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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.

Summary Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. Purpose Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. Methods We conducted a structured comparative analysis of existing CPGs in the AP region using a “5IQ” model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. Results Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. Conclusion The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.

To compare central corneal thickness (CCT) measurements by scanning slit topography (SST), infrared pachymetry (IRP), and ultrasound pachymetry (USP), and their agreement in normal and post-laser in situ keratomileusis (LASIK) eyes. Sixty normal and 35 post-LASIK subjects were recruited. Only one eye from each subject was analyzed. Non-contact pachymetry was performed first, and the order for SST (Orbscan IIz) and IRP (Tonoref III) was randomized for each patient, to be followed by contact USP (Echoscan US-4000). Pearson’s correlation, paired t test, and Bland–Altman plots were used to investigate association, difference, and agreement among different instruments respectively. The measurements obtained with the instruments were highly correlated. Compared to CCT determined by USP (CCTUSP), CCT determined by SST (after correction with acoustic factor) (CCTSSTC) was thicker by 7 µm in normal eyes (P

Immune checkpoint inhibitors (ICIs) have forged a new direction for the treatment of cancer. However, ICIs – programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors – are also known to cause immune-related adverse events (irAEs). Rheumatological adverse events are uncommon and often low grade, but flares of underlying rheumatological diseases may be triggered. Guidelines are available for the effective management of the rheumatological adverse events that more frequently arise from the use of ICIs, such as inflammatory arthritis, inflammatory myopathies, Sjogren syndrome, scleroderma, and polymyalgia rheumatica and eosinophilic fasciitis.

Objectives To investigate the prognostic values of preoperative platelet-to-lymphocyte ratio (PLR) and platelet-related indices in advanced hypopharyngeal squamous cell carcinoma (HPSCC). Methods The data of 247 eligible advanced HPSCC patients were reviewed retrospectively. Pretreatment haematological parameters were categorised into two groups based on the result of X-tile, and several variates were assessed using chi-square test, Kaplan-Meier method, Cox univariate and multivariate analysis. Results The optimal cut-off points of 171.4 for PLR, 260 × 109 /L for platelet, 10.4 fL for mean platelet volume (MPV) and 16.5% for platelet distribution width were defined. The haematological parameters PLR and MPV, postoperative metastasis and internal jugular vein invasion were statistically significant in OS and DFS analyses (P 171.4) or high MPV (>10.4 fL) was significantly associated with worse OS and DFS (P Conclusions The preoperative levels of PLR and MPV could be considered as independent prognostic predictors in patients with advanced HPSCC.

Background: The various pathological types of non-squamous cell carcinomas (nSCCs) of the larynx accounted for about 5% laryngeal malignancies, but the knowledge regarding these pathologica...

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.

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.

Objective: We explored the antitumor effect of dual PI3K/mTOR inhibitor combined with autophagy suppression on laryngeal squamous cell carcinoma (LSCC) and its underlying mechanism.Methods: Hep-2 and AMC-HN-8 cell lines were treated with the Akt inhibitor LY294002, mTOR inhibitor rapamycin, and dual inhibitor NVP-BEZ235 separately. The biological characteristics of in vitro proliferation, cell cycle, apoptosis, migration, invasion, and autophagy were analyzed, and the expression levels of PI3K/Akt/mTOR pathway-related proteins were also measured. The in vivo effects of NVP-BEZ235 combined with inhibition of autophagy using pharmacological inhibitor was further assessed.Results: Compared with Akt or mTOR inhibitor, NVP-BEZ235 had the most significant biological effects on LSCC cells. When combined with various autophagy inhibitors, along with siRNA against ATG7, NVP-BEZ235 showed a synergic antitumor effect in LSCC through increasing cell apoptosis and death both in vitro and vivo.Conclusion: NVP-BEZ235 exerted stronger antitumor effects on LSCC, especially when combined with the autophagy inhibitor, providing convincing experimental data for new molecular targeted therapy for LSCC.

Introduction With the rise in Caesarean deliveries, complications related to the procedure are increasingly encountered. Sonography has an indispensable role in the assessment of these complications and is often the first-line investigation of choice. Topic description: Part 2 of this pictorial review summarises the non-pregnant and pregnancy-related complications of Caesarean deliveries. Discussion Non-pregnant complications include Caesarean scar defects, scar endometriosis and malpositioned intrauterine devices. Complications related to future gestations include scar ectopic pregnancy, abnormal placentation and intrapartum uterine dehiscence or rupture. Key sonographic features of these conditions are illustrated. Pitfalls, mimics, limitations and indications for cross-sectional imaging are discussed. Conclusion Sound knowledge of the sonographic features of common non-pregnant and pregnancy-related complications of Caesarean delivery will facilitate accurate diagnosis, timely management and improved patient outcomes.

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.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.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.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.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.

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.

Up to 80% of patients with breast cancer are reported to use complementary and alternative medicine (CAM). Despite this high prevalence, many healthcare providers have little knowledge and education surrounding this topic and may be inadequately prepared to discuss such therapies with their patients. Given this knowledge gap, the purpose of this study was to systematically identify the quantity and assess the quality of CAM recommendations in clinical practice guidelines (CPGs) for the treatment and/or management of breast cancer. Thirty-four CPGs were deemed eligible, 5 of which mentioned CAM, and 4 of which made CAM recommendations. Eligible CPGs containing CAM recommendations were assessed with the AGREE II instrument. Scaled domain percentages from highest to lowest were (% overall, % CAM) as follows: scope and purpose (100.0%, 100.0%), editorial independence (100.0%, 100.0%), clarity of presentation (97.2%, 80.6%), rigour of development (80.2%, 80.2%), stakeholder involvement (88.9%, 77.8%), and applicability (58.3%, 58.3%). CPGs with favourable scores may provide practitioners with guidance on safe and effective use of CAM therapies. A need exists to improve the quality of CAM recommendations in CPGs.

