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  1. Yee AWM, Oo PS, Aye SN, Lim WJ, Chee VCX, Krishnappa P
    Med J Malaysia, 2023 Jan;78(1):98-108.
    PMID: 36715199
    INTRODUCTION: Since constant long-term exposure to formaldehyde endangers the health of laboratory personnel, sugar-based natural products have become interesting alternative fixatives to formaldehyde because of their preservative and antibacterial properties. However, there are controversial findings on the fixative effects of natural fixatives. This study systematically reviews the evidence comparing natural fixatives' types, dilutions, fixative properties and staining quality in normal tissues and histopathological specimens.

    MATERIALS AND METHODS: A comprehensive search was performed for studies comparing the natural fixatives- and formaldehyde-fixed tissues using databases from inception to January 2022: PubMed, Ovid Medline and Google Scholar. Two independent reviewers did data extraction. The data were pooled for the type of natural fixatives, their concentrations and fixative qualities compared to formaldehyde.

    RESULTS: Fifteen studies were included in this systematic review. Nine studies used one natural fixative with different dilutions, while six used several natural fixatives to compare their fixative properties with formaldehyde. The most used natural fixative was honey (n = 12) followed by jaggery (n = 8), sugar (n = 3) and others (n = 1). Honey showed the most promising results in fixation and staining, which are compatible with formalin. Jaggery and sugar also showed the possibility of replacing formaldehyde in tissue fixation and staining in smaller tissue samples.

    CONCLUSION: Natural fixatives showed promising results in tissue fixation. However, optimising the concentrations and conditions of natural fixatives is difficult because of the different chemical constituents and production steps. More comprehensive studies are necessary for application.

  2. Naing C, Reid SA, Aye SN, Htet NH, Ambu S
    PLoS One, 2019;14(5):e0217643.
    PMID: 31141558 DOI: 10.1371/journal.pone.0217643
    Leptospirosis is probably the most widespread zoonotic disease in the world especially in tropical countries. There has been an increase in individual studies, which assessed the frequency of leptospirosis in flood conditions. Some studies showed contact with floods was significantly associated with the occurrence of leptospirosis while other studies reported differently. The objective of this meta-analysis was to synthesize the evidence on the risk factors which are associated with human leptospirosis following flooding. We set up the inclusion criteria and searched for the original studies, addressing leptospirosis in human with related to flood in health-related electronic databases including PubMed, Embase, Ovid Medline, google scholar and Scopus sources. We used the terms 'leptospirosis', 'flood', 'risk factor' and terms from the categories were connected with "OR" within each category and by "AND" between categories. The initial search yielded 557 citations. After the title and abstract screening, 49 full-text papers were reviewed and a final of 18 observational studies met the pre-specified inclusion criteria. Overall, the pooled estimates of 14 studies showed that the contact with flooding was a significant factor for the occurrence of leptospirosis (pooled OR: 2.19, 95%CI: 1.48-3.24, I2:86%). On stratification, the strength of association was greater in the case-control studies (pooled OR: 4.01, 95%CI: 1.26-12.72, I2:82%) than other designs (pooled OR:1.77,95%CI:1.18-2.65, I2:87%). Three factors such as 'being male'(pooled OR:2.06, 95%CI:1.29-2.83), the exposure to livestock animals (pooled OR: 1.95, 95%CI:1.26-2.64), the lacerated wound (pooled OR:4.35, 95%CI:3.07-5.64) were the risk factors significantly associated with the incidence of leptospirosis following flooding in the absence of within-study heterogeneity (I2: 0%). We acknowledge study limitations such as publication bias and type 2 statistical errors. We recommended flood control and other environmental modifications that are expected to reduce the risk of leptospiral infection, and a multi-sectoral effort to this aspect would have long-term benefits.
  3. Naing C, Whittaker MA, Htet NH, Aye SN, Mak JW
    PLoS One, 2019;14(12):e0225882.
    PMID: 31856172 DOI: 10.1371/journal.pone.0225882
    BACKGROUND: The WHO recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Hence, monitoring the efficacy of antimalarial drugs is a key component of malaria control and elimination. The published randomized trials that assessed comparisons of ACTs for treating uncomplicated falciparum malaria reported conflicting results in treatment efficacy. A network meta-analysis is an extension of pairwise meta-analysis that can synthesize evidence simultaneously from both direct and indirect treatment comparisons. The objective was to synthesize evidence on the comparative efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region.

