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Spinal Muscular Atrophy (SMA) is a neurodegenerative motor neuron disorder resulting from a homozygous mutation of the survival of motor neuron 1 (SMN1) gene. The gene product, SMN protein, functions in RNA biosynthesis in all tissues. In humans, a nearly identical gene, SMN2, rescues an otherwise lethal phenotype by producing a small amount of full-length SMN protein. SMN2 copy number inversely correlates with disease severity. Identifying other novel biomarkers could inform clinical trial design and identify novel therapeutic targets.To identify novel candidate biomarkers associated with disease severity in SMA using unbiased proteomic, metabolomic and transcriptomic approaches.A cross-sectional single evaluation was performed in 108 children with genetically confirmed SMA, aged 2-12 years, manifesting a broad range of disease severity and selected to distinguish factors associated with SMA type and present functional ability independent of age. Blood and urine specimens from these and 22 age-matched healthy controls were interrogated using proteomic, metabolomic and transcriptomic discovery platforms. Analyte associations were evaluated against a primary measure of disease severity, the Modified Hammersmith Functional Motor Scale (MHFMS) and to a number of secondary clinical measures.A total of 200 candidate biomarkers correlate with MHFMS scores: 97 plasma proteins, 59 plasma metabolites (9 amino acids, 10 free fatty acids, 12 lipids and 28 GC/MS metabolites) and 44 urine metabolites. No transcripts correlated with MHFMS.In this cross-sectional study, "BforSMA" (Biomarkers for SMA), candidate protein and metabolite markers were identified. No transcript biomarker candidates were identified. Additional mining of this rich dataset may yield important insights into relevant SMA-related pathophysiology and biological network associations. Additional prospective studies are needed to confirm these findings, demonstrate sensitivity to change with disease progression, and assess potential impact on clinical trial design.Clinicaltrials.gov NCT00756821.

BACKGROUNDThe universal presence of a gene (SMN2) nearly identical to the mutated SMN1 gene responsible for Spinal Muscular Atrophy (SMA) has proved an enticing incentive to therapeutics development. Early disappointments from putative SMN-enhancing agent clinical trials have increased interest in improving the assessment of SMN expression in blood as an early "biomarker" of treatment effect.METHODSA cross-sectional, single visit, multi-center design assessed SMN transcript and protein in 108 SMA and 22 age and gender-matched healthy control subjects, while motor function was assessed by the Modified Hammersmith Functional Motor Scale (MHFMS). Enrollment selectively targeted a broad range of SMA subjects that would permit maximum power to distinguish the relative influence of SMN2 copy number, SMA type, present motor function, and age.RESULTSSMN2 copy number and levels of full-length SMN2 transcripts correlated with SMA type, and like SMN protein levels, were lower in SMA subjects compared to controls. No measure of SMN expression correlated strongly with MHFMS. A key finding is that SMN2 copy number, levels of transcript and protein showed no correlation with each other.CONCLUSIONThis is a prospective study that uses the most advanced techniques of SMN transcript and protein measurement in a large selectively-recruited cohort of individuals with SMA. There is a relationship between measures of SMN expression in blood and SMA type, but not a strong correlation to motor function as measured by the MHFMS. Low SMN transcript and protein levels in the SMA subjects relative to controls suggest that these measures of SMN in accessible tissues may be amenable to an "early look" for target engagement in clinical trials of putative SMN-enhancing agents. Full length SMN transcript abundance may provide insight into the molecular mechanism of phenotypic variation as a function of SMN2 copy number.TRIAL REGISTRYClinicaltrials.gov NCT00756821.

