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  1. Banerjee R, Ali RAR, Wei SC, Adsul S
    Gut Liver, 2020 11 15;14(6):685-698.
    PMID: 33191310 DOI: 10.5009/gnl19209
    The advent of biologics and biologic therapy has transformed the management of inflammatory bowel disease (IBD) with enhanced early and adequate responses to treatment, fewer hospitalizations, a reduced need for surgery, and unprecedented outcomes including complete mucosal and histologic healing. However, an important issue with the use of anti-tumor necrosis factor (anti-TNF) agents in IBD is the increased risk of tuberculosis (TB). This is compounded by the diagnostic dilemma when differentiating between Crohn's disease and gastrointestinal TB, and the potentially serious consequences of initiating an incorrect treatment in the case of misdiagnosis. The interplay between IBD and TB is most relevant in Asia, where more than 60% of the 10.4 million new TB cases in 2016 were reported. A number of studies have reported an increased risk of TB with anti-TNF agents, including in patients who had tested negative for TB prior to treatment initiation. The limited evidence currently available regarding adhesion molecule antagonists such as vedolizumab suggests a comparatively lower risk of TB, thus making them a promising option for IBD management in TBendemic regions. This comprehensive review examines the available literature on the risk of TB with the use of biologics in the TB-endemic regions of Asia, focusing on the diagnostic dilemma, the risk of reactivation, and the optimized management algorithms for latent and active disease.
  2. Chew D, Zhiqin W, Ibrahim N, Ali RAR
    Intest Res, 2018 10;16(4):509-521.
    PMID: 30369231 DOI: 10.5217/ir.2018.00074
    The patient-physician relationship has a pivotal impact on the inflammatory bowel disease (IBD) outcomes. However, there are many challenges in the patient-physician relationship; lag time in diagnosis which results in frustration and an anchoring bias against the treating gastroenterologist, the widespread availability of medical information on the internet has resulted in patients having their own ideas of treatment, which may be incongruent from the treating physicians' goals resulting in patient physician discordance. Because IBD is an incurable disease, the goal of treatment is to sustain remission. To achieve this, patients may have to go through several lines of treatment. The period of receiving stepping up, top down or even accelerated stepping up medications may result in a lot of frustration and anxiety for the patient and may compromise the patient-physician relationship. IBD patients are also prone to psychological distress that further compromises the patient-physician relationship. Despite numerous published data regarding the medical and surgical treatment options available for IBD, there is a lack of data regarding methods to improve the therapeutic patient-physician relationship. In this review article, we aim to encapsulate the challenges faced in the patient-physician relationship and ways to overcome in for an improved outcome in IBD.
  3. Ghafar MYA, Yaakup H, Ali RAR, Shah SA
    J Nutr Health Aging, 2020;24(10):1066-1072.
    PMID: 33244562 DOI: 10.1007/s12603-020-1494-1
    OBJECTIVES: To evaluate the impact of a microbial cell preparation (MCP®) (Hexbio®; comprising MCP® BCMC® strains) on stool frequency, consistency, and constipation-related symptoms in elderly patients with multiple chronic medical conditions.

    DESIGN: Randomised control trial.

    SETTING: Medical outpatient and medical/surgical in-patient unit in single tertiary center.

    PARTICIPANT: Patients aged ≥ 60 years who experience constipation and have multiple chronic medical conditions.

    METHODS: Participants with constipation were blindly randomized into either a treatment (MCP® BCMC® strains) or a placebo group. The treatment was administered twice daily.

    MEASUREMENT: Gastrointestinal symptoms and stool habits were assessed over a week during the intervention via the use of a questionnaire and stool diary.

    RESULTS: Stool frequency was seen to be higher and the improvement in stool consistency was more significant in the treatment group than in the placebo group (p =<0.001). A significant improvement in symptoms was demonstrated in patients who received MCP® BCMC® strains,specifically with respect to straining (p = < 0.001) and a sensation of incomplete evacuation (p = < 0.001). reduction in anorectal blockage symptoms and the need for manual stool evacuation was also demonstrated, but this finding was not statistically significant. Significant adverse events were not observed.

    CONCLUSIONS: An improvement in stool frequency and consistency was reported in elderly patients with chronic medical conditions following the administration of MCP® BCMC® strains.

