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Zebrafish phenotypic screen identifies novel Notch antagonists

Velaithan V, Okuda KS, Ng MF, Samat N, Leong SW, Faudzi SM, et al.

Invest New Drugs, 2017 04;35(2):166-179.
PMID: 28058624 DOI: 10.1007/s10637-016-0423-y

Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors. Subsequent secondary screens using HEK293T cells overexpressing truncated Notch1 (HEK293TΔE) identified 2 compounds, EDD3 and 3H4MB, to be potential Notch antagonists. Both compounds reduced protein expression of NOTCH1, Notch intracellular domain (NICD) and hairy and enhancer of split-1 (HES1) in HEK293TΔE and downregulated Notch target genes. Importantly, EDD3 treatment of human oral cancer cell lines demonstrated reduction of Notch target proteins and genes. EDD3 also inhibited proliferation and induced G0/G1 cell cycle arrest of ORL-150 cells through inducing p27KIP1. Our data demonstrates the utility of the zebrafish phenotypic screen and identifying EDD3 as a promising Notch antagonist for further development as a novel therapeutic agent.
Erratum to: Zebrafish phenotypic screen identifies novel Notch antagonists

Velaithan V, Okuda KS, Ng MF, Samat N, Leong SW, Faudzi SM, et al.

Invest New Drugs, 2017 04;35(2):250.
PMID: 28185040 DOI: 10.1007/s10637-017-0437-0
Fulltext Evaluation of immature platelet fraction as a marker of dengue fever progression

Looi KW, Matsui Y, Kono M, Samudi C, Kojima N, Ong JX, et al.

Int J Infect Dis, 2021 Sep;110:187-194.
PMID: 34302960 DOI: 10.1016/j.ijid.2021.07.048

OBJECTIVES: Progression of dengue is often associated with thrombocytopenia resulting from viral-induced bone marrow suppression and immune-mediated peripheral platelet consumption. Immature platelet fraction (IPF), which can be measured using a haematology analyser, is a precursor indicating platelet formation in the bone marrow. This study evaluated the trend of IPF as an early recovery indicator of platelets in dengue patients with thrombocytopenia, and its relationship with severe dengue in conjunction with reticulocyte count.
METHODS: Hospitalized patients with dengue were enrolled and followed-up daily until discharge. Blood investigations included daily full blood counts and IPF measured using a haematology analyser.
RESULTS: In total, 287 patients with confirmed dengue were enrolled in this study, 25 of whom had severe dengue. All patients had a decreasing trend in platelet count in the first week of illness, concomitant with an increasing trend in the percentage of immature platelets to total platelets (IPF%) for more than 3 days prior to platelet recovery. IPF% was significantly increased in patients with severe dengue compared with patients with non-severe dengue on days 3-5 after the onset of fever. Reticulocyte count increased significantly in patients with severe dengue on day 5.
CONCLUSIONS: IPF can be utilized as an early recovery indicator of platelets in patients with dengue and thrombocytopenia.
Fulltext Complementary Analytical Platforms of NMR Spectroscopy and LCMS Analysis in the Metabolite Profiling of Isochrysis galbana

Bustamam MSA, Pantami HA, Azizan A, Shaari K, Min CC, Abas F, et al.

Mar Drugs, 2021 Mar 02;19(3).
PMID: 33801258 DOI: 10.3390/md19030139

This study was designed to profile the metabolites of Isochrysis galbana, an indigenous and less explored microalgae species. 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Liquid Chromatography-Mass Spectrometry (LCMS) were used to establish the metabolite profiles of five different extracts of this microalga, which are hexane (Hex), ethyl acetate (EtOAc), absolute ethanol (EtOH), EtOH:water 1:1 (AqE), and 100% water (Aq). Partial least square discriminant analysis (PLS-DA) of the generated profiles revealed that EtOAc and Aq extracts contain a diverse range of metabolites as compared to the other extracts with a total of twenty-one metabolites, comprising carotenoids, polyunsaturated fatty acids, and amino acids, that were putatively identified from the NMR spectra. Meanwhile, thirty-two metabolites were successfully annotated from the LCMS/MS data, ten of which (palmitic acid, oleic acid, α-linolenic acid, arachidic acid, cholesterol, DHA, DPA, fucoxanthin, astaxanthin, and pheophytin) were similar to those present in the NMR profile. Another eleven glycerophospholipids were discovered using MS/MS-based molecular network (MN) platform. The results of this study, besides providing a better understanding of I.galbana's chemical make-up, will be of importance in exploring this species potential as a feed ingredient in the aquaculture industry.
Fulltext Thermal Tolerance and Physiological Changes in Mud Crab, Scylla paramamosain Crablet at Different Water Temperatures

Syafaat MN, Azra MN, Mohamad F, Che-Ismail CZ, Amin-Safwan A, Asmat-Ullah M, et al.