BackgroundDigital health interventions (DHIs) are a central focus of health care transformation efforts, yet their uptake in practice continues to fall short of their potential. In order to achieve their desired outcomes and impact, DHIs need to reach their target population and need to be used. Many factors can rapidly intersect between this dynamic of users and interventions. The application of theories, models, and frameworks (TMFs) can facilitate the systematic understanding and explanation of the complex interactions between users, practices, technology, and health system factors that underpin research questions. There remains a gap in our understanding of how TMFs have been applied to guide the evaluation of DHIs with real-world health system operations. ObjectiveThis study aims to map TMFs used in studies to guide the evaluation of DHIs. The objectives are to (1) describe the TMFs and the constructs they target, (2) identify how TMFs have been prospectively used (ie, their roles) in primary studies to evaluate DHIs, and (3) to reflect on the relevance and utility of our findings for knowledge users. MethodsThis scoping review was conducted in partnership with knowledge users using an integrated knowledge translation approach. We included papers (eg, reports; empirical quantitative, qualitative, and mixed methods studies; conference proceedings; and dissertations) if primary insights resulting from the application of TMFs were presented. Any type of DHI was eligible. Papers published from 2000 and onward were mainly identified from the following databases: MEDLINE (Ovid), CINAHL Complete (EBSCOhost), PsycINFO (Ovid), EBM Reviews (Ovid), and Embase (Ovid). ResultsA total of 156 studies published between 2000 and 2022 were included. A total of 68 distinct TMFs were identified across 85 individual studies. In more than half (85/156, 55%) of the included studies, 1 of following 6 prevailing TMFs were reported: Consolidated Framework for Implementation Research (n=39); the Reach, Effectiveness, Adoption, Implementation, and Maintenance Framework (n=17); the Technology of Acceptance Model (n=16); the Unified Theory on Acceptance and Use of Technology (n=12); the Diffusion of Innovation Theory (n=10); and Normalization Process Theory (n=9). The most common intended roles of the 6 TMFs were to inform data collection (n=86), to inform data analysis (n=69), and to identify key constructs that may serve as barriers and facilitators (n=52). ConclusionsAs TMFs are most often reported to be applied to support data collection and analysis, researchers should consider more clearly synthesizing key insights as practical use cases to both increase the relevance and digestibility of their findings. There is also a need to adapt or develop guidelines for better reporting DHIs and the use of TMFs to guide evaluation. Hence, it would contribute to ensuring ongoing technology transformation efforts are evidence and theory informed rather than anecdotally driven.

BackgroundFederated digital identifiers (FDIs) have been cited to improve the interoperability of data and information management while enhancing the privacy of individuals verifying their identity on the web. Many countries around the world have implemented FDIs in various sectors, such as banking and government. Similarly, FDIs could improve the experience for those wanting to access their health care information; however, they have only been introduced in a few jurisdictions around the world, and their impact remains unclear. ObjectiveThe main objective of this environmental scan was to describe how FDIs have been established and implemented to enable patients’ access to health care. MethodsWe conducted this study in 2 stages, with the primary stage being a rapid review, which was supplemented by a targeted gray literature search. Specifically, the rapid review was conducted through a database search of MEDLINE and Embase, which generated a list of countries and their services that use FDIs in health care. This list was then used to conduct a targeted gray literature search using the Google search engine. ResultsA total of 93 references from the database and targeted Google searches were included in this rapid review. FDIs were implemented in health care in 11 countries (Australia, Belgium, Canada, Denmark, Estonia, Finland, Iceland, Norway, Singapore, Sweden, and Taiwan) and exclusively used with a patient-accessible electronic health record system through a single sign-on interface. The most common FDIs were implemented nationally or provincially, and establishing them usually required individuals to visit a bank or government office in person. In contrast, some countries, such as Australia, allow individuals to verify their identities entirely on the web. We found that despite the potential of FDIs for use in health care to facilitate the amalgamation of health information from different data sources into one platform, the adoption of most health care services that use FDIs remained below 30%. The exception to this was Australia, which had an adoption rate of 90%, which could be correlated with the fact that it leveraged an opt-out consent model. ConclusionsThis rapid review highlights key features of FDIs across regions and elements associated with higher adoption of the patient-accessible electronic health record systems that use them, like opt-out registration. Although FDIs have been reported to facilitate the collation of data from multiple sources through a single sign-on interface, there is little information on their impact on care or patient experience. If FDIs are used to their fullest potential and implemented across sectors, adoption rates within health care may also improve.

