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Fulltext A call for a global COVID-19 Neuro Research Coalition

Winkler AS, Knauss S, Schmutzhard E, Leonardi M, Padovani A, Abd-Allah F, et al.

Lancet Neurol, 2020 06;19(6):482-484.
PMID: 32470416 DOI: 10.1016/S1474-4422(20)30150-2
A case of severe Plasmodium knowlesi in a splenectomized patient

Boo YL, Lim HT, Chin PW, Lim SY, Hoo FK

Parasitol Int, 2016 Feb;65(1):55-57.
PMID: 26454133 DOI: 10.1016/j.parint.2015.10.003

Plasmodium knowlesi, a zoonotic malaria, is now considered the fifth species of Plasmodium causing malaria in humans. With its 24-hour erythrocytic stage of development, it has raised concern regarding its high potential in replicating and leading to severe illness. Spleen is an important site for removal of parasitized red blood cells and generating immunity. We reported a case of knowlesi malaria in a non-immune, splenectomized patient. We observed the delay in parasite clearance, high parasitic counts, and severe illness at presentation. A thorough search through literature revealed several case reports on falciparum and vivax malaria in splenectomized patients. However, literature available for knowlesi malaria in splenectomized patient is limited. Further studies need to be carried out to clarify the role of spleen in host defense against human malaria especially P. knowlesi.
A comparison of dabigatran and warfarin for stroke prevention in elderly Asian population with nonvalvular atrial fibrillation: An audit of current practice in Malaysia

Yap SH, Ng YP, Roslan A, Kolanthaivelu J, Koh KW, P'ng HS, et al.

Med J Malaysia, 2017 12;72(6):360-364.
PMID: 29308774 MyJurnal

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia with significant morbidity and mortality in relation to thromboembolic stroke. Our study aimed to evaluate the safety and efficacy of dabigatran in stroke prevention in elderly patient with nonvalvular AF with regard to the risk of ischemic stroke and intracranial haemorrhage (ICH) in real-world setting.
METHODS: A retrospective cohort study of 200 patients on dabigatran and warfarin from January 2009 till September 2016 was carried out. Data were collected for 100 patients on dabigatran and 100 patients on warfarin.
RESULTS: The mean follow-up period was 340.7±322.3 days for dabigatran group and 410.5±321.2 days for warfarin group. The mean time in therapeutic range (TTR) was 52±18.7%. The mean CHA2DS2 -VASc score for dabigatran group was 4.4±1.1 while 5.0±1.5 for warfarin group. None in dabigatran group experienced ischemic stroke compared to one patient in warfarin group (p=0.316). There was one patient in dabigatran group suffered from ICH compared to none in warfarin group (p=0.316). Four patients in warfarin group experienced minor bleeding, while none from dabigatran group (p=0.043).
CONCLUSION: Overall bleeding events were significantly lower in dabigatran group compared to warfarin group. In the presence of suboptimal TTR rates and inconveniences with warfarin therapy, non-vitamin-K antagonist oral anticoagulants (NOAC) are the preferred agents for stroke prevention in elderly Asian patients for nonvalvular AF.
A rare case of streptococcus mitis infective endocarditis complicated by heart failure in a lactating mother with recurrent breast engorgement

Hakimah S, Liyana Najwa IM, Hoo FK, Siti Zulaikha Z, Haikal Hafiz W, Tan WM

Malays Fam Physician, 2019;14(2):36-38.
PMID: 31827735
Fulltext A report of three cases of untreated Graves' disease associated with pancytopenia in Malaysia

Rafhati AN, See CK, Hoo FK, Badrulnizam LB

Electron Physician, 2014;6(3):877-82.
PMID: 25763162 DOI: 10.14661/2014.877-882

Generally, clinical presentations of Graves' disease range from asymptomatic disease to overt symptomatic hyperthyroidism with heat intolerance, tremor, palpitation, weight loss, and increased appetite. However, atypical presentation of Graves' disease with hematological system involvement, notably pancytopenia, is distinctly uncommon. Hereby, we present and discuss a series of three untreated cases of Graves' disease clinically presented with pancytopenia and the hematological abnormalities that responded well to anti-thyroid treatment. With resolution of the thyrotoxic state, the hematological parameters improved simultaneously. Thus, it is crucial that anti-thyroid treatment be considered in patients with Graves' disease and pancytopenia after a thorough hematological evaluation.
A survey on smartphone dependence and psychological effects among undergraduate students in a Malaysian University

Nasser NS, Loh JL, Rashid AA, Sharifat H, Ahmad U, Ibrahim B, et al.

