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  1. Development of a novel questionnaire to assess knowledge, attitude and practice towards medical disorders in pregnancy among clinicians
    Tan TL, Lau Q, Chiew SC, Thanusha, Mahmoud D, Manisha
    Med J Malaysia, 2024 Jan;79(1):52-59.
    PMID: 38287758
    INTRODUCTION: Maternal medicine is important and complex. It focuses on the care of mothers with comorbidities or medical disorders during pregnancy. To date, there are limited tools to assess clinicians' knowledge, attitude and practice (KAP) in this field.

    MATERIALS AND METHODS: This study aims to develop and validate a questionnaire measuring the KAP of clinicians towards maternal medicine. Literature reviews, item generation and multiple experts' reviews were conducted during the questionnaire development phase. Convenient sampling was undertaken for this cross-sectional survey. A total of 168 clinicians from one tertiary hospital and three health clinics participated in thepilot testing using the modified questionnaire. In addition, test-retest was performed on 30 participants to examine its reliability, whilst exploratory factor analysis (EFA) was undertaken to determine its construct validity.

    RESULTS: This finalised questionnaire contained 36 items with excellent content validity. Pertaining to test-retest reliability, all knowledge domain items showed Kappa values > 0.20, except item K29; attitude domain items overall Cronbach's alpha was 0.787 with corrected item-total correlation > 0.300 and lastly, all items in practice domain achieved intra-class correlation index > 0.700, except P2.5. EFA supported four factor structures, but six items were removed due to the following reasons: cross loading, negative or poor loading factor (< 0.3).

    CONCLUSION: Overall, this instrument has an acceptable psychometric property, content validity, internal reliability and construct validity. It is hope that this questionnaire would be validated in other populations and be used in future research to enrich our understanding of clinicians' KAP towards maternal medicine.

  2. Association of dengue serotypes and its complications: a retrospective cohort study
    Lau Q, Lee ZM, Shunmugarajoo A, Tan CY, Azmel A, Yap SY
    Med J Malaysia, 2023 May;78(3):372-378.
    PMID: 37271848
    INTRODUCTION: Dengue fever is an arthropod-borne disease and has a wide clinical spectrum. It is hypothesised that dengue serotypes could be a possible factor for such phenomena and therefore be a possible predictor for the development of severe dengue.

    METHOD: A retrospective cohort study was done to explore the association between dengue serotypes and the various complications. All patients who underwent dengue serotyping from 1st January to 31st December 2018 in Tengku Ampuan Rahimah Hospital were selected. Serotypes were randomly done for admitted dengue patients. Notes were then retrieved for data collection. Secondary outcomes like length of stay and highest lactate level were also studied. Data analysis was done using SPSS version 20.

    RESULT: A total of 193 patient records were included in the analysis. Chi-square test for independence indicated that the proportion of dengue complications between male and female were significantly different (χ2(1) = 11.37, p = 0.001). Dengue serotype was not associated with the development of dengue complications, total number of dengue complications, length of admission, lactate level and survival among the serotypes. Results of the binary logistic regression showed that men have thrice the odds (AOR = 3.3, 95% CI: 1.6 6.7) for developing dengue complications. One patient was found to be co-infected with serotype 2 and 3.

    CONCLUSION: Our study did not reveal any association between the different dengue virus serotypes and its complications. Therefore, all dengue infection should be approached with equal meticulousness. There are possibilities that apart from serotype, dengue genotype and lineage would determine clinical outcome. However, more studies are required to study such associations.

  3. Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance
    Saunus JM, Quinn MC, Patch AM, Pearson JV, Bailey PJ, Nones K, et al.
    J Pathol, 2015 Nov;237(3):363-78.
    PMID: 26172396 DOI: 10.1002/path.4583
    Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2)  = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting HER3, which is broadly over-expressed and activated in BMs, independent of primary site and systemic therapy.
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