Animals (Basel), 2021 Apr 16;11(4).
PMID: 33923853 DOI: 10.3390/ani11041146

This study was carried out to determine the physiological changes (survival, growth, molting cycle, sex differentiation, and gill condition) of mud crab, Scylla paramamosain crablet at different water temperatures of 24, 28 and 32 °C, and ambient temperature of 27 to 30 °C. Thermoregulatory behavior, represented by preferred temperature (29.83 ± SD 2.47 °C), critical thermal minimum (17.33 ± SD 0.58 °C), critical thermal maximum (40 ± SD 0.00 °C), and thermal tolerance interval (22.67 ± SD 0.58 °C), were checked for Crablet 1 stage only (with ambient temperature as acclimation temperature).Both low (24 °C) and high (32 °C) temperatures were associated with lower growth performance, and survival rate (p < 0.05), in comparison with both 28 °C and ambient temperature treatments.Male ratio at low temperaturetreatment (24 °C) was higher (80.09 ± SD 18.86%) than for other treatments (p < 0.05), observed as 44.81 ± D 10.50%, 41.94 ± SD 19.44%, and 76.30 ± SD 5.13% for 28 °C, 32 °C and ambient temperature treatments, respectively. However, there was no significant difference observed between 24 °C, 28 °C, and ambient temperature treatments. Anatomical alterations of gill lamellae of S. paramamosain crablet for both 32 °C, and 24 °C treatments, appeared thinner and paler than at both 28 °C, and ambient temperature treatments. Based on this study, temperature of 28 to 30 °C was recommended as the optimal temperature for the long-term nursery phase of S. paramamosain.
Fulltext Detection of respiratory viruses in adults with suspected COVID-19 in Kuala Lumpur, Malaysia

Chong YM, Chan YF, Jamaluddin MFH, Hasan MS, Pang YK, Ponnampalavanar S, et al.

J Clin Virol, 2021 Dec;145:105000.
PMID: 34739838 DOI: 10.1016/j.jcv.2021.105000

BACKGROUND: Reports of co-circulation of respiratory viruses during the COVID-19 pandemic and co-infections with SARS-CoV-2 vary. However, limited information is available from developing countries.
OBJECTIVES: We aimed to investigate the incidence of respiratory viruses in adult patients with suspected COVID-19 in Kuala Lumpur, Malaysia.
STUDY DESIGN: We collected 198 respiratory samples from adult patients hospitalized with suspected COVID-19 in a single teaching hospital in Kuala Lumpur in February-May 2020 and tested combined oro-nasopharyngeal swabs with the NxTAG Respiratory Pathogen Panel (Luminex) and Allplex RV Essential (Seegene) assays. Forty-five negative samples further underwent viral metagenomics analysis.
RESULTS: Of the 198 samples, 74 (37.4%) had respiratory pathogens, including 56 (28.3%) with SARS-CoV-2 and 18 (9.1%) positive for other respiratory pathogens. There were five (2.5%) SARS-CoV-2 co-infections, all with rhinovirus/enterovirus. Three samples (6.7%; 3/45) had viruses identified by metagenomics, including one case of enterovirus D68 and one of Saffold virus genotype 6 in a patient requiring ICU care. Most of the COVID-19 patients (91.1%; 51/56) had mild symptoms but 5.4% (3/56) died.
CONCLUSION: During the early COVID-19 period, common respiratory viruses other than SARS-CoV-2 only accounted for 9.1% of hospitalization cases with ARI and co-infections with SARS-CoV-2 were rare. Continued surveillance is important to understand the impact of COVID-19 and its associated public health control measures on circulation of other respiratory viruses. Metagenomics can identify unexpected or rare pathogens, such as Saffold virus, which is rarely described in adults.
Fulltext Genetic linkage map of a high yielding FELDA deli×yangambi oil palm cross

Seng TY, Mohamed Saad SH, Chin CW, Ting NC, Harminder Singh RS, Qamaruz Zaman F, et al.