Med J Malaysia, 2020 07;75(4):356-362.
PMID: 32723994

OBJECTIVE: Problematic smartphone use (PSU) is the development of pathological dependence at the expense of performing activities of daily living, thus having negative health and psychological impact on the users. Previous PSU studies focused on medical students and little is known regarding its effect on students undergoing other courses. The objective of this study is to identify the pattern of smartphone usage and determine the psychological factors affecting PSU among undergraduate students in Malaysia and compare the pattern among students from different fields of study.
METHOD: A prospective cross-sectional study was conducted using the validated Smartphone Addiction Scale-Malay version (SAS-M) questionnaire. One-way ANOVA was used to determine the correlation between the PSU among the students categorised by their ethnicity, hand dominance and by their field of study. MLR analysis was applied to predict PSU based on socio-demographic data, usage patterns, psychological factors and fields of study.
RESULTS: A total of 1060 students completed the questionnaire. Most students had some degree of problematic usage of the smartphone. Students used smartphones predominantly to access SNAs, namely Instagram. Longer duration on the smartphone per day, younger age at first using a smartphone and underlying depression carried higher risk of developing PSU, whereas the field of study (science vs. humanities based) did not contribute to an increased risk of developing PSU.
CONCLUSION: Findings from this study can help better inform university administrators about at- risk groups of undergraduate students who may benefit from targeted intervention designed to reduce their addictive behaviour patterns.
Fulltext Acute coronary syndrome in young adults from a Malaysian tertiary care centre

Hoo FK, Foo YL, Lim SM, Ching SM, Boo YL

Pak J Med Sci, 2016 Jul-Aug;32(4):841-845.
PMID: 27648025

Acute coronary syndrome (ACS) is one of the leading cause of morbidity and mortality worldwide. It is relatively uncommon in young adults as compared to the older population. Our objective was to assess the prevalence, demographic distribution, and risk factors for acute coronary syndrome (ACS) in patients less than 45 years of age admitted to a Malaysian tertiary care centre.
Acute disseminated encephalomyelitis in dengue viral infection

Wan Sulaiman WA, Inche Mat LN, Hashim HZ, Hoo FK, Ching SM, Vasudevan R, et al.

J Clin Neurosci, 2017 Sep;43:25-31.
PMID: 28625589 DOI: 10.1016/j.jocn.2017.05.033

Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature.
An Intriguing Case of Purple Urine Bag Syndrome

Wan Sulaiman WA, Hoo FK, Inche Mat LN

Am J Med Sci, 2017 May;353(5):e9.
PMID: 28502345 DOI: 10.1016/j.amjms.2016.11.022
Fulltext Analysis of the association between CFH Y402H polymorphism and response to intravitreal ranibizumab in patients with neovascular age-related macular degeneration (nAMD)

Mohamad NA, Ramachandran V, Ismail P, Mohd Isa H, Chan YM, Ngah NF, et al.

Bosn J Basic Med Sci, 2018 Aug 01;18(3):260-267.
PMID: 29579408 DOI: 10.17305/bjbms.2018.2493

Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular form of AMD (nAMD) may be due to polymorphisms in the complement factor H gene (CFH). This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE) regimen. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170) polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49) and non-responder (n = 84) group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018). Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05). Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.
Fulltext Anti-Wolbachia therapy for onchocerciasis & lymphatic filariasis: Current perspectives

Wan Sulaiman WA, Kamtchum-Tatuene J, Mohamed MH, Ramachandran V, Ching SM, Sazlly Lim SM, et al.

