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2. A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study.

Author

Lu, X, Liu, Z, Cui, Q, Liu, F, Li, J, Niu, X, Shen, C, Hu, D, Huang, K, Chen, J, Xing, X, Zhao, Y, Lu, F, Liu, X, Cao, J, Chen, S, Ma, H, Yu, L, Wu, X, Li, Y, Zhang, H, Mo, X, Zhao, L, Huang, J, Wang, L, Wen, W, Shu, X-O, Takeuchi, F, Koh, W-P, Tai, ES, Cheng, C-Y, Wong, TY, Chang, X, Chan, MY-Y, Gao, W, Zheng, H, Chen, K, He, J, Tang, CS-M, Lam, KSL, Tse, H-F, Cheung, CYY, Takahashi, A, Kubo, M, Kato, N, Terao, C, Kamatani, Y, Sham, PC, Heng, C-K, Hu, Z, Chen, YE, Wu, T, Shen, H, Willer, CJ, Gu, D, Lu, X, Liu, Z, Cui, Q, Liu, F, Li, J, Niu, X, Shen, C, Hu, D, Huang, K, Chen, J, Xing, X, Zhao, Y, Lu, F, Liu, X, Cao, J, Chen, S, Ma, H, Yu, L, Wu, X, Li, Y, Zhang, H, Mo, X, Zhao, L, Huang, J, Wang, L, Wen, W, Shu, X-O, Takeuchi, F, Koh, W-P, Tai, ES, Cheng, C-Y, Wong, TY, Chang, X, Chan, MY-Y, Gao, W, Zheng, H, Chen, K, He, J, Tang, CS-M, Lam, KSL, Tse, H-F, Cheung, CYY, Takahashi, A, Kubo, M, Kato, N, Terao, C, Kamatani, Y, Sham, PC, Heng, C-K, Hu, Z, Chen, YE, Wu, T, Shen, H, Willer, CJ, and Gu, D

Abstract

AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS. CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.

Published
2022

3. Cardiac remodelling - Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology

Author

Gonzalez, A, Richards, AM, de Boer, RA, Thum, T, Arfsten, H, Hulsmann, M, Falcao-Pires, I, Diez, J, Foo, RSY, Chan, MY, Aimo, A, Anene-Nzelu, CG, Abdelhamid, M, Adamopoulos, S, Anker, SD, Belenkov, Y, Gal, TB, Cohen-Solal, A, Bohm, M, Chioncel, O, Delgado, V, Emdin, M, Jankowska, EA, Gustafsson, F, Hill, L, Jaarsma, T, Januzzi, JL, Jhund, PS, Lopatin, Y, Lund, LH, Metra, M, Milicic, D, Moura, B, Mueller, C, Mullens, W, Nunez, J, Piepoli, MF, Rakisheva, A, Ristic, AD, Rossignol, P, Savarese, G, Tocchetti, CG, Van Linthout, S, Volterrani, M, Seferovic, P, Rosano, G, Coats, AJS, and Bayes-Genis, A

Subjects
Tissue, Cells, Biomarkers, Remodeling
Abstract

Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.

Published
2022

4. High-grade ductal carcinoma in-situ detected by microcalcification within borderline phyllodes tumour: A report of a case and literature review

Author

Tse Gm, Yuen Wn, Li Jjx, and Chan My

Subjects
In situ, Pathology, medicine.medical_specialty, Text mining, business.industry, Medicine, Microcalcification, Ductal carcinoma, medicine.symptom, business
Abstract

BackgroundPhyllodes tumour is a rare biphasic neoplasm of the breast that mostly affects middle aged women. Ductal carcinoma in-situ and microcalcifications occurring within phyllodes tumours are documented but are rare findings. Primary surgical excision with adjuvant therapies remains the mainstay of treatment.Case presentationWe report a case of a 42-year-old woman with high-grade ductal carcinoma in-situ within a borderline phyllodes tumour. Radiologically, clumps of microcalcification were detected within the lesion. Local excision followed by total mastectomy with axillary dissection was then performed. No tumour recurrence was detected up to a period of 8 years.ConclusionPresence of microcalcifications within a phyllodes tumour should alert clinicians and pathologists of possible coexisting carcinoma components. Stromal and epithelial components of these lesions should be evaluated separately when formulating a management plan.

Published
2021

5. Brainhack: Developing a culture of open, inclusive, community-driven neuroscience

Author

Gau, R, Noble, S, Heuer, K, Bottenhorn, KL, Bilgin, IP, Yang, YF, Huntenburg, JM, Bayer, JMM, Bethlehem, RAI, Rhoads, SA, Vogelbacher, C, Borghesani, V, Levitis, E, Wang, HT, Van Den Bossche, S, Kobeleva, X, Legarreta, JH, Guay, S, Atay, SM, Varoquaux, GP, Huijser, DC, Sandström, MS, Herholz, P, Nastase, SA, Badhwar, AP, Dumas, G, Schwab, S, Moia, S, Dayan, M, Bassil, Y, Brooks, PP, Mancini, M, Shine, JM, O'Connor, D, Xie, X, Poggiali, D, Friedrich, P, Heinsfeld, AS, Riedl, L, Toro, R, Caballero-Gaudes, C, Eklund, A, Garner, KG, Nolan, CR, Demeter, DV, Barrios, FA, Merchant, JS, McDevitt, EA, Oostenveld, R, Craddock, RC, Rokem, A, Doyle, A, Ghosh, SS, Nikolaidis, A, Stanley, OW, Uruñuela, E, Anousheh, N, Arnatkeviciute, A, Auzias, G, Bachar, D, Bannier, E, Basanisi, R, Basavaraj, A, Bedini, M, Bellec, P, Benn, RA, Berluti, K, Bollmann, S, Bradley, C, Brown, J, Buchweitz, A, Callahan, P, Chan, MY, Chandio, BQ, Cheng, T, Chopra, S, Chung, AW, Close, TG, Combrisson, E, Cona, G, Constable, RT, Cury, C, Dadi, K, Damasceno, PF, Das, S, De Vico Fallani, F, DeStasio, K, Dickie, EW, Dorfschmidt, L, Duff, EP, DuPre, E, Dziura, S, Esper, NB, Esteban, O, Fadnavis, S, Flandin, G, Flannery, JE, Flournoy, J, Forkel, SJ, Gau, R, Noble, S, Heuer, K, Bottenhorn, KL, Bilgin, IP, Yang, YF, Huntenburg, JM, Bayer, JMM, Bethlehem, RAI, Rhoads, SA, Vogelbacher, C, Borghesani, V, Levitis, E, Wang, HT, Van Den Bossche, S, Kobeleva, X, Legarreta, JH, Guay, S, Atay, SM, Varoquaux, GP, Huijser, DC, Sandström, MS, Herholz, P, Nastase, SA, Badhwar, AP, Dumas, G, Schwab, S, Moia, S, Dayan, M, Bassil, Y, Brooks, PP, Mancini, M, Shine, JM, O'Connor, D, Xie, X, Poggiali, D, Friedrich, P, Heinsfeld, AS, Riedl, L, Toro, R, Caballero-Gaudes, C, Eklund, A, Garner, KG, Nolan, CR, Demeter, DV, Barrios, FA, Merchant, JS, McDevitt, EA, Oostenveld, R, Craddock, RC, Rokem, A, Doyle, A, Ghosh, SS, Nikolaidis, A, Stanley, OW, Uruñuela, E, Anousheh, N, Arnatkeviciute, A, Auzias, G, Bachar, D, Bannier, E, Basanisi, R, Basavaraj, A, Bedini, M, Bellec, P, Benn, RA, Berluti, K, Bollmann, S, Bradley, C, Brown, J, Buchweitz, A, Callahan, P, Chan, MY, Chandio, BQ, Cheng, T, Chopra, S, Chung, AW, Close, TG, Combrisson, E, Cona, G, Constable, RT, Cury, C, Dadi, K, Damasceno, PF, Das, S, De Vico Fallani, F, DeStasio, K, Dickie, EW, Dorfschmidt, L, Duff, EP, DuPre, E, Dziura, S, Esper, NB, Esteban, O, Fadnavis, S, Flandin, G, Flannery, JE, Flournoy, J, and Forkel, SJ

