Natural history study of hepatic glycogen storage disease type IV and comparison to Gbe1ys/ys model.

BackgroundGlycogen storage disease type IV (GSD IV) is an ultrarare autosomal recessive disorder that causes deficiency of functional glycogen branching enzyme and formation of abnormally structured glycogen termed polyglucosan. GSD IV has traditionally been categorized based on primary hepatic or neuromuscular involvement, with hepatic GSD IV subclassified as discrete subtypes: classic (progressive) and nonprogressive.MethodsTo better understand the progression of liver disease in GSD IV, we present clinical and histopathology data from 23 patients from around the world and characterized the liver involvement in the Gbe1ys/ys knockin mouse model.ResultsWe propose an alternative to the established subtype-based terminology for characterizing liver disease in GSD IV and recognize 3 tiers of disease severity: (i) "severe progressive" liver disease, (ii) "intermediate progressive" liver disease, and (iii) "attenuated" liver disease. Analysis of liver pathology revealed that risk for liver failure cannot be predicted from liver biopsy findings alone in individuals affected by GSD IV. Moreover, analysis of postmortem liver pathology from an individual who died over 40 years after being diagnosed with nonprogressive hepatic GSD IV in childhood verified that liver fibrosis did not regress. Last, characterization of the liver involvement in a mouse model known to recapitulate the adult-onset neurodegenerative form of GSD IV (Gbe1ys/ys mouse model) demonstrated hepatic disease.ConclusionOur findings challenge the established subtype-based view of GSD IV and suggest that liver disease severity among patients with GSD IV represents a disease continuum.Trial registrationClinicalTrials.gov NCT02683512FundingNone.

An exploratory randomised trial investigating feasibility, potential impact and cost effectiveness of link workers for people living with multimorbidity attending general practices in deprived urban communities.

BACKGROUND: Social prescribing link workers are non-health or social care professionals who connect people with psychosocial needs to non-clinical community supports. They are being implemented widely, but there is limited evidence for appropriate target populations or cost effectiveness. This study aimed to explore the feasibility, potential impact on health outcomes and cost effectiveness of practice-based link workers for people with multimorbidity living in deprived urban communities. METHODS: A pragmatic exploratory randomised trial with wait-list usual care control and blinding at analysis was conducted during the COVID 19 pandemic (July 2020 to January 2021). Participants had two or more ongoing health conditions, attended a general practitioner (GP) serving a deprived urban community who felt they may benefit from a one-month practice-based social prescribing link worker intervention.. Feasibility measures were recruitment and retention of participants, practices and link workers, and completion of outcome data. Primary outcomes at one month were health-related quality of life (EQ-5D-5L) and mental health (HADS). Potential cost effectiveness from the health service perspective was evaluated using quality adjusted life years (QALYs), based on conversion of the EQ-5D-5L and ICECAP-A capability index to utility scoring. RESULTS: From a target of 600, 251 patients were recruited across 13 general practices. Randomisation to intervention (n = 123) and control (n = 117) was after baseline data collection. Participant retention at one month was 80%. All practices and link workers (n = 10) were retained for the trial period. Data completion for primary outcomes was 75%. There were no significant differences identified using mixed effects regression analysis in EQ-5D-5L (MD 0.01, 95% CI -0.07 to 0.09) or HADS (MD 0.05, 95% CI -0.63 to 0.73), and no cost effectiveness advantages. A sensitivity analysis that considered link workers operating at full capacity in a non-pandemic setting, indicated the probability of effectiveness at the €45,000 ICER threshold value for Ireland was 0.787 using the ICECAP-A capability index. CONCLUSIONS: While the trial under-recruited participants mainly due to COVID-19 restrictions, it demonstrates that robust evaluations and cost utility analyses are possible. Further evaluations are required to establish cost effectiveness and should consider using the ICE-CAP-A wellbeing measure for cost utility analysis. REGISTRATION: This trial is registered on ISRCTN. TITLE: Use of link workers to provide social prescribing and health and social care coordination for people with complex multimorbidity in socially deprived areas. TRIAL ID: ISRCTN10287737. Date registered 10/12/2019. Link: https://www.isrctn.com/ISRCTN10287737.

An evaluation of the social deprivation practice grant in Irish general practice.

