East Midlands Evidence Repository: Recent submissions
Now showing items 21-40 of 9535
-
Transcriptomic analysis of plasma small extracellular vesicles identifies potential diagnostic biomarkers for Parkinson's disease dementiaIntroductionBlood-based biomarkers that can aid diagnosis of Parkinson's Disease (PD) dementia (PDD), and predict PDD onset in people with PD are urgently needed. Plasma small extracellular vesicles (SEV) reflect molecular changes in living human brain. Next-generation RNA-sequencing (RNA-Seq) of PDD plasma SEV can advance our understanding of PDD molecular pathology, and identify blood-based biomarkers. Hence, we conducted the first comprehensive transcriptomic analysis of PDD plasma SEV.
-
Mixed-methods non-randomised single-arm feasibility study assessing delivery of a remote vocational rehabilitation intervention for patients with serious injury : the ROWTATE studyObjectives This study aimed to evaluate the feasibility of delivering a vocational rehabilitation intervention (Return to Work After Trauma—ROWTATE), remotely to individuals recovering from traumatic injuries. The primary objectives were to assess therapists’ training and competence, adapt the intervention and training for remote delivery and assess the feasibility and fidelity of remote delivery to inform a definitive randomised controlled trial.Design A mixed-methods feasibility study incorporating (1) telerehabilitation qualitative literature review, (2) qualitative interviews preintervention and postintervention with therapists and patients, (3) a team objective structured clinical examination to assess competency, (4) usefulness of training, attitudes towards (15-item Evidence-Based Practice Attitude Scale) and confidence in (4-item Evidence Based Practice Confidence Scale) evidence-based practice, intervention delivery confidence (8-bespoke questions) and intervention behaviour determinants (51-items Theoretical Domains Framework) and (5) single-arm intervention delivery feasibility study.Setting The study was conducted in two UK Major Trauma Centres. The intervention and training were adapted for remote delivery due to the COVID-19 pandemic.Participants Therapists: Seven occupational therapists (OTs) and clinical psychologists (CPs) were trained, and six participated in competency assessment. Seven OTs and CPs participated in preintervention interviews and surveys; six completed post-intervention interviews and four completed post-training surveys. Patients: 10 patients were enrolled in the single-arm feasibility study and 4 of these participated in postintervention qualitative interviews. Inclusion criteria included therapists involved in vocational rehabilitation delivery and patients admitted to major trauma centres. Exclusion criteria included participation in other vocational rehabilitation trials or those who had returned to work or education for at least 80% of preinjury hours. Intervention: The ROWTATE vocational rehabilitation intervention was delivered remotely by trained OTs and CPs. Training included competency assessments, mentoring and adaptation for telerehabilitation. The intervention was delivered over multiple sessions, with content tailored to individual patient needs.Results Therapists found the training useful, reported positive attitudes (Evidence-Based Practice Attitude Scale mean=2.9 (SD 0.9)) and high levels of confidence in delivering evidence-based practice (range 75%–100%) and the ROWTATE intervention (range 80%–100%). Intervention barriers identified pretraining became facilitators post-training. Half the therapists needed additional support post-training through mentoring or additional training. The intervention and training were successfully adapted for remote delivery. High levels of fidelity (intervention components delivered: OTs=84.5%, CPs=92.9%) and session attendance rates were found (median: OT=97%, CP=100%). Virtually all sessions were delivered remotely (OT=98%, CP=100%). The intervention was acceptable to patients and therapists; both considered face-to-face delivery where necessary was important.Conclusions The ROWTATE intervention was delivered remotely with high fidelity and attendance and was acceptable to patients and therapists. Definitive trial key changes include modifying therapist training, competency assessment, face-to-face intervention delivery where necessary and addressing lower fidelity intervention components.Trial registration number ISRCTN74668529.Data are available on reasonable request. The data that participants have consented to share will become available to potential researchers at the end of the ROWTATE research programme. Requests detailing the research aims and use of the data should be sent to the research team via email: ROWTATE@nottingham.ac.uk.
