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Objectives: To facilitate earlier diagnosis of autoimmune rheumatic diseases (ARDs), we aimed to 1) develop START, a novel multimedia-based symptom appraisal tool for ARDs and 2) pilot test START among established ARD cases and non-ARD controls., Methods: We developed START using a social cognitive theory-based theoretical framework and consensus-based lists of ARDs and manifestations from our previous work. START was revised through reviews by an expert panel of rheumatologists and cognitive debriefing interviews (CDIs) with patients newly referred for assessment of ARDs. We pilot tested START to evaluate its sensitivity, specificity and test-retest reliability in detecting patients with known ARDs., Results: Of the 59 manifestations of ARDs identified from our previous work, 33 reached expert consensus for content validity, 26 were removed because they were non-specific or late features of ARDs. Similar manifestations were grouped, resulting in 19 items. The phrasing and formatting of items in START were revised based on findings from the CDIs with 36 patients and expert panel review. Visual illustrations such as photos and drawings were included to improve comprehension of items in START, using an online platform for implementation. Pilot testing in 145 patients with ARDs, 133 patients with non-ARDs and 155 healthy controls found that the sensitivity, specificity and test-retest reliability in detecting patients with any ARDs were 86.2%, 80.9% and 0.789, respectively., Conclusion: A novel multimedia-based symptom appraisal tool for ARDs was developed, which addresses the limitations of existing tools and exhibited promising sensitivity and specificity in detecting patients with known ARDs., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Cytologically indeterminate thyroid nodules (Bethesda class III or IV) carry a 10-40% risk of malignancy. Diagnostic lobectomies are frequently performed but negative surgeries incur unnecessary costs on the healthcare system, potential complications, and negative impacts on quality of life. Molecular tests (MTs) have been developed to reduce unnecessary surgeries. However, well-validated, high-performance MTs are often expensive, and their cost-effectiveness has not been studied in the Asian population. This study evaluates the rate of unnecessary surgery in the setting without MT (our current practice) and the cost-effectiveness of introducing a commercially available MT for the management of cytologically indeterminate thyroid nodules in a modernized city in Asia. Methods: Management decisions and outcomes of consecutive Bethesda III or IV thyroid nodules in a tertiary endocrine surgery center in Hong Kong were evaluated. Costs of health service provided by the public health system, which covers >90% of healthcare service in the city, were retrieved. A decision tree model was developed to compare the cost-effectiveness in avoiding unnecessary surgeries of current practice versus routine MT from a public healthcare provider's perspective. In our current practice, MT was not available, and patients with indeterminate nodules received either upfront lobectomy, repeat fine needle aspiration cytology (FNAC), or active surveillance. Results: Over a 4-year period, 2157 FNACs were performed. After exclusion, 1957 FNACs were analyzed, and 18.6% were Bethesda III or IV. Thirty-six percent of these cytologically indeterminate nodules received upfront surgery, with 28% having malignancy in final pathology, that is, 72% of surgeries were unnecessary. Routine MT could reduce 82 unnecessary surgeries/year, 26% more than current practice. Routine MT resulted in an incremental cost-effectiveness ratio of Hong Kong dollar (HKD) 49,102 (US dollar [USD] 6314) per unnecessary surgery. Sensitivity analysis showed test cost of MT contributed significantly to incremental cost-effectiveness ratio. Lowering the commercial price of MT to below HKD 8044 (USD 1031) would render routine MT cost-saving. Conclusion: Currently, a high rate of unnecessary surgeries is being performed for cytologically indeterminate thyroid nodules. MT was more effective in reducing unnecessary surgeries than current practice, but at a higher cost. MT will become cost-saving if the test cost could be lowered.

Distal renal tubular acidosis (dRTA) is a significant clinical expression of Sjögren's syndrome (SS). While SS-related dRTA is traditionally linked to impaired H + -ATPase, we report a unique case demonstrating selectively decreased anion exchanger 1 (AE1) expression with preserved H + -ATPase expression. A 16-year-old girl with SS presented with muscle weakness, difficulty in ambulation, and severe hypokalemia. Laboratory studies revealed non-anion gap metabolic acidosis, elevated urinary potassium excretion, and overt proteinuria. Renal histology identified a notably reduced expression of AE1 but normal H + -ATPase in intercalated cells, a previously undescribed finding. Despite high-dose potassium and bicarbonate supplementation, her hypokalemia and metabolic acidosis showed inadequate response; however, the clinical condition improved dramatically following corticosteroid therapy. This case sheds light on an atypical SS-associated dRTA mechanism characterized by selective AE1 impairment, presumed to be mediated by autoantibodies. The discovery accentuates AE1's critical role in SS-induced renal pathology and underscores the efficacy of steroids in the management of SS-related dRTA., Competing Interests: Declarations. Ethics approval and consent to participate: Informed consents from all participants was given before study and the protocol was approved by the Institutional Review Board of CGMH in Taiwan. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

OBJECTIVE: To summarize the content and critically appraise the quality and applicability of recent clinical practice guidelines (CPGs) for nonpharmacological, nonsurgical management of spine pain. DESIGN: Systematic review of CPGs. LITERATURE SEARCH: Six databases and seven guideline clearinghouses. STUDY SELECTION CRITERIA: Included de novo CPGs for nonpharmacological, nonsurgical management of spine pain designed for any primary health care providers, published in English, Arabic, French, or traditional Chinese within the past 12 years. DATA SYNTHESIS: Five reviewers independently appraised the guidelines using AGREE II and AGREE-REX. Interrater agreements were calculated for each domain and the total score of these tools using the intraclass correlation coefficient (2, 1) with absolute agreement. RESULTS: We included 30 CPGs, primarily (90%) developed in Western countries, which contained 404 recommendations. High-quality CPGs consistently recommended exercise therapy and multimodal care, encompassing a combination of exercises, mobilization/manipulation, education, alternative medicine, and cognitive-behavioral treatments. Generally, CPGs did not recommend assistive (eg, corsets and orthosis) devices or electro/thermotherapies (eg, therapeutic ultrasound and transcutaneous electrical nerve stimulation). Approximately half of the CPGs demonstrated good methodological quality according to AGREE II, whereas the rest were of poor quality. On the AGREE-REX assessment, one third of the recommendations were of excellent quality. CONCLUSION: Although recent guidelines frequently recommended exercise therapy and multimodal care for the management of spine pain, their recommendations often overlooked demographics and comorbidities. Despite methodological improvements, most CPGs lacked simple clinical applicability and considerations of knowledge users' values. J Orthop Sports Phys Ther 2025;55(1):1-14. Epub 4 November 2024. doi:10.2519/jospt.2024.12729 .

Singapore, located strategically at the meeting point of the Malacca Strait and the South China Sea, has established itself as a global financial and economic hub. Despite its small geographical size, Singapore is home to over 5 million people from diverse cultural backgrounds. The city-state's medical education landscape has evolved significantly over the past century. Originally, Singapore had only one undergraduate medical school, the NUS Yong Loo Lin School of Medicine, established in 1905. Over time, this institution has grown into Singapore's largest and oldest medical school. NUS Medicine's vision centres on developing highly competent, values-driven, and inspired healthcare professionals to transform the practice of medicine and improve health worldwide. A curriculum overhaul in 2020 introduced new educational components to prepare future healthcare professionals for the challenges of Singapore's resilient healthcare system. This includes proficiency in integrated care, collaboration across disciplines, and leveraging AI and data science in clinical decision-making. The introduction of a common curriculum in August 2023 for Medicine, Nursing, Dentistry, and Pharmacy undergraduates further aligns with Singapore's 'Healthier SG' vision, ensuring that graduates are well-equipped to meet the evolving needs of the healthcare landscape. The common curriculum aims to address professional hierarchies and foster interprofessional collaboration among students from diverse academic backgrounds. By promoting frequent interaction and a team-oriented mindset, the curriculum seeks to instil a collective approach to healthcare, emphasising the importance of interprofessional practice in achieving the broader goals of healthcare delivery. This paper describes the reforms that took place and how the challenges were mitigated in a research-intensive top-ranked academic medical institution. This strategic alignment of medical education with national healthcare priorities underscores NUS Medicine's commitment to transforming medical practice and improving health outcomes in Singapore and beyond.

Background: Child abuse in Taiwan is a major societal concern that severely affects the well-being of children. Despite the complexity in detecting abuse, reports of child abuse are increasing, evidenced by a rise in cases and heightened awareness. This study utilizes judicial judgments as a lens to understand the varied interpretations of child abuse by clinical and forensic experts and explores the broader epidemiological trends of such abuse within the declining youth population of Taiwan., Methods: We conducted a retrospective study by analyzing official court judgments on child abuse allegations judged from 2008 to 2022 from the online database of Judicial Yuan. Furthermore, the study analyzed demographic factors, injury patterns, and opinions from various experts., Results: The results reveal that severe criminal cases of child abuse predominantly involve biological fathers as the primary offenders and physical abuse as the most common form of maltreatment. Victims are typically aged less than 5 years, which frequently leads to an unfavorable prognosis. Analysis also highlights the TEN-4-FACESp acronym as a highly predictive indicator of child abuse and underscores the prevalence of abusive head trauma (AHT). Moreover, the findings emphasize ongoing disparities in opinions between forensic medical examiners and clinical physicians, especially in AHT cases, which potentially influences judicial decisions., Conclusions: In summary, the study reveals ongoing disagreements between forensic medical examiners and clinical physicians, especially in cases of AHT, which may impact judicial decisions. Promoting consensus through interdisciplinary collaboration and improved communication can aid in revealing the truth in child abuse cases., (© 2024. The Author(s).)

