Development and feasibility testing of an evidence-based occupational therapy program for adults with both Down syndrome and dementia

This paper describes the development of a home-based occupational therapy intervention program for people with Down syndrome who experience early on-set dementia causing a decline in their performance skills and increasing care dependency on their informal caregivers. A six-step methodological process adapted from the Medical Research Council framework for developing and evaluating complex interventions was formulated to develop an evidence-based occupational therapy program for people with both Down syndrome and dementia and their informal caregivers. The first two steps gathered evidence through systematic reviews of the literature and determined the scope of current occupational therapy practice. The gathered evidence was synthesised in step three to develop a client-centred occupational therapy intervention program for persons with both Down syndrome and dementia and their informal caregivers. In steps four and five, opinions were sought from occupational therapists working in this area of practice on the content of the developed program and its feasibility within the Australian disability services context. The final testing step can be conducted in the future using a single-case experimental design study. It is important to use rigorous frameworks and gather comprehensive evidence using multiple methods to develop interventions for small heterogeneous populations. The developed occupational therapy program for persons with both Down syndrome and dementia and their informal caregivers appears feasible to be implemented within the Australian disability services; however, funding limitations imposes barriers for its implementation in clinical practice

Effectiveness of Training in Changing Allied Health Students’ Cultural Competency Skills

Purpose: Allied health students require cultural competence training to help them act as caring, ethical, and socially responsible health professionals. There is a lack of evidence for the effectiveness of cultural competence training changing the cultural skill level of allied health students or their behaviour in clinical practice. Method: We conducted a systematic search of the literature to examine the effectiveness of cultural competence training in changing allied health student cultural competency skills. CINAHL, Embase, ERIC, Medline and Scopus databases were searched from inception until August 2017. Search terms represented the population (e.g. allied health students), and cultural competence training. Two reviewers independently screened all retrieved studies and abstracts, then full text papers against inclusion criteria. All included studies were critically appraised, and data was extracted for analysis. Results: Of the initial 9,076 database hits, 15 intervention studies met the inclusion criteria; indicating this is a nascent area of research. Fourteen of the 15 studies demonstrated that cultural competence training provided to allied health students could significantly increase their perceived cultural competence skills, with effect sizes ranging from small to very large. Training was predominately conducted using traditional classroom teaching activities. The review identified that this field of research is dominated by the model and survey tool devised by Campinha-Bacote with a focus on skills required for patient assessment, rather than patient outcomes. Conclusions and possibly recommendations: Cultural competence training can improve allied health students’ perceived level of cultural competence skills for clinical practice. To ensure an effective translation of skill development to clinical practice, tertiary institutions seeking to develop and evaluate cultural competency training programs should focus on teaching cultural competency skills that lead to improved patient outcomes

Perspectives of choice and control in daily life for people following brain injury: A qualitative systematic review and meta-synthesis

Background and Objective: Acquired brain injury (ABI) can result in considerable life changes. Having choice and control over daily life is valued by people following ABI. This meta-synthesis will analyse and integrate international research exploring perspectives of choice and control in daily life following ABI. Methods: Databases were searched from 1980 to 13 January 2022 for eligible qualitative studies. After duplicates were removed, 22,768 studies were screened by title and abstract, and 241 studies received full-text assessment with 56 studies included after pearling. Study characteristics and findings were extracted that related to personal perspectives on choice and control by people with an ABI (including author interpretation and quotes). Data from each study were coded and then segments of coded data across the studies were compared to create multiple broad categories. Findings: Findings were then reduced from categories into 3 overarching themes with 12 subthemes. These themes were: (1) feeling like a second-class citizen; (2) reordering life and (3) choosing a path. Participants with an ABI tussled between their feelings of loss following brain injury and their thinking about how they start to regain control and become agents of their own choices. The themes describe their sense of self, their changed self and their empowered self in relation to ‘choice and control’. Conclusions: Re-engaging with choice and control after ABI is dynamic and can be challenging. Health professionals and supporters need to facilitate a gradual and negotiated return to agency for people following ABI. A sensitive and person-centred approach is needed that considers the readiness of the person with ABI to reclaim choice and control at each stage of their recovery. Clear service or process indicators that are built on lived experience research are needed to facilitate changes in service delivery that are collaborative and inclusive. Patient or Public Contribution: This review included the voices of 765 people living with ABI and was conducted by a diverse team of allied health professionals with practice knowledge and research experience with people following ABI. Twenty-nine of the 56 included studies had participants contributing to their design or analysis

Identifying preferred features of weight loss programs for adults with or at risk of type 2 diabetes: a discrete choice experiment with 3,960 adults in the U.K.