-
Investigating the disturbance in cortical glutamate and GABA function in psychosis and its origins and consequencesWe investigated the longstanding idea that the onset of psychotic symptoms in schizophrenia arises from an early phase of glutamate neurotoxicity, possibly related to loss of GABA restraint, oxidative stress or inflammation, that cumulatively results in a later phase of synaptic loss in keeping with magnetic resonance spectroscopy (MRS) evidence of reduced glutamate in schizophrenia, especially in older patients. We evaluated this hypothesis in a 3-centre MRS study to determine whether abnormalities in glutamate in dorsal anterior cingulate cortex (dACC) differed between people with minimally treated ‘Recent’ onset schizophrenia and an ‘Established’ group with > 10 years of illness. We tested the hypothesised mechanisms of reduced GABA in either or both dACC and occipital cortex, and depletion of dACC glutathione, a measure of central inflammation. We explored predicted associations between MRS variables, circulating cytokines and clinical symptoms. The Established group showed significantly greater dACC glutamate deficit than the Recent group which was not accounted for by lifetime exposure to antipsychotic drugs or by their greater CRP or IL-6 levels nor was the deficit associated with glutathione depletion. The greater dACC glutamate deficit in established illness is compatible with loss of synapses occurring after onset of symptoms but there was little to suggest underpinning excitotoxicity, inflammation, or oxidative stress. GABA was reduced in patients versus controls across dACC and occipital voxels. Only dACC GABA content correlated significantly with symptoms, lower content with greater positive and negative symptoms across both groups and this is supportive of a pathophysiological role of GABA in psychosis.
-
Safety and efficacy of IL-23 inhibitors in patients with moderate to severe ulcerative colitis: a systematic review and meta-analysis of randomized controlled trialsBackground and objective Targeting the interleukin-23 (IL-23) pathway is an emerging therapeutic strategy for moderate to severe ulcerative colitis (UC). This systematic review and meta-analysis evaluated the efficacy and safety of IL-23 inhibitors for induction and maintenance therapy in UC. Methods A systematic search of PubMed, Cochrane, and Google Scholar was conducted up to May 2025 to identify randomized controlled trials (RCTs) of IL-23 inhibitors (mirikizumab, risankizumab, guselkumab) in UC. Data were analyzed using Review Manager (RevMan 5.4) with a random-effects model. Results Seven RCTs (four induction, three maintenance) including 4203 patients were analyzed. IL-23 inhibitors significantly increased clinical remission during both induction (RR 1.52) and maintenance (RR 1.62). Rates of histo-endoscopic healing were also higher with IL-23 blockade in both induction (RR 2.53) and maintenance (RR 1.81). Importantly, IL-23 inhibitors were associated with a reduced risk of serious adverse events during induction (RR 0.39), with no significant difference observed during maintenance (RR 0.68). Other outcomes, including clinical response and corticosteroid-free remission, also consistently favored IL-23 blockade. Conclusion IL-23 inhibitors provide significant improvements in clinical remission and mucosal healing, with a favorable safety profile, particularly during induction therapy in moderate to severe UC.
