Displaying publications 21 - 34 of 34 in total

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  1. Cheong SC, Chandramouli GV, Saleh A, Zain RB, Lau SH, Sivakumaren S, et al.
    Oral Oncol, 2009 Aug;45(8):712-9.
    PMID: 19147396 DOI: 10.1016/j.oraloncology.2008.11.002
    Oral squamous cell carcinoma (OSCC) is a world health problem and is associated with exposure to different risk factors. In the west, smoking and alcohol consumption are considered to be the main risk factors whilst in India and southeast Asia, betel quid (BQ) chewing is predominant. In this study, we compared the gene expression patterns of oral cancers associated with BQ chewing to those caused by smoking using Affymetrix microarrays. We found that 281 genes were differentially expressed between OSCC and normal oral mucosa regardless of aetiological factors including MMP1, PLAU, MAGE-D4, GNA12, IFITM3 and NMU. Further, we identified 168 genes that were differentially expressed between the BQ and smoking groups including CXCL-9, TMPRSS2, CA12 and RNF24. The expression of these genes was validated using qPCR using independent tissue samples. The results demonstrate that whilst common genes/pathways contribute to the development of oral cancer, there are also other gene expression changes that are specific to certain risk factors. The findings suggest that different carcinogens activate or inhibit specific pathways during cancer development and progression. These unique gene expression profiles should be taken into consideration when developing biomarkers for future use in prognostic or therapeutic applications.
  2. Haron N, Zain RB, Nabillah WM, Saleh A, Kallarakkal TG, Ramanathan A, et al.
    Telemed J E Health, 2017 03;23(3):192-199.
    PMID: 27541205 DOI: 10.1089/tmj.2016.0128
    INTRODUCTION: This study examined the concordance in clinical diagnosis of high-risk lesions in the oral cavity and referral decisions between clinical oral examination (COE) and teledentistry.

    MATERIALS AND METHODS: Sixteen individuals with a range of oral potentially malignant disorders (OPMD) and normal oral mucosa were included. Five areas of the oral cavity were photographed by three dentists using mobile phone cameras with 5 MP-13 MP resolutions. On the same day, the patients were given COE by two oral medicine specialists (OMS) and 3 weeks later, they reviewed the images taken using the phone, and concordance was examined between the two by Kappa statistics. The sensitivity and specificity of clinical diagnosis using the phone images were also measured. Pre- and post-program questionnaires were answered by both the dentists and the OMS to determine the feasibility of integrating teledentistry in their clinical practice.

    RESULTS: The Kappa values in determining the presence of lesion, category of lesion (OPMD or not), and making referral decision were moderate to strong (0.64-1.00). The overall sensitivity was more than 70% and specificity was 100%. The false negative rate decreased as the camera resolution increased. All dentists agreed that the process could facilitate early detection of oral mucosal lesion, and was easy to use in the clinic.

    CONCLUSIONS: This study provides evidence that teledentistry can be used for communication between primary care and OMS and could be readily integrated into clinical setting for patient management.

  3. Saleh A, Yang YH, Wan Abd Ghani WM, Abdullah N, Doss JG, Navonil R, et al.
    Asian Pac J Cancer Prev, 2012;13(4):1217-24.
    PMID: 22799308
    BACKGROUND AND AIM: Less than 50% of oral cancer cases are diagnosed at early stages of the disease and this is in part due to poor awareness and lack of knowledge on the signs and symptoms of oral cancer. This study sought to measure the baseline awareness of oral cancer in Malaysia and aimed to increase public awareness and knowledge of oral cancer using a mass media campaign.

    METHODS: Baseline awareness and impact of the campaign was measured using self-administered questionnaires sent via email to individuals. The campaign was aired on two national television channels and the reach was monitored through an independent programme monitoring system.

    RESULTS: 78.2% of respondents had heard of oral cancer, and this increased significantly after the campaign. However, the ability to recognize signs and symptoms remains unchanged. We found that the level of awareness differed between the distinct ethnic subgroups and the reach of the campaign was not uniform across all ethnicities.

