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Prostate cancer (PCa) is the second most common cancer diagnosed in men. While radical prostatectomy and radiotherapy are often successful in treating localised disease, post-treatment recurrence is common. As the androgen receptor (AR) and androgen hormones play an essential role in prostate carcinogenesis and progression, androgen deprivation therapy (ADT) is often used to deprive PCa cells of the pro-proliferative effect of androgens. ADTs act by either blocking androgen biosynthesis (e.g. abiraterone) or blocking AR function (e.g. bicalutamide, enzalutamide, apalutamide, darolutamide). ADT is often effective in initially suppressing PCa growth and progression, yet emergence of castrate-resistant PCa and progression to neuroendocrine-like PCa following ADT are major clinical challenges. For this reason, there is an urgent need to identify novel approaches to modulate androgen signalling to impede PCa progression whilst also preventing or delaying therapy resistance.The mechanistic convergence of androgen and epitranscriptomic signalling offers a potential novel approach to treat PCa. The epitranscriptome involves covalent modifications of mRNA, notably, in the context of this review, the N(6)-methyladenosine (m6A) modification. m6A is involved in the regulation of mRNA splicing, stability, and translation, and has recently been shown to play a role in PCa and androgen signalling. The m6A modification is dynamically regulated by the METTL3-containing methyltransferase complex, and the FTO and ALKBH5 RNA demethylases.Given the need for novel approaches to treat PCa, there is significant interest in new therapies that target m6A that modulate AR expression and androgen signalling. This review critically summarises the potential benefit of such epitranscriptomic therapies for PCa patients.

Background: There is a lack of physician ethnic and gender diversity amongst surgical specialties. This study analyzes the literature that promotes diversity amongst surgical trainees. Specifically, this study sought to answer (i) how the number of publications regarding diversity in orthopaedic surgery compares to other surgical specialties, (ii) how the number of publications amongst all surgical subspecialties trends over time and (iii) which specific topics regarding diversity are discussed in the surgical literature. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to query articles from PubMed, Web of Science, Embase and the Cumulative Index to Nursing and Allied Health Literature. Broad inclusion criteria for both ethnic and gender diversity of any surgical specialty were utilized. Results: Our query resulted 1429 publications, of which 408 duplicates were removed, and 701 were excluded on title and abstract screening, leaving 320 to be included. The highest number of related publications was in orthopaedic surgery (n = 73) followed by general surgery (n = 56). Out of 320 total articles, 260 (81.3 %) were published after 2015, and 56 of 73 (76.7 %) orthopaedic-specific articles were published after 2015. Conclusion: Orthopaedic surgery published the most about ethnic and gender diversity, however, still remains one of the least diverse surgical specialties. With the recent increase in publications on diversity in surgical training, close attention should be paid to ethnic and gender diversity amongst surgical trainees over the coming years. Should diversity remain stagnant, diversification efforts may need to be restructured to achieve a diverse surgeon workforce. Key message: Orthopaedic surgery is the surgical subspecialty that publishes the most about trainee ethnic and gender diversity followed by general surgery. With most of this literature being published over the last eight years, it is imperative to pay close attention to the ethnic and gender landscape of the surgeon workforce over the coming years.

Objective: This study aimed to develop and pilot test a new framework for the adaptation of patient decision aids (PtDAs) using a specific case example of contraceptive method PtDAs for Chinese-speaking migrant women. Methods: We developed a novel approach for adaptation – the PACE (Population And ContExt adaption of decision aids) framework – that incorporated both existing models and frameworks and innovative elements. It involves six stages: selection and appraisal; review by content experts; content validity and usability pre-testing; translation; decisional needs assessment; and perceived acceptability, usability and feasibility testing. We then followed the framework to pilot and adapt a suite of PtDAs on contraceptive methods for Chinese-speaking migrant women in Australia. Twenty healthcare providers and 22 Chinese migrant women participated during the stages five and six. Results: The pilot resulted in adapted PtDAs that were acceptable to end users. For future research, we proposed further recommendations and considerations based on lessons learnt, which include flexibility in applying the framework and considering an additional real-world evaluation step. Conclusion: Adaptation of PtDAs required a multi-stage and multidisciplinary team-based and pragmatic approach as exemplified in the application of the PACE framework. Innovation: The PACE framework developed and piloted in this study fills a crucial gap in knowledge about how to adapt PtDAs for new populations and contexts and provides an innovative and systemic approach to guide the adaptation process.

Background & Aims: Treatment of alcohol use disorder (AUD) improves survival in patients with alcohol-related cirrhosis. However, medications for alcohol use disorder (MAUD) are underutilized in this population, partially due to concerns regarding drug-induced liver injury (DILI). Our aim was to evaluate the safety of naltrexone in patients with cirrhosis. Methods: This was a retrospective study of patients with cirrhosis who were prescribed naltrexone using the VOCAL (Veterans Outcomes and Costs Associated with Liver Disease) database. Patients with new initiation of naltrexone after diagnosis of cirrhosis who had liver enzymes checked within a 3-month time frame were included. A chart review was performed on patients who developed alanine aminotransferase or alkaline phosphatase elevations to more than 2× or 5× the upper limit of normal, respectively. The RUCAM (Roussel Uclaf causality assessment method) was used to determine if DILI occurred. Results: A total of 3,285 patients with cirrhosis were initiated on naltrexone, of whom 2,940 had laboratory testing during the high-risk DILI period. Only 2% of patients had liver enzyme elevations, and among those, 30 (48%) were classified as “DILI excluded” and 32 (52%) were classified as “DILI unlikely”. No patients were classified as possible, probable, or highly probable DILI. No deaths or new decompensations were attributed to naltrexone. Conclusions: Naltrexone in patients with cirrhosis was not associated with development of DILI using RUCAM scoring. Naltrexone appears to be safe in patients with compensated and decompensated cirrhosis. Impact and Implications: Naltrexone is an effective medication for treating alcohol use disorder but is underutilized in patients with underlying liver disease due to historical concerns regarding hepatotoxicity. This retrospective study shows no drug-induced liver injury in a large cohort of patients with cirrhosis with new initiation of naltrexone. This study may encourage providers to prescribe naltrexone to patients with existing liver disease with ongoing alcohol use disorder.

Abstract Exploring the molecular basis of disease severity in rare disease scenarios is a challenging task provided the limitations on data availability. Causative genes have been described for Congenital Myasthenic Syndromes (CMS), a group of diverse minority neuromuscular junction (NMJ) disorders; yet a molecular explanation for the phenotypic severity differences remains unclear. Here, we present a workflow to explore the functional relationships between CMS causal genes and altered genes from each patient, based on multilayer network community detection analysis of complementary biomedical information provided by relevant data sources, namely protein-protein interactions, pathways and metabolomics. Our results show that CMS severity can be ascribed to the personalized impairment of extracellular matrix components and postsynaptic modulators of acetylcholine receptor (AChR) clustering. This work showcases how coupling multilayer network analysis with personalized -omics information provides molecular explanations to the varying severity of rare diseases; paving the way for sorting out similar cases in other rare diseases.

Abstract Background The EURO-NMD Registry collects data from all neuromuscular patients seen at EURO-NMD's expert centres. In-kind contributions from three patient organisations have ensured that the registry is patient-centred, meaningful, and impactful. The consenting process covers other uses, such as research, cohort finding and trial readiness. Results The registry has three-layered datasets, with European Commission-mandated data elements (EU-CDEs), a set of cross-neuromuscular data elements (NMD-CDEs) and a dataset of disease-specific data elements that function modularly (DS-DEs). The registry captures clinical, neuromuscular imaging, neuromuscular histopathology, biological and genetic data and patient-reported outcomes in a computer-interpretable format using selected ontologies and classifications. The EURO-NMD registry is connected to the EURO-NMD Registry Hub through an interoperability layer. The Hub provides an entry point to other neuromuscular registries that follow the FAIR data stewardship principles and enable GDPR-compliant information exchange. Four national or disease-specific patient registries are interoperable with the EURO-NMD Registry, allowing for federated analysis across these different resources. Conclusions Collectively, the Registry Hub brings together data that are currently siloed and fragmented to improve healthcare and advance research for neuromuscular diseases.

