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Understanding readmission after hip fracture : a mixed methods study protocolINTRODUCTION: Around 75 000 people suffer from hip fractures yearly in the United Kingdom (UK) leading to significant mortality and morbidity. Although mortality has dropped from 8% to 5% between 2013 and 2023 after hip fractures, those undergoing surgery for hip fractures have a 30-day readmission rate which has remained stagnant at around 11% over the same decade in the UK.This study protocol describes a mixed-methods investigation (The ARTHUR Study-avoiding readmission after hip fracture) which aims to understand and offer solutions to prevent avoidable 30-day readmission after hip fracture surgery. The study will focus on two hospitals in acute and community settings in a large urban and ethnically diverse city in the UK. METHODS AND ANALYSIS: We describe two work packages.Work Package One (WP1) involves analysis of 5 year's worth of routinely collected health data provided by PIONEER, a Health Data Research UK data hub in Acute Care for our local population. Work Package Two (WP2) will involve semistructured interviews with patients, carers or family members as well as non-participant observations of hospital processes to understand systems-based issues related to readmissions after hip fracture surgery. Although recruitment may be an issue, our timeline for recruitment reflects this. We also aim to recruit a diverse population, which has often been under-represented in studies into hip fractures and aim to explore relevant interventions which can be widely generalisable. ETHICS AND DISSEMINATION: This protocol was submitted via IRAS: 330074 and obtained UK NHS REC approval via the West Midlands Coventry and Warwickshire Research Ethics Committee (REC 23/WM/0242) on 25 January 2024. The results of this study will be published in relevant scientific journals and presented at orthopaedic, fragility fracture and geriatric specialty conferences and scientific meetings. A lay summary of the findings will be publicly available on the HRA website.
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Understanding and guiding technology use in dementia : a pan-European mapping and consensus studyIntroduction: Dementia is a leading cause of disability worldwide, and its prevalence is expected to rise significantly by the year 2050. Assistive technologies (AT) have emerged as promising tools to promote independence and quality of life. The COVID-19 pandemic prompted an increased uptake of AT among people with dementia, exposing important limitations in digital literacy, accessibility, and support.MethodsThis pan-European study mapped recent research initiatives involving digital technology use by people with dementia during the pandemic and synthesised a set of recommendations for supporting the use of AT by people with dementia, and its development, using the Delphi method.ResultsThe mapping exercise identified 28 relevant projects, highlighting the types of technologies used during the pandemic and the settings in which they were implemented. Video-conferencing platforms were the most reported projects. More than half of the projects and initiatives (n = 17) were adapted to include digital technologies due to the pandemic. The subsequent Delphi consensus study incorporated input from experts by experience and produced 18 evidence-based recommendations, adapted from this mapping exercise and a previous scoping review.DiscussionKey findings emphasise involving people with dementia in technology design, ensuring equitable access, and providing adequate training and support. The recommendations offer a practical, consensus-based framework to improve the efficacy of AT adoption, with implications extending beyond pandemic contexts to improve dementia care globally.
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Organisational variation in Recovery College implementation : 31-college qualitative studyBACKGROUND: By 2021, we found that 88 Recovery Colleges were operating in England. Recovery Colleges adhere to shared principles including adult education and co-production, but are also heterogeneous, varying in the populations they serve, their sources of funding and access to resources. Previous research has not explored the organisational factors that influence the set-up of Recovery Colleges, nor the factors which facilitate or pose challenges to their sustainable operation. AIMS: To identify how Recovery Colleges vary in their operation and to ascertain how organisational factors facilitate or hinder the set-up, running and sustainability of English Recovery Colleges. METHOD: Semi-structured interviews with 31 Recovery College managers across England were analysed using framework analysis. RESULTS: Four themes were identified: Recovery College pioneers; Adapting to the local context; Degree of autonomy within the National Health Service; and Ongoing organisational work. Colleges were commonly established by key individuals from diverse backgrounds, leveraging their organisational positions and lived experience to facilitate implementation. Colleges were adapted to fit local contexts, shaped by factors including existing services, regional demographics and community resources. Colleges varied in their relations with key funders, with some operating comparatively autonomously and others tied closely to their 'parent' organisations. Sustaining college operations involved ongoing organisational work to respond to changing pressures. CONCLUSIONS: Recovery Colleges exhibit consistent values and aims oriented around supporting recovery through education and co-production but are diverse in their operation. These colleges are highly complex interventions, and their sustainability requires organisational agility to manage competing pressures.