Abstract Background Recent research has shown that pregnant individuals experience weight stigma throughout gestation, including negative comments and judgement associated with gestational weight gain (GWG). Weight bias internalization (WBI) is often a result of exposure to weight stigma and is detrimental to biopsychological health outcomes. The purpose of this study was to explore WBI in pregnancy and compare scores based on maternal weight-related factors including pre-pregnancy body mass index (BMI), obesity diagnosis and excessive GWG. Methods Pregnant individuals in Canada and USA completed a modified version of the Adult Weight Bias Internalization Scale. Self-reported pre-pregnancy height and weight were collected to calculate and classify pre-pregnancy BMI. Current weight was also reported to calculate GWG, which was then classified as excessive or not based on Institute of Medicine (2009) guidelines. Participants indicated if they were diagnosed with obesity by a healthcare provider. Inferential analyses were performed comparing WBI scores according to pre-pregnancy BMI, excessive GWG, and obesity diagnosis. Significance was accepted as p

Objective To examine the extent and nature of evidence on the use of the environmental scan (ES) in the health services delivery literature.Design Scoping review.Methods This scoping review followed the five-stage scoping review methodology outlined by Khalil et al. A Peer Review of Electronic Search Strategies was completed. Seven electronic databases and the grey literature were searched. Pairs of researchers independently performed two levels of screening and data extraction. Data were analysed using qualitative content and thematic analysis.Results Ninety-six studies were included in the scoping review. Researchers conducted ESs for many purposes, the most common being to examine the current state of programmes, services or policies. Recommendations were informed by ESs in 20% of studies. Most common data collection methods were literature review (71%), key informant or semistructured interviews (46%) and surveys (35%). Over half (53%) of the studies used a combination of passive (looking at information eg, literature, policies, guidelines) and active (looking for information eg, surveys, interviews) approaches to data collection. Person sources of data (eg, healthcare stakeholders, community representatives) and non-person sources of data (eg, documents, electronic databases, the web) were drawn on to a similar extent. The thematic analysis of the definitions/descriptions yielded several themes including instrument of discovery, knowledge synthesis, forward-looking and decision making. Research gaps identified included absence of a standard definition, inconsistencies in terminology and lack of guiding frameworks in the health services delivery context.Conclusion ESs were conducted to gather evidence and to help inform decision making on a range of policy and health services delivery issues across the continuum of care. Consistency in terminology, a consensus definition and more guidance on ES design may help provide structure for researchers and other stakeholders, and ultimately advance ES as a methodological approach. A working definition of ES in a health services delivery context is presented.

OBJECTIVE:Fetal exposure to an intrauterine environment affected by maternal obesity and excessive gestational weight gain increases the likelihood of infants born large for gestational age and childhood obesity. This study examined behavioural factors and lifestyle practices associated with women's perceived attainability of meeting the 2009 Institute of Medicine (IOM) weight gain guidelines. METHODS:Cross-sectional data were collected from pregnant (n = 320) and postpartum (n = 1179) women who responded to the validated Canadian Electronic Maternal (EMat) health survey. Consenting women completed the survey through REDCap™ a secure, web-based data capture platform. Multiple logistic regression analyses were used to evaluate correlates associated with meeting or not meeting IOM recommendations. Odds ratios (ORs) were adjusted for relevant behavioural and sociodemographic covariates. RESULTS:There were no significant differences between adjusted and unadjusted ORs for self-efficacy, barriers, and facilitators to weight gain during pregnancy. Women who reported worry regarding weight gain were significantly less likely to meet IOM guidelines (OR = 0.48, 95% CI = 0.33-0.69). Perceived controllability of behaviour was significantly associated with meeting IOM guidelines. An internal locus of control for weight gain was associated with an increased odds of meeting guidelines when women perceived to be in control of their weight gain (OR = 1.75, 95% CI = 1.29-2.37), healthy and exercised (OR = 1.91, 95% CI = 1.34-2.71), and when no barriers to healthy weight gain were perceived (OR = 1.43, 95% CI = 1.04-1.95); whereas, an external locus of control in which women viewed weight gain as beyond their control, was associated with a significantly reduced odds of achieving guidelines (OR = 0.58, 95% CI = 0.39-0.88). CONCLUSIONS:Self-efficacy and perceived controllability of behaviour are key factors to consider when developing pregnancy-specific interventions to help women achieve guideline-concordant weight gain and ensure the downstream health of both mother and infant.