Update to the effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial

Abstract: Background: MYRIAD (My Resilience in Adolescence) is a superiority, parallel group, cluster randomised controlled trial designed to examine the effectiveness and cost-effectiveness of a mindfulness training (MT) programme, compared with normal social and emotional learning (SEL) school provision to enhance mental health, social-emotional-behavioural functioning and well-being in adolescence. The original trial protocol was published in Trials (accessible at https://doi.org/10.1186/s13063-017-1917-4). This included recruitment in two cohorts, enabling the learning from the smaller first cohort to be incorporated in the second cohort. Here we describe final amendments to the study protocol and discuss their underlying rationale. Methods: Four major changes were introduced into the study protocol: (1) there were changes in eligibility criteria, including a clearer operational definition to assess the degree of SEL implementation in schools, and also new criteria to avoid experimental contamination; (2) the number of schools and pupils that had to be recruited was increased based on what we learned in the first cohort; (3) some changes were made to the secondary outcome measures to improve their validity and ability to measure constructs of interest and to reduce the burden on school staff; and (4) the current Coronavirus Disease 2019 (SARS-CoV-2 or COVID-19) pandemic both influences and makes it difficult to interpret the 2-year follow-up primary endpoint results, so we changed our primary endpoint to 1-year follow-up. Discussion: These changes to the study protocol were approved by the Trial Management Group, Trial Steering Committee and Data and Ethics Monitoring Committees and improved the enrolment of participants and quality of measures. Furthermore, the change in the primary endpoint will give a more reliable answer to our primary question because it was collected prior to the COVID-19 pandemic in both cohort 1 and cohort 2. Nevertheless, the longer 2-year follow-up data will still be acquired, although this time-point will be now framed as a second major investigation to answer some new important questions presented by the combination of the pandemic and our study design. Trial registration: International Standard Randomised Controlled Trials ISRCTN86619085. Registered on 3 June 2016

Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)

Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies comine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV ‘Treatment as Prevention’ (TasP) in PWID

A scoping review of interventions designed to support parents with mental illness that would be appropriate for parents with psychosis

The experience of psychosis can present additional difficulties for parents, over and above the normal challenges of parenting. Although there is evidence about parenting interventions specifically targeted at parents with affective disorders, anxiety, and borderline personality disorder, there is currently limited evidence for parents with psychotic disorders. It is not yet known what, if any, interventions exist for this population, or what kinds of evaluations have been conducted. To address this, we conducted a scoping review to determine (1) what parenting interventions have been developed for parents with psychosis (either specifically for, or accessible by, this client group), (2) what components these interventions contain, and (3) what kinds of evaluations have been conducted. The eligibility criteria were broad; we included any report of an intervention for parents with a mental health diagnosis, in which parents with psychosis were eligible to take part, that had been published within the last 20 years. Two reviewers screened reports and extracted the data from the included reports. Thirty-eight studies of 34 interventions were included. The findings show that most interventions have been designed either for parents with any mental illness or parents with severe mental illness, and only two interventions were trialed with a group of parents with psychosis. After noting clusters of intervention components, five groups were formed focused on: (1) talking about parental mental illness, (2) improving parenting skills, (3) long-term tailored support for the whole family, (4) groups for parents with mental illness, and (5) family therapy. Twenty-three quantitative evaluations and 13 qualitative evaluations had been conducted but only eight interventions have or are being evaluated using a randomized controlled trial (RCT). More RCTs of these interventions are needed, in addition to further analysis of the components that are the most effective in changing outcomes for both the parent and their children, in order to support parents with psychosis and their families

Bed nuclei of the stria terminalis modulate memory consolidation via glucocorticoid-dependent and -independent circuits.

There is extensive evidence that glucocorticoid hormones enhance memory consolidation, helping to ensure that emotionally significant events are well remembered. Prior findings suggest that the anteroventral region of bed nuclei of the stria terminalis (avBST) regulates glucocorticoid release, suggesting the potential for avBST activity to influence memory consolidation following an emotionally arousing learning event. To investigate this issue, male Sprague-Dawley rats underwent inhibitory avoidance training and repeated measurement of stress hormones, immediately followed by optogenetic manipulations of either the avBST or its projections to downstream regions, and 48 h later were tested for retention. The results indicate that avBST inhibition augmented posttraining pituitary-adrenal output and enhanced the memory for inhibitory avoidance training. Pretreatment with a glucocorticoid synthesis inhibitor blocked the memory enhancement as well as the potentiated corticosterone response, indicating the dependence of the memory enhancement on glucocorticoid release during the immediate posttraining period. In contrast, posttraining avBST stimulation decreased retention yet had no effect on stress hormonal output. Subsequent experiments revealed that inhibition of avBST input to the paraventricular hypothalamus enhanced stress hormonal output and subsequent retention, whereas stimulation did not affect either. Conversely, stimulation-but not inhibition-of avBST input to the ventrolateral periaqueductal gray impaired consolidation, whereas neither manipulation affected glucocorticoid secretion. These findings indicate that divergent pathways from the avBST are responsible for the mnemonic effects of avBST inhibition versus stimulation and do so via glucocorticoid-dependent and -independent mechanisms, respectively

γ-Protocadherins Interact with Neuroligin-1 and Negatively Regulate Dendritic Spine Morphogenesis

