Novel Candidate Genes Identified in the Brain during Nociception in Common Carp (Cyprinus carpio) and Rainbow Trout (Oncorhynchus mykiss)

Recent studies have demonstrated that teleost fish possess nociceptors that detect potentially painful stimuli and that the physiological properties of these fibres are markedly similar to those found in mammals. This finding led to suggestions of possible pain perception in fish, contrary to the view that the sensory response in these animals is limited to the spinal cord and hindbrain and as such is reflexive. Therefore, the aim of this study was to determine if the brain is active at the molecular level by using a microarray analysis of gene expression in the forebrain, midbrain and hindbrain of two fish species. A comparison between the two species at different time points showed that many genes were differentially regulated in response to a noxious stimulus compared with controls. A number of genes that are involved in mammalian nociception, such as brain-derived neurotrophic factor (BDNF) and the cannabinoid CB1 receptor were regulated in the fish brain after a nociceptive event. Novel candidates that showed significant regulation in both species were also identified. In particular, the Van Gogh-like 2 gene, was regulated in both carp and trout and should be pursued to establish its precise role in nociception

Behavioural Analysis of a Nociceptive Event in Fish: Comparisons Between Three Species Demonstrate Specific Responses

Nociception is the sensory mechanism by which potentially harmful stimuli are detected in animals and humans. The behavioural responses to noxious stimulation have been studied in two fish species thus far. However, since species-specific differences are seen in mammals, more species need to be examined to determine whether nociceptive responses are generic in fish. The present study investigated the behavioural and respiratory response to an acute noxious or potentially painful stimulus in common carp (Cyprinus carpio), zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss). Behavioural parameters such as frequency of swimming, use of cover and any anomalous behaviour were measured along with ventilation rate before and after noxious stimulation in the carp and zebrafish. Although no differences in behavioural or ventilation rate response were observed between noxiously stimulated carp and control fish, anomalous behaviours of rocking from side to side and rubbing of lips against the tank walls were observed in two of the five fish. In contrast, zebrafish displayed a significant reduction in frequency of swimming and an increase in ventilation rate, which was similar to the results obtained from rainbow trout. Zebrafish did not display any anomalous behaviour. These dissimilarities in response to potentially painful stimulation demonstrate that there are species-specific behavioural and physiological responses to a nociceptive event in fish

Investigation of Van Gogh-like 2 mRNA Regulation and Localisation in Response to Nociception in the Brain of Adult Common Carp (Cyprinus carpio)

The Van Gogh-like 2 (vangl2) gene is typically associated with planar cell polarity pathways, which is essential for correct orientation of epithelial cells during development. The encoded protein of this gene is a transmembrane protein and is highly conserved through evolution. Van Gogh-like 2 was selected for further study on the basis of consistent regulation after a nociceptive stimulus in adult common carp and rainbow trout in a microarray study. An in situ hybridisation was conducted in the brain of mature common carp (Cyprinus carpio), 1.5 and 3 h after a nociceptive stimulus comprising of an acetic acid injection to the lips of the fish and compared with a saline-injected control. The vangl2 gene was expressed in all brain regions, and particularly intensely in neurons of the telencephalon and in ependymal cells. In the cerebellum, a greater number (P = 0.018) of Purkinje cells expressed vangl2 after nociception (n=7) compared with controls (n = 5). This regulation opens the possibility that vangl2 is involved in nociceptive processing in the adult fish brain and may be a novel target for central nociception in vertebrates

A core outcome set for nonpharmacological community-based interventions for people living with dementia at home: A systematic review of outcome measurement instruments

YesIt is questionable whether existing outcome measurement instruments (OMIs) in dementia research reflect what key stakeholders' value. We attained consensus from over 300 key stakeholders, including people living with dementia, and identified 13 core outcome items for use in nonpharmacological and community-based interventions for people with dementia living at home. In this systematic review we review OMIs that have previously been used in dementia care research to determine how, or even if, the 13 core outcome items can be measured. We extracted self-reported OMIs from trials, reviews and reports of instrument development. Searches were undertaken in the ALOIS database, Medline, PsycINFO, CINAHL, socINDEX and COSMIN database. We aimed to assess the psychometric properties of OMI items for face validity with the core outcome items, content validity, internal consistency and responsiveness. We held a co-research workshop involving people living with dementia and care partners in order to ratify the findings. In total 347 OMIs were located from 354 sources. Of these 76 OMIs met the inclusion criteria. No OMIs were deemed to have sufficient face validity for the COS items, and no OMIs proceeded to further assessment. The 'best' available OMI is the Engagement and Independence in Dementia Questionnaire (EID-Q). This study provides a practical resource for those designing dementia research trials. Being able to measure the COS items would herald a paradigm shift for dementia research, be responsive to what key stakeholders value and enhance the ability to make comparisons.This study was funded jointly by the Economic and Social Research Council (ESRC) and the National Institute for Health Research (NIHR). ESRC is part of UK Research and Innovation (UKRI)