    CONCLUSION: This substantial study to measure the oral cancer awareness in Malaysia provides important baseline data for the planning of public health policies. Despite encouraging evidence that a mass media campaign could increase the awareness of oral cancer, further research is required to address the acceptability, comprehensiveness and effectiveness. Furthermore, different campaign approaches may be required for specific ethnic groups in a multi-ethnic country such as Malaysia.

  4. Chai SJ, Pua KC, Saleh A, Yap YY, Lim PV, Subramaniam SK, et al.
    J Clin Virol, 2012 Sep;55(1):34-9.
    PMID: 22739102 DOI: 10.1016/j.jcv.2012.05.017
    Nasopharyngeal carcinoma (NPC) is an Epstein-Barr Virus (EBV)-associated cancer that is the fifth most common cancer in Malaysia. Early and accurate diagnoses are critical for patient prognosis. Unfortunately, early detection of NPC is still a challenge and the cost of more accurate imaging protocols is prohibitive in developing countries like Malaysia.
  5. Zanaruddin SN, Saleh A, Yang YH, Hamid S, Mustafa WM, Khairul Bariah AA, et al.
    Hum Pathol, 2013 Mar;44(3):417-26.
    PMID: 23026198 DOI: 10.1016/j.humpath.2012.06.007
    The presence of lymph node (LN) metastasis significantly affects the survival of patients with oral squamous cell carcinoma (OSCC). Successful detection and removal of positive LNs are crucial in the treatment of this disease. Current evaluation methods still have their limitations in detecting the presence of tumor cells in the LNs, where up to a third of clinically diagnosed metastasis-negative (N0) patients actually have metastasis-positive LNs in the neck. We developed a molecular signature in the primary tumor that could predict LN metastasis in OSCC. A total of 211 cores from 55 individuals were included in the study. Eleven proteins were evaluated using immunohistochemical analysis in a tissue microarray. Of the 11 biomarkers evaluated using receiver operating curve analysis, epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2/neu), laminin, gamma 2 (LAMC2), and ras homolog family member C (RHOC) were found to be significantly associated with the presence of LN metastasis. Unsupervised hierarchical clustering-demonstrated expression patterns of these 4 proteins could be used to differentiate specimens that have positive LN metastasis from those that are negative for LN metastasis. Collectively, EGFR, HER-2/neu, LAMC2, and RHOC have a specificity of 87.5% and a sensitivity of 70%, with a prognostic accuracy of 83.4% for LN metastasis. We also demonstrated that the LN signature could independently predict disease-specific survival (P = .036). The 4-protein LN signature validated in an independent set of samples strongly suggests that it could reliably distinguish patients with LN metastasis from those who were metastasis-free and therefore could be a prognostic tool for the management of patients with OSCC.
  6. Zhou XD, Targher G, Byrne CD, Somers V, Kim SU, Chahal CAA, et al.
    Hepatol Int, 2023 Aug;17(4):773-791.
    PMID: 37204656 DOI: 10.1007/s12072-023-10543-8
    BACKGROUND: Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists.

    METHODS AND RESULTS: A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management.

    CONCULSIONS: The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.

  7. Younossi ZM, Alqahtani SA, Alswat K, Yilmaz Y, Keklikkiran C, Funuyet-Salas J, et al.
    J Hepatol, 2024 Mar;80(3):419-430.
    PMID: 37984709 DOI: 10.1016/j.jhep.2023.11.004
    BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers.

    METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey.

    RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%).

    CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties.

    IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

  8. Younossi ZM, AlQahtani SA, Funuyet-Salas J, Romero-Gómez M, Yilmaz Y, Keklikkiran C, et al.
    JHEP Rep, 2024 Jul;6(7):101066.
    PMID: 39022387 DOI: 10.1016/j.jhepr.2024.101066
    BACKGROUND & AIMS: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL.

    METHODS: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination.

    RESULTS: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease.

    CONCLUSIONS: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD.

    IMPACT AND IMPLICATIONS: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.