BACKGROUND: The Inverse Care Law states that availability of good medical care varies inversely with the need for it in the population served. In 2019 the main medical union and the Department of Health in Ireland, agreed on funding a Social Deprivation Practice grant for GP practices in urban deprived areas. AIM: The aim of this study was to examine the implementation and impact of the Social Deprivation Practice Grant in participating General Practices. DESIGN & SETTING: A mixed methods study with sequential design based in Irish General Practice. METHOD: Data were collected using a questionnaire and online semi-structured interviews with GPs and practice staff. Data were analysed separately, and the findings compared to examine the extent to which they converged or diverged. RESULTS: There were 25 survey responses and nine interviews. All practices reported the grant was beneficial and most practices utilised the grant to fund additional doctor hours (17/25). Both surveys and interviews indicated that a small amount of additional funding allowed additional clinical need in areas of deprivation to be addressed but there were some barriers identified in accessing the grant and implementing planned expenditure. CONCLUSION: Delivery of healthcare in areas of socioeconomic deprivation presents significant challenges. While there were some problems with implementation, the introduction of a small, targeted grant for GP practices in areas of social deprivation allowed those practices to enhance their services with tailored initiatives seeking to meet the needs of their patient populations.

Exploration of Evaluation Practices in Social Prescribing Services in Ireland: A Cross-Sectional Observational Study.

National health services in Ireland and the UK fund the majority of social prescribing services and have issued recommendations for evaluation. However, it is not known what outcomes are prioritised for evaluation within individual services and what evaluation methods are used to capture recommended outcomes. A survey was carried out to examine evaluation practices of social prescribing services on the island of Ireland. This study used a cross-sectional observational design. The sample was all the staff involved in delivering and/or managing SP services on the island of Ireland. Questionnaires were distributed at a national SP conference and online. Closed-response questions were analysed using descriptive statistics. Content analysis was used for open-ended questions. Eighty-four usable surveys were returned (50% from the Republic of Ireland and 50% from Northern Ireland). All respondents (100%) agreed on the importance of measuring SP outcomes. The most frequently measured outcomes were health and well-being (89.2%) and loneliness (84%). The least frequently measured outcome was the satisfaction of healthcare professionals referring to SP: 78.4% of respondents never measured this outcome. The most frequently used measurement tool was the Short Warwick Edinburgh Mental Well-Being Scale, with 38/76 (50%) respondents using this measure. There was a lack of standardised measures identified for some outcomes. For example, 70% of respondents reported always measuring physical activity (PA), but only four respondents identified a specific PA measure. In open-ended questions, respondents recommended flexibility in evaluation methods to reflect the complexity and individualised focus of SP. They also identified the need for protected time to complete evaluations and recommended a national strategy to inform priorities in evaluations. This study demonstrates a wide variation on the island of Ireland on how SP services are measuring outcomes, with many outcomes rarely or never measured using standardised measures. Agreement is needed on a core outcome set for social prescribing in order to guide service delivery and evaluations.

Embedding formal and experiential public and patient involvement training in a structured PhD programme: process and impact evaluation.

BACKGROUND: Incorporating Public and Patient Involvement (PPI) into doctoral research is valued by PhD funders and scholars. Providing early career researchers with appropriate training to develop skills to conduct meaningful PPI involvement is important. The Health Research Board (HRB) Collaborative Doctoral Award in MultiMorbidity programme (CDA-MM) embedded formal PPI training in its structured education. The four participating PhD scholars established a PPI panel comprising people living with two or more chronic conditions, presenting an opportunity for experiential PPI training. This study aimed to evaluate the process and impact of embedding PPI training in a structured PhD programme. METHODS: This study was a longitudinal mixed-methods evaluation, conducted over 24 months (June 2020 to June 2022). A process evaluation provided an understanding of how PPI was embedded and explored the experiences of key stakeholders involved. An impact evaluation assessed the impact of embedding PPI training in the programme. Participants included PhD scholars, PPI contributors and PhD supervisors. The data collection and analysis was led by an independent researcher not aligned with the CDA-MM. Data collection methods included five focus groups, individual interviews (n = 6), an impact log, activity logs and group reflections. Qualitative data were analysed using thematic and content analysis and quantitative data analysed using descriptive statistics. RESULTS: Embedding formal and experiential PPI training in a structured PhD programme is feasible. Both approaches to training are fundamental to building PPI capacity. Involvement of an experienced and knowledgeable PPI lead throughout is perceived as critical. The PPI panel approach offered a good example of embedded consultation and worked well in a structured PhD programme, providing PhD scholars with ample opportunities for learning about PPI and its implementation. For PPI contributors, culture was the most important indicator of quality and was positively evaluated. Key roles for PhD supervisors were identified. Embedding formal and experiential PPI training impacted positively on many different aspects of individual PhD research projects and on PhD scholars as researchers. There were positive impacts for PPI contributors and PhD supervisors. CONCLUSIONS: Embedding formal and experiential PPI training in a structured PhD programme is a novel approach. The evaluation has identified a number of lessons that can inform future doctoral programmes seeking to embed formal and experiential PPI training.

