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  1. Sung JJ, Chiu PW, Chan FKL, Lau JY, Goh KL, Ho LH, et al.
    Gut, 2018 10;67(10):1757-1768.
    PMID: 29691276 DOI: 10.1136/gutjnl-2018-316276
    Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  2. Yap PR, Mahadeva S, Goh KL
    Aliment Pharmacol Ther, 2013 Nov;38(10):1321-2.
    PMID: 24134501 DOI: 10.1111/apt.12497
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  3. Ang D, Lee YY, Clarke JO, Lynch K, Guillaume A, Onyimba F, et al.
    Ann N Y Acad Sci, 2020 12;1481(1):154-169.
    PMID: 32428279 DOI: 10.1111/nyas.14369
    Gastroesophageal reflux disease (GERD) is a common condition characterized by troublesome symptoms or esophageal mucosal lesions attributed to excessive esophageal acid exposure. Various pathophysiological mechanisms account for GERD, including impaired esophageal peristalsis and anatomical or physiological defects at the esophagogastric junction (EGJ). Endoscopy identifies GERD complications and detects potential alternative diagnoses. However, if symptoms persist despite proton pump inhibitor therapy, functional esophageal tests are useful to characterize reflux burden and define the symptom association profile. Ambulatory pH or pH-impedance monitoring measures the 24-h acid exposure time, which remains the most reproducible reflux metric and predicts response to antireflux therapy. Apart from identifying peristaltic dysfunction, esophageal high-resolution manometry defines the morphology and contractile vigor (EGJ-CI) of the EGJ. Novel metrics obtained from pH-impedance monitoring include the postreflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance, which augment the diagnostic value of pH-impedance testing. Mucosal impedance can also be recorded using a probe inserted through a gastroscope, or a novel balloon catheter with arrays of impedance electrodes inserted following sedated endoscopy. The latest developments in functional esophageal tests define the GERD phenotype based on pathogenesis, reflux exposure, structural or motility disorders, and symptom burden, facilitating appropriate treatment.
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  4. Lee HL, Chua SS, Mahadeva S
    J Dig Dis, 2018 Jun;19(6):342-349.
    PMID: 29732728 DOI: 10.1111/1751-2980.12607
    OBJECTIVE: To evaluate regular non-steroidal anti-inflammatory drug (NSAID) users for dyspepsia, as well as to assess the effect of preventive measures, and the reasons for non-adherence to gastroprotective agents (GPA) from a real-world perspective.
    METHODS: A prospective longitudinal study was conducted among outpatients with regular NSAID usage. The presence of dyspepsia was assessed by locally validated versions of the Leeds dyspepsia questionnaire (LDQ), GPA and the participants' adherence to the drugs were assessed at recruitment and 2 weeks later. GPA was defined as the use of antisecretory medications or cyclooxygenase-2 inhibitors.
    RESULTS: Initially, 409 participants (mean age 52.3 ± 14.6 years, 60.6% females, 48.4% treated for musculoskeletal pain) were recruited. At recruitment, 50.9% of the participants had at least one upper gastrointestinal symptom. Complete data for follow-up analysis were collected from 158 participants who were naive NSAID users, had no prior gastrointestinal medication and who could be contacted. At 2-week follow-up there was no significant difference in the LDQ score change between NSAID users treated with GPA and those did not. However, there was a greater reduction in abdominal pain/discomfort (8.8% vs 5.0%, P 
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use
  5. Qua CS, Manikam J, Goh KL
    J Dig Dis, 2010 Aug;11(4):244-8.
    PMID: 20649738 DOI: 10.1111/j.1751-2980.2010.00445.x
    OBJECTIVE:
    To re-examine the efficacy and tolerability of 1-week proton pump inhibitor triple therapy as a first-line Helicobacter pylori (H. pylori) eradication therapy.

    METHODS:
    Consecutive participants with a positive rapid urease test during an outpatient upper endoscopy were included. All participants were given pantoprazole 40 mg b.i.d., amoxycillin 1 g b.i.d. and clarithromycin 500 mg b.i.d. for 1 week. They were asked to return after 1 week to report any side effects related to the medications and to check for compliance. Successful eradication was defined by negative (13)C-urea breath test at least 4 weeks after the completion of therapy.

