Stakeholder perceptions of complementary and alternative medicine from people living with rare diseases in Northern Ireland.

INTRODUCTION: Only five percent of rare diseases have an orthodox modern medicine treatment available, therefore patients often utilise complementary and alternative medicines (CAMs) to help manage their condition. Several CAMs are supported by scientific evidence as effective for aiding management of rare diseases, however the methodological rigour of published literature may be sub-optimal and it can be difficult to show that an outcome is a direct result of the CAM intervention. Patients and healthcare professionals must weigh up the safety, efficacy, practical logistics, and financial implications of utilising CAMs for rare diseases. This study aimed to elucidate perspectives of stakeholders, (individuals with rare diseases, carers, family members, CAMs practitioners and healthcare professionals) on the usage of CAMs for rare diseases across Northern Ireland. METHODS: An online survey was open January - February 2019 (n = 29 responses). Themes identified from the survey were then discussed with stakeholders in a semi-structured discussion workshop in March, 2019. RESULTS: Patients with rare diseases reported CAMs as effective in the management of their condition, in particular acupuncture, dietary supplements, herbal medicines, homeopathy, hydrotherapy / swimming, kinesiology, mindfulness, pilates, reflexology, tai chi, and yoga. In this study, seven survey respondents experienced a negative side effect from CAMs. Workshop participants raised the lack of information available about CAMs and rare disease. Both the survey and workshop identified inequality of access with participants reporting CAMs to be expensive and expressing a desire for more therapies to be available within the United Kingdom (UK) National Healthcare Service (NHS). CONCLUSIONS: Many patients with rare diseases report that CAMs are helpful in the management of their condition. More information, high quality research, and education about CAMs is required for patients and healthcare professionals to help make informed decisions about the usage of CAMs for rare diseases. Improved communication, information, and health and social care in general would help individuals be more confident and knowledgeable about therapeutic options in relation to their rare disease(s).

Feasibility of home-based exercise training during adjuvant treatment for metastatic castrate-resistant prostate cancer patients treated with an androgen receptor pathway inhibitor (EXACT).

BACKGROUND: Exercise is an effective adjuvant therapy that can alleviate treatment-related toxicities for men with prostate cancer (PC). However, the feasibility of delivering exercise training to men with advanced disease and the wider impact on clinical outcomes remain unknown. The purpose of the EXACT trial was to determine the feasibility and effects of home-based exercise training in men with metastatic castrate-resistant prostate cancer (mCRPC). METHODS: Patients with mCRPC receiving ADT + an androgen receptor pathway inhibitor (ARPI) were prescribed 12 weeks of home-based, remotely monitored, moderate intensity, aerobic and resistance exercise. Feasibility was assessed using recruitment, retention and adherence rates. Safety and adverse events were monitored throughout, with functional and patient-reported outcomes captured at baseline, post-intervention and at 3-month follow-up. RESULTS: From the 117 screened, 49 were deemed eligible and approached, with 30 patients providing informed consent (61% recruitment rate). Of those who consented, 28 patients completed baseline assessments, with 24 patients completing the intervention and 22 completing follow-up (retention rates: 86% and 79% respectively). Task completion was excellent throughout, with no intervention-related adverse events recorded. Self-reported adherence to the overall intervention was 82%. Exercise training decreased mean body mass (-1.5%), improved functional fitness (> 10%) and improved several patient-reported outcomes including clinically meaningful changes in fatigue (p = 0.042), FACT-G (p = 0.054) and FACT-P (p = 0.083), all with moderate effect sizes. CONCLUSION: Home-based exercise training, with weekly remote monitoring, was feasible and safe for men with mCRPC being treated with an ARPI. Given that treatment-related toxicities accumulate throughout the course of treatment, and as a result, negatively impact functional fitness and health-related quality of life (HRQoL), it was positive that exercise training improved or prevented a decline in these clinically important variables and could better equip patients for future treatment. Collectively, these preliminary feasibility findings support the need for a definitive, larger RCT, which downstream may lead to the inclusion of home-based exercise training as part of adjuvant care for mCRPC.

Caregiver Burden in Informal Caregivers of Patients in Saudi Arabia Receiving Hemodialysis: A Mixed-Methods Study.

