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  1. Suleiman AB, Mathews A, Jegasothy R, Ali R, Kandiah N
    Bull World Health Organ, 1999;77(2):190-3.
    PMID: 10083722
    A confidential system of enquiry into maternal mortality was introduced in Malaysia in 1991. The methods used and the findings obtained up to 1994 are reported below and an outline is given of the resulting recommendations and actions.
    PIP: This is a report on the methods, findings, resulting recommendations and actions of a study on maternal mortality in Malaysia during the period 1991-94. Maternal death was defined as the death of a woman while pregnant or within 42 days following termination of pregnancy from any cause related to the pregnancy or its management but not from accidental causes. Between 1991 and 1994 there were 1066 reported maternal deaths, and the maternal mortality ratios for the successive years were respectively 44, 48, 46 and 39 per 100,000 live births. The primary causes of maternal death were postpartum hemorrhage (24%), hypertensive disorders of pregnancy (16%), obstetric pulmonary embolism (13%), and associated medical conditions (7%). Analysis of the 375 deaths from 1992 - 1993 showed that the maternal mortality ratio was 53/100,000 live births for deliveries performed at home, 36/100,000 in government hospitals, and 21/100,000 in private institutions. Shortcomings among health personnel were detected in several cases; these involved failure to diagnose, failure to appreciate the severity of a patient's condition, inadequate therapy, and inappropriate, delayed or failed adherence to protocols. The high proportion of maternal mortality associated with substandard care demonstrates that it is important to make the standard of care more widely available. Reports have been circulated to institutions and organizations providing maternal care and to medical schools. Articles and case histories have been published, and many new protocols and procedures have been developed. Furthermore, seminars have been organized and training modules have been distributed to all involved in the provision of maternity care.
  2. Kandiah N, Lekhraj R, Paranjothy S, Gill AK
    Med J Malaysia, 1980 Mar;34(3):211-20.
    PMID: 7412661
    A pilot study on the epidemiology of hypertension was carried out in 3 out of the 8 districts in the state of Selangor, namely Klang, Sabak Bernam and UIu Langat. stratified random sampling, 435 households were selected for the study. Eventually 312 (72%) households were surveyed: 963 (94%) out of the 1,030 persons aged 15 years and above living in the selected households were interviewed, and 957 of them were examined. The mean age of the respondents was 33 years. Taking a systolic pressure of more than 140 mmHg and/or diastolic pressure of more than 90 mmHg as hypertension, 1 in every 7 of those equal and mor.e than 15 years of age had hypertension, i.e. 140/0. 5.40/0 had a systolic pressure of equal and more than 160 mmHg, and 4.7% had a diastolic pressure of equal and more than 95 mmHg. The study showed that there was a significant rise in the prevalence rates with age in both sexes. There was no significant difference in the prevalence rates among. the sexes, ethnic groups (Malays, Chinese and Indians) and urban and rural areas. The mean systolic pressure ranged from 112-147 mmHg and diastolic from 69 - 73 mmHg. Hypertension was significantly more common among smokers (18.1%) than nonsmokers. There was no significant relationship between hypertension and tea, coffee and alcohol consumption. Hypertension was significantly more common among those with no physical activity (34.8%) as compared with those with physical activity (13.5%). 67% of the hypertensives were aware of their illness but only 36.1% of them were under treatment.
  3. Kandiah N, Pai MC, Senanarong V, Looi I, Ampil E, Park KW, et al.
    Clin Interv Aging, 2017;12:697-707.
    PMID: 28458525 DOI: 10.2147/CIA.S129145
    Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE-BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.
  4. Lim L, Ng TP, Ong AP, Tan MP, Cenina AR, Gao Q, et al.
    Alzheimers Res Ther, 2018 01 22;10(1):6.
    PMID: 29370825 DOI: 10.1186/s13195-017-0333-z
    BACKGROUND: Cognitive screeners are imperative for early diagnosis of dementia. The Visual Cognitive Assessment Test (VCAT) is a language-neutral, visual-based test which has proven useful for a multilingual population in a single-center study. However, its performance utility is unknown in a wider and more diverse Southeast Asian cohort.

    METHODS: We recruited 164 healthy controls (HC) and 120 cognitively impaired (CI) subjects- 47 mild cognitive impairment (MCI) and 73 mild Alzheimer's disease (AD) dementia participants, from four countries between January 2015 and August 2016 to determine the usefulness of a single version of the VCAT, without translation or adaptation, in a multinational, multilingual population. The VCAT was administered along with established cognitive evaluation.

    RESULTS: The VCAT, without local translation or adaptation, was effective in discriminating between HC and CI subjects (MCI and mild AD dementia). Mean (SD) VCAT scores for HC and CI subjects were 22.48 (3.50) and 14.17 (5.05) respectively. Areas under the curve for Montreal Cognitive Assessment (0.916, 95% CI 0.884-0.948) and the VCAT (0.905, 95% CI 0.870-0.940) in discriminating between HCs and CIs were comparable. The multiple languages used to administer VCAT in four countries did not significantly influence test scores.

    CONCLUSIONS: The VCAT without the need for language translation or cultural adaptation showed satisfactory discriminative ability and was effective in a multinational, multilingual Southeast Asian population.