Published
2021

6. Development and evaluation of a technology-enhanced, enquiry-based learning program on managing neonatal extravasation injury: A pre-test/post-test mixed-methods study.

Author

Chau, JPC, Lo, SHS, Chan, KM, Chan, MY, Lee, VWY, Lam, SKY, Choi, KC, Thompson, DR, Chau, JPC, Lo, SHS, Chan, KM, Chan, MY, Lee, VWY, Lam, SKY, Choi, KC, and Thompson, DR

Abstract

BACKGROUND: Extravasation injury remains a significant preventable cause of morbidity and mortality in neonates. Equipping nursing students with the requisite knowledge and skills is essential for appropriate prevention, early detection, and management of extravasation injury. OBJECTIVES: To develop a technology-enhanced, enquiry-based learning program for nursing students on the prevention and management of neonatal extravasation injury and examine its impact on their knowledge, approaches to studying and experience of learning. DESIGN: A pre-test/post-test study with qualitative evaluation. SETTINGS: Two university pre-registration nursing programs in Hong Kong. PARTICIPANTS: A total of 192 senior-year nursing students. METHODS: A novel learning program was developed comprising 25 scenario-based video vignettes supplemented with critical-thinking exercises, discussion guides, interactive games, reading materials and a 3-hour in-class interactive workshop. Students received unlimited online access to the program. Data were collected at baseline and one-month post-workshop. Outcomes were students' level of knowledge of prevention and management of extravasation injuries and related care, approaches to studying, and experience of learning. Paired t-tests were performed on pre- post-test outcome data and individual semi-structured interviews were conducted at one-month post-workshop, transcribed verbatim and analyzed thematically. RESULTS: There were statistically significant improvements in students' level of knowledge and use of a deep approach to learning at one month compared with baseline. Students were highly satisfied with the program, appreciating the video vignettes and interactive small group discussions with academics and clinicians. Suggestions for enhancing the program included more time for the workshop, interaction with clinicians, and details on the administration of neonatal medications and dosages. CONCLUSIONS: This study showed that a novel technolo

Published
2021

7. Shared reference materials harmonize lipidomics across MS-based detection platforms and laboratories[S]

Author

Triebl, A, Burla, B, Selvalatchmanan, J, Oh, J, Tan, SH, Chan, MY, Mellett, NA, Meikle, PJ, Torta, F, Wenk, MR, Triebl, A, Burla, B, Selvalatchmanan, J, Oh, J, Tan, SH, Chan, MY, Mellett, NA, Meikle, PJ, Torta, F, and Wenk, MR

Abstract

Quantitative MS of human plasma lipids is a promising technology for translation into clinical applications. Current MS-based lipidomic methods rely on either direct infusion (DI) or chromatographic lipid separation methods (including reversed phase and hydrophilic interaction LC). However, the use of lipid markers in laboratory medicine is limited by the lack of reference values, largely because of considerable differences in the concentrations measured by different laboratories worldwide. These inconsistencies can be explained by the use of different sample preparation protocols, method-specific calibration procedures, and other experimental and data-reporting parameters, even when using identical starting materials. Here, we systematically investigated the roles of some of these variables in multiple approaches to lipid analysis of plasma samples from healthy adults by considering: 1) different sample introduction methods (separation vs. DI methods); 2) different MS instruments; and 3) between-laboratory differences in comparable analytical platforms. Each of these experimental variables resulted in different quantitative results, even with the inclusion of isotope-labeled internal standards for individual lipid classes. We demonstrated that appropriate normalization to commonly available reference samples (i.e., "shared references") can largely correct for these systematic method-specific quantitative biases. Thus, to harmonize data in the field of lipidomics, in-house long-term references should be complemented by a commonly available shared reference sample, such as NIST SRM 1950, in the case of human plasma.

Published
2020

9. An evaluation of the effectiveness of patient-controlled analgesia after spinal surgery

Author

White, Carole L., Pokrupa, Ronald P., and Chan, My Hoa

Subjects
Back, Analgesia -- Innovations
Abstract

Patient-controlled analgesia (PCA) is safe and effective for patients undergoing spinal surgery. Results in a study comparing its effectiveness in 60 patients undergoing this type of operation and randomly assigned to receive intramuscular injections on a PRN basis, the standard approach to postoperative analgesia, or PCA, showed that the PCA group reported lower levels of pain and were walking earlier than patients receiving standard analgesia., The purpose of this study was to evaluate the effectiveness of patient-con trolled analgesia (PCA) in patients undergoing spinal surgery. Sixty patients undergoing spinal surgery were randomly assigned to receive PCA or the standard approach to postoperative analgesia (intramuscular injections on an "as needed" basis). Information on pain intensity at rest and with activity, total daily amount of analgesia, presence of adverse effects, length of time to ambulation and length of hospital stay was collected on all patients. Patients in the PCA group reported lower levels of pain, both at rest and with activity, and were ambulating earlier than patients receiving standard analgesia. There were no differences between the groups in total daily analgesic intake, presence of adverse effects and length of hospital stay. These data suggest that PCA is a safe, effective approach to managing pain after spinal surgery., Introduction Pain continues to be a major concern for patients undergoing surgery. Despite important advances in the understanding of narcotic analgesic mechanisms and drug delivery techniques, adequate pain relief often [...]

Published
1998

10. Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia.

Author

Han, Y, Dorajoo, R, Chang, X, Wang, L, Khor, C-C, Sim, X, Cheng, C-Y, Shi, Y, Tham, YC, Zhao, W, Chee, ML, Sabanayagam, C, Tan, N, Wong, TY, Tai, E-S, Liu, J, Goh, DYT, Yuan, J-M, Koh, W-P, van Dam, RM, Low, AF, Chan, MY-Y, Friedlander, Y, Heng, C-K, Han, Y, Dorajoo, R, Chang, X, Wang, L, Khor, C-C, Sim, X, Cheng, C-Y, Shi, Y, Tham, YC, Zhao, W, Chee, ML, Sabanayagam, C, Tan, N, Wong, TY, Tai, E-S, Liu, J, Goh, DYT, Yuan, J-M, Koh, W-P, van Dam, RM, Low, AF, Chan, MY-Y, Friedlander, Y, and Heng, C-K

Abstract

Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising three Chinese studies and one Malay study (Total N = 2,169 CAD cases and 7,376 controls). Top hits (P < 5 × 10-8) were further evaluated in 291 CAD cases and 1,848 controls of Asian Indians. Using all datasets, we validated recently identified loci associated with CAD. The involvement of known canonical pathways in CAD was tested by Ingenuity Pathway Analysis. We identified a missense SNP (rs2075291, G > T, G185C) in APOA5 for CAD that reached robust genome-wide significance (Meta P = 7.09 × 10-10, OR = 1.636). Conditional probability analysis indicated that the association at rs2075291 was independent of previously reported index SNP rs964184 in APOA5. We further replicated 10 loci previously identified among predominantly Europeans (P: 1.33 × 10-7-0.047). Seven pathways (P: 1.10 × 10-5-0.019) were identified. We identified a missense SNP, rs2075291, in APOA5 associated with CAD at a genome-wide significance level and provided new insights into pathways contributing to the susceptibility to CAD in the multi-ethnic populations from Southeast Asia.

