Place of death in Parkinson's disease and related disorders in England and Wales: post-pandemic trends and implications for care planning.

BACKGROUND: With growing emphasis on palliative care for neurodegenerative conditions, understanding trends in place of death helps improve quality of end-of-life care for people with Parkinson's disease and related disorders (PDRDs), focusing allocation of resources and training and identifying inequalities. OBJECTIVES: Review national and regional place of death trends for people with PDRD including pre- and post-pandemic trends. METHODS: Mortality data for England and Wales (March 2018 and July 2022) were analysed with summary statistics and interrupted time series, exploring place of death for those who died with PDRD, with and without coexisting dementia, with reference to all deaths in England and Wales. RESULTS: Of 2,415,566 adult deaths, 56,790 included mention of PDRD. Hospital deaths were most common in people with PDRD (39.17%), followed by care homes (38.84%). People with PDRD were half as likely to die in hospice compared with the general population (2.03 vs 4.94%). Proportion of care home deaths fell significantly after March 2020 (40.6-37%, P = 0.035). Regionally, London was an outlier with a lower proportion of deaths occurring in care homes with a higher proportion of hospital deaths. CONCLUSION: Place of death for people with PDRD is changing, with more hospice and home deaths. People with PDRD, particularly those with co-existent dementia, are less likely to access inpatient hospice care than the general population. Since the COVID-19 pandemic, the proportion of care home deaths has reduced significantly with an increase in home deaths, with implications for service and resource allocation.

Mental Imagery to Reduce Alcohol-related harm in patients with alcohol use disorder and alcohol-related liver damaGE: the MIRAGE randomised pilot trial results.

OBJECTIVE: The healthcare burden of alcohol-related liver disease (ARLD) is increasing. ARLD and alcohol use disorder (AUD) is best managed by reduction or cessation of alcohol use, but effective treatments are lacking. We tested whether people with ARLD and AUD admitted to hospital could be recruited to and retained in a trial of Functional Imagery Training (FIT), a psychological therapy that uses mental imagery to reduce alcohol craving. We conducted a multicentre randomised pilot trial of treatment as usual (TAU) versus FIT+TAU in people admitted to hospital with ARLD and AUD. DESIGN: Participants were randomised to TAU (a single session of brief intervention) or FIT+TAU (TAU with one hospital-based FIT session then eight telephone sessions over 6 months). Pilot outcomes included recruitment rate and retention at day 180. Secondary outcomes included fidelity of FIT delivery, alcohol use, and severity of alcohol dependence. RESULTS: Fifty-four participants (mean age 49; 63% male) were recruited and randomised, 28 to TAU and 26 to FIT+TAU. The retention rate at day 180 was 43%. FIT was delivered adequately by most alcohol nurses. 50% of intervention participants completed FIT sessions 1 and 2. There were no differences in alcohol use or severity of alcohol dependence between treatment groups at day 180. CONCLUSION: Participants with ARLD and AUD could be recruited to a trial of FIT versus FIT+TAU. However, retention at day 180 was suboptimal. Before conducting a definitive trial of FIT in this patient group, modifications in the intervention and recruitment/retention strategy must be tested. TRIAL REGISTRATION NUMBER: ISRCTN41353774.

Improved Structure and Function in Early-Detected Second-Eye Neovascular Age-Related Macular Degeneration: FASBAT/Early Detection of Neovascular Age-Related Macular Degeneration Report 1.