Four PhD scholars participated in the CDA-MM. They received training and support from a PPI lead on how to conduct PPI in research. They established a PPI panel of people with two or more ongoing health conditions, to enable PhD scholars to get input from PPI contributors and learn how to do PPI well. An evaluation study was conducted to explore how the PhD scholars conducted PPI, how well it worked, the difference it made and to identify messages for PhD scholars wishing to involve PPI contributors. For the evaluation, the PPI contributors, PhD scholars and PhD supervisors were asked about their experiences and views. For many of the PPI contributors, being part of the CDA-MM PPI panel was their first experience of being involved in PPI. The ongoing support they received from PhD scholars was important. For them, relationships and the way that meetings are conducted matter for doing PPI well. They liked working in small groups and on concrete issues. They found the time they were expected to give was reasonable and within acceptable limits. They preferred in-person meetings. According to PPI contributors, when PPI is done well, it has benefits for the research, particularly ensuring that plain language is used and jargon avoided when researchers communicate with people with two or more ongoing health conditions. PhD scholars benefit from getting the patient perspective and learning how to communicate their research to patients. PPI contributors benefit in many different ways. Some PPI contributors argued that the PPI advisory panel worked so well in the CDA-MM that no changes were needed, whereas others would like to explore different ways of being involved in research.

Diagnosis and management of glycogen storage disease type IV, including adult polyglucosan body disease: A clinical practice resource.

Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disorder caused by pathogenic variants in GBE1 which results in reduced or deficient glycogen branching enzyme activity. Consequently, glycogen synthesis is impaired and leads to accumulation of poorly branched glycogen known as polyglucosan. GSD IV is characterized by a remarkable degree of phenotypic heterogeneity with presentations in utero, during infancy, early childhood, adolescence, or middle to late adulthood. The clinical continuum encompasses hepatic, cardiac, muscular, and neurologic manifestations that range in severity. The adult-onset form of GSD IV, referred to as adult polyglucosan body disease (APBD), is a neurodegenerative disease characterized by neurogenic bladder, spastic paraparesis, and peripheral neuropathy. There are currently no consensus guidelines for the diagnosis and management of these patients, resulting in high rates of misdiagnosis, delayed diagnosis, and lack of standardized clinical care. To address this, a group of experts from the United States developed a set of recommendations for the diagnosis and management of all clinical phenotypes of GSD IV, including APBD, to support clinicians and caregivers who provide long-term care for individuals with GSD IV. The educational resource includes practical steps to confirm a GSD IV diagnosis and best practices for medical management, including (a) imaging of the liver, heart, skeletal muscle, brain, and spine, (b) functional and neuromusculoskeletal assessments, (c) laboratory investigations, (d) liver and heart transplantation, and (e) long-term follow-up care. Remaining knowledge gaps are detailed to emphasize areas for improvement and future research.

Health status of Syrian refugees in Ireland - research and routine data informing service provision.

INTRODUCTION: The Irish government agreed to accept up to 4000 Syrian refugees for resettlement in Ireland in 2016. Prior to their arrival in Ireland, health screening was carried out by the International Organisation for Migration. GP assessments to address immediate health needs and facilitate integration into local primary care were conducted on arrival. METHODS: Cross-sectional data from a self-completed questionnaire among Syrian Refugees aged 16 years and older resident in emergency reception centres (EROCs) are reported along with data from GP assessments. The questionnaire, comprising validated instruments, was developed for a similar study in Norway. RESULTS: From the research questionnaires, two-thirds of the respondents reported their overall health status to be good or very good. The most common health condition was headache and the most common medications used were painkillers. Those experiencing chronic pain were three times less likely to rate their general health as good compared with those without pain. From the GP assessment data, we identified that 28% had high blood pressure, 61% were assessed to be in need of dental care and 32% of refugees were found to have an issue with their vision. DISCUSSION: Our findings were communicated to the Health Service Executive via the Partnership for Health Equity and informed a change in service provision in relation to dental services in EROCs. In terms of further action, we conclude that pain is an important symptom to consider in terms of diagnosis and treatment, and impact on health status.