Published
2017

11. Random blinded rechecking of sputum acid-fast bacilli smear using fluorescence microscopy: 8 years' experience

Author

C.W. Yip, Yu Kw, Tang Hs, Kai Man Kam, Cheung Wf, and Chan My

Subjects
Pulmonary and Respiratory Medicine, Background fluorescence, medicine.medical_specialty, Quality Assurance, Health Care, Reference laboratory, Sensitivity and Specificity, Mycobacterium, medicine, Humans, False Positive Reactions, False Negative Reactions, Tuberculosis, Pulmonary, Retrospective Studies, Bacteriological Techniques, Staining and Labeling, business.industry, Sputum, High-Throughput Screening Assays, Surgery, Infectious Diseases, Microscopy, Fluorescence, Acid-fast, Hong Kong, medicine.symptom, business, Nuclear medicine
Abstract

BACKGROUND The Hong Kong TB Reference Laboratory is a high volume laboratory examining around 400 sputum acid-fast bacilli smears daily using fluorescence microscopy (FM). OBJECTIVE To assess the effectiveness of blinded rechecking applied to FM in a high-throughput laboratory. METHOD From 2003, 2.5% (5% in 2003 and 2004) of all smears were randomly selected, relabelled and assigned to each technician (rechecker) in turn. These smears were restained and re-examined. Discordance between initial screener and rechecker was resolved by a controller. RESULTS From 2003 to 2010, low false-negative (LFN) errors (0.10-0.27%) were within the critical values, at 85% (1 year) and 90% (7 years) sensitivity. However, LFN error (0.28-0.62%) among recheckers was prominent. There were also low false-positive (LFP) cases (0.13-0.75%), but subsequent cultures showed these to be mycobacteria culture-positive. This relatively poor performance among the recheckers might be due to background fluorescence increase after restaining and/or inefficiency of the rechecking procedure. CONCLUSION In a high-throughput laboratory, blind rechecking is a good means of quality assurance. To minimise false LFP, problems due to restaining should be resolved before blinded rechecking can be generally applied in the field for FM where mycobacterial cultures are not routinely performed.

Published
2012

13. Relationship between body mass index and fracture risk is mediated by bone mineral density

Author

Chan, MY, Frost, SA, Center, JR, Eisman, JA, and Nguyen, TV

Subjects
Aged, 80 and over, Male, Middle Aged, Anatomy & Morphology, Femoral Neck Fractures, Body Mass Index, Radiography, Sex Factors, Risk Factors, Bone Density, Humans, Female, Prospective Studies, Aged
Abstract

© 2014 American Society for Bone and Mineral Research. The relationship between body mass index (BMI) and fracture risk is controversial. We sought to investigate the effect of collinearity between BMI and bone mineral density (BMD) on fracture risk, and to estimate the direct and indirect effect of BMI on fracture with BMD being the mediator. The study involved 2199 women and 1351 men aged 60 years or older. BMI was derived from baseline weight and height. Femoral neck BMD was measured by dual-energy X-ray absorptiometry (DXA; GE-LUNAR, Madison, WI, USA). The incidence of fragility fracture was ascertained by X-ray reports from 1991 through 2012. Causal mediation analysis was used to assess the mediated effect of BMD on the BMI-fracture relationship. Overall, 774 women (35% of total women) and 258 men (19%) had sustained a fracture. Approximately 21% of women and 20% of men were considered obese (BMI ≥ 30). In univariate analysis, greater BMI was associated with reduced fracture risk in women (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.85 to 0.99) and in men (HR 0.77; 95% CI, 0.67 to 0.88). After adjusting for femoral neck BMD, higher BMI was associated with greater risk of fracture in women (HR 1.21; 95% CI, 1.11 to 1.31) but not in men (HR 0.96; 95% CI, 0.83 to 1.11). Collinearity had minimal impact on the BMD-adjusted results (variance inflation factor [VIF]=1.2 for men and women). However, in mediation analysis, it was found that the majority of BMI effect on fracture risk was mediated by femoral neck BMD. The overall mediated effect estimates were -0.048 (95% CI, -0.059 to -0.036; p

Published
2014

14. The ARID domain of the H3K4 demethylase RBP2 binds to a DNA CCGCCC motif

Author

Tu S, Li-Jung Juan, Cheng An, Chan My, Lin Ph, Ying-Ta Wu, Chunhua Yuan, Tsai, and Yu-Ching Teng

Subjects
Histone H3 Lysine 4, HMG-box, Fluorescent Antibody Technique, Protein Serine-Threonine Kinases, Structure-Activity Relationship, Structural Biology, Transcription (biology), parasitic diseases, Demethylase activity, Humans, Promoter Regions, Genetic, Nuclear Magnetic Resonance, Biomolecular, Molecular Biology, Transcription factor, biology, fungi, Retinol-Binding Proteins, Cellular, DNA, humanities, Biochemistry, KDM5A, biology.protein, Demethylase, geographic locations, Protein Binding, Transcription Factors, Binding domain
Abstract

The histone H3 lysine 4 demethylase RBP2 contains a DNA binding domain, the AT-rich interaction domain (ARID). We solved the structure of ARID by NMR, identified its DNA binding motif (CCGCCC) and characterized the binding contacts. Immunofluorescence and luciferase assays indicated that ARID is required for RBP2 demethylase activity in cells and that DNA recognition is essential to regulate transcription.

Published
2008

15. Abstracts of the 21st International Isotope Society (UK group) symposium: synthesis and applications of labelled compounds 2012

Author

Arstad, E, Badar, A, Baxter, A, Bower, JF, Cable, KM, Carroll, MA, Chan, MY, Charlton, M, Christlieb, M, Cornelissen, B, Cox, LR, Davis, B, Dilworth, JR, El-Emir, E, Ellames, GJ, Galante, E, Geach, N, Gee, AD, Gouverneur, V, Gregson, TJ, Hendry, D, Hueting, R, Hussien, K, Ilyas, T, Jenkins, DD, Kersemans, V, Knagg, E, Koepp, M, Kohler, AD, Krauser, JA, Launay, GG, Lockley, WJ, Lythgoe, MF, Manthorpe, DP, McEwen, A, Muschel, RJ, Oldfield, MF, Passchier, J, Pedley, RB, Rajkumar, V, Reed, CD, Robson, M, Roe, SJ, Ryan, JJ, Sander, K, Shipley, N, Smart, SC, Smith, N, Spurr, DW, Taylor, KR, Tredwell, M, Whitehead, DM, Woolley, G, and Yan, R

Abstract

The 21st annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK, on Friday 12th October 2012. The meeting was attended by around 60 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral and poster presentations on isotopic chemistry and applications of labelled compounds or of chemistry with potential implications for isotopic synthesis. Both short-lived and long-lived isotopes were represented, as were stable isotopes. The symposium programme was divided into a morning session chaired by Professor Chris Willis (University of Bristol, UK) and afternoon sessions chaired by Mr Mike Chappelle (Quotient Biosciences, UK) and by Dr Sofia Pascu (University of Bath, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, Stevenage, UK).