PURPOSE: Visual acuity (VA) and structural biomarker assessment before and 24-months after early detection and routine treatment of second-eye involvement with neovascular age-related macular degeneration (nAMD) and additional comparison with the first eye affected. DESIGN: Prospective, 22-center observational study of participants with unilateral nAMD in the Early Detection of Neovascular AMD (EDNA) study, coenrolled into the Observing Fibrosis, Macular Atrophy and Subretinal Highly Reflective Material, Before and After Intervention with anti-VEGF Treatment (FASBAT) study for an additional 2-year follow-up. PARTICIPANTS: Older adults (> 50 years) with new onset nAMD in the first eye. METHODS: Assessment of both eyes with OCT, color fundus photography (CFP), clinic-measured VA, and quality of life (QoL). MAIN OUTCOME MEASURES: Prevalence of atrophy, subretinal hyperreflective material (SHRM), intraretinal fluid (IRF), subretinal fluid (SRF), and changes in VA over the study duration in both the first and second eyes affected with nAMD. Composite QoL scores over time. RESULTS: Of 431 participants recruited to the FASBAT study, the second eye converted to nAMD in 100 participants at a mean of 18.9 months. Visual acuity was 18 letters better at the time of early diagnosis in the second eye compared with conventional diagnosis in the first eye (72.9 vs. 55.6 letters). Visual acuity remained better in the second eye 24.9 months postconversion, at 69.5 letters compared with 59.7 letters at a similar matched time point in the first eye (18.9 months). A greater proportion of participants had vision > 70 letters in the second eye versus the first eye, 24.9 months postconversion (61 vs. 35). Prevalence of SHRM and IRF was lower in the second eye compared with the first eye 24.9 months postconversion. However, SRF prevalence was greater in the second eye 24.9 months postconversion. The development and progression of total area of atrophy appears similar in both eyes. Mean composite QoL scores increased over time, with a significant correlation between VA for the second eye only 24.9 months postconversion. CONCLUSION: This study has shown that early detection of exudative AMD in the second eye is associated with reduced prevalence of SHRM and IRF and greater VA, which is significantly correlated with maintained QoL. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The potential for medicinal cannabis to help manage challenging behaviour in people with intellectual disability: A perspective review.

BACKGROUND: Around 2% of the population have intellectual disabilities. Over one-third people with intellectual disabilities (PwID) present with 'challenging behaviour', which nosologically and diagnostically is an abstract concept. Challenging behaviour is influenced by a range of bio-psycho-social factors in a population, which is unable to suitably comprehend and/or communicate concerns. This predisposes to poor health and social outcomes. There is no evidence-based treatments for managing challenging behaviour. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are being trialled for a range of disorders, which are over-represented in PwID and provoke challenging behaviours, such as severe epilepsy, spasticity, post-traumatic stress disorder, social phobia, pain, etc. METHODS: This perspective review explores the different conditions, which benefit from medicinal CBD/THC preparations, by analysing recent literature from neurobiological, pre-clinical and clinical studies related to the topic. The evidence is synthesised to build an argument of the therapeutic benefits and challenges of medicinal cannabis to manage severe challenging behaviour in PwID. RESULTS: There is developing evidence of medicinal CBD/THC improving psychiatric and behavioural presentations in general. In particular, there is emergent proof in certain key areas of influence of medicinal CBD/THC positively supporting challenging behaviour, for example in children with neurodevelopmental disorders. However, there are significant challenges in employing such treatments in vulnerable populations such as PwID. CONCLUSION: Further clinical research for the considered use of medicinal CBD/THC for challenging behaviour management in PwID is needed. Strong co-production with experts with lived experience is needed for further testing to be done in this exciting new area.

Treatment of age-related macular degeneration with aflibercept using a treat, extend and fixed protocol; A 4-year study of treatment outcomes, durability, safety and quality of life (An extension to the MATE randomised controlled trial).

PURPOSE: Data are limited pertaining to the long-term benefits of aflibercept treatment for neovascular age-related macular degeneration (nAMD). The aim of this study was to provide outcomes, safety, durability and quality-of-life data with aflibercept using a modified treat, extend and fixed regime over 4 years. METHODS: Prospective, multicentre, single cohort observational study of treatment-naïve nAMD participants treated with aflibercept as 2-year extension of the MATE-trial that compared early and late Treat-and-Extend for 2 years. Refracted ETDRS best corrected visual acuity (BCVA), central retinal thickness (CRT), treatment interval and adverse events were assessed. Quality-of-life was measured using the Macular Disease Dependent Quality of Life (MacDQoL) and Macular Disease Treatment Satisfaction Questionnaires (MacTSQ). RESULTS: Twenty-six of 40 participants completing the MATE-trial were enrolled with 20 completing the total 4-year study. Mean BCVA was 60.7 at Month 0 and 64.8 ETDRS letters at Month 48 while CRT decreased from 423.7 µm to 292.2 µm. Five participants discontinued treatment due to inactivity. The mean number of treatments and visits for the remaining participants was 27 and 30.0, respectively, with treatment intervals extended to 12 weeks in four participants at Month 48. Both AMD-specific QoL and treatment satisfaction remained stable between Months 0 and 48 and mean BCVA significantly correlated with AMD-specific QoL scores at Months 12, 24 and 48. CONCLUSIONS: Results suggest that BCVA can be maintained over 48 months when following a treat-extend-and-fix regimen of aflibercept with intervals out to 12 weeks, while maintaining AMD-specific QoL and treatment satisfaction.

Longitudinal realist evaluation of the Dementia PersonAlised Care Team (D-PACT) intervention: protocol.