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Online remote behavioural intervention for Tics (ORBIT-UK) : protocol of a single cohort usability studyIntroduction Tourette syndrome is a common, disabling childhood-onset condition. Exposure and response prevention (ERP) is an effective treatment for tics, yet access remains limited due to a shortage of trained therapists and uneven geographical distribution of services. The ORBIT trial demonstrated that internet-delivered ERP is both clinically and cost-effective, but was developed on a university research platform, not suitable for widescale roll-out. To enable adoption by the National Health Service (NHS) in England, ORBIT has been redeveloped on an NHS compliant platform. This study will evaluate the usability, acceptability and preliminary outcomes of ORBIT on the new platform within an NHS tic disorder service.Methods and analysis This single-cohort usability study will recruit 20 children and young people (aged 9–17) with tics and their chosen supporters (parents/carers). Participants will receive a 10-week online ERP intervention supported by trained coaches. Outcomes include uptake, adherence, system usability, satisfaction and clinical measures such as the Yale Global Tic Severity Scale, Parent Tic Questionnaire and Goal-Based Outcomes. Qualitative feedback will be collected via semi-structured exit interviews. Usability metrics and adverse events will be monitored throughout.Ethics and dissemination The study has received ethical approval from North West Greater Manchester Research Ethics Committee (ref: 25/NW/0107). The findings from the study will inform future NHS adoption. The results will be submitted for publication in peer-reviewed journals.Trial registration number ISRCTN82718960. Registered 10 July 2025. https://doi.org/10.1186/ISRCTN82718960
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Neurological adverse effects of antipsychotic medication in children and young peopleNeurological adverse effects (NAEs) are commonly reported in individuals treated with antipsychotic medications. Children and young people (CYP) may be particularly susceptible to these effects, but few studies have focused on the risk of NAEs in this population. This review provides an overview of the published literature on NAEs in CYP with an emphasis on data from randomised placebo-controlled trials. Most antipsychotics are associated with sedative effects that may impair daily functioning. Akathisia, dystonia and parkinsonism are commonly reported in CYP, although rating scale assessments typically show minimal changes from baseline in short-term randomised studies. Tardive dyskinesia appears to be less common in CYP than in adults, but data are limited. Some antipsychotics, in particular clozapine, are associated with a reduced seizure threshold, but it is unclear whether CYP may be more vulnerable than adults and available studies are subject to various confounding factors. Neuroleptic malignant syndrome, a rare and potentially fatal adverse drug reaction, has been reported in CYP treated with both first-generation and second-generation antipsychotics. Data on risk factors and management strategies for NAEs are largely from studies in adults and may not be relevant to CYP. Future studies should aim to resolve some of the current uncertainties. In particular, within-subject “self-controlled” studies using prospectively collected data from large databases would help to clarify the incidence and risk factors, in particular for less common NAEs, while controlling for possible confounders.
