Systematic review of tools to measure outcomes for young children with autism spectrum disorder

BACKGROUND: The needs of children with autism spectrum disorder (ASD) are complex and this is reflected in the number and diversity of outcomes assessed and measurement tools used to collect evidence about children's progress. Relevant outcomes include improvement in core ASD impairments, such as communication, social awareness, sensory sensitivities and repetitiveness; skills such as social functioning and play; participation outcomes such as social inclusion; and parent and family impact.

OBJECTIVES: To examine the measurement properties of tools used to measure progress and outcomes in children with ASD up to the age of 6 years. To identify outcome areas regarded as important by people with ASD and parents.

METHODS: The MeASURe (Measurement in Autism Spectrum disorder Under Review) research collaboration included ASD experts and review methodologists. We undertook systematic review of tools used in ASD early intervention and observational studies from 1992 to 2013; systematic review, using the COSMIN checklist (Consensus-based Standards for the selection of health Measurement Instruments) of papers addressing the measurement properties of identified tools in children with ASD; and synthesis of evidence and gaps. The review design and process was informed throughout by consultation with stakeholders including parents, young people with ASD, clinicians and researchers.

RESULTS: The conceptual framework developed for the review was drawn from the International Classification of Functioning, Disability and Health, including the domains 'Impairments', 'Activity Level Indicators', 'Participation', and 'Family Measures'. In review 1, 10,154 papers were sifted - 3091 by full text - and data extracted from 184; in total, 131 tools were identified, excluding observational coding, study-specific measures and those not in English. In review 2, 2665 papers were sifted and data concerning measurement properties of 57 (43%) tools were extracted from 128 papers. Evidence for the measurement properties of the reviewed tools was combined with information about their accessibility and presentation. Twelve tools were identified as having the strongest supporting evidence, the majority measuring autism characteristics and problem behaviour. The patchy evidence and limited scope of outcomes measured mean these tools do not constitute a 'recommended battery' for use. In particular, there is little evidence that the identified tools would be good at detecting change in intervention studies. The obvious gaps in available outcome measurement include well-being and participation outcomes for children, and family quality-of-life outcomes, domains particularly valued by our informants (young people with ASD and parents).

CONCLUSIONS: This is the first systematic review of the quality and appropriateness of tools designed to monitor progress and outcomes of young children with ASD. Although it was not possible to recommend fully robust tools at this stage, the review consolidates what is known about the field and will act as a benchmark for future developments. With input from parents and other stakeholders, recommendations are made about priority targets for research.

FUTURE WORK: Priorities include development of a tool to measure child quality of life in ASD, and validation of a potential primary outcome tool for trials of early social communication intervention.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002223.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Home on a care order: who the children are and what the care order is for

Compared to children in other placements, there is much less known about the characteristics and needs of children in the UK who are returned to their birth parents with a care order still in place. That is in spite of evidence to suggest they face more difficulties than young people in other placements. Based on a 2009 census of looked after children in Northern Ireland, just under 10% (n = 193) were found to be living at home under a care order. Case file reviews were conducted for a quarter of these young people (n = 47) to generate descriptive statistics showing a very diverse population. That was followed by semi-structured interviews with members of eight families (ten children and eight birth parent/s), providing transcripts for thematic analysis. Nearly half of the young people whose case files were reviewed had experienced at least one home placement breakdown, but nearly two thirds had a stable last home placement. Care orders appeared to serve two functions: to give legal authority to social services for the monitoring of placements, and to facilitate family access to family support services. Replacing some care orders with supervision orders might better align legal status and actual function.

Swellable polymer films containing Au nanoparticles for point-of-care therapeutic drug monitoring using surface-enhanced Raman spectroscopy