Indian J Med Res, 2019 06;149(6):706-714.
PMID: 31496523 DOI: 10.4103/ijmr.IJMR_454_17

Onchocerciasis and lymphatic filariasis (LF) are human filarial diseases belonging to the group of neglected tropical diseases, leading to permanent and long-term disability in infected individuals in the endemic countries such as Africa and India. Microfilaricidal drugs such as ivermectin and albendazole have been used as the standard therapy in filariasis, although their efficacy in eliminating the diseases is not fully established. Anti-Wolbachia therapy employs antibiotics and is a promising approach showing potent macrofilaricidal activity and also prevents embryogenesis. This has translated to clinical benefits resulting in successful eradication of microfilarial burden, thus averting the risk of adverse events from target species as well as those due to co-infection with loiasis. Doxycycline shows potential as an anti-Wolbachia treatment, leading to the death of adult parasitic worms. It is readily available, cheap and safe to use in adult non-pregnant patients. Besides doxycycline, several other potential antibiotics are also being investigated for the treatment of LF and onchocerciasis. This review aims to discuss and summarise recent developments in the use of anti-Wolbachia drugs to treat onchocerciasis and LF.
Fulltext Antimicrobial stewardship program in a Malaysian district hospital: First year experience

Sing DY, Boo YL, Mukhlis R, Chin PW, Hoo FK

Pak J Med Sci, 2016 Jul-Aug;32(4):999-1004.
PMID: 27648056

Backgrounds & Objective: Antimicrobial resistance is an alarming public health threat that requires urgent global solution. Implementation of antimicrobial stewardship program (ASP) is an essential practice element for healthcare institutions in gate-keeping judicious antimicrobial use. This study highlighted the development, first year experience, and result of the implementation of ASP utilizing persuasive and restrictive approaches in a Malaysian district hospital.
Methods: An observational study was conducted between January 2015 to December 2015 on implementation of ASP among hospitalized inpatients age 12 years old and above.
Results: Recommendations were provided for 60% of cases (110 patients) with the average acceptance rate of 83.33%. Majority of the interventions were to stop the antimicrobial therapy (30.3%), and the most common audited antimicrobials was Piperacillin/Tazobactam (25.5%), followed by Meropenem (11.82%), Amoxicillin/Clavulanate and Vancomycin (8.18%) respectively. The concordance rate towards authorization policy was increased in 2015 (71.59% of cases) as compared before the implementation of ASP in 2014 (60.6% of cases). Restrictive enforcement under ASP had been shown to improve significantly adherence rate towards antimicrobials authorization policy (p-value: 0.004).
Conclusion: ASP was successfully implemented in a district hospital. Future studies on its clinical outcomes are important to evaluate its effectiveness as well as focus on the improvement to the pre-existing strategies and measures.
KEY WORDS: Antimicrobial stewardship, Anti-Infective agents, Drug resistance, Malaysia, Rural hospital
Fulltext Association Analysis of 14 Candidate Gene Polymorphism with Depression and Stress among Gestational Diabetes Mellitus

Lee KW, Ching SM, Ramachandran V, Tusimin M, Mohd Nordin N, Chong SC, et al.

Genes (Basel), 2019 11 30;10(12).
PMID: 31801286 DOI: 10.3390/genes10120988

The association of candidate genes and psychological symptoms of depression, anxiety, and stress among women with gestational diabetes mellitus (GDM) in Malaysia was determined in this study, followed by the determination of their odds of getting psychological symptoms, adjusted for socio-demographical background, maternal, and clinical characteristics. Single nucleotide polymorphisms (SNPs) recorded a significant association between SNP of EPHX2 (rs17466684) and depression symptoms (AOR = 7.854, 95% CI = 1.330-46.360) and stress symptoms (AOR = 7.664, 95% CI = 1.579-37.197). Associations were also observed between stress symptoms and SNP of OXTR (rs53576) and (AOR = 2.981, 95% CI = 1.058-8.402) and SNP of NRG1 (rs2919375) (AOR = 9.894, 95% CI = 1.159-84.427). The SNP of EPHX2 (rs17466684) gene polymorphism is associated with depression symptoms among Malaysian women with GDM. SNP of EPHX2 (rs17466684), OXTR (rs53576) and NRG1 (rs2919375) are also associated with stress symptoms.
Fulltext Association of HTRA1 and ARMS2 gene polymorphisms with response to intravitreal ranibizumab among neovascular age-related macular degenerative subjects

Mohamad NA, Ramachandran V, Mohd Isa H, Chan YM, Ngah NF, Ching SM, et al.