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Mood monitoring, mood tracking, and ambulatory assessment interventions in depression and bipolar disorder : systematic review and meta-analysis of randomized controlled trialsBACKGROUND: Mood monitoring is widely used by people with depression and bipolar disorder (BD) to prevent relapse and improve insight into their condition, but it is unclear if these interventions have an impact on symptoms and for whom. As the capacity for passive mood monitoring increases, it is vital to improve our understanding of frequent mood assessment. OBJECTIVE: This systematic review and meta-analysis assessed the effect of mood monitoring interventions in people with depression and BD to decrease relapse risk and symptoms of depression and mania. METHODS: We conducted a systematic review and meta-analysis (PROSPERO, International Prospective Register of Systematic Reviews: CRD42023396473) and reported results according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Randomized controlled trials with clinically important follow-up periods were identified via multiple database searches and rated for risk of bias using the Cochrane Risk of Bias tool. The primary outcomes were symptoms of depression and mania. Available data were pooled to calculate standardized mean differences (SMDs) for the primary outcomes: severity of depression, bipolar depression, and mania/hypomania. RESULTS: We included 8 trials of 1230 participants and 6 different mood monitoring protocols. In BD, meta-analysis found a small but not statistically significant effect of mood monitoring interventions on decreasing mania symptoms (6 comparisons, n=873; SMD 0.16, 95% CI-0.34 to 0.01; P=.06) and no effect on bipolar depression (6 comparisons, n=873; SMD -0.08, 95% CI -0.31 to 0.15; P=.02). In depression, we found a small effect in decreasing symptoms of depression of borderline statistical significance at 12 months (2 comparisons, n=262; SMD -0.25, 95% CI -0.49 to 0.00; P=.05) but not at 6 months (2 comparisons, n=268; SMD -0.21, 95% CI -0.54 to 0.12; P=.21). There was an absence of evidence on the effect of mood monitoring on decreased relapse rates or readmission rates. Studies had a low risk of bias. There was no evidence on mood monitoring through ecological momentary assessment. CONCLUSIONS: Overall mood monitoring interventions do not increase or decrease mood symptoms in people with BD, nor is there robust evidence of such effects in people with unipolar depression. Further research is merited on different forms of mood monitoring and to determine under what circumstances mood monitoring might have beneficial or adverse effects. These results initially suggest that ambulatory assessment does not induce large placebo effects or significantly negatively or positively affect mood, and thus that mood monitoring may be an appropriate outcome measure for research or for clinical practice.
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Mind the Gap : a systematic review of barriers, facilitators, and experiences of care transitions for people living with dementia and their informal caregiversBACKGROUND AND OBJECTIVES: Care transitions for people living with dementia are critical periods requiring coordinated, person-centered support. Effective transitions can reduce caregiver burden, prevent adverse outcomes, and improve care quality. However, the barriers, facilitators, and lived experiences during transitions remain poorly understood. This systematic review synthesizes evidence on these factors from the perspectives of people with dementia and their informal caregivers. RESEARCH DESIGN AND METHODS: A comprehensive search across MEDLINE, CINAHL, PsycINFO, ProQuest, and Web of Science identified 67 eligible English-language studies published from 2018 to 2023. Quality appraisal used Joanna Briggs Institute tools. The protocol was registered on PROSPERO: CRD42023452669. RESULTS: Four themes captured the barriers, facilitators, and experiences shaping care transitions for people with dementia and their caregivers. Systemic influences included fragmented governance, funding and policy inconsistencies, and structural challenges in care coordination and delivery, mitigated by proactive planning and integrated care. Health and social care workforce factors highlighted gaps in dementia training, staffing, and communication, with empathetic, informed staff improving transitions. Emotions and decision-making reflected caregiver burden, uncertainty, and advocacy, eased by early guidance and peer support. Cultural, social and situational influences showed how values, socioeconomic status, and rurality affected transition choices, underscoring the need for culturally sensitive, person-centered support. DISCUSSION AND IMPLICATIONS: Care transitions remain complex, shaped by systemic, workforce, emotional, and cultural factors. Addressing inequities and coordination gaps is critical for more integrated transitional care. Strengthening dementia-specific training, home-based care models, and culturally responsive communication may improve continuity, person-centeredness, and caregiver support.
