Publications by authors named "M G E H Lam"

1,702 Publications

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Reliability and validity of Six-Spot Step Test (SSST) in stroke survivors.

Eur J Phys Rehabil Med 2021 Jun 15. Epub 2021 Jun 15.

School of Nursing, The Hong Kong Polytechnic University, Hong Kong.

Background: The Six-Spot Step Test (SSST) was originally developed to assess walking ability while challenging balance during walking in patients with multiple sclerosis. It provides more comprehensive information on ambulatory abilities than several existing measures such as the Timed Up & Go test (TUG test), the Functional Gait Assessment, and the Dynamic Gait Index. To assess the advanced balance control ability of stroke survivors, we modified the SSST to serve this purpose.

Aim: The aim of this study was to expand the current understanding of the psychometric properties of the SSST using healthy older adults and stroke survivors.

Design: This study adopted an experimental design.

Setting: University-affiliated neurorehabilitation laboratory.

Population: A total of 50 study participants, including 25 chronic stroke survivors and 25 healthy older adults, were recruited from the community.

Methods: The SSST was administered to the stroke survivors twice (day 1 & 2) with a 1-week interval. The Fugl-Meyer assessment for the lower extremities (FMA-LE), the Berg Balance scale (BBS), the limit of stability (LOS) test, the Timed Up & Go test (TUG test), and the Chinese version of the Community Integration Measures (CIM-C) were assessed on day 1 by random order. The healthy control group was assessed with the Six-Spot Step Test only on day 1.

Results: The SSST showed excellent inter-rater, intra-rater, and test-retest reliability (intraclass correlation coefficient>0.95, p<0.001). Significant correlations were found between SSST performance and the FMA-LE results (r=0.517, p<0.05), BBS scores (q r =-0.531, p<0.05), and TUG test scores (r =0.828, p<0.001). The MDC in the mean SSST time for the affected leg and the unaffected leg in stroke survivors was 6.05s. The cutoff time was 10.11s (sensitivity, 80%; specificity, 92%) when kicking obstacles with the affected leg and 10.18s (sensitivity, 80%; specificity, 92%) when kicking obstacles with the unaffected leg.

Conclusions: The SSST was a reliable test and showed a significant correlation with FMA-LE scores, BBS scores, and TUG test times in stroke survivors.

Clinical Rehabilitation Impact: The SSST can be used to assess the advanced balance control of stroke survivors.
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http://dx.doi.org/10.23736/S1973-9087.21.06799-XDOI Listing
June 2021

Large-scale evaluation of the Positive and Negative Syndrome Scale (PANSS) symptom architecture in schizophrenia.

Asian J Psychiatr 2021 Jun 3;62:102732. Epub 2021 Jun 3.

Research Division, Institute of Mental Health, Singapore; Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, United States; Feinstein Institute of Medical Research, The Zucker Hillside Hospital, New York, United States. Electronic address:

Although the Positive and Negative Syndrome Scale (PANSS) is widely utilized in schizophrenia research, variability in specific item loading exist, hindering reproducibility and generalizability of findings across schizophrenia samples. We aim to establish a common PANSS factor structure from a large multi-ethnic sample and validate it against a meta-analysis of existing PANSS models. Schizophrenia participants (N = 3511) included in the current study were part of the Singapore Translational and Clinical Research Program (STCRP) and the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE). Exploratory Factor Analysis (EFA) was conducted to identify the factor structure of PANSS and validated with a meta-analysis (N = 16,171) of existing PANSS models. Temporal stability of the PANSS model and generalizability to individuals at ultra-high risk (UHR) of psychosis were evaluated. A five-factor solution best fit the PANSS data. These were the i) Positive, ii) Negative, iii) Cognitive/disorganization, iv) Depression/anxiety and v) Hostility factors. Convergence of PANSS symptom architecture between EFA model and meta-analysis was observed. Modest longitudinal reliability was observed. The schizophrenia derived PANSS factor model fit the UHR population, but not vice versa. We found that two other domains, Social Amotivation (SA) and Diminished Expression (DE), were nested within the negative symptoms factor. Here, we report one of the largest transethnic factorial structures of PANSS symptom domains (N = 19,682). Evidence reported here serves as crucial consolidation of a common PANSS structure that could aid in furthering our understanding of schizophrenia.
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http://dx.doi.org/10.1016/j.ajp.2021.102732DOI Listing
June 2021

Methylation-eQTL Analysis in Cancer Research.