Aim To develop and user test an evidence-based patient decision aid for children and adolescents who are considering anterior cruciate ligament (ACL) reconstruction.Design Mixed-methods study describing the development of a patient decision aid.Setting A draft decision aid was developed by a multidisciplinary steering group (including various types of health professionals and researchers, and consumers) informed by the best available evidence and existing patient decision aids.Participants People who ruptured their ACL when they were under 18 years old (ie, adolescents), their parents, and health professionals who manage these patients. Participants were recruited through social media and the network outreach of the steering group.Primary and secondary outcomes Semistructured interviews and questionnaires were used to gather feedback on the decision aid. The feedback was used to refine the decision aid and assess acceptability. An iterative cycle of interviews, refining the aid according to feedback and further interviews, was used. Interviews were analysed using reflexive thematic analysis.Results We conducted 32 interviews; 16 health professionals (12 physiotherapists, 4 orthopaedic surgeons) and 16 people who ruptured their ACL when they were under 18 years old (7 were adolescents and 9 were adults at the time of the interview). Parents participated in 8 interviews. Most health professionals, patients and parents rated the aid’s acceptability as good-to-excellent. Health professionals and patients agreed on most aspects of the decision aid, but some health professionals had differing views on non-surgical management, risk of harms, treatment protocols and evidence on benefits and harms.Conclusion Our patient decision aid is an acceptable tool to help children and adolescents choose an appropriate management option following ACL rupture with their parents and health professionals. A clinical trial evaluating the potential benefit of this tool for children and adolescents considering ACL reconstruction is warranted.

Inclusion at academic events is facing increased scrutiny as the communities these events serve raise their expectations for who can practically attend. Active efforts in recent years to bring more diversity to academic events have brought progress and created momentum. However, we must reflect on these efforts and determine which underrepresented groups are being disadvantaged. Inclusion at academic events is important to ensure diversity of discourse and opinion, to help build networks, and to avoid academic siloing. All of these contribute to the development of a robust and resilient academic field. We have developed these Ten Simple Rules both to amplify the voices that have been speaking out and to celebrate the progress of many Equity, Diversity, and Inclusivity practices that continue to drive the organisation of academic events. The Rules aim to raise awareness as well as provide actionable suggestions and tools to support these initiatives further. This aims to support academic organisations such as the Deep Learning Indaba, Neuromatch Academy, the IBRO-Simons Computational Neuroscience Imbizo, Biodiversity Information Standards (TDWG), Arabs in Neuroscience, FAIRPoints, and OLS (formerly Open Life Science). This article is a call to action for organisers to reevaluate the impact and reach of their inclusive practices.

The rise of mRNA as a novel vaccination strategy presents new opportunities to confront global disease. Double-stranded RNA (dsRNA) is an impurity byproduct of the in vitro transcription reaction used to manufacture mRNA that may affect the potency and safety of the mRNA vaccine in patients. Careful quantitation of dsRNA during manufacturing is critical to ensure that residual dsRNA is minimized in purified mRNA drug substances. In this work, we describe the development and implementation of a sandwich Enzyme-Linked Immunosorbent Assay (ELISA) to quantitate nanogram quantities of residual dsRNA contaminants in mRNA process intermediates using readily available commercial reagents. This sandwich ELISA developed in this study follows a standard protocol and can be easily adapted to most research laboratory environments. Additionally, a liquid handler coupled with an automated robotics system was utilized to increase assay throughput, improve precision, and reduce the analyst time requirement. The final automated sandwich ELISA was able to measure

This article aims to explore the ethical issues arising from attempts to diversify genomic data and include individuals from underserved groups in studies exploring the relationship between genomics and health. We employed a qualitative synthesis design, combining data from three sources: 1) a rapid review of empirical articles published between 2000 and 2022 with a primary or secondary focus on diversifying genomic data, or the inclusion of underserved groups and ethical issues arising from this, 2) an expert workshop and 3) a narrative review. Using these three sources we found that ethical issues are interconnected across structural factors and research practices. Structural issues include failing to engage with the politics of knowledge production, existing inequities, and their effects on how harms and benefits of genomics are distributed. Issues related to research practices include a lack of reflexivity, exploitative dynamics and the failure to prioritise meaningful co-production. Ethical issues arise from both the structure and the practice of research, which can inhibit researcher and participant opportunities to diversify data in an ethical way. Diverse data are not ethical in and of themselves, and without being attentive to the social, historical and political contexts that shape the lives of potential participants, endeavours to diversify genomic data run the risk of worsening existing inequities. Efforts to construct more representative genomic datasets need to develop ethical approaches that are situated within wider attempts to make the enterprise of genomics more equitable.

IntroductionThe knowledge complexity and varied delivery formats in pharmacology education can leave students unprepared in essential pharmacotherapy skills. This significantly influences their ways of thinking and working in clinical environments, resulting in a challenging clinical transition. This need demands pedagogical innovations to strengthen pharmacology education and improve learners’ skills and competencies in pharmacotherapy. This evidence-based realist review aimed to examine the contextual factors and program theories or causal mechanisms crucial for effective pedagogical interventions in pharmacology, seeking to answer the question of ‘what works for whom, under what circumstances, how, and why’.MethodThe realist synthesis was initiated after retrieving data from Medline (OVID), Cochrane, EBSCO hosted ERIC, SCOPUS, and Embase (OVID) including other sources for additional records. The preliminary analysis enabled the establishment of context, mechanism, and outcome configurations (CMOC) and formulation and refinement of the initial program theory regarding the pedagogical interventions in pharmacology. Data synthesis iteration helped to identify the relevant context and unravel its relationships with underlying causal mechanisms through which said interventions generate outcomes of interest.ResultsA realist review analyzed 1,217 records and identified 75 articles examining a range of educational interventions from individual efforts to faculty-wide curriculum changes in pharmacology education. The key contexts for pharmacology education were troublesome content, traditional delivery methods, inadequate and limited opportunities for knowledge integration, and application. Active participation in interactive learning, along with enjoyment and motivation, was proposed as a causal mechanism for optimizing cognitive load and achieving positive outcomes. The outcomes of the review include subjective perceptions of improved confidence and satisfaction, objective measurements of high post-test scores.DiscussionPedagogical scaffolding in constructivist learning environments helps students overcome challenges in learning troublesome pharmacology knowledge. Considering the human cognitive system’s processing capacity, these interventions improve learning by effectively using cognitive resources. Innovations that focus on enhancing cognitive load through task construction can also promote positive emotional experiences in students, such as engagement and enjoyment, as explained by flow theory. A constructive learning environment, where the cognitive load is optimized and high flow is achieved, can maximize the impact of pedagogical interventions in pharmacology.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=160441, PROSPERO (CRD42020160441).