    METHODS: Relevant randomized trials that assessed efficacy of antimalarial drugs for patients having uncomplicated falciparum malaria in Asian region were searched in health-related databases. We evaluated the methodological quality of the included studies with the Cochrane risk of bias tool. Main outcome was treatment success at day 28 as determined by the absence of parasiteamia. We performed network meta-analysis of the interventions in the trials, and assessed the overall quality of evidence using the GRADE approach.

    RESULTS: Seventeen randomized trials (n = 5043) were included in this network meta-analysis study. A network geometry was formed with 14 antimalarial treatment options such as artemether-lumefantrine (AL), artemisinin-piperaquine, artesunate-amodiaquine, artesunate-mefloquine (ASMQ), artesunate-chloroquine, artesunate-mefloquine home treatment, artesunate-mefloquine 2-day course, artesunate plus sulfadoxine-pyrimethamine, chloroquine, dihydroartemisinin-piperaquine (DHP), dihydroartemisinin-piperaquine home treatment, dihydroartemisinin-piperaquine 4-day course, dihydroartemisinin-piperaquine and added artesunate, sulfadoxine-pyrimethamine. A maximum number of trials included was DHP compared to ASMQ (n = 5). In general, DHP had better efficacy than AL at day 28 (DHP vs AL: OR 2.5, 95%CI:1.08-5.8). There is low certainty evidence due to limited number of studies and small trials.

    DISCUSSION/ CONCLUSIONS: The findings suggest the superiority of DHP (3-day course) to AL and other comparator ACTs are with the overall low/very low quality of evidence judgements. Moreover, one drug regimen is better than another is only if current drug-resistance patterns are at play. For example, the AL might be better than DHP in areas where both artemisinin and piperaquine resistance patterns are prevalent. For substantiation, well-designed larger trials from endemic countries are needed. In the light of benefit versus harm concept, future analysis with safety information is recommended.

  4. Billy TJ, Sreeramareddy CT, Oo PS, Aye SN
    Nicotine Tob Res, 2024 Mar 22;26(4):508-511.
    PMID: 37819726 DOI: 10.1093/ntr/ntad198
    INTRODUCTION: Exposure to tobacco imagery creates a positive impression about smoking and is associated with youth smoking uptake.

    METHODS: From the list of movies released during 2015-2019, we selected the top 10 movies per year rated by the Malaysian Film Development Corporation. Two researchers coded tobacco imagery in each movie considering 5-minute time intervals as a unit. The 5-minute interval coding was adopted from previous research for comparability. Frequencies and the average occurrence of tobacco imagery were compared by movie language, genre, and age categorization.

    RESULTS: In 50 movies analyzed, there were a total of 1037 five-minute intervals of which 26 (52%) movies and 277 (26.7%) of intervals tobacco imagery were present. Brand appearances were absent and health warnings about tobacco use were present in just one movie. The proportions of intervals containing actual use, paraphernalia, and implied use were 63.5%, 22.0%, and 14.5%. Tobacco imagery of actual use, paraphernalia, and implied use was present in 25, 20, and 10 movies, respectively. In those movies with tobacco imagery, the average number of occurrences of actual use, paraphernalia, and implied use was 3 (interquartile range [IQR] 2-11.5), 2.5 (IQR 1.3-4.0), and 1 (IQR 1-4), respectively. Movies classified as "p13" (median 6, IQR 6-13) and "18" (median 5, IQR 0-15) had higher average occurrences of tobacco imagery than "U" movies (median 0, IQR 0-2; p = .028).

    CONCLUSIONS: The lack of health warnings despite the presence of tobacco imagery in Malaysian movies calls for measures to regulate tobacco-related content and reclassify such movies as "for adults-only."

    IMPLICATIONS: Tobacco imagery was prevalent in Malaysian movies that are allowed viewing by individuals aged 13 years and above. A review of the age categorization of Malaysian movies and the placement of health warnings in movies is needed. A comprehensive implementation of the ban on tobacco advertisements, promotion, and sponsorship should also include a ban on tobacco imagery in movies.

  5. Naing C, Htet NH, Aye SN, Aung HH, Tanner M, Whittaker MA
    Malar J, 2022 Feb 16;21(1):50.
    PMID: 35172833 DOI: 10.1186/s12936-022-04082-0
    BACKGROUND: Achieving malaria elimination requires the targeting of the human reservoir of infection, including those patients with asymptomatic infection. The objective was to synthesise evidence on the accuracy of the rapid-onsite diagnostic tests (RDTs) and microscopy for the detection of asymptomatic malaria as part of the surveillance activities in Asian countries.

    METHODS: This was a meta-analysis of diagnostic test accuracy. Relevant studies that evaluated the diagnostic performance of RDTs and microscopy for detection of asymptomatic malaria were searched in health-related electronic databases. The methodological quality of the studies included was assessed using the QUADAS-2 tool.