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Mri changes following treatment of Glp-1 analogue, liraglutide in Alzheimer's diseaseBackground: Preclinical evidence in transgenic models of Alzheimer's disease (AD) suggests that liraglutide, a GLP1 analogue, exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and reducing insulin resistance, and increasing the proliferation of neuronal progenitor cells. ELAD is a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild to moderate AD conducted at 24 centres in the UK. Method(s): As a part of this study, a total of 204 Alzheimer's participants were randomised to receive either liraglutide or placebo as a daily subcutaneous injection for 12 months. All subjects underwent volumetric MRI scans at baseline and during follow up. Volumetric changes from baseline to follow up in MRI scans were evaluated using both regional volume analysis and voxel based morphometric analysis Result: MRI analysis demonstrated that temporal lobe volume, total grey matter volume and frontoparietal volume change was lower in liraglutide treated patients compared to the placebo group. Voxel based morphometry (VBM) analysis demonstrated that liraglutide-treated participants showed a slower reduction in whole cortical grey matter, frontal, temporal and parietal lobe volume in participants treated with liraglutide compared to placebo. Conclusion(s): In the ELAD study, participants with mild to moderate AD who received liraglutide had slower reduction in MRI volume and cognition compared to the placebo demonstrating a potential benefit of liraglutide in the treatment of Alzheimer's disease. These findings highlight the potential of GLP-1 analogues in the treatment of Alzheimer's disease.
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Evaluation of liraglutide in the treatment of Alzheimer's diseaseBackground Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue licensed for the treatment of type 2 diabetes. Preclinical evidence in transgenic models of Alzheimer’s disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. Methods ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild to moderate Alzheimer’s dementia, conducted at several centres in the UK – (NCT01843075). [18F]FDG-PET and MRI brain scans of all patients will be performed at baseline and after 12 months treatment with liraglutide or matching placebo. Once enrolled, all subjects had a neuropsychological battery of tests All scans and tests will be repeated after 12 months. A total of 204 participants were randomised to receive either liraglutide or placebo as a daily subcutaneous injection for 12 months. The primary objective was to evaluate the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to 12-month follow-up in participants with Alzheimer’s disease receiving treatment with liraglutide compared to those receiving placebo. The key secondary outcomes were the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer’s Disease Assessment Scale – Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer’s Disease Cooperative Study – Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes were 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. Results The study demonstrated that liraglutide treated patients performed significantly better than placebo arm in temporal lobe and whole cortical MRI volume and cognitive function measured by ADAS-EXEC (ADAS-Cog with Executive domains of the Neuropsychological Test Battery). Conclusion This demonstrates that GLP1 analogues can improve cognitive function and MRI volume in AD subjects and could be a potential treatment for treatment for Alzheimer's
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Early onset dementia : clinical utility of cerebrospinal fluid amyloidbeta and tau measures in diagnosing mild cognitive impairmentBackground: The differentiation of a preclinical or prodromal Alzheimer's disease (AD) is challenging particularly in patients with Early Onset Alzheimer's or Related Dementias (EOARD). The first clinical symptoms of AD during the prodromal phase are mild cognitive impairment (MCI), with some younger adults presenting with depression or anxiety. We report a local practice on utilising diagnostic lumbar puncture to investigate the cause of MCI for the diagnosis of EOARD at a tertiary neurocognitive referral centre. Method(s): The study was approved by the Ethic Committee (Ref:18/EM/0292). 30 participants aged 32-68 years old at the onset of symptoms (mean 62 years; 61% female) from the Nottingham EOARD clinics (UK) were included. Clinical diagnosis was based on clinical presentation, neurocognitive profile, radiological features (MRI, FDG-PET CT) and CSF amyloidbeta1-42/1-40 (Abeta), total tau and Thr181-phosphorylated tau measurements. Patients were classified into three groups according to the clinical diagnosis: a)MCI secondary to Alzheimer's disease as defined by NIA-AA Research Framework [n=16]. b)Subjective Cognitive impairment, stable impairment in cognitive battery with no evidence of neurodegeneration on neuroimaging or abnormal levels of Amyloidb/tau in the CSF [n=9]. c)Other neurodegenerative conditions [n=5] (Table). Result(s): In patients with MCI, the CSF total tau and Thr181-phosphorylated tau levels showed a non-linear relationship with age, with an inverse U-shaped curve reaching the highest level at the age of 55 years, followed by a significant decline in the following decade (Figure). In contrast, the CSF Abeta level decreased in the MCI group, independently of age, and was associated with the neuropsychological measures of memory impairment (p=0.037). In contrast, total and phosphorylated CSF tau levels did not correlate with the cognitive performance measures. Similarly, the principal component analysis confirmed that the clinical diagnosis of Alzheimer's MCI (as per the NIA-AA criteria) correlated with the CSF Abeta loss. Conclusion(s): In Early Onset Alzheimer's disease, the low levels of CSF Abeta appear to be more sensitive than the total and 181Thr-phosphorylated tau measures in differentiating Alzheimer's MCI from other forms of dementia. Further work on larger samples of EOARD in clinical practice will address the cost effectiveness due to making an earlier diagnosis.
