Displaying publications 1 - 20 of 30 in total

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  1. Chua J, Tham YC, Liao J, Zheng Y, Aung T, Wong TY, et al.
    Ophthalmology, 2014 Oct;121(10):2013-22.
    PMID: 24950592 DOI: 10.1016/j.ophtha.2014.04.041
    PURPOSE:
    To determine the ethnic differences in the distribution of intraocular pressure (IOP) and central corneal thickness (CCT) in a multi-ethnic Asian population by self-reported ethnicity and genetic ancestry.
    DESIGN:
    Population-based, cross-sectional study.
    PARTICIPANTS:
    A total of 10 033 adults (3353 Chinese, 3280 Malays, and 3400 Indians) aged >40 years.
    METHODS:
    Participants underwent standardized systemic and ocular examinations and interviewer-administered questionnaires for risk factor assessment. The IOP readings were obtained by Goldmann applanation tonometry (Haag-Streit, Konig, Switzerland) before pupil dilation. The CCT was measured with ultrasound pachymetry. Genetic ancestry was derived using principal component (PC) analysis. Regression models were used to investigate the association of IOP and CCT with potential risk factors and genetic ancestry.
    MAIN OUTCOME MEASURES:
    Intraocular pressure and CCT.
    RESULTS:
    After excluding participants with a history of glaucoma surgery or medication, refractive surgery, corneal edema, or corneal dystrophy, IOP and CCT readings were available for 3251 Chinese, 3232 Malays, and 3317 Indians. The mean IOP readings in the Chinese, Malay, and Indian participants were 14.3±3.1, 15.3±3.7, and 15.8±2.9 mmHg, respectively (P 
  2. Cheung CM, Li X, Cheng CY, Zheng Y, Mitchell P, Wang JJ, et al.
    Ophthalmology, 2014 Aug;121(8):1598-603.
    PMID: 24661862 DOI: 10.1016/j.ophtha.2014.02.004
    To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons.
  3. Chan JCY, Chee ML, Tan NYQ, Cheng CY, Wong TY, Sabanayagam C
    Nutr Diabetes, 2018 03 07;8(1):16.
    PMID: 29549238 DOI: 10.1038/s41387-018-0018-0
    AIMS: To examine the association of body mass index (BMI) with the incidence of diabetes mellitus (DM) and diabetic retinopathy (DR) in Asians.

    METHODS: We analysed data from 4101 adults (Malay, n = 1901 and Indian, n = 2200) who participated in the baseline (2004-2009) and 6-year follow-up (2011-2015) of two independent population-based studies with similar methodology in Singapore. BMI was categorised into normal (<25 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). DM was diagnosed as random plasma glucose ≥200 mg/dL, HbA1c ≥6.5% or self-reported physician diagnosed DM. DR was assessed from retinal photographs graded using a standard protocol. The associations of baseline BMI with incident DM and DR was examined using multivariable poisson regression models adjusting for potential confounders including duration of DM, family history of DM and HbA1c.

    RESULTS: The incidence of DM was 12.8% and among 1586 participants with DM, the incidence of DR was 17.6% over a median follow-up period of 6.2 years. Compared to those with BMI 

  4. Tan CH, Hilal S, Xu X, Vrooman H, Cheng CY, Wong TY, et al.
    J Alzheimers Dis, 2020;73(4):1501-1509.
    PMID: 31958085 DOI: 10.3233/JAD-190866
    There is a need to elucidate the combined influence of neurodegeneration and cerebrovascular disease (CeVD) on cognitive impairment, especially in diverse populations. Here, we evaluated 840 multiethnic individuals (mean age = 70.18) across the disease spectrum from the Epidemiology of Dementia in Singapore study. First, we determined whether a validated quantitative MRI score of mixed pathology is associated with clinical diagnosis and whether the score differed between ethnicities (Chinese, Malays, and Indians). We then evaluated whether the score was associated with multidomain cognitive impairment and if additional measures of CeVD were further associated with cognitive impairment. We found that lower quantitative MRI scores were associated with severity of clinical diagnosis and Chinese individuals had the highest quantitative MRI scores, followed by Indians and Malays. Lower quantitative MRI scores were also associated with lower performance in attention, language, visuoconstruction, visuomotor, visual, and verbal memory domains. Lastly, the presence of intracranial stenosis and cortical cerebral microinfarcts, but not cerebral microbleeds, were associated with memory performance beyond quantitative MRI scores. Taken together, our results demonstrate the utility of using multiple MRI markers of neurodegeneration and CeVD for identifying multiethnic Asians with the greatest cognitive impairment due to mixed pathology.
  5. Tan AG, Tham YC, Chee ML, Mitchell P, Cumming RG, Sabanayagam C, et al.
    Clin Exp Ophthalmol, 2020 07;48(5):580-592.
    PMID: 32255547 DOI: 10.1111/ceo.13757
    IMPORTANCE: Long-term data on age-related cataract, a leading cause of blindness and visual impairment, is scarce in Asian populations.