The 22 γ-Protocadherin (γ-Pcdh) cell adhesion molecules are critical for the elaboration of complex dendritic arbors in the cerebral cortex. Here, we provide evidence that the γ-Pcdhs negatively regulate synapse development by inhibiting the postsynaptic cell adhesion molecule, neuroligin-1 (Nlg1). Mice lacking all γ-Pcdhs in the forebrain exhibit significantly increased dendritic spine density in vivo, while spine density is significantly decreased in mice overexpressing one of the 22 γ-Pcdh isoforms. Co-expression of γ-Pcdhs inhibits the ability of Nlg1 to increase spine density and to induce presynaptic differentiation in hippocampal neurons in vitro. The γ-Pcdhs physically interact in cis with Nlg1 both in vitro and in vivo, and we present evidence that this disrupts Nlg1 binding to its presynaptic partner neurexin1β. Together with prior work, these data identify a mechanism through which γ-Pcdhs could coordinate dendrite arbor growth and complexity with spine maturation in the developing brain

An Evaluation of the Relative Effectiveness of Function-Based Consequent and Antecedent Interventions in a Preschool Setting

Although there is substantial functional behavioral assessment (FBA) literature suggesting that function-based interventions are effective for improving problem behavior, only a limited number of studies have examined the effectiveness of function-based antecedent versus consequent interventions. Additionally, although there has been a recent increase in the number of studies conducted in the K–12 school setting, only a limited number of studies have included children in the preschool setting. The present study extends existing literature by examining the effectiveness of function-based antecedent versus consequent interventions for reducing problem behavior and increasing appropriately engaged behavior for preschool children without cognitive disabilities. Following an FBA of 4 children, the effectiveness of a function-based antecedent (i.e., noncontingent reinforcement [NCR]) was compared with a function-based consequent (i.e., differential reinforcement of alternative behavior [DRA]) intervention using an alternating treatments design. Results indicated that both function-based NCR and DRA were effective for decreasing problem behavior and increasing appropriately engaged behavior, with function-based NCR being more effective than DRA for 2 of 4 participants

Giving primacy to the voices of people affected by cancer (PABC) in shaping educational innovations - An exploratory qualitative study

BackgroundThe number of adults diagnosed with cancer is increasing. Life beyond cancer poses many challenges for individuals and their families; many of those challenges are characterised by health uncertainties both physical and emotional. Evidence suggests that appropriate education improves care and patient outcomes specifically reducing the long‐term adverse effects of cancer and its treatments and increasing adjustment. Less evidence exists as to how meeting holistic rehabilitation needs, monitoring those surviving cancer long‐term, and supporting self‐management are enabled by health care professional (HCP) education.AimsThe aims of this study were to explore the experiences of people affected by cancer (PABC) as a long‐term condition and to use the themes emerging from their experiences to develop online bespoke educational resources/tools.Methods and ResultsA project team of professionals and PABC worked together on a qualitative study to explore the challenges and consequences of life beyond cancer. This paper presents the data from the exploratory focus group, analysed using thematic analysis to identify both common and unique perspectives in PABC experiences. Four themes were identified: the meaning of “survivorship”; the impact of cancer; long‐term needs/expectations; and the role of HCPs and education in meeting needs. These themes were compared with existing literature to enable understanding and “sense making” of the participants' life beyond cancer and to inform the development of the educational resources based on a fictitious patient story to be presented in a future publication.ConclusionsDerived from the PABC stories, a scripted story digitally recorded has been embedded with information and resources. Consultation with additional patient, professional, and public groups helped develop the work into an educational module for nurses and allied health care professionals

Giving primacy to the voices of people affected by cancer (PABC) in shaping educational innovations—An exploratory qualitative study

BackgroundThe number of adults diagnosed with cancer is increasing. Life beyond cancer poses many challenges for individuals and their families; many of those challenges are characterised by health uncertainties both physical and emotional. Evidence suggests that appropriate education improves care and patient outcomes specifically reducing the long‐term adverse effects of cancer and its treatments and increasing adjustment. Less evidence exists as to how meeting holistic rehabilitation needs, monitoring those surviving cancer long‐term, and supporting self‐management are enabled by health care professional (HCP) education.AimsThe aims of this study were to explore the experiences of people affected by cancer (PABC) as a long‐term condition and to use the themes emerging from their experiences to develop online bespoke educational resources/tools.Methods and ResultsA project team of professionals and PABC worked together on a qualitative study to explore the challenges and consequences of life beyond cancer. This paper presents the data from the exploratory focus group, analysed using thematic analysis to identify both common and unique perspectives in PABC experiences. Four themes were identified: the meaning of “survivorship”; the impact of cancer; long‐term needs/expectations; and the role of HCPs and education in meeting needs. These themes were compared with existing literature to enable understanding and “sense making” of the participants' life beyond cancer and to inform the development of the educational resources based on a fictitious patient story to be presented in a future publication.ConclusionsDerived from the PABC stories, a scripted story digitally recorded has been embedded with information and resources. Consultation with additional patient, professional, and public groups helped develop the work into an educational module for nurses and allied health care professionals

Behavioral Disturbances in Estrogen-Related Receptor alpha-Null Mice

Eating disorders, such as anorexia nervosa and bulimia nervosa, are common and severe mental illnesses of unknown etiology. Recently, we identified a rare missense mutation in the transcription factor estrogen-related receptor alpha (ESRRA) that is associated with the development of eating disorders. However, little is known about ESRRA function in the brain. Here, we report that Esrra is expressed in the mouse brain and demonstrate that Esrra levels are regulated by energy reserves. Esrra-null female mice display a reduced operant response to a high-fat diet, compulsivity/behavioral rigidity, and social deficits. Selective Esrra knockdown in the prefrontal and orbitofrontal cortices of adult female mice recapitulates reduced operant response and increased compulsivity, respectively. These results indicate that Esrra deficiency in the mouse brain impairs behavioral responses in multiple functional domains