BACKGROUND: Different dementia support roles exist but evidence is lacking on which aspects are best, for whom, and in what circumstances, and on their associated costs and benefits. Phase 1 of the Dementia PersonAlised Care Team programme (D-PACT) developed a post-diagnostic primary care-based intervention for people with dementia and their carers and assessed the feasibility of a trial. AIM: Phase 2 of the programme aims to 1) refine the programme theory on how, when, and for whom the intervention works; and 2) evaluate its value and impact. DESIGN & SETTING: A realist longitudinal mixed-methods evaluation will be conducted in urban, rural, and coastal areas across South West and North West England where low-income or ethnic minority populations (for example, South Asian) are represented. Design was informed by patient, public, and professional stakeholder input and phase 1 findings. METHOD: High-volume qualitative and quantitative data will be collected longitudinally from people with dementia, carers, and practitioners. Analyses will comprise the following: 1) realist longitudinal case studies; 2) conversation analysis of recorded interactions; 3) statistical analyses of outcome and experience questionnaires; 4a) health economic analysis examining costs of delivery; and 4b) realist economic analysis of high-cost events and 'near misses'. All findings will be synthesised using a joint display table, evidence appraisal tool, triangulation, and stakeholder co-analysis. CONCLUSION: The realist evaluation will describe how, why, and for whom the intervention does or does not lead to change over time. It will also demonstrate how a non-randomised design can be more appropriate for complex interventions with similar questions or populations.

The MATE trial: a multicentre, mixed-methodology, pilot, randomised controlled trial in neovascular age-related macular degeneration.

BACKGROUND/OBJECTIVES: In healthcare research investigating complex interventions, gaps in understanding of processes can be filled by using qualitative methods alongside a quantitative approach. The aim of this mixed-methods pilot trial was to provide feasibility evidence comparing two treatment regimens for neovascular age-related macular degeneration (nAMD) to inform a future large-scale randomised controlled trial (RCT). SUBJECTS/METHODS: Forty-four treatment-naïve nAMD patients were followed over 24 months and randomised to one of two treatment regimens: standard care (SC) or treat and extend (T&E). The primary objective evaluated feasibility of the MATE trial via evaluations of screening logs for recruitment rates, nonparticipation and screen fails, whilst qualitative in-depth interviews with key study staff evaluated the recruitment phase and running of the trial. The secondary objective assessed changes in visual acuity and central retinal thickness (CRT) between the two treatment arms. RESULTS: The overall recruitment rate was 3.07 participants per month with a 40.8% non-participation rate, 18.51% screen-failure rate and 15% withdrawal/non-completion rate. Key themes in the recruitment phase included human factors, protocol-related issues, recruitment processes and challenges. Both treatment regimens showed a trend towards a visual acuity gain at month 12 which was not maintained at month 24, whilst CRT reduced similarly in both regimens over the same time period. These were achieved with one less treatment following a T&E regimen. CONCLUSION: This mixed-methodology, pilot RCT achieved its pre-defined recruitment, nonparticipation and screen failure rates, thus deeming it a success. With some minor protocol amendments, progression to a large-scale RCT will be achievable.

Impact of digital technologies on self-efficacy in people with Parkinson's: a scoping review protocol.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurological disease globally, for which currently no one definitive cause or cure exists. Estimates suggest that 145 000 people with Parkinson's (PwP) live in the UK. PD presents with motor and non-motor symptoms fluctuating significantly in and between individuals continually throughout the day. PD adversely affects activities of daily living, quality of life and well-being. Self-efficacy is an important belief to improve for PwP as it enables the individual to develop confidence in their ability to exert control over their own motivation, behaviour and social environment. This scoping review aims to identify digital technologies which have been shown to positively impact on promoting self-efficacy in PwP. METHODS AND ANALYSES: Six bibliographic databases MEDLINE, PsycINFO, Web of Science, CINAHL, EMBASE and IEEE Xplore will be searched from the date of their inception to the May 2023. The primary outcome will be to identify interventions which are associated with a change in self-efficacy in PwP to enable positive and negative outcomes, as well as safety to be evaluated. The secondary outcomes of this review will focus on the intervention's proposed mechanisms for success, particularly looking at the impact they had on positive behaviour change(s) or modification(s) on study participants. ETHICS AND DISSEMINATION: This scoping review will not require ethical approval as it will use data collected from previously published primary studies. The findings of this review will be published in peer-reviewed journals and widely disseminated.