Introduction Low back pain (LBP) is commonly treated with opioid analgesics despite evidence that these medicines provide minimal or no benefit for LBP and have an established profile of harms. International guidelines discourage or urge caution with the use of opioids for back pain; however, doctors and patients lack practical strategies to help them implement the guidelines. This trial will evaluate a multifaceted intervention to support general practitioners (GPs) and their patients with LBP implement the recommendations in the latest opioid prescribing guidelines.Methods and analysis This is a cluster randomised controlled trial that will evaluate the effect of educational outreach visits to GPs promoting opioid stewardship alongside non-pharmacological interventions including heat wrap and patient education about the possible harms and benefits of opioids, on GP prescribing of opioids medicines dispensed. At least 40 general practices will be randomised in a 1:1 ratio to either the intervention or control (no outreach visits; GP provides usual care). A total of 410 patient–participants (205 in each arm) who have been prescribed an opioid for LBP will be enrolled via participating general practices. Follow-up of patient–participants will occur over a 1-year period. The primary outcome will be the cumulative dose of opioid dispensed that was prescribed by study GPs over 1 year from the enrolment visit (in morphine milligram equivalent dose). Secondary outcomes include prescription of opioid medicines, benzodiazepines, gabapentinoids, non-steroidal anti-inflammatory drugs by study GPs or any GP, health services utilisation and patient-reported outcomes such as pain, quality of life and adverse events. Analysis will be by intention to treat, with a health economics analysis also planned.Ethics and dissemination The trial received ethics approval from The University of Sydney Human Research Ethics Committee (2022/511). The results will be disseminated via publications in journals, media and conference presentations.Trial registration number ACTRN12622001505796.

Background: Dementia with Lewy bodies (DLB) is an important cause of dementia with a range of clinical manifestations, including motor, neuropsychiatric, and autonomic symptoms. Compared with more common forms of dementia such as Alzheimer’s disease, DLB has been the focus of significantly fewer treatment studies, often with diverse outcome measures, making comparison and clinical implementation difficult. A core outcome set (COS) can address this by ensuring that data are comparable, relevant, useful, and usable for making the best healthcare decisions. Methods: Using a multi-stage approach, development of the DLB-COS will include the following stages: (1) A systematic review, following PRISMA guidelines to create an initial long list of outcomes; (2) A two-round online Delphi including clinicians, scientists, policymakers, and individuals with lived experience of DLB and their representatives; (3) An online consensus meeting to agree on the final core list of outcomes (the final DLB-COS) for use in research and clinical practice; (4) A literature search to identify appropriate measurement instruments for the DLB-COS outcomes; (5) A final consensus meeting of the professional stakeholders who attended the online consensus meeting to agree on the instruments that should be used to measure the outcomes in the DLB-COS; and (6) Global dissemination. Discussion: This is a multi-stage project to develop a COS to be used in treatment trials for DLB. A DLB-COS will ensure the selection of relevant outcomes and will identify the instruments to be used to measure DLB globally.

Objective To develop and user-test a patient decision aid portraying the benefits and harms of non-surgical management and surgery for Achilles tendon ruptures.Design Mixed methods.Setting A draft decision aid was developed using guidance from a multidisciplinary steering group and existing patient decision aids. Participants were recruited through social media.Participants People who have previously sustained an Achilles tendon rupture and health professionals who manage these patients.Primary and secondary outcomes Semi-structured interviews and questionnaires were used to gather feedback on the decision aid from health professionals and patients who had previously suffered an Achilles tendon rupture. The feedback was used to redraft the decision aid and assess acceptability. An iterative cycle of interviews, redrafting according to feedback and further interviews was used. Interviews were analysed using reflexive thematic analysis. Questionnaire data were analysed descriptively.Results We interviewed 18 health professionals (13 physiotherapists, 3 orthopaedic surgeons, 1 chiropractor, 1 sports medicine physician) and 15 patients who had suffered an Achilles tendon rupture (median time since rupture was 12 months). Most health professionals and patients rated the aid’s acceptability as good-excellent. Interviews showcased agreement among health professionals and patients on most aspects of the decision aid: introduction, treatment options, comparing benefits and harms, questions to ask health professionals and formatting. However, health professionals had differing views on details about Achilles tendon retraction distance, factors that modify the risk of harms, treatment protocols and evidence on benefits and harms.Conclusion Our patient decision aid is an acceptable tool to both patients and health professionals, and our study highlights the views of key stakeholders on important information to consider when developing a patient decision aid for Achilles tendon rupture management. A randomised controlled trial evaluating the impact of this tool on the decision-making of people considering Achilles tendon surgery is warranted.

Background: The advancement of otologic surgery in low-resource settings has been limited by the cost and transport of surgical equipment. This study compared the transportation costs of an otologic microscopic surgical setup (MSS) versus an endoscopic surgical setup (ESS) in low- and low to middle-income countries (LMICs) for surgical teaching. Methods: Dimensions of microscopes, endoscopes and associated surgical instruments were used to calculate shipping costs from Minneapolis, MN, USA to Kenya, Haiti and Sri Lanka. Results: The average cost of internationally shipping the ESS is less than the MSS in Kenya (ESS: USD 1344.03; MSS: USD 20,947.00; p = 0.370), Haiti (ESS: USD 549.11; MSS: USD 1679.00; p < 0.05) and Sri Lanka (ESS: USD 945.38; MSS: USD 8490.57; p = 0.377). Freight shipping was required for the MSS while the ESS can be packed into an international checked bag for USD 35.00 USD. Discussion: The ESS has fewer logistical barriers than the MSS, making the endoscope a feasible option for surgical teaching in LMICs.

Summary: TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of TSPEAR is unknown. The clinical features, the mutation spectrum, and the underlying mechanisms of ARED14 are poorly understood. Combining data from new and previously published individuals established that ARED14 is primarily characterized by dental anomalies such as conical tooth cusps and hypodontia, like those seen in individuals with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed that most of the pathogenic TSPEAR missense variants likely destabilize the β-propeller of the protein. Analysis of 100000 Genomes Project (100KGP) data revealed multiple founder TSPEAR variants across different populations. Mutational and recombination clock analyses demonstrated that non-Finnish European founder variants likely originated around the end of the last ice age, a period of major climatic transition. Analysis of gnomAD data showed that the non-Finnish European population TSPEAR gene-carrier rate is ∼1/140, making it one of the commonest AREDs. Phylogenetic and AlphaFold structural analyses showed that TSPEAR is an ortholog of drosophila Closca, an extracellular matrix-dependent signaling regulator. We, therefore, hypothesized that TSPEAR could have a role in enamel knot, a structure that coordinates patterning of developing tooth cusps. Analysis of mouse single-cell RNA sequencing (scRNA-seq) data revealed highly restricted expression of Tspear in clusters representing enamel knots. A tspeara−/−;tspearb−/− double-knockout zebrafish model recapitulated the clinical features of ARED14 and fin regeneration abnormalities of wnt10a knockout fish, thus suggesting interaction between tspear and wnt10a. In summary, we provide insights into the role of TSPEAR in ectodermal development and the evolutionary history, epidemiology, mechanisms, and consequences of its loss of function variants.

Nominal Group Technique (NGT) is a structured approach to consensus development and data collection driven by problem-solving, idea inception and prioritisation. Challenges of the coronavirus disease 2019 (COVID-19) pandemic necessitated the development of a virtual (vNGT) model to recruit participants from diverse locations and time zones. Our reflections reveal the opportunities and challenges of using Zoom© for NGT sessions, resulting in more effective engagement and focus with fewer distractions compared to in-person meetings. The 12 tips provide practical suggestions for expanding the versatility of NGT in a virtual environment. These recommendations cover every aspect of the process, including the person, place, and object, from planning the sessions, and utilising technology resources effectively, to ensuring a seamless implementation to desirable outcomes. The paper strives to assist individuals in effectively using the online NGT as a substitute for in-person events, promoting effective management of remote participants even during unprecedented times of quarantine and physical distancing.

Objective: This study aimed to explore the perceived acceptability, usefulness, and feasibility of a suite of encounter decision aids (DAs) on contraceptive methods with Chinese migrant women living in Australia and healthcare providers. Methods: Semi-structured in-depth interviews with 22 Chinese migrant women and twenty healthcare providers were conducted. Transcribed data were analysed using the qualitative content analysis method. Results: Women perceived the DAs to be informative and useful. They suggested making the DAs available outside the clinical settings. Healthcare providers perceived the DAs to be comprehensive and valuable in informing women about contraceptive methods. Some providers had concerns as to the information load and the length of the DAs. Such concerns were eased when provided with an explanation of how to use the DAs. Most women and healthcare providers preferred the numerical format for side-effect probability information presentation. Conclusion: Making the encounter DAs available in both the Chinese and English languages can be valuable in assisting Chinese migrant women in making informed decisions about contraceptive methods. Innovation: This study is the first to evaluate the acceptability and perceived feasibility of patient decision aids with members of a migrant community in Australia. The findings highlight the need for disseminating the DAs both within and outside the clinical settings.