(1) Background: Long-term caregiving for patients receiving hemodialysis (HD), is associated with physical and psychological stress, which may impact on the well-being and quality of life of caregivers. Due to a lack of understanding of the experiences of informal caregivers of patients receiving HD, especially in Saudi Arabia, this study aimed to measure burden in informal caregivers of patients receiving HD, examine the factors that predict caregiver burden (CB), and explore the experience of burden in caregivers of patients receiving HD. (2) Methods: This study used a mixed-methods, sequential, explanatory design, which consisted of two phases. Phase 1 involved a cross-sectional study design, with a convenience sample of 61 caregivers of patients on maintenance HD for at least 3 months. All caregivers in the study completed the Arabic version of the Zarit Burden Interview to identify caregiver burden. Phase 2 of the study involved a qualitative descriptive design involving semi-structured interviews with nine caregivers. (3) Results: Study findings indicate that caregivers did not experience severe burden. Being older, a female caregiver and having comorbidities was positively associated with increased levels of caregiver burden. In the qualitative phase of the study, a number of important factors emerged that may contribute to a reduction in caregiver burden, including social support, cultural acceptance, and religious influences. (4) Conclusion and impact: CB was found to be low when a comparison was made with other studies using similar populations. Understanding the factors that influence caregiver burden will contribute to the accurate assessment of caregiver burden and help reduce burden in informal caregivers, patients with renal failure, and others with chronic illnesses worldwide.

Children and young people's experiences of living with rare diseases: An integrative review.

PROBLEM: Rare diseases are any disease affecting fewer than five people in 10,000. More than 8000 rare diseases and 50-75% of all rare diseases affect children. The purpose of this review was to critically appraise and synthesize existing literature relating to the impact of rare diseases on children's day-to-day lives. ELIGIBILITY CRITERIA: An integrative literature review was conducted using the CINAHL Plus, PsycINFO, and PubMed databases. Studies were included if they were a primary source was published between the years 2005 and 2019 and written in the English language. SAMPLE: Eight primary sources met the inclusion criteria. RESULTS: Seven main themes emerged from the review as follows: (i) the experience of stigmatisations, (ii) self-consciousness, (iii) restrictions in independent living, (iv) developing resilience/coping strategies, (v) psychological and emotional impact, (vi) social impact vs social connectedness and (vii) transition challenges. CONCLUSIONS: The experience of having a rare illness differed across different age groups. Children (typically aged 3-10) with rare diseases generally view themselves and their lives the same way like their healthy peers. They were more likely to report being adaptive and resilient than those aged 12 or older. Young people reported being different compared to young children, and they faced numerous challenges related to their illness. IMPLICATIONS FOR PRACTICE: To provide the best possible level of care for children and families with rare disorders, health services must be informed and equipped to provide the necessary supports specific to the unique needs of children and young people living with rare diseases.

Carer reported experiences: Supporting someone with a rare disease.

This exploratory study aimed to gain an understanding of carer reported experiences derived specifically from persons caring for someone with a rare disease. The survey took place online on the SmartSurvey platform from November 2019 to January 2020. The facilitated workshop took place in Bangor Carnegie Library, Northern Ireland. To be eligible to participate in the online survey respondents had to be adults caring for someone with a rare disease. Fifty-seven respondents took part, 15.8% male, 84.2% female. Thirty-two attendees were part of the facilitated workshop. While carers reported several positive aspects of their caring role, the majority of comments highlighted challenges such as sub-optimal interactions with healthcare professionals, insufficient (or absent) emotional, psychological and social support, lack of financial support and lack of awareness of existing support services. It is important that strategies are put in place to ensure that carers are given the time they need to care for themselves, and that awareness is raised of what support options are available for carers of people with a rare disease(s) from health and social care providers, charities or support groups.

The effect of different COVID-19 public health restrictions on mobility: A systematic review.

BACKGROUND: In response to the COVID-19 pandemic, most countries have introduced non-pharmaceutical interventions, such as stay-at-home orders, to reduce person-to-person contact and break trains of transmission. The aim of this systematic review was to assess the effect of different public health restrictions on mobility across different countries and cultures. The University of Bern COVID-19 Living Evidence database of COVID-19 and SARS-COV-2 publications was searched for retrospective or prospective studies evaluating the impact of COVID-19 public health restrictions on Google Mobility. Titles and abstracts were independently screened by two authors. Information from included studies was extracted by one researcher and double checked by another. Risk of bias of included articles was assessed using the Newcastle Ottowa Scale. Given the heterogeneous nature of the designs used, a narrative synthesis was undertaken. From the search, 1672 references were identified, of which 14 were included in the narrative synthesis. All studies reported data from the first wave of the pandemic, with Google Mobility Scores included from January to August 2020, with most studies analysing data during the first two months of the pandemic. Seven studies were assessed as having a moderate risk of bias and seven as a low risk of bias. Countries that introduced more stringent public health restrictions experienced greater reductions in mobility, through increased time at home and reductions in visits to shops, workplaces and use of public transport. Stay-at-home orders were the most effective of the individual strategies, whereas mask mandates had little effect of mobility. CONCLUSIONS: Public health restrictions, particularly stay-at-home orders have significantly impacted on transmission prevention behaviours. Further research is required to understand how to effectively address pandemic fatigue and to support the safe return back to normal day-to-day behaviours.