    BACKGROUND: We report the 6-year incidence and progression of age-related cataract and associated risk factors in Malay adults living in Singapore.

    DESIGN: Population-based cohort study.

    PARTICIPANTS: A total of 3280 Malays aged 40+ years participated in baseline examinations of the Singapore Malay Eye Study (2004-2006). Six years later, 1901 (72.1% of eligible) baseline participants were re-examined.

    METHODS: Cataract was assessed using lens photos, taken during eye examinations, following the Wisconsin Cataract Grading System.

    MAIN OUTCOMES AND MEASURES: Incidence and progression of cortical, nuclear and posterior subcapsular (PSC) cataract. Poisson regression models and generalized estimating equations models (with Poisson link) were used to assess factors associated with cataract incidence and progression, respectively, adjusting for age, sex and other risk factors.

    RESULTS: Age-adjusted 6-year incidence of cortical, nuclear and PSC cataract was 14.1%, 13.6% and 8.7%, respectively, and was strongly age-related (P for trend

  6. Lim EWL, Chee ML, Sabanayagam C, Majithia S, Tao Y, Wong TY, et al.
    Invest Ophthalmol Vis Sci, 2019 05 01;60(6):1889-1897.
    PMID: 31042796 DOI: 10.1167/iovs.19-26810
    Purpose: The purpose of this study was to investigate the association between sleep (duration and quality) and symptoms of dry eye in Singapore Malay and Indian adults.

    Methods: This was a prospective cross-sectional study. A total of 3303 subjects aged 40 years and above from two large population-based cohorts, the Singapore Malay Eye Study-2 (n = 1191, 2011-2013) and the Singapore Indian Eye Study-2 (n = 2112, 2013-2015), were included. The presence of symptoms of dry eye was defined as having at least one of six symptoms often or all the time. Sleep questionnaires included the Epworth Sleepiness Scale, Berlin Questionnaire, STOP-bang questionnaire, and Insomnia Severity Index. Poor sleep quality was defined as meeting the respective questionnaire thresholds. General health questionnaires (including sleep duration) and standardized ocular and systemic tests were also used.

    Results: Of 3303 participants, 6.4% had excessive sleepiness, 20.5% had high risk for sleep apnea, 2.7% had clinical insomnia, and 7.8% had <5 hours of sleep. These sleep factors were associated with symptoms of dry eye. After adjusting for relevant demographic, medical, and social factors, the following were associated with higher odds of symptoms of dry eye: excessive sleepiness (Epworth Sleepiness Scale: odds ratio [OR] = 1.77 [1.15-2.71]), high risk of sleep apnea (Berlin Questionnaire: OR = 1.55 [1.17-2.07], STOP-Bang Questionnaire: OR = 2.66 [1.53-4.61]), clinical insomnia (Insomnia Severity Index: OR = 3.68 [2.17-6.26]) and <5 hours of sleep (OR = 1.73 [1.17-2.57], reference sleep duration 5-9 hours). Sleep apnea, insomnia, and sleep duration were each shown to be independently associated with symptoms of dry eye.

    Conclusion: Short sleep duration and poor quality are both significantly and independently associated with symptoms of dry eye.