PLoS One, 2011;6(11):e26593.
PMID: 22069457 DOI: 10.1371/journal.pone.0026593

Enroute to mapping QTLs for yield components in oil palm, we constructed the linkage map of a FELDA high yielding oil palm (Elaeis guineensis), hybrid cross. The parents of the mapping population are a Deli dura and a pisifera of Yangambi origin. The cross out-yielded the average by 8-21% in four trials all of which yielded comparably to the best current commercial planting materials. The higher yield derived from a higher fruit oil content. SSR markers in the public domain - from CIRAD and MPOB, as well as some developed in FELDA - were used for the mapping, augmented by locally-designed AFLP markers. The female parent linkage map comprised 317 marker loci and the male parent map 331 loci, both in 16 linkage groups each. The number of markers per group ranged from 8-47 in the former and 12-40 in the latter. The integrated map was 2,247.5 cM long and included 479 markers and 168 anchor points. The number of markers per linkage group was 15-57, the average being 29, and the average map density 4.7 cM. The linkage groups ranged in length from 77.5 cM to 223.7 cM, with an average of 137 cM. The map is currently being validated against a closely related population and also being expanded to include yield related QTLs.
Bioassay-guided identification of an anti-inflammatory prenylated acylphloroglucinol from Melicope ptelefolia and molecular insights into its interaction with 5-lipoxygenase

Shaari K, Suppaiah V, Wai LK, Stanslas J, Tejo BA, Israf DA, et al.

Bioorg Med Chem, 2011 Nov 1;19(21):6340-7.
PMID: 21958738 DOI: 10.1016/j.bmc.2011.09.001

A bioassay-guided investigation of Melicope ptelefolia Champ ex Benth (Rutaceae) resulted in the identification of an acyphloroglucinol, 2,4,6-trihydroxy-3-geranylacetophenone or tHGA, as the active principle inhibiting soybean 15-LOX. The anti-inflammatory action was also demonstrated on human leukocytes, where the compound showed prominent inhibitory activity against human PBML 5-LOX, with an IC(50) value of 0.42 μM, very close to the effect produced by the commonly used standard, NDGA. The compound concentration-dependently inhibited 5-LOX product synthesis, specifically inhibiting cysteinyl leukotriene LTC(4) with an IC(50) value of 1.80 μM, and showed no cell toxicity effects. The anti-inflammatory action does not seem to proceed via redox or metal chelating mechanism since the compound tested negative for these bioactivities. Further tests on cyclooxygenases indicated that the compound acts via a dual LOX/COX inhibitory mechanism, with greater selectivity for 5-LOX and COX-2 (IC(50) value of 0.40 μM). The molecular features that govern the 5-LOX inhibitory activity was thus explored using in silico docking experiments. The residues Ile 553 and Hie 252 were the most important residues in the interaction, each contributing significant energy values of -13.45 (electrostatic) and -5.40 kcal/mol (electrostatic and Van der Waals), respectively. The hydroxyl group of the phloroglucinol core of the compound forms a 2.56Å hydrogen bond with the side chain of the carboxylate group of Ile 553. Both Ile 553 and Hie 252 are crucial amino acid residues which chelate with the metal ion in the active site. Distorting the geometry of these ligands could be the reason for the inhibition activity shown by tHGA. The molecular simulation studies supported the bioassay results and served as a good model for understanding the way tHGA binds in the active site of human 5-LOX enzyme.
Inhibition of prostaglandin E(2) production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation

Rullah K, Mohd Aluwi MF, Yamin BM, Abdul Bahari MN, Wei LS, Ahmad S, et al.

Bioorg Med Chem Lett, 2014 Aug 15;24(16):3826-34.
PMID: 25027933 DOI: 10.1016/j.bmcl.2014.06.061

The discovery of potent inhibitors of prostaglandin E2 (PGE2) synthesis in recent years has been proven to be an important game changer in pharmaceutical industry. It is known that excessive production of PGE2 triggers a vast array of biological signals and physiological events that contributes to inflammatory diseases such as rheumatoid arthritis, atherosclerosis, cancer, and pain. In this Letter, we report the synthesis of a series of minor prenylated chalcones and flavonoids which was found to be significantly active in suppressing the PGE2 production secreted by lipopolysaccharide-induced mouse macrophage cells (RAW 264.7). Among the compounds tested, 14b showed a dose-response inhibition of PGE2 production with an IC50 value of 2.1 μM. The suppression upon PGE2 secretion was not due to cell death since 14b did not reduce the cell viability in close proximity to the PGE2 inhibition concentration. The obtained atomic coordinates for the single-crystal XRD of 14b was then applied in the docking simulation to determine the potential important binding interactions with murine COX-2 and mPGES-1 putative binding sites.
Psychosocial risk factors and cognitive decline in people living with HIV: results from the Malaysian HIV and aging (MHIVA) study

Neelamegam M, Ahmad A, Chong ML, Wong PL, Zulhaimi NS, Cysique L, et al.