Participatory research to improve medication reconciliation for older adults in the community.

INTRODUCTION: Medication reconciliation, a technique that assists in aligning a care team's understanding of an individual's true medication regimen, is vital to optimize medication use and prevent medication errors. Historically, most medication reconciliation research has focused on institutional settings and transitional care, with comparatively little attention given to medication reconciliation in community settings. To optimize medication reconciliation for community-dwelling older adults, healthcare professionals and older adults must be engaged in co-designing processes that create sustainable approaches. METHODS: Academic researchers, older adults, and community- and health system-based healthcare professionals engaged in a participatory process to better understand medication reconciliation barriers and co-design solutions. The initiative consisted of two participatory research approaches: (1) Sparks Innovation Studios, which synthesized professional expertise and opinions, and (2) a Community Consultation Studio with older adults. Input from both groups informed a list of possible solutions and these were ranked based on evaluative criteria of feasibility, person-centeredness, equity, and sustainability. RESULTS: Sparks Innovation Studios identified a lack of ownership, fragmented healthcare systems, and time constraints as the leading barriers to medication reconciliation. The Community Consultation Studio revealed that older adults often feel dismissed in medical encounters and perceive poor communication with and among providers. The Community Consultation Studio and Sparks Innovation Studios resulted in four highly-ranked solutions to improve medication reconciliation: (1) support for older adults to improve health literacy and ownership; (2) ensuring medication indications are included on prescription labels; (3) trainings and incentives for front-line staff in clinic settings to become champions for medication reconciliation; and (4) electronic health record improvements that simplify active medication lists. CONCLUSION: Engaging community representatives with academic partners in the research process enhanced understanding of community priorities and provided a practical roadmap for innovations that have the potential to improve the well-being of community-dwelling older adults.

Patient and general practitioner experiences of implementing a medication review intervention in older people with multimorbidity: Process evaluation of the SPPiRE trial.

INTRODUCTION: The SPPiRE cluster randomized controlled trial found that a general practitioner (GP)-delivered medication review that incorporated screening for potentially inappropriate prescriptions (PIP), a brown bag review and a patient priority assessment, resulted in a significant but small reduction in the number of medicines and no significant reduction in PIP. This process evaluation aims to explore the experiences of GPs and patients and the potential for system-wide implementation. METHODS: The trial included 51 general practices and 404 participants with multimorbidity aged ≥65 years, prescribed ≥15 medicines. The process evaluation used mixed methods and ran parallel to the trial. Quantitative data was collected from the SPPiRE intervention website and analysed descriptively. Qualitative data on medication changes were collected from intervention GPs (18/26) and a purposive sample of intervention patients (27/208) via semi-structured telephone interviews. All interviews were transcribed verbatim and analysed using a thematic analysis. Qualitative and quantitative data were integrated using a triangulation protocol. RESULTS: The analysis generated two themes, intervention implementation and mechanisms of action, and both were underpinned by the theme of context. Intervention delivery varied among practices and 45 patients (28%) had no review, primarily due to insufficient GP time. 80% of reviewed patients had ≥1 PIP identified, 59% had ≥1 problem identified during the brown bag review and 79% had ≥1 priority recorded. The brown bag review resulted in the most deprescription of medications. GPs and patients responded positively to the intervention but most GPs did not engage with the patient priority-setting process. GPs identified a lack of integration into practice software and resources as barriers to future implementation. CONCLUSION: The SPPiRE intervention had a small effect in reducing the number of medicines and this was primarily mediated through the brown bag review. The context of resource shortages and deep-seated views around medical decision-making influenced intervention implementation. PATIENT OR PUBLIC CONTRIBUTION: Qualitative data on the implementation of the medication review and their wider views on their medicines was collected from older people with multimorbidity through semi-structured telephone interviews. CLINICAL TRIAL REGISTRATION: The SPPiRE trial was registered prospectively on the ISRCTN registry (ISRCTN12752680).