OBJECTIVE: To understand preferences for features of weight loss programs among adults with or at risk of type 2 diabetes in the U.K. RESEARCH DESIGN AND METHODS: We conducted a discrete choice experiment with 3,960 U.K. adults living with overweight (n = 675 with type 2 diabetes). Preferences for seven characteristics of weight loss programs were analyzed. Simulations from choice models using the experimental data predicted uptake of available weight loss programs. Patient groups comprising those who have experience with weight loss programs, including from minority communities, informed the experimental design. RESULTS: Preferences did not differ between individuals with and without type 2 diabetes. Preferences were strongest for type of diet. Healthy eating was most preferred relative to total diet replacement (odds ratio [OR] 2.24; 95% CI 2.04–2.44). Individual interventions were more popular than group interventions (OR 1.40; 95% CI 1.34–1.47). Participants preferred programs offering weight loss of 10–15 kg (OR 1.37; 95% CI 1.28–1.47) to those offering loss of 2–4 kg. Online content was preferred over in-person contact (OR 1.24; 95% CI 1.18–1.30). There were few differences in preferences by gender or ethnicity, although weight loss was more important to women than to men, and individuals from ethnic minority populations identified more with programs where others shared their characteristics. Modeling suggested that tailoring programs to individual preferences could increase participation by ∼17 percentage points (68% in relative terms). CONCLUSIONS: Offering a range of weight loss programs targeting the preferred attributes of different patient groups could potentially encourage more people to participate in weight loss programs and support those living with overweight to reduce their weight

Assessing performance of pathogenicity predictors using clinically relevant variant datasets

Background: Pathogenicity predictors are integral to genomic variant interpretation but, despite their widespread usage, an independent validation of performance using a clinically relevant dataset has not been undertaken. Methods: We derive two validation datasets: an 'open' dataset containing variants extracted from publicly available databases, similar to those commonly applied in previous benchmarking exercises, and a 'clinically representative' dataset containing variants identified through research/diagnostic exome and panel sequencing. Using these datasets, we evaluate the performance of three recent meta-predictors, REVEL, GAVIN and ClinPred, and compare their performance against two commonly used in silico tools, SIFT and PolyPhen-2. Results: Although the newer meta-predictors outperform the older tools, the performance of all pathogenicity predictors is substantially lower in the clinically representative dataset. Using our clinically relevant dataset, REVEL performed best with an area under the receiver operating characteristic curve of 0.82. Using a concordance-based approach based on a consensus of multiple tools reduces the performance due to both discordance between tools and false concordance where tools make common misclassification. Analysis of tool feature usage may give an insight into the tool performance and misclassification. Conclusion: Our results support the adoption of meta-predictors over traditional in silico tools, but do not support a consensus-based approach as in current practice.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This work was supported by the Wellcome Trust [WT200990/Z/16/Z] and [WT200990/A/16/Z]published version, submitted versio

In vivo 18F-flortaucipir PET does not accurately support the staging of progressive supranuclear palsy

Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by neuro-glial tau pathology. A new staging system for PSP pathology at post-mortem has been described and validated. We used a data-driven approach to test whether post-mortem pathological staging in PSP can be reproduced in vivo with 18F-flortaucipir PET. Methods: N=42 patients with probable PSP and N=39 controls underwent 18F-flortaucipir PET. Conditional inference tree analyses on regional binding potential values identified absent/present pathology thresholds to define in vivo staging. Following the staging system for PSP pathology, the combination of absent/present values across all regions was evaluated to assign each participant to in vivo stages. Analysis of variance was applied to analyse differences among means of disease severity between stages. In vivo staging was compared with post-mortem staging in N=9 patients who also had post-mortem confirmation of the diagnosis and stage. Results: Stage assignment was estimable in 41 patients: N=10 patients were classified in stage I/II, N=26 in stage III/IV, N=5 in stage V/VI, while N=1 was not classifiable. An explorative sub-staging identified N=2 patients in stage I, N=8 in stage II, N=9 in stage III, N=17 in stage IV and N=5 in stage V. However, the nominal 18F-flortaucipir derived stage was not associated with clinical severity and was not indicative of pathology staging at post-mortem. Conclusion: 18F-flortaucipir PET in vivo does not correspond to neuropathological staging in PSP. This analytic approach, seeking to mirror in vivo the neuropathology staging with PET-to-autopsy correlational analyses might enable in vivo staging with next-generation PET tracers for tau, but further evidence and comparison with post-mortem data are needed.This study was co-funded by the Cambridge University Centre for Parkinson-Plus (RG95450); the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014), including their financial support for the Cambridge Brain Bank; the PSP Association (“MAPT-PSP” award); the Alzheimer’s Research UK East-Network pump priming grant; the Wellcome trust (220258); the Medical Research Council (MR/P01271X/1; G1100464); the Association of British Neurologists, Patrick Berthoud Charitable Trust (RG99368); Alzheimer’s Society (443 AS JF 18017); the Evelyn Trust (RG84654), and RCUK/UKRI (via a Research Innovation Fellowship awarded by the Medical Research Council to CHWG - MR/R007446/1); the Guarantors of Brain (G101149). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care