Background: Relationship of caffeine intake and consumption of caffeinated beverages, such as tea and coffee, with bone health remains controversial. This study aimed to evaluate whether genetically determined caffeine intake from tea or coffee has causal effects on overall total body bone mineral density (TB-BMD) and fracture. We also assessed the association with TB-BMD in five age strata., Methods: Using two-sample Mendelian randomization approach, summary statistics were retrieved from genome-wide association studies (GWAS)/GWAS meta-analyses of caffeine intake from tea (n = 395 866)/coffee (n = 373 522), TB-BMD (n = 66 628), and fracture (n = 426 795). Inverse variance weighted method was adopted as the main univariable analysis. Multivariable analysis was conducted to evaluate whether the causal effect is independent., Results: In univariable analysis, genetically determined caffeine intake from tea had positive association with overall TB-BMD (per SD increase in genetically determined caffeine intake, beta of TB-BMD [in SD]: 0.166; 95% confidence interval (CI): 0.006-0.326) and inverse association with fracture (OR = 0.79; 95% CI: 0.654-0.954). Genetically determined caffeine intake from coffee was also positively associated with overall TB-BMD (beta = 0.231; 95% CI: 0.093-0.369). The association remained significant after adjustment for smoking in multivariable analysis. Genetically determined caffeine intake from tea or coffee was both positively associated with TB-BMD in the age strata of 45-60 years, but we lacked evidence of association in other strata., Conclusions: Genetically, caffeine intake from tea or coffee may be beneficial to bone health. Due to the ascertainment method of caffeine intake from tea, our study also implied genetically higher tea consumption may improve TB-BMD and lower fracture risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: SARS-CoV-2 posed a threat to children during the early phase of Omicron wave because many patients presented with febrile seizures. The study aimed to investigate predicting factors for acute encephalopathy of children infected by SARS-CoV-2 Omicron variant presenting with febrile seizures., Methods: The retrospective study analyzed data from pediatric patients who visited the emergency department of Chang Gung Memorial Hospital in Taiwan between April and July 2022. We specifically focused on children with COVID-19 who presented with febrile seizures, collecting demographic, clinical, and laboratory data at the pediatric emergency department, as well as final discharge diagnoses. Subsequently, we conducted a comparative analysis of the clinical and laboratory characteristics between patients diagnosed with acute encephalopathy and those with other causes of febrile seizures., Results: Overall, 10,878 children were included, of which 260 patients presented with febrile seizures. Among them, 116 individuals tested positive for SARS-CoV-2 and of them, 14 subsequently developed acute encephalopathy (12%). Those with acute encephalopathy displayed distinctive features, including older age (5.1 vs. 2.6 years old), longer fever duration preceding the first seizure (1.6 vs. 0.9 days), cluster seizure (50% vs. 16.7%), status epilepticus (50% vs. 13.7%) and occurrences of bradycardia (26.8% vs. 0%) and hypotension (14.3% vs. 0%) in the encephalopathy group. Besides, the laboratory findings in the encephalopathy group are characterized by hyperglycemia (mean (95% CI) 146 mg/dL (95% CI 109-157) vs. 108 mg/dL (95% CI 103-114) and metabolic acidosis (mean (95% CI) pH 7.29(95% CI 7.22-7.36) vs. 7.39 (95%CI 7.37-7.41))., Conclusions: In pediatric patients with COVID-19-related febrile seizures, the occurrence of seizures beyond the first day of fever, bradycardia, clustered seizures, status epilepticus, hyperglycemia, and metabolic acidosis should raise concerns about acute encephalitis/encephalopathy. However, the highest body temperature and the severity of leukocytosis or C-reactive protein levels were not associated with poor outcomes., (© 2024. The Author(s).)

Background/purpose: Fibroblast growth factor (FGF) 5 is a member of the FGF family that functions as a regulator of tissue growth and regeneration. Aberrant FGF5 expression has been previously associated with the progression of a number of different malignancies. However, its potential role in oral cancer remains unclear. In this study, we explored the relationship between the expression of FGF5 protein in oral squamous cell carcinomas (OSCCs) and the clinicopathological parameters of OSCCs and whether the expression of FGF5 protein in OSCCs could be a prognostic factor for OSCC patients., Methods: The FGF5 protein expression was examined in 64 OSCC and 34 normal oral mucosal specimens by immunohistochemical staining. Stress induced upregulation and intracellular redistribution of FGF5 were verified using xenograft animal model and OSCC cell lines., Results: The mean FGF5 protein labelling index was significantly higher in OSCC than in normal oral mucosal samples, with high FGF5 protein labelling index (>58%) being correlated with advanced stage and poor survival of OSCC patients. Apart from the peri-cytoplasmic staining pattern characteristic of paracrine growth factors, FGF5 protein was localized as distinct punctate structures in the cytoplasm of advanced stage or stressed-induced cells. This redistribution and upregulation of FGF5 protein could be sustained after termination of the stress induction in cell line and xenograft animal models., Conclusion: FGF5 can be induced by cellular stress and risk factors of OSCC, where high expression levels of FGF5 is potentially a useful parameter for predicting OSCC progression and patient survival., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: This study explores interprofessional collaboration amongst healthcare professionals in patient education., Methods: A systematic review was conducted. A search in seven databases was conducted from 2011 to 2022 and screened against the inclusion criteria. Quality appraisal was done independently by two reviewers. Studies were extracted and synthesised using the data-based convergent synthesis design., Results: Twenty-one studies were included. Five themes on factors affecting interprofessional collaboration in patient education emerged: 1) role clarification, 2) communication infrastructure, 3) shared space for collaboration, 4) interprofessional trust, and 5) organisational support., Conclusion: Findings highlighted the importance of developing trustful relationships within the multidisciplinary team in delivering patient education. Channels for additional infrastructural support, guidelines and training in patient education delivery is required. Future research could explore patients' perspectives on how their learning needs in patient education may be optimised through a multidisciplinary approach., Practice Implications: Healthcare leaders could promote shared goals within the team by facilitating a common space and time for interprofessional team rounding, and by developing shared patient education resources and documentation processes. Interprofessional education focusing on the delivery of team-based patient education could be implemented to foster understanding of the interdependent role of multidisciplinary healthcare professionals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: Social cognitive theory (SCT) has been successfully employed to improve symptom appraisal and help-seeking among patients with various conditions but is yet to be applied in the context of autoimmune rheumatic diseases (ARDs). This study aimed to explore the applicability of SCT in and possible approaches to improving symptom appraisal and help-seeking of patients with ARDs, one of the key barriers to earlier diagnosis., Methods: Semi-structured interviews were conducted with 33 ARD patients with a prolonged pre-diagnosis interval (>3 months). We coded the transcripts deductively using SCT as the overarching framework and inductively for approaches identified from the interviews., Results: All six main concepts of SCT (behavioral capacity, expectations, self-efficacy, observational learning, reinforcements, and reciprocal determinism) were observed in the three stages of symptom appraisal and help-seeking (detection, interpretation, and response) of patients with ARDs. While many participants reported that they were able and confident to detect their symptoms, they lacked the behavioral capacity and self-efficacy to interpret symptoms correctly, which resulted in delayed help-seeking and diagnosis. Possible approaches to address this suggested by participants (such as education of the general population) could improve behavioral capacity and self-efficacy in symptom interpretation and enhance expectations, observational learning, reinforcements, and reciprocal determinism in symptom response., Conclusion: Lack of behavioral capacity and self-efficacy was observed in symptom interpretation of patients with ARDs, which resulted in delayed help-seeking. Approaches could target the behavioral capacity and self-efficacy for symptom interpretation to facilitate early help-seeking and, in turn, earlier diagnosis among individuals with possible ARDs., (© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Hemodialysis patients have a markedly increased risk of cardiovascular (CV) morbidity and mortality. Oxidative stress plays a pathogenic role in the progression of atherosclerosis and CV disease among chronic hemodialysis patients. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) content in leukocyte deoxyribonucleic acid (DNA) has been shown as a sensitive and well-known biomarker of oxidant-induced DNA damage in chronic hemodialysis patients., Methods: We conducted a retrospective cohort study to investigate the association of leukocyte 8-OHdG and CV events and deaths in patients of chronic hemodialysis. In this study, 217 chronic hemodialysis patients were recruited from 2016 to 2021. The 8-OHdG content of leukocyte DNA was measured by a high-performance liquid chromatography electrochemical detection method. Study outcomes were CV events as well as CV and all-cause deaths. The patients were followed until May 2021., Results: The median follow-up period was 34.8 months. At the end of May 2021, 57 first CV events and 89 all-CV events occurred. Among the first and all CV events, 17 (29.8%) and 32 (36.0%) were fatal, respectively. Multivariate Cox regression analysis showed per 1/10 5 dG increment in leukocyte 8-OHdG values increased risk of CV events (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.10-1.41; p < 0.001), CV death (aHR, 1.27; 95% CI, 1.03-1.72; p = 0.034), and all-cause death (aHR, 1.11; 95% CI, 1.01-1.30; p = 0.038)., Conclusion: This is the first study to demonstrate that oxidative stress assessed by 8-OHdG levels of leukocyte DNA predicted CV events as well as CV and all-cause deaths among chronic hemodialysis patients., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: A substantial proportion of individuals with COVID-19 experienced cognitive impairment after resolution of SARS-CoV-2 infection. We aimed to evaluate whether genetic liability to SARS-CoV-2 infection per se , or more severe COVID-19, is causally linked to cognitive deficit., Methods: We firstly performed univariable Mendelian randomization (MR) analysis to examine whether genetic liability to SARS-CoV-2 infection, hospitalized and severe COVID-19 is causally associated with cognitive performance. To dissect the causal pathway, multivariable MR (MVMR) analysis was conducted by adjusting for five inflammatory markers [C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, and tumour necrosis factor α, as proxies of systemic inflammation]., Results: In univariable MR analysis, host genetic liability to SARS-CoV-2 infection was associated with lower cognitive performance [inverse variance weighted (IVW) analysis, estimate: -0.023; 95% Confidence Interval (CI): -0.038 to -0.009]. Such causal association was attenuated in MVMR analysis when we adjusted for the five correlated inflammatory markers in one analysis (IVW analysis, estimate: -0.022; 95% CI: -0.049 to 0.004). There was insufficient evidence of association for genetic liability to hospitalized and severe COVID-19 with cognitive performance., Conclusion: The causal effect of host genetic liability to SARS-CoV-2 infection on reduced cognitive performance may be mediated by systemic inflammation. Future studies examining whether anti-inflammatory agents could alleviate cognitive impairment in SARS-CoV-2-infected individuals are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tang, Li and Cheung.)