  5. Lock C, Kwok J, Kumar S, Ahmad-Annuar A, Narayanan V, Ng ASL, et al.
    PMID: 30687707 DOI: 10.3389/fmed.2018.00357
    Normal pressure hydrocephalus (NPH) is a syndrome comprising gait disturbance, cognitive decline and urinary incontinence that is an unique model of reversible brain injury, but it presents as a challenging spectrum of disease cohorts. Diffusion Tensor Imaging (DTI), with its ability to interrogate structural white matter patterns at a microarchitectural level, is a potentially useful tool for the confirmation and characterization of disease cohorts at the clinical-research interface. However, obstacles to its widespread use involve the need for consistent DTI analysis and interpretation tools across collaborator sites. We present the use of DTI profiles, a simplistic methodology to interpret white matter injury patterns based on the morphology of diffusivity parameters. We examined 13 patients with complex NPH, i.e., patients with NPH and overlay from multiple comorbidities, including vascular risk burden and neurodegenerative disease, undergoing extended CSF drainage, clinical assessments, and multi-modal MR imaging. Following appropriate exclusions, we compared the morphology of DTI profiles in such complex NPH patients (n = 12, comprising 4 responders and 8 non-responders) to exemplar DTI profiles from a cohort of classic NPH patients (n = 16) demonstrating responsiveness of white matter injury to ventriculo-peritoneal shunting. In the cohort of complex NPH patients, mean age was 71.3 ± 7.6 years (10 males, 2 females) with a mean MMSE score of 21.1. There were 5 age-matched healthy controls, mean age was 73.4 ± 7.2 years (1 male, 4 females) and mean MMSE score was 26.8. In the exemplar cohort of classic NPH patients, mean age was 74.7 ± 5.9 years (10 males, 6 females) and mean MMSE score was 24.1. There were 9 age-matched healthy controls, mean age was 69.4 ± 9.7 years (4 males, 5 females) and mean MMSE score was 28.6. We found that, despite the challenges of acquiring DTI metrics from differing scanners across collaborator sites and NPH patients presenting as differing cohorts along the spectrum of disease, DTI profiles for responsiveness to interventions were comparable. Distinct DTI characteristics were demonstrated for complex NPH responders vs. non-responders. The morphology of DTI profiles for complex NPH responders mimicked DTI patterns found in predominantly shunt-responsive patients undergoing intervention for classic NPH. However, DTI profiles for complex NPH non-responders was suggestive of atrophy. Our findings suggest that it is possible to use DTI profiles to provide a methodology for rapid description of differing cohorts of disease at the clinical-research interface. By describing DTI measures morphologically, it was possible to consistently compare white matter injury patterns across international collaborator datasets.
  6. Kandiah N, Ong PA, Yuda T, Ng LL, Mamun K, Merchant RA, et al.
    CNS Neurosci Ther, 2019 02;25(2):288-298.
    PMID: 30648358 DOI: 10.1111/cns.13095
    BACKGROUND: The Ginkgo biloba special extract, EGb 761® has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer's disease (AD).

    METHODS: To guide clinical practice in the Asian region, the Asian Clinical Expert Group on Neurocognitive Disorders compiled evidence-based consensus recommendations regarding the use of EGb 761® in neurocognitive disorders with/without cerebrovascular disease.

    RESULTS: Key randomized trials and robust meta-analyses have demonstrated significant improvement in cognitive function, neuropsychiatric symptoms, activities of daily living (ADL) and quality of life with EGb 761® versus placebo in patients with mild-to-moderate dementia. In those with mild cognitive impairment (MCI), EGb 761® has also demonstrated significant symptomatic improvement versus placebo. World Federation of Societies of Biological Psychiatry guidelines list EGb 761® with the same strength of evidence as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) antagonists e.g. memantine (Grade 3 recommendation; Level B evidence). Only EGb 761® had Level B evidence in improving cognition, behaviour, and ADL in both AD and vascular dementia patients. Safety analyses show EGb 761® to have a positive risk-benefit profile. While concerns have been raised regarding a possible increased bleeding risk, several randomized trials and two meta-analyses have not supported this association.

    CONCLUSIONS: The Expert Group foresee an important role for EGb 761® , used alone or as an add-on therapy, in the treatment of MCI and dementias, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists. EGb 761® should be used in alignment with local clinical practice guidelines.

  7. Kandiah N, Chan YF, Chen C, Dasig D, Dominguez J, Han SH, et al.
    CNS Neurosci Ther, 2021 Feb;27(2):149-162.
    PMID: 33352000 DOI: 10.1111/cns.13536
    BACKGROUND: Mild cognitive impairment (MCI) is a neurocognitive state between normal cognitive aging and dementia, with evidence of neuropsychological changes but insufficient functional decline to warrant a diagnosis of dementia. Individuals with MCI are at increased risk for progression to dementia; and an appreciable proportion display neuropsychiatric symptoms (NPS), also a known risk factor for dementia. Cerebrovascular disease (CVD) is thought to be an underdiagnosed contributor to MCI/dementia. The Ginkgo biloba extract, EGb 761® , is increasingly being used for the symptomatic treatment of cognitive disorders with/without CVD, due to its known neuroprotective effects and cerebrovascular benefits.

    AIMS: To present consensus opinion from the ASian Clinical Expert group on Neurocognitive Disorders (ASCEND) regarding the role of EGb 761® in MCI.

    MATERIALS & METHODS: The ASCEND Group reconvened in September 2019 to present and critically assess the current evidence on the general management of MCI, including the efficacy and safety of EGb 761® as a treatment option.

    RESULTS: EGb 761® has demonstrated symptomatic improvement in at least four randomized trials, in terms of cognitive performance, memory, recall and recognition, attention and concentration, anxiety, and NPS. There is also evidence that EGb 761® may help delay progression from MCI to dementia in some individuals.

    DISCUSSION: EGb 761® is currently recommended in multiple guidelines for the symptomatic treatment of MCI. Due to its beneficial effects on cerebrovascular blood flow, it is reasonable to expect that EGb 761® may benefit MCI patients with underlying CVD.

    CONCLUSION: As an expert group, we suggest it is clinically appropriate to incorporate EGb 761® as part of the multidomain intervention for MCI.

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