Exploring the impact of ineligibility on individuals expressing interest in a trial aimed at improving daily functioning regarding perceptions of self, research and likelihood of future participation.

BACKGROUND: Eligibility guidelines in research trials are necessary to minimise confounds and reduce bias in the interpretation of potential treatment effects. There is limited extant research investigating how being deemed ineligible for such trials might impact patients' perceptions of themselves and of research. Better understanding of the impact of patient ineligibility could enhance design and implementation of future research studies. METHODS: Eight semi-structured telephone interviews were conducted to explore the impact of ineligibility on self-perceptions; perceptions regarding the nature of research; and the likelihood of expressing interest in future research. Data were collected and analysed thematically through inductive, interpretive phenomenological analysis (IPA). RESULTS: Five themes emerged regarding the experience of being deemed ineligible: (1) Being deemed ineligible is emotion and reaction evoking; (2) 'Doing your bit': Helping others and increasing the value of research; (3) Communication of ineligibility; (4) Appreciation for those who express interest; and (5) Subsequent perceptions and attitudes towards research. CONCLUSIONS: The results suggest that being deemed ineligible can elicit negative emotional outcomes but is not likely to change perceptions of or attitudes towards research, possibly due to a desire to help similar others. Ineligibility can impact future participation in some cases, thus reducing the recruitment pool for subsequent research studies. Recommendations are provided to help minimise this risk. Advising of ineligibility in a personal way is recommended: with enhanced clarity regarding the reasoning behind the decision; providing opportunities to ask questions; and ensuring that appreciation for the patient's time and interest are communicated.

Investigating the physical activity, health, wellbeing, social and environmental effects of a new urban greenway: a natural experiment (the PARC study).

BACKGROUND: Evidence for the health benefits of urban green space tends to stem from small, short-term quasi-experimental or cross-sectional observational research, whilst evidence from intervention studies is sparse. The development of an urban greenway (9 km running along 3 rivers) in Northern Ireland provided the opportunity to conduct a natural experiment. This study investigated the public health impact of the urban greenway on a range of physical activity, health, wellbeing, social, and perceptions of the environment outcomes. METHODS: A repeated cross-sectional household survey of adult residents (aged ≥16 years) who lived ≤1-mile radius of the greenway (intervention sample) and > 1-mile radius of the greenway (control sample) was conducted pre (2010/2011) and 6-months post implementation (2016/2017). We assessed changes in outcomes pre- and post-intervention follow-up including physical activity behaviour (primary outcome measure: Global Physical Activity Questionnaire), quality of life, mental wellbeing, social capital and perceptions of the built environment. Linear regression was used to calculate the mean difference between post-intervention and baseline measures adjusting for age, season, education, car ownership and deprivation. Multi-level models were fitted using a random intercept at the super output area (smallest geographical unit) to account for clustering within areas. The analyses were stratified by distance from the greenway and deprivation. We assessed change in the social patterning of outcomes over time using an ordered logit to make model-based outcome predictions across strata. RESULTS: The mean ages of intervention samples were 50.3 (SD 18.9) years at baseline (n = 1037) and 51.7 (SD 19.1) years at follow-up (n = 968). Post-intervention, 65% (adjusted OR 0.60, 95% CI 0.35 to 1.00) of residents who lived closest to the greenway (i.e., ≤400 m) and 60% (adjusted OR, 0.64 95% CI 0.41 to 0.99) who lived furthest from the greenway (i.e.,≥1200 m) met the physical activity guidelines - 68% of the intervention sample met the physical activity guidelines before the intervention. Residents in the most deprived quintiles had a similar reduction in physical activity behaviour as residents in less deprived quintiles. Quality of life at follow-up compared to baseline declined and this decline was significantly less than in the control area (adjusted differences in mean EQ5D: -11.0 (95% CI - 14.5 to - 7.4); - 30.5 (95% CI - 37.9 to - 23.2). Significant change in mental wellbeing was not observed despite improvements in some indicators of social capital. Positive perceptions of the local environment in relation to its attractiveness, traffic and safety increased. CONCLUSIONS: Our findings illustrate the major challenge of evaluating complex urban interventions and the difficulty of capturing and measuring the network of potential variables that influence or hinder meaningful outcomes. The results indicate at this stage no intervention effect for improvements in population-level physical activity behaviour or mental wellbeing. However, they show some modest improvements for secondary outcomes including positive perceptions of the environment and social capital constructs. The public health impact of urban greenways may take a longer period of time to be realised and there is a need to improve evaluation methodology that captures the complex systems nature of urban regeneration.