Objective: Long diagnostic delay remains an unsolved problem in many autoimmune rheumatic diseases (ARDs). One of the major contributing factors is poor symptom appraisal and the resulting delays in help-seeking by patients themselves. We therefore aimed to understand the symptom appraisal and help-seeking experience among patients with ARDs in a multiethnic urban Asian population and to explore its influencing factors., Methods: Semistructured interviews with 33 patients with ARDs were audio recorded and transcribed verbatim. We coded the transcripts deductively using the reported 3 stages of symptom appraisal (detection, interpretation, and response) as the framework, and inductively for newly emerging themes and subthemes., Results: All 3 stages of the symptom appraisal and help-seeking journey (ie, symptom detection [by self and by others], symptom interpretation [causes, consequences, and required actions] and symptom response [no action, self-management, seeking help from nonhealthcare professionals, and seeking help from healthcare professionals]) were observed among patients. Interactions among these 3 stages were also observed: symptom interpretation was found to influence subsequent symptom detection, and the outcome of symptom response was found to influence both subsequent symptom detection and symptom interpretation. Various personal and socioenvironmental factors (eg, knowledge and cultural beliefs about the symptom) that influenced symptom appraisal and help-seeking were identified from the interviews., Conclusion: The symptom appraisal and help-seeking journey of patients with ARDs is an iterative process of detection, interpretation, and response, and is influenced by various personal and socioenvironmental factors. Addressing modifiable factors could shorten the symptom appraisal and help-seeking interval and improve patient outcomes.

Importance: Endovascular treatment is not recommended for aortic pathologies in patients with connective tissue diseases (CTDs) other than in redo operations and as bridging procedures in emergencies. However, recent developments in endovascular technology may challenge this dogma., Objective: To assess the midterm outcomes of endovascular aortic repair in patients with CTD., Design, Setting, and Participants: For this descriptive retrospective study, data on demographics, interventions, and short-term and midterm outcomes were collected from 18 aortic centers in Europe, Asia, North America, and New Zealand. Patients with CTD who had undergone endovascular aortic repair from 2005 to 2020 were included. Data were analyzed from December 2021 to November 2022., Exposure: All principal endovascular aortic repairs, including redo surgery and complex repairs of the aortic arch and visceral aorta., Main Outcomes and Measures: Short-term and midterm survival, rates of secondary procedures, and conversion to open repair., Results: In total, 171 patients were included: 142 with Marfan syndrome, 17 with Loeys-Dietz syndrome, and 12 with vascular Ehlers-Danlos syndrome (vEDS). Median (IQR) age was 49.9 years (37.9-59.0), and 107 patients (62.6%) were male. One hundred fifty-two (88.9%) were treated for aortic dissections and 19 (11.1%) for degenerative aneurysms. One hundred thirty-six patients (79.5%) had undergone open aortic surgery before the index endovascular repair. In 74 patients (43.3%), arch and/or visceral branches were included in the repair. Primary technical success was achieved in 168 patients (98.2%), and 30-day mortality was 2.9% (5 patients). Survival at 1 and 5 years was 96.2% and 80.6% for Marfan syndrome, 93.8% and 85.2% for Loeys-Dietz syndrome, and 75.0% and 43.8% for vEDS, respectively. After a median (IQR) follow-up of 4.7 years (1.9-9.2), 91 patients (53.2%) had undergone secondary procedures, of which 14 (8.2%) were open conversions., Conclusions and Relevance: This study found that endovascular aortic interventions, including redo procedures and complex repairs of the aortic arch and visceral aorta, in patients with CTD had a high rate of early technical success, low perioperative mortality, and a midterm survival rate comparable with reports of open aortic surgery in patients with CTD. The rate of secondary procedures was high, but few patients required conversion to open repair. Improvements in devices and techniques, as well as ongoing follow-up, may result in endovascular treatment for patients with CTD being included in guideline recommendations.

Background: Interprofessional communication is needed to enhance the early recognition and management of patients with sepsis. Preparing medical and nursing students using virtual reality simulation has been shown to be an effective learning approach for sepsis team training. However, its scalability is constrained by unequal cohort sizes between medical and nursing students. An artificial intelligence (AI) medical team member can be implemented in a virtual reality simulation to engage nursing students in sepsis team training., Objective: This study aimed to evaluate the effectiveness of an AI-powered doctor versus a human-controlled doctor in training nursing students for sepsis care and interprofessional communication., Methods: A randomized controlled trial study was conducted with 64 nursing students who were randomly assigned to undertake sepsis team training with an AI-powered doctor (AI-powered group) or with medical students using virtual reality simulation (human-controlled group). Participants from both groups were tested on their sepsis and communication performance through simulation-based assessments (posttest). Participants' sepsis knowledge and self-efficacy in interprofessional communication were also evaluated before and after the study interventions., Results: A total of 32 nursing students from each group completed the simulation-based assessment, sepsis and communication knowledge test, and self-efficacy questionnaire. Compared with the baseline scores, both the AI-powered and human-controlled groups demonstrated significant improvements in communication knowledge (P=.001) and self-efficacy in interprofessional communication (P<.001) in posttest scores. For sepsis care knowledge, a significant improvement in sepsis care knowledge from the baseline was observed in the AI-powered group (P<.001) but not in the human-controlled group (P=.16). Although no significant differences were found in sepsis care performance between the groups (AI-powered group: mean 13.63, SD 4.23, vs human-controlled group: mean 12.75, SD 3.85, P=.39), the AI-powered group (mean 9.06, SD 1.78) had statistically significantly higher sepsis posttest knowledge scores (P=.009) than the human-controlled group (mean 7.75, SD 2.08). No significant differences were found in interprofessional communication performance between the 2 groups (AI-powered group: mean 29.34, SD 8.37, vs human-controlled group: mean 27.06, SD 5.69, P=.21). However, the human-controlled group (mean 69.6, SD 14.4) reported a significantly higher level of self-efficacy in interprofessional communication (P=.008) than the AI-powered group (mean 60.1, SD 13.3)., Conclusions: Our study suggested that AI-powered doctors are not inferior to human-controlled virtual reality simulations with respect to sepsis care and interprofessional communication performance, which supports the viability of implementing AI-powered doctors to achieve scalability in sepsis team training. Our findings also suggested that future innovations should focus on the sociability of AI-powered doctors to enhance users' interprofessional communication training. Perhaps in the nearer term, future studies should examine how to best blend AI-powered training with human-controlled virtual reality simulation to optimize clinical performance in sepsis care and interprofessional communication., Trial Registration: ClinicalTrials.gov NCT05953441; https://clinicaltrials.gov/study/NCT05953441., (©Sok Ying Liaw, Jian Zhi Tan, Khairul Dzakirin Bin Rusli, Rabindra Ratan, Wentao Zhou, Siriwan Lim, Tang Ching Lau, Betsy Seah, Wei Ling Chua. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 26.07.2023.)

