Patient and public involvement in preclinical and medical research: Evaluation of an established programme in a Discovery-Based Medical Research Institute.

BACKGROUND AND CONTEXT: Involving people with lived experience of health conditions and the public (consumers) in health research is supported by policy, practice and research funding schemes. However, consumer involvement programmes in discovery-based preclinical research settings are uncommon. Few formal evaluations of these programmes are reported in the literature. OBJECTIVE: This study aimed to evaluate an established patient and public involvement programme operating in a major Australian Discovery-Based Medical Research Institute (DBMRI) to inform programme development and the wider field. DESIGN AND PARTICIPANTS: A multimethods programme evaluation incorporating demographic, descriptive and qualitative data obtained through consumer/researcher co-developed online surveys and semistructured virtual interviews. Programme participants (n = 111) were invited to complete an online survey seeking feedback on their experience of involvement, programme processes and perceived impacts. A purposive sample of 25 participants was interviewed. Descriptive data were analysed using explanatory statistics and qualitative data from surveys and interviews were thematically analysed. RESULTS: This consumer involvement programme was found to be useful and meaningful for most participants, with specific examples of perceived added value. Consumers most commonly engaged with researchers to inform research development, prepare funding applications or strengthen lay communication of science. Genuine consumer-researcher interactions, relationship development and mutual respect were key elements in a positive experience for participants. Opportunities to 'give back', to learn and to ground research in lived experience were identified programme strengths and benefits. Developing researcher training in how to work with consumers, increasing the diversity of the consumer group membership and expanding the range of consumer activities were identified opportunities for improvement. Organisational support and adequate programme resourcing were identified as key enablers. CONCLUSION: Discovery-based preclinical research is often viewed as being distant from clinical application; therefore, consumer involvement may be considered less relevant. However this study identified value in bringing a strong consumer voice to the discovery-based research process through a coordinated, organisation-wide approach with the potential for application in similar preclinical research settings. PATIENT OR PUBLIC CONTRIBUTION: Four consumer partners from the DBMRI Consumer Advisory Panel were actively engaged in developing this programme evaluation. Specifically, these consumer partners co-developed and pilot-tested surveys and interview guides, reviewed and commented on project data analysis and reporting and also contributed as co-authors by editing the manuscript.

Let's CHAT (community health approaches to) dementia in Aboriginal and Torres Strait Islander communities: protocol for a stepped wedge cluster randomised controlled trial.

BACKGROUND: Documented rates of dementia and cognitive impairment not dementia (CIND) in older Aboriginal and Torres Strait Islander Peoples is 3-5 times higher than the rest of the population, and current evidence suggests this condition is under-diagnosed and under-managed in a clinical primary care setting. This study aims to implement and evaluate a culturally responsive best practice model of care to optimise the detection and management of people with cognitive impairment and/or dementia, and to improve the quality of life of carers and older Aboriginal and Torres Islander Peoples with cognitive impairment. METHODS/DESIGN: The prospective study will use a stepped-wedge cluster randomised controlled trial design working with 12 Aboriginal Community Controlled Health Services (ACCHSs) across four states of Australia. Utilising a co-design approach, health system adaptations will be implemented including (i) development of a best practice guide for cognitive impairment and dementia in Aboriginal and Torres Strait Islander communities (ii) education programs for health professionals supported by local champions and (iii) development of decision support systems for local medical software. In addition, the study will utilise a knowledge translation framework, the Integrated Promoting Action on Research Implementation in Health Services (iPARIHS) Framework, to promote long-term sustainable practice change. Process evaluation will also be undertaken to measure the quality, fidelity and contextual influences on the outcomes of the implementation. The primary outcome measures will be rates of documentation of dementia and CIND, and evidence of improved management of dementia and CIND among older Indigenous peoples attending Aboriginal and Torres Strait Islander primary care services through health system changes. The secondary outcomes will be improvements to the quality of life of older Indigenous peoples with dementia and CIND, as well as that of their carers and families. DISCUSSION: The Let's CHAT Dementia project will co-design, implement and evaluate a culturally responsive best practice model of care embedded within current Indigenous primary health care. The best practice model of care has the potential to optimise the timely detection (especially in the early stages) and improve the ongoing management of people with dementia or cognitive impairment. TRIAL REGISTRATION: ACTRN12618001485224. Date of registration: 04 of September 2019.