Background: Long-term implant durability is a key concern when considering total hip arthroplasty (THA) in young patients. The ideal bearing surface used in these patients remains unknown. The purpose of this study was to analyze trends in THA bearing surface use from 2006 to 2016 using a large, pediatric national database. Methods: This was a retrospective review from January 1, 2006, to December 31, 2016, using the Kids’ Inpatient Database. International Classification of Diseases, 9th revision and 10th revision codes were used to identify patients who underwent THA and create cohorts based on bearing surfaces: metal-on-metal, metal-on-polyethylene, ceramic-on-polyethylene (CoP), and ceramic-on-ceramic (CoC). Annual utilization of each bearing surface and associated patient and hospital demographics were analyzed. Results: A total of 1004 THAs were identified during the 11-year study period. The annual number of THAs performed increased by 169% from 2006 to 2016. The mean patient age was 17.1 years. The most prevalent bearing surface used in 2006 was CoC (37.3%), metal-on-metal (31.8%) in 2009, and CoP in 2012 and 2016 (50.6% and 64.8%, respectively). From 2006 to 2016, utilization of CoP increased from 5.0% to 64.8%, representing a 1196% increase over the study period. Conclusions: The number of THAs performed in pediatric patients is increasing significantly. Although CoC was previously the most commonly used bearing surface in this patient population, CoP is currently the most common. Further investigation is needed to determine whether bearing longevity and clinical outcomes with CoP are superior to other bearing surfaces.

Background: Dementia with Lewy bodies (DLB) is an important cause of dementia with a range of clinical manifestations, including motor, neuropsychiatric, and autonomic symptoms. Compared with more common forms of dementia such as Alzheimer’s disease, DLB has been the focus of significantly fewer treatment studies, often with diverse outcome measures, making comparison and clinical implementation difficult. A core outcome set (COS) can address this by ensuring that data are comparable, relevant, useful, and usable for making the best healthcare decisions. Methods: Using a multi-stage approach, development of the DLB-COS will include the following stages: (1) A systematic review, following PRISMA guidelines to create an initial long list of outcomes; (2) A two-round online Delphi including clinicians, scientists, policymakers, and individuals with lived experience of DLB and their representatives; (3) An online consensus meeting to agree on the final core list of outcomes (the final DLB-COS) for use in research and clinical practice; (4) A literature search to identify appropriate measurement instruments for the DLB-COS outcomes; (5) A final consensus meeting of the professional stakeholders who attended the online consensus meeting to agree on the instruments that should be used to measure the outcomes in the DLB-COS; and (6) Global dissemination. Discussion: This is a multi-stage project to develop a COS to be used in treatment trials for DLB. A DLB-COS will ensure the selection of relevant outcomes and will identify the instruments to be used to measure DLB globally.

The core structure of the extracellular basement membrane is made up of self-assembling networks of collagen and laminin which associate with each other through the bridging adapter proteins including the sulfated monomeric glycoprotein nidogen. While collagen and laminin are known to support platelet adhesion and activation via β1 integrins and glycoprotein (GP) VI, respectively, whether nidogen contributes to platelet activation and hemostasis is unknown. In this study, we demonstrate that recombinant human nidogen-1 supports platelet adhesion and stimulates platelet activation in a phospholipase-C γ-2 (PLCγ2), Src and Syk kinase-dependent manner downstream. Platetet adhesion to nidogen-1 was inhibited by blocking the platelet receptors GPVI and β1 integrins. Platelet adhesion to nidogen-1 activated the IκB kinase (IKK) complex, while pharmacological inhibition of IKK blocked platelet spreading on nidogen. Taken together our results suggest that nidogen may play a redundant role in hemostasis by activating platelets downstream of GPVI.

Abstract Background In Australia, ethnic Chinese people are one of the largest, youngest and fastest growing overseas-born groups. Yet, little is known about their perceptions of contraceptive methods and their experiences with choosing one. Decisions about contraceptive methods are preference sensitive. Understanding the influencing factors of Chinese migrant women’s contraceptive method choice and practices will help cater to their decision-making needs in a culturally sensitive and responsive way. Methods A qualitative study design underpinned by critical realism approach was used to explore Chinese migrant women’s perceptions and experiences of choosing contraceptive methods. Semi-structured interviews were conducted with 22 women who self-identified as being ethnically Chinese and had been living in Australia for no more than 10 years. The interview guide was adapted from the Ottawa Decision Support Framework. Majority of the interviews were conducted in Mandarin Chinese. Transcribed data was analysed using thematic analysis method. Results Four major themes were identified, including: ‘every medicine is part poison: hormonal contraceptives cause harm to the body’; ‘intrauterine device, a device used in the past for married women’; ‘it takes two (or one) to decide, depending on the relationship dynamics and contraception preferences’; and ‘it is not necessary to seek medical advice in choosing contraceptive methods’. Conclusions Our findings suggest that Chinese migrant women’s perceptions and experiences of choosing contraceptive methods are influenced by complex personal, cultural, societal and inter-relational factors. Chinese migrant women were cautious of using hormonal methods due to fears of side-effects, including reduced or absent menstrual bleeding. Women were also reluctant to consider intrauterine devices as options due to associating them with past experiences of other women and themselves and also fears of potential complications. There was a reluctant attitude towards seeking medical advice regarding contraception due to beliefs that needing to use contraception is not an illness requiring treatment. Such findings are likely to be useful in increasing healthcare professionals’ and policy makers’ understanding of Chinese migrant women’s contraceptive method preferences, beliefs and behaviours. They also help to develop culturally and linguistically sensitive strategies, which goes beyond the provision of contraceptive counselling, in assisting Chinese migrant women’s decision-making needs.

Abstract Background Rare diseases are individually rare but globally affect around 6% of the population, and in over 70% of cases are genetically determined. Their rarity translates into a delayed diagnosis, with 25% of patients waiting 5 to 30 years for one. It is essential to raise awareness of patients and clinicians of existing gene and variant-specific therapeutics at the time of diagnosis to avoid that treatment delays add up to the diagnostic odyssey of rare diseases’ patients and their families. Aims This paper aims to provide guidance and give detailed instructions on how to write homogeneous systematic reviews of rare diseases’ treatments in a manner that allows the capture of the results in a computer-accessible form. The published results need to comply with the FAIR guiding principles for scientific data management and stewardship to facilitate the extraction of datasets that are easily transposable into machine-actionable information. The ultimate purpose is the creation of a database of rare disease treatments (“Treatabolome”) at gene and variant levels as part of the H2020 research project Solve-RD. Results Each systematic review follows a written protocol to address one or more rare diseases in which the authors are experts. The bibliographic search strategy requires detailed documentation to allow its replication. Data capture forms should be built to facilitate the filling of a data capture spreadsheet and to record the application of the inclusion and exclusion criteria to each search result. A PRISMA flowchart is required to provide an overview of the processes of search and selection of papers. A separate table condenses the data collected during the Systematic Review, appraised according to their level of evidence. Conclusions This paper provides a template that includes the instructions for writing FAIR-compliant systematic reviews of rare diseases’ treatments that enables the assembly of a Treatabolome database that complement existing diagnostic and management support tools with treatment awareness data.