    RESULTS:
    A total of 191 patients were recruited into the study, of whom 81 were male (42.4%) and 110 female (57.6%), with a mean age of 55.6 (range 21-88) years. Overall 26 patients (13.6%) defaulted follow up and five patients were not compliant (taking less than 85%) with the medications. Per-protocol and intention-to-treat eradication rates were 84.4% (95% CI: 78.6-89.9%) and 71.2% (95% CI: 64.5-77.6%), respectively. Overall 68 participants (42.5%) reported no side effects, followed by 58 (36.3%) with a taste disturbance, 16 (10.0%) with epigastric pain, 15 (9.4%) with diarrhea, 13 (8.1%) with nausea or vomiting, 12 (7.5%) with loss of appetite, nine (5.6%) with dizziness and two (1.3%) with an allergic skin rash, none of which was severe.

    CONCLUSION:
    The current regime using pantoprazole, amoxycillin and clarithromycin is highly tolerable and effective and should continue to be recommended as a first-line therapy for H. pylori eradication in our setting.
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  6. Ford AC, Mahadeva S, Carbone MF, Lacy BE, Talley NJ
    Lancet, 2020 11 21;396(10263):1689-1702.
    PMID: 33049222 DOI: 10.1016/S0140-6736(20)30469-4
    Dyspepsia is a complex of symptoms referable to the gastroduodenal region of the gastrointestinal tract and includes epigastric pain or burning, postprandial fullness, or early satiety. Approximately 80% of individuals with dyspepsia have no structural explanation for their symptoms and have functional dyspepsia. Functional dyspepsia affects up to 16% of otherwise healthy individuals in the general population. Risk factors include psychological comorbidity, acute gastroenteritis, female sex, smoking, use of non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. The pathophysiology remains incompletely understood, but it is probably related to disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and alterations in gastrointestinal microbiota, mucosal and immune function, and CNS processing. Although technically a normal endoscopy is required to diagnose functional dyspepsia, the utility of endoscopy in all patients with typical symptoms is minimal; its use should be restricted to people aged 55 years and older, or to those with concerning features, such as weight loss or vomiting. As a result of our incomplete understanding of its pathophysiology, functional dyspepsia is difficult to treat and, in most patients, the condition is chronic and the natural history is one of fluctuating symptoms. Eradication therapy should be offered to patients with functional dyspepsia who test positive for Helicobacter pylori. Other therapies with evidence of effectiveness include proton pump inhibitors, histamine-2 receptor antagonists, prokinetics, and central neuromodulators. The role of psychological therapies is uncertain. As our understanding of the pathophysiology of functional dyspepsia increases, it is probable that the next decade will see the emergence of truly disease-modifying therapies for the first time.
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  7. Goh KL, Manikam J, Qua CS
    Aliment Pharmacol Ther, 2012 May;35(9):1097-102.
    PMID: 22404486 DOI: 10.1111/j.1365-2036.2012.05054.x
    BACKGROUND:
    H. pylori eradication failures are difficult to treat and rescue therapies often consist of complex treatment regimens.

    AIM:
    To determine an effective and practical rescue therapeutic strategy for H. pylori treatment failures using two consecutive regimens: first rescue therapy - rabeprazole 20 mg t.d.s. and amoxicillin 1 g t.d.s. for 2 weeks and for failures a further second rescue therapy - rabeprazole 20 mg b.d., levofloxacin 500 mg b.d., amoxicillin 1 g b.d. for a further 2 weeks.

    METHODS:
    Consecutive patients who failed the proton pump inhibitor (PPI) 1-week triple therapy were recruited for the study. H. pylori status was determined by a C(13) urea breath test.