Published
2013

16. Absolute fracture-risk prediction by a combination of calcaneal quantitative ultrasound and bone mineral density

Author

Chan, MY, Nguyen, ND, Center, JR, Eisman, JA, and Nguyen, TV

Subjects
musculoskeletal diseases, Aged, 80 and over, Male, Models, Statistical, Femur Neck, Middle Aged, Endocrinology & Metabolism, Calcaneus, Fractures, Bone, Absorptiometry, Photon, Risk Factors, Predictive Value of Tests, Bone Density, Humans, Female, Aged, Ultrasonography
Abstract

Quantitative ultrasound measurement (QUS) and bone mineral density (BMD) have each been shown to predict fracture risk in women. The present study examined whether a combination of QUS and BMD could improve the predictive accuracy of fracture risk. This is a population-based prospective study which involved 454 women and 445 men aged 62-89 years. Femoral neck BMD (FNBMD) was measured by DXA and calcaneal QUS was measured as broadband ultrasound attenuation (BUA) by a CUBA sonometer. Fragility fracture was ascertained by X-ray reports during the follow-up period, which took place between mid-1989 and 2009. During the follow-up period (median 13 years, range 11-15), 75 men and 154 women sustained a fragility fracture. In women, the model with FNBMD and BUA had a higher AUC compared to that without BUA (0.73 vs. 0.71 for any fracture, 0.81 vs. 0.77 for hip fracture, and 0.72 vs. 0.70 for vertebral fracture). Reclassification analysis yielded a total net reclassification improvement of 7.3%, 11.1%, and 5.2% for any, hip, and vertebral fractures, respectively. For men, the addition of BUA to FNBMD did not improve the predictive power for any, hip, or vertebral fracture. These results suggest that calcaneal QUS is an independent predictor of fracture risk and that a combination of QUS and BMD measurement could improve the predictive accuracy of fracture risk in elderly women. © 2011 Springer Science+Business Media, LLC.

Published
2011

18. VA Health Care: Actions Needed to Address Higher-Than-Expected Demand for the Family Caregiver Program

Author

GOVERNMENT ACCOUNTABILITY OFFICE WASHINGTON DC, Williamson, Randall B, Anderson, Bonnie, Caison, Frederick, Davis, Christine, Hamann, Cathy, Hamiliton, Jaquelyn, Nguyen, Giao N, Sondheim, Chan-My J, GOVERNMENT ACCOUNTABILITY OFFICE WASHINGTON DC, Williamson, Randall B, Anderson, Bonnie, Caison, Frederick, Davis, Christine, Hamann, Cathy, Hamiliton, Jaquelyn, Nguyen, Giao N, and Sondheim, Chan-My J

Abstract

VHA s Family Caregiver Program is designed to provide support and services to family caregivers of post-9/11 veterans who have a serious injury incurred or aggravated in the line of duty. The program provides approved primary family caregivers with a monthly financial stipend as well as training and other support services, such as counseling and respite care., Report to Congressional Requesters

Published
2014

19. Bone mineral density and association of osteoarthritis with fracture risk

Author

Chan, MY, Center, JR, Eisman, JA, Nguyen, TV, Chan, MY, Center, JR, Eisman, JA, and Nguyen, TV

Abstract

Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. OBJECTIVE: High body mass index (BMI) is associated with increased risk of osteoarthritis (OA) and reduced risk of fragility fracture. However, the relationship between fragility fracture and OA remained unclear. This study sought to investigate the effect of bone mineral density (BMD) in the OA-fracture relationship.METHODS: Data from 2412 women and 1452 men aged >45 years in the Dubbo Osteoporosis Epidemiology Study (DOES) were analyzed. Individuals have been followed for up to 22 years (median: 7.5 years; range: 0.1-22 years). Femoral neck BMD (FNBMD) and lumbar spine BMD (LSBMD) was measured by dual energy X-ray absorptiometry (DXA) (GE LUNAR, Madison, WI). The presence of OA was ascertained at baseline by self-reported diagnosis. The incidence of low-trauma fracture was ascertained from X-ray reports.RESULTS: Overall, 29% of women and 26% of men had reported a diagnosis of OA. Fracture risk was significantly higher in women with OA than those without OA (Hazard ratio (HR) = 1.50; 95% confidence interval (CI), 1.28-1.76). However, the association was mainly observed in women with osteopenic BMD (HR = 1.74; 95% CI, 1.38-2.17) and normal-BMD (HR = 1.50; 95% CI, 1.06-2.13) and not in those with osteoporosis. Further analysis revealed that osteopenic women with OA had significant increase in risk of vertebral (HR = 1.85; 95% CI, 1.24-2.75) and limb fracture (HR = 2.49; 95% CI, 1.77-3.48), but not in hip fracture. In men, no comparable relationship was found before and after adjustment for covariates.CONCLUSION: Women with OA have an increased risk of fragility fracture, and the risk was mainly observed in non-osteoporotic group.

Published
2014

20. Quantitative ultrasound and fracture risk prediction in non-osteoporotic men and women as defined by WHO criteria

Author

Chan, MY, Nguyen, ND, Center, JR, Eisman, JA, Nguyen, TV, Chan, MY, Nguyen, ND, Center, JR, Eisman, JA, and Nguyen, TV

Abstract

This study sought to determine the association between calcaneal quantitative ultrasound (QUS) and fracture risk in individuals without osteoporosis according to the World Health Organization criteria (i.e., BMD T-score > -2.5). We found that calcaneal QUS is an independent predictor of fracture risk in women with non-osteoporotic bone mineral density (BMD). Introduction: More than 50 % of women and 70 % of men who sustain a fragility fracture have BMD above the osteoporotic threshold (T-score > -2.5). Calcaneal QUS is associated with fracture risk. This study aimed to test the hypothesis that low calcaneal QUS is associated with increased fracture risk in individuals with non-osteoporotic BMD. Methods: We included 312 women and 390 men aged 62-90 years with BMD T-score > -2.5 at femoral neck. QUS was measured in broadband ultrasound attenuation (BUA) at the calcaneus using a CUBA sonometer. BMD was measured at the femoral neck (FNBMD) by dual energy X-ray absorptiometry using GE Lunar DPX-L densitometer. The incidences of any fragility fracture were ascertained by X-ray reports during the follow-up period from 1994 to 2011. Results: Of the 702 participants, 26 % of women (n = 80/312) and 14 % of men (n = 53/390) experienced at least one fragility fracture during the follow-up period. In women, after adjusting for covariates, increased risk of any fracture was significantly associated with decreased BUA (HR = 1.50; 95 % CI, 1.13-1.99). Compared with that of FNBMD, the models with BUA, in women, had greater AUC (0.71, 0.85, 0.71 for any, hip and vertebral fracture, respectively), and yielded a net reclassification improvement of 16.4 % (P = 0.009) when combined with FNBMD. In men, BUA was not significantly associated with fracture risk before and after adjustment. Conclusion: These results suggest that calcaneal BUA is an independent predictor of fracture risk in women with non-osteoporotic BMD. © 2012 International Osteoporosis Foundation and National Osteoporosis F