AIDS Care, 2024 Aug;36(8):1041-1049.
PMID: 37666210 DOI: 10.1080/09540121.2023.2254543

HIV-associated mortality has improved with the advent of antiretroviral therapy, yet neurocognitive decline persists. We assessed the association between psychosocial risk factors and cognitive function among Malaysian PLWH. Data of virally suppressed PLWH (n = 331) on stable ART, from the Malaysian HIV and Aging study was assessed. Psychosocial factors were assessed using the Lubben Social Network Scale-6 (social isolation) and Depression Anxiety Stress Scale-21 (DASS-21). The Montreal Cognitive Assessment (MoCA) with normative standards for the Malaysian population was used to determine cognitive function. Linear and logistic regression were used to assess the associations between cognition, and psychosocial risk factors. Median age of participants was 43.8 years (IQR 37.7-51.0). Participants were predominantly male (82.8%), with secondary education or higher (85.2%). Participants were on ART for 5.7 years (IQR 3.0-9.7), with a mean MoCA score of 24.6 (±3.7). Social isolation was found in 34.6% of participants, and severe depression, severe stress, and severe anxiety in 10.6%, 15.4%, and 6.0% respectively. After adjusting for demographic, clinical, and HIV parameters, MoCA scores were significantly associated with severe stress (β = -0.11, p = 0.02) and having marginal friendship ties (β = -0.13, p = 0.03). Social isolation and severe stress are associated with neurocognitive impairment in PLWH.
Remodeling in Aortic Stenosis With Reduced and Preserved Ejection Fraction: Insight on Motion Abnormality Via 3D + Time Personalized LV Modeling in Cardiac MRI

Chuah SH, Tan LK, Md Sari NA, Chan BT, Hasikin K, Lim E, et al.

J Magn Reson Imaging, 2024 Apr;59(4):1242-1255.
PMID: 37452574 DOI: 10.1002/jmri.28915

BACKGROUND: Increased afterload in aortic stenosis (AS) induces left ventricle (LV) remodeling to preserve a normal ejection fraction. This compensatory response can become maladaptive and manifest with motion abnormality. It is a clinical challenge to identify contractile and relaxation dysfunction during early subclinical stage to prevent irreversible deterioration.
PURPOSE: To evaluate the changes of regional wall dynamics in 3D + time domain as remodeling progresses in AS.
STUDY TYPE: Retrospective.
POPULATION: A total of 31 AS patients with reduced and preserved ejection fraction (14 AS_rEF: 7 male, 66.5 [7.8] years old; 17 AS_pEF: 12 male, 67.0 [6.0] years old) and 15 healthy (6 male, 61.0 [7.0] years old).
FIELD STRENGTH/SEQUENCE: 1.5 T Magnetic resonance imaging/steady state free precession and late-gadolinium enhancement sequences.
ASSESSMENT: Individual LV models were reconstructed in 3D + time domain and motion metrics including wall thickening (TI), dyssynchrony index (DI), contraction rate (CR), and relaxation rate (RR) were automatically extracted and associated with the presence of scarring and remodeling.
STATISTICAL TESTS: Shapiro-Wilk: data normality; Kruskal-Wallis: significant difference (P
Fulltext Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents

Leong SW, Faudzi SM, Abas F, Aluwi MF, Rullah K, Wai LK, et al.