  4. Makharia GK, Singh P, Catassi C, Sanders DS, Leffler D, Ali RAR, et al.
    PMID: 34980921 DOI: 10.1038/s41575-021-00552-z
    Coeliac disease is a systemic disorder characterized by immune-mediated enteropathy, which is caused by gluten ingestion in genetically susceptible individuals. The clinical presentation of coeliac disease is highly variable and ranges from malabsorption through solely extra-intestinal manifestations to asymptomatic. As a result, the majority of patients with coeliac disease remain undiagnosed, misdiagnosed or experience a substantial delay in diagnosis. Coeliac disease is diagnosed by a combination of serological findings of disease-related antibodies and histological evidence of villous abnormalities in duodenal biopsy samples. However, variability in histological grading and in the diagnostic performance of some commercially available serological tests remains unacceptably high and confirmatory assays are not readily available in many parts of the world. Currently, the only effective treatment for coeliac disease is a lifelong, strict, gluten-free diet. However, many barriers impede patients' adherence to this diet, including lack of widespread availability, high cost, cross-contamination and its overall restrictive nature. Routine follow-up is necessary to ensure adherence to a gluten-free diet but considerable variation is evident in follow-up protocols and the optimal disease management strategy is not clear. However, these challenges in the diagnosis and management of coeliac disease suggest opportunities for future research.
  5. Sharif R, Mohammad NMA, Jia Xin Y, Abdul Hamid NH, Shahar S, Ali RAR
    Nutr Cancer, 2021 Dec 29.
    PMID: 34965818 DOI: 10.1080/01635581.2021.2022167
    Current evidence suggests that dietary and lifestyle factors may play an important role in colorectal cancer risk but there are only a few studies that investigated their relationship with colorectal adenomas (CRA), the precursors for colorectal cancer. A case-control study was conducted to determine the relationship between dietary and lifestyle factors associated with CRA risk among 125 subjects with CRA and 150 subjects without CRA at Hospital Canselor Tuanku Muhriz UKM (HCTM), Malaysia. We used dietary history questionnaire (DHQ) and International Physical Activity Questionnaire-Short Form (IPAQ) to estimate the diet and physical activity. The findings of this study showed that male gender [OR = 2.71 (95% CI= 1.01-7.27)], smoking [OR = 6.39 (95% CI= 1.04-39.30)], family history of cancer [OR = 6.39 (95% CI= 1.04-39.30)], high body fat percentage [OR = 1.25 (95% CI= 1.04-1.51)], high calorie and fat intake [OR = 1.03 (95% CI= 1.01-1.06)], [OR = 1.01 (95% CI= 0.95-1.09)] and red meat intake more than 100 g per day [OR = 1.02 (95% CI= 1.01-1.04)] increased CRA risk. High fiber [OR = 0.78 (95% CI= 0.64-0.95)] and calcium intake [OR = 0.78 (95% CI= 0.98-1.00)] was found to decrease CRA risk. Some of these modifiable risk factors could be advocated as lifestyle interventions to reduce risk of CRA.
  6. Shafiee NH, Razalli NH, Mokhtar NM, Tan E, Ali RAR
    Intest Res, 2022 Jan;20(1):124-133.
    PMID: 33472341 DOI: 10.5217/ir.2020.00050
    BACKGROUND/AIMS: Substantial proportions of patients with constipation-predominant irritable bowel syndrome (IBS-C) linked their symptoms with particular intake of foods. However, there is lack of current data regarding the intake among IBS-C patients before any dietary interventions. Thus, this study aimed to evaluate the dietary adequacy among IBS-C against the standard recommended nutrient intake (RNI) and healthy controls.

    METHODS: A retrospective case-control study was conducted involving IBS-C patients and healthy control subjects. A validated 126-food items frequency questionnaire was administered to all the subjects to assess their dietary intake, guided by dietitians. The calculated nutrients intake for IBS-C patients was then compared against the standard RNI and healthy controls.

    RESULTS: A total of 306 subjects were recruited, among which 218 were diagnosed with IBS-C and 88 were included as healthy controls. IBS-C patients had significantly lower intake of wholegrain products, fried foods, dairy products, fruits, and vegetables compared to healthy controls. The daily intake of energy, certain macronutrients, and micronutrients among IBS-C patients was significantly lower than the healthy subjects. Less than 5% of IBS-C patients and healthy subjects achieved the standard recommendation for dietary fiber. Also, various vitamin intake (B1, B2, B6, folate, B12, E, K, and potassium) among IBS-C patients did not meet the standard RNI.

    CONCLUSIONS: Dietary intakes of IBS-C patients did not meet the recommended intake for Malaysian and showed the nutritional inadequacies compared to the control subjects. Our study highlighted the importance of dietary evaluation prior to planning strategies for dietary intervention targeting IBS-C patients.