Abstract Background There is no available evidence for the prevalence of early labour admission to hospital or its association with rates of intervention and clinical outcomes in Australia. The objectives of this study were to: estimate the prevalence of early labour admission in one hospital in Australia; compare rates of clinical intervention, length of hospital stay and clinical outcomes for women admitted in early (

BackgroundMany countries remain in the grip of the COVID-19 global pandemic, with a considerable journey still ahead toward normalcy and free mobility. Contact tracing smartphone apps are among a raft of measures introduced to reduce spread of the virus, but their uptake depends on public choice. ObjectiveThe objective of this study was to ascertain the views of citizens in Wales on their intended use of a COVID-19 contact tracing smartphone app, including self-proposed reasons for or against use and what could lead to a change of decision. MethodsWe distributed an anonymous survey among 4000 HealthWise Wales participants in May 2020. We adopted a mixed methods approach: responses to closed questions were analyzed using descriptive and inferential statistics; open question responses were analyzed and grouped into categories. ResultsA total of 976 (24.4%) people completed the survey. Smartphone usage was 91.5% overall, but this varied among age groups. In total, 97.1% were aware of contact tracing apps, but only 67.2% felt sufficiently informed. Furthermore, 55.7% intended to use an app, 23.3% refused, and 21.0% were unsure. The top reasons for app use were as follows: controlling the spread of the virus, mitigating risks for others and for oneself, and increasing freedoms. The top reasons against app use were as follows: mistrusting the government, concerns about data security and privacy, and doubts about efficacy. The top response for changing one’s mind about app use from being willing to being unwilling was that nothing would; that is, they felt that nothing would cause them to become unwilling to use a contact tracing app. This was also the top response for changing one’s mind from being unwilling to being willing to use contact tracing apps. Among those who were unsure of using contact tracing apps, the top response was the need for more information. ConclusionsRespondents demonstrated a keenness to help themselves, others, society, and the government to avoid contracting the virus and to control its spread. However, digital inclusion varied among age groups, precluding participation for some people. Nonetheless, unwillingness was significant, and considering the nature of the concerns raised and the perceived lack of information, policy and decision-makers need to do more to act openly, increase communication, and demonstrate trustworthiness if members of the public are to be confident in using an app.

Introduction Data from the Association of American Medical Colleges' Medical School Graduation Questionnaire show persistent trends of medical student mistreatment nationwide. To reduce the barriers and increase actionable reporting of mistreatment, we integrated peer-facilitated learning environment sessions led by a group of trained third- and fourth-year medical students in all core clinical clerkships. Methods During the 2018–2019 academic year, third-year medical students were recruited, oriented, and trained to act as facilitators of sessions on mistreatment. The sessions occurred once every clerkship block, using a standardized session introduction and guide. After a 6-month pilot, new medical students were recruited and worked as scribe/facilitator pairs, receiving an additional 1.5-hour training midyear, which was evaluated with a postworkshop survey. Results Thirty-eight students implemented 43 peer-facilitated sessions and completed deidentified minutes of each session, which were shared with clerkship directors and the Medical Education Office for review. Survey data from midyear facilitator training indicated that facilitators highly agreed peer-led sessions were an important avenue for students to process experiences of mistreatment (3.9 out of 4), understood barriers to reporting (3.8 out of 4) and definitions of mistreatment (3.6 out of 4), and felt confident to facilitate these sessions (3.6 out of 4). Discussion Peer-facilitated sessions offer a method to learn more about student experiences with mistreatment in real time and create a new avenue for communication between faculty and students. Assembling a stable core team of third- and fourth-year students trained in facilitation skills ensures the sustainability and relevance of the program.

This review article discusses the diagnoses and treatment of patients with multiple endocrine neoplasia type 1 (MEN 1). The most common tumors associated with MEN 1 are located in the pancreas, pituitary, and parathyroid glands. Less common tumors include neuroendocrine tumors of the lung and thymus, adrenal tumors, and cutaneous lesions. This article describes the diagnosis, clinical manifestations, treatment, and surveillance of tumors associated with patients who are diagnosed with MEN 1.

Abstract Background Struggling medical students is an under-researched in medical education. It is known, however, that early identification is important for effective remediation. The aim of the study was to determine the predictive effect of medical school admission tools regarding whether a student will struggle academically. Methods Data comprise 700 students from the University of New South Wales undergraduate medical program. The main outcome of interest was whether these students struggled during this 6-year program; they were classified to be struggling they failed any end-of-phase examination but still graduated from the program. Discriminate Function Analysis (DFA) assessed whether their pre-admission academic achievement, Undergraduate Medicine Admission Test (UMAT) and interview scores had predictive effect regarding likelihood to struggle. Results A lower pre-admission academic achievement in the form of Australian Tertiary Admission Rank (ATAR) or Grade Point Average (GPA) were found to be the best positive predictors of whether a student was likely to struggle. Lower UMAT and poorer interview scores were found to have a comparatively much smaller predictive effect. Conclusion Although medical admission tests are widely used, medical school rarely use these data for educational purposes. The results of this study suggest admission test data can predict who among the admitted students is likely to struggle in the program. Educationally, this information is invaluable. These results indicate that pre-admission academic achievement can be used to predict which students are likely to struggle in an Australian undergraduate medicine program. Further research into predicting other types of struggling students as well as remediation methods are necessary.

Abstract Background There is limited evidence on how to implement shared decision-making (SDM) interventions in routine practice. We conducted a qualitative study, embedded within a 2 × 2 factorial cluster randomized controlled trial, to assess the acceptability and feasibility of two interventions for facilitating SDM about contraceptive methods in primary care and family planning clinics. The two SDM interventions comprised a patient-targeted intervention (video and prompt card) and a provider-targeted intervention (encounter decision aids and training). Methods Participants were clinical and administrative staff aged 18 years or older who worked in one of the 12 clinics in the intervention arm, had email access, and consented to being audio-recorded. Semi-structured telephone interviews were conducted upon completion of the trial. Audio recordings were transcribed verbatim. Data collection and thematic analysis were informed by the 14 domains of the Theoretical Domains Framework, which are relevant to the successful implementation of provider behaviour change interventions. Results Interviews (n = 29) indicated that the interventions were not systematically implemented in the majority of clinics. Participants felt the interventions were aligned with their role and they had confidence in their skills to use the decision aids. However, the novelty of the interventions, especially a need to modify workflows and change behavior to use them with patients, were implementation challenges. The interventions were not deeply embedded in clinic routines and their use was threatened by lack of understanding of their purpose and effect, and staff absence or turnover. Participants from clinics that had an enthusiastic study champion or team-based organizational culture found these social supports had a positive role in implementing the interventions. Conclusions Variation in capabilities and motivation among clinical and administrative staff, coupled with inconsistent use of the interventions in routine workflow contributed to suboptimal implementation of the interventions. Future trials may benefit by using implementation strategies that embed SDM in the organizational culture of clinical settings.

Abstract Background Women value receiving quality interpersonal care during abortion services, yet no measure exists to assess this outcome from patients’ perspectives. We sought to adapt the Interpersonal Quality in Family Planning care scale (Dehlendorf et al., American Journal of Obstetrics Gynaecology 10.1016/j.ajog.2016.01.173, 2016) for use in abortion care. Methods We adapted items from the original scale for the abortion context, and conducted cognitive interviews to explore the acceptability, understandability, and importance of the adapted items. Adults who spoke English and/or Spanish, had an abortion in the past year, and lived in the US were eligible to participate. Interview memos were analyzed concurrently with data collection to refine the measure in stages. Results We interviewed 26 participants. Items were tested over seven stages and led to four main changes. First, we revised three items to reflect concepts perceived as important to the specific decision-making context of abortion. Second, we removed two items that emerged as potentially inappropriate for this context. Third, we modified language in four items to improve their appropriateness for this context (e.g., ‘telling me’ to ‘explaining’; ‘letting me say’ to ‘listening to’). Fourth, we modified language in three items to improve their clarity. Three items remained unchanged, as there was consistent agreement on their importance, understandability, and relevance. Conclusions The resulting 10-item measure, the Interpersonal Quality in Abortion Care scale, was perceived to be highly important, understandable, and feasible to complete. Future psychometric evaluation can prepare it for use in clinical practice to ensure women feel adequately informed and supported during abortion care.