Bioinformatics 2021 Jun 12. Epub 2021 Jun 12.

Department of Biostatistics, Epidemiology and Informatics, The University of Pennsylvania, Philadelphia, PA 19104-6021, USA.

Motivation: DNA methylation is a key epigenetic factor regulating gene expression. While promoter methylation has been well studied, recent publications have revealed that functionally important methylation also occurs in intergenic and distal regions, and varies across genes and tissue types. Given the growing importance of inter-platform integrative genomic analyses, there is an urgent need to develop methods to discover and characterize gene-level relationships between methylation and expression.

Results: We introduce a novel sequential penalized regression approach to identify methylation-expression quantitative trait loci (methyl-eQTLs), a term that we have coined to represent, for each gene and tissue type, a sparse set of CpG loci best explaining gene expression and accompanying weights indicating direction and strength of association. Using TCGA and MD Anderson colorectal cohorts to build and validate our models, we demonstrate our strategy better explains expression variability than current commonly used gene-level methylation summaries. The methyl-eQTLs identified by our approach can be used to construct gene-level methylation summaries that are maximally correlated with gene expression for use in integrative models, and produce a tissue-specific summary of which genes appear to be strongly regulated by methylation. Our results introduce an important resource to the biomedical community for integrative genomics analyses involving DNA methylation.

Availability And Implementation: We produce an R Shiny app (https://rstudio-prd-c1.pmacs.upenn.edu/methyl-eQTL/) that interactively presents methyl-eQTL results for colorectal, breast, and pancreatic cancer. The source R code for this work is provided in the supplement.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab443DOI Listing
June 2021

Emergency department management of severely injured children in New South Wales.

Emerg Med Australas 2021 Jun 8. Epub 2021 Jun 8.

Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

Objective: Presentations to EDs for major paediatric injury are considerably lower than for adults. International studies report lower levels of critical intervention, including intubation, required in injured children. A New South Wales study demonstrated an adverse event rate of 7.6% in children with major injury. Little is known about the care and interventions received by children presenting to Australian EDs with major injury.

Methods: The ED care of injured children <16 years who ultimately received definitive care at a New South Wales Paediatric Trauma Centre between July 2015 and September 2016, and had an Injury Severity Score ≥9, required intensive care admission or died were included.

Results: There were 491 injured children who received treatment at 64 EDs, half (49.4%, n = 243) were treated initially in a Paediatric Trauma Centre. One third (32.8%) sustained an Injury Severity Score >12, more than half (n = 251, 51.1%) of children were classified as a triage category 1 or 2, and 38.3% received trauma team activation. Critical intervention was infrequent. Intubation was documented in 9.2% (n = 45), needle thoracostomy and activation of massive transfusion protocol in two (0.4%) and eight (1.6%) had intraosseous access established. Only a small proportion (14.7%, n = 63) had two or more observations outside the normal range.

Conclusion: A small proportion of children arriving in the ED post-major trauma have deranged clinical observations and receive critical interventions. The limited exposure in the management of trauma in paediatric patients requires measures to ensure clinicians have adequate training, skills and confidence to manage these clinical presentations in all EDs.
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http://dx.doi.org/10.1111/1742-6723.13805DOI Listing
June 2021

Genome wide study of tardive dyskinesia in schizophrenia.

Transl Psychiatry 2021 Jun 8;11(1):351. Epub 2021 Jun 8.

Research Division, Institute of Mental Health, Singapore, Singapore.

Tardive dyskinesia (TD) is a severe condition characterized by repetitive involuntary movement of orofacial regions and extremities. Patients treated with antipsychotics typically present with TD symptomatology. Here, we conducted the largest GWAS of TD to date, by meta-analyzing samples of East-Asian, European, and African American ancestry, followed by analyses of biological pathways and polygenic risk with related phenotypes. We identified a novel locus and three suggestive loci, implicating immune-related pathways. Through integrating trans-ethnic fine mapping, we identified putative credible causal variants for three of the loci. Post-hoc analysis revealed that SNPs harbored in TNFRSF1B and CALCOCO1 independently conferred three-fold increase in TD risk, beyond clinical risk factors like Age of onset and Duration of illness to schizophrenia. Further work is necessary to replicate loci that are reported in the study and evaluate the polygenic architecture underlying TD.
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http://dx.doi.org/10.1038/s41398-021-01471-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187404PMC
June 2021