    RESULTS: Ten studies assessing RDT and/or microscopy were identified. The diagnostic accuracies in all these studies were verified by PCR. Overall, the pooled sensitivities of RDT, as well as microscopy for detection of any malaria parasites in asymptomatic participants, were low, while their pooled specificities were almost ideal. For the detection of Plasmodium falciparum, pooled sensitivity by RDT (59%, 95%CI:16-91%) or microscopy (55%, 95%CI: 25-82%) were almost comparable. For detection of Plasmodium vivax, pooled sensitivity of RDT (51%, 95% CI:7-94%) had also the comparable accuracy of microscopy (54%, 95%CI,11-92%). Of note are the wide range of sensitivity and specificity.

    CONCLUSION: The findings of this meta-analysis suggest that RDTs and microscopy have limited sensitivity and are inappropriate for the detection of asymptomatic Plasmodium infections. Other methods including a combination of PCR-based strategies, Loop-Mediated Isothermal Amplification (LAMP) technique must be considered to target these infections, in order to achieve malaria elimination. However, more data is needed for the wide acceptance and feasibility of these approaches. Studies to explore the role of asymptomatic and sub-patent infections in the transmission of malaria are of critical importance and are recommended.

  6. Win TT, Aye SN, Lau Chui Fern J, Ong Fei C
    J Gastrointestin Liver Dis, 2020 Jun 03;29(2):191-198.
    PMID: 32530986 DOI: 10.15403/jgld-818
    BACKGROUND AND AIMS: The latest meta-analysis on the role of aspirin on various cancers was published in early 2018. By including the latest and updated primary observational studies, we aimed to conduct this systematic review and meta-analysis to synthesize stronger evidence on the role of aspirin in reducing gastric cancer (GC) risk.

    METHODS: The PubMed, Scopus, and MEDLINE databases were systematically searched up to December 2019 to identify relevant studies. Random-effects model was used to calculate summary ORs and 95%CI for I 2 >50%. If the heterogeneity is not significant, the fixed-effects model was used. Overall analysis of the studies, inverse variance weighting after transforming the estimates of each study into log OR and its standard error were used.

    RESULTS: 21 studies were included in this meta-analysis. Results showed that aspirin significantly reduced the GC risk (OR=0.64, 95%CI=0.54-0.76) with substantial heterogeneity (I 2 =96%). Effect of GC risk reduction in low dose (OR=0.80, 95%CI=0.59-1.09) is slightly greater than high dose aspirin (OR=1.08, 95%CI=0.77-1.52). Protective effect of aspirin uses >5 years (OR=0.67, 95%CI=0.34-1.31) was greater than <5 years (OR=1.01, 95%CI=0.72-1.43) Conclusion: In conclusion, this meta-analysis showed that low dose aspirin with longer duration of more than 5 years were associated with a statistically significant reduction in GC risk. However, due to possible confounding variables and bias, these results should be cautiously treated.

  7. Win TT, Aye SN, Abdul Hamad NS, Tuan Sharif SE
    Indian J Cancer, 2021 1 7;58(2):262-266.
    PMID: 33402586 DOI: 10.4103/ijc.IJC_528_19
    The primary retroperitoneal serous adenocarcinoma (PRSAC) is a rare malignant tumor of the retroperitoneum. It shares the same pathological and biological behavior with ovarian serous carcinoma. Most of the cases develop as peritoneal adenocarcinoma and rarely occur in the retroperitoneum. It is reported as serous surface papillary carcinoma of the peritoneum and extraovarian peritoneal serous papillary carcinoma. We present a case of PRSAC in a 60-year-old woman. Only 11 cases of PRSAC have been reported from 1983 to 2019. Histopathological features with immunohistochemical expressions are important to diagnose PRSAC. The outcome and survival mainly depend on the possibility of surgical resection. Molecular genetics of PRSAC should also be studied in relation with its ovarian counterpart.
  8. Sreeramareddy CT, Aye SN, Venkateswaran SP
    BMC Public Health, 2021 02 03;21(1):277.
    PMID: 33535993 DOI: 10.1186/s12889-021-10347-1
    BACKGROUND: National-level prevalence of tobacco use and betel quid chewing, and associated socio-demographic factors were estimated using first-ever, Myanmar Demographic Health Survey, 2015-16.

    METHODS: Questions about tobacco smoking, smokeless tobacco use, and betel quid chewing were used to create outcome variables such as tobacco smoking, smokeless tobacco use, and 'dual use' (tobacco use and betel quid chewing). Sex-stratified weighted prevalence rates, distribution by socio-demographic factors were presented. Association of demographic factors with tobacco and/or betel quid chewing was assessed by multinomial logistic regression.