Abstract Background The optical accessibility of the eye and technological advances in ophthalmic diagnostics have put ophthalmology at the forefront of data-driven medicine. The focus of this study is rare eye disorders, a group of conditions whose clinical heterogeneity and geographic dispersion make data-driven, evidence-based practice particularly challenging. Inter-institutional collaboration and information sharing is crucial but the lack of standardised terminology poses an important barrier. Ontologies are computational tools that include sets of vocabulary terms arranged in hierarchical structures. They can be used to provide robust terminology standards and to enhance data interoperability. Here, we discuss the development of the ophthalmology-related component of two well-established biomedical ontologies, the Human Phenotype Ontology (HPO; includes signs, symptoms and investigation findings) and the Orphanet Rare Disease Ontology (ORDO; includes rare disease nomenclature/nosology). Methods A variety of approaches were used including automated matching to existing resources and extensive manual curation. To achieve the latter, a study group including clinicians, patient representatives and ontology developers from 17 countries was formed. A broad range of terms was discussed and validated during a dedicated workshop attended by 60 members of the group. Results A comprehensive, structured and well-defined set of terms has been agreed on including 1106 terms relating to ocular phenotypes (HPO) and 1202 terms relating to rare eye disease nomenclature (ORDO). These terms and their relevant annotations can be accessed in http://www.human-phenotype-ontology.org/ and http://www.orpha.net/; comments, corrections, suggestions and requests for new terms can be made through these websites. This is an ongoing, community-driven endeavour and both HPO and ORDO are regularly updated. Conclusions To our knowledge, this is the first effort of such scale to provide terminology standards for the rare eye disease community. We hope that this work will not only improve coding and standardise information exchange in clinical care and research, but also it will catalyse the transition to an evidence-based precision ophthalmology paradigm.

Abstract Background Value-based health care aims to optimize the balance of patient outcomes and health care costs. To improve value in perinatal care using this strategy, standard outcomes must first be defined. The objective of this work was to define a minimum, internationally appropriate set of outcome measures for evaluating and improving perinatal care with a focus on outcomes that matter to women and their families. Methods An interdisciplinary and international Working Group was assembled. Existing literature and current measurement initiatives were reviewed. Serial guided discussions and validation surveys provided consumer input. A series of nine teleconferences, incorporating a modified Delphi process, were held to reach consensus on the proposed Standard Set. Results The Working Group selected 24 outcome measures to evaluate care during pregnancy and up to 6 months postpartum. These include clinical outcomes such as maternal and neonatal mortality and morbidity, stillbirth, preterm birth, birth injury and patient-reported outcome measures (PROMs) that assess health-related quality of life (HRQoL), mental health, mother-infant bonding, confidence and success with breastfeeding, incontinence, and satisfaction with care and birth experience. To support analysis of these outcome measures, pertinent baseline characteristics and risk factor metrics were also defined. Conclusions We propose a set of outcome measures for evaluating the care that women and infants receive during pregnancy and the postpartum period. While validation and refinement via pilot implementation projects are needed, we view this as an important initial step towards value-based improvements in care.

The objective of this study was to assess the psychometric properties of IntegRATE—a 4-item patient-reported measure of integration in health care delivery—under controlled conditions. Adults who reported having received health care in the previous year were exposed to a fictional health care scenario featuring good, mixed, or poor integration on 1 or 2 occasions. They were then asked to imagine themselves as a patient in the scenario and complete IntegRATE and other measures. The data collected were analyzed to assess the discriminative, concurrent, and divergent validity of IntegRATE and its test–retest reliability and responsiveness using both “sum score” and “top score” scoring approaches. Six-hundred people participated in the study with 190 taking part on 2 occasions. The IntegRATE sum score demonstrated discriminative validity, concurrent validity, divergent validity, and responsiveness and partially demonstrated test–retest reliability. The IntegRATE top score demonstrated concurrent validity, divergent validity, and responsiveness and partially demonstrated discriminative validity and test–retest reliability. We conclude that the IntegRATE sum score exhibits encouraging psychometric properties and performs more optimally than the IntegRATE top score.

Background: Universal Health Coverage has become a political priority for many African countries yet there are clear challenges in achieving this goal. Though social health insurance is considered a mechanism for providing financial protection, less well documented in the literature is evidence from countries in Africa who are at various stages of adopting this financing strategy as a way to improve health insurance coverage for their populations. Objectives: The study investigates whether social health insurance schemes are effectively and efficiently covering all groups. The objective is to provide evidence of how these schemes have been implemented and whether the fundamental goals are met. The selected countries are Ghana, Rwanda, Tanzania, Kenya and Ethiopia. The study draws lessons from the literature about how policy tools can be used to reduce financial barriers whilst ensuring a broad geographic coverage in Africa. Methods: The study relies primarily on a review of literature, both documented and grey matter, which include key documents such as government health policy documents, strategic plans, health financing policy documents, Universal Health Coverage policy documents, published literature, unpublished documents, media reports and National Health Accounts reports. Results: The results show that each of the selected countries relies on a plurality of health insurance schemes with each targeting different groups. Additionally, many of the Social Health Insurance programs start by covering the formal sector first, with the hope of covering other groups in the informal sector at a later stage. Health insurance coverage for poor groups is very low, with targeting mechanisms to cover the poor in the form of exemptions and waivers achieving no desirable results. Conclusions: The ability for Social Health Insurance programs to cover all groups has been limited in the selected countries. Hence, relying solely on social health insurance schemes to achieve Universal Health Coverage may not be plausible in Africa. Also, highly fragmented risk pools impede efforts to widen the insurance pools and promote cross-subsidies.

The Liverpool Citizens’ Jury was a public consultation on the use of health data to tackle the significant problem of Antimicrobial Resistance (AMR) and is the first step in creating a local AMR network with national and international relevance. The 18 jurors were tasked with learning about AMR as it relates to research and considered how organisations might collect, share and utilise pseudo-anonymised patient data. The overarching aim is to produce a new model supporting societal change focused on Antibiotic Guardianship and to combat the public health challenge of AMR. The model will be implemented in the UK and provided to an international network enabling global knowledge transfer.

Introduction: The long-term health and wellbeing of adoptees is under-researched. One reason for this has been limited data accessibility regarding the adoption process, and another is a practice common in some UK jurisdictions of changing the NHS number (or equivalent) at adoption, as part of creating the new identity. The SAIL Databank holds data from the Wales Children and Family Court Advisory and Support Service (Cafcass Cymru), together with children’s social care data, and can link these with routine health and administrative data in anonymised form. However, because the linkage key at SAIL is based on an encryption of the NHS number, working with pre- and post-adoption records for longitudinal research remains a major challenge. We set out to explore the legal implications of, and social support for, linking these records for use in anonymised form for longitudinal research. Methods: We reviewed the main legislation and regulations governing the use of data about adoptees in England and Wales. We gauged support for a social licence in Wales by carrying out interviews with individuals who had been involved in the adoptions process, and by engaging with general public groups for their views. We drew out the main emerging themes and, in combination with the review, propose a way forward. Results: The legal review indicated that there are provisions in the Family Procedure Rules (England and Wales) and the General Data Protection Regulation that can be relied upon for the lawful processing of adoption data into anonymised form for research. The main points of concern about linking pre- and post-adoption records were privacy, data security, the need to limit the number of organisations involved in data sharing, and re-identification risk. The over-riding message was favourable with longitudinal research seen as strongly beneficial. Conclusion: This study has indicated that in Wales, there is no legal impediment, nor major objection from individuals involved in the adoptions process, as well as the general public for the use of adoption data in anonymised form, in a data safe haven. This includes the linkage of pre- and post‑adoption records to enable novel longitudinal research to take place. The provisos were that robust safeguards must be in place, and that the research should aim to benefit adoptees and to improve policy and practice. We conclude that it is reasonable to proceed with caution to develop practical ways to link pre- and post‑adoption records in a data safe haven.