Published
2013

21. Absolute fracture-risk prediction by a combination of calcaneal quantitative ultrasound and bone mineral density

Author

Chan, MY, Nguyen, ND, Center, JR, Eisman, JA, Nguyen, TV, Chan, MY, Nguyen, ND, Center, JR, Eisman, JA, and Nguyen, TV

Abstract

Quantitative ultrasound measurement (QUS) and bone mineral density (BMD) have each been shown to predict fracture risk in women. The present study examined whether a combination of QUS and BMD could improve the predictive accuracy of fracture risk. This is a population-based prospective study which involved 454 women and 445 men aged 62-89 years. Femoral neck BMD (FNBMD) was measured by DXA and calcaneal QUS was measured as broadband ultrasound attenuation (BUA) by a CUBA sonometer. Fragility fracture was ascertained by X-ray reports during the follow-up period, which took place between mid-1989 and 2009. During the follow-up period (median 13 years, range 11-15), 75 men and 154 women sustained a fragility fracture. In women, the model with FNBMD and BUA had a higher AUC compared to that without BUA (0.73 vs. 0.71 for any fracture, 0.81 vs. 0.77 for hip fracture, and 0.72 vs. 0.70 for vertebral fracture). Reclassification analysis yielded a total net reclassification improvement of 7.3%, 11.1%, and 5.2% for any, hip, and vertebral fractures, respectively. For men, the addition of BUA to FNBMD did not improve the predictive power for any, hip, or vertebral fracture. These results suggest that calcaneal QUS is an independent predictor of fracture risk and that a combination of QUS and BMD measurement could improve the predictive accuracy of fracture risk in elderly women. © 2011 Springer Science+Business Media, LLC.

Published
2012

22. Novel quantized DCT for video encoder optimization

Author

Wang, HL, Chan, MY, Kwong, S., Kok, CW, Wang, HL, Chan, MY, Kwong, S., and Kok, CW

Abstract

A novel technique is proposed to reduce the computational complexity of discrete cosine transform (DCT)-based video encoders. The proposed method merges the DCT and quantization into a single procedure, which is referred to as the novel quantized DCT (NQDCT), such that the DCT output does not need to be explicitly quantized. Thus, a lot of computations related to quantization can be saved. The video encoder's performance using NQDCT is evaluated by comparing it with those using the traditional separate DCT and quantization method and the quantized DCT (QDCT) method. Simulation results demonstrate that the proposed NQDCT outperforms the other two methods in improving the real-time performance for video encoding.

Published
2006

23. Construction of the nearest neighbor embracing graph of a point set

Author

Chan, MY, Chen, DZ, Chin, FYL, Wang, CA, Chan, MY, Chen, DZ, Chin, FYL, and Wang, CA

Abstract

This paper gives optimal algorithms for the construction of the Nearest Neighbor Embracing Graph (NNE-graph) of a given point set V of size n in the k-dimensional space (k-D) for k = 2,3. The NNE-graph provides another way of connecting points in a communication network, which has lower expected degree at each point and shorter total length of connections with respect to those using Delaunay triangulation. In fact, the NNE-graph can also be used as a tool to test whether a point set is randomly generated or has some particular properties. We show that in 2-D the NNE-graph can be constructed in optimal Theta(n(2)) time in the worst case. We also present an O(n log n + nd) time algorithm, where d is the Omega(log n)-th largest degree in the utput NNE-graph. The algorithm is optimal when d=O(log n). The algorithm is also sensitive to the structure of the NNE-graph, for instance when d=g.(log n), the number of edges in NNE-graph is bounded by O(gn log n) for any value g with 1 <= g <= n/log n. We finally propose an O(n log n + nd log d{*}) time algorithm for the problem in 3-D, where d and d{*} are the Omega(log n/log log n)-th largest vertex degree and the largest vertex degree in the NNE-graph, respectively. The algorithm is optimal when the largest vertex degree of the NNE-graph d{*} is O(log n/log log n).

Published
2006

27. Selective electroplating between metal and semiconductor electrodes

Author

Lo, TC, Chan, MY, Lo, TC, and Chan, MY

Abstract

A self-planarizing Au metallization process by selective electrolytic plating was developed for metal interconnections in the submicron range. This process is superior to the conventional gold metallization process and economically viable due to its simplicity and no use of ion-milling. The reaction mechanism of the selective plating between metal and semiconductor electrodes was studied. Voltammetry showed that a much higher deposition potential is required for an oxidized TiW electrode than that for an Au electrode. In this paper, we use the existing TiW barrier layer as part of the electrode during Au plating. Through an O-2 plasma treatment, which is an exiting step for photoresist ashing, we turn the TiW electrode from metallic into semiconducting. Under optimized electrolytic plating conditions, we can selectively plate Au wires into dielectric trenches while leaving the oxidized TiW field free of Au.

Published
1996

28. Ethnic differences in physical pain sensitivity: role of acculturation.

Author

Chan MY, Hamamura T, Janschewitz K, Chan, Michelle Y P, Hamamura, Takeshi, and Janschewitz, Kristin

Abstract

Although research suggests that Asian Americans are more reactive to physical pain than European Americans, some evidence suggests that the observed differences in ethnicity may actually reflect Asian Americans' differing levels of acculturation. Two studies were conducted to test this hypothesis. In Study 1, first- and second-generation Asian Americans and European Americans took part in a cold pressor task. Evidence of heightened pain responses was found only among first-generation Asian Americans. Study 2 further controlled for ethnicity and replicated this pattern in finding heightened pain reactions among mainland Chinese students in Hong Kong relative to Hong Kong Chinese students. These findings suggest a role for acculturation in accounting for ethnic differences in physical pain sensitivity. [ABSTRACT FROM AUTHOR]

Published
2013
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35. A comparison of the pharmacodynamic profiles of nomifensine and amitriptyline in normal subjects.