Hum Genomics, 2019 02 22;13(1):13.
PMID: 30795802 DOI: 10.1186/s40246-019-0197-3

BACKGROUND: The association of HTRA1 rs11200638 and ARMS2 rs10490924 gene polymorphisms with response to intravitreal ranibizumab therapy among neovascular AMD (nAMD) subjects in Malaysia was determined in this study, followed by the expression of HTRA1 and ARMS2 genes.
RESULTS: Both single nucleotide polymorphisms (SNPs) recorded a significant association between nAMD and controls with HTRA1 rs11200638 at P = 0.018 (OR = 1.52, 95% CI = 1.07-215) and ARMS2 rs10490924 at P
Bilateral Motor Cortex Control for Left Thumb Movement: An Incidental Finding Through Functional MRI (fMRI)

Rashid A, Suppiah S, Hoo FK, Masiran R

BMJ Case Rep, 2018 Jan 04;2018.
PMID: 29301796 DOI: 10.1136/bcr-2017-221129

We report a case of a healthy, right-hand dominant young male who was a volunteer for a pilot run of a functional MRI (fMRI) study. The fMRI was performed with a 3.0 Tesla MRI scanner using a finger tapping task-based activity. The subjects were instructed to perform flexion of the right thumb and left thumb consecutively (activation task) and neuronal activation in bilateral primary motor cortex (PMC) were observed during each task. One particular subject demonstrated bilateral PMC activation during the left-thumb movement task, instead of the expected activation of the contralateral PMC alone.
Fulltext Bilateral optic neuritis with maculopathy: A rare manifestation of dengue fever

Boo YL, Lim SY, Chin PW, Hoo FK

Malays Fam Physician, 2017;12(1):32-34.
PMID: 28503273 MyJurnal

Dengue fever is a common mosquito-borne disease, which is endemic in tropical and subtropical countries. Bilateral optic neuropathy is a relatively unusual dengue-related ocular complication. Here, we present a case of bilateral optic neuritis with maculopathy complicating dengue infection.
Fulltext Case report: Incomplete penetrance of autosomal dominant myotonia congenita caused by a rare CLCN1 variant c.1667T>A (p.I556N) in a Malaysian family

Musa NH, Thilakavathy K, Mohamad NA, Kennerson ML, Inche Mat LN, Loh WC, et al.

Front Genet, 2022;13:972007.
PMID: 36659963 DOI: 10.3389/fgene.2022.972007

Myotonia congenita (MC) is a rare neuromuscular disease caused by mutations within the CLCN1 gene encoding skeletal muscle chloride channels. MC is characterized by delayed muscle relaxation during contraction, resulting in muscle stiffness. There is a lack of MC case reports and data on the prevalence among Malaysians. We report a clinical case of a 50-year-old woman presents with muscle stiffness and cramp episodes that started in early childhood. She had difficulty initiating muscle movement and presented with transient muscle weakness after rest, which usually improved after repeated contraction (warm-up phenomenon). She was diagnosed with MC after myotonic discharge on electromyography (EMG). Her brother had similar symptoms; however, no additional family members showed MC symptoms. Serum creatine kinase levels were elevated in both the proband and her brother with 447 U/L and 228 U/L recorded, respectively. Genetic analysis by whole-exome sequencing (WES) revealed a previously reported pathogenic CLCN1 gene variant c.1667T>A (p.I556N). Genetic screening of all family members revealed that the same variant was observed in the children of both the proband and her brother; however, the children did not present with either clinical or electrophysiological MC symptoms. The multiplex ligation-dependent probe amplification (MLPA) analysis conducted identified neither exon deletion nor duplication in CLCN1. In conclusion, this report describes the first case of MC in Malaysia in which incomplete penetrance observed in this family is caused by a known pathogenic CLCN1 variant.
Correction: Vitamin D status and clinical implications in the adult population of Malaysia: a position paper by the Malaysian Vitamin D Special Interest Group

Lee JK, Chee WSS, Foo SH, Lee VKM, Sallehuddin H, Khor HM, et al.