  9. Al Saleh A, Jamee A, Sulaiman K, Sobhy M, Gamra H, Alkindi F, et al.
    PLoS One, 2024;19(1):e0296056.
    PMID: 38206951 DOI: 10.1371/journal.pone.0296056
    BACKGROUND: The Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa (PEACE MENA) is a prospective registry program in Arabian countries that involves in patients with acute myocardial infarction (AMI) or acute heart failure (AHF).

    METHODS: This prospective, multi-center, multi-country study is the first report of the baseline characteristics and outcomes of inpatients with AMI who were enrolled during the first 14-month recruitment phase. We report the clinical characteristics, socioeconomic, educational levels, and management, in-hospital, one month and one-year outcomes.

    RESULTS: Between April 2019 and June 2020, 1377 patients with AMI were enrolled (79.1% males) from 16 Arabian countries. The mean age (± SD) was 58 ± 12 years. Almost half of the population had a net income < $500/month, and 40% had limited education. Nearly half of the cohort had a history of diabetes mellitus, hypertension, or hypercholesterolemia; 53% had STEMI, and almost half (49.7%) underwent a primary percutaneous intervention (PCI) (lowest 4.5% and highest 100%). Thrombolytics were used by 36.2%. (Lowest 6.45% and highest (90.9%). No reperfusion occurred in 13.8% of patients (lowest was 0% and highest 72.7%).Primary PCI was performed less frequently in the lower income group vs. high income group (26.3% vs. 54.7%; P<0.001). Recurrent ischemia occurred more frequently in the low-income group (10.9% vs. 7%; P = 0.018). Re-admission occurred in 9% at 1 month and 30% at 1 year, whereas 1-month mortality was 0.7% and 1-year mortality 4.7%.

    CONCLUSION: In the MENA region, patients with AMI present at a young age and have a high burden of cardiac risk factors. Most of the patients in the registry have a low income and low educational status. There is heterogeneity among key performance indicators of AMI management among various Arabian countries.

  10. Pecoits-Filho R, Okpechi IG, Donner JA, Harris DCH, Aljubori HM, Bello AK, et al.
    Kidney Int Suppl (2011), 2020 Mar;10(1):e3-e9.
    PMID: 32149004 DOI: 10.1016/j.kisu.2019.11.001
    A large gap between the number of people with end-stage kidney disease (ESKD) who received kidney replacement therapy (KRT) and those who needed it has been recently identified, and it is estimated that approximately one-half to three-quarters of all people with ESKD in the world may have died prematurely because they could not receive KRT. This estimate is aligned with a previous report that estimated that >3 million people in the world died each year because they could not access KRT. This review discusses the reasons for the differences in treated and untreated ESKD and KRT modalities and outcomes and presents strategies to close the global KRT gap by establishing robust health information systems to guide resource allocation to areas of need, inform KRT service planning, enable policy development, and monitor KRT health outcomes.
  11. Nongpiur ME, Khor CC, Jia H, Cornes BK, Chen LJ, Qiao C, et al.
    PLoS Genet, 2014 Mar;10(3):e1004089.
    PMID: 24603532 DOI: 10.1371/journal.pgen.1004089
    Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
  12. Zhang L, El-Shabrawi M, Baur LA, Byrne CD, Targher G, Kehar M, et al.
    Med, 2024 Jul 12;5(7):797-815.e2.
    PMID: 38677287 DOI: 10.1016/j.medj.2024.03.017
    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts.

    METHODS: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management.

    FINDINGS: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD.

    CONCLUSIONS: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD.

    FUNDING: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).

  13. Li Z, Allingham RR, Nakano M, Jia L, Chen Y, Ikeda Y, et al.
    Hum Mol Genet, 2015 Jul 01;24(13):3880-92.
    PMID: 25861811 DOI: 10.1093/hmg/ddv128
    Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.
  14. Vithana EN, Khor CC, Qiao C, Nongpiur ME, George R, Chen LJ, et al.
    Nat Genet, 2012 Oct;44(10):1142-1146.
    PMID: 22922875 DOI: 10.1038/ng.2390
    Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.
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