Author

Chan, MY, Ehsanullah, R, Wadsworth, J, and McEwen, J

Abstract

1 Six healthy male volunteers participated in a double-blind placebo crossover comparison of the pharmacodynamic profiles of single oral doses of 75 mg nomifensine and 50 mg amitriptyline. 2 Nomifensine treatment did not influence salivary flow and did not significantly affect psychomotor performance (critical flicker fusion, pursuit rotor and reaction time): in addition nomifensine had no significant effect on subjective measurements of sedation and concentration. 3 By contrast, amitriptyline treatment significantly reduced salivary flow and was associated with significant sedation and reduced concentration: significant changes in psychomotor performance were also noted. 4 Plasma concentrations of amitriptyline and nomifensine were measured at 2 h. The respective median concentration values were 55.0 ng/ml and 52.0 ng/ml. 5 Ex vivo platelet amine uptake of dopamine (DA) and 5- hydroxytryptamine (5HT) was measured 2 h after each treatment. Both nomifensine and amitriptyline treatment significantly inhibited DA uptake to a similar extent. Amitriptyline treatment additionally inhibited 5-HT uptake. [ABSTRACT FROM AUTHOR]

Published
1980
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36. An Evaluation of the Effectiveness of PatientControlled Analgesia After Spinal Surgery

Author

White, Carole L., Pokrupa, Ronald P., and Chan, My Hoa

Abstract

The purpose of this study was to evaluate the effectiveness of patientcontrolled analgesia PCA in patients undergoing spinal surgery. Sixty patients undergoing spinal surgery were randomly assigned to receive PCA or the standard approach to postoperative analgesia intramuscular injections on an “as needed” basis. Information on pain intensity at rest and with activity, total daily amount of analgesia, presence of adverse effects, length of time to ambulation and length of hospital stay was collected on all patients. Patients in the PCA group reported lower levels of pain, both at rest and with activity, and were ambulating earlier than patients receiving standard analgesia. There were no differences between the groups in total daily analgesic intake, presence of adverse effects and length of hospital stay. These data suggest that PCA is a safe, effective approach to managing pain after spinal surgery.

Published
1998

41. Quantitative automated assessment of myocardial perfusion at cardiac catheterization.

Author

Boyle AJ, Schuleri KH, Lienard J, Vaillant R, Chan MY, Zimmet JM, Mazhari R, Centola M, Feigenbaum G, Dib J, Kapur NK, Hare JM, Resar JR, Boyle, Andrew J, Schuleri, Karl H, Lienard, Jean, Vaillant, Regis, Chan, Michael Y, Zimmet, Jeffrey M, and Mazhari, Ramesh

Abstract

Perfusion assessed in the cardiac catheterization laboratory predicts outcomes after myocardial infarction. The aim of this study was to investigate a novel method of assessing perfusion using digital subtraction angiography to generate a time-density curve (TDC) of myocardial blush, incorporating epicardial and myocardial perfusion. Seven pigs underwent temporary occlusion of the left anterior descending coronary artery for 60 minutes. Angiography was performed in the same projections before, during, and after occlusion. Perfusion parameters were obtained from the TDC and compared with Thrombolysis In Myocardial Infarction (TIMI) frame count and myocardial perfusion grade. In addition, safety and feasibility were tested in 8 patients after primary percutaneous coronary intervention. The contrast density differential between the proximal artery and the myocardium derived from the TDC correlated well with TIMI myocardial perfusion grade (R = 0.54, p <0.001). The arterial transit time derived from the TDC correlated with TIMI frame count (R = 0.435, p = 0.011). Using a cutoff of 2.4, the density/time ratio, a ratio of density differential to transit time, had sensitivity and specificity of 100% for coronary arterial occlusion. The positive and negative predictive values were 100%. The generation of a TDC was safe and feasible in 7 patients after acute myocardial infarctions, but the correlation between TDC-derived parameters and TIMI parameters did not reach statistical significance. In conclusion, this novel method of digital subtraction angiography with rapid, automated, quantitative assessment of myocardial perfusion in the cardiac catheterization laboratory correlates well with established angiographic measures of perfusion. Further studies to assess the prognostic value of this technique are warranted. [ABSTRACT FROM AUTHOR]

Published
2008
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42. Fasxiator, a novel factor XIa inhibitor from snake venom, and its site-specific mutagenesis to improve potency and selectivity

Author

W. Chen, Leonardo Carvalho, R. M. Kini, T. S. Kang, Mark Y. Chan, Chen, W, Carvalho, LPD, Chan, MY, Kini, RM, and Kang, TS

Subjects
Male, Snake venom, Bungarus, medicine.drug_class, Protein Conformation, Molecular Sequence Data, Pharmacology, Biology, Binding, Competitive, Ferric Compounds, Factor XIa, Structure-Activity Relationship, Chlorides, In vivo, medicine, Potency, Animals, Humans, Carotid Stenosis, Amino Acid Sequence, IC50, Blood Coagulation, Prothrombin time, Carotid artery thrombosis, medicine.diagnostic_test, Dose-Response Relationship, Drug, Anticoagulant, Anticoagulants, Thrombosis, Hematology, Protease inhibitors, Bungarotoxins, Protease inhibitor (biology), Recombinant Proteins, Mice, Inbred C57BL, Disease Models, Animal, Kinetics, Coagulation, Immunology, Mutation, Mutagenesis, Site-Directed, Prothrombin Time, Partial Thromboplastin Time, medicine.drug, Partial thromboplastin time, Factor Xa Inhibitors
Abstract

Background: Bleeding remains a major limitation of standard anticoagulant drugs that target the extrinsic and common coagulation pathways. Recently, intrinsic coagulation factors are increasingly being investigated as alternative targets for developing anticoagulant drugs with lower bleeding risk.Objectives: Goals were to (i) identify novel anticoagulants selectively targeting intrinsic coagulation pathway and (ii) characterize and further improve the properties of the identified anticoagulants. Methods and Results: We have isolated and sequenced a specific factor XIa (FXIa) inhibitor, henceforth named Fasxiator, from the venom of the banded krait snake, Bungarus fasciatus. It is a Kunitz-type protease inhibitor that prolonged activated partial thromboplastin time without significant effects on prothrombin time. Fasxiator was recombinantly expressed (rFasxiator), purified, and characterized to be a slow-type inhibitor of FXIa that exerts its anticoagulant activities (doubled activated partial thromboplastin time at ~ 3 μmol L–1) by selectively inhibiting human FXIa in in vitro assays. A series of mutants were subsequently generated to improve the potency and selectivity of recombinant rFasxiator. rFasxiatorN17R,L19E showed the best balance between potency (IC50 ~ 1 nmol L–1) and selectivity (> 100 times). rFasxiatorN17R,L19E is a competitive slow-type inhibitor of FXIa (Ki = 0.86 nmol L–1), possesses anticoagulant activity that is ~ 10 times stronger in human plasma than in murine plasma, and prolonged the occlusion time of mice carotid artery in FeCl3-induced thrombosis models. Conclusion: We have isolated an exogenous FXIa specific inhibitor, engineered it to improve its potency by ~ 1000 times and demonstrated its in vitro and in vivo efficacy. These proof-of-principle data supported the further development of Fasxiator as a novel anticoagulant candidate. Refereed/Peer-reviewed

Published
2014

43. Plasma ceramides as biomarkers for microvascular disease and clinical outcomes in diabetes and myocardial infarction.