    RESULTS: Among men, prevalence (%) of tobacco use and betel quid chewing was 40.9 (95% CI 38.1, 42.1) and 58.9 (95% CI 56.3, 61.6) respectively. Among women tobacco use was 3.7 (95% CI 2.0, 4.3) and betel quid chewing 18.2 (95% CI 16.4, 20.0). Among men prevalence of either tobacco or betel quid and 'dual use' was 50.4 (95% CI 48.5, 52.3) and 25.0 (95% CI 23.1, 26.8) respectively, whereas among women the corresponding rates were 17.9 (95% CI 16.2, 19.6) and 2.0 (95% CI 1.6, 2.9). Smokeless tobacco use was low (

  9. Sreeramareddy CT, Aye SN
    BMC Public Health, 2021 06 24;21(1):1209.
    PMID: 34167508 DOI: 10.1186/s12889-021-11201-0
    BACKGROUND: Hardcore smoking behaviours and test of hardening are seldom reported from low-and-middle-income countries (LMICs). We report country-wise changes in smoking behaviors between two sequential surveys and explored ecologically the relationship between MPOWER scores and smoking behaviors including hardcore smoking.

    METHODS: We analysed sequential Global Adult Tobacco Survey (GATS) data done at least at five years interval in 10 countries namely India, Bangladesh, China, Mexico, Philippines, Russia, Turkey, Ukraine, Uruguay, and Vietnam. We estimated weighted prevalence rates of smoking behaviors namely current smoking (both daily and non-daily), prevalence of hardcore smoking (HCS) among current smokers (HCSs%) and entire surveyed population (HCSp%), quit ratios (QR), and the number of cigarettes smoked per day (CPD). We calculated absolute and relative (%) change in rates between two surveys in each country. Using aggregate data, we correlated relative change in current smoking prevalence with relative change in HCSs% and HCSp% as well as explored the relationship of MPOWER score with relative change in smoking behaviors using Spearman' rank correlation test.

    RESULTS: Overall daily smoking has declined in all ten countries lead by a 23% decline in Russia. In India, Bangladesh, and Philippines HCSs% decreased as the smoking rate decreased while HCSs% increased in Turkey (66%), Vietnam (33%) and Ukraine (15%). In most countries, CPD ranged from 15 to 20 sticks except in Mexico (7.8), and India (10.4) where CPD declined by 18 and 22% respectively. MPOWER scores were moderately correlated with HCSs% in both sexes (r = 0.644, p = 0.044) and HCSp% (r = 0.632, p = 0.05) and among women only HCSs% (r = 0.804, p = 0.005) was significantly correlated with MPOWER score.

    CONCLUSION: With declining smoking prevalence, HCS had also decreased and quit rates improved. Ecologically, a positive linear relationship between changes in smoking and HCS is a possible evidence against 'hardening'. Continued monitoring of the changes in quitting and hardcore smoking behaviours is required to plan cessation services.

  10. Sharmni Vishnu K, Win TT, Aye SN, Basavaraj AK
    BMC Cancer, 2022 Nov 05;22(1):1139.
    PMID: 36335316 DOI: 10.1186/s12885-022-10225-y
    BACKGROUND: Triple negative breast cancer (TNBC) is clinically aggressive breast cancer with a poor prognosis. Approximately 20% of TNBC has been found to express programmed death ligand 1 (PD-L1), making it a potential therapeutic target. As a PD-L1 inhibitor, atezolizumab is a recently approved immunotherapeutic drug for TNBC, this meta-analysis (MA) was aimed to review the randomized controlled trial studies (RCTs) of combined atezolizumab and nab-paclitaxel in the treatment of TNBC and synthesize the evidence-based results on its effectiveness and safety.

    METHOD: We searched PubMed, Embase, EBSCOhost and ClinicalTrials.gov for the eligible RCTs which compared the efficacy and safety of combined atezolizumab and nab-paclitaxel with nab-paclitaxel alone. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse effects (AEs).

    RESULTS: A total of six RCTs were included in this MA. For efficacy, although OS was not significantly prolonged with combined atezolizumab and nab-paclitaxel (HR 0.90, 95% CI [0.79, 1.01], p=0.08), this combination therapy significantly improved PFS (HR 0.72, 95% CI [0.59, 0.87], p=0.0006) and ORR (RR 1.25, 95% CI [0.79, 1.01] p<0.00001). For safety, any AEs, haematological, gastrointestinal, and liver AEs showed no statistically significant differences between the atezolizumab and nab-paclitaxel combination group and nab-paclitaxel alone group. However, serious AEs, high grade, dermatological, pulmonary, endocrine, and neurological AEs were significantly lower with nab-paclitaxel alone compared to atezolizumab and nab-paclitaxel combined (p-value range from <0.00001 to 0,02).