  7. Hung TH, Hsu SC, Cheng CY, Choo KB, Tseng CP, Chen TC, et al.
    Oncotarget, 2014 Dec 15;5(23):12273-90.
    PMID: 25401518
    Multidrug resistance in cancer cells arises from altered drug permeability of the cell. We previously reported activation of the Wnt pathway in ABCB1-overexpressed human uterus sarcoma drug-resistant MES-SA/Dx5 cells through active β-catenin and associated transactivation activities, and upregulation of Wnt-targeting genes. In this study, Wnt5A was found to be significantly upregulated in MES-SA/Dx5 and MCF7/ADR2 cells, suggesting an important role for the Wnt5A signaling pathway in cancer drug resistance. Higher cAMP response elements and Tcf/Lef transcription activities were shown in the drug-resistant cancer cells. However, expression of Wnt target genes and CRE activities was downregulated in Wnt5A shRNA stably-transfected MES-SA/Dx5 cells. Cell viability of the drug-resistant cancer cells was also reduced by doxorubicin treatment and Wnt5A shRNA transfection, or by Wnt5A depletion. The in vitro data were supported by immunohistochemical analysis of 24 paired breast cancer biopsies obtained pre- and post-chemotherapeutic treatment. Wnt5A, VEGF and/or ABCB1 were significantly overexpressed after treatment, consistent with clinical chemoresistance. Taken together, the Wnt5A signaling pathway was shown to contribute to regulating the drug-resistance protein ABCB1 and β-catenin-related genes in antagonizing the toxic effects of doxorubicin in the MDR cell lines and in clinical breast cancer samples.
  8. Chai X, Low KY, Tham YC, Chee ML, Thakur S, Zhang L, et al.
    Invest Ophthalmol Vis Sci, 2020 08 03;61(10):37.
    PMID: 32821913 DOI: 10.1167/iovs.61.10.37
    Purpose: Genome-wide association studies have identified several genes associated with glaucoma. However, their roles in the pathogenesis of glaucoma remain unclear, particularly their effects on retinal nerve fiber layer (RNFL) thickness. The aim of this study was to investigate the associations between the identified glaucoma risk genes and RNFL thickness.

    Methods: A total of 3843 participants (7,020 healthy eyes) were enrolled from the Singapore Epidemiology of Eye Diseases (SEED) study, a population-based study composing of three major ethnic groups-Malay, Indian, and Chinese-in Singapore. Ocular examinations were performed, and spectral-domain optical coherence tomography (SD-OCT) was used to measure circumpapillary RNFL thickness. We selected 35 independent glaucoma-associated genetic loci for analysis. An linear regression model was conducted to determine the association of these variants with circumpapillary RNFL, assuming an additive genetic model. We conducted association analysis in each of the three ethnic groups, followed by a meta-analysis of them.

    Results: The mean age of the included participants was 59.4 ± 8.9 years, and the mean RFNL thickesss is 92.3 ± 11.2 µm. In the meta-analyses, of the 35 glacuoma loci, we found that only SIX6 was significantly associated with reduction in global RNFL thickness (rs33912345; β = -1.116 um per risk allele, P = 1.64E-05), and the effect size was larger in the inferior RNFL quadrant (β = -2.015 µm, P = 2.9E-6), and superior RNFL quadrant (β = -1.646 µm, P = 6.54E-5). The SIX6 association were consistently observed across all three ethnic groups. Other than RNFL, we also found several genetic varaints associated with vertical cuo-to-disc ratio (ATOH7, CDKN2B-AS1, and TGFBR3-CDC7), rim area (SIX6 and CDKN2B-AS1), and disc area (SIX6, ATOH7, and TGFBR3-CDC7). The association of SIX6 rs33912345 with NRFL thickness remained similar after further adjusting for disc area and 3 other disc parameter associated SNPs (ATOH7, CDKN2B-AS1, and TGFBR3-CDC7).

    Conclusions: Of the 35 glaucoma identified risk loci, only SIX6 is significantly and independently associated with thinner RNFL. Our study further supports the involvement of SIX6 with RNFL thickness and pathogensis of glaucoma.