Alcohol consumption, which affects the structure and composition of the laryngeal microbiota, is one of the most important risk factors for laryngeal squamous cell cancer (LSCC). Our results demonstrated that Fusobacterium nucleatum (F. nucleatum) highly enriched in LSCC was associated with poor prognosis. F. nucleatum increased miR-155-5p and miR-205-5p expression to suppress alcohol dehydrogenase 1B and transforming growth factor beta receptor 2 expression by activating TLR4- and MYD88-dependent innate immune signaling, resulting in ethanol metabolism reprogramming to accumulate F. nucleatum and PI3K/AKT signaling pathway activation to promote epithelial-mesenchymal transition in LSCC, further promoting uncontrolled LSCC progression and metastasis. Therefore, the positive feed-forward loop between F. nucleatum and ethanol metabolism reprogramming promotes cell proliferation, migration, and invasion to affect LSCC patient prognosis. The amount of F. nucleatum is a potential prognostic biomarker, a finding yielding valuable insight into clinical management and may potentially improving the oncologic outcome of LSCC patients.

Background Interprofessional rounds are increasingly applied in providing patient-centered team care delivery. Students from six health care courses in medicine, nursing, pharmacy, physiotherapy, occupational therapy, and social work formed interprofessional teams to undertake an interprofessional education (IPE) on virtual reality simulation–based interprofessional rounds. This study aimed to evaluate health care students’ perspectives on the transferability of the IPE virtual reality simulation learning to clinical practice. Method Three focus group discussions were conducted. Results Three themes emerged: “gaining insights into mutual roles,” whereby students better understood the different interprofessional roles of other team members, “seeing the patient as a whole” to foster patient-centered care, and “gaps in real-world application” due to system and structure constraints. Conclusions Early exposure to team care through IPE virtual reality simulation can foster understandings of the interdependent roles of health care professionals toward patient-centered care. For greater clinical impact, a further recommendation is to supplement with workplace-based team training to contextualize learning with practice settings.

Summary 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.

BackgroundOlder 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.MethodsTeams 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.ResultsTwo 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 p 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.ConclusionTriGen, 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 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. 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. 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. 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.

Brain tumor diagnostics is achieved by combining morphology assessment and biomarker identification. However, the inter-observer variability of the histopathological diagnosis and lack of distinctive biomarkers makes these diagnoses particularly challenging. Recently, the potential for methylation-based characterization has been developed for brain tumors. To provide accurate and efficient brain tumor diagnostics, The Jackson Laboratory developed a DNA methylation array (Illumina Infinium HD Methylation EPIC), combining the “Classifier” established by the German Cancer Research Center (DKFZ), which can identify 82 distinct central nervous system tumors. Here we present a pediatric patient referred to us for medulloblastoma subtype classification by the methylation profile. Surprisingly, the array classified the tumor type as atypical teratoid/rhabdoid tumor (ATRT), subclass SHH. Also, the CNV profile indicated the SMARCB1/INI1 heterozygous deletion as part of the chromosome 22q deletion typically seen in ATRT, and absent was the isochromosome 17q commonly associated with medulloblastoma. Immunohistochemistry confirmed the loss of SMARCB1/INI1 expression leading to ATRT. Additionally, our NGS panel found a novel SMARCB1/INI1 frameshift variant c.1150delG (p.Ala384fs) in the last exon (exon 9). Although this variant is not expected to induce nonsense-mediated mRNA decay, it is located in the ATP-dependent nucleosome-remodeling complex domain Sfh1/SNF5 (IPR017393), which is associated with cell proliferation and differentiation. In addition, ClinVar reported several pathogenic/likely pathogenic variants in this domain, further supporting SMARCB1/INI1 c.1150delG which, together with the SMARCB1/INI1 deletion, may contribute to the loss of SMARCB1/INI1 expression, resulting in ATRT. We have identified the ATRT misclassification by the methylation profile and characterized a novel SMARCB1/INI1 variant c.1150delG most likely contributing to ATRT. We further propose that the DNA methylation profile will significantly improve the brain tumor diagnostics for cases with ambiguous, or contradictory histology and molecular profiles.

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.

The use of magnetic resonance imaging (MRI)-conditional permanent pacemakers has increased significantly. In this meta-analysis, we examine the safety of MRI-conditional pacing systems in comparison with conventional systems. An electronic search was performed using major databases, including studies that compared the outcomes of interest between patients receiving MRI-conditional pacemakers (MRI group) versus conventional pacemakers (control group). Six studies (5 retrospective and 1 prospective non-randomised) involving 2,118 adult patients were identified. The MRI-conditional pacemakers, deployed in 969 patients, were all from a single manufacturer (Medtronic Pacing System with 5086 leads). The rate of pacemaker lead dislodgement (atrial and ventricular) was significantly higher in the MRI group (3% vs. 1%, OR 2.47 (95% CI 1.26; 4.83), p = 0.008). The MRI group had a significantly higher rate of pericardial complications (2% vs. 1%, OR 4.23 (95% CI 1.18; 15.10), p = 0.03) and a numerically higher overall complication rate in comparison with the conventional group (6% vs. 3%, OR 2.02 (95% CI 0.88; 4.66), p = 0.10) but this was not statistically significant. In this meta-analysis, the rates of pacemaker lead dislodgement and pericardial complications were significantly higher with the Medtronic MRI-conditional pacing system.