Effect of social prescribing link workers on health outcomes and costs for adults in primary care and community settings: a systematic review.

OBJECTIVES: To establish the evidence base for the effects on health outcomes and costs of social prescribing link workers (non-health or social care professionals who connect people to community resources) for people in community settings focusing on people experiencing multimorbidity and social deprivation. DESIGN: Systematic review and narrative synthesis using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. DATA SOURCES: Cochrane Database, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, EU Clinical Trials Register, CINAHL, Embase, Global Health, PubMed/MEDLINE, PsycInfo, LILACS, Web of Science and grey literature were searched up to 31 July 2021. A forward citation search was completed on 9 June 2022. ELIGIBILITY CRITERIA: Controlled trials meeting the Cochrane Effectiveness of Practice and Organisation of Care (EPOC) guidance on eligible study designs assessing the effect of social prescribing link workers for adults in community settings on any outcomes. No language restrictions were applied. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data, evaluated study quality using the Cochrane EPOC risk of bias tool and judged certainty of the evidence. Results were synthesised narratively. RESULTS: Eight studies (n=6500 participants), with five randomised controlled trials at low risk of bias and three controlled before-after studies at high risk of bias, were included. Four included participants experiencing multimorbidity and social deprivation. Four (n=2186) reported no impact on health-related quality of life (HRQoL). Four (n=1924) reported mental health outcomes with three reporting no impact. Two US studies found improved ratings of high-quality care and reduced hospitalisations for people with multimorbidity experiencing deprivation. No cost-effectiveness analyses were identified. The certainty of the evidence was low or very low. CONCLUSIONS: There is an absence of evidence for social prescribing link workers. Policymakers should note this and support evaluation of current programmes before mainstreaming. PROSPERO REGISTRATION NUMBER: CRD42019134737.

A novel approach to characterize phenotypic variation in GSD IV: Reconceptualizing the clinical continuum.

Purpose: Glycogen storage disease type IV (GSD IV) has historically been divided into discrete hepatic (classic hepatic, non-progressive hepatic) and neuromuscular (perinatal-congenital neuromuscular, juvenile neuromuscular) subtypes. However, the extent to which this subtype-based classification system accurately captures the landscape of phenotypic variation among GSD IV patients has not been systematically assessed. Methods: This study synthesized clinical data from all eligible cases of GSD IV in the published literature to evaluate whether this disorder is better conceptualized as discrete subtypes or a clinical continuum. A novel phenotypic scoring approach was applied to characterize the extent of hepatic, neuromuscular, and cardiac involvement in each eligible patient. Results: 146 patients met all inclusion criteria. The majority (61%) of those with sufficient data to be scored exhibited phenotypes that were not fully consistent with any of the established subtypes. These included patients who exhibited combined hepatic-neuromuscular involvement; patients whose phenotypes were intermediate between the established hepatic or neuromuscular subtypes; and patients who presented with predominantly cardiac disease. Conclusion: The application of this novel phenotypic scoring approach showed that-in contrast to the traditional subtype-based view-GSD IV may be better conceptualized as a multidimensional clinical continuum, whereby hepatic, neuromuscular, and cardiac involvement occur to varying degrees in different patients.

A protocol for the evaluation of the process and impact of embedding formal and experiential Public and Patient Involvement training in a structured PhD programme.

BACKGROUND: Incorporating Public and Patient Involvement (PPI) into doctoral research is valued by PhD scholars. The importance of providing early career researchers with appropriate education and training to develop skills to conduct meaningful involvement has been articulated. The Collaborative Doctoral Award in MultiMorbidity (CDA-MM) PhD programme embedded formal PPI training as a postgraduate education component. Four PhD scholars taking part in the CDA-MM established a PPI panel comprising people, and carers of people, living with multimorbidity (≥2 chronic conditions), presenting an opportuning for experiential PPI training. The proposed study aims to evaluate the process and impact of formal and experiential PPI training during a PhD programme. DESIGN: Embedding PPI training in a PhD programme is a novel approach. This evaluation will include a process evaluation to provide an understanding of the workings of the PPI panel and explore the experiences of key stakeholders involved, and an impact evaluation to assess the impact of embedding PPI training in a PhD programme. This study is a longitudinal mixed-methods evaluation, conducted over 24 months. Participants include PhD scholars, PPI contributors and PhD supervisors. An independent researcher not aligned with the CDA-MM will lead the evaluation. Data collection methods include focus groups, individual interviews, an impact log and group reflections. Qualitative data will be analysed using thematic and content analysis and quantitative data will be analysed using descriptive statistics. DISCUSSION: This evaluation will report the learnings from embedding formal and experiential PPI training and education across a PhD programme.