Community Health Worker Support for Disadvantaged Patients With Multiple Chronic Diseases: A Randomized Clinical Trial.

OBJECTIVES: To determine whether a community health worker (CHW) intervention improved outcomes in a low-income population with multiple chronic conditions. METHODS: We conducted a single-blind, randomized clinical trial in Philadelphia, Pennsylvania (2013-2014). Participants (n = 302) were high-poverty neighborhood residents, uninsured or publicly insured, and diagnosed with 2 or more chronic diseases (diabetes, obesity, tobacco dependence, hypertension). All patients set a disease-management goal. Patients randomly assigned to CHWs also received 6 months of support tailored to their goals and preferences. RESULTS: Support from CHWs (vs goal-setting alone) led to improvements in several chronic diseases (changes in glycosylated hemoglobin: -0.4 vs 0.0; body mass index: -0.3 vs -0.1; cigarettes per day: -5.5 vs -1.3; systolic blood pressure: -1.8 vs -11.2; overall P = .08), self-rated mental health (12-item Short Form survey; 2.3 vs -0.2; P = .008), and quality of care (Consumer Assessment of Healthcare Providers and Systems; 62.9% vs 38%; P < .001), while reducing hospitalization at 1 year by 28% (P = .11). There were no differences in patient activation or self-rated physical health. CONCLUSIONS: A standardized CHW intervention improved chronic disease control, mental health, quality of care, and hospitalizations and could be a useful population health management tool for health care systems. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01900470.

A mixed methods systematic review on the effects of arts interventions for children and young people at-risk of offending, or who have offended on behavioural, psychosocial, cognitive and offending outcomes: A systematic review.

Background: Young people who enter the justice system experience complex health and social needs, and offending behaviour is increasingly recognised as a public health problem. Arts interventions can be used with the aim of preventing or reducing offending or reoffending. Objectives: 1. To evaluate evidence on the effectiveness and impact of arts interventions on keeping children and young people safe from involvement in violence and crime. 2. To explore factors impacting the implementation of arts interventions, and barriers and facilitators to participation and achievement of intended outcomes. 3. To develop a logic model of the processes by which arts interventions might work in preventing offending behaviours. Search Methods: We searched AMED, Academic Search Complete; APA PsycInfo; CINAHL Plus; ERIC; SocIndex; SportDiscus, Medline, CENTRAL, Web of Science, Scopus, PTSDPubs and Performing Arts Periodicals Database, Sage, the US National Criminal Justice Reference Service, the Global Policing and British Library EThOS databases, and the National Police Library from inception to January 2023 without language restrictions. Selection Criteria: We included randomised and non-randomised controlled trials and quasi-experimental study designs. We included qualitative studies conducted alongside intervention trials investigating experiences and perceptions of participants, and offering insight into the barriers and facilitators to delivering and receiving arts interventions. We included qualitative and mixed methods studies focused on delivery of arts interventions. We included studies from any global setting. We included studies with CYP (8-25 years) who were identified as at-risk of offending behaviour (secondary populations) or already in the criminal justice system (tertiary populations). We included studies of interventions involving arts participation as an intervention on its own or alongside other interventions. Primary outcomes were: (i) offending behaviour and (ii) anti-pro-social behaviours. Secondary outcomes were: participation/attendance at arts interventions, educational attainment, school attendance and engagement and exclusions, workplace engagement, wellbeing, costs and associated economic outcomes and adverse events. Data Collection and Analysis: We included 43 studies (3 quantitative, 38 qualitative and 2 mixed methods). We used standard methodological procedures expected by The Campbell Collaboration. We used GRADE and GRADE CERQual to assess the certainty of and confidence in the evidence for quantitative and qualitative data respectively. Main Results: We found insufficient evidence from quantitative studies to support or refute the effectiveness of arts interventions for CYP at-risk of or who have offended for any outcome. Qualitative evidence suggested that arts interventions may lead to positive emotions, the development of a sense of self, successful engagement in creative practices, and development of positive personal relationships. Arts interventions may need accessible and flexible delivery and are likely to be engaging if they have support from staff, family and community members, are delivered by professional artists, involve culturally relevant activity, a youth focus, regularity and a sustainable strategy. We found limited evidence that a lack of advocacy, low funding, insufficient wider support from key personnel in adjacent services could act as barriers to success. Methodological limitations resulted in a judgement of very low confidence in these findings. Authors' Conclusions: We found insufficient evidence from quantitative studies to support or refute the effectiveness of arts interventions for CYP at-risk of offending or who have offended for any outcome. We report very low confidence about the evidence for understanding the processes influencing the successful design and delivery of arts interventions in this population of CYP and their impact on behavioural, psychosocial, cognitive and offending outcomes.