Routinely used interventions to improve attachment in infants and young children: a national survey and two systematic reviews.

BACKGROUND: Attachment refers to an infant's innate tendency to seek comfort from their caregiver. Research shows that attachment is important in promoting healthy social and emotional development. Many parenting interventions have been developed to improve attachment outcomes for children. However, numerous interventions used in routine practice have a limited evidence base, meaning that we cannot be sure if they are helpful or harmful. OBJECTIVES: This research aimed to conduct a large-scale survey to identify what interventions are being used in UK services to improve child attachment; conduct a systematic review to evaluate the evidence for parenting attachment interventions; and develop recommendations for future research and practice. DESIGN AND METHODS: We worked closely with our Expert Reference Group to plan a large-scale survey focused on relevant UK services. We then conducted two systematic reviews. One searched for all randomised controlled trial evidence for any attachment parenting intervention. The second searched for all research for the top 10 routinely used interventions identified from the survey. RESULTS: The survey collected 625 responses covering 734 UK services. The results identified the 10 most commonly used interventions. The responses showed a limited use of validated measures and a wide variety of definitions of attachment. For the first review, seven studies were included from 2516 identified records. These were combined with results from previous reviews conducted by the team. Meta-analyses showed that, overall, parenting interventions are effective in reducing disorganised attachment (pooled odds ratio 0.54, 95% confidence interval 0.39 to 0.77) and increasing secure attachment (pooled odds ratio 1.85, 95% confidence interval 1.36 to 2.52). The second review searched the literature for the top 10 routinely used interventions identified by the survey; 61 studies were included from 1198 identified records. The results showed that many of the most commonly used interventions in UK services have a weak evidence base and those with the strongest evidence base are not as widely used. CONCLUSIONS: There is a need for better links between research and practice to ensure that interventions offered to families are safe and effective. Possible reasons for the disparity include the cost and accessibility of training. There is also a need for improved understanding by professionals regarding the meaning of attachment. LIMITATIONS: Although the survey had good geographical spread, most respondents were based in England. For review 2 we were unable to access a large number of papers; however, we conducted extensive reference checking to account for this. FUTURE WORK: There is a need for robust research to test the efficacy of routinely used attachment interventions. Research could also explore why routinely used interventions are not consistently subject to thorough evaluation; how to embed dissemination, cost-effectiveness, fidelity and sustainability into research; and how to keep clinical practice up to date with research developments. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019137362. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 2. See the NIHR Journals Library website for further project information.

Attachment refers to an infant's natural instinct to seek comfort from their main carers. There are four ways in which infants show attachment ('attachment patterns'). These are known as secure, insecure-avoidant, insecure-resistant and disorganised. Secure attachment usually occurs with consistent and responsive parenting/caregiving and is linked with positive social and emotional child development. Inconsistent, neglectful or abusive parenting/caregiving can lead to problems with attachment, including disorganised attachment, and is linked to poorer outcomes. Parenting support, education and therapies help parents improve infant attachment and their child's outcomes. We surveyed UK services to see what they offered families with attachment problems. A total of 734 UK services responded. This identified 10 therapies or support packages most commonly offered to parents. We checked what research had been done on these. We found very little. We found 61 studies of support packages with quite good evidence, but these were generally not ones offered by UK services. We also looked in detail at research for all types of support/therapies to improve attachment. We looked for the best research (called 'randomised controlled trials'); 26 studies had tested therapies to see if they improved secure attachment and 20 had tested whether or not they improved (i.e. reduced) disorganised attachment. We found that these therapies or support packages are good at increasing secure attachment and improving disorganised attachment. Mostly they did this by helping parents/caregivers improve caregiving and particularly how sensitive and responsive they are to their child and their needs. Currently, practice is not following research, and research is not being done to properly evaluate current practice. We need to improve the evidence and the way it links to practice, including how those organising and paying for services are made aware of up-to-date research to make sure that the best treatments are available. High-quality training for staff is also important.

Comparison of Diagnostic Profiles of Deaf and Hearing Children with a Diagnosis of Autism.

There is limited research comparing the presentation of autism in deaf and hearing children and young people. These comparisons are important to facilitate accurate diagnosis, as rates of misdiagnosis and delay in diagnosis amongst deaf children and young people are high. The aim of this study was to compare diagnostic assessment profiles of a UK cohort of autistic deaf and hearing children and young people. The Autism Diagnostic Interview-Revised-Deaf adaptation was completed with the parents of 106 children and young people (deaf children = 65; hearing children = 41). The majority of items explored showed no significant differences between deaf and hearing children and young people. Differences were found in peer relationships, where autistic deaf participants were less likely to respond to the approaches of other children or play imaginatively with peers. These findings need to be taken into consideration by clinicians in the assessment process.