Author

Junqueira DL, Cavalcanti AB, Sallum JMF, Yasaki E, de Andrade Jesuíno I, Stach A, Negrelli K, de Oliveira Silva L, Lopes MA, Caixeta A, Chan MY, Ching J, Carvalho VM, Faccio AT, Tsutsui J, Rizzatti E, Fonseca RA, Summers S, Fonseca HA, Rochitte CE, Krieger JE, and de Carvalho LP

Abstract

Background: Ceramides have recently been identified as novel biomarkers associated with diabetes mellitus (DM) and major adverse cardiac and cerebrovascular events (MACCE). This study aims to explore their utility in diagnosing microvascular disease., Methods: This study prospectively enrolled 309 patients from 2018 to 2020 into three groups: healthy controls (Group 1, N = 51), DM patients without acute myocardial infarction (AMI) (Group 2, N = 150), and DM patients with AMI (Group 3, N = 108). We assessed outcomes using stress perfusion cardiac magnetic resonance (CMR) imaging for coronary microvascular disease (CMD) (Outcome 1), retinography for retinal microvascular disease (RMD) (Outcome 2), both CMD and RMD (Outcome 3), and absence of microvascular disease (w/o MD) (outcome 4). We evaluated the classification performance of ceramides using receiver operating characteristic (ROC) analysis and multiple logistic regression. 11-ceramide panel previously identified by our research group as related to macrovascular disease were used., Results: Average glycated hemoglobin (HbA1c) values were 5.1% in Group 1, 8.3% in Group 2, and 7.6% in Group 3. Within the cohort, CMD was present in 59.5% of patients, RMD in 25.8%, both CMD and RMD in 18.8%, and w/o MD in 38.5%. The AUC values for the reference ceramide ratios were as follows: CMD at 0.66 (p = 0.012), RMD at 0.61 (p = 0.248), CMD & RMD at 0.64 (p = 0.282), and w/o MD at 0.67 (p = 0.010). In contrast, the AUC values using 11-ceramide panel showed significant improvement in the outcomes prediction: CMD at 0.81 (p = 0.001), RMD at 0.73 (p = 0.010), CMD & RMD at 0.73 (p = 0.04), and w/o MD at 0.83 (p = 0.010). Additionally, the plasma concentration of C14.0 was notably higher in the w/o MD group (p < 0.001)., Conclusions: Plasma ceramides serve as potential predictors for health status and microvascular disease phenotypes in diabetic patients., (© 2024. The Author(s).)

Published
2024
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44. Global burden of cardiovascular diseases: projections from 2025 to 2050.

Author

Chong B, Jayabaskaran J, Jauhari SM, Chan SP, Goh R, Kueh MTW, Li H, Chin YH, Kong G, Anand VV, Wang JW, Muthiah M, Jain V, Mehta A, Lim SL, Foo R, Figtree GA, Nicholls SJ, Mamas MA, Januzzi JL, Chew NWS, Richards AM, and Chan MY

Abstract

Aims: The prediction of future trends in cardiovascular disease (CVD) mortality and their risk factors can assist policy-makers in healthcare planning. This study aims to project geospatial trends in CVDs and their underlying risk factors from 2025 to 2050., Methods and Results: Using historical data on mortality and disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2019 study, encompassing the period of 1990 to 2019, Poisson regression was performed to model mortality and DALYs associated with CVD and its associated risk factors from 2025 to 2050. Subgroup analysis was based on GBD super-regions. Between 2025 and 2050, a 90.0% increase in cardiovascular prevalence, 73.4% increase in crude mortality, and 54.7% increase in crude DALYs are projected, with an expected 35.6 million cardiovascular deaths in 2050 (from 20.5 million in 2025). However, age-standardized cardiovascular prevalence will be relatively constant (-3.6%), with decreasing age-standardized mortality (-30.5%) and age-standardized DALYs (-29.6%). In 2050, ischaemic heart disease will remain the leading cause of cardiovascular deaths (20 million deaths) while high systolic blood pressure will be the main cardiovascular risk factor driving mortality (18.9 million deaths). Central Europe, Eastern Europe, and Central Asia super-region is set to incur the highest age-standardized cardiovascular mortality rate in 2050 (305 deaths per 100 000 population)., Conclusion: In the coming decades, the relatively constant age-standardized prevalence of global CVD suggests that the net effect of summative preventative efforts will likely continue to be unchanged. The fall in age-standardized cardiovascular mortality reflects the improvement in medical care following diagnosis. However, future healthcare systems can expect a rapid rise in crude cardiovascular mortality, driven by the ageing global populace. The continued rise in CVD burden will largely be attributed to atherosclerotic diseases., Registration: Not applicable., Competing Interests: Conflict of interest: M.Y.C. receives speaker’s fees and research grants from Astra Zeneca, Abbott Technologies and Boston Scientific. M.Y.C receives salary support from a National Medical Research Council Clinician Scientist Award-Senior Category (MOH-000280-00). N.W.S.C. has received research grant support from NUHS Seed Fund, National University of Singapore Yong Loo Lin School of Medicine's Academic Fellowship Scheme, the NUHS Clinician Scientist Program, and National Medical Research Council Research Training Fellowship. J.L.J. is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Jana Care, Janssen, Novartis, Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. A.M.R. holds the New Zealand Heart Foundation Chair of cardiovascular Studies; and has received advisory board fees and/or grant support from Roche Diagnostics, Novo Nordisk, Abbott Laboratories, Thermo Fisher, Medtronic, Sphingotec, Novartis and Astra Zeneca. The remaining authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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45. Health Services Costs of Clinical Heart Failure With Reduced Ejection Fraction in Singapore.

Author

Senanayake S, Kularatna S, Lee ASY, Lee A, Lau YH, Hausenloy DJ, Yeo KK, Chan MY, Wong RCC, Loh SY, Sim KLD, Weien C, and Graves N

Abstract

Objectives: This study aimed to estimate the annual healthcare burden of heart failure (HF) with reduced ejection fraction (<40%) in Singapore., Methods: Retrospective longitudinal descriptive cohort study was conducted using a linked national administrative data set (Singapore Cardiovascular Longitudinal Outcomes Database). In Singapore, during 2011, there were a total of 3267 HF-related hospital admissions. Among these, 1631 patients (49.9%), who had an ejection fraction of less than 40%, were followed up for 9 years. The primary outcomes were annual healthcare costs related to hospital admissions and outpatient visits., Results: There was a consistent decline in HF-related hospital admissions over the years, and the average per-hospital admission cost and average cost per day for HF varied over the 9 years. The average all-cause per-patient admission cost remained stable annually, ranging between S$16 000 and S$18 800. In the final year of life, there was a significant increase in both all-cause and HF-related hospital admission costs (by 24% and 54% from the previous year, respectively), and this rise in costs reflected increased frequency of admissions and longer hospital stays. There was an upward trend in the cost of outpatient visits as the patients neared death., Conclusions: Hospital-based HF care imposes a significant financial impact on Singapore's healthcare system. This suggests a need for cost-efficient management strategies to reduce the reliance on hospital-based treatment, thus mitigating economic pressures on the healthcare system., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Published
2024
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47. Feasibility of structuring electronic health record data to facilitate real-world data research: ICAREdata methods applied to multicenter cancer clinical trials.