    CONCLUSION: Atezolizumab combined with nab-paclitaxel was associated with improved outcomes in the treatment of TNBC; however, this combination resulted in more toxicity compared to nab-paclitaxel alone. While nab-paclitaxel alone produced chemotherapy-related AEs, the combination of atezolizumab with nab-paclitaxel produced AEs, especially immune-related AEs such as haematological, pulmonary, endocrine, and neurological AEs.

    TRIAL REGISTRATION: This research work of systematic review has been registered on PROSPERO (Registration number: CRD42022297952).

  11. Qyi YZ, Aung HH, Aye SN, Tung WS, Naing C
    BMC Cancer, 2023 Oct 24;23(1):1027.
    PMID: 37875868 DOI: 10.1186/s12885-023-11509-7
    BACKGROUND: Gastric cancer has a complex aetiology including genetic factors. Individual case-control studies of toll like receptor (TLR) 9 (-1237 T/C, -1486 T/C) polymorphisms in the gastric cancer risk were available, and they showed variation in the findings. Therefore, we performed a meta-analysis to synthesize the evidence on the association between polymorphisms of TLR 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer using data from eligible studies.

    METHODS: This study followed the PRISMA 2020 Checklist. Studies were searched in health-related databases. The methodological quality of studies was evaluated with the use of Newcastle-Ottawa Scale criteria. The summary odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and the risk of gastric cancer using five genetic models. Stratification was done by ethnic groups. For the robustness of the analysis, a leave-one-out meta-analysis was performed.

    RESULTS: Eight case-control studies with 3,644 participants (1914 cases, 1730 controls) were conducted across six countries. Half of the studies were conducted in China. In the NOS methodological quality assessment, only three studies received a high-quality rating (i.e., a score of ≥ 7). TLR 9 (-1486 T/C) polymorphism and the risk of gastric cancer were assessed in six studies, four of Asian ethnicity and two of non-Asian. Under the dominant model, only in the Asian ethnic group showed a marginally and significantly increased risk of gastric cancer (overall: OR = 1.22, 95%CI = 0.90-1.67, I2 = 56%; Asian: OR = 1.24, 95%CI = 1.00-1.54, I2 = 0%, non-Asian: OR = 1.25, 95%CI = 0.38-4.09, I2 = 89%). Under the recessive model in the absence of heterogeneity, only the Asian group had a significantly higher risk of developing gastric cancer (overall: OR = 1.4, 95% CI = 0.74-2.64, I2 = 85%; Asian: OR: 1.41, 95% CI = 1.07-1.86, I2 = 0%, non-Asian: OR = 1.18, 95% CI = 0.12-11.76, I2 = 97%). Under the heterozygous model, there was no significant association with the risk of gastric cancer overall or among any ethnic subgroup. Under the homozygous model in the absence of heterogeneity, only the Asian group had a significantly higher risk of gastric cancer (overall, OR = 1.47, 95% CI = 0.76-2.86, I2 = 82%; Asian: OR = 1.54, 95% CI = 1.13-2.1, I2 = 0%; non-Asian: OR = 1.19, 95% CI = 0.1-14.33, I2 = 96%). Under the allele model, a significantly increased risk of gastric cancer was observed only in the Asian group (overall: OR = 1.23, 95% CI = 0.89-1.71, I2 = 84%; Asian: OR = 1.22, 95% CI = 1.05-1.41, I2 = 0%; non-Asian: OR = 1.24, 95% CI = 0.34-4.59, I2 = 97%). Four studies investigated the association between TLR 9 (-1237 T/C) polymorphism and the risk of developing gastric cancer. Under any of the five genetic models, there was no association between TLR 9 (-1237 T/C) and the development of gastric cancer in overall or in any ethnic subgroup. Sensitivity analysis revealed that the effect was unstable. With a small number of studies with a small number of participants, we addressed the issue of insufficient power for drawing conclusions.

    CONCLUSIONS: The findings suggested that TLR9 (-1486 T/C) may play a role in the risk of gastric cancer specific to the Asian ethnic group. To substantiate the findings on the association between these two polymorphisms (TLR9 -1237 T/C, -1486 T/C) and the risk of gastric cancer, future well-designed case-control studies with a sufficient number of participants in multi-ethnic groups are recommended.

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