-
Free fatty acids correlate with the interleukin-1 beta and interleukin-1 receptor antagonist in the early subacute phase of strokeInflammation contributes to the pathogenesis of ischaemic stroke both as a long-term causal factor and through the inflammatory cascade in acute stroke. Interleukin-1 beta (IL-1β) is a potent pro-inflammatory molecule, while interleukin-1 receptor antagonist (IL-1Ra) acts as its antagonist. Free fatty acids (FFAs) play a role in atherosclerosis formation and serve as substrates for inflammatory molecules. This study aimed to determine the potential interplay between FFAs, IL-1β, and IL-1Ra in stroke patients. A prospective analysis was conducted on 73 ischaemic stroke patients. All participants had their FFA, IL-1β, and IL-1Ra levels assessed. Significant correlations between IL-1β and certain FFAs were detected: C15:0 pentadecanoic acid (rho = 0.488), C15:1 cis-10 pentadecanoic acid (rho = 0.473), C17:1 cis-10 heptadecanoic acid (rho = 0.411), C18:0 stearic acid (rho = 0.302), C24:0 lignoceric acid (rho = −0.280), C24:1 nervonic acid (rho = −0.276), C18:2n6t linoleic acid (rho = −0.272), C17:0 heptadecanoic acid (rho = 0.241), and C13:0 tridecanoic acid (rho = 0.238). After multivariate analysis C15:0 pentadecanoic acid remained statistically significant. The strongest correlation was found between IL-1Ra and fatty acids: C15:1 cis-10-pentadecanoid acid (rho = −0.357), C18:2n6t linoleic acid (rho 0.341) and C24:1 nervonic acid (rho 0.302), but after multivariate analysis significantly correlated remained: C22:1n9 13 erucic acid (rho = 0.299), C18:3n6 gamma-linoleic acid (rho = 0.277), with close to significant correlation with C22:4n6 docosatetraenoate (rho = −0.241, p = 0.055). Certain FFAs may play a role in enhancing both pro- and anti-inflammatory responses in the early subacute phase of stroke, where inflammatory and resolving processes are ongoing. Fatty acids such as C15:0 pentadecanoic acid, C15:1 cis-10 pentadecanoic acid and C22:4n6 docosatetraenoate might be involved in pro-inflammatory responses, while C22:1n9 13 erucic acid and C18:3n6 gamma-linoleic acid in the anti-inflammatory pathways with the overlay of IL-1β and IL-1Ra.
-
Febrile convulsion and cervical lymphadenopathy as initial presentation of incomplete node-first Kawasaki disease.Node-first Kawasaki disease (NFKD) is an atypical variant of Kawasaki disease (KD), presenting with fever and cervical lymphadenopathy before other classical features appear. This presentation often mimics bacterial cervical lymphadenitis (BCL), leading to misdiagnosis and treatment delays. We report a toddler initially treated for presumed BCL after presenting with a febrile convulsion and isolated lymphadenopathy. Failure to respond to antibiotics and the later appearance of rash, conjunctivitis and a small coronary artery aneurysm on echocardiography led to the diagnosis of incomplete NFKD. This case underscores the importance of early consideration of incomplete or atypical KD criteria in children with persistent fever and lymphadenopathy unresponsive to antibiotics. Delaying diagnosis until full clinical criteria develop may increase the risk of coronary complications. Early use of cardiac biomarkers, echocardiography and awareness of incomplete KD criteria can help distinguish KD from BCL, enabling timely diagnosis and treatment to improve outcomes.
-
Evaluating advanced clinical practitioners' engagement with the four pillars of advanced practice in the UK: a scoping reviewAims/Background Despite national frameworks outlining the four pillars of advanced practice (clinical practice, leadership and management, education, and research), engagement of Advanced Clinical Practitioners (ACPs) in the UK remains inconsistent, and significant challenges persist. This scoping review aimed to explore ACPs’ engagement with each pillar and to identify both successful and challenging factors. Methods A scoping review was conducted following Arksey and O’Malley’s framework in 2005 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A systematic search was undertaken across five databases (CINAHL, MEDLINE, Scopus, PsycInfo, and Cochrane Library) and grey literature sources. The search covered studies published from 2017 to 2025, in line with the introduction of the Multi-professional Framework. A three-stage screening process was used to identify eligible studies, and data were extracted using a standardised form. Thematic analysis was employed to synthesise the findings. Results Thirty-three studies met the inclusion criteria. The review identified strong ACP engagement in clinical practice, including contributions to direct patient care, improved patient satisfaction, and reduced waiting times. However, engagement with the leadership, education, and research pillars was inconsistent and often limited by excessive workload, lack of protected time, and ambiguity in role definitions. Structural variation across National Health Service (NHS) trusts further contributed to disparities in advanced clinical practice role development and utilisation. Conclusion Advanced clinical practice roles are firmly embedded in clinical care but remain underutilised in leadership, research, and education. Addressing these disparities requires clearer career pathways, organisational investment, and structured policy support to enable ACPs to contribute fully across all four pillars of practice.