Background:The interval between symptom onset and diagnosis can often be longer than is ideal in autoimmune rheumatic diseases (ARDs).Objectives:We aimed to characterise this interval among patients newly diagnosed with ARDs in a multi-ethnic Asian population and to identify factors associated with a longer interval.Methods:We used Scott’s model of pathways to treatment to characterise the interval between symptom onset and diagnosis into 4 intervals: #1 between symptom onset and first seeking medical attention, #2 between first medical attention and rheumatology referral, #3 between rheumatology referral and first rheumatology assessment, and #4 between first rheumatology assessment and diagnosis. Linear regression models were used to identify factors associated with a longer the overall interval between symptom onset and diagnosis and Interval #1.Results:Among 259 patients (age: 51±15 years, female: 71%, most common three ARDs: rheumatoid arthritis (n = 75), axial spondyloarthritis (n = 40) and psoriatic arthritis (n = 35)), the median overall interval was 11.5 months. Interval #1 (median = 4.9 months) was significantly longer than the other intervals (Table 1). Patients with axial spondyloarthritis had a significantly longer overall interval (median = 38.7 months) and Interval #1 (median = 26.6 months) compared to patients with RA (median = 7.6 and 3.5 months, respectively), PsA (median = 7.0 and 2.6 months, respectively) and the other ARDs. Gender was the only patient-related factor significantly associated with the overall interval (reference = male, coefficient = -15.3, p = 0.033) in regression models.Conclusion:A longer than ideal interval between symptom onset and diagnosis was observed among patients with ARDs. This was primarily due to a relatively long interval between symptom onset and first seeking medical attention, and highlights the importance of interventions targeting patients prior to first medical attention in reducing the duration between symptom onset and diagnosis.References:[1]Scott SE, Walter FM, Webster A, Sutton S, Emery J. The model of pathways to treatment: conceptualization and integration with existing theory. Br J Health Psychol. 2013;18(1):45-65.Table 1.Interval between symptom onset and diagnosisOverall interval, months, median (lower and upper quartiles)†Interval #1, months, median (lower and upper quartiles)Interval #2, months, median (lower and upper quartiles)Interval #3, months, median (lower and upper quartiles)Interval #4, months, median (lower and upper quartiles)Overall(n = 259)11.5(4.7 – 36.0)4.9(1.0 – 24.0)0.3(0.0 – 3.9)1.5(0.8 – 1.8)0.0(0.0 – 1.2)RA(n = 75)7.6(3.1 – 14.8)3.5(1.3 – 11.6)0.2(0.0 – 2.5)1.3(0.6 – 1.6)0.0(0.0 – 0.2)AxSpA(n = 40)38.7(9.6 – 66.7)26.6(4.2 – 56.1)1.6(0.0 – 7.6)1.6(1.2 – 2.3)0.0(0.0 – 2.0)PsA(n = 35)7.0(3.0 – 28.4)2.6(0.2 – 11.3)0.5(0.2 – 3.9)1.6(0.6 – 1.7)0.0(0.0 – 0.0)Seronegative IA(n = 21)12.0(4.7 – 22.8)6.4(1.9 – 34.4)0.1(0.0 – 4.6)1.4(1.3 – 1.5)0.0(0.0 – 0.8)SjS(n = 27)14.2(6.0 – 48.0)4.6(0.6 – 19.0)0.3(0.0 – 3.9)1.6(0.9 – 1.9)0.8(0.0 – 2.3)UCTD(n = 27)15.7(5.1 – 39.8)2.2(0.7 – 24.0)0.8(0.1 – 8.1)1.6(0.5 – 1.8)1.2(0.0 – 2.1)Other ARDs(n = 34)8.1(5.3 – 36.0)6.3(0.9 – 31.7)0.2(0.0 – 1.1)1.5(1.2 – 1.8)0.3(0.0 – 1.1)Overall interval and Intervals #1-4: refer to abstract for definitions; RA: rheumatoid arthritis; axSpA: axial spondyloarthritis; PsA: psoriatic arthritis; IA: inflammatory arthritis; SjS: Sjögren’s syndrome; UCTD: undifferentiated connective tissue disease; other ARDs: systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, palindromic rheumatism and overlap syndromes.†Intervals #1-4 did not sum to the overall interval mainly due to the fact that Intervals #1-4 might not available for all patients.Disclosure of Interests:None declared

Objectives To estimate the 3-month direct and indirect costs associated with osteoporotic fractures from both the hospital's and patient's perspectives in Singapore and to compare the cost between acute and prevalent osteoporotic fractures. Methods Resource use and expenditure data were collected using interviewer-administered questionnaires at baseline and at a 3-month follow-up between July 2013 and January 2014. Estimated osteoporotic fracture–related costs included hospitalizations, accident and emergency room visits, outpatient physician visits, laboratory tests, medications, transportation, health care and community services, special equipment and home/car modifications, and productivity loss. Results A total of 67 patients agreed to participate, giving a response rate of 64.4%. The mean (median) 3-month direct medical cost from the hospital's perspective was found to be SGD 3,886.90 (SGD 413.10), of which 74.2% was accounted for by inpatient services, 25.2% by outpatient services, and 0.6% by accident and emergency services. Moreover, considerable variation (SD = SGD 2,615.40) was observed in the costs of outpatient rehabilitation services. Findings were similar when the patient's perspective was taken. The total costs, with both direct and indirect costs included, were SGD 11,438.70 (acute) and SGD 1,015.40 (prevalent), of which 34.7% and 8.0%, respectively, were accounted for by inpatient services. Conclusions Hospitalization was associated with the highest cost borne by both the hospital and the patient, and informal care dominated indirect costs. Better knowledge of the financial consequences of fragility fractures could enable proactive and preventive measures to be undertaken, especially at sites of care with high cost drivers.