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Dysfunctional cerebral glucose transport in Alzheimer’s diseaseBackground: Glucose is the primary energy source required for the homeostatic function of the brain. Glucose transporter 1 (GLUT1) present at the blood-brain barrier is a key regulator of glucose transport into the brain. Reduced GLUT1 expression is shown to exacerbate Alzheimer's pathology in rodent models. Here we aimed to establish whether there are regional differences in ineffective glucose transport amongst people living with Alzheimer's disease. Method(s): 125 participants diagnosed with Alzheimer's dementia, with an [18F]FDG scan with atrial input were enrolled. All participants underwent 3-tesla magnetic resonance imaging and [18F]FDG scan with continuous and discrete arterial sampling. Spectral analysis was performed to create 1-minute input-response function parametric maps. To produce glucose transfer maps we applied the following equation; K1 * Ca / tau (K1 = 1-minute IRF map, Ca = Plasma glucose concentration, tau = 1.48 a lumped constant). Glucose transfer maps were then coregistered to the participants' structural MRI and normalised to MNI space. Regional mean glucose transfer was then calculated for the anterior cingulate cortex, frontal lobe, hippocampus, parahippocampus, occipital lobe, parietal lobe, posterior cingulate cortex, striatum, temporal lobe, and thalamus. A within-subject ANOVA was then performed to evaluate the regional differences in cerebral glucose transport. Result(s): The parahippocampus exhibited the lowest rate of glucose transfer in comparison to all other regions (p < 0.001), followed by the hippocampus. The striatum and occipital lobe demonstrated the regions of the highest mean glucose transportation from blood to the brain. In terms of brain lobes, the temporal lobe showed the lowest rates of glucose transfer, followed by the parietal lobe, then frontal and occipital (p < 0.001). Conclusion(s): We demonstrate dysfunctional BBB glucose transport in Alzheimer's disease, with prominent glucose transport abnormalities localised in the parahippocampus. Impaired glucose transport was most apparent within temporal lobe structures. Targeting glucose transfer may be an effective way of treating Alzheimer's disease.
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Differential expression of 5mC epigenomic regulators in Alzheimer's diseaseBackground Epigenetic processes are molecular mechanisms that contribute to the pathogenesis of neurodegenerative diseases. 5-methylcytosine (5mC) and the oxidised state, 5-formilcytosine (5fC), are known transcriptional regulators moderated by sets of writer, reader, and eraser effector proteins. We propose that gene expression variation in DNA effector proteins may contribute to Alzheimer’s Disease (AD) neuropathology. We also aimed to characterize the distribution of 5fC modifications across brain regions and within cellular compartments to better understand the role of 5mC/5fC modifications in AD. Methods RNA sequencing data for 17 effector proteins obtained from the Aging, Dementia and Traumatic Brain Injury Study was analysed to assess variation in abundance of 5mC writers, readers, and erasers. Gene expression data were compared across four brain regions in 51 AD and 56 healthy control samples, and between Braak and CERAD neuropathological scales. In addition, we examined the presence and distribution of 5fC by immunofluorescence (IF) across four brain regions in sections from healthy individuals. Results Transcripts of DNA methylation writers DNMT1, DNMT3A and DNMT3B were found increased in the AD cohort across 3 brain regions, whilst the reader UHRF1 mRNA was decreased in the same assessment. GADD45B and AICDA, DNA methylation erasers, showed changes in mRNA abundance across Braak and CERAD neuropathological load groupings. IF analysis indicated 5fC modification to be highly abundant in dentate gyrus and within the cytoplasm of hippocampal mossy cells and of neurons in cortical layer III. Within neuronal cells, we observed 5fC partially colocalizing with mitochondria especially within hippocampal neurons. Conclusion Our findings indicate that changes in 5mC/5hmC/5fC effector protein expression are associated with AD and its neuropathology. The characterisation of 5fC localisation in human brain indicates high abundance within the cytoplasm of hippocampal cells suggesting that 5fC may be involved in pre- and post-transcriptional control of memory processing pathways and, when disrupted, may lead to neurodegenerative disease. References: Sanchez-Mut JV, et al. Transl Psychiatry. 2016; Miller JA, et al. Elife. 2017; Bachman, M., et al. Nat Chem Biol. 2015; Zhang Y, Zhou C. DNA Repair (Amst). 2019; Aging, Dementia and TBI Study (2017) Available from Allen Brain Atlas