Significant lifetime enhancement, up to an eight-fold increase in T 90 , has been demonstrated in blue organic light-emitting diode (OLED) devices through the deuteration of host and hole transport materials. We observed a progressive increase in T 90 using a series of anthracene-based hydrocarbon hosts with incremental deuteration in the emitting layer. In addition, we realized further lifetime improvement using a deuterated hole-transport layer along with the deuterated emitting layer. To elucidate the deuteration effects, we utilized laser desorption/ionization-time-of-flight (LDI-TOF) mass spectrometry for in situ UV irradiation to induce photodegradation and immediate chemical analysis of the resultant photodegradation species. Adducts between the host and moieties from transport materials were identified in UV-degraded films comprising a mixture of host and transport materials, indicating that similar species could be produced in OLED devices using these materials. Deuteration, in effect, mediated the formation of these adduct species, presumably electroluminescence quenchers, and thus improved the device lifetime. An approximate agreement was obtained between the kinetic isotope effect of the photodegradation reactions and the enhancement in device lifetime with deuteration.

Early detection and treatment of osteoporosis can help to prevent debilitating fractures in the elderly. The osteoporosis self-assessment tool for Asians can be used as a screening tool to stratify patients for bone densitometry. It is most cost-effective for post-menopausal women aged 70 and males aged 75., Purpose: To determine the cost-effectiveness of selective bone densitometry (SBD) using the Osteoporosis Self-Assessment Tool for Asians (OSTA) as a risk-stratifying tool for the three predominant races (Chinese, Malay and Indian) in Singapore., Methods: Decision analytical models were developed using a Markov model. Three scenarios were compared: no bone densitometry, SBD using the OSTA as a pre-screening tool and universal bone densitometry. Those diagnosed with osteoporosis were treated with five years of alendronate therapy. Data sources were from Singapore epidemiological studies, healthcare cost figures and published literature. Measurements include life years, quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratios (ICER)., Results: Compared to no bone densitometry, SBD using the OSTA would cost between $40,679 and $73,909 per QALY gained for men aged 75-80 and $22,386 to $58,185 per QALY gained for post-menopausal women aged 70-80. Universal bone densitometry would cost $157,955 to $177,127 per QALY gained for men aged 75-80 and $40,179 to $66,112 per QALY gained for post-menopausal women aged 70 to 80 compared to SBD., Conclusion: In general, osteoporosis screening was the most cost-effective for Malays and the least cost-effective for Indians. However, a general guideline should still be applied to the Singaporean population, as further explained later. Overall, the most cost-effective strategy for males would be using OSTA as a risk-stratifying tool at age 75. For post-menopausal women, SBD should be used for women aged 70, while universal bone densitometry should be used for women aged 75-80., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Aim: To consolidate the evidence around the experiences of nursing undergraduates and faculty members navigating through remote and online education during the COVID-19 pandemic., Background: The Coronavirus disease 2019 caused by the SARS-CoV-2 Virus (COVID-19) has placed massive pressure on healthcare, economic and education systems globally. Restrictive social distancing policies and public health measures necessitated educational institutions to switch from face-to-face to remote and online education to sustain the learning process. These changes have created an uncertain path and undue stress for healthcare learners and faculty, especially for professional roles that traditionally require more hands-on and access to clinical practice particularly pre-licensure nursing students. As such, there is an urgent need to consolidate evidence on the experiences of nursing undergraduates and faculty members as they navigate the rapid transition from face-to-face to remote and online education to ensure continuity of learning in achieving optimal learning outcomes and to support them during current and future public health crises., Design: A systematic review and meta-synthesis of the qualitative literature was undertaken using Sandelowski and Barroso's approach., Methods: Six electronic databases, CINAHL, Embase, ERIC, PsycINFO, PubMed and Scopus, were searched systematically using the eligibility criteria from December 2019 to September 2022. The Critical Appraisal Skills Program checklist for qualitative studies was used to conduct the critical appraisal of the selected articles., Results: Forty-seven studies were included in this review, which encapsulates the experiences of 3052 undergraduates and 241 faculty members. An overarching meta-theme 'Remote and online education: a rollercoaster ride', emerged along with three main meta-themes: (1) Transition to remote and online education: A turbulent road, (2) Acceptance of the untravelled road, (3) Hopes and recommendations for the road ahead., Conclusion: To improve nursing undergraduates' and faculty member's navigation of remote and online education, more institutions should move towards establishing hybrid education as the new 'normal' and exercise prudence in the organisation and delivery of curriculum, teaching, well-being and clinical attachment contingencies of their healthcare courses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Thyroid dysfunction has been observed among some patients with coronavirus disease (COVID-19). It is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (or its severity) leads to the development of thyroid dysfunction, or vice versa. In this study, we examined the bi-directional causal relationship between host genetic liability to three COVID-19 phenotypes (including SARS-CoV-2 infection, hospitalized and severe COVID-19) and three thyroid dysfunction traits (including hyperthyroidism, hypothyroidism, and autoimmune thyroid disease [AITD]) and three continuous traits of thyroid hormones (including thyrotropin [TSH] and free thyroxine [fT4] within reference range, and TSH in full range). Methods: Summary statistics from the largest available meta-analyses of human genome-wide association studies were retrieved for the following variables: SARS-CoV-2 infection ( n  = 1,348,701), COVID-19 hospitalization ( n  = 1,557,411), severe COVID-19 ( n  = 1,059,456), hyperthyroidism ( n  = 51,823), hypothyroidism ( n  = 53,423), AITD ( n  = 755,406), TSH within reference range ( n  = 54,288), fT4 within reference range ( n  = 49,269), and TSH in full range ( n  = 119,715). Using a two-sample Mendelian randomization (MR) approach, the inverse-variance weighted (IVW) method was adopted as the main MR analysis. Weighted median, contamination mixture, MR-Egger, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods were applied as sensitivity analyses. Results: Host genetic susceptibility to SARS-CoV-2 infection was causally associated with hypothyroidism in the main IVW analysis (per doubling in prevalence of SARS-CoV-2 infection, odds ratio [OR] = 1.335; 95% confidence interval [CI]: 1.167-1.526; p  = 2.4 × 10 -5 , surpassing the Bonferroni multiple-testing threshold). Similar causal estimates were observed in the sensitivity analyses (weighted median: OR = 1.296; CI: 1.066-1.575; p  = 9 × 10 -3 ; contamination mixture: OR = 1.356; CI: 1.095-1.818; p  = 0.013; MR-Egger: OR = 1.712; CI: 1.202-2.439; p  = 2.92 × 10 -3 , and MR-PRESSO: OR = 1.335; CI: 1.156-1.542; p  = 5.73 × 10 -4 ). Host genetic liability to hospitalized or severe COVID-19 was not associated with thyroid dysfunction or thyroid hormone levels. In the reverse direction, there was no evidence to suggest that genetic predisposition to thyroid dysfunction or genetically determined thyroid hormone levels altered the risk of the COVID-19 outcomes. Conclusions: This bi-directional MR study supports that host response to SARS-CoV-2 viral infection plays a role in the causal association with increased risk of hypothyroidism. Long-term follow-up studies are needed to confirm the expected increased hypothyroidism risk.