  9. Liang KH, Lu YH, Niu CW, Chang SK, Chen YR, Cheng CY, et al.
    J Hum Genet, 2020 Jul;65(7):619-625.
    PMID: 32246049 DOI: 10.1038/s10038-020-0745-7
    The Fabry disease-causing mutation, the GLA IVS4+919G>A (designated GLA IVS4), is very prevalent in patients with hypertrophic cardiomyopathy in Taiwan. This X-linked mutation has also been found in patients in Kyushu, Japan and Southeast Asia. To investigate the age and the possible ancestral origin of this mutation, a total of 33 male patients with the GLA IVS4+919G>A mutation, born in Taiwan, Japan, Singapore, Malaysia, Vietnam, and the Fujian and Guangdong provinces of China, were studied. Peripheral bloods were collected, and the Ilumina Infinium CoreExome-24 microarray was used for dense genotyping. A mutation-carrying haplotype was discovered which was shared by all 33 patients. This haplotype does not exist in 15 healthy persons without the mutation. Rather, a wide diversity of haplotypes was found in the vicinity of the mutation site, supporting the existence of a single founder of the GLA IVS4 mutation. The age of the founder mutation was estimated by the lengths of the mutation-carrying haplotypes based on the linkage-disequilibrium decay theory. The first, second, and third quartile of the age estimates are 800.7, 922.6, and 1068.4 years, respectively. We concluded that the GLA IVS4+919G>A mutation originated from a single mutational event that occurred in a Chinese chromosome more than 800 years ago.
  10. Gupta P, Majithia S, Fenwick EK, Gan ATL, Tham YC, Poh S, et al.
    Transl Vis Sci Technol, 2020 04;9(5):11.
    PMID: 32821483 DOI: 10.1167/tvst.9.5.11
    Purpose: The purpose of this study was to determine the rates of, and factors associated with, eyecare utilization and spectacle affordability among Singaporeans with vision impairment (VI).

    Methods: We included adults with VI from their second visit of the Singapore Epidemiology of Eye Disease Study. Data on eyecare utilization and spectacle affordability were collected. Low eyecare utilization was defined as no eye check ever or eye checks not even once per year in reference to at least once per year. Difficulty affording glasses was defined as glasses being rated as expensive in reference to not expensive.

    Results: There were 985 adults (14.5%; 415 Malays, 260 Indian, and 310 Chinese; mean age [SD]: 69.5 [10.2] years; 55.4% women) with VI who answered the above questions, were included. Of these, 624 (63.4%) wore glasses. The rates of low eyecare utilization and difficulty affording eyeglasses were 31% and 63%, respectively. Compared to Chinese (23.8%) and Indians (18.8%), Malays (57.4%) had the highest rates of low eyecare utilization (P < 0.001), and most difficulty affording eyeglasses (47.2% vs. 26.1% and 26.6% in Chinese and Indians, respectively; P < 0.001). Younger age, low socioeconomic status, absence of diabetes, absence of self-reported eye conditions, and poor vision were independently associated with low eyecare utilization, whereas older age and female sex was associated with difficulty affording glasses.

    Conclusions: In this multi-ethnic population with VI, almost one-third had low eyecare utilization and nearly two-thirds reported difficulty affording eyeglasses.

    Translational Relevance: This will inform strategies, such as tailored eyecare utilization awareness campaigns and awareness of available subsidy schemes for at-risk Singaporeans, such as Malays.

  11. Man REK, Veerappan AR, Tan SP, Fenwick EK, Sabanayagam C, Chua J, et al.
    Ocul Surf, 2017 Oct;15(4):742-748.
    PMID: 28442380 DOI: 10.1016/j.jtos.2017.04.004
    PURPOSE: To evaluate the incidence of symptomatic dry eye disease (SDED) and associated risk factors in a well-characterized cohort of ethnic Malays in Singapore.

    METHODS: We included 1682 participants (mean age [SD]: 57 [10]years; 55.4% female) without SDED from the Singapore Malay Eye Study (SiMES), a population-based longitudinal study with baseline examination (SiMES-1) conducted between 2004 and 2006, and follow-up examination (SiMES-2) conducted between 2010 and 2013. SDED was considered to be present if a participant answered "often" or "all the time" to any of the six questions from the Salisbury Eye Evaluation Study dry eye questionnaire. Age-standardized incidence of SDED was calculated as the crude 6-year cumulative incidence standardized to Singapore's population census. Gender-stratified multivariable log-binomial regression models were utilized to determine the independent risk factors of incident SDED.

    RESULTS: At the 6-year follow-up, 86 of 1682 participants had developed SDED, which was equivalent to an age-standardized 6-year incidence of 5.1% (95% CI 4.1-6.4%). There were no differences in the incidence of SDED between men and women (P = 0.9). Multivariable models revealed that presence of glaucoma and poorer self-rated health were independently associated with incident SDED in men (P = 0.003 and 0.03, respectively), while contact lens wear (P = 0.002), history of thyroid disease (P = 0.03), and having had cataract surgery (P = 0.02) were predictive of incident SDED in women.