Factors Associated with Burden in Caregivers of Patients with End-Stage Kidney Disease (A Systematic Review).

BACKGROUND: Caring for a patient with end-stage kidney disease (ESKD) is highly stressful and can impact negatively on the physical and psychological well-being of caregivers. To accurately assess caregiver burden (CB), health care providers (HCPs) need to identify characteristics associated with an increase in CB. AIM: The aim of this review is to explore CB in caregivers of adult patients with ESKD and to identify characteristics associated with any increase in CB. METHOD: A comprehensive literature search was completed using five electronic databases. Medline, Embase, CINHAL, PsycINFO, and Scopus. The Joanna Briggs Institute checklist (JBI) was used to quality appraise full text papers included in the review. No time limit for the date of publication of studies was employed, to enable the inclusion of more extensive literature. RESULTS: A total of 38 relevant studies from 18 countries were identified and included in the review. A variety of patient and caregiver factors can impact positively or negatively on CB, including socio-demographic factors of patients and caregivers, disease-related factors, situational and relational factors, environmental factors, and psychological factors. CONCLUSION: This review provides awareness to HCPs of the important factors associated with CB, when assessing or targeting interventions for caregivers experiencing burden.

Development of a complex arts-based intervention for patients with end-stage kidney disease whilst receiving haemodialysis.

BACKGROUND: Patients with end-stage kidney disease who receive haemodialysis experience a protracted treatment regimen that can result in an increased risk of depression and anxiety. Arts-based interventions could address this unique issue; however, no arts-based interventions have been developed for delivery within a haemodialysis unit and evaluation within a randomised controlled trials (RCTs). AIM: To develop a complex arts-based intervention for patients with end-stage kidney disease whilst receiving haemodialysis. METHODS: The development process utilised the Arts in Health framework (Fancourt, 2017). The framework was addressed through the establishment of an interdisciplinary advisory group, collaboration and consultation with stakeholders, a scoping and realist review, shadowing of artists-in-residence, personal arts practice and logic modelling. RESULTS: The intervention involved six 1-h long, one-to-one facilitated sessions focused on creative writing and visual art. Patients could choose between art form and self-select a subject matter. The sessions had a primary focus on skill development and were delivered using principles derived from the psychological theory of flow. CONCLUSION: The Arts in Health framework provided an appropriate and pragmatic approach to intervention development. Complex arts-based interventions can be developed for the purpose of evaluation within a trial framework. This intervention was designed to strike a balance between standardised components, and a person-centred approach necessary to address existential boredom.

A nonrandomised pilot study to examine the feasibility and acceptability of reflexology in patients undergoing hospital-based haemodialysis (solitude study).

BACKGROUND: Patients with end-stage kidney disease, receiving haemodialysis can experience complications-hypotension, headache, muscle cramp, chest pain, nausea and vomiting. Patients who experience all or some of these symptoms will often report reduced health-related quality of life (HRQOL) and poor sleep quality, which may lead to increased morbidity and mortality. OBJECTIVE: The objective of this pilot study is to evaluate the feasibility of a larger randomised controlled trial to determine the effect of foot reflexology on a cohort of patients undergoing hospital-based haemodialysis. DESIGN: A nonrandomised pilot study using a multimethod approach. PARTICIPANTS: Twenty patients undergoing hospital-based haemodialysis treatment. MEASUREMENTS: HRQOL and quality of sleep were measured using the SF-12 Health Survey and the Pittsburgh Sleep Quality Index (PSQI). Semi-structured interviews were completed with 10 patients, exploring their experiences, opinions and perceptions of the intervention. RESULTS: There was an increase in the mean scores examining the total physical health and mental health components of the SF-12. All corresponding p values were statistically significant following the intervention. The mean total sleep score postintervention signified positive changes in sleep quality, with the corresponding p values being statistically significant. The study established the feasibility of the intervention and the benefits for patients undergoing haemodialysis. CONCLUSION: This pilot study demonstrated the possibility of recruiting and retaining patients undergoing haemodialysis to a reflexology study. The study did not impact the haemodialysis routine and was positively received. The intervention showed statistically significant improvements in patients' HRQOL and sleep quality.