Objectives: Poor symptom appraisal (detection, interpretation and response to symptoms) plays a major role in prolonged prediagnosis interval in various health conditions. Theories and models have been proposed to study the symptom appraisal process but how they could be employed to improve symptom appraisal remains unclear. We therefore aimed to review approaches to improving symptom appraisal in the literature and to develop a theoretical framework that could guide the development of approaches to improving symptom appraisal among individuals in the general population., Design: Systematic review., Data Sources: Medline, Web of Science, PsycINFO, Embase, CINAHL and Scopus were searched from inception to 30 March 2021., Eligibility Criteria: We included original articles in English in which approaches to improve the detection, interpretation or response to symptoms for symptomatic individuals were described. We excluded articles in which approaches were developed to improve symptom appraisal among healthcare professionals., Data Extraction and Synthesis: A predefined data extraction form was used to extract the development, characteristics and evaluation of approaches to improving symptom appraisal. This formed the basis for the narrative synthesis., Results: Of 19 046 publications identified from the literature search, 112 were selected for full-text review and 29 approaches comprising provision of knowledge of symptoms/signs and additional components (eg, symptom self-examination and comparison) for symptom appraisal were included in the synthesis. Less than half (41.4%) of these approaches were developed based on theories/models. Interestingly, despite the variety of theories/models adopted in developing these approaches, the components of these approaches were similar., Conclusion: Symptom appraisal is an essential process in a patient's journey that can be targeted to facilitate early diagnosis but is largely unstudied. Building on the literature, we proposed a theoretical framework and approaches to improving symptom appraisal. This could facilitate early identification of a variety of health conditions in the general population., Trial Registration Number: CRD42021279500., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Metastasis is the principal cause of breast cancer mortality. Vaccines targeting breast cancer antigens have yet to demonstrate clinical efficacy, and there remains an unmet need for safe and effective treatment to reduce the risk of metastasis, particularly for people with triple-negative breast cancer (TNBC). Certain glycolipids can act as vaccine adjuvants by specifically stimulating natural killer T (NKT) cells to provide a universal form of T-cell help., Methods: We designed and made a series of conjugate vaccines comprising a prodrug of the NKT cell-activating glycolipid α-galactosylceramide covalently linked to tumor-expressed peptides, and assessed these using E0771- and 4T1-based breast cancer models in vivo . We employed peptides from the model antigen ovalbumin and from clinically relevant breast cancer antigens HER2 and NY-ESO-1., Results: Glycolipid-peptide conjugate vaccines that activate NKT cells led to antigen-presenting cell activation, induced inflammatory cytokines, and, compared with peptide alone or admixed peptide and α-galactosylceramide, specifically enhanced CD8 + T-cell responses against tumor-associated peptides. Primary tumor growth was delayed by vaccination in all tumor models. Using 4T1-based cell lines expressing HER2 or NY-ESO-1, a single administration of the relevant conjugate vaccine prevented tumor colonisation of the lung following intravenous inoculation of tumor cells or spontaneous metastasis from breast, respectively., Conclusion: Glycolipid-peptide conjugate vaccines that activate NKT cells prevent lung metastasis in breast cancer models and warrant investigation as adjuvant therapies for high-risk breast cancer., Competing Interests: IH and GP are inventors on patents licensed to or owned by biotech start‐up Avalia Immunotherapies Limited., (© 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Full-spectrum flow cytometry is now routinely used in many laboratories internationally, and the demand for this technology is rapidly increasing. With capacity to use larger and more complex staining panels, standardized protocols are required for optimal panel design and analysis. Importantly, for ex vivo analysis, tissue preparation methods also need to be optimized to ensure samples are truly representative of tissues in situ. This is particularly relevant given the recent interest in adaptive immune cells that form residency in specific organs. Here we provide optimized protocols for tissue processing and phenotyping of memory T cells and natural killer T (NKT) cell subsets from liver, lung, spleen, and lymph node using full-spectrum flow cytometry. We provide a 21-color antibody panel for identification of different memory subsets, including tissue-resident memory T (T RM ) cells, which are increasingly regarded as important effectors in adaptive immunity. We show that processing procedures can affect outcomes, with liver T RM cells particularly sensitive to heat, such that accurate evaluation requires fast processing at defined temperatures. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Processing mouse liver for flow cytometric analysis of memory T and NKT cell subsets Basic Protocol 2: Processing mouse spleen for flow cytometric analysis of memory T and NKT cell subsets Basic Protocol 3: Processing mouse lungs for flow cytometric analysis of memory T and NKT cell subsets Basic Protocol 4: Processing mouse lymph nodes for flow cytometric analysis of memory T and NKT cell subsets Basic Protocol 5: Staining and flow cytometric analysis of samples for memory T and NKT cell subsets Support Protocol: Obtaining cell counts from flow cytometry data., (© 2022 Wiley Periodicals LLC.)

In this paper, we consider a stochastic optimization model for a surgical scheduling problem with a single operating room. The goal is to determine the optimal start times of multiple elective surgeries within a single day. The term "optimal" is defined as the largest surgically related utility value while achieving a given threshold defined by the performance variation of a reference solution. The optimization problem is analytically intractable because it involves quantities such as expectation and variance formulations. This implies that traditional mathematical programming techniques cannot be directly applied. We propose a decision support algorithm, which is a fully sequential procedure using variance screening in the first phase, and then employing multiple attribute utility theory to select the best solution in the second phase. The numerical experiments show that the proposed algorithm can find a promising solution in a reasonable amount of time., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Improving interprofessional communication and collaboration is necessary to facilitate the early identification and treatment of patients with sepsis. Preparing undergraduate medical and nursing students for the knowledge and skills required to assess, escalate, and manage patients with sepsis is crucial for their entry into clinical practice. However, the COVID-19 pandemic and social distancing measures have created the need for interactive distance learning to support collaborative learning., Objective: This study aimed to evaluate the effect of sepsis interprofessional education on medical and nursing students' sepsis knowledge, team communication skills, and skill use in clinical practice., Methods: A mixed methods design using a 1-group pretest-posttest design and focus group discussions was used. This study involved 415 undergraduate medical and nursing students from a university in Singapore. After a baseline evaluation of the participants' sepsis knowledge and team communication skills, they underwent didactic e-learning followed by virtual telesimulation on early recognition and management of sepsis and team communication strategies. The participants' sepsis knowledge and team communication skills were evaluated immediately and 2 months after the telesimulation. In total, 4 focus group discussions were conducted using a purposive sample of 18 medical and nursing students to explore their transfer of learning to clinical practice., Results: Compared with the baseline scores, both the medical and nursing students demonstrated a significant improvement in sepsis knowledge (P<.001) and team communication skills (P<.001) in immediate posttest scores. At the 2-month follow-up, the nursing students continued to have statistically significantly higher sepsis knowledge (P<.001) and communication scores (P<.001) than the pretest scores, whereas the medical students had no significant changes in test scores between the 2-month follow-up and pretest time points (P=.99). A total of three themes emerged from the qualitative findings: greater understanding of each other's roles, application of mental models in clinical practice, and theory-practice gaps. The sepsis interprofessional education-particularly the use of virtual telesimulation-fostered participants' understanding and appreciation of each other's interprofessional roles when caring for patients with sepsis. Despite noting some incongruities with the real-world clinical practice and not encountering many sepsis scenarios in clinical settings, participants shared the application of mental models using interprofessional communication strategies and the patient assessment framework in their daily clinical practice., Conclusions: Although the study did not show long-term knowledge retention, the use of virtual telesimulation played a critical role in facilitating the application of mental models for learning transfer and therefore could serve as a promising education modality for sepsis training. For a greater clinical effect, future studies could complement virtual telesimulation with a mannequin-based simulation and provide more evidence on the long-term retention of sepsis knowledge and clinical skills performance., (©Wei Ling Chua, Sim Leng Ooi, Gene Wai Han Chan, Tang Ching Lau, Sok Ying Liaw. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 18.04.2022.)

Background: The development of interprofessional competencies through an evidence-based program is paramount to nurture a collaborative practice-ready workforce for patient-centered care and safety., Aims: To describe an implementation science approach for translation of an evidence-based virtual reality simulation-based interprofessional education (VR-Sim-IPE) program into medical and nursing curriculums, and to evaluate the implementation outcomes., Methods: Implementation strategies from the "Expert Recommendations for Implementing Change" were used to support implementation of the VR-Sim-IPE program. This included recruiting and training 28 practicing clinicians as facilitators to deliver the program to 599 medical and nursing students. Proctor's conceptual framework for implementation outcomes was applied with multiple data collection methods to evaluate the VR-Sim-IPE program. An online survey was administered to measure the levels of acceptability, appropriateness, feasibility, and adoption. Forty-four sessions of structured observations were carried out to examine the facilitators' implementation fidelity. Individual interviews were conducted with 15 facilitators to identify the facilitators and barriers to the program implementation. An implementation cost analysis was also conducted., Results: Both facilitators and students had positive perceptions of the acceptability, adoption, appropriateness, and feasibility of the VR-Sim-IPE program. Facilitators were observed to implement the program with high fidelity, including program adherence, dosage, quality of delivery, and student responsiveness. While opportunities to contribute and learn, as well as receiving training and support, were identified as facilitators to implementation, the lack of familiarity with the virtual environment, varying levels of student participation, and facilitating interprofessional groups were reported barriers. The implementation costs amounted to USD45,648.50., Conclusion: The evaluation of implementation outcomes identifies strategies for future implementation that could potentially enhance program acceptance, reduce implementation cost, improve penetration, and achieve program sustainability. These include increasing facilitation group size, preparing students to be active participants, and incorporating interprofessional facilitation skills in facilitators' training., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Early exposure to formula milk increases the likelihood of cow's milk sensitization and food allergies in the later childhood. However, the underlying mechanisms are multifactorial and unclear. Fifty-five children from a follow-up birth cohort study were grouped into exclusive breastfeeding (EBF, n = 33) and formula feeding (EFF, n = 22) in the first six months of life. Urinary metabolites were longitudinally assessed and analyzed at 6 months, 1, and 2 years of age using 1 H-nuclear magnetic resonance (NMR) spectroscopy. Integrated analysis of metabolic profiling associated with formula feeding and milk sensitization related to IgE reactions was also investigated. Twenty-two metabolites were significantly obtained in the EFF set at age 0.5, whereas nine metabolites were predominantly obtained in the milk sensitization set at age 1. A subsequent analysis of metabolic change from 6 months to age 1 identified eight metabolites, including 3-methyl-2-oxovaleric acid, glutarate, lysine, N-phenylacetylglycine, N,N-dimethylglycine, 3-indoxysulfate, 2-oxoglutaric acid, and pantothenate associated with formula feeding and milk sensitization with same trend variation. Among them, 3-indoxysulfate, N-phenylacetylglycine, and N,N-dimethylglycine were gut microbial-derived without IgE association. By contrast, 3-methyl-2-oxovaleric acid, glutarate, and lysine were IgE related associated with formula feeding contributing to milk sensitization ( p < 0.05). Longitudinal urinary metabolomic analysis provides molecular insight into the mechanism of formula feeding associated with milk sensitization. Gut microbial-derived metabolites associated with formula feeding and IgE associated metabolites related to branched-chain amino acid metabolism play roles in developing sensitization and allergic symptoms in response to formula feeding.