Molecules, 2014 Oct 09;19(10):16058-81.
PMID: 25302700 DOI: 10.3390/molecules191016058

A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma (IFN-γ)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Twelve compounds (9, 25, 28, 43, 63, 64, 81, 83, 84, 86, 88 and 97) exhibited greater or similar NO inhibitory activity in comparison with curcumin (14.7 ± 0.2 µM), notably compounds 88 and 97, which demonstrated the most significant NO suppression activity with IC50 values of 4.9 ± 0.3 µM and 9.6 ± 0.5 µM, respectively. A structure-activity relationship (SAR) study revealed that the presence of a hydroxyl group in both aromatic rings is critical for bioactivity of these molecules. With the exception of the polyphenolic derivatives, low electron density in ring-A and high electron density in ring-B are important for enhancing NO inhibition. Meanwhile, pharmacophore mapping showed that hydroxyl substituents at both meta- and para-positions of ring-B could be the marker for highly active diarylpentanoid derivatives.
Nitric oxide inhibitory activity and antioxidant evaluations of 2-benzoyl-6-benzylidenecyclohexanone analogs, a novel series of curcuminoid and diarylpentanoid derivatives

Leong SW, Mohd Faudzi SM, Abas F, Mohd Aluwi MF, Rullah K, Lam KW, et al.

Bioorg Med Chem Lett, 2015 Aug 15;25(16):3330-7.
PMID: 26071636 DOI: 10.1016/j.bmcl.2015.05.056

A series of twenty-four 2-benzoyl-6-benzylidenecyclohexanone analogs were synthesized and evaluated for their nitric oxide inhibition and antioxidant activity. Six compounds (3, 8, 10, 17, 18 and 19) were found to exhibit significant NO inhibitory activity in LPS/IFN-induced RAW 264.7 macrophages, of which compound 10 demonstrated the highest activity with the IC50 value of 4.2 ± 0.2 μM. Furthermore, two compounds (10 and 17) displayed antioxidant activity upon both the DPPH scavenging and FRAP analyses. However, none of the 2-benzoyl-6-benzylidenecyclohexanone analogs significantly scavenged NO radical. Structure-activity comparison suggested that 3,4-dihydroxylphenyl ring is crucial for bioactivities of the 2-benzoyl-6-benzylidenecyclohexanone analogs. The results from this study and the reports from previous studies indicated that compound 10 could be a candidate for further investigation on its potential as a new anti-inflammatory agent.
Regional assessment of LV wall in infarcted heart using tagged MRI and cardiac modelling

Jahanzad Z, Liew YM, Bilgen M, McLaughlin RA, Leong CO, Chee KH, et al.

Phys Med Biol, 2015 May 21;60(10):4015-31.
PMID: 25919317 DOI: 10.1088/0031-9155/60/10/4015

A segmental two-parameter empirical deformable model is proposed for evaluating regional motion abnormality of the left ventricle. Short-axis tagged MRI scans were acquired from 10 healthy subjects and 10 postinfarct patients. Two motion parameters, contraction and rotation, were quantified for each cardiac segment by fitting the proposed model using a non-rigid registration algorithm. The accuracy in motion estimation was compared to a global model approach. Motion parameters extracted from patients were correlated to infarct transmurality assessed with delayed-contrast-enhanced MRI. The proposed segmental model allows markedly improved accuracy in regional motion analysis as compared to the global model for both subject groups (1.22-1.40 mm versus 2.31-2.55 mm error). By end-systole, all healthy segments experienced radial displacement by ~25-35% of the epicardial radius, whereas the 3 short-axis planes rotated differently (basal: 3.3°; mid: -1° and apical: -4.6°) to create a twisting motion. While systolic contraction showed clear correspondence to infarct transmurality, rotation was nonspecific to either infarct location or transmurality but could indicate the presence of functional abnormality. Regional contraction and rotation derived using this model could potentially aid in the assessment of severity of regional dysfunction of infarcted myocardium.
General practitioners' knowledge, attitude and prescribing of antibiotics for upper respiratory tract infections in Selangor, Malaysia: findings and implications

Hassali MA, Kamil TK, Md Yusof FA, Alrasheedy AA, Yusoff ZM, Saleem F, et al.