Large (10 × 10 cm) sheets of surface-enhanced Raman spectroscopy (SERS) active polymer have been prepared by stabilising metal nanoparticle aggregates within dry hydroxyethylcellulose (HEC) films. In these films the aggregates are protected by the polymer matrix during storage but in use they are released when aqueous analyte droplets cause the films to swell to their gel form. The fact that these "Poly-SERS" films can be prepared in bulk but then cut to size and stored in air before use means that they provide a cost effective and convenient method for routine SERS analysis. Here we have tested both Ag and Au Poly-SERS films for use in point-of-care monitoring of therapeutic drugs, using phenytoin as the test compound. Phenytoin in water could readily be detected using Ag Poly-SERS films but dissolving the compound in phosphate buffered saline (PBS) to mimic body fluid samples caused loss of the drug signal due to competition for metal surface sites from Cl^- ions in the buffer solution. However, with Au Poly-SERS films there was no detectable interference from Cl^- and these materials allowed phenytoin to be detected at 1.8 mg L^-1, even in PBS. The target range of detection of phenytoin in therapeutic drug monitoring is 10-20 mg L^-1. With the Au Poly-SERS films, the absolute signal generated by a given concentration of phenytoin was lower for the films than for the parent colloid but the SERS signals were still high enough to be used for therapeutic monitoring, so the cost in sensitivity for moving from simple aqueous colloids to films is not so large that it outweighs the advantages which the films bring for practical applications, in particular their ease of use and long shelf life.

Recruiting faith and non-faith based schools, adolescents and parents to a cluster randomised sexual-health trial: experiences, challenges and lessons from the mixed-methods Jack Feasibility Trial

Background: The move toward evidence-based education has led to increasing numbers of randomised trials in schools. However, the literature on recruitment to non-clinical trials is relatively underdeveloped, when compared to that of clinical trials. Recruitment to school-based randomised trials is, however, challenging; even more so when the focus of the study is a sensitive issue such as sexual health. This article reflects on the challenges of recruiting post-primary schools, adolescent pupils and parents to a cluster randomised feasibility trial of a sexual health intervention, and the strategies employed to address them.
Methods: The Jack Trial was funded by the UK National Institute for Health Research (NIHR). It comprised a feasibility study of an interactive film-based sexual health intervention entitled If I Were Jack, recruiting over 800 adolescents from eight socio-demographically diverse post-primary schools in Northern Ireland. It aimed to determine the facilitators and barriers to recruitment and retention to a school-based sexual health trial and identify optimal multi-level strategies for an effectiveness study. As part of an embedded process evaluation, we conducted semi-structured interviews and focus groups with principals, vice-principals, teachers, pupils and parents recruited to the study as well as classroom observations and a parents’ survey.
Results: With reference to Social Learning Theory, we identified a number of individual, behavioural and environmental level factors which influenced recruitment. Commonly identified facilitators included perceptions of the relevance and potential benefit of the intervention to adolescents, the credibility of the organisation and individuals running the study, support offered by trial staff, and financial incentives. Key barriers were prior commitment to other research, lack of time and resources, and perceptions that the intervention was incompatible with pupil or parent needs or the school ethos.
Conclusions: Reflecting on the methodological challenges of recruiting to a school-based sexual health feasibility trial, this study highlights pertinent general and trial-specific facilitators and barriers to recruitment, which will prove useful for future trials with schools, adolescent pupils and parents.

Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Feasibility Studies and Physicochemical Characterisation

Engineered cocrystals offer an alternative solid drug form with tailored physicochemical properties. Interestingly, although cocrystals provide many new possibilities, they also present new challenges, particularly in regard to their design and large-scale manufacture. Current literature has primarily focused on the preparation and characterization of novel cocrystals typically containing only the drug and coformer, leaving the subsequent formulation less explored. In this paper we propose, for the first time, the use of hot melt extrusion for the mechanochemical synthesis of pharmaceutical cocrystals in the presence of a meltable binder. In this approach, we examine excipients that are amenable to hot melt extrusion, forming a suspension of cocrystal particulates embedded in a pharmaceutical matrix. Using ibuprofen and isonicotinamide as a model cocrystal reagent pair, formulations extruded with a small molecular matrix carrier (xylitol) were examined to be intimate mixtures wherein the newly formed cocrystal particulates were physically suspended in a matrix. With respect to formulations extruded using polymeric carriers (Soluplus and Eudragit EPO, respectively), however, there was no evidence within PXRD patterns of either crystalline ibuprofen or the cocrystal. Importantly, it was established in this study that an appropriate carrier for a cocrystal reagent pair during HME processing should satisfy certain criteria including limited interaction with parent reagents and cocrystal product, processing temperature sufficiently lower than the onset of cocrystal Tm, low melt viscosity, and rapid solidification upon cooling.

Comparing long-term placements for young children in care: Does type of placement really matter?