    RESULTS:
    One hundred and forty-nine patients received the first rescue therapy. Seven were not compliant to medication/defaulted follow-up. Eradication success- first rescue therapy: per protocol (PP) analysis-107/142 (75.4%) (95% CI (68.3-82.4%) and intention to treat (ITT) analysis-107/149 (71.8%) 95% CI (64.6-79.0%). Thirty-one of 35 patients who failed the first rescue therapy received the second rescue therapy. All were compliant with medications. Eradication success- PP and ITT was 28/31 (90.3%) 95% CI (74.2-98.0%). The cumulative eradication rate using both rescue therapies: PP analysis- 135/138 (97.8%) 95% CI: (93.8-99.6%), ITT analysis- 135/149 (90.6%) 95% CI: (84.7-94.8%).

    CONCLUSIONS:
    A 2-week high dose PPI-amoxicillin dual therapy followed by a PPI-amoxicillin-levofloxacin triple therapy were highly successful in achieving eradication in H. pylori treatment failures.
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  8. Lee YY, Wu JCY
    Gastroenterology, 2018 06;154(8):2018-2021.e1.
    PMID: 29730025 DOI: 10.1053/j.gastro.2018.04.030
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  9. Mohd H, Qua CS, Wong CH, Azman W, Goh KL
    J Gastroenterol Hepatol, 2009 Feb;24(2):288-93.
    PMID: 19054255 DOI: 10.1111/j.1440-1746.2008.05702.x
    Gastroesophageal reflux disease is thought to be the commonest cause of 'non-cardiac chest pain'. The use of proton-pump inhibitors resulting in improvement in the chest pain symptom would support this causal association.
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  10. Hartono JL, Qua CS, Goh KL
    Dig Dis Sci, 2011 Jan;56(1):90-6.
    PMID: 20467897 DOI: 10.1007/s10620-010-1275-5
    AIMS: To compare the esophageal sensitivity to acid and saline in patients with symptomatic and asymptomatic erosive reflux disease (ERD), non-erosive reflux disease (NERD) and controls, and to assess the response to proton-pump inhibitors in patients with symptomatic ERD and NERD.

    METHODOLOGY: Patients with GERD and a control group of healthy asymptomatic volunteers were recruited. All subjects underwent esophagogastroduodenoscopy and the acid-saline perfusion test. Symptomatic ERD and NERD patients were given rabeprazole 20 mg twice daily for 2 weeks and their response to treatment assessed.

    RESULTS: A total of 105 subjects were recruited: ERD=37 (symptomatic=24, asymptomatic=13), NERD=34 and controls=34. During saline perfusion, only the NERD group recorded a significantly higher sensitivity score compared to controls (2.74±7.28 vs. 0) (p=0.035). During acid perfusion, symptomatic ERD (15.42±13.42) and NERD (16.71±15.04) had significantly higher scores versus controls and asymptomatic ERD patients (both p<0.001). The mean %∆ reflux symptom score following treatment was significantly higher in symptomatic ERD patients compared to NERD patients (89.08±21.67 vs. 58.53±32.54; p<0.001).

    CONCLUSIONS: Patients with NERD were a generally hypersensitive group while asymptomatic ERD patients represent a hyposensitive group of patients which merits further study.

    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use
  11. Xiao Y, Zhang S, Dai N, Fei G, Goh KL, Chun HJ, et al.
    Gut, 2020 02;69(2):224-230.
    PMID: 31409606 DOI: 10.1136/gutjnl-2019-318365
    OBJECTIVE: To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO).

    DESIGN: In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs).

    RESULTS: In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively.

    CONCLUSION: Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms.

    TRIAL REGISTRATION NUMBER: NCT02388724.

    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  12. Ram M R, Teh X, Rajakumar T, Goh KL, Leow AHR, Poh BH, et al.
    J Antimicrob Chemother, 2019 01 01;74(1):11-16.
    PMID: 30403784 DOI: 10.1093/jac/dky401
    Objectives: Eradication of Helicobacter pylori is influenced by susceptibility to antimicrobial agents, elevated bacterial load and degree of acid inhibition, which can be affected by genotypes of drug-metabolizing enzymes [cytochrome P450 (CYP) 2C19 polymorphism]. Theoretically, the choice and dose of proton pump inhibitor may also influence the suppression of H. pylori infection. The CYP2C19 genotype has recently been found to have an impact on peptic ulcer healing, H. pylori eradication and therapeutic efficacy of proton pump inhibitors.