Primary care-based link workers providing social prescribing to improve health and social care outcomes for people with multimorbidity in socially deprived areas (the LinkMM trial): Pilot study for a pragmatic randomised controlled trial.

INTRODUCTION: Individuals with multimorbidity in deprived areas experience worse health outcomes and fragmented care. Research suggests that primary care-based link workers providing social prescribing have potential to improve health and well-being. This paper reports the results of a pilot study conducted in preparation for a randomised controlled trial (RCT) that aims to test the effectiveness of primary care-based link workers providing social prescribing in improving health outcomes for people with multimorbidity who attend general practices in deprived areas in Ireland. METHODS: An uncontrolled pilot study of an intervention based on the Glasgow Deep End links worker programme, in a single general practice, tested the feasibility and acceptability of planned processes for a RCT. Outcomes were recruitment and retention rates and acceptability of the trial processes and intervention to patients, general practitioners (GPs) and the link worker. Structured interviews were conducted with six patients, the link worker and two GPs within the practice and analysed using descriptive qualitative analysis. Feedback from a Public Patient Involvement group and an Implementation Advisory Group of key stakeholders was incorporated into the evaluation process. RESULTS: Twelve out of 14 patients completed the intervention. Selection and recruitment processes were lengthier than expected. GPs recommended including psychosocial need in the selection process. Interviewed patients, the GPs and the link worker were positive about the intervention. CONCLUSION: A range of adaptations were identified for the main trial, mainly considering psychosocial need in the selection process to reflect normal referral pathways. This has resulted in a pragmatic RCT design.

Link workers providing social prescribing and health and social care coordination for people with multimorbidity in socially deprived areas (the LinkMM trial): protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Link workers are non-health or social care professionals based in primary care who support people to develop and achieve a personalised set of health and social goals by engaging with community resources. Link workers have been piloted in areas of deprivation, but there remains insufficient evidence to support their effectiveness. Multimorbidity is increasing in prevalence, but there are limited evidence-based interventions. This paper presents the protocol for a randomised controlled trial (RCT) that will test the effectiveness of link workers based in general practices in deprived areas in improving health outcomes for people with multimorbidity. METHODS AND ANALYSIS: The protocol presents the proposed pragmatic RCT, involving 10 general practitioner (GP) practices and 600 patients. Eligible participants will be community dwelling adults with multimorbidity (≥two chronic conditions) identified as being suitable for referral to a practice-based link worker. Following baseline data collection, the patients will be randomised into intervention group that will meet the link worker over a1-month period, or a 'wait list' control that will receive usual GP care. Primary outcomes are health-related quality of life as assessed by EQ-5D-5L and mental health assessed by Hospital Anxiety and Depression Scale. Secondary outcomes are based on the core outcome set for multimorbidity. Data will be collected at baseline and on intervention completion at 1 month using questionnaires self-completed by participants and GP records. Parallel process and economic analyses will be conducted to explore participants' experiences and examine cost-effectiveness of the link worker intervention. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Irish College of General Practitioners Ethics Committee. The findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN10287737;Pre-results.

Protocol for a mixed methods process evaluation of the LinkMM randomised controlled trial "Use of link workers to provide social prescribing and health and social care coordination for people with complex multimorbidity in socially deprived areas".

Background  Multimorbidity, defined as two or more chronic conditions is increasing in prevalence and is associated with increased health care use, fragmented care and poorer health outcomes. Link workers are non-health or social care professionals who support people to connect with resources in their community to improve their well-being, a process commonly referred to as social prescribing. The use of link workers in primary care may be an effective intervention in helping those with long-term conditions manage their illness and improve health and well-being, but the evidence base in limited. The LinkMM study is a randomised controlled trial of the effectiveness of link workers based in primary care, providing social prescribing and health and social care coordination for people with multimorbidity. The aim of the LinkMM process evaluation is to investigate the implementation of the link worker intervention, mechanisms of impact and influence of the specific context on these, as per the Medical Research Council framework, using quantitative and qualitative methods. Methods  Quantitative data will be gathered from a number of sources including researcher logbooks, participant baseline questionnaires, client management database, and will be analysed using descriptive statistics. Semi structured interviews with participants will investigate their experiences of the intervention. Interviews with link workers, practices and community stakeholders will explore how the intervention was implemented and barriers and facilitators to this. Thematic analysis of interview transcripts will be conducted. Discussion  The process evaluation of the LinkMM trial will provide important information allowing a more in-depth understanding of how the intervention worked and lessons for future wider scale implementation.