CD or not CD, that is the question - a digital interobserver agreement study in coeliac disease

OBJECTIVE: Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of IgA tTG and haemoglobin (Hb) data improves the inter-observer agreement of diagnosis.DESIGN: We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase one, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase two, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data.RESULTS: We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen's kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen's kappa coefficient of 0.67 (±0.09).CONCLUSION: We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited inter-observer agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the important of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using AI.<br/

Comparative grading scales, statistical analyses, climber descriptors and ability grouping: International Rock Climbing Research Association position statement

The research base for rock climbing has expanded substantially in the past 3 decades as worldwide interest in the sport has grown. An important trigger for the increasing research attention has been the transition of the sport to a competitive as well as recreational activity and the potential inclusion of sport climbing in the Olympic schedule. The International Rock Climbing Research Association (IRCRA) was formed in 2011 to bring together climbers, coaches and researchers to share knowledge and promote collaboration. This position statement was developed during and after the 2nd IRCRA Congress which was held in Pontresina, in September 2014. The aim of the position statement is to bring greater uniformity to the descriptive and statistical methods used in reporting rock climbing research findings. To date there is a wide variation in the information provided by researchers regarding the climbers’ characteristics and also in the approaches employed to convert from climbing grading scales to a numeric scale suitable for statistical analysis. Our paper presents details of recommended standards of reporting that should be used for reporting climber characteristics and provides a universal scale for the conversion of climbing grades to a number system for statistical analysis

Genetic and Non-Genetic Influences during Pregnancy on Infant Global and Site Specific DNA Methylation: Role for Folate Gene Variants and Vitamin B12

Inter-individual variation in patterns of DNA methylation at birth can be explained by the influence of environmental, genetic and stochastic factors. This study investigates the genetic and non-genetic determinants of variation in DNA methylation in human infants. Given its central role in provision of methyl groups for DNA methylation, this study focuses on aspects of folate metabolism. Global (LUMA) and gene specific (IGF2, ZNT5, IGFBP3) DNA methylation were quantified in 430 infants by Pyrosequencing®. Seven polymorphisms in 6 genes (MTHFR, MTRR, FOLH1, CβS, RFC1, SHMT) involved in folate absorption and metabolism were analysed in DNA from both infants and mothers. Red blood cell folate and serum vitamin B12 concentrations were measured as indices of vitamin status. Relationships between DNA methylation patterns and several covariates viz. sex, gestation length, maternal and infant red cell folate, maternal and infant serum vitamin B12, maternal age, smoking and genotype were tested. Length of gestation correlated positively with IGF2 methylation (rho = 0.11, p = 0.032) and inversely with ZNT5 methylation (rho = −0.13, p = 0.017). Methylation of the IGFBP3 locus correlated inversely with infant vitamin B12 concentration (rho = −0.16, p = 0.007), whilst global DNA methylation correlated inversely with maternal vitamin B12 concentrations (rho = 0.18, p = 0.044). Analysis of common genetic variants in folate pathway genes highlighted several associations including infant MTRR 66G>A genotype with DNA methylation (χ2 = 8.82, p = 0.003) and maternal MTHFR 677C>T genotype with IGF2 methylation (χ2 = 2.77, p = 0.006). These data support the hypothesis that both environmental and genetic factors involved in one-carbon metabolism influence DNA methylation in infants. Specifically, the findings highlight the importance of vitamin B12 status, infant MTRR genotype and maternal MTHFR genotype, all of which may influence the supply of methyl groups for DNA methylation. In addition, gestational length appears to be an important determinant of infant DNA methylation patterns

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year