Developing a Management Guide (the DemPower App) for Couples Where One Partner Has Dementia: Nonrandomized Feasibility Study

YesPromoting the health and well-being of couples where one partner has dementia is an overlooked area of care practice. Most postdiagnostic services currently lack a couple-centered approach and have a limited focus on the couple relationship. To help address this situation, we developed a tablet-based self-management guide (DemPower) focused on helping couples enhance their well-being and relationship quality. The aim of this study is to investigate the feasibility and acceptability of the DemPower app. A nonrandomized feasibility design was used to evaluate the DemPower intervention over 3 months among couples where a partner had a diagnosis of dementia. The study recruited 25 couples in the United Kingdom and 19 couples in Sweden. Outcome measures were obtained at baseline and postintervention. The study process and interventions were evaluated at various stages. The study was completed by 48% (21/44) of couples where one partner had dementia, of whom 86% (18/21) of couples accessed all parts of the DemPower app. Each couple spent an average of 8 hours (SD 3.35 hours) using the app during the study period. In total, 90% (19/21) of couples reported that all sections of DemPower were useful in addressing various aspects of daily life and helped to focus on how they interacted in their relationship. Of the 4 core subjects on which the DemPower app was structured, home and neighborhood received the highest number of visits. Couples used activity sections more often than the core subject pages. The perception of DemPower's utility varied with each couple's lived experience of dementia, geographic location, relationship dynamics, and opportunities for social interaction. A 5.2-point increase in the dementia quality of life score for people with dementia and a marginal increase in the Mutuality scale (+1.23 points) for caregiver spouses were found. Design and navigational challenges were reported in the DemPower app. The findings suggest that the DemPower app is a useful resource for couples where one partner has dementia and that the implementation of the app requires the support of memory clinics to reach couples at early diagnosis. ISRCTN Registry ISRCTN10122979; http://www.isrctn.com/ISRCTN10122979.Economic and Social Research Council (ESRC) and National Institute for Health Research (NIHR). This research is part of Work Programme 6 of the ESRC/NIHR Neighborhoods and Dementia mixed methods study (reference ES/L001772/1

What is important to people with dementia living at home? A set of core outcome items for use in the evaluation of non-pharmacological community-based health and social care interventions

YesObjectives: Inconsistency in outcome measurement in dementia care trials impedes the comparisons of effectiveness between trials. The key aim of this study is to establish an agreed standardised core outcome set (COS) for use when evaluating non-pharmacological health and social care interventions for people with dementia living at home. Method: We used a mixed-methods research design, including substantive qualitative research with five key stakeholders groups. We consulted with people living with dementia for many aspects of this research. We applied a modified two-round 54 item Delphi approach to attain consensus on core outcomes. The COS was finalised in a face-to-face consensus meeting in 2018. Results: Of the 288 who completed round 1 (21 people living with dementia, 58 care partners, 137 relevant health and social care professionals, 60 researchers, 12 policy makers), 246 completed round 2 (85% response rate). Twenty participants attended the consensus meeting. We reached consensus for the inclusion of 13 outcome items. Conclusion: We identified 13 outcome items which are considered core; many relate to social health. Providing there are adequate measures, measuring these core outcome items will enhance comparisons for effectiveness making trial evidence more useful. The items will provide commissioners and service planners with information on what types of interventions are most likely to be valued highly by people living with dementia.This study was funded jointly by the Economic and Social Research Council (ESRC) and the National Institute for Health Research (NIHR). ESRC is part of UK Research and Innovation

The Role of Primary Care in Service Provision for People with Severe Mental Illness in the United Kingdom