  7. Devi J, Chan TT, Lui R, Ali RAR, Women in GI Focus Group, Emerging Leaders Committee, Asian Pacific Association of Gastroenterology
    J Gastroenterol Hepatol, 2023 Dec;38(12):2047-2049.
    PMID: 37743674 DOI: 10.1111/jgh.16353
  8. Ankasha SJ, Shafiee MN, Wahab NA, Ali RAR, Mokhtar NM
    Oncol Rev, 2018 Jan 30;12(1):344.
    PMID: 29989022 DOI: 10.4081/oncol.2018.344
    MicroRNA (miRNA) is a small non-coding RNA with an established function to regulate genes at the post-transcriptional level leading to suppression or degradation of its messenger RNA expression (mRNA). Its dysregulation plays a vital role in a variety of biological and pathological processes including cancer. A lot of algorithms have been established to predict the target sites of miRNA, but experimentally identifying and validating its target region is still lacking. Guidance in experimental procedures is really needed to find genuine miRNA targets. Therefore, in this review, we provide an outline on the workflow in predicting and validating the targeted sites of miRNA using several methods as a guideline for the scientists. The final outcome of this type of experiment is essential to explore the major impact of miRNAmRNA interaction involved in the biological processes and to assist miRNA-based drug development in the future.
  9. Ananthakrishnan AN, Bernstein CN, Iliopoulos D, Macpherson A, Neurath MF, Ali RAR, et al.
    Nat Rev Gastroenterol Hepatol, 2018 Jan;15(1):39-49.
    PMID: 29018271 DOI: 10.1038/nrgastro.2017.136
    A number of environmental factors have been associated with the development of IBD. Alteration of the gut microbiota, or dysbiosis, is closely linked to initiation or progression of IBD, but whether dysbiosis is a primary or secondary event is unclear. Nevertheless, early-life events such as birth, breastfeeding and exposure to antibiotics, as well as later childhood events, are considered potential risk factors for IBD. Air pollution, a consequence of the progressive contamination of the environment by countless compounds, is another factor associated with IBD, as particulate matter or other components can alter the host's mucosal defences and trigger immune responses. Hypoxia associated with high altitude is also a factor under investigation as a potential new trigger of IBD flares. A key issue is how to translate environmental factors into mechanisms of IBD, and systems biology is increasingly recognized as a strategic tool to unravel the molecular alterations leading to IBD. Environmental factors add a substantial level of complexity to the understanding of IBD pathogenesis but also promote the fundamental notion that complex diseases such as IBD require complex therapies that go well beyond the current single-agent treatment approach. This Review describes the current conceptualization, evidence, progress and direction surrounding the association of environmental factors with IBD.
  10. Ibrahim A, Ali RAR, Manaf MRA, Ahmad N, Tajurruddin FW, Qin WZ, et al.
    PLoS One, 2020;15(12):e0244680.
    PMID: 33382780 DOI: 10.1371/journal.pone.0244680
    OBJECTIVE: We determined the effectiveness of a multi-strain probiotic (Hexbio®) containing microbial cell preparation MCP®BCMC® on constipation symptoms and gut motility in PD patients with constipation.

    METHODS: PD patients with constipation (ROME III criteria) were randomized to receive a multi-strain probiotic (Lactobacillus sp and Bifidobacterium sp at 30 X 109 CFU) with fructo-oligosaccaride or placebo (fermented milk) twice daily for 8 weeks. Primary outcomes were changes in the presence of constipation symptoms using 9 items of Garrigues Questionnaire (GQ), which included an item on bowel opening frequency. Secondary outcomes were gut transit time (GTT), quality of life (PDQ39-SI), motor (MDS-UPDRS) and non-motor symptoms (NMSS).

    RESULTS: Of 55 recruited, 48 patients completed the study: 22 received probiotic and 26 received placebo. At 8 weeks, there was a significantly higher mean weekly BOF in the probiotic group compared to placebo [SD 4.18 (1.44) vs SD 2.81(1.06); (mean difference 1.37, 95% CI 0.68, 2.07, uncorrected p<0.001)]. Patients in the probiotic group reported five times higher odds (odds ratio = 5.48, 95% CI 1.57, 19.12, uncorrected p = 0.008) for having higher BOF (< 3 to 3-5 to >5 times/week) compared to the placebo group. The GTT in the probiotic group [77.32 (SD55.35) hours] reduced significantly compared to placebo [113.54 (SD 61.54) hours]; mean difference -36.22, 95% CI -68.90, -3.54, uncorrected p = 0.030). The mean change in GTT was 58.04 (SD59.04) hour vs 20.73 (SD60.48) hours respectively (mean difference 37.32, 95% CI 4.00, 70.63, uncorrected p = 0.028). No between-groups differences were observed in the NMSS, PDQ39-SI, MDS-UPDRS II and MDS-UPDRS III scores. Four patients in the probiotics group experienced mild reversible side effects.

