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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 Vitamin D deficiency during pregnancy and its associated factors among third trimester Malaysian pregnant women

Woon FC, Chin YS, Ismail IH, Batterham M, Abdul Latiff AH, Gan WY, et al.

PLoS One, 2019;14(6):e0216439.
PMID: 31233513 DOI: 10.1371/journal.pone.0216439

BACKGROUND: Despite perennial sunshine, vitamin D deficiency is prevalent among Malaysians especially pregnant women. This study determines the vitamin D status and its associated factors among third trimester pregnant women attending government health clinics in Selangor and Kuala Lumpur, Malaysia.

METHODS: Information on socio-demographic characteristics, obstetrical history, and sun exposure were obtained through face-to-face interviews. Vitamin D intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). Serum 25-hydroxyvitamin D concentration was measured and classified as deficient (< 30 nmol/L), insufficient (30-50 nmol/L), and sufficient (≥ 50 nmol/L).

RESULTS: Of the 535 pregnant women recruited, 42.6% were vitamin D deficient. They consumed an average of 8.7 ± 6.7 μg of vitamin D daily. A total of 80.4% of the vitamin D were obtained from the food sources, while 19.6% were from dietary supplements. Fish and fish products showed the highest contribution to vitamin D intake (35.8%). The multivariable generalized linear mixed models, with clinic as a random effect, indicates that higher intake of vitamin D is associated with lower odds of vitamin D deficiency among pregnant women (OR = 0.96; 95% CI = 0.93-0.99). The odds of having vitamin D deficiency was reduced by 87% in non-Malays (OR = 0.14; 95% CI = 0.05-0.41) compared to Malays. No associations were found between age, educational level, monthly household income, work status, gravidity, parity, pre-pregnancy body mass index, total hours of sun exposure, total percentage of body surface area, and sun exposure index per day with vitamin D deficiency.

CONCLUSION: Vitamin D deficiency is prevalent among Malaysian pregnant women. Considering the possible adverse obstetric and fetal outcomes of vitamin D deficiency during pregnancy, future nutrition education should emphasise on vitamin D-fortified foods consumption among pregnant women by taking into consideration ethnic differences.
VEGF Polymorphisms Among Neovascular Age-Related Macular Degenerative Subjects in a Multiethnic Population

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

Genet Test Mol Biomarkers, 2017 Oct;21(10):600-607.
PMID: 28926292 DOI: 10.1089/gtmb.2017.0079

AIM: To determine the association of vascular endothelial growth factor (VEGF) polymorphisms with neovascular age-related macular degeneration (nAMD).
MATERIALS AND METHODS: One hundred thirty-five nAMD patients and 135 controls were recruited to determine the association of the -460 C/T, the -2549 I/D, and the +405 G/C polymorphisms with the VEGF gene. Genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, and association analyses were conducted using chi-square analysis and logistic regression analysis.
RESULTS: A significant association was observed between nAMD and the VEGF +405 G/C genotypes (p = 0.002) and alleles (odds ratio = 1.36, 95% confidence interval = 1.12-1.62, p = < 0.001) compared with the controls. This association was confirmed by logistic regression analyses, using two different genetic models (additive and dominant) resulting in p-values of p = 0.001 and p
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
Effectiveness of Mediterranean Diet on Daytime Sleepiness among Individuals with Type 2 Diabetes Mellitus in Oman

AlAufi NS, Chan YM, Chin YS, Ahmad N, Mohd-Yusof BN, Waly MI, et al.

Sleep Sci, 2024 Mar;17(1):e45-e54.
PMID: 38545248 DOI: 10.1055/s-0043-1773786

Background Sleep disturbance is a major complaint among individuals with diabetes mellitus and may be augmented by dietary interventions. The objective of this randomized controlled trial was to determine the effectiveness of a Mediterranean diet intervention on daytime sleepiness among individuals with type 2 diabetes mellitus (T2DM) in Oman. Methods In total, 134 eligible individuals with T2DM (61 and 73 participants in the intervention and control groups, respectively) were recruited. The intervention participants underwent a 6-month Mediterranean diet intervention consisting of individual dietary counseling, cooking classes, phone calls, and social media messages, while the control group continued with standard diabetes care. Daytime sleepiness was assessed using the Epworth Sleepiness Scale. All data was analyzed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, USA). Results Daytime sleepiness was evident, with ∼ 30% of the participants experiencing it, with no significant difference between control and intervention participants at baseline. There was a significant reduction in daytime sleepiness in both the intervention and control groups after 6 months, with daytime sleepiness significantly lower in the intervention group, with a modest difference of 42.56% ( p
Prevalence and treatment patterns of ranibizumab and photodynamic therapy in a tertiary care setting in Malaysia

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

Int J Ophthalmol, 2017;10(12):1889-1897.
PMID: 29259909 DOI: 10.18240/ijo.2017.12.16

AIM: To describe the prevalence and changes in treatment patterns of ranibizumab and photodynamic therapy (PDT) among retinal disease patients who attended the Ophthalmology Clinic in the tertiary care Hospital Selayang from 2010 to 2014.

METHODS: Study subjects were recruited retrospectively using the Electronic Medical Record (EMR) database software in Hospital Selayang. Demographic data, medical history, diagnostic procedure, treatments and diagnosis of patients were recorded.

RESULTS: The five-year analysis included 821 patients with a mean age of 65.9±11.73y. Overall, there were a higher number of males (63.1%) and a higher number of Chinese (47.4%) patients. Among the 821 patients, 62.9% received ranibizumab injection followed by 19.2% PDT therapy and 17.9% had ranibizumab combined with PDT therapy. Age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) were the most common retinal eye diseases reported, recording prevalence of 25.0% and 45.6%, respectively. The trend in ranibizumab treatment was reported to increase while PDT showed a decrease in trend from year 2010 to 2014. In terms of treatment, following multiple logistic regression, AMD was associated with the subjects being more likely to have received ranibizumab monotherapy (P<0.001) while PCV was associated with more likely to have received PDT (P<0.001) and PDT combined with ranibizumab therapy (P<0.001).

CONCLUSION: The tertiary care setting in Malaysia is consistent with management of patients from other countries whereby ranibizumab is the most common treatment given to patients with AMD, while PCV patients most commonly receive PDT and ranibizumab combined with PDT therapy.

Study site: Ophthalmology Clinic, Hospital Selayang