Background: The SAIL Databank is a data safe haven established in 2007 at Swansea University (Wales). It was set up to create new opportunities for research using routinely-collected health and other public service datasets in linkable anonymised form. SAIL forms the bedrock of other Population Data Science initiatives made possible by the data and safe haven environment. Aim: The aim of this paper is to provide an overview of public involvement and engagement in connection with the SAIL Databank and related Population Data Science initiatives. Approach: We have a public involvement and engagement policy for SAIL in the context of Population Data Science. We established a Consumer Panel to provide advice on the work of SAIL and associated initiatives, including on proposed uses of SAIL data. We reviewed the topics discussed and provide examples of advice to researchers. We carried out a survey with members on their experiences of being on the Panel and their perceptions of the work of SAIL. We have a programme of wider public engagement and provide illustrations of this work. Discussion: We summarise what this paper adds and some lessons learned. In the rapidly developing area of Population Data Science it is important that people feel welcome, that they are encouraged to ask questions and are provided with digestible information and adequate consideration time. Citizens have provided us with valuable anticipated and unanticipated opinions and novel viewpoints. We seek to take a pragmatic approach, prioritising the communication modes that allow maximum public input commensurate with the purpose of the activity. Conclusion: This paper has set out our policy, rationale, scope and practical approaches to public involvement and engagement for SAIL and our related Population Data Science initiatives. Although there will be jurisdictional, cultural and organizational differences, we believe that the material covered in this paper will be of interest to other data focused enterprises across the world.

The global coronavirus pandemic has clearly demonstrated the great urgency to collect and use patient data effectively to understand, track and manage the spread of Covid-19. The value of patient data in this pandemic is undeniable, however considerations around how - and by whom - such data should be collected, accessed and used, and for what purposes, remain to be fully debated and resolved. Who decides, and how such decisions are made remain unclear. We argue that public engagement and deliberation are essential for good governance and are key to establish and maintain a legitimate social licence for data practices around Covid-19.

Introduction Advances in genomic medicine contribute to increased demand for clinical genetics services and require physicians to understand the interprofessional practice of this field. Medical students receive a foundation in genetics during preclinical studies, but variability in clinical experience may limit knowledge of and recruitment into this clinical specialty. In this resource, we describe an approach for simulating exposure to the practice of clinical genetics during the core pediatrics clerkship. Methods Prior to class, students researched and considered a mock genetics case. In class, each of four small groups discussed two cases demonstrating varied presentations, with facilitation by genetic counseling students. Each case highlighted the variability in presentation, testing, management strategies, and psychosocial issues of a genetics case. Groups reported out to the class, and individuals completed an anonymous evaluation survey. Results Surveys were distributed to nine of 10 pilot sessions (210 of 235 students) with a response rate of 48%. Students frequently reported no previous exposure to seeing patients with genetics professionals, indicated a preference for learning in case discussion format over traditional lectures, and felt the format helped them apply clinical skills and reasoning. Medical students appreciated the opportunity to interact with genetic counseling students in an interdisciplinary setting and desired further educational opportunities regarding delivering complex information to patients and their families. Discussion This session expanded exposure to clinical genetics content and professionals, serving as an important foundation for further development of genetic knowledge during clinical training.

Abstract Background Congenital myasthenic syndromes (CMS) are a heterogeneous group of inherited neuromuscular disorders sharing the common feature of fatigable weakness due to defective neuromuscular transmission. Despite rapidly increasing knowledge about the genetic origins, specific features and potential treatments for the known CMS entities, the lack of standardized classification at the most granular level has hindered the implementation of computer-based systems for knowledge capture and reuse. Where individual clinical or genetic entities do not exist in disease coding systems, they are often invisible in clinical records and inadequately annotated in information systems, and features that apply to one disease but not another cannot be adequately differentiated. Results We created a detailed classification of all CMS disease entities suitable for use in clinical and genetic databases and decision support systems. To avoid conflict with existing coding systems as well as with expert-defined group-level classifications, we developed a collaboration with the Orphanet nomenclature for rare diseases, creating a clinically understandable name for each entity and placing it within a logical hierarchy that paves the way towards computer-aided clinical systems and improved knowledge bases for CMS that can adequately differentiate between types and ascribe relevant expert knowledge to each. Conclusions We suggest that data science approaches can be used effectively in the clinical domain in a way that does not disrupt preexisting expert classification and that enhances the utility of existing coding systems. Our classification provides a comprehensive view of the individual CMS entities in a manner that supports differential diagnosis and understanding of the range and heterogeneity of the disease but that also enables robust computational coding and hierarchy for machine-readability. It can be extended as required in the light of future scientific advances, but already provides the starting point for the creation of FAIR (Findable, Accessible, Interoperable and Reusable) knowledge bases of data on the congenital myasthenic syndromes.

Abstract Background Pediatric pain is associated to patient weight and demographics in specialized settings, but pain prevalence and its associated patient attributes in general pediatric outpatient care are unknown. Our objective was to determine the rate of positive pain screenings in pediatric primary care and evaluate the relationship between reported pain and obesity, demographics, and exam findings during routine pediatric encounters. Methods Cross-sectional observational study of 26,180 patients ages 2 to 19 seen in five urban pediatric primary care clinics between 2009 and 2016. Data were collected from systematic screening using a computerized clinical decision support system. Multivariable logistic regressions were used to analyze the association between pain reporting and obesity (body mass index), age, sex, race, season, insurance status, clinic site, prior pain reporting, pain reporting method, and exam findings. Results Pain was reported by the patient or caregiver in 14.9% of visits. In adjusted models, pain reporting was associated with obesity (Odds Ratio (OR) 1.23, 95% Confidence Intervals (CI) 1.11–1.35) and severe obesity (OR 1.32, CI 1.17–1.49); adolescents (OR 1.47, CI 1.33–1.61); and females (OR 1.21, CI 1.12–1.29). Pain reported at the preceding visit increased odds of pain reporting 2.67 times (CI 2.42–2.95). Abnormal abdominal, extremity, ear, nose, throat, and lymph node exams were associated with pain reporting. Pain reporting increased in minority races within clinics that predominantly saw a concordant race. Conclusions Pain is common in general pediatric encounters, and occurs more frequently in obese children and those who previously reported pain. Pain reporting may be influenced by seasonal variation and clinic factors. Future pediatric pain screening may be guided by associated risk factors to improve identification and targeted healthcare interventions.

An amendment to this paper has been published and can be accessed via the original article.

Abstract This article provides a critical overview of the ethics and governance of genetic biobank research, using the Athlome Consortium as a large scale instance of collaborative sports genetic biobanking. We present a traditional model of written informed consent for the acquisition, storage, sharing and analysis of genetic data and articulate the challenges to it from new research practices such as genetic biobanking. We then articulate six possible alternative consent models: verbal consent, blanket consent, broad consent, meta consent, dynamic consent and waived consent. We argue that these models or conceptions of consent must be articulated in the context of the complexities of international legislation and non legislative national and international biobank governance frameworks and policies, those which govern research in the field of sports genetics. We discuss the tensions between individual rights and public benefits of genomic research as a critical ethical issue, particularly where benefits are less obvious, as in sports genomics. The inherent complexities of international regulation and biobanking governance are challenging in a relatively young field. We argue that there is much nuanced ethical work still to be done with regard to governance of sports genetic biobanking and the issues contained therein.