BACKGROUND Routine stress testing is commonly used after percutaneous coronary intervention (PCI) to detect in-stent restenosis or suboptimal procedure results; however, recent studies suggest that such testing is rarely indicated. Our main objectives were to assess temporal trends in utilization of stress testing and to determine factors associated with its use. METHODS We conducted an observational study involving all patients who had undergone PCI in Ontario, Canada, from Apr. 1, 2004, to Mar. 31, 2012. The main outcome was stress testing within 2 years after PCI. We constructed multivariable logistic regression models to determine factors associated with the use of stress tests. RESULTS Our cohort consisted of 128 380 patients who underwent PCI procedures. The 2-year rate of stress testing declined significantly, from 68.1% among patients who underwent PCI in 2004 to 60.4% in 2012 (p < 0.001). Similar reductions were observed regardless of patients' risk of restenosis and type of stent received. Patients who were older or had diabetes mellitus, prior myocardial infarction, heart failure or other comorbidities were significantly less likely to undergo stress testing. In contrast, patients with higher income and those whose PCI was performed in a nonteaching hospital were significantly more likely to undergo stress testing. INTERPRETATION We observed a decrease in the use of stress testing after PCI procedures over time. However, stress tests were not performed in accordance with patients' higher baseline risk of adverse outcomes or risk of restenosis. Instead, many nonclinical factors, such as patients' socioeconomic status and hospitals' teaching status, were associated with higher use of stress tests.

Non-alcoholic fatty liver disease (NAFLD) is a continuous spectrum of diseases characterized by excessive lipid accumulation in hepatocytes. NAFLD progresses from simple liver steatosis to non-alcoholic steatohepatitis and, in more severe cases, to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Because of its growing worldwide prevalence, various animal models that mirror both the histopathology and the pathophysiology of each stage of human NAFLD have been developed. The selection of appropriate animal models continues to be one of the key questions faced in this field. This review presents a critical analysis of the histopathology and pathogenesis of NAFLD, the most frequently used and recently developed animal models for each stage of NAFLD and NAFLD-induced HCC, the main mechanisms involved in the experimental pathogenesis of NAFLD in different animal models, and a brief summary of recent therapeutic targets found by the use of animal models. Integrating the data from human disease with those from animal studies indicates that, although current animal models provide critical guidance in understanding specific stages of NAFLD pathogenesis and progression, further research is necessary to develop more accurate models that better mimic the disease spectrum, in order to provide both increased mechanistic understanding and identification/testing of novel therapeutic approaches. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

IgG4-related disease (IgG4-RD) is a rare fibroinflammatory, multisystemic condition with a relapsing-remitting progression.1 The level of serum IgG4 correlates with inflammatory activity and organ involvement.1 Glucocorticoids are first line for IgG4-RD, but there are numerous adverse effects with chronic use.2 Dupilumab is a monoclonal antibody that acts on the interleukin 4 (IL-4) receptor alpha, shared by the IL-4 and IL-13 receptors.1 IL-4 causes isotype switching from IgM to IgG4 and IL-13 is implicated in fibrosis.3 Thus, it was postulated by the authors to investigate dupilumab as a novel steroid-sparing treatment for IgG4-RD. A 67-year-old man with no known allergies and a history of sensory neural hearing loss, recurrent bronchitis, spinal stenosis, moderate positional obstructive sleep apnoea, asthma, atopic dermatitis (which caused swelling around his eyes) and allergic rhinoconjunctivitis underwent extensive investigations over the past 2 years due to suspected IgG4-RD. The patient’s initial complaint was pruritic erythematous lesions on the legs, arms, chest and palms. …

The Asia -Pacific Bone Academy (APBA) Fracture Liaison Service (FLS) Focus Group educational initiative has stimulated activity across the Asia -Pacific region with the intention of supporting widespread implementation of new FLS. In 2017, the APBA FLS Focus Group developed a suite of tools to support implementation of FLS across the Asia-Pacific region as a component of a multi-faceted educational initiative. This article puts this initiative into context with a narrative review describing the burden of fragility fractures in the region, the current secondary fracture prevention care gap and a summary of emerging best practice. The results of a survey to evaluate the impact of the APBA educational initiative is presented, in addition to commentary on recent activities intended to improve the care of individuals who sustain fragility fractures across the Asia -Pacific. A FLS Toolbox for Asia-Pacific was developed which included the following sections:1. The burden of fragility fractures in the Asia-Pacific region.2. A summary of evidence for FLS in the Asia-Pacific.3. A generic, fully referenced FLS business plan template.4. Potential cost savings accrued by each country, based on a country-specific FLS Benefits Calculator.5. How to start and expand FLS programmes in the Asia-Pacific context.6. A step-by-step guide to setting up FLS in countries in the Asia-Pacific region.7. Other practical tools to support FLS establishment.8. FLS online resources and publications.The FLS Toolbox was provided as a resource to support FLS workshops immediately following the 5th Scientific Meeting of the Asian Federation of Osteoporosis Societies (AFOS) held in Kuala Lumpur in October 2017. The FLS workshops addressed three key themes:• The FLS business case.• Planning the FLS patient pathway.• The role of the FLS coordinator in fragility fracture care management.A follow-up survey of 142 FLS workshop participants was conducted in August-September 2018. The survey included questions regarding how FLS were developed, funded, the scope of service provision and the support provided by the educational initiative. Almost one-third (30.3%) of FLS workshop participants completed the survey. Survey responses were reported for those who had established a FLS at the time the survey was conducted and, separately, for those who had not established a FLS. Findings for those who had established a FLS included:• 78.3% of respondents established a multidisciplinary team to develop the business case for their FLS.• 87.0% of respondents stated that a multidisciplinary team was established to design the patient pathway for their FLS.• 26.1% of respondents stated that their FLS has sustainable funding.• The primary source of funding for FLS was from public hospitals (83.3%) as compared with private hospitals (16.7%).Most hospitals that had not established a FLS at the time the survey was conducted were either in the process of setting-up a FLS (47%) or had plans in place to establish a FLS for which approval is being sought (29%). The primary barrier to establishing a new FLS was lack of sustainable funding. The APBA FLS Focus Group educational initiative has stimulated activity across the Asia-Pacific region with the intention of supporting widespread implementation of new FLS. A second edition of the FLS Toolbox is in development which is intended to complement ongoing efforts throughout the region to expedite widespread implementation of FLS.