Background: In an age disrupted by COVID-19 pandemic, three-dimensional virtual world (3DVW) offers an opportunity for healthcare students from different higher education institutions to participate in interprofessional education. Despite its growing evidence, there is a need to unravel the complex learning process in order to ensure high quality of interprofessional education delivery., Aim: This study aimed to explore the experiences of healthcare students and facilitators on the use of 3DVW for interprofessional team-based virtual simulation., Methods: Interprofessional teams, each comprising six different healthcare students (Medicine, Nursing, Pharmacy, Physiotherapy, Occupational Therapy, and Medical Social Work) and two clinicians who acted as facilitators, logged into the 3DVW from their own remote locations to participate in team-based care delivery that included an interprofessional bedside round and a family conference. A qualitative descriptive study was conducted on a purposive sample of 30 healthcare students and 12 facilitators using focus group discussions and individual interviews., Results: Four themes emerged from their experiences: the "wow experience", authentic experience on collaborative care, ease of learning, and preeminent role of the facilitator. The simulation provided the "wow" experiences through contextual, collaborative and experiential learning approaches. Despite technical challenges, the participants were wooed by the comforts of learning from home and the psychological safety in virtual environment. The facilitators played a critical role in optimizing learning engagement to win learners over., Conclusion: Our study explicates how attention to the "wow, woo and win" trilateral factors can transform the interprofessional learning experiences offered by 3DVW simulation. Future developments in the use of this learning technology should include developing the clinicians' facilitation skills and the provision of technical support to make this 3DVW a success calls in winning students' learning engagement., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Rheumatoid arthritis (RA) is a major health burden in Asia Pacific affecting the quality of life of patients and consuming healthcare resources. According to recent estimates from the World Health Organization-International League Against Rheumatism-Community Oriented Program for Control of Rheumatic Diseases, prevalence is around 0.3%-0.5%. Management guidelines have helped to improve treatment across this diverse region. To gain better insight into current real-world management applications in view of these guidelines, virtual meetings were conducted in mid-2020 to explore perspectives of rheumatologists and patients, as well as discuss the impact of coronavirus disease 2019 on RA management. Patients and rheumatologists from Hong Kong, Malaysia, Singapore, the Philippines, Thailand, India, Pakistan, and Taiwan were included, representing a diverse mix of healthcare systems, wealth, ethnicity and culture. Despite many countries having prospered in recent years, similar challenges in RA diagnosis and treatment were identified. The daily impact and patient experience of RA were also similar across countries, marked by "silent" pain and disability, and universal misunderstanding of the disease. Late diagnosis and treatment, and barriers to access to appropriate treatment, remain problematic. The experience shared by Taiwan offers a glimmer of hope, however, wherein patient advocacy groups have succeeded in being included in policy-making decisions and securing access to advanced treatment. Real-world solutions that pay heed to the unique local needs and diversity of Asia Pacific are required to improve RA management, which will take time. In the interim, help can be sought from the trained, non-rheumatologist community to reduce some of the disease burden., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

The COVID-19 pandemic has significantly disrupted medical education, particularly affecting clinical-year students. Educational institutions often had to halt, shorten or impose significant restrictions on their hospital rotations due to strict infection control and social-distancing guidelines implemented in tertiary healthcare institutions, as well as manpower and logistical constraints amid the pandemic. Thus, distance-based learning platforms such as online lectures and case-based teaching were increasingly adopted in place of bedside and face-to-face tutorials. While interactive virtual case-based discussions are generally useful in imparting clinical reasoning skills to medical students, they are unfortunately not able to fully replicate the experience of clerking, examining and managing real patients in the wards, which is a quintessential process towards building clinical acumen and attaining core clinical competencies. Therefore, for final year medical students who are preparing for their Bachelor of Medicine and Bachelor of Surgery (MBBS) examinations, many are naturally concerned by how learning in this "new normal" may affect their ability to make the transition to become competent junior doctors. As such, we seek to share our learning experiences as the first batch of medical students to have completed our entire final year of clinical education amid the COVID-19 pandemic, and offer 4 practical suggestions to future batches of students on how to adapt and optimise clinical learning under these circumstances: actively engaging in virtual learning, making the most of every clinical encounter, learning how to construct peer teaching/practice sessions, and maintaining physical and psychological well-being.

Aim: The interval between symptom onset and diagnosis (pre-diagnosis interval) can at times be longer than is ideal in patients with autoimmune rheumatic diseases (ARDs). In this study, we aimed to characterize this interval and to identify its associated factors., Method: We characterized pre-diagnosis interval into 4 intervals: Interval #1 between symptom onset and first visit to healthcare professionals; Interval #2 between first visit to healthcare professionals and rheumatology referral; Interval #3 between rheumatology referral and first rheumatology assessment; and Interval #4 between first rheumatology assessment and diagnosis. Median regression models were used to identify factors associated with longer pre-diagnosis interval and Interval #1., Results: Among 259 patients (median age = 52.0 [41.6-61.9] years, 71% female, rheumatoid arthritis [n = 75], axial spondyloarthritis [axSpA] [n = 40] and psoriatic arthritis [n = 35]), median pre-diagnosis interval was 11.5 (4.7-36.0) months. Interval #1 (median = 4.9 months) was significantly longer than Intervals #2-#4 (median = 0.3, 1.5, and 0.0 months, respectively). Patients with axSpA had significantly longer pre-diagnosis interval (median = 38.7 months) and Interval #1 (median = 26.6 months) than patients with the other ARDs. Median regression suggested that patients referred from specialty care had significantly longer pre-diagnosis interval (median difference = 7.7 months) and Interval #1 (median difference = 6.4 months) compared to those referred from primary care., Conclusion: A long pre-diagnosis interval was observed among patients with ARDs (especially axSpA), due largely to a long interval between symptom onset and the first visit to healthcare professionals. This highlights the importance of interventions targeting patients prior to their first visit to healthcare professionals in reducing pre-diagnosis interval., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Assessment and treatment pathways based on age-specific intervention thresholds in Singapore using FRAX paths can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low risk., Purpose: Intervention thresholds for the treatment of osteoporosis have been based historically on the measurement of bone mineral density. The development of FRAX® has permitted a more accurate assessment of fracture risk. The aim of the present study was to explore treatment paths and characteristics of women selected for treatment in Singapore based on FRAX., Methods: The approach to the setting of intervention and assessment thresholds used the methodology adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Singapore. The methodology was applied to women age 50 years or more drawn from the population-based Singapore Chinese Health Study (SCHS) cohort. Missing data for the calculation of FRAX was simulated using data from Chinese cohorts from Hong Kong., Results: Intervention thresholds expressed as a 10-year probability of a major osteoporotic fracture ranged from 2.9% at the age of 50 years increasing to 32% at the age of 90 years. A total of 1927 of 29,323 women (7%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 3019 women (10.3%) would be eligible for treatment on the basis of age-dependent thresholds. The mean BMD T-score of women so selected was -2.94., Conclusion: Probability-based assessment of fracture risk using age-specific intervention thresholds was developed for Singapore to help guide decisions about treatment.

Background: Older persons consume disproportionately more healthcare resources than younger persons. Tri-Generational HomeCare (TriGen), a service-learning program, aims to reduce hospital admission rates amongst older patients with frequent admissions. The authors evaluated the educational and patient outcomes of TriGen., Methods: Teams consisting of healthcare undergraduates and secondary school (SS) students - performed fortnightly home visits to patients over 6 months. Self-administered scales were used to evaluate the educational outcomes in knowledge and attitudes towards the older people and nine domains of soft skills pre- and post-intervention. Patients' reported satisfaction and clinical outcomes were also assessed., Results: Two hundred twenty-six healthcare undergraduates and 359 SS students participated in the program from 2015 to 2018. Response rates were 80.1 and 62.4% respectively. One hundred six patients participated in TriGen. There was a significant increase in Kogan's Attitudes towards Old People Scale (KOP) scores for healthcare undergraduates and SS students with a mean increase of 12.8 (95%CI: 9.5-16.2, p <  0.001) and 8.3 (95%CI: 6.2-10.3, p <  0.001) respectively. There was a significant increase in Palmore Facts on Aging Quiz (PFAQ) score for SS students but not for healthcare undergraduates. Most volunteers reported that TriGen was beneficial across all nine domains assessed. There was also a significant decrease in hospital admission rates (p = 0.006) and emergency department visits (p = 0.004) during the 6-month period before and after the program. Fifty-one patients answered the patient feedback survey. Of this, more than 80% reported feeling less lonely and happier., Conclusion: TriGen, a student-initiated, longitudinal, inter-generational service-learning program consisting of SS students and healthcare undergraduates can reduce ageism, develop soft skills, inculcate values amongst SS students and healthcare undergraduates. In addition, TriGen potentially reduces hospital admissions and emergency department visits, and loneliness amongst frequently admitted older patients.