-
Evaluation of a pro-recovery training intervention (REFOCUS-RETAFORM) in specialist mental health services across France : stepped-wedge cluster randomised controlled trial protocolWhile recovery orientation is national policy in many countries, evidence remains limited for the effectiveness at a service level. This paper describes the protocol for implementing a pro-recovery training intervention (REFOCUS-RETAFORM) in specialist mental health services across France. The aim is to evaluate whether REFOCUS-RETAFORM plus usual care leads to improved outcomes for adolescent and adult mental health service users compared with usual care alone.
-
Course review: Yorkshire clinical courses - essential plastic surgery skills for junior doctors courseCircumspectus Medicinae Course Review: Yorkshire Clinical Courses - Essential Plastic Surgery Skills for Junior Doctors Course Rajananthanan, Asveny MBChB Author Information Annals of Plastic Surgery 96(1):p 7-9, January 2026. | DOI: 10.1097/SAP.0000000000004543 Buy Abstract Plain Language Summary Contemporary medical curricula exhibits substantial gaps in plastic surgery education, with 70 percent of medical students completing their training without formal exposure to the specialty. The Essential Plastic Surgery Skills (EPS) course addresses these educational deficits through simulation-based learning for junior trainees. The 2-day program, conducted at Waterton Park Hotel, Wakefield, attracted a global audience from medical students to general practitioners. Faculty comprised 17 experienced educators providing 1:3 teacher to student ratios with continuous feedback and personalised instruction. Day 1 covered fundamental skills including skin closure, lesion excision, and tendon repair using biological specimens. Day 2 advanced to burns management, skin grafting, flap reconstruction and microsurgical techniques utilising porcine and poultry models. Course evaluation demonstrated adequate simulation equipment with sufficient time allocation for comprehensive skill development. The EPS course bridges the gap between undergraduate and postgraduate surgical training through simulation, addressing practical skill deficits while providing skill acquisition opportunities in a controlled learning environment. The program represents structured experience for those trainees interested in seeking broad plastic surgery exposure or transferable surgical skills.
-
The role of community nurses in rash examination, assessment and managementCommunity nurses play a significant role in the identification, assessment and treatment of rashes and associated skin conditions. It is important for them to be familiar with the location, pattern, appearance and feel of different types of rashes for timely diagnoses and escalation, if required. This article explores the processes of inspection, palpation, diagnostic tools and management strategies relevant to community nursing practice.
-
Cross-cultural comparison of recovery college implementation between Japan and England : corpus-based discourse analysisRecovery Colleges (RCs) are mental health learning communities, operated in 28 countries across cultures. However, the RC operational model is informed by Western countries sharing similar cultural characteristics such as individualism and short-term orientation. How RC operational model needs to be adapted to non-Western culture remains unknown. We investigated how RCs are introduced to the public in two countries with contrasting cultural characteristics: Japan (collectivism, long-term) and England (individualism, short-term). Corpus-based discourse analysis on 22,827 words from promotional texts (13 RCs in Japan, 61 in England) revealed that both countries emphasised mental illness lived experiences. In Japan, the focus was on the relational and long-term aspects of recovery. In England, the focus was on personal learning and skill acquisition. People attending RCs in Japan may anticipate experiencing collectivistic and long-term elements, which are viewed unfavourably in the operational model. Findings suggest refinements to the operational model to include under-represented cultural characteristics.
-
‘From band 2 to enhanced clinical practitioner apprentice’Gav Oxby reflects on his decade-long career journey in the NHS, going from a band 2 to become an enhanced clinical practitioner apprentice.