Background: IL-6 plays an important role in B cell hyperactivity and immunopathology of systemic lupus erythematosus (SLE), and may have a direct role in mediating tissue damage [1]. Elevated levels of serum circulating immune complexes (CICs) have been described in SLE but the relationship with disease activity in our multi-ethnic Asian patients remains unclear. Objectives: To determine the correlation between disease activity and the levels of CICs, serum and urine IL-6 in a Singapore cohort of multi-ethnic Asian SLE patients. Methods: Serum levels of CICs, IL-6 and urine IL-6 were measured in 88 SLE patients using CIC-C1q and high sensitivity IL-6 ELISAs. All patients fulfilled the 1997 revised American College of Rheumatology (ACR) classification criteria. Clinical and laboratory manifestations, therapy, disease activity and damage at the time of sample collection was collated. Disease activity was scored with the SLE Activity Measure-revised (SLAM-R) and damage with the ACR/Systemic Lupus International Collaborating Clinic SLE damage index (SDI). The correlation between disease activity score and CICs, serum and urine IL-6 were assessed using Spearman’s correlation. Receiver operator characteristic (ROC) curve analysis was performed to assess the performance of the individual biomarkers in discriminating SLE disease activity. Results: The cohort of 88 patients were predominantly female (n = 78, 89.6%), with a mean age of 40 years±13.1. The majority were of Chinese ethnicity (n = 73, 83%), 13% were Malay (n = 11) and 4 individuals were of other races. The mean disease duration was 98.4 months ± 86.4. The mean scores of SLAM-R and SDI were 2.9 ± 2.2 and 0.9 ± 0.9 respectively. SLE disease manifestations at the time of sample collection included mucocutaneous involvement (5.7%) and active urine sediment (28.7%). 77% had hypocomplementaemia and 70.1% had elevated titres of anti-dsDNA antibody. The majority were on corticosteroids (75.9%) and hydroxycholoroquine (65.5%). Immunosuppressive drugs included azathioprine in 37.9%, mycophenolate in 6.9%, intravenous pulse cyclophosphamide in 6.9% and cyclosporin in 1 patient. There was significant positive correlation between SLAM-R and serum CICs (R = 0.4121, p Conclusion: Our study observed significant correlation between levels of serum circulating immune complexes, serum and urine IL-6 with SLE disease activity in our multi-ethnic Asian patient cohort. ROC curve analysis suggests that serum CICs and urine IL-6 may serve as sensitive biomarkers to identify SLE patients at risk of flares. Reference: [1] Tackey E, et al. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus. 2004;13(5):339-43. Disclosure of Interests: None declared

Objective: High levels of red cell distribution width (RDW) may be associated with adverse outcomes in patients with cancer. The purpose of the present study was to investigate the prognostic impact of pretreatment RDW levels on overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) in a large cohort of male laryngeal squamous cell cancer (LSCC) patients.Methods: A total of 809 LSCC patients who were treated between 2007 and 2011 at the Eye & ENT Hospital of Fudan University were enrolled and evaluated retrospectively. OS, CSS, and DFS were analyzed using the Kaplan–Meier method. To evaluate the prognostic significance of RDW levels, univariate, and multivariate Cox analyses were applied.Results: Higher pretreatment RDW levels were significantly associated with high death events, red blood cell count, hemoglobin, radiotherapy, operation therapy, and advanced tumor stage (p < 0.05). From the univariate analysis, we observed that the higher (13.2–13.5%) and the highest (>13.5%) quartiles of RDW level were consistent factors for poor OS, CSS, and DFS in LSCC patients. In the multivariate analysis, after adjusting for confounding factors, the higher and highest quartiles of RDW levels were identified as independent prognostic factors in male LSCC patients.Conclusion: Higher pretreatment RDW levels were demonstrated to be associated with poor clinical outcome in male LSCC patients and might be novel markers for patient stratification in LSCC management.

Introduction Conventional cytogenetics (CC) is important in diagnosis, therapy, monitoring of post-transplant bone marrow, and prognosis assessment of acute lymphoblastic leukemia (ALL). However, due to the nature of ALL, CC often encounters difficulties of complex karyotype, poor chromosome morphology, low mitotic index, or normal cells dividing only. In contrast, chromosomal microarray analysis (CMA) showed a specificity >99% and a sensitivity of 100% in chronic lymphocytic leukemia (CLL) patients. Here, we report our experience with CMA on adult ALL patients. Methods Thirty-three bone marrow/blood samples from ALL patients (aged 18-79 years, median 44) at diagnosis/relapse, analyzed by CC and/or fluorescence in situ hybridization (FISH), were recruited. Chromosomal microarray analysis results were compared with CC. Fluorescence in situ hybridization analysis, if available, was applied when there was a discrepancy. Results Copy-neutral loss-of-heterozygosity (CN-LOH) was found in 8 cases (24.2%). Only CN-LOH at 9p was recurrent (3 cases, 9.1%). Copy number alterations (CNAs) were detected in 6 of 9 cases (66.7%) with normal karyotypes, in 3 of 5 cases (60.0%) with sole "balanced" translocations, and in 18 of 19 cases (94.7%) with complex karyotypes. Common CNAs involved CDKN2A/2B (30.3%), IKZF1 (27.3%), PAX5 (9.1%), RB1 (9.1%), BTG1 (6.7%), and ETV6 (6.7%), which regulate cell cycle, B lymphopoiesis, or act as tumor suppressors in ALL. Copy number alteration detection rate by CMA was 81.8% (27 of 33 cases) as compared to 57.6% (19 of 33 cases) by CC. Conclusion Incorporation of CMA as a routine clinical test at the time of diagnosis/relapse, in conjunction with CC and/or FISH, is highly recommended.