Mixed-methods feasibility cluster randomised controlled trial of a paramedic-administered breathlessness management intervention for acute-on-chronic breathlessness (BREATHE): study findings.

Introduction: One-fifth of emergency department presentations by ambulance are due to acute-on-chronic breathlessness. We explored the feasibility of an evaluation-phase, cluster randomised controlled trial (cRCT) of the effectiveness and cost-effectiveness of a paramedic-administered, non-pharmacological breathlessness intervention for people with acute-on-chronic breathlessness at ambulance call-out (BREATHE) regarding breathlessness intensity and conveyance to hospital. Methods: This mixed-methods, feasibility cRCT (ISRCTN80330546) randomised paramedics to usual care or intervention plus usual care. Retrospective patient consent to use call-out data (primary end-point) and prospective patient/carer consent for follow-up was sought. Potential primary outcomes included breathlessness intensity (numerical rating scale) and conveyance. Follow-up included: interviews with patients/carers and questionnaires at 14 days, 1 and 6 months; paramedic focus groups and surveys. Results: Recruitment was during COVID-19, with high demands on paramedics and fewer call-outs by eligible patients. We enrolled 29 paramedics; nine withdrew. Randomisation/trial procedures were acceptable. Paramedics recruited 13 patients, not meeting recruitment target (n=36); eight patients and three carers were followed-up. Data quality was good but insufficient for future sample size estimation. The intervention did not extend call-out time, was delivered with fidelity and was acceptable to patients, carers and paramedics. There were no repeat call-outs within 48 h. All trained paramedics strongly recommended BREATHE as a highly relevant, simple intervention. Conclusion: Patient recruitment to target was not feasible during the pandemic. Training and intervention were acceptable and delivered with fidelity. Results include valuable information on recruitment, consent, attrition and data collection that will inform the design and delivery of a definitive trial.

Parkinson's disease - palliative care needs assessment tool: adaptation and psychometric testing.

OBJECTIVE: Parkinson's disease is a progressive, life-limiting disease, which benefits from structured palliative care. Systematic recognition and triage of needs helps facilitate care, allows focused referral to specialist palliative care and aids sustainability of services. Existing palliative care tools for Parkinson's are patient/caregiver completed and focus on quantification rather than identification of the need. The Needs Assessment Tool: Progressive Disease in Cancer was designed for rapid identification of unmet needs in cancer. We describe adaptation and psychometric testing of the tool for Parkinson's disease (NAT:Parkinson's disease). METHODS: Set in secondary care, Parkinson's disease outpatient clinics in the UK, this study included people with Parkinson's, age >18, including all disease stages. People with atypical Parkinsonian syndromes were excluded. Adaptation was made using systematic review and focus groups. Construct validity was tested in 50 consecutive patients against established patient and caregiver measures, analysed with Kendall's Tau B. Inter-rater reliability, using video consultations, were calculated in broad range of clinicians involved in Parkinson's disease care using a weighted kappa; 0-0.2=slight, 0.21-0.40=fair, 0.41-0.60=moderate, 0.61-0.80=substantial and p<0.05 indicative of statistically significant agreement. RESULTS: Validity was substantial for two, moderate for five and fair for four constructs. Inter-rater reliability was substantial for one, moderate for three and fair for six constructs. Two constructs failing to demonstrate fair reliability did show very high percentage agreement. CONCLUSION: Findings support the suitability of the NAT:Parkinson's disease for everyday clinical use in the identification and triage of unmet palliative need for people with Parkinson's disease.

Implementing Affordable Socially Assistive Pet Robots in Care Homes Before and During the COVID-19 Pandemic: Stratified Cluster Randomized Controlled Trial and Mixed Methods Study.