This study examines the use of tweaa [tɕʏɪaa], an Akan emotive interjection that expresses “contempt” for a person, in the Corpus of GhanaWeb Comments in Ghana's 2016 Election (CGCGE16). CGCGE16 comprises reader comments posted in the build-up to Ghana's presidential elections in December 2016 on www.ghanaweb.com, a news website that guarantees freedom of speech and ensures citizen participation in online sociopolitical discussions. The study employs the semantic explication method of the Natural Semantic Metalanguage (NSM) approach to unpack the meaning of tweaa to give a fuller understanding of its rhetorical power in online political discourse. It points out that tweaa is derogatory and expresses lack of respect for the user's target, thus, according to traditional Ghanaian values, its use is unacceptable, especially during asymmetrical interactions. Citizens, however, hide behind the shield of anonymity online platforms guarantee, and their ability to circumvent traditional gatekeepers of acceptable speech forms during online discourse, and freely use tweaa to vent their feelings against authority figures. Keywords: Tweaa, Interjection of contempt, NSM, Politics, CGCGE16, Ghana

This paper highlights the folk perception of impoliteness among Ghanaians in view of Watts’ (2003) notion of first order impoliteness. The study showed that impoliteness is not just an opposite of politeness, but the manifestation of non-cooperation, disapproval, and mutual antipathy through certain communicative behaviours that signal disrespect. These communicative behaviours include ‘interrupting others’, the use of ‘invectives’ and the use of ‘offensive non-verbal forms of communication (NVCs)’. The use of these impolite communicative behaviours destabilizes interpersonal relationships and shows that a speaker is communicatively incompetent. The study also proposed the ‘pardonability scale of impoliteness’. This scale showed that among Ghanaians, the use of invectives is the most offensive and least pardonable impolite communicative behaviour while the use of offensive NVCs is the least offensive and most pardonable impolite communicative behaviour. It was also noted that the degree of offensiveness or pardonability in the order of the arrangement displayed on the scale, is not strictly tied to all speech events.

The reaction of 2,6-diformyl-4-methylphenol (DFMF) with 1-amino-2-propanol (AP) and tris(hydroxymethyl)aminomethane (THMAM) was investigated in the presence of Cobalt(II) salts, (X = ClO4−, CH3CO2−, Cl−, NO3−), sodium azide (NaN3), and triethylamine (TEA). In one pot, the variation in Cobalt(II) salt results in the self-assembly of dinuclear, tetranuclear, and H-bonding-directed polynuclear coordination complexes of Cobalt(III), Cobalt(II), and mixed-valence CoIICoIII: [Co2III(H2L−1)2(AP−1)(N3)](ClO4)2 (1), [Co4(H2L−1)2(µ3-1,1,1-N3)2(µ-1,1-N3)2Cl2(CH3OH)2]·4CH3OH (2), [Co2IICo2III(HL−2)2(µ-CH3CO2)2(µ3-OH)2](NO3)2·2CH3CH2OH (3), and [Co2IICo2III (H2L12−)2(THMAM−1)2](NO3)4 (4). In 1, two cobalt(III) ions are connected via three single atom bridges; two from deprotonated ethanolic oxygen atoms in the side arms of the ligands and one from the1-amino-2-propanol moiety forming a dinuclear unit with a very short (2.5430(11) Å) Co-Co intermetallic separation with a coordination number of 7, a rare feature for cobalt(III). In 2, two cobalt(II) ions in a dinuclear unit are bridged through phenoxide O and μ3-1,1,1-N3 azido bridges, and the two dinuclear units are interconnected by two μ-1,1-N3 and two μ3-1,1,1-N3 azido bridges generating tetranuclear cationic [Co4(H2L−1)2(µ3-1,1,1-N3)2(µ-1,1-N3)2Cl2(CH3OH)2]2+ units with an incomplete double cubane core, which grow into polynuclear 1D-single chains along the a-axis through H-bonding. In 3, HL2− holds mixed-valent Co(II)/Co(III) ions in a dinuclear unit bridged via phenoxide O, μ-1,3-CH3CO2−, and μ3-OH− bridges, and the dinuclear units are interconnected through two deprotonated ethanolic O in the side arms of the ligands and two μ3-OH− bridges generating cationic tetranuclear [Co2IICo2III(HL−2)2(µ-CH3CO2)2(µ3-OH)2]2+ units with an incomplete double cubane core. In 4, H2L1−2 holds mixed-valent Co(II)/Co(III) ions in dinuclear units which dimerize through two ethanolic O (μ-RO−) in the side arms of the ligands and two ethanolic O (μ3-RO−) of THMAM bridges producing centrosymmetric cationic tetranuclear [Co2IICo2III (H2L1−2)2(THMAM−1)2]4+ units which grow into 2D-sheets along the bc-axis through a network of H-bonding. Bulk magnetization measurements on 2 demonstrate that the magnetic interactions are completely dominated by an overall ferromagnetic coupling occurring between Co(II) ions.

The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) is a patient satisfaction survey utilized for hospital reimbursement calculations. It is not, however, considered a valid measure of individual physician performance. The object of this study was to determine if the “Tool to Assess Inpatient Satisfaction with Care from Hospitalists” (TAISCH) instrument could be leveraged to improve patient satisfaction. A pragmatic pre/post study was conducted with adult inpatients admitted to either teaching or non-teaching general internal medicine services at a large mid-western academic medical center. TAISCH surveys were administered to patients (n=192) who were able to identify their hospitalist provider by name or photograph. An intervention consisting of performance cards (n=20) and group reflection sessions (n=13) was carried out. Pre- and post-intervention TAISCH surveys were administered over a period of approximately 18 months. Coinciding pre- and post-intervention HCAHPS scores were also collected. The results show physicians received significantly higher scores following the intervention on “checking for understanding” (4.63 vs. 4.82, p=0.026) and “confidence in provider” (4.45 vs. 4.64, p=0.048). Pre- and post-intervention HCAHPS “Top Box” scores were no different for any of the three doctor communication questions (explain p=0.086, listen p=0.19, courtesy and respect p=0.19). The TAISCH survey, while providing feedback that is more detailed, actionable, and individually attributable than the HCAHPS, is time and resource intensive and appears to be insufficient in isolation to improve patient perceptions of their hospitalist physician.

Professor Michael Larsen, who is a member of the ERN-EYE Ontology Study Group and co-chair of Workgroup on Retinal Rare Eye Diseases (WG1), was inadvertently omitted from the author list in the Acknowledgements section of the original article [1].

Given the need for access to patient-facing materials in multiple languages, this study aimed to develop and pilot test an accurate and understandable translation of CollaboRATE, a three-item patient-reported measure of shared decision-making, for Spanish-speaking patients in the United States (US).We followed the Translate, Review, Adjudicate, Pre-test, Document (TRAPD) survey translation protocol. Cognitive interviews were conducted with Spanish-speaking adults within an urban Massachusetts internal medicine clinic. For the pilot test, all patients with weekday appointments between May 1 and May 29, 2015 were invited to complete CollaboRATE in either English or Spanish upon exit. We calculated the proportion of respondents giving the best score possible on CollaboRATE and compared scores across key patient subgroups.Four rounds of cognitive interviews with 26 people were completed between January and April 2015. Extensive, iterative refinements to survey items between interview rounds led to final items that were generally understood by participants with diverse educational backgrounds. Pilot data collection achieved an overall response rate of 73 percent, with 606 (49%) patients completing Spanish CollaboRATE questionnaires and 624 (51%) patients completing English CollaboRATE questionnaires. The proportion of respondents giving the best score possible on CollaboRATE was the same (86%) for both the English and Spanish versions of the instrument.Our translation method, guided by emerging best practices in survey and health measurement translation, encompassed multiple levels of review. By conducting four rounds of cognitive interviews with iterative item refinement between each round, we arrived at a Spanish language version of CollaboRATE that was understandable to a majority of cognitive interview participants and was completed by more than 600 pilot questionnaire respondents.