Children as innovators: harnessing the creative expertise of children to address practical and psychosocial challenges of the coronavirus disease 2019 (COVID-19) pandemic - COVISION study protocol.

Background: We are currently in a period of transition, from the pre-COVID-19 (coronavirus disease 2019) era and the initial reactive lockdowns, to now the ongoing living with and potentially the after COVID-19 period. Each country is at its own individual stage of this transition, but many have gone through a period of feeling adrift; disconnected from normal lives, habits and routines, finding oneself betwixt and between stages, similar to that of liminality. Children and young people have been particularly affected. Aim: To increase the understanding of home and community-based strategies that contribute to children and young people's capacity to adjust to societal changes, both during and after pandemics. Moreover, to identify ways in which children's actions contribute to the capacity of others to adjust to the changes arising from the pandemic. The potential for these activities to influence and contribute to broader social mobilisation will be examined and promoted. Research design: To achieve the aim of this study, a participatory health research approach will be taken. The overarching theoretical framework of the COVISION study is that of liminality. The study design includes four work packages: two syntheses of literature (a rapid realist review and scoping review) to gain an overview of the emerging international context of evidence of psychosocial mitigations and community resilience in pandemics, and more specifically COVID-19; qualitative exploration of children and young people's perspective of COVID-19 via creative outlets and reflections; and participatory learning and action through co-production.

Complex arts-based interventions for patients receiving haemodialysis: A realist review.

Many patients with end-stage kidney disease require haemodialysis, a treatment that requires attending hospital three times a week for four hours each visit. This treatment impacts profoundly on mental health. Arts-based interventions for patients receiving haemodialysis could address the impact of this treatment; however, there is no consensus on methods of implementation and mechanisms underlying these interventions in specific clinical contexts. Using a realist approach, relevant articles were synthesised to inform theory relating to the mechanism and implementation of complex arts-based interventions for haemodialysis patients. The theoretical framework includes two implementation phases, firstly delivery of person-centred art activities during haemodialysis and secondly, display of completed artwork. This intervention triggers mechanisms including flow and social capital. Implementation is hindered by constraints of the haemodialysis unit and patients' lack of confidence in their artistic skills. These issues can be addressed through aflexible approach to implementation and support from healthcare professionals.

Improvements needed to support people living and working with a rare disease in Northern Ireland: current rare disease support perceived as inadequate.

BACKGROUND: Many people living and working with rare diseases describe consistent difficulties accessing appropriate information and support. In this study an evaluation of the awareness of rare diseases, alongside related information and educational resources available for patients, their families and healthcare professionals, was conducted in 2018-2019 using an online survey and semi-structured interviews with rare disease collaborative groups (charities, voluntary and community groups) active across Northern Ireland (NI). METHODS: This study had 2 stages. Stage 1 was an online survey and stage 2 involved semi-structured interviews both with rare disease collaborative groups in Northern Ireland. The surveys and interviews were used to locate existing resources as well as identify gaps where the development of further resources would be appropriate. RESULTS: Ninety-nine rare disease collaborative groups engaged with the survey with 31 providing detailed answers. Resources such as information, communication, 'registries', online services, training and improvements to support services were queried. Excellent communication is an important factor in delivering good rare disease support. Training for health professionals was also highlighted as an essential element of improving support for those with a rare disease to ensure they approach people with these unique and challenging diseases in an appropriate way. Carers were mentioned several times throughout the study; it is often felt they are overlooked in rare disease research and more support should be in place for them. Current care/support for those with a rare disease was highlighted as inadequate. Nine semi-structured interviews were conducted with rare disease collaborative groups. Reoccurring themes included a need for more effective information and communication, training for health professionals, online presence, support for carers, and involvement in research. CONCLUSIONS: All rare disease collaborative groups agreed that current services for people living and working with a rare disease are not adequate. An important finding to consider in future research within the rare disease field is the inclusion of carers perceptions and experiences in studies. This research provides insight into the support available for rare diseases across Northern Ireland, highlights unmet needs, and suggests approaches to improve rare disease support.

A mixed-methods feasibility study of an arts-based intervention for patients receiving maintenance haemodialysis.