PROTOCOL: A mixed methods systematic review on the effects of arts interventions for at-risk and offending children and young people on behavioural, psychosocial, cognitive and offending outcomes.

This is the protocol for a Campbell systematic review. The proposed systematic review question is: What is the effectiveness of arts interventions for at-risk and offending children and young people (8-25 years)? There are three objectives: (1) To evaluate evidence on the effectiveness and impact of arts interventions on keeping children safe from involvement in violence and crime; (2) To synthesise evidence on factors impacting the implementation of arts interventions, and barriers and facilitators to participation and achievement of intended outcomes; (3) To develop a theory-of-change approach to ensure the development of an evidence-led framework of the processes by which arts interventions might work in preventing offending behaviours.

Spinal manual therapy interventions for pediatric patients: a systematic review.

OBJECTIVE: Although much has been written about the efficacy of manual therapy interventions for adults with headaches or spinal pain, little research has focused on the use of these interventions in pediatric patients. The purpose of this systematic review was to evaluate the evidence for spinal manual therapy (SMT) interventions in patients 4-17 years old with headaches and/or mechanical spinal pain. METHODS: A search for relevant studies published in the past 15 years was conducted on MEDLINE, CINAHL, Cochrane Central Register of Randomized Control Trials, PEDro, PubMed, and Sports Discus. Only English language articles were reviewed. Studies had to include at least one outcome measure for pain, function, or quality of life. Studies evaluating post-operative interventions, or those in which the interventions were directed at influencing excessive spinal curvatures, were excluded. Case reports and studies that did not limit analysis of the results to the pediatric population were also excluded. RESULTS: Two randomized control trials and two studies offering lower levels of evidence were identified in the literature search. The latter studies were prospective cohort studies. The four studies were evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. DISCUSSION: There are very little data in the literature to support or refute the use of SMT interventions in pediatric patients. Further research is required to establish a strong evidence-based foundation for use of these interventions in children.

Pre-operative neurodevelopmental assessment in young children undergoing cardiac surgery in central South Africa: feasibility and clinical value.

BACKGROUND: Pre-operative neurodevelopmental assessment in children with congenital heart disease may assist in the early identification of children at risk for or presenting with developmental delays. This study determined the pre-operative neurodevelopmental status of young children undergoing cardiac surgery in central South Africa. Feasibility and clinical value of pre-operative assessment were also evaluated. METHODS: Children 30 months and younger, scheduled to undergo cardiac surgery, were recruited into this prospective observational analytical study. Neurodevelopmental status was assessed using the Bayley-III and neuromotor examination. Variables associated with developmental performance were determined using ANOVAs. Sociodemographic and medical information were collected using a self-developed questionnaire. Pre-operative neurodevelopmental assessment was completed for 40 children at a median age of 7.4 months, including 30 children without and 10 with Down syndrome. Mean cardiac disease severity was moderate. The inclusion rate for pre-operative developmental assessment was 68%, limited mainly by environmental barriers. RESULTS: Children with Down syndrome had significantly poorer motor (p < 0.0001), cognitive (p < 0.0001) and language performance (p < 0.001) compared to children without Down syndrome. Apart from Down syndrome, disease severity (p = 0.02), younger age at first cardiac surgery (p < 0.01) and growth failure (p = 0.04) were significantly associated with poorer cognitive, language and motor performance, respectively. Just more than half of the children without (n = 16) and all children with Down syndrome (n = 10) scored below one standard deviation of the test mean score (scores < 85) on at least one of the Bayley-III subscales, meeting the criteria for referral to rehabilitation therapies, including physiotherapy, occupational therapy and/or speech therapy. CONCLUSION: Pre-operative neurodevelopmental assessment may be of high importance in South Africa to identify children at developmental risk, facilitating early referral to rehabilitation therapies.