    CONCLUSION: This study showed that consumption of a multi-strain probiotic (Hexbio®) over 8 weeks improved bowel opening frequency and whole gut transit time in PD patients with constipation.

  11. Chan FKL, Wong MCS, Chan AT, East JE, Chiu HM, Makharia GK, et al.
    Gut, 2023 Jul;72(7):1240-1254.
    PMID: 37019620 DOI: 10.1136/gutjnl-2023-329429
    Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.
  12. Khoo XH, Chong CW, Talha AM, Philip K, Teh CS, Isa AM, et al.
    J Gastroenterol Hepatol, 2023 Aug;38(8):1259-1268.
    PMID: 36908030 DOI: 10.1111/jgh.16174
    BACKGROUND AND AIM: The gut microbiota in irritable bowel syndrome (IBS) is known to vary with diet. We aim to (i) analyze the gut microbiota composition of IBS patients from a multi-ethnic population and (ii) explore the impact of a low FODMAP diet on gastrointestinal symptoms and gut microbiota composition among IBS patients.

    METHODS: A multi-center study of multi-ethnic Asian patients with IBS was conducted in two phases: (i) an initial cross-sectional gut microbiota composition study of IBS patients and healthy controls, followed by (ii) a single-arm 6-week dietary interventional study of the IBS patients alone, exploring clinical and gut microbiota changes.

    RESULTS: A total of 34 adult IBS patients (IBS sub-types of IBS-D 44.1%, IBS-C 32.4%, and IBS-M 23.5%) and 15 healthy controls were recruited. A greater abundance of Parabacteroides species with lower levels of bacterial fermenters and short-chain fatty acids producers were found among IBS patients compared with healthy controls. Age and ethnicity were found to be associated with gut microbiota composition. Following a low FODMAP dietary intervention, symptom and quality of life improvement were observed in 24 (70.6%) IBS patients. Symptom improvement was associated with adherence to the low FODMAP diet (46.7% poor adherence vs 92.9% good adherence, P = 0.014), and gut microbiota patterns, particularly with a greater abundance of Bifidobacterium longum, Anaerotignum propionicum, and Blautia species post-intervention.

    CONCLUSION: Gut microbiota variation in multi-ethnic IBS patients may be related to dietary intake and may be helpful to identify patients who are likely to respond to a low FODMAP diet.

  13. Greuter T, Bertoldo F, Rechner R, Straumann A, Biedermann L, Zeitz J, et al.
    J Pediatr Gastroenterol Nutr, 2017 08;65(2):200-206.
    PMID: 27801751 DOI: 10.1097/MPG.0000000000001455
    BACKGROUND: There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD).

    METHODS: Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively.

    RESULTS: A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, P = 0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, P = 0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, P = 0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%).

    CONCLUSIONS: In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy.

  14. Leddin D, Omary MB, Veitch A, Metz G, Amrani N, Aabakken L, et al.
    J Clin Gastroenterol, 2021 10 8;55(10):823-829.
    PMID: 34617932 DOI: 10.1097/MCG.0000000000001619
    Climate change has been described as the greatest public health threat of the 21st century. It has significant implications for digestive health. A multinational team with representation from all continents, excluding Antarctica and covering 18 countries, has formulated a commentary which outlines both the implications for digestive health and ways in which this challenge can be faced.
  15. Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al.
    Intest Res, 2019 Jul;17(3):285-310.
    PMID: 31146509 DOI: 10.5217/ir.2019.00026
    The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
  16. Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al.
    J Gastroenterol Hepatol, 2019 Aug;34(8):1296-1315.
    PMID: 30848854 DOI: 10.1111/jgh.14648
    The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.
  17. Mak JWY, Sun Y, Limsrivilai J, Abdullah M, Kaibullayeva J, Balderramo D, et al.
    BMC Med Res Methodol, 2023 May 25;23(1):129.
    PMID: 37231405 DOI: 10.1186/s12874-023-01944-2
    BACKGROUND: There is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development.

    METHODS: Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn's disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis.

    RESULTS: Through November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting.

    CONCLUSIONS: The GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries.

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