BACKGROUND: Haemodialysis can negatively impact quality of life and mental health. Arts-based interventions used successfully in other settings to improve health and well-being, could help address the impact of haemodialysis. This study aimed to evaluate the feasibility and acceptability of conducting a randomised controlled trial (RCT) of an arts-based intervention for patients receiving haemodialysis. METHODS: A parallel convergent mixed-methods design was used, including a pilot cluster RCT and qualitative process evaluation. Phase 1 evaluated recruitment and retention rates through a pilot cluster RCT at a single haemodialysis unit in Northern Ireland. Participants included patients who received haemodialysis for ESKD, were over the age of 18 and had the capacity to consent. These participants were randomised to the intervention or control group according to their haemodialysis shift. The intervention involved six one-hour, one-to-one facilitated arts sessions during haemodialysis. Phase 2 explored intervention and trial acceptability through a qualitative process evaluation using semi-structured interviews based on the RE-AIM framework. Participants included 13 patients who participated in phase 1 of the study, including 9 participants from the experimental group and four participants from the control group, and nine healthcare professionals who were present on the unit during implementation. RESULTS: Out of 122 outpatient haemodialysis patients, 94 were assessed as eligible for participation. Twenty-four participants were randomised, meaning 80% of the target sample size was recruited and the attrition rate at 3 months was 12.5% (n = 3). Participants viewed the arts as more accessible and enjoyable than anticipated following implementation. All participants who started the intervention (n = 11) completed the full six sessions. Qualitative benefits of the intervention suggest improvements in mental well-being. Patient choice and facilitation were important factors for successful implementation. CONCLUSION: An arts-based intervention for patients receiving haemodialysis is acceptable for both patients and healthcare professionals, and a definitive trial is feasible. The intervention may help improve mental-wellbeing in patients receiving haemodialysis, but this requires further investigation in a definitive trial. TRIAL REGISTRATION: The trial was prospectively registered on clinicaltrials.gov on 14/8/2018, registration number NCT03629496 .

A scoping review and proposed workflow for multi-omic rare disease research.

BACKGROUND: Patients with rare diseases face unique challenges in obtaining a diagnosis, appropriate medical care and access to support services. Whole genome and exome sequencing have increased identification of causal variants compared to single gene testing alone, with diagnostic rates of approximately 50% for inherited diseases, however integrated multi-omic analysis may further increase diagnostic yield. Additionally, multi-omic analysis can aid the explanation of genotypic and phenotypic heterogeneity, which may not be evident from single omic analyses. MAIN BODY: This scoping review took a systematic approach to comprehensively search the electronic databases MEDLINE, EMBASE, PubMed, Web of Science, Scopus, Google Scholar, and the grey literature databases OpenGrey / GreyLit for journal articles pertaining to multi-omics and rare disease, written in English and published prior to the 30th December 2018. Additionally, The Cancer Genome Atlas publications were searched for relevant studies and forward citation searching / screening of reference lists was performed to identify further eligible articles. Following title, abstract and full text screening, 66 articles were found to be eligible for inclusion in this review. Of these 42 (64%) were studies of multi-omics and rare cancer, two (3%) were studies of multi-omics and a pre-cancerous condition, and 22 (33.3%) were studies of non-cancerous rare diseases. The average age of participants (where known) across studies was 39.4 years. There has been a significant increase in the number of multi-omic studies in recent years, with 66.7% of included studies conducted since 2016 and 33% since 2018. Fourteen combinations of multi-omic analyses for rare disease research were returned spanning genomics, epigenomics, transcriptomics, proteomics, phenomics and metabolomics. CONCLUSIONS: This scoping review emphasises the value of multi-omic analysis for rare disease research in several ways compared to single omic analysis, ranging from the provision of a diagnosis, identification of prognostic biomarkers, distinct molecular subtypes (particularly for rare cancers), and identification of novel therapeutic targets. Moving forward there is a critical need for collaboration of multi-omic rare disease studies to increase the potential to generate robust outcomes and development of standardised biorepository collection and reporting structures for multi-omic studies.

Rinse-free hand wash for reducing absenteeism among preschool and school children.