    CONCLUSION: One in twenty adult Malays developed SDED over a 6-year period. Risk factors for incident SDED were different between men and women. Future studies and public health interventions should consider this gender-specific difference in risk factors.
  12. Cheung CMG, Ong PG, Neelam K, Tan PC, Shi Y, Mitchell P, et al.
    Ophthalmology, 2017 09;124(9):1305-1313.
    PMID: 28501376 DOI: 10.1016/j.ophtha.2017.03.056
    PURPOSE: To determine the 6-year incidence of early and late age-related macular degeneration (AMD) in a Singaporean Malay population and to validate the Age-Related Eye Disease Study (AREDS) simplified severity scale in Asians.

    DESIGN: Prospective, population cohort study.

    PARTICIPANTS: The Singapore Malay Eye Study baseline participants (age, ≥40 years; 2006-2008) were followed up in 2011 through 2013, and 1901 of 3280 of eligible participants (72.1%) took part.

    METHODS: Fundus photographs were graded using the Wisconsin AMD grading system.

    MAIN OUTCOME MEASURES: Incidence of early and late AMD.

    RESULTS: Gradable fundus photographs were available for 1809 participants who attended both baseline and 6-year follow-up examinations. The age-standardized incidences of early and late AMD were 5.89% (95% confidence interval [CI], 4.81-7.16) and 0.76% (95% CI, 0.42-1.29), respectively. The 5-year age-standardized incidence of early AMD (calculated based on the 6-year incidence) was lower in our population (5.58%; 95% CI, 4.43-7.01) compared with the Beaver Dam Eye Study population (8.19%). The incidence of late AMD in our population was similar to that of the Beaver Dam Eye Study population (0.98% [95% CI, 0.49-1.86] vs. 0.91%), the Blue Mountains Eye Study population (1.10% [95% CI, 0.52-9.56] vs. 1.10%), and the Hisayama Study population (1.09% [95% CI, 0.54-4.25] vs. 0.84%). The incidence of late AMD increased markedly with increasing baseline AREDS score (step 0, 0.23%; step 4, 9.09%).

    CONCLUSIONS: This study documented the incidence of early and late AMD in a Malay population. The AREDS simplified severity scale is useful in predicting the risk of late AMD development in Asians.

  13. Teo ZL, Sun CZ, Chong CCY, Tham YC, Takahashi K, Majithia S, et al.
    Ophthalmol Retina, 2022 Nov;6(11):1080-1088.
    PMID: 35580772 DOI: 10.1016/j.oret.2022.05.010
    OBJECTIVE: To describe the normative quantitative parameters of the macular retinal vasculature, as well as their systemic and ocular associations using OCT angiography (OCTA).

    DESIGN: Population-based, cross-sectional study.

    SUBJECTS: Adults aged > 50 years were recruited from the third examination of the population-based Singapore Malay Eye Study.

    METHODS: All participants underwent a standardized comprehensive examination and spectral-domain OCTA (Optovue) of the macula. OCT angiography scans that revealed pre-existing retinal disease, revealed macular pathology, and had poor quality were excluded.

    MAIN OUTCOME MEASURES: The normative quantitative vessel densities of the superficial layer, deep layer, and foveal avascular zone (FAZ) were evaluated. Ocular and systemic associations with macular retinal vasculature parameters were also evaluated in a multivariable analysis using linear regression models with generalized estimating equation models.

    RESULTS: We included 1184 scans (1184 eyes) of 749 participants. The mean macular superficial vessel density (SVD) and deep vessel density (DVD) were 45.1 ± 4.2% (95% confidence interval [CI], 37.8%-51.4%) and 44.4 ± 5.2% (95% CI, 36.9%-53.2%), respectively. The mean SVD and DVD were highest in the superior quadrant (48.7 ± 5.9%) and nasal quadrant (52.7 ± 4.6%), respectively. The mean FAZ area and perimeter were 0.32 ± 0.11 mm2 (95% CI, 0.17-0.51 mm) and 2.14 ± 0.38 mm (95% CI, 1.54-2.75 mm), respectively. In the multivariable regression analysis, female sex was associated with higher SVD (β = 1.25, P ≤ 0.001) and DVD (β = 0.75, P = 0.021). Older age (β = -0.67, P < 0.001) was associated with lower SVD, whereas longer axial length (β = -0.42, P = 0.003) was associated with lower DVD. Female sex, shorter axial length, and worse best-corrected distance visual acuity were associated with a larger FAZ area. No association of a range of systemic parameters with vessel density was found.