BACKGROUND: Robot pets may assist in the challenges of supporting an aging population with growing dementia prevalence. Prior work has focused on the impacts of the robot seal Paro on older adult well-being, but recent studies have suggested the good acceptability and implementation feasibility of more affordable devices (Joy for All [JfA] cats and dogs). OBJECTIVE: We aimed to address the limited effectiveness research on JfA devices. METHODS: We conducted an 8-month, stratified, cluster randomized controlled trial in 8 care homes in Cornwall, United Kingdom. Over 4 months, 4 care homes each received 2 JfA devices (1 cat and 1 dog; intervention group), and 4 homes received care as usual (control group). Psychometrics were collected before and after the intervention to compare the change from baseline to follow-up between the groups. In the final 4 months, all 8 care homes received devices, but only qualitative data were collected owing to COVID-19 and reduced capacity. The primary outcome was neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI] Nursing Home version). Care provider burden was a secondary outcome (occupational disruptiveness NPI subscale), alongside the Challenging Behavior scale, the Holden communication scale, the Campaign to End Loneliness questionnaire, and medication use. Qualitative data were collected through care staff observation calendars and end-of-study interviews to understand use, experience, and impact. We also collected demographic data and assessed dementia severity. In total, 253 residents had robot interaction opportunities, and 83 were consented for direct data collection. RESULTS: There was a significant difference in the total change from baseline to follow-up between the intervention and control groups for NPI (P<.001) and occupational disruptiveness (P=.03). Neuropsychiatric symptoms increased in the control group and decreased in the intervention group. No significant difference was seen for communication issues or challenging behavior. For NPI subdomains, there were significant differences from baseline to follow-up in delusions (P=.03), depression (P=.01), anxiety (P=.001), elation (P=.02), and apathy (P=.009), all of which decreased in the intervention group and increased slightly in the control group. The summative impact results suggested that most residents (46/54, 85%) who interacted with robots experienced a positive impact. Those who interacted had significantly higher dementia severity scores (P=.001). The qualitative results suggested good adoption, acceptability, and suitability for subjectively lonely individuals and lack of a novelty effect through sustained use, and demonstrated that the reasons for use were entertainment, anxiety, and agitation. CONCLUSIONS: Affordable robot pets hold potential for improving the well-being of care home residents and people with dementia, including reducing neuropsychiatric symptoms and occupational disruptiveness. This work suggests no novelty effect and contributes toward understanding robot pet suitability. Moreover, interactions were more common among residents with more moderate/severe dementia and those subjectively lonely. TRIAL REGISTRATION: ClinicalTrials.gov NCT04168463; https://www.clinicaltrials.gov/ct2/show/NCT04168463.

Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of IBS with diarrhoea (IBS-D).

OBJECTIVE: Irritable bowel syndrome with diarrhoea (IBS-D) is a common and challenging condition that significantly reduces quality of life. Enterosgel (polymethylsiloxane polyhydrate) is an intestinal adsorbent which sequesters harmful molecules and is safe and effective in acute infective diarrhoea. This randomised controlled multicentre trial aimed to investigate its safety and efficacy in patients with IBS-D. DESIGN: After a 2-week screening phase, participants were randomised into an 8-week double-blind phase, followed by an 8-week open-label and follow-up phase. Participants recorded stool consistency, pain and global symptoms in e-diaries and questionnaires. The primary outcome was the percentage of responders on a composite abdominal pain (≥30% decrease in the weekly score) and stool consistency (50% reduction in days per week with at least one stool of BSFS type 6 or 7) score during at least 4 weeks of the treatment period. RESULTS: 440 patients with IBS-D were randomised to the double-blind phase with 393 continuing to the open-label phase. The Primary outcome responder rate by intention-to-treat for enterosgel versus placebo was 37.4% vs 24.3% (OR 1.95, NNT 8, p=0.002). Enterosgel also improved stool consistency (48.5% vs 32.5%, p<0.0001) abdominal pain (53.3% vs 40.2%, p=0.003), stool frequency (treatment effect -0.32 (-0.62 to -0.02)) and urgency (treatment effect -0.59 (-0.85 to -0.33)). 60% of patients reported adequate relief of symptoms after open-label treatment. Adverse event frequency was similar in both groups, with no serious events attributable to enterosgel. CONCLUSION: Enterosgel is safe and effective in IBS-D, providing an alternative to the limited current treatment options. TRIAL REGISTRATION NUMBER: ISRCTN17149988.

Mental Imagery to Reduce Alcohol-related harm in patients with alcohol dependence and alcohol-related liver damaGE: the MIRAGE pilot trial protocol.