Introduction Given the often-advanced stage of ovarian cancer upon diagnosis, many patients may seek complementary and alternative medicine (CAM), however, when improperly used, such therapies can be detrimental. Healthcare providers rely on clinical practice guidelines to give evidence-based advice. The objective of this study was to identify the quantity and assess the quality of CAM recommendations in ovarian cancer treatment and/or management in clinical practice guidelines. Methods MEDLINE, EMBASE and CINAHL were systematically searched from 2009 to April 2020, in addition to the Guidelines International Network, the National Center for Complementary and Integrative Health, and Google websites. Had CAM recommendations been found, the guidelines would have been assessed with the Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. Results Fifteen eligible ovarian cancer guidelines were identified from 432 unique search results. No eligible guidelines made mention or recommendations of CAM. The guidelines focused on treatment with conventional therapies including surgery, chemotherapy, and radiation therapy. Conclusion The quality of CAM recommendations in ovarian cancer treatment could not be assessed and compared with overall guideline recommendations. Given that a large proportion of ovarian cancer patients use CAM, this lack of therapy recommendations for the treatment and/or management of ovarian cancer reflects a major knowledge gap. Future guidelines should consider incorporating evidence-based CAM in their recommendations given that clinicians require this information in order to inform important shared-decision making discussions regarding safe and effective CAM use with their patients.

BACKGROUND Adamantinomatous craniopharyngioma (ACP) is the primary subtype of craniopharyngioma in children, frequently with mutations in exon 3 of the CTNNB1 gene. Most ACP consists of both a solid tumor and one or more cysts. Despite surgical resection of the solid tumor followed by radiation, recurrence involving the cystic component is common, suggesting that the cyst wall contains tumor cells. We present here conclusive molecular pathology evidence of the presence of tumor cells in the cyst wall similar to those in the solid tumor. METHODS We used standard H&E staining and immunohistochemistry (IHC) to compare the histopathology characteristics between the matched cyst wall and solid tumor of 11 cases of ACP as well as their CTNNB1 expression and exon 3 mutation. RESULTS Samples of the cyst wall and solid tumor were collected separately during the operation of 11 cases of ACP through careful dissection. The cyst wall showed the nested cell clusters and peripheral palisading epithelium which are identical to those in the solid tumor. The cyst wall and solid tumor both showed Ki67 and nuclear β-catenin expression by IHC. There is no difference in the transcription level of CTNNB1 between the cyst wall and the solid tumor, both being significantly higher than that in normal brain tissue. Exon 3 mutations of the CTNNB1 gene of the cyst wall and the solid tumor are identical in each case. CONCLUSION Follow-up of clinical cases suggests that tumor cells in residual cyst wall may be the cause of recurrence after surgery.

Background The BRUISE CONTROL trial (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial) demonstrated that a strategy of continued warfarin during cardiac implantable electronic device surgery was safe and reduced the incidence of clinically significant pocket hematoma (CSH). CSH was defined as a post-procedure hematoma requiring further surgery and/or resulting in prolongation of hospitalization of at least 24 h, and/or requiring interruption of anticoagulation. Previous studies have inconsistently associated hematoma with the subsequent development of device infection; reasons include the retrospective nature of many studies, lack of endpoint adjudication, and differing subjective definitions of hematoma. Objectives The BRUISE CONTROL INFECTION (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial Extended Follow-Up for Infection) prospectively examined the association between CSH and subsequent device infection. Methods The study included 659 patients with a primary outcome of device-related infection requiring hospitalization, defined as 1 or more of the following: pocket infection; endocarditis; and bloodstream infection. Outcomes were verified by a blinded adjudication committee. Multivariable analysis was performed to identify predictors of infection. Results The overall 1-year device-related infection rate was 2.4% (16 of 659). Infection occurred in 11% of patients (7 of 66) with previous CSH and in 1.5% (9 of 593) without CSH. CSH was the only independent predictor and was associated with a >7-fold increased risk of infection (hazard ratio: 7.7; 95% confidence interval: 2.9 to 20.5; p Conclusions CSH is associated with a significantly increased risk of infection requiring hospitalization within 1 year following cardiac implantable electronic device surgery. Strategies aimed at reducing hematomas may decrease the long-term risk of infection. (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial [BRUISE CONTROL]; NCT00800137 )

Health care systems and hospitals in several countries have implemented Fracture Liaison Services (FLSs). Success rates of FLSs with regard to osteoporosis assessment and treatment, fracture reduction, and adherence to osteoporosis medications have been reported by several groups including ours. A significant drop-out rate among patients in these programs may occur. This has not been evaluated before. We explored the factors correlating with nonadherence among a multiethnic population of patients in the FLS at our institution, the largest tertiary teaching hospital in South East Asia. Our secondary objective was to explore whether patients who defaulted follow-up visits continued to be compliant with medications. A retrospective analysis of our FLS's computerized database was performed. Of 938 patients followed up more than 2 years, 237 defaulted at various time points. A significant percentage of patients who dropped out of the program opined that it was because the follow-up visits were too time consuming. Non-Chinese patients were more likely than Chinese (adjusted hazard ratio [aHR] = 1.98, 1.33–2.94), patients with primary school education and below were more likely than those with secondary school and above education (aHR = 1.65, 1.11–2.45) and those with nonvertebral and/or multiple fractures were more likely than those with spine fractures (aHR = 1.38, 1.06–1.81) to be nonadherent. A fraction of patients who defaulted continued to fill osteoporosis medication prescriptions. Median medication possession ratio among the patients who defaulted was 12.3% (interquartile range: 4.1%–36.7%) at 2 years. Persistence ranged from 15.1% to 20.8% and from 1.9% to 7.5% at 1 and 2 years, respectively after defaulting from the program. Our study, which to the best of our knowledge is the first of its kind, provides insight into the factors correlating with nonadherence to FLSs. Knowledge of the challenges faced by patients may be of help to health care providers interested in developing FLSs.

This capsule commentary, Capsule Commentary on Liaw et al., "Getting everyone on the same page": interprofessional team training to develop shared mental models on interprofessional rounds," was to have accompanied the article, DOI: https://doi.org/10.1007/s11606-019-05320-z, which appeared in the December 2019 issue.

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.