BACKGROUND: Illness-related absenteeism is an important problem among preschool and school children for low-, middle- and high- income countries. Appropriate hand hygiene is one commonly investigated and implemented strategy to reduce the spread of illness and subsequently the number of days spent absent. Most hand hygiene strategies involve washing hands with soap and water, however this is associated with a number of factors that act as a barrier to its use, such as requiring running water, and the need to dry hands after cleaning. An alternative method involves washing hands using rinse-free hand wash. This technique has a number of benefits over traditional hand hygiene strategies and may prove to be beneficial in reducing illness-related absenteeism in preschool and school children. OBJECTIVES: 1. To assess the effectiveness of rinse-free hand washing for reducing absenteeism due to illness in preschool and school children compared to no hand washing, conventional hand washing with soap and water or other hand hygiene strategies. 2. To determine which rinse-free hand washing products are the most effective (if head-to-head comparisons exist), and what effect additional strategies in combination with rinse-free hand washing have on the outcomes of interest. SEARCH METHODS: In February 2020 we searched CENTRAL, MEDLINE, Embase, CINAHL, 12 other databases and three clinical trial registries. We also reviewed the reference lists of included studies and made direct contact with lead authors of studies to collect additional information as required. No date or language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials (RCTs), irrespective of publication status, comparing rinse-free hand wash in any form (hand rub, hand sanitizer, gel, foam etc.) with conventional hand washing using soap and water, other hand hygiene programs (such as education alone), or no intervention. The population of interest was children aged between two and 18 years attending preschool (childcare, day care, kindergarten, etc.) or school (primary, secondary, elementary, etc.). Primary outcomes included child or student absenteeism for any reason, absenteeism due to any illness and adverse skin reactions. DATA COLLECTION AND ANALYSIS: Following standard Cochrane methods, two review authors (out of ZM, CT, CL, CS, TB), independently selected studies for inclusion, assessed risk of bias and extracted relevant data. Absences were extracted as the number of student days absent out of total days. This was sometimes reported with the raw numbers and other times as an incidence rate ratio (IRR), which we also extracted. For adverse event data, we calculated effect sizes as risk ratios (RRs) and present these with 95% confidence intervals (CIs). We used standard methodological procedures expected by Cochrane for data analysis and followed the GRADE approach to establish certainty in the findings. MAIN RESULTS: This review includes 19 studies with 30,747 participants. Most studies were conducted in the USA (eight studies), two were conducted in Spain, and one each in China, Colombia, Finland, France, Kenya, Bangladesh, New Zealand, Sweden, and Thailand. Six studies were conducted in preschools or day-care centres (children aged from birth to < five years), with the remaining 13 conducted in elementary or primary schools (children aged five to 14 years). The included studies were judged to be at high risk of bias in several domains, most-notably across the domains of performance and detection bias due to the difficulty to blind those delivering the intervention or those assessing the outcome. Additionally, every outcome of interest was graded as low or very low certainty of evidence, primarily due to high risk of bias, as well as imprecision of the effect estimates and inconsistency between pooled data. For the outcome of absenteeism for any reason, the pooled estimate for rinse-free hand washing was an IRR of 0.91 (95% CI 0.82 to 1.01; 2 studies; very low-certainty evidence), which indicates there may be little to no difference between groups. For absenteeism for any illness, the pooled IRR was 0.82 (95% CI 0.69 to 0.97; 6 studies; very low-certainty evidence), which indicates that rinse-free hand washing may reduce absenteeism (13 days absent per 1000) compared to those in the 'no rinse-free' group (16 days absent per 1000). For the outcome of absenteeism for acute respiratory illness, the pooled IRR was 0.79 (95% CI 0.68 to 0.92; 6 studies; very low-certainty evidence), which indicates that rinse-free hand washing may reduce absenteeism (33 days absent per 1000) compared to those in the 'no rinse-free' group (42 days absent per 1000). When evaluating absenteeism for acute gastrointestinal illness, the pooled estimate found an IRR of 0.79 (95% CI 0.73 to 0.85; 4 studies; low-certainty evidence), which indicates rinse-free hand washing may reduce absenteeism (six days absent per 1000) compared to those in the 'no rinse-free' group (eight days absent per 1000). There may be little to no difference between rinse-free hand washing and 'no rinse-free' group regarding adverse skin reactions with a RR of 1.03 (95% CI 0.8 to 1.32; 3 studies, 4365 participants; very low-certainty evidence). Broadly, compliance with the intervention appeared to range from moderate to high compliance (9 studies, 10,749 participants; very-low certainty evidence); narrativley, no authors reported substantial issues with compliance. Overall, most studies that included data on perception reported that teachers and students perceived rinse-free hand wash positively and were willing to continue its use (3 studies, 1229 participants; very-low certainty evidence). AUTHORS' CONCLUSIONS: The findings of this review may have identified a small yet potentially beneficial effect of rinse-free hand washing regimes on illness-related absenteeism. However, the certainty of the evidence that contributed to this conclusion was low or very low according to the GRADE approach and is therefore uncertain. Further research is required at all levels of schooling to evaluate rinse-free hand washing regimens in order to provide more conclusive, higher-certainty evidence regarding its impact. When considering the use of a rinse-free hand washing program in a local setting, there needs to be consideration of the current rates of illness-related absenteeism and whether the small beneficial effects seen here will translate into a meaningful reduction across their settings.