-
Compassion-focused therapy for mental health : international perspectivesThis book aims to explore the application of Compassion-Focused Therapy (CFT) within international contexts, acknowledging the nuances of mental health and well-being across different regions. By integrating principles of compassion with cultural sensitivity, it offers a comprehensive guide for mental health professionals to effectively address the needs of clients based in various regions of the world. Through case studies, research findings, and practical interventions, this book illuminates how CFT can be tailored and adapted to resonate with the values, beliefs, and norms of different cultures, ultimately promoting greater inclusivity and effectiveness in therapeutic practice.
-
Analysis of conceptual overlap among formal thought disorder rating scales in psychosis : a systematic semantic synthesis [Article in press]Measuring Formal Thought Disorder (FTD), a common, cross-diagnosed symptom dimension across mental disorders, is plagued by numerous inconsistencies. Clinicians use either FTD-specific scales or items from generic scales. While these tools are based on extensive clinical observations, they suffer from inconsistent terminology. Different scales may use the same term for distinct concepts or different terms for the same concept. This lack of conceptual standardization prevents the identification of underlying FTD subconstructs. By using natural language processing, we compared the definitions, labeling and overlap of FTD symptoms, i.e., the definitions of single items, across psychopathological scales. We used a three-pronged validation approach to analyze semantic clusters of single definitions of FTD scale psychopathological items. First, we used sentence-BERT to divide 30 Thought and Language Disorder scale (TALD) items into positive or negative FTD clusters, validating this approach by checking for correspondence with published factor-analytic divisions (approach validation). Second, we created a sparse item-to-item similarity matrix from 103 items across seven scales to identify semantically converging cross-scale FTD items; a clinician-researcher described the resulting four clusters, and we compared our automated classification with that of six blinded experts to establish expert-machine semantic correspondence. Finally, we analyzed data from 98 participants (49 healthy controls and 49 schizophrenia/affective psychosis), identifying the highest-correlating Clinical Language Disorder Scale (CLANG) item for each Thought, Language and Communication (TLC) scale item and mapping these to our BERT-derived clusters to establish data-level correspondence. When assigning TALD items to BERT-derived positive or negative FTD groupings, we observed a 73% match with prior factor analyses. The BERT-informed clustering of cross-scale items highlighted four coherent FTD groupings: (1) muddled communication & incomprehension, (2) abrupt topic shifts, (3) inconsistent narrative structure, (4) restricted speech. Expert raters showed moderate-to-high overlap (Fleiss’ kappa = 0.617) with computational clusters. A binomial test indicated that at the level of individual participants, correlations among CLANG-TLC item pairs were significantly more likely than chance to fall into the expected semantic cluster (p < 0.001). FTD rating scales measure overlapping, semantically related constructs that drive item-level correlations. Semantic clustering acts as a novel method to harmonize multi-scale data and pinpoint discrepancies between expert and machine classifications. Computational linguistics has the potential to improve consistency across rating scales especially when measuring complex constructs such as FTD.
-
Clinical effectiveness of music interventions for dementia and depression in older people (MIDDEL) : a multinational, cluster-randomised controlled trialBackground: Dementia and depression are among the leading causes of global disease burden. Effective and scalable interventions are needed to address the effect of these conditions, and music interventions are a promising non-pharmacological approach. The aim of this study was to determine the effectiveness of music interventions on depressive symptoms among care home residents with dementia in Australia, Germany, the Netherlands, Norway, Türkiye, and the UK.