Patterns and Outcomes of Diagnosis Disclosure to Youth with Autism Spectrum Disorder.

OBJECTIVE: Although the benefits of diagnosis disclosure have been recognized for a number of pediatric medical conditions, there is a paucity of research about the process by which youth with autism spectrum disorder (ASD) are informed about their diagnosis. The aim of this study was to systematically characterize the antecedents, correlates, and outcomes of diagnosis disclosure to youth with ASD. METHODS: In this cross-sectional study, parents and guardians of youth with ASD (ages 8-25) completed a detailed online questionnaire about their experiences with diagnosis disclosure. The perceived impact of disclosure on affected youth was also assessed. RESULTS: Five hundred seventy-five parents of youth with ASD (mean age: 14 years) completed the questionnaire, of whom 81% reported their affected child had been told that he or she had ASD. Most youth who had been told about their diagnosis (86%) were currently aware that they had ASD, according to the parent report. Youth awareness of the diagnosis was reported to be associated with improved self-advocacy skills (60%), enhanced self-awareness of personal strengths (69%) and weaknesses (68%), and other benefits. Youth who had sought information about ASD from support groups and other individuals with ASD had better outcomes regarding self-esteem [adjusted odds ratio = 2.73, 95% confidence interval: (1.34, 3.98)] and acceptance of the diagnosis (p = 0.001) than those who exclusively learned about ASD from other sources. CONCLUSION: Given the numerous potential benefits of diagnosis disclosure, there is a need for physicians and other professionals to support parents in educating youth with ASD about their diagnosis.

Correlates of genetic attributions among parents of children in the USA with developmental disabilities.

INTRODUCTION: As technologies for identifying causal genetic variants in children with autism spectrum disorders (ASD) and other developmental conditions continue to advance, there is a need to understand the factors that influence parental beliefs about the causes of their child's disabilities. This study assessed the correlates of etiologic attributions among US parents of children with ASD, intellectual disability (ID), and/or developmental delay (DD). METHODS: Data were obtained from the Centers for Disease Control and Prevention's nationally representative Survey of Pathways to Diagnosis and Services. Respondents were classified according to whether their child had ASD without ID or DD (ASD-only), ASD with ID and/or DD (ASD+ID/DD), or ID and/or DD without ASD (ID/DD-only). Respondents rated the extent to which they believed that genetics/heredity and environmental exposures (prenatal and/or postnatal) had contributed to their child's condition. Logistic regression analyses and chi-square tests were used to assess the relationship between parental beliefs and child characteristics. RESULTS: The parents of children with comorbid ASD and ID/DD were found to be significantly less likely than those in the other condition groups to attribute their child's condition to genetics. Within the ASD+ID/DD group, parental endorsement of genetics was lower among those who reported a history of language regression (p=0.006). CONCLUSION: Further research is needed to evaluate the impact of parental genetic attributions on medical decision-making.

Effectiveness of link workers providing social prescribing on health outcomes and costs for adult patients in primary care and community settings. A protocol for a systematic review of the literature.

Introduction: The use of link workers for social prescribing and health and social care coordination is increasing, but there is insufficient data to demonstrate their effectiveness or for whom they work best. Multimorbidity is increasing in prevalence and affects those living in deprived areas ten years earlier than affluent areas. This systematic review aims to examine the evidence for the effectiveness and costs of link workers in improving health outcomes. We will also look for evidence for the use of link workers specifically for people living with multimorbidity and in deprived areas. Methods: Databases of published and grey literature will be searched for randomised and non-randomised controlled trials examining use of link workers based in primary care for community dwelling adults compared to usual care. Primary outcomes will be health related quality of life and mental health. Data on costs will be extracted. Studies will be selected for inclusion by title and abstract review by two reviewers. A Preferred Reporting Items for Systematic Reviews (PRISMA) flow diagram will document the selection process. A standardised form will be used to extract data. Data quality will be assessed using the Cochrane Risk of Bias tool for randomised controlled trials, a narrative synthesis will be completed and the GRADE assessment tool used to comment on evidence quality. A meta-analysis of effect size of primary outcomes and subgroup analysis for multimorbidity and social deprivation will be performed if there are sufficient comparable data. Conclusion: This systematic review will give an important overview of the evidence for the use of link workers providing social prescribing and health and social care coordination in primary care. This will help inform intervention development and guide policy makers on whether these interventions are cost effective and which groups stand to benefit most. Prospero registration: CRD42019134737 (04/07/2019).

