin-3 adaptor SPOP.

Protein ubiquitination in eukaryotic cells is mediated by diverse E3 ligase enzymes that each target specific substrates. The cullin E3 ligase complexes are the most abundant class of E3 ligases; they contain various cullin components that serve as scaffolds for interaction with substrate-recruiting adaptor proteins. SPOP is a BTB-domain adaptor of the cullin-3 E3 ligase complexes; it selectively recruits substrates via its N-terminal MATH domain, whereas its BTB domain mediates dimerization and interactions with cullin-3. It has recently been recognized that the high-order oligomerization of SPOP enhances the ubiquitination of substrates. Here, a dimerization interface in the SPOP C-terminus is identified and it is shown that the dimerization interfaces of the BTB domain and of the C-terminus act independently and in tandem to generate high-order SPOP oligomers. The crystal structure of the dimeric SPOP C-terminal domain is reported at 1.5 Šresolution and it is shown that Tyr353 plays a critical role in high-order oligomerization. A model of the high-order SPOP oligomer is presented that depicts a helical organization that could enhance the efficiency of substrate ubiquitination.