A Randomized Noninferiority Trial of Wearing Adjustable Glasses versus Standard and Ready-made Spectacles among Chinese Schoolchildren: Wearability and Evaluation of Adjustable Refraction III.

PURPOSE: To compare wear of standard, adjustable, and ready-made glasses among children. DESIGN: Randomized, controlled, open-label, noninferiority trial. PARTICIPANTS: Students aged 11 to 16 years with presenting visual acuity (VA) ≤6/12 in both eyes, correctable to ≥6/7.5, subjective spherical equivalent refractive error (SER) ≤-1.0 diopters (D), astigmatism and anisometropia both <2.00 D, and no other ocular abnormalities. METHODS: Participants were randomly allocated (1:1:1) to standard glasses, ready-made glasses, or adjustable glasses based on self-refraction. We recorded glasses wear on twice-weekly covert evaluation by head teachers (primary outcome), self-reported and investigator-observed wear, best-corrected visual acuity (BCVA) (not prespecified), children's satisfaction, and value attributed to glasses. MAIN OUTCOME MEASURE: Proportion of glasses wear on twice-weekly covert evaluation by head teachers over 2 months. RESULTS: Among 379 eligible participants, 127 were allocated to standard glasses (mean age, 13.7 years; standard deviation [SD], 1.0 years; 54.3% were male), 125 to ready-made (mean age, 13.6; SD, 0.83; 45.6%), and 127 to adjustable (mean age, 13.4 years; SD, 0.85; 54.3%). Mean wear proportion of adjustable glasses was significantly lower than for standard glasses (45% vs. 58%; P = 0.01), although the adjusted difference (90% confidence interval [CI], -19.0% to -3.0%) did not meet the prespecified inferiority threshold of 20%. Self-reported (90.2% vs. 84.8%, P = 0.64) and investigator-observed (44.1% vs. 33.9%, P = 0.89) wear did not differ between standard and adjustable glasses, nor did satisfaction with (P = 0.97) or value attributed to study glasses (P = 0.55) or increase in quality of life (5.53 [SD, 4.47] vs. 5.68 [SD, 4.34] on a 100-point scale, P > 0.30). Best-corrected visual acuity with adjustable glasses was better (P < 0.001) than with standard glasses. Change in power of study lenses at the end of the study (adjustable: 0.65 D, 95% CI, 0.52-0.79; standard, 0.01 D; 95% CI, -0.006 to 0.03, P < 0.001) was greater for adjustable glasses, although interobserver variation in power measurements may explain this. Lens scratches and frame damage were more common with adjustable glasses, whereas lens breakage was less common than for standard glasses. CONCLUSIONS: Proportion of wear was lower with adjustable glasses, although VA was better and measures of satisfaction and quality of life were not inferior to standard glasses.

Systematic review of differential methylation in rare ophthalmic diseases.

Rare ophthalmic diseases have a devastating impact on a patient's vision and consequently negatively affect their independence, ability to work and overall quality of life. Methylation is an important emerging biomarker of disease and may improve understanding of rare ophthalmic disorders. This systematic review sought to identify and evaluate literature on methylation and rare ophthalmic disease. MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews and grey literature resources were searched for publications prior to 20 August 2019. Articles written in English which featured key terms such as 'methylation' and rare ophthalmic diseases were included. Titles, abstracts, keywords and full texts of publications were screened, as well as reference lists for reverse citations and Web of Science 'cited reference search' for forward citation searching. Study characteristics were extracted, and methodological rigour appraised using a standardised template. Fourteen articles were selected for full inclusion. Rare ophthalmic conditions include congenital fibrosis of extraocular muscles, retinitis pigmentosa, Fuchs endothelial corneal dystrophy, granular corneal dystrophy, choroideraemia, brittle cornea syndrome, retinopathy of prematurity, keratoconus and congenital cataracts. Outcomes include identification of methylation as contributor to disease and identification of potential novel therapeutic targets. The studies included were heterogeneous with no scope for meta-analysis following review; a narrative synthesis was undertaken. Differential methylation has been identified in a small number of rare ophthalmic diseases and few studies have been performed to date. Further multiomic research will improve understanding of rare eye diseases and hopefully lead to improved provision of diagnostic/prognostic biomarkers, and help identify novel therapeutic targets.