Study protocol for a process evaluation of a cluster randomised controlled trial to reduce potentially inappropriate prescribing and polypharmacy in patients with multimorbidity in Irish primary care (SPPiRE).

Background: Multimorbidity (the presence of two or more chronic conditions) is associated with poorer health outcomes, particularly for patients with significant polypharmacy (≥15 medications), due to the higher risk of adverse events and drug interactions. The SPPiRE study will assess the effectiveness of a complex intervention to support general practitioners (GPs) to reduce potentially inappropriate prescribing and consider deprescribing in older people with multimorbidity and significant polypharmacy. The aim of the SPPiRE process evaluation is to understand how and why the intervention is effective or ineffective and to explore the potential for system wide implementation of the intervention using the Medical Research Council general themes of context, implementation and mechanism of impact. Methods: The SPPiRE study is a clustered randomised controlled trial (RCT), aiming to recruit 55 general practices and 400 patients (≥65 years) on ≥15 medications throughout the Republic of Ireland. This mixed-methods process evaluation of the SPPiRE study will integrate both quantitative and qualitative data. Quantitative data will be collected on use of the intervention elements and from GP questionnaires. Qualitative data will be collected from semi-structured telephone interviews with all intervention GPs and a purposeful sample of patients from intervention practices. The topic guide will explore barriers and facilitators to participation and implementation of the intervention. Quantitative data will be analysed using descriptive statistics. Interviews will be transcribed and analysed using thematic analysis. Quantitative and qualitative data will be then be integrated. Discussion: The SPPiRE cluster RCT will provide evidence regarding the effectiveness and practicability of delivering a structured medication review in reducing polypharmacy and potentially inappropriate prescribing for patients with multimorbidity. This process evaluation will provide information on how the intervention was implemented, how it was or was not effective and the potential for a system wide implementation. Trial registration: ISRCTN 12752680, registration: 20/10/2016.

Early disease progression of Hurler syndrome.

BACKGROUND: Newborn screening for mucopolysaccharidosis type I (MPS I) shows promise to improve outcomes by facilitating early diagnosis and treatment. However, diagnostic tests for MPS I are of limited value in predicting whether a child will develop severe central nervous system disease associated with Hurler syndrome, or minimal or no central nervous system involvement associated with the attenuated phenotypes (Hurler-Scheie and Scheie syndromes). Given that the optimal treatment differs between Hurler syndrome and the attenuated MPS I phenotypes, the absence of a reliable prognostic biomarker complicates clinical decision making for infants diagnosed through newborn screening. Information about the natural history of Hurler syndrome may aid in the management of affected infants, contribute to treatment decisions, and facilitate evaluation of treatment effectiveness and prognosis. Thus, the aim of this study was to characterize the progression and timing of symptom onset in infants with Hurler syndrome. RESULTS: Clinical data from 55 patients evaluated at a single center were retrospectively reviewed. Information about each child's medical history was obtained following a standardized protocol including a thorough parent interview and the review of previous medical records. All patients underwent systematic physical and neurodevelopmental evaluations by a multidisciplinary team. Nearly all patients (98%) showed signs of disease during the first 6 months of life. Common early disease manifestations included failed newborn hearing screen, respiratory symptoms, difficulty latching, and otitis media. Other symptoms such as kyphosis, corneal clouding, cardiac disease, joint restrictions, and enlarged head circumference typically appeared slightly later (median age, 8-10 months). During the first 12 months, gross motor development was the most severely affected area of functioning, and a significant number of patients also experienced language delays. Cognition was typically preserved during this period. CONCLUSIONS: In this large cohort of patients with Hurler syndrome, the vast majority showed signs and symptoms of disease during the first months of life. More research is needed to determine the extent to which early clinical manifestations of MPS I can predict phenotype and treatment outcomes.