Despite an increase in absolute numbers, the age-standardized incidence of hip fractures in Singapore declined in the period 2000 to 2017. Among the three major ethnic groups, Chinese women had the highest fracture rates but were the only group to show a temporal decline. A study published in 2001 predicted a 30–50% increase in Singapore hip fracture incidence rates over the ensuing 30 years. To test that prediction, we examined the incidence of hip fracture in Singapore from 2000 to 2017. We carried out a population-based study of hip fractures among Singapore residents aged ≥ 50 years. National medical insurance claims data were used to identify admissions with a primary discharge diagnosis of hip fracture. Age-adjusted rates, based on the age distribution of the Singapore population of 2000, were analyzed separately by sex and ethnicity (Chinese, Malay, or Indian). Over the 18-year study period, 36,082 first hip fractures were recorded. Total hip fracture admissions increased from 1487 to 2729 fractures/year in the years 2000 to 2017. Despite this absolute increase, age-adjusted fracture rates declined, with an average annual change of − 4.3 (95% CI − 5.0, − 3.5) and − 1.1 (95% CI − 1.7, − 0.5) fractures/100,000/year for women and men respectively. Chinese women had 1.4- and 1.9-fold higher age-adjusted rates than Malay and Indian women: 264 (95% CI 260, 267) versus 185 (95% CI 176, 193) and 141 (95% CI 132, 150) fractures/100,000/year, respectively. Despite their higher fracture rates, Chinese women were the only ethnic group exhibiting a decline, most evident in those ≥ 85 years, in age-adjusted fracture rate of − 5.3 (95% CI − 6.0, − 4.5) fractures/100,000/year. Although the absolute number of fractures increased, steep drops in elderly Chinese women drove a reduction in overall age-adjusted hip fracture rates. Increases in the older population will lead to a rise in total number of hip fractures, requiring budgetary planning and new preventive strategies.

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.

We report a case of a 61-year-old woman with a large atrial septal defect (ASD) that was detected incidentally on chest radiography and computed tomography when she presented with sepsis. Echocardiography confirmed a large secundum ASD with left-to-right shunt flow, right heart dilatation and severe pulmonary hypertension. The patient had a poor clinical outcome despite intensive care and eventually passed away. Haemodynamically significant ASDs have a known association with increased morbidity and mortality, and their early detection and closure cannot be understated. This article aimed to highlight the imaging features of ASD, with special emphasis on the routine chest radiograph. The pathophysiology and clinical manifestations of ASD are also briefly discussed.

Intramural esophageal dissection is an uncommon condition, involving the separation of the esophageal mucosa from the muscular layers. To our knowledge, the temporal evolution of intramural esophageal dissection on computed tomography has not been previously demonstrated. We present a case of a 51-year-old male who first presented to the emergency department with fever, odynophagia, and dysphagia. He was treated for acute tonsillitis and discharged, but presented again after 10 days with worsening symptoms. A series of radiographs and computed tomography studies, with 3D reconstruction and cinematic virtual fly-through, in these 2 admissions depicts the temporal evolution of intramural hematoma to subsequent intramural esophageal dissection. Recognizing its appearance on imaging is invaluable in distinguishing it from other important differential diagnoses. A complete description of the case, relevant radiologic imaging, and review of the relevant literature are provided.

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases, which include simple liver steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). It is a burgeoning health problem worldwide in line with the trend towards unhealthy diet and increased prevalence of obesity and type 2 diabetes mellitus (T2DM). Many animal models that illustrate both the histology and pathology of human NAFLD have been established. It is important to choose an animal model that best conforms to the aim of the study. This chapter presents a critical analysis of the histopathology and pathogenesis of NAFLD and the most commonly used and recently developed animal models of hepatic steatosis, NASH and NAFLD-induced hepatocellular carcinoma (NAFLD-HCC). The main mechanisms involved in the experimental pathogenesis of NAFLD in various animal models were also discussed. This chapter also includes a brief summary of recent therapeutic targets found using animal models. Although current animal models provide important guidance in understanding the pathogenesis and development of NAFLD, future study is essential to develop more precise models that better mimic the disease spectrum for both improved mechanistic understanding and identification of novel therapeutic options.

Background & Aims: The role of macrophages in fibrosing steatohepatitis is largely unclear. We characterized the origin and molecular mechanisms of macrophages and its targeted therapy in fibrosing steatohepatitis. Methods: Fibrosing steatohepatitis was established in Alms1 mutant (foz/foz) and C57BL/6 wildtype mice fed high-fat/high-cholesterol (HFHC) or methionine-and choline-deficient (MCD) diet. Bone marrow transplantation (BMT) was performed to track the macrophage origin in fibrosing steatohepatitis. Macrophages were depleted by liposomal clodronate. Primary macrophages were isolated from bone marrow for adoptive transfer into mice. Results: Macrophage infiltration is significantly induced in two mouse models of fibrosing steatohepatitis and human NASH-fibrosis patients. Bone marrow-derived macrophages (BMMs) contribute to the hepatic macrophage accumulation in experimental fibrosing steatohepatitis. Hepatic BMMs depletion by liposomal clodronate significantly attenuated fibrosing steatohepatitis. This effect was associated with reduced hepatic stellate cell (HSC) activation, collagen deposition and hepatic expression of key pro-fibrotic factors (TIMP1, TIMP2 and TGFβ1) and endoplasmic reticulum (ER) stress markers (GRP78, IRE1α and PDI). Conversely, adoptive transfer of BMMs significantly aggravated fibrosing steatohepatitis. Moreover, macrophage conditioned medium directly promoted the phenotypic transition of primary quiescent HSCs to activated HSCs; enhanced activation and proliferation (P

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. To review and generate consensus on best practices of fracture liaison service (FLS) in the Asia-Pacific (AP) region. 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. 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. 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.