INTRODUCTION: In the UK, alcohol use is the main driver of chronic liver disease and each year results in over 1 million unplanned hospital admissions and over 25 000 deaths from alcohol-related liver disease (ArLD). The only effective treatment to prevent progression of liver damage is reducing or ceasing alcohol consumption. Psychological and pharmacological therapies for alcohol misuse are ineffective in patients with ArLD. Functional imagery training (FIT) is a novel psychological therapy that builds on motivational interviewing techniques with multisensory imagery. This pilot trial aims to test the feasibility of training alcohol liaison nurses to deliver FIT therapy and of recruiting and retaining patients with ArLD and alcohol dependence to a randomised trial of FIT and treatment as usual (TAU) versus TAU alone. METHODS AND ANALYSIS: This is a randomised pilot trial of FIT and TAU versus TAU alone in 90 patients with ArLD and alcohol dependence admitted to one of four UK centres. The primary objectives are to estimate rates of screening, recruitment, randomisation, retention, adherence to FIT/TAU and a preliminary assessment of the FIT intervention in the ArLD population. Data from the pilot study will be used to finalise the design of a definitive randomised controlled trial to assess the effectiveness and cost-effectiveness of FIT. The proposed primary outcome measure for the definitive trial is self-reported alcohol use assessed using timeline follow-back. ETHICS AND DISSEMINATION: Research ethics approval was given by the Yorkshire and Humber-Bradford Leeds Research Ethics Committee (reference: 21/YH/0044). Eligible patients will be approached and written informed consent obtained prior to participation. Results will be disseminated through peer-reviewed open access journals, international conferences and a lay summary published on the Trials Unit website and made available to patient groups. TRIAL REGISTRATION NUMBER: ISRCTN41353774.

Analysis of oxidative stress, inflammation and endothelial function following intravenous iron in chronic kidney disease in the Iron and Heart Trial.

Iron deficiency commonly affects patients with chronic kidney disease and has an important burden in disease trajectory and quality of life; nonetheless current guidelines do not advocate treatment of iron-deficiency without anemia in this patient group. Concerns exist regarding the potential effects of intravenous iron on oxidative stress, inflammation, and endothelial function. As part of a multicenter double-blinded randomized controlled clinical trial, we examined the effects of a single dose of intravenous iron vs. placebo on biomarkers of oxidative stress, inflammation and endothelial function in non-anemic iron deficient patients (serum ferritin < 100 µg/L and/or transferrin saturation < 20%) with chronic kidney disease (stage 3b-5). Fifty-four individuals were randomized to receive ferric derisomaltose (n = 26) or placebo (n = 28). Ferric derisomaltose was associated with a non-significant decrease in mean F2-isoprostane and no effect on thiobarbituric acid reactive substances when compared to placebo throughout follow up. No effect on inflammatory markers was observed. A modest but statistically significant rise in E-selectin was noted in the intravenous iron group at 1 month and 3 month follow-up (p = 0.030 and p = 0.002 respectively). These results suggest ferric derisomaltose administration in non-dialysis dependent chronic kidney disease patients who are iron deficient does not induce prolonged oxidative stress or inflammation. Larger trials are required to quantify the benefit of intravenous iron administration in this patient group.

Adapting and validating the Autism Diagnostic Interview - Revised for use with deaf children and young people.

LAY ABSTRACT: Autism assessment processes need to improve for deaf children as they are currently being diagnosed later than their hearing counterparts and misdiagnosis can occur. We took one of the most commonly used parent developmental interviews for autism spectrum disorder the Autism Diagnostic Interview-Revised and adapted it using international expert advice. Modifications were proposed and agreed by the expert panel for 45% of items; the remaining 55% of items were unchanged. We then tested the revised version, adapted for deaf children (Autism Diagnostic Interview-Revised Deaf Adaptation), in a UK sample of 78 parents/carers of deaf children with autism spectrum disorder and 126 parents/carers with deaf children without autism spectrum disorder. When compared to National Institute for Health and Care Excellence guideline standard clinical assessments, the Autism Diagnostic Interview-Revised Deaf Adaptation diagnostic algorithm threshold scores could identify those deaf children with a definite diagnosis (true autism spectrum disorder positives) well (sensitivity of 89% (79%-96%)) and those deaf children who did not have autism spectrum disorder (true autism spectrum disorder negatives) well (specificity of 81% (70%-89%)). Our findings indicate that the Autism Diagnostic Interview-Revised Deaf Adaptation is likely to prove a useful measure for the assessment of deaf children with suspected autism spectrum disorder and that further research would be helpful.

Australia-modified Karnofsky Performance Scale and physical activity in COPD and lung cancer: an exploratory pooled data analysis.