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Liraglutide in mild to moderate Alzheimer’s disease : a phase 2b clinical trialLiraglutide, a glucagon-like peptide 1 (GLP-1) agonist and antidiabetic drug, has shown neuroprotective effects in animal models. In this study, we aimed to evaluate the safety and efficacy of liraglutide in mild to moderate Alzheimer’s disease syndrome. ‘Evaluating liraglutide in Alzheimer’s disease’ (ELAD) is a multicenter, randomized, double-blind, placebo-controlled phase 2b trial in 204 participants with mild to moderate Alzheimer’s disease syndrome with no diabetes. Participants received daily injections of liraglutide or placebo for 52 weeks. They underwent fluorodeoxyglucose positron emission tomography, magnetic resonance imaging and detailed neuropsychometric evaluations. The primary outcome was a change in cerebral glucose metabolic rate. Secondary outcomes were safety and tolerability and cognitive changes. The primary outcome showed no significant differences in cerebral glucose metabolism (difference = −0.17; 95% confidence interval: −0.39 to 0.06; P = 0.14) between the two groups. The secondary outcome—score on the Alzheimer’s Disease Assessment Scale-Executive domain (ADAS-Exec)—performed better in liraglutide-treated patients compared to placebo (0.15; 95% confidence interval: 0.03−0.28; unadjusted P = 0.01). No significant differences were observed in Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) (−0.58; 95% confidence interval: −3.13 to 1.97; unadjusted P = 0.65) or Clinical Dementia Rating-Sum of Boxes (CDR-SoB) (−0.06; 95% confidence interval: −0.57 to 0.44; unadjusted P = 0.81) scores. Liraglutide was generally safe and well tolerated in non-diabetic patients with Alzheimer’s disease. ClinicalTrials.gov identifier: NCT01843075.
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The user experience of ambulatory assessment and mood monitoring in depression : a systematic review and meta-synthesisThe preferences and opinions of individuals with depression will likely be fundamental for the success of mood monitoring interventions, or for ambulatory assessment approaches as methods of data collection. Concerns have been raised regarding negative psychological effects of repeated mood assessment. This systematic review and meta-synthesis of qualitative studies assessed the user experience of mood monitoring and ambulatory assessment procedures. This included: barriers and facilitators to use for people with depression and for clinicians, negative psychological effects and the intended purpose of use. Eight electronic databases were searched and mixed-methods studies were included. Qualitative studies were rated for risk of bias. Fourteen studies were identified. We identified seven overarching concepts: negative psychological effects, perceived effectiveness, difficulties in completing questionnaires, sharing with others, desired features, purpose of mood monitoring, and clinician barriers/facilitators. While many participants found the mood monitoring/ambulatory assessment therapeutic and positive, many participants reported negative consequences from ambulatory assessment/mood monitoring. Future protocols should monitor negative psychological effects, whether they are long-lasting and consider testing the incorporation of additional therapeutic elements to manage them. We report additional key concepts that are likely to improve the user experience, engagement, attrition, usability and acceptability of ambulatory assessment/mood monitoring protocols for people with depression.
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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.
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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.
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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.
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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.
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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.
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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.