This article was migrated. The article was marked as recommended. Background: Healthcare professionals are playing an important role in the recent COVID-19 outbreak. It is crucial that the health systems maintain their ability to train students and residents during this time. However, there is a paucity of literature on the measures taken by higher education institutions to ensure academic continuity. The aim of this article is to share the systematic measures that were taken during the COVID-19 pandemic by Yong Loo Lin School of Medicine, National University of Singapore. Methods: We discussed our multi-faceted approach to protect students, staff and patients/ standardized patients during the COVID-19 outbreak that occurred during a pivotal time in the school's academic calendar. Results: Our approach to ensuring academic continuity and quality were based on best practices in the following areas: 1) A coordinated leadership and management process 2) Prioritising safety for all stakeholders 3) Dissemination of information amongst the stakeholders in a transparent and efficient way, and 4) Maintaining the rigour and quality of training. Conclusion: The initiatives were implemented as we leveraged on the available infrastructure and the collective team efforts of all involved. Further research will be done to evaluate the usefulness of these measures. We hope that this article would be a useful reference for other schools as they evaluate their pandemic preparedness in the event that the COVID-19 outbreak affects their country or similar crisis event in the future., (Copyright: © 2020 Samarasekera DD et al.)

Background: Interprofessional team training is needed to improve nurse-physician communication skills that are lacking in clinical practice. Using simulations has proven to be an effective learning approach for team training. Yet, it has logistical constraints that call for the exploration of virtual environments in delivering team training., Objective: This study aimed to evaluate a team training program using virtual reality vs conventional live simulations on medical and nursing students' communication skill performances and teamwork attitudes., Methods: In June 2018, the authors implemented nurse-physician communication team training using communication tools. A randomized controlled trial study was conducted with 120 undergraduate medical and nursing students who were randomly assigned to undertake team training using virtual reality or live simulations. The participants from both groups were tested on their communication performances through team-based simulation assessments. Their teamwork attitudes were evaluated using interprofessional attitude surveys that were administered before, immediately after, and 2 months after the study interventions., Results: The team-based simulation assessment revealed no significant differences in the communication performance posttest scores (P=.29) between the virtual and simulation groups. Both groups reported significant increases in the interprofessional attitudes posttest scores from the baseline scores, with no significant differences found between the groups over the 3 time points., Conclusions: Our study outcomes did not show an inferiority of team training using virtual reality when compared with live simulations, which supports the potential use of virtual reality to substitute conventional simulations for communication team training. Future studies can leverage the use of artificial intelligence technology in virtual reality to replace costly human-controlled facilitators to achieve better scalability and sustainability of team-based training in interprofessional education., Trial Registration: ClinicalTrials.gov NCT04330924; https://clinicaltrials.gov/ct2/show/NCT04330924., (©Sok Ying Liaw, Sim Win Ooi, Khairul Dzakirin Bin Rusli, Tang Ching Lau, Wilson Wai San Tam, Wei Ling Chua. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 08.04.2020.)

Aim: The efficacy of anti-lymphoma vaccines that exploit the cellular adjuvant properties of activated natural killer T (NKT) cells were examined in mouse models of CNS lymphoma. Materials & methods: Vaccines were prepared by either loading the NKT cell agonist, α-galactosylceramide onto irradiated and heat-shocked B- and T-lymphoma cells, or chemically conjugating α-galactosylceramide to MHC-binding peptides from a lymphoma-associated antigen. Vaccine efficacy was analyzed in mice bearing intracranial tumors. Results: Both forms of vaccine proved to be effective in preventing lymphoma engraftment through activity of T cells that accessed the CNS. Established lymphoma was harder to treat with responses constrained by Tregs, but this could be overcome by depleting Tregs prior to vaccination. Conclusion: Simply designed NKT cell-activating vaccines enhance T-cell responses and have the potential to protect against CNS lymphoma development or prevent CNS relapse. To be effective against established CNS lymphoma, vaccines need to be combined with Treg suppression.

Aim: This study aimed to evaluate the effect of a team training program to support shared mental model (SMM) development in interprofessional rounds., Design and Participants: A three-arm randomized controlled trial study was conducted for interprofessional teams of 207 health profession learners who were randomized into three groups., Program Description: The full team training program included a didactic training part on cognitive tools and a virtual simulation to support clinical teamwork in interprofessional round. Group 1 was assigned to the full program, group 2 to the didactic part, and group 3 (control group) with no intervention. The main outcome measure was team performance in full scale simulation. Secondary outcome was interprofessional attitudes., Program Evaluation: Teamwork performance and interprofessional attitude scores of the full intervention group were significantly higher (P < 0.05) than those of the control group. The two intervention groups had significantly higher (P < 0.05) attitude scores on interprofessional teamwork compared with the control group., Discussion: Our study indicates the need of both cognitive tools and experiential learning modalities to foster SMM development for the delivery of optimal clinical teamwork performances. Given its scalability and practicality, we anticipate a greater role for virtual simulations to support interprofessional team training.

Purpose: This study aims to estimate the health and economic burden of osteoporosis in Singapore from 2017 to 2035, and to quantify the impact of increasing the treatment rate of osteoporosis., Methods: Population forecast data of women and men aged 50 and above in Singapore from 2017 to 2035 was used along with prevalence rates of osteoporosis to project the osteoporosis population over time. The population projections by sex and age group were used along with osteoporotic fracture incidence rates by fracture type (hip, vertebral, other), and average direct and indirect costs per case to forecast the number of fractures, the total direct health care costs, and the total indirect costs due to fractures in Singapore. Data on treatment rates and effects were used to model the health and economic impact of increasing treatment rate of osteoporosis, using different hypothetical levels., Results: Between 2017 and 2035, the incidence of osteoporotic fractures is projected to increase from 15,267 to 24,104 (a 57.9% increase) F 10,717 to 17,225 (a 60.7% increase) and M 4550 to 6878 (a 51.2% increase). The total economic burden (including direct costs and indirect costs to society) associated with these fractures is estimated at S$183.5 million in 2017 and is forecasted to grow to S$289.6 million by 2035. However, increasing the treatment rate for osteoporosis could avert up to 29,096 fractures over the forecast period (2017-2035), generating cumulative total cost savings of up to S$330.6 million., Conclusion: Efforts to improve the detection, diagnosis, and treatment of osteoporosis are necessary to reduce the growing clinical, economic, and societal burden of fractures in Singapore.

Background: Collaborative learning in interprofessional team care delivery across different healthcare courses and institutions is constrained by geographical locations and tedious scheduling. Three dimensional virtual environments (3D-VE) are a viable and innovative tool to bring diverse healthcare students to learn together., Aim: The aim of this study is to describe the development of a 3D-VE and to evaluate healthcare students' experiences of their collaborative learning in the environment., Method: A mixed methods study design was employed. Participants from six healthcare courses (Medicine, Nursing, Pharmacy, Physiotherapy, Occupational Therapy, and Medical Social Work) were recruited from three institutions to form six interprofessional teams to participate in team care delivery via a 3D-VE. Pre- and post-tests were conducted to evaluate the students' attitudes toward healthcare teams and interprofessional collaboration. Four focus groups were conducted with 27 healthcare students after they completed questionnaires to evaluate their perceived usability, the sociability of computer-supported collaborative learning, and senses of presence. Interview transcripts were analyzed using thematic analysis., Result: The students demonstrated significant improvements in their attitudes toward healthcare teams (p < 0.05) and interprofessional collaboration (p < 0.001) after the collaborative learning. Four themes emerged from the focus group discussions: "feeling real", whereby the students felt immersed in their own roles; the virtual environment was perceived as "less threatening" compared to face-to-face interactions; "understanding each other's roles" among different healthcare professionals; and there were some "technical hiccups" related to sound quality and navigation. The participants reported positively on the usability (mean 3.48, SD 0.64), feasibility (mean 3.39, SD 0.60) and perceived sense of presence (mean 107.24, SD 17.78) of the 3D-VE in supporting collaborative learning., Conclusion: Given its flexibility, practicality, and scalability, this 3D-VE serves as a promising tool for collaborative learning across different healthcare courses and institutions in preparing for future collaborative-ready workforces., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Context: The shift in medical education from time-based learning to outcome-based learning has drawn much attention to entrustable professional activities (EPAs) as an ideal assessment framework to translate competencies into clinical practice. Given the relative novelty of EPAs, this review aims to highlight research gaps and explore and consolidate available evidence pertaining to the development and implementation of EPAs in health care., Method: Arksey and O'Malley's scoping review framework was used to present the findings. The authors performed a systematic search of PubMed, Embase, CINAHL, Scopus, MedNar, OpenGrey and ProQuest Dissertation and Theses for English articles published from the inception of each database to May 2018. A manual search of the reference lists of the included studies was conducted and an expert panel was consulted. Two reviewers screened the articles for eligibility using the inclusion criteria. All authors extracted key data and analysed the data descriptively. Thematic analysis was used to categorise the results into themes., Results: Eighty articles were included in the review. All articles were published between 2010 and 2018. Three major themes and eight sub-themes were generated: (i) development of EPAs (frameworks for EPA development and implementation, identifying core or specialty-specific EPAs, and EPAs for faculty development), (ii) evaluation of EPAs and EPA entrustment factors (revised curriculum, entrustment decisions for professional activities, and feedback on implemented EPAs and the development process), and (iii) future directions and recommendations for EPAs (implementation of EPAs in undergraduate medical education and specific disciplines, and other criticisms and recommendations for EPAs)., Conclusions: Entrustable professional activities are an essential means to translate competencies into observable and measurable clinical practice. However, high-level evidence-based research on the efficacy, development and implementation of EPAs for specific target groups (i.e. undergraduates and staff) and geographical regions (i.e. Asia and Africa) is still lacking, which suggests a direction for future research., (© 2019 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