Expert Rev Anti Infect Ther, 2015 Apr;13(4):511-20.
PMID: 25704246 DOI: 10.1586/14787210.2015.1012497

BACKGROUND: Antibiotics are widely prescribed especially for upper respiratory tract infections (URTIs). Their irrational use can increase costs and resistance.
AIM: Assess knowledge, attitude and prescribing of antibiotics for URTIs in Selangor, Malaysia, using a cross-sectional survey among general practitioners (GPs) working in private clinics in 2011.
RESULTS: One hundred and thirty-nine physicians completed the questionnaire (response rate = 34.8%). 49.6% (n = 69) agreed antibiotics are helpful in treating URTIs, with most GPs agreeing antibiotics may reduce URTI duration and complications. The majority of GPs reported they felt patients expected antibiotics, with 36.7% (n = 51) agreeing patients would change doctors if they did not prescribe antibiotics and 21.6% (n = 30) agreeing when requested they prescribe antibiotics even if they believe them to be unnecessary. When assessed against six criteria, most GPs had a moderate level of knowledge of prescribing for URTIs. However, antibiotic prescriptions could be appreciably reduced.
CONCLUSION: Further programs are needed to educate GPs and patients about antibiotics building on current initiatives.
KEYWORDS: Malaysia; antibiotics; education programs; irrational use of medicines; patients; physicians; respiratory tract infections
Fulltext Antibiotics in surgical wards: use or misuse? A newly industrialized country's perspective

Lim MK, Lai PSM, Ponnampalavanar SS, Syed Omar SF, Taib NA, Yusof MY, et al.

J Infect Dev Ctries, 2015 Nov 30;9(11):1264-71.
PMID: 26623636 DOI: 10.3855/jidc.6731

INTRODUCTION: Studies exploring the appropriateness of therapeutic antibiotic use among surgical patients are limited, particularly in developing countries. Therefore, the aim of our study was to determine the appropriateness of antibiotics prescribed in a surgical setting in Malaysia.
METHODOLOGY: A prospective observational study was conducted in two surgical wards at a tertiary hospital in Malaysia from November 2012-July 2013. Data was collected using a case report form. The appropriateness of antibiotic therapy was based on compliance with either the Malaysian National Antibiotic Guidelines 2008 or International Clinical Practice Guidelines and determined by an expert panel (consisting of two infectious disease consultants and a pharmacist).
RESULTS: Over the study period, a total of 593 antibiotic courses were prescribed for 129 patients (4.6±3.4 antibiotics/patient). Only 34 (26.4%) patients received appropriate antibiotic therapy, whilst 95 (73.6%) patients received at least one course of inappropriate antibiotic therapy. The prevalence of inappropriate antibiotic use was 214 (66.3%) and 55 (42.0%) for prophylactic and therapeutic purposes, respectively. The most common causes of inappropriate prophylactic antibiotics were inappropriate timing 20 (36.4%) and inappropriate duration of prophylaxis 19 (34.5%). In cases of inappropriate timing, 9 (45%) were administered too late while 6 (30%) were too early. In contrast, inappropriate choice of antibiotics (42.1%) and inappropriate indication (40.7%) were the most common reasons encountered for inappropriate therapeutic antibiotics.
CONCLUSION: Our study suggests considerable inappropriate use of both prophylactic and therapeutic antibiotics in the surgical wards; highlighting an urgent need for antibiotic stewardship initiatives in this setting.
Fulltext Barriers and Facilitators to Implementing Project ECHO in Malaysia During the COVID-19 Pandemic

Walters SM, Li WP, Saifi R, Azwa I, Syed Omar SF, Collier ZK, et al.

J Int Assoc Provid AIDS Care, 2022;21:23259582221128512.
PMID: 36177542 DOI: 10.1177/23259582221128512

Objective: In Malaysia, HIV is concentrated among key populations who experience barriers to care due to stigma and healthcare discrimination. The COVID-19 pandemic has increased barriers to healthcare. Project ECHO (Extension for Community Healthcare Outcomes) is a transformative tele-education strategy that could improve HIV prevention and treatment. Methods: Practicing physicians who were aged 18 years or older and had internet access participated in asynchronous online focus groups. Results: Barriers to Project ECHO were conflicting priorities, time constraints, and technology. Facilitators included content and format, dedicated time, asynchronized flexible programming, incentives, and ensuring technology was available. Conclusion: Project ECHO is a promising intervention that can increase physicians' knowledge and skill set in specialty medicine during the COVID-19 pandemic. Interventionists in Malaysia in particular, but also in general, should consider these barriers and facilitators when developing Project ECHO as they may aid in developing a more robust program and increase participation.
Fulltext "I want the doctors to know that I am as bright as a candle": : Experiences with and Hopes for Doctor Interactions Among Malaysian Key Populations and People Living with HIV

Earnshaw VA, Cox J, Wong PL, Saifi R, Walters S, Azwa I, et al.