Introduction The beneficial effects of biologic disease-modifying anti-rheumatic drugs (bDMARDs), such as tumour necrosis factor inhibitors (anti-TNF) in active ankylosing spondylitis (AS) are well established. The significant costs on patients in the absence of financial subsidization can limit their use. The objective was to describe a consensus development process on recommendations for government-assisted funding of biologic therapy for AS patients in Singapore. Methods Evidence synthesis followed by a modified RAND/UCLA Appropriateness Method (RAM) was used. Eleven rheumatologists rated indications for therapies for different proposed clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate 10 practice recommendations. Results It was agreed that a bDMARD (anti-TNF) is indicated if a patient has active AS with a Bath Ankylosing Spondylitis Activity Index (BASDAI) ≥ 4 and spinal pain of ≥ 4 cm on visual analogue scale (VAS) on two occasions at least 12 weeks apart, despite being on a minimum of two sequential non-steroidal anti-inflammatory drugs at maximal tolerated dose for at least 4 weeks, in addition to adherence to an appropriate physiotherapy program for at least 3 months. To qualify for continued biologic therapy, a patient must have documentation of response every 3 months and at least 50% improvement in BASDAI and reduction of spinal pain VAS ≥ 2 cm. Conclusion A validated and feasible consensus process can enable pragmatic standardized recommendations to be developed for bDMARD subsidization for AS patients in a local Asian context.

Background: Many patients with chest pain do not receive follow-up from a physician after discharge from the emergency department despite significant survival benefit associated with follow-up care. Our objective was to evaluate factors associated with physician follow-up to understand this gap in practice. Methods: We conducted an observational study involving patients at high risk who were assessed for chest pain and discharged from an emergency department in Ontario between April 2004 and March 2010. We used multivariable logistic regression to determine the association of clinical and nonclinical characteristics with physician follow-up. Results: We identified 56 767 patients, of whom 25.1% did not receive any follow-up by a physician, 69.0% were seen by their primary care physician, and 17.3% were seen by a cardiologist within 30 days. Patients who had medical comorbidities and cardiac conditions such as myocardial infarction or heart failure were less likely to have follow-up. In contrast, a previous visit to a primary care physician was associated with the highest odds of having physician follow-up (odds ratio [OR] 6.44, 95% confidence interval [CI] 5.91–7.01). Similarly, a previous visit to a cardiologist was strongly associated with follow-up by a cardiologist (OR 3.01, 95% CI 2.85–3.17). Patients evaluated in emergency departments with the highest tertile of chest pain volume were more likely to receive follow-up from any physician (OR 1.52, 95% CI 1.31–1.77) and from a cardiologist (OR 2.04, 95% CI 1.61–2.57). Interpretation: Nonclinical factors are strongly associated with physician follow-up for patients with chest pain after discharge from the emergency department. However, patients with comorbidities and at higher risk for future adverse events are less likely to receive follow-up care.

OBJECTIVE Patients can potentially monitor disease activity of RA through self-assessed swollen joints (clinical synovitis), but reliability is poor. The objective is to evaluate the use of education by US feedback on the ability of patients to assess for clinical synovitis in RA. METHODS We performed a 6 month, single-centre, randomized controlled trial on patients with established RA to study the effect of education on self-assessment of joints that included initial brief patient training on tender (TJC) and swollen (SJC) joint counts followed by US feedback every 3 months vs standard care without education. Patient and physician independently performed 28-joint counts at each visit. Outcome variables included the percentage of patients with good agreement with physician-derived swollen joints [prevalence-adjusted bias-adjusted kappa (PABAK) >0.6] as well as agreement in the SJC (Bland and Altman 95% limits of agreement), feasibility/patient satisfaction survey and disease activity at 6 months. RESULTS Of the 101 randomized patients, 95 were included (51 in the education arm and 44 in the standard care arm). At 6 months there was a significant difference in the proportion of patients with swollen joint PABAK >0.6 in the education arm compared with standard care (98 vs 85%, P = 0.02). Limits of agreement for the SJC difference between physician and patients were reduced only in the education arm. The training method is considered feasible, with 94% of patients reporting it as useful. A trend of higher rates of disease remission (28-joint DAS

Dual-chamber (DDD) and VDD pacing are recognized alternatives for patients with advanced atrioventricular (AV) conduction abnormalities and spared sinus node function. The comparative data between these 2 modes are limited.A literature search was performed using multiple major databases. Outcomes of interest were (1) adverse events including incidence of atrial fibrillation (AF) and (2) procedural parameters. Odds ratio (OR) was reported for dichotomous variables and standardized mean difference (SMD) for continuous variables.Eight controlled studies (7 cohorts and 1 randomized controlled trial: total 1942 patients) were included. VDD mode was used in 922 patients. Mean follow-up period for the VDD group was 51 ± 24 months. There was a trend toward lower overall adverse events in the VDD group (9.6% vs 11.6%; OR, 0.74 [95% confidence interval (CI), 0.51-1.05; P = 0.09]). Shorter implantation and fluoroscopy times were noted with VDD pacing (46.2 ± 12 vs 65.9 ± 20 minutes; SMD, -0.96 [95% CI, -1.26 to -0.66; P0.0001] and 4.6 ± 1 vs 9.3 ± 0.4 minutes; SMD, -0.83 [95% CI, -1.38 to -0.29; P = 0.003], respectively). Mean P-wave amplitude was significantly lower in VDD (1.5 ± 0.8 mV vs 3.1 ± 0.9 mV; P = 0.02). The incidence of AF was lower in the VDD group but it did not reach statistical significance (7.5% vs 13.0%; OR, 0.7; 95% CI, 0.39-1.27; P = 0.24).This meta-analysis suggests that VDD is a reasonable alternative to DDD pacemakers with lower pneumothorax risk and shorter implantation and fluoroscopy times. More high-quality data are required to definitively compare the 2 strategies.

Summary To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = –0·436, P < 0·01), levels of anti-dsDNA antibody (r = –0·347, P