Osteoporos Int, 2023 Nov;34(11):1851-1852.
PMID: 37505306 DOI: 10.1007/s00198-023-06865-w
Fulltext Cue-Reactivity Among Young Adults With Problematic Instagram Use in Response to Instagram-Themed Risky Behavior Cues: A Pilot fMRI Study

Nasser NS, Sharifat H, Rashid AA, Hamid SA, Rahim EA, Loh JL, et al.

Front Psychol, 2020;11:556060.
PMID: 33224051 DOI: 10.3389/fpsyg.2020.556060

Background: Problematic Instagram use (PIGU), a specific type of internet addiction, is prevalent among adolescents and young adults. In certain instances, Instagram acts as a platform for exhibiting photos of risk-taking behavior that the subjects with PIGU upload to gain likes as a surrogate for gaining peer acceptance and popularity.
Aims: The primary objective was to evaluate whether addiction-specific cues compared with neutral cues, i.e., negative emotional valence cues vs. positive emotional valence cues, would elicit activation of the dopaminergic reward network (i.e., precuneus, nucleus accumbens, and amygdala) and consecutive deactivation of the executive control network [i.e., medial prefrontal cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC)], in the PIGU subjects.
Method: An fMRI cue-induced reactivity study was performed using negative emotional valence, positive emotional valence, and truly neutral cues, using Instagram themes. Thirty subjects were divided into PIGU and healthy control (HC) groups, based on a set of diagnostic criteria using behavioral tests, including the Modified Instagram Addiction Test (IGAT), to assess the severity of PIGU. In-scanner recordings of the subjects' responses to the images and regional activity of the neural addiction pathways were recorded.
Results: Negative emotional valence > positive emotional valence cues elicited increased activations in the precuneus in the PIGU group. A negative and moderate correlation was observed between PSC at the right mPFC with the IGAT scores of the PIGU subjects when corrected for multiple comparisons [r = -0.777, (p < 0.004, two-tailed)].
Conclusion: Addiction-specific Instagram-themed cues identify the neurobiological underpinnings of Instagram addiction. Activations of the dopaminergic reward system and deactivation of the executive control network indicate converging neuropathological pathways between Instagram addiction and other types of addictions.
Fulltext Current Insights on Dyslipidaemia Management for Prevention of Atherosclerotic Cardiovascular Disease: A Malaysian Perspective

Wan Ahmad WA, Rosman A, Bavanandan S, Mohamed M, Kader MASA, Muthusamy TS, et al.

Malays J Med Sci, 2023 Feb;30(1):67-81.
PMID: 36875188 DOI: 10.21315/mjms2023.30.1.6

Dyslipidaemia is highly prevalent in the Malaysian population and is one of the main risk factors for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) is recognised as the primary target of lipid-lowering therapy to reduce the disease burden of ASCVD. Framingham General CV Risk Score has been validated in the Malaysian population for CV risk assessment. The Clinical Practice Guidelines (CPG) on the management of dyslipidaemia were last updated in 2017. Since its publication, several newer randomised clinical trials have been conducted with their results published in research articles and compared in meta-analysis. This underscores a need to update the previous guidelines to ensure good quality care and treatment for the patients. This review summarises the benefits of achieving LDL-C levels lower than the currently recommended target of < 1.8mmol/L without any safety concerns. In most high and very high-risk individuals, statins are the first line of therapy for dyslipidaemia management. However, certain high-risk individuals are not able to achieve the LDL-C goal as recommended in the guideline even with high-intensity statin therapy. In such individuals, lower LDL-C levels can be achieved by combining the statins with non-statin agents such as ezetimibe and PCSK9 inhibitors. Emerging non-statin lipid-lowering therapies and challenges in dyslipidaemia management are discussed in this article. The review also summarises the recent updates on local and international guidelines for dyslipidaemia management.

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