This paper presents findings from the third phase of a longitudinal study, entitled Care Pathways and Outcomes, which has been tracking the placements and measuring outcomes for a population of children (n = 374) who were under the age of five and in care in Northern Ireland on the 31st March 2000. It explores how a sub-sample of these children at age nine to 14 years old were getting on in the placements provided for them, in comparative terms across five placement types: adoption; foster care; kinship foster care (with relatives); on Residence Order; and living with birth parents. This specifically focused on the development of attachment and self-concept from the perspective of the children, and behavioural and emotional function, and parenting stress, from the perspective of parents and carers. Findings showed no significant placement effect from the perspective of children, and a statistically weak, but descriptively compelling, effect from the perspective of parents. The findings challenge the notion of adoption as the gold standard in long-term placements, specifically from the perspective of children in terms of their parent/carer attachments and self-concept, and highlight what appears to be the central importance of placement longevity for delivering positive longer-term outcomes for these children, irrespective of placement type.

Thromboxane A2 receptor (TBXA2R) is a potent survival factor for triple negative breast cancers (TNBCs)

Triple Negative Breast Cancer (TNBC) is defined by the lack of ERα, PR expression and HER2 overexpression and is the breast cancer subtype with the poorest clinical outcomes. Our aim was to identify genes driving TNBC proliferation and/or survival which could represent novel therapeutic targets. We performed microarray profiling of primary TNBCs and generated differential genelists based on clinical outcomes following the chemotherapy regimen FEC (5-Fluorouracil/Epirubicin/Cyclophosphamide -‘good’ outcome no relapse > 3 years; ‘poor’ outcome relapse < 3 years). Elevated expression of thromboxane A2 receptor (TBXA2R) was observed in ‘good’ outcome TNBCs. TBXA2R expression was higher specifically in TNBC cell lines and TBXA2R knockdowns consistently showed dramatic cell killing in TNBC cells. TBXA2R mRNA and promoter activities were up-regulated following BRCA1 knockdown, with c-Myc being required for BRCA1-mediated transcriptional repression. We demonstrated that TBXA2R enhanced TNBC cell migration, invasion and activated Rho signalling, phenotypes which could be reversed using Rho-associated Kinase (ROCK) inhibitors. TBXA2R also protected TNBC cells from DNA damage by negatively regulating reactive oxygen species levels. In summary, TBXA2R is a novel breast cancer-associated gene required for the survival and migratory behaviour of a subset of TNBCs and could provide opportunities to develop novel, more effective treatments.

The Family Model - A transgenerational approach to mental health in families: personal, clinical, educational, research, systems and policy perspectives

The Family Model – A transgenerational approach to mental health in families This workshop will provide an overview on The Family Model (TFM) and its use in promoting and facilitating a trans­generational family focus in Mental Health services, over the past 10­ - 15 years. Each of the speakers will address a different perspective, including service user/consumer, clinical practice, education & training, research and policy. Adrian Falkov (chair) will provide an overview of TFM to set the scene and a ‘policy to practice’ perspective, based on use of TFM in Australia. Author: Heide Lloyd. The Family Model ­ A personal (consumer/patient) perspective | United Kingdom Heide will provide a description of her experiences as a child, adult, parent & grandparent, using TFM as the structure around which to ‘weave’ her story and demonstrate how TFM has assisted her in understanding the impact of symptoms on her & family and how she has used it in her management of symptoms and recovery (personal perspective). The Family Model ­ Education & training perspective ­ Marie Diggins | United Kingdom PhD Bente Weimand | Norway Authors: ­ Marie Diggins | United Kingdom PhD Bente Weimand | Norway This combined (UK & Norwegian) presentation will cover historical background to TFM and its use in eLearning (the Social Care Institute for Excellence)and a number of other UK initiatives, together with a description of the postgraduate masters course at the University Oslo/Akershus, using TFM. The Family Model ­ A research perspective PhD Anne Grant | Northern Ireland Author: PhD Anne Grant | Ireland Anne Grant will describe how she used TFM as the theoretical framework for her PhD looking at family focused (nursing) practice in Ireland. The Family Model ­ A service systems perspective ­ Mary Donaghy | Northern Ireland Authors: PhD Adrian Falkov | Australia ­ Mary Donaghy | N Ireland Mary Donaghy will discuss how TFM has been used to support & facilitate a cross service ‘whole of system’ change program in Belfast (NI) to achieve improved family focused practice. She will demonstrate its utility in achieving a broader approach to service design, delivery and evaluation.