-
Predictors of psychological well-being during imposed prolonged absence from workBackground Between March 2020 and September 2021, 11.7 million employee jobs were furloughed through the UK Coronavirus Job Retention Scheme (JRS). Imposed work absence shielded workers from job loss, but furloughed workers had increased risk of poor mental health compared to those who stayed working. Understanding the factors that mitigate psychological distress during imposed work absence can inform actions to be taken in future crises. Aims To explore the relationships between (a) work and home demands with well-being outcomes, and (b) personal and organisational resources with well-being outcomes, during periods of imposed prolonged absence and uncertainty. Methods We analysed online survey data collected with furloughed workers in the UK ‘Wellbeing of the Workforce Study’. Measures included psychological well-being, anxiety, life satisfaction, job insecurity, home demands (quantitative and emotional), organisational support for work-family balance, and personal resources (resilience, purpose, and coping ability). Results Psychological well-being was associated positively with quantitative home demands (β = 0.24, p < 0.05) and personal resources (β = 0.45, p < 0.001). Life satisfaction was associated negatively with emotional demands at home (β = –0.26, p < 0.05) and positively with personal resources (β = 0.30, p < 0.05). Perceived job insecurity was positively associated with anxiety (β = 0.36, p < 0.001). Conclusions Job-related factors are less influential during periods of employment uncertainty compared to personal and home resources. Decision-makers should provide psychological support during periods of job uncertainty and bolster the essential benefits of personal and home resources. Moving forwards, these findings may have broader applicability to other challenges and crises, such as suspension from work, or role changes resulting from organisational restructuring.
-
Involving carers in therapy for adults with intellectual disabilities : a systematic review of client, carer and therapist perspectivesBACKGROUND: Adaptations are frequently reported when delivering therapy to people with an intellectual disability, including the involvement of carers. This review aimed to understand the experience of carer involvement from the perspective of the person, therapist and caregiver. METHODS: A systematic search of six databases and of reference lists was conducted. The quality of the included studies was assessed using an adapted version of the Critical Appraisal Skills Programme qualitative checklist. Data was synthesised using meta-ethnography. RESULTS: Sixteen studies were included but their quality varied. Five third-order constructs were identified: safety, therapeutic process, relationships, personal impact on carer and improving the experience. CONCLUSION: Findings suggest that carer involvement can be a positive experience and aid the therapy process. However, this depended on several factors including carer motivation and consistency. Confidentiality issues were highlighted. Limitations of studies included poor reporting on participant demographics and small samples. Future research and clinical implications are suggested.
-
Investigating inequalities in admissions of young people out-of-area or to adult psychiatric wards : a qualitative studyHigh occupancy rates and uneven bed distribution throughout England mean some young people are admitted to Child and Adolescent Mental Health Service beds out-of-area or to adult psychiatric wards in Adult Mental Health Services. No previous research has investigated how the characteristics of young people, families, or services may influence the impact of these types of admissions.
-
Impact of music interventions on depression in care home residents with dementia : UK results from music interventions for depression and dementia in elderly care RCTBackground: We report UK findings from Music Interventions for Depression and Dementia in Elderly care (MIDDEL), a cross-national, clustered, randomised trial undertaken in 2018–2023 to evaluate the effectiveness of music interventions for depression symptoms in care home residents living with dementia (NCT03496675, clinicaltrials.gov (accessed on 1 December 2024)). The trial compared the effects of Group Music Therapy (GMT) with Recreational Choir Singing (RCS); GMT and RCS combined; and treatment as usual (TAU). Methods: In the intervention arms, the protocolized music interventions were delivered in care home units twice per week for three months, then once per week for three months. The primary outcome was depressive symptoms after six months, measured by MADRS. Secondary outcomes included well-being—EQ-5D-5L, Visual Analogue Scale (VAS); quality of life—QOL-AD; symptoms of dementia—SIB-8, NPI-Q; and caregiver distress—NPI-Q. The change in MADRS score from baseline to 6 months was assessed using a linear mixed-effects model. We report the multivariate model having both treatments as predictors, both unadjusted and adjusted, for the interaction between the treatments. Results: The UK trial started in 2022 after the pandemic lockdown, when 16 care home units were recruited and randomised, four per arm; 192 residents aged over 65 with depression and dementia participated. An ITT analysis of 146 participants retained at 6 months found neither intervention had a significant positive effect on any outcome. Significant unfavourable effects were found for RCS participants on MADRS, NPI symptom severity, and EQ-VAS. The combination of RCS + GMT had a detrimental effect on caregiver distress. Conclusions: MIDDEL UK findings do not support the use of GMT or RCS to alleviate depression in care home residents with dementia.