OBJECTIVES: Patient-relevant measures of functional status are required in chronic obstructive pulmonary disease (COPD) and lung cancer in clinical practice and research. We explored the relationship between the Australia-modified Karnofsky Performance Scale (AKPS) and measures of functional capacity and physical activity in these patient groups. METHODS: Pooled clinical trial data were analysed to explore the relationship between AKPS and average daily steps (ADS), 6 min walk distance (6MWD), and body mass index, airflow obstruction, dyspnoea and exercise score (COPD group). Receiver operator characteristic curves were produced to compare sensitivity and specificity of cut-offs (no dependency >70, high dependency <60) and area under the curve (AUC). RESULTS: Seven clinical trials included people with COPD (n=79) and lung cancer (n=150). To detect an AKPS of >70, the optimal ADS cut-points were COPD, 3342 steps (AUC 0.88, 95% CI 0.79 to 0.97, sensitivity 82%, specificity 76%), and lung cancer, 3380 steps (AUC 0.72, 95% CI 0.64 to 0.81, sensitivity 61%, specificity 74%), and for 6MWD (COPD only) 242 m (AUC 0.72, 95% CI 0.63 to 0.81, sensitivity 73%, specificity 34%). CONCLUSIONS: An AKPS score is strongly related to ADS in people with COPD and lung cancer. The AKPS may be useful in clinical practice and research to indicate levels of physical activity where ADS and 6 min walk test are not possible. Longitudinal data are needed to confirm these findings.

Mental wellbeing in bereaved carers: A Health Survey for England population study.

OBJECTIVES: The experience of caregiving may affect carers' well-being into bereavement. We explored associations between mental well-being and previous experience of bereavement of, and caring for, someone close at the end-of-life. METHODS: An end-of-life set of questions was included in population-based household survey administered to adults (age 16 years and above). We used univariable regression to explore the cross-sectional relationship between our primary outcome (Warwick-Edinburgh Mental Well-being Scale (WEMWBS)) and possible explanatory variables: sociodemographic; death and bereavement including ability to continue with their life; disease and carer characteristics; service use and caregiving experience. RESULTS: The analysis dataset included 7606 of whom 5849 (77%) were not bereaved, 1174 (15%) were bereaved but provided no care and 583 (8%) were bereaved carers. WEMWBS was lower in the oldest age class (85 years and above) in both bereaved groups compared with not bereaved (p<0.001). The worst WEMWBS scores were seen in the 'bereaved but no care' group who had bad/very bad health self-assessed general health (39.8 (10.1)) vs 41.6 (9.5)) in those not bereaved and 46.4 (10.7) in bereaved carers. Among the bereaved groups, those who would not be willing to care again had lower WEMWBS scores than those who would (48.3 (8.3) vs 51.4 (8.4), p=0.024). CONCLUSION: Mental well-being in bereavement was worse in people with self-reported poor/very poor general health and those with a worse caregiving experience. Although causality cannot be assumed, interventions to help people with worse mental and physical health to care, so that their experience is as positive as possible, should be explored prospectively.

'Hospice inpatient deep vein thrombosis detection (HIDDen) in advanced non-malignant diseases': a longitudinal pilot study.

OBJECTIVES: To gain preliminary data regarding the prevalence of proximal deep vein thrombosis (DVT) in those with non-malignant conditions admitted to specialist palliative care units (SPCUs). METHODS: Data were collected as part of a prospective longitudinal observational study in five SPCUs in England, Wales and Northern Ireland (Registration: ISRCTN97567719) to estimate the prevalence of proximal femoral vein DVT in people admitted to SPCUs. The primary outcome for this exploratory substudy was the prevalence of DVT in patients with non-malignant palliative conditions. Consecutive consenting adults underwent bilateral femoral vein ultrasonography within 48 hours of admission. Data were collected on symptoms associated with venous thromboembolism. Patients were ineligible if the estimated prognosis was <5 days. Cross-sectional descriptive analysis was conducted on baseline data and prevalence estimates presented with 95% CIs. RESULTS: 1390 patients were screened, 28 patients had non-malignant disease and all were recruited. The mean age 68·8 (SD 12·0), range 43-86 years; men 61%; survival mean 86 (SD 108.5) range 1-345 days. No patient had a history of venous thromboembolism. Four (14%) were receiving thromboprophylaxis. Of 22 evaluable scans, 8 (36%, 95% CI: 17% to 59%) showed femoral vein DVT. The level of reported relevant symptoms (leg oedema, leg pain, chest pain and breathlessness) was high irrespective of the presence of DVT. CONCLUSIONS: Our exploratory data indicate one in three people admitted to an SPCU with non-malignant disease had a femoral vein DVT. Although definitive conclusions cannot be drawn, these data justify a larger prospective survey.