Author

George S, Campbell N, Hillman SL, Harlos ES, Stein DWJ, Chan MY, Chow SL, Elrahi CL, Quina AC, Kokolus MC, Casagni MD, Weiss M, Anderson DM, Stadler WM, Hoff OC, Rivera DR, Kluetz PG, Mandrekar SJ, and Piantadosi S

Abstract

Background: The use of electronic health record (EHR) data for research is limited by a lack of structure and a standard data model. The objective of the ICAREdata (Integrating Clinical Trials and Real-World Endpoints Data) project was to structure key research data elements in EHRs using a minimal Common Oncology Data Elements (mCODE) data model to extract and transmit data., Methods: The ICAREdata project captured two EHR data elements essential to clinical trials: cancer disease status and treatment plan change. The project was implemented in clinical sites participating in Alliance for Clinical Trials in Oncology trials. Data were extracted from EHRs and sent by secure Fast Healthcare Interoperability Resource messaging (a standard for exchanging EHRs) to a database. Selected elements were compared with corresponding data from the trial's electronic data capture (EDC) system, Medidata Rave., Results: By December 2023, data were extracted and transmitted from 10 sites for 35 patients, involving 367 clinical encounters across 15 clinical trials. Data through March 2023 demonstrated that concordance for the elements treatment plan change and cancer disease status was 79% and 34%, respectively. When disease evaluation was reported by both EHR and EDC (n = 15), there was 87% agreement on cancer disease status., Conclusions: Documentation, extraction, and aggregation of structured data elements in EHRs using mCODE and ICAREdata methods is feasible in multi-institutional cancer clinical trials. EDC as a reference data set allowed assessment of the completeness of EHR data capture. Future initiatives will focus on elements with shared definitions in clinical and research environments and efficient workflows., Plain Language Summary: Clinical trials use electronic case report forms to report data, and data must be manually entered on these forms, which is costly and time consuming. ICAREdata methods use structured, organized data from clinical trials that can be more easily shared instead having to enter free text into electronic health records., (© 2024 The MITRE Corporation and The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Published
2024
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48. Efficacy of T-cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis.

Author

Chiang SCC, Covill LE, Tesi B, Campbell TM, Schlums H, Nejati-Zendegani J, Mördrup K, Wood S, Theorell J, Sekine T, Al-Herz W, Akar HH, Belen FB, Chan MY, Devecioglu O, Aksu T, Ifversen M, Malinowska I, Sabel M, Unal E, Unal S, Introne WJ, Krzewski K, Gilmour KC, Ehl S, Ljunggren HG, Nordenskjöld M, Horne A, Henter JI, Meeths M, and Bryceson YT

Subjects
Humans, Adolescent, Child, Adult, Female, K562 Cells, Male, Child, Preschool, Middle Aged, Infant, Young Adult, Aged, Sensitivity and Specificity, Prospective Studies, Receptors, Antigen, T-Cell metabolism, Receptors, Antigen, T-Cell genetics, Exocytosis, T-Lymphocytes, Cytotoxic immunology, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic immunology, Lymphohistiocytosis, Hemophagocytic genetics, Lymphohistiocytosis, Hemophagocytic pathology, Killer Cells, Natural immunology, Killer Cells, Natural metabolism
Abstract

Abstract: Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder associated with autosomal recessive variants in genes required for perforin-mediated lymphocyte cytotoxicity. A rapid diagnosis is crucial for successful treatment. Although defective cytotoxic T lymphocyte (CTL) function causes pathogenesis, quantification of natural killer (NK)-cell exocytosis triggered by K562 target cells currently represents a standard diagnostic procedure for primary HLH. We have prospectively evaluated different lymphocyte exocytosis assays in 213 patients referred for evaluation for suspected HLH and related hyperinflammatory syndromes. A total of 138 patients received a molecular diagnosis consistent with primary HLH. Assessment of Fc receptor-triggered NK-cell and T-cell receptor (TCR)-triggered CTL exocytosis displayed higher sensitivity and improved specificity for the diagnosis of primary HLH than routine K562 cell-based assays, with these assays combined providing a sensitivity of 100% and specificity of 98.3%. By comparison, NK-cell exocytosis after K562 target cell stimulation displayed a higher interindividual variability, in part explained by differences in NK-cell differentiation or large functional reductions after shipment. We thus recommend combined analysis of TCR-triggered CTL and Fc receptor-triggered NK-cell exocytosis for the diagnosis of patients with suspected familial HLH or atypical manifestations of congenital defects in lymphocyte exocytosis., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Published
2024
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49. The prognostic value of metabolic dysfunction-associated steatotic liver disease in acute myocardial infarction: A propensity score-matched analysis.

Author

Kong G, Cao G, Koh J, Chan SP, Zhang A, Wong E, Chong B, Jauhari SM, Wang JW, Mehta A, Figtree GA, Mamas MA, Ng G, Chan KH, Chai P, Low AF, Lee CH, Yeo TC, Yip J, Foo R, Tan HC, Huang DQ, Muthiah M, Chan MY, Loh PH, and Chew NWS

Subjects
Humans, Male, Female, Middle Aged, Prognosis, Aged, Singapore epidemiology, Fatty Liver complications, Fatty Liver mortality, Risk Factors, Retrospective Studies, Myocardial Infarction mortality, Myocardial Infarction complications, Myocardial Infarction epidemiology, Propensity Score
Abstract

Aim: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined., Methods: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. The Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality., Results: In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 2.4 years. The MASLD group had higher rates of obesity, diabetes and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs. 3.6%, p < .001) at 30 days, with unfavourable mortality rates sustained in the long-term (18.3% vs. 14.5%, p = .001) compared with those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (hazard ratio 1.330, 95% confidence interval 1.106-1.598, p = .002)., Conclusion: MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI., (© 2024 John Wiley & Sons Ltd.)

Published
2024
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50. Incidence and Outcomes of Cardiocerebral Infarction: A Cohort Study of 2 National Population-Based Registries.

Author

Ho JS, Zheng H, Tan BY, Ho AF, Foo D, Foo LL, Lim PZ, Liew BW, Ahmad A, Chan BPL, Chang HM, Kong KH, Young SH, Tang KF, Chua T, Hausenloy DJ, Yeo TC, Tan HC, Yip JWL, Chai P, Venketasubramanian N, Chan MY, Yeo LL, and Sia CH

Abstract

Background: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone., Methods: We performed a retrospective cohort study of 120 531 patients with AMI and AIS from the national stroke and AMI registries in Singapore. Patients were categorized into AMI only, AIS only, synchronous CCI (same-day), and metachronous CCI (within 1 week). The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular mortality. The mortality risks were compared using Cox regression. Multivariable models were adjusted for baseline demographics, clinical variables, and treatment for AMI or AIS., Results: Of 127 919 patients identified, 120 531 (94.2%) were included; 74 219 (61.6%) patients had AMI only, 44 721 (37.1%) had AIS only, 625 (0.5%) had synchronous CCI, and 966 (0.8%) had metachronous CCI. The mean age was 67.7 (SD, 14.0) years. Synchronous and metachronous CCI had a higher risk of 30-day mortality (synchronous: adjusted HR [aHR], 2.41 [95% CI, 1.77-3.28]; metachronous: aHR, 2.80 [95% CI, 2.11-3.73]) than AMI only and AIS only (synchronous: aHR, 2.90 [95% CI, 1.87-4.51]; metachronous: aHR, 4.36 [95% CI, 3.03-6.27]). The risk of cardiovascular mortality was higher in synchronous and metachronous CCI than AMI (synchronous: aHR, 3.03 [95% CI, 2.15-4.28]; metachronous: aHR, 3.41 [95% CI, 2.50-4.65]) or AIS only (synchronous: aHR, 2.58 [95% CI, 1.52-4.36]; metachronous: aHR, 4.52 [95% CI, 2.95-6.92]). In synchronous CCI, AMI was less likely to be managed with PCI and secondary prevention medications ( P <0.001) compared with AMI only., Conclusions: Synchronous CCI occurred in 1 in 200 cases of AIS and AMI. Synchronous and metachronous CCI had higher mortality than AMI or AIS alone.

Published
2024
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