    CONCLUSIONS: This study provided normative macular vasculature parameters in an adult Asian population, which may serve as reference values for quantitative interpretation of OCTA data in normal and disease states.

  14. Chai JF, Kao SL, Wang C, Lim VJ, Khor IW, Dou J, et al.
    J Clin Endocrinol Metab, 2020 Dec 01;105(12).
    PMID: 32936915 DOI: 10.1210/clinem/dgaa658
    CONTEXT: Glycated hemoglobin A1c (HbA1c) level is used to screen and diagnose diabetes. Genetic determinants of HbA1c can vary across populations and many of the genetic variants influencing HbA1c level were specific to populations.

    OBJECTIVE: To discover genetic variants associated with HbA1c level in nondiabetic Malay individuals.

    DESIGN AND PARTICIPANTS: We conducted a genome-wide association study (GWAS) analysis for HbA1c using 2 Malay studies, the Singapore Malay Eye Study (SiMES, N = 1721 on GWAS array) and the Living Biobank study (N = 983 on GWAS array and whole-exome sequenced). We built a Malay-specific reference panel to impute ethnic-specific variants and validate the associations with HbA1c at ethnic-specific variants.

    RESULTS: Meta-analysis of the 1000 Genomes imputed array data identified 4 loci at genome-wide significance (P 

  15. Chen JM, Su YC, Cheng CY, Chang CJ, Hsu LM, Shin SD, et al.
    J Neurotrauma, 2024 Dec;41(23-24):2590-2601.
    PMID: 39264870 DOI: 10.1089/neu.2023.0392
    The optimal prehospital blood pressure in patients following traumatic brain injury (TBI) remains controversial. We aimed to assess the association between the systolic blood pressure (SBP) at emergency department triage and patient outcomes following isolated moderate-to-severe TBI. We conducted a cross-national multicenter retrospective cohort study using the Pan-Asia Trauma Outcomes Study database from January 1, 2016, to November 30, 2018. The enrollees were adult patients with isolated moderate-to-severe TBI defined by the International Classification of Diseases code, a Glasgow Coma Scale (GCS) <13 at triage, and a nonhead Abbreviated Injury Scale ≤3. The studied variables were SBPs at triage categorized into different ranges. The primary outcome was 30-day mortality, and the secondary outcome was poor functional status at hospital discharge defined by the modified Rankin Scale ≥4. Multivariable logistic regression was applied to adjust for confounders including country, sex, age, mechanism of injury, prehospital vascular access, respiratory rate, GCS, oxygen saturation, intubation, Injury Severity Score, head surgery, intensive care unit admission, and length of hospital stay. Subgroup analyses were performed on different severity of TBI. A total of 785 patients (median age, 42 years; male patients 77.5%; mean SBP at triage, 136.3 ± 33.1 mmHg) were included in the primary analysis. The lowest 30-day mortality rate existed in patients with SBP of 100-119 mmHg. Taking it as baseline, the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of SBP <100 mmHg, 120-139 mmHg, 140-159 mmHg, and ≥160 mmHg were 7.05 (2.51-19.78), 3.14 (1.14-8.65), 2.91 (1.04-8.17), and 3.28 (1.14-9.42). As for the secondary outcome, the aORs and 95% CIs were 1.36 (0.68-2.68) of <100 mmHg, 0.99 (0.57-1.70) of 120-139 mmHg, 1.23 (0.67-2.25) of 140-159 mmHg, and 1.52 (0.78-2.95) of ≥160 mmHg. Subgroup analyses revealed trends of the best outcomes in both moderate and severe TBI patients with SBP 100-119 mmHg, whereas statistical significance appeared only in patients with severe TBI. SBP of 110-119 mmHg at triage is associated with the lowest 30-day mortality in patients following isolated moderate-to-severe TBI and possibly related to a better functional outcome.
  16. Wong LP, Ong RT, Poh WT, Liu X, Chen P, Li R, et al.
    Am J Hum Genet, 2013 Jan 10;92(1):52-66.
    PMID: 23290073 DOI: 10.1016/j.ajhg.2012.12.005
    Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies.
  17. Li H, Jiang Z, Guan Z, Bao Y, Liu Y, Hu T, et al.
    Sci Bull (Beijing), 2025 Mar 30;70(6):934-942.
    PMID: 39947986 DOI: 10.1016/j.scib.2025.01.034
    Diabetes poses a considerable global health challenge, with varying levels of diabetes knowledge among healthcare professionals, highlighting the importance of diabetes training. Large Language Models (LLMs) provide new insights into diabetes training, but their performance in diabetes-related queries remains uncertain, especially outside the English language like Chinese. We first evaluated the performance of ten LLMs: ChatGPT-3.5, ChatGPT-4.0, Google Bard, LlaMA-7B, LlaMA2-7B, Baidu ERNIE Bot, Ali Tongyi Qianwen, MedGPT, HuatuoGPT, and Chinese LlaMA2-7B on diabetes-related queries, based on the Chinese National Certificate Examination for Primary Diabetes Care in China (NCE-CPDC) and the English Specialty Certificate Examination in Endocrinology and Diabetes of Membership of the Royal College of Physicians of the United Kingdom. Second, we assessed the training of primary care physicians (PCPs) without and with the assistance of ChatGPT-4.0 in the NCE-CPDC examination to ascertain the reliability of LLMs as medical assistants. We found that ChatGPT-4.0 outperformed other LLMs in the English examination, achieving a passing accuracy of 62.50%, which was significantly higher than that of Google Bard, LlaMA-7B, and LlaMA2-7B. For the NCE-CPFC examination, ChatGPT-4.0, Ali Tongyi Qianwen, Baidu ERNIE Bot, Google Bard, MedGPT, and ChatGPT-3.5 successfully passed, whereas LlaMA2-7B, HuatuoGPT, Chinese LLaMA2-7B, and LlaMA-7B failed. ChatGPT-4.0 (84.82%) surpassed all PCPs and assisted most PCPs in the NCE-CPDC examination (improving by 1 %-6.13%). In summary, LLMs demonstrated outstanding competence for diabetes-related questions in both the Chinese and English language, and hold great potential to assist future diabetes training for physicians globally.
  18. Gunasekeran DV, Zheng F, Lim GYS, Chong CCY, Zhang S, Ng WY, et al.
    Front Med (Lausanne), 2022;9:875242.
    PMID: 36314006 DOI: 10.3389/fmed.2022.875242
    BACKGROUND: Many artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract.