We report on the chemical lithiation of long microscale helices composed of densely packed amorphous silicon (aSi) nanofibrils, fabricated by glancing angle deposition (GLAD) through e-beam evaporation. In situ electron microscopy and companion finite element modeling demonstrate that the nanofibrillar structure of the aSi helices allows for 2 orders of magnitude faster effective rates for Li diffusion ( D 0 = 10 -10 cm 2 /s) compared to solid aSi nanowires, while also averting fragmentation during lithiation. More importantly, it is shown that specific helical geometries can accommodate large, lithium-induced, volumetric expansions without shape distortion. A major advantage of the helical nanostructures is that the compressive force generated due to lithiation-induced expansion is an order of magnitude smaller than in straight nanocolumns that permanently buckle during lithiation. Thus, GLAD-fabricated films composed of dense periodic microscale helices with properly designed coil geometries are highly suitable for robust, high-capacity Li + anodes.

Activated NKT cells can stimulate antigen-presenting cells leading to enhanced peptide antigen-specific immunity. However, administration of potent NKT cell agonists like α-galactosylceramide (α-GalCer) can be associated with release of high levels of cytokines, and in some situations, hepatotoxicity. Here we show that it is possible to provoke sufficient NKT cell activity to stimulate strong antigen-specific T cell responses without these unwanted effects. This was achieved by chemically conjugating antigenic peptides to α-galactosylphytosphingosine (α-GalPhs), an NKT cell agonist with very weak activity based on structural characterisation and biological assays. Conjugation improved delivery to antigen-presenting cells in vivo, while use of a cathepsin-sensitive linker to release the α-GalPhs and peptide within the same cell promoted strong T cell activation and therapeutic anti-tumour responses in mice. The conjugates activated human NKT cells and enhanced human T cell responses to a viral peptide in vitro. Accordingly, we have demonstrated a means to safely exploit the immunostimulatory properties of NKT cells to enhance T cell activation for virus- and tumour-specific immunity.

Fluorescent Cd metal-organic frameworks (MOFs), [Cd 2 (dicarboxylate) 2 (NI-bpy-44) 2 ] (dicarboxylate=benzene-1,4-dicarboxylate (1,4-bdc, 1), 2-bromobenzene-1,4-dicarboxylate (Br-1,4-bdc, 2), 2-nitrobenzene-1,4-dicarboxylate (NO 2 -1,4-bdc, 3), biphenyl-4,4'-dicarboxylate (bpdc, 4); NI-bpy-44=N-(pyridin-4-yl)-4-(pyridin-4-yl)-1,8-naphthalimide)), featuring non- and twofold interpenetrating pcu-type bipillared-layer open structures with sufficient free voids of 58.4, 51.4, 51.5, and 41.4 %, respectively, have been hydro(solvo)thermally synthesized. MOFs 1-4 emitted solid-state blue or cyan fluorescence emissions at 447±7 nm, which mainly arose from NI-bpy-44 and are dependent on the incorporated solvents. After immersing the crystalline samples in different solvents, that is, H 2 O and DMSO (1 and 2) as well as nitrobenzene and phenol (1-4), they exhibited a remarkable fluorescence quenching effect, whereas o-xylene and p-xylene (4) caused significant fluorescence enhancement. The sensing ability of MOFs 1-4 toward nitro compounds carried out in the vapor phase showed that nitrobenzene and 2-nitrophenol displayed detectable fluorescence quenching with 1, 2, and 4 whereas 4-nitrotoluene was an effective fluorescence quencher for 1 and 2; this is most likely attributed to their electron-deficient properties and higher vapor pressures. Moreover, MOFs 1-4 are highly reusable for quick capture of volatile iodine, as supported by clear crystal color change and also by immense fluorescence quenching responses owing to the donor-acceptor interaction. Low-pressure CO 2 adsorption isotherms indicate that activated materials 1'-4' are inefficient at taking up CO 2 ., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this article the name of the sixth author, E. Michael Lewiecki was rendered incorrectly. The publisher regrets this error and apologizes for the inconvenience caused.

The Fracture Liaison Service (FLS) Consensus Meeting endorsed by the International Osteoporosis Foundation (IOF), Asian Federation of Osteoporosis Societies (AFOS), and Asia Pacific Osteoporosis Foundation (APOF) was hosted by the Taiwanese Osteoporosis Association on October 14, 2017. International and domestic experts reviewed the 13 Best Practice Framework (BPF) standards and concluded that all standards were generally applicable in the Asia-Pacific region and needed only minor modifications to fit the healthcare settings in the region., Purpose: To review and generate consensus on best practices of fracture liaison service (FLS) in the Asia-Pacific (AP) region., Methods: In October 2017, the Taiwanese Osteoporosis Association (TOA) invited experts from the AP region (n = 23), the Capture the Fracture Steering Committee (n = 2), and the USA (n = 1) to join the AP region FLS Consensus Meeting in Taipei. After two rounds of consensus generation, the recommendations on the 13 Best Practice Framework (BPF) standards were reported and reviewed by the attendees. Experts unable to attend the on-site meeting reviewed the draft, made suggestions, and approved the final version., Results: Because the number of FLSs in the region is rapidly increasing, experts agreed that it was timely to establish consensus on benchmark quality standards for FLSs in the region. They also agreed that the 13 BPF standards and the 3 levels of standards were generally applicable, but that some clarifications were necessary. They suggested, for example, that patient and family education be incorporated into the current standards and that communication with the public to promote FLSs be increased., Conclusions: The consensus on the 13 BPF standards reviewed in this meeting was that they were generally applicable and required only a few advanced clarifications to increase the quality of FLSs in the region.

Traditional Chinese medicine (TCM)-based herbal therapies have gained increasing popularity worldwide, raising concerns of its efficacy, safety profile and potential interactions with Western medications. Antithrombotic agents are among the most common prescription drugs involved in herb-drug interactions, and this article focused on aspirin, one of the most widely used antiplatelet agents worldwide. We discussed herbs that have potential interactions by exploring Western and TCM approaches to thrombotic events. Common TCM indications for these herbs were also highlighted, including possible scenarios of their concurrent usage with aspirin. With greater awareness and understanding of potential herb-drug interactions, TCM and Western physicians may collaborate more closely to identify, treat and, most importantly, prevent adverse drug events., (Copyright: © Singapore Medical Association.)

Mannosylated ovalbumin (Man-OVA) prepared by modification of carboxyl groups with p-aminophenyl α-d-mannopyranoside shows an increase of net positive charge, which may enhance its binding to bacterial membrane. Thus, we aimed to investigate whether Man-OVA exerts antibacterial activity on Escherichia coli and Staphylococcus aureus via membrane-perturbing effect. Man-OVA inhibited the growth of E. coli and S. aureus, whereas ovalbumin (OVA) did not show any antibacterial activity. Moreover, Man-OVA induced an increase in the membrane permeability of E. coli and S. aureus, which was positively correlated to its bactericidal action. Morphological examination using scanning electron microscopy revealed that Man-OVA disrupted the bacterial membrane integrity. Destabilization of the lipopolysaccharide (LPS) layer and inhibition of lipoteichoic acid (LTA) biosynthesis in the cell wall increased the bactericidal effect of Man-OVA. In contrast to OVA, Man-OVA also induced leakage of bacterial membrane-mimicking liposomes. Color transformation of phospholipid/polydiacetylene membrane assay revealed that the membrane-interaction mode of Man-OVA was distinct from that of OVA. LPS and LTA suppressed the membrane-damaging activity of Man-OVA, whereas an increase in the Man-OVA concentration attenuated the inhibitory action of LPS and LTA. Taken together, our data indicate that the bactericidal activity of Man-OVA depends strongly on its ability to induce membrane permeability., (Copyright © 2017 Elsevier Inc. All rights reserved.)