Severe mental illness is a serious and potentially life changing set of conditions. This paper describes and analyses patient characteristics and service usage over one year of a representative cohort of people with a diagnosis of severe mental illness across England, including contacts with primary and secondary care and continuity of care

Trial baseline characteristics of a cluster randomised controlled trial of a school-located obesity prevention programme; the Healthy Lifestyles Programme (HeLP) trial

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background We have developed a healthy lifestyles programme (HeLP) for primary school aged children (9–10 years), currently being evaluated in a definitive cluster randomised controlled trial. This paper descriptively presents the baseline characteristics of trial children (BMI, waist circumference, % body fat, diet and physical activity) by gender, cluster level socio-economic status, school size and time of recruitment into the trial. Methods Schools were recruited from across the South West of England and allocated 1:1 to either intervention (HeLP) or control (usual practice) stratified by the proportion of children eligible for free school meals (FSM, 1 Year 5 class). The primary outcome is change in body mass index standard deviation score (BMI sds) at 24 months post-randomisation. Secondary outcomes are BMI sds at 18 months, waist circumference and percentage body fat sds at 18 and 24 months, proportion of children classified as underweight, overweight and obese at 18 and 24 months, physical activity (for a sub-sample) and food intake at 18 months. Results At baseline 11.4% and 13.6% of children were categorised as overweight or obese respectively. A higher percentage of girls than boys (25.3% vs 24.8%) and children from schools in FSM category 2 (28.2% vs 23.2%) were overweight or obese. Children were consuming a mean (range) of 4.15 (0–13) energy dense snacks (EDS) and 3.23 (0–9) healthy snacks (HS) per day with children from schools in FSM category 2 consuming more EDS and negative food markers and less HS and positive food markers. Children spent an average 53.6 min per day (11.9 to 124.8) in MVPA and thirteen hours (779.3 min) per day (11 h to 15 h) doing less than ‘light’ intensity activity. Less than 5% of children achieved the Departments of Health’s recommendation of 60 min of MVPA every day. Conclusion We have excellent completeness of baseline data for all measures and have achieved compliance to accelerometry not seen before in other large scale studies. Our anthropometric baseline data is representative of local and national data for children this age and reflects the gender and socio-economic variations expected of children this age in relation to physical activity and weight status.The definitive trial of HeLP is funded by the UK National Institute for Health Research (NIHR) Public Health Research Programme (10/3010/01) and a full report will be published on the NIHR website. Intervention materials and delivery was funded by the Peninsula College of Medicine and Dentistry. PenCLAHRC provided methodological support during the transition from the exploratory trial to the definitive evaluation

Evaluation of a primary care-based collaborative care model (PARTNERS2) for people with diagnoses of schizophrenia, bipolar, or other psychoses: study protocol for a cluster randomised controlled trial

YesCurrent NHS policy encourages an integrated approach to provision of mental and physical care for individuals with long term mental health problems. The 'PARTNERS2' complex intervention is designed to support individuals with psychosis in a primary care setting. The trial will evaluate the clinical and cost-effectiveness of the PARTNERS2 intervention. This is a cluster randomised controlled superiority trial comparing collaborative care (PARTNERS2) with usual care, with an internal pilot to assess feasibility. The setting will be primary care within four trial recruitment areas: Birmingham & Solihull, Cornwall, Plymouth, and Somerset. GP practices are randomised 1:1 to either (a) the PARTNERS2 intervention plus modified standard care ('intervention'); or (b) standard care only ('control'). PARTNERS2 is a flexible, general practice-based, person-centred, coaching-based intervention aimed at addressing mental health, physical health, and social care needs. Two hundred eligible individuals from 39 GP practices are taking part. They were recruited through identification from secondary and primary care databases. The primary hypothesis is quality of life (QOL). Secondary outcomes include: mental wellbeing, time use, recovery, and process of physical care. A process evaluation will assess fidelity of intervention delivery, test hypothesised mechanisms of action, and look for unintended consequences. An economic evaluation will estimate its cost-effectiveness. Intervention delivery and follow-up have been modified during the COVID-19 pandemic. The overarching aim is to establish the clinical and cost-effectiveness of the model for adults with a diagnosis of schizophrenia, bipolar, or other types of psychoses.PARTNERS2 is funded by the National Institute for Health Research (NIHR) under its Programme Grant for Applied Research Programme (grant number: RP-PG- 200625). This research was also supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events