    METHODS: This was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning.

    RESULTS: One thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10-12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63-0.83.

    CONCLUSION: Ophthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology.

  19. Wong WM, Tham YC, Ayton LN, Britten-Jones AC, Edwards TL, Grigg J, et al.
    Asia Pac J Ophthalmol (Phila), 2024;13(5):100098.
    PMID: 39366638 DOI: 10.1016/j.apjo.2024.100098
    PURPOSE: The objective of this paper is to shed light on the current landscape of genotyping practices, phenotyping practices and availability of essential vision rehabilitation management for inherited retinal diseases (IRD) in the Asia-Pacific (APAC) Region.

    METHODS: The 62-item questionnaire was distributed electronically via email. The questions covered five domains: (1) structure of the IRD service and registry/database; (2) genotyping practices; (3) genetic counselling; (4) deep phenotyping practices; (5) low-vision rehabilitation services.

    RESULTS: The survey was completed by 36 of 45 centres in twelve countries and regions in APAC. Among these centres, 42 % reported managing more than 1000 patients. Notably, 39 % of centres lack an IRD database or registry, and 44 % of centres have tested less than one-quarter of their IRD patients. The majority of centres (67 %) do not have genetic counsellors. While there was consistency in the imaging-based investigations, there was marked heterogeneity for functional testing using electrophysiology and formal perimetry. Only 34 % of centres confirmed the availability of access to low-vision assistive devices.

    CONCLUSIONS: This study reveals several critical gaps in managing IRDs in the APAC region. These include the lack of IRD database/registry in one-third of centres, a substantial proportion of patients remaining genetically undiagnosed, and limited availability of genetic counsellors. The findings also underscore a need to harmonise investigations for evaluating retinal function and identify areas for improvement in the provision of low-vision rehabilitation services.

  20. Nongpiur ME, Khor CC, Jia H, Cornes BK, Chen LJ, Qiao C, et al.
    PLoS Genet, 2014 Mar;10(3):e1004089.
    PMID: 24603532 DOI: 10.1371/journal.pgen.1004089
    Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
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