Maladaptive avoidance patterns in Parkinson's disease are exacerbated by symptoms of depression.

Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder, characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta. Given that dopamine is critically involved in learning and other cognitive processes, such as working memory, dopamine loss in PD has been linked both to learning abnormalities and to cognitive dysfunction more generally in the disease. It is unclear, however, whether avoidance behavior is impacted in PD. This is significant, as this type of instrumental behavior plays an important role in both decision-making and emotional (dys) function. Consequently, the aim of the present study was to examine avoidance learning and operant extinction in PD using a computer-based task. On this task, participants control a spaceship and attempt to shoot an enemy spaceship to gain points. They also learn to hide in safe areas to protect from (i.e., avoid) aversive events (on-screen explosions and point loss). The results showed that patients with PD (N = 25) acquired an avoidance response during aversive periods to the same extent as healthy age-matched controls (N = 19); however, patients demonstrated greater hiding during safe periods not associated with aversive events, which could represent maladaptive generalization of the avoidance response. Furthermore, this impairment was more pronounced during the extinction phase, and in patients who reported higher levels of depression. These results demonstrate for the first time that PD is associated with maladaptive avoidance patterns, which could possibly contribute to the emergence of depression in the disease.

Neutralization of vascular endothelial growth factor antiangiogenic isoforms is more effective than treatment with proangiogenic isoforms in stimulating vascular development and follicle progression in the perinatal rat ovary.

Inhibition of vascular endothelial growth factor A (VEGFA) signal transduction arrests vascular and follicle development. Because antiangiogenic VEGFA isoforms are proposed to block proangiogenic VEGFA isoforms from binding to their receptors, we hypothesized that proangiogenic isoforms promote and antiangiogenic isoforms inhibit these processes. The antiangiogenic isoforms Vegfa_165b and Vegfa_189b were amplified and sequenced from rat ovaries. The Vegfa_165b sequence was 90% homologous to human VEGFA_165B. Quantitative RT-PCR determined that Vegfa_165b mRNA was more abundant around Embryonic Day 18, but Vegfa_189b lacked a distinct pattern of abundance. Antiangiogenic VEGFA isoforms were localized to pregranulosa and granulosa cells of all follicle stages and to theca cells of advanced-stage follicles. To determine the effects of VEGFA isoforms in developing ovaries, Postnatal Day 3/4 rat ovaries were cultured with VEGFA_164 or an antibody to antiangiogenic isoforms (anti-VEGFAxxxB). Treatment with 50 ng/ml of VEGFA_164 resulted in a 93% increase in vascular density (P < 0.01), and treated ovaries were composed of fewer primordial follicles (stage 0) and more developing follicles (stages 1-4) than controls (P < 0.04). Ovaries treated with 5 ng/ml of VEGFAxxxB antibody had a 93% increase in vascular density (P < 0.02), with fewer primordial and early primary follicles (stage 1) and more primary, transitional, and secondary follicles (stages 2, 3, and 4, respectively) compared with controls (P < 0.005). We conclude that neutralization of antiangiogenic VEGFA isoforms may be a more effective mechanism of enhancing vascular and follicular development in perinatal rat ovaries than treatment with the proangiogenic isoform VEGFA_164.