AIDS Behav, 2023 Jul;27(7):2103-2112.
PMID: 36472685 DOI: 10.1007/s10461-022-03942-9

Stigma in healthcare settings is a pernicious barrier to HIV prevention and treatment in contexts with strong HIV-related structural stigma. Previous work has documented substantial stigma towards key populations and people living with HIV (PLWH) among Malaysian doctors. The perspectives of Malaysian key populations and PLWH, however, remain understudied. In 2021, 34 Malaysian participants representing key populations and PLWH engaged in a photovoice study designed to qualitatively explore their experiences with and hopes for doctor interactions. Many participants reported stigma from their doctors, perceiving that doctors view them as not normal, sinful, misguided, and incapable. Several emphasized that they wear figurative masks to conceal aspects of themselves from doctors. Yet, many also remain hopeful for constructive relationships with doctors. They want their doctors to know that they are bright, capable, kind, and valuable. Interventions are needed to address stigma among doctors working in contexts with strong structural stigma.
Poor HIV-Related Outcomes in Older Adults Newly Diagnosed With HIV: A 4-Year Retrospective Analysis From a Single Site in Asia

Wong HY, Wong PL, Bador MK, Chong ML, Shenoi S, Rozanova J, et al.

J Acquir Immune Defic Syndr, 2023 May 01;93(1):64-72.
PMID: 36716735 DOI: 10.1097/QAI.0000000000003169

BACKGROUND: In resource-limited settings, HIV-related services are often targeted to younger key populations, although increasing reports have found that adults ≥50 years now account for among the highest increase in new HIV diagnosis. We assessed the proportion of new HIV infections among older adults (≥50 years) and compared their sociodemographics, risk behaviors, and HIV-related outcomes to newly diagnosed younger adults (<50 years).
METHODS: This retrospective analysis included all new HIV diagnosis from 2016 to 2019 at the University of Malaya Medical Centre, Malaysia. Trends of HIV diagnosis was assessed using join point regression analysis, and characteristics between the older and younger adults were compared using χ 2 test or Mann-Whitney U test. Kaplan-Meier analysis and log-rank test were used to compare the survival probability in both age groups.
RESULTS: From a total of 594 new HIV diagnosis between 2016 and 2019, 11.5% (N = 68) were among older adults with an annual percent increase of 5.50%. Older adults were more likely ethnic Indians ( P < 0.001), acquired HIV through heterosexual contact ( P = 0.001), had late presentation to care ( P = 0.003), and multimorbidity ( P < 0.001). Immunological responses after 12 months on antiretroviral therapy were comparable in both the groups. Older adults had a higher probability of death compared with younger adults (adjusted hazard ratio 1.81, 95% confidence interval: 1.02 to 3.23, P = 0.043) after adjusting for sex, mode of HIV transmission, late presentation to care, antiretroviral therapy initiation, and multimorbidity.
CONCLUSION: Older adults diagnosed with HIV were associated with late care presentation and increased mortality. There is an urgent need to enhance uptake of HIV testing and linkage to care among older individuals in our setting.
Causes, risks and care circumstances associated with death in older adults diagnosed with HIV in a tertiary centre in Malaysia

Wong HY, Pui Li W, Abdul Kahar MKB, Chong ML, Shenoi S, Rozanova J, et al.

Int J STD AIDS, 2024 May 09.
PMID: 38722271 DOI: 10.1177/09564624241250378

BACKGROUND: A substantial number of older adults succumb soon after HIV diagnosis despite ART. We explored the causes, risk factors and circumstances before death among older adults acquring HIV.
METHODS: We recruited individuals newly diagnosed at our centre from 2016-2020 and analysed data of those who died. Patients were stratified to older (≥50 years) or younger (<50 years) based on their age at diagnosis and attributes were compared. The Cox proportional multivariable model was used to identify factors associated with all-cause mortality.
RESULTS: Among 75 deaths reported, the majority of deaths were AIDS-related and late presentation was common in both age groups. The majority of deaths occurred in the first 12 months after care presentation and over two-thirds in both groups disengaged from care prior to death. Older age remained an independent factor associated with death after adjusting for confounders including opportunistic infections, late presentation to care, ART initiation and chronic comorbidities at presentation.
CONCLUSION: Most causes of death in our setting were AIDS-related and associated with late care presentation both in young and older individuals, although older age at diagnosis remained an independent risk factor. Our findings highlight the urgent need to encourage prompt ART initiation following diagnosis, especially in older adults.

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