    Methods: Here, we investigated the impact of the CYP2C19 genotype polymorphism and the success of triple therapy (fluoroquinolones/metronidazole/clarithromycin) on antibiotic-resistant strains in eradicating H. pylori in human subjects with non-ulcer dyspepsia (NUD), in human subjects with peptic ulcer disease (PUD) and in asymptomatic human subjects (positive and negative for H. pylori infection).

    Results: Based on the CYP2C19 genotypes, determined by Droplet Digital PCR (ddPCR) analysis, we found 11.2%, 62.5% and 26.3% corresponding to rapid metabolizers, intermediate metabolizers and poor metabolizers, respectively. However, we did not find any significant effect for homozygous ABCB1 or CYP2C19*2 and CYP2C19*3 alleles. We detected several participants heterozygous for both ABCB1 and CYP2C19*2, CYP2C19*3 and CYP2C19*17 loci. The participants heterozygous for both ABCB1 and CYP2C19*2 and *3 loci should be defined as intermediate and poor metabolizers according to the haplotype analysis in the NUD, PUD and asymptomatic subjects.

    Conclusions: Consequently, fluoroquinolones/metronidazole/clarithromycin-based triple therapies can be used to eradicate H. pylori infection, if one does not know the CYP2C19 genotype of the patient.

    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  13. Quach DT, Vilaichone RK, Luu MN, Lee YY, Ang TL, Miftahussurur M, et al.
    Helicobacter, 2023 Dec;28(6):e13018.
    PMID: 37634226 DOI: 10.1111/hel.13018
    BACKGROUND: Multidrug-resistant Helicobacter pylori strains are emerging in Southeast Asia. This study evaluates the region's real-world practice in H. pylori management.

    MATERIALS AND METHODS: Physicians who managed H. pylori eradication in daily practice across 10 Southeast Asian countries were invited to participate in an online questionnaire, which included questions about the local availability of antimicrobial susceptibility tests (ASTs) and their preferred eradication regimens in real-world practice. An empiric regimen was considered inappropriate if it did not follow the local guidelines/consensus, particularly if it contained antibiotics with a high reported resistance rate or was recommended not to be empirically used worldwide.

    RESULTS: There were 564 valid responses, including 314 (55.7%) from gastroenterologists (GIs) and 250 (44.3%) from non-GI physicians. ASTs were unavailable in 41.7%. In countries with low and intermediate clarithromycin resistance, the most common first-line regimen was PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) (72.7% and 73.2%, respectively). Regarding second-line therapy, the most common regimen was bismuth-based quadruple therapy, PBMT (PPI, bismuth, metronidazole, tetracycline) (50.0% and 59.8%, respectively), if other regimens were used as first-line treatment. Concomitant therapy (PPI, amoxicillin, clarithromycin, metronidazole) (30.5% and 25.9%, respectively) and PAL (PPI, amoxicillin, levofloxacin) (22.7% and 27.7%, respectively) were favored if PBMT had been used as first-line treatment. In countries with high clarithromycin resistance, the most common first-line regimen was PBMT, but the utilization rate was only 57.7%. Alarmingly, PAC was prescribed in 27.8% of patients, ranking as the second most common regimen, and its prescription rate was higher in non-GI physicians than GI physicians (40.1% vs. 16.2%, p 

    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use
  14. Xiong L, Gong X, Siah KT, Pratap N, Ghoshal UC, Abdullah M, et al.
    J Gastroenterol Hepatol, 2017 Aug;32(8):1450-1456.
    PMID: 28084664 DOI: 10.1111/jgh.13730
    BACKGROUND AND AIM: Information on real world treatment experiences of patients with functional bowel disorders is lacking from Asia. This study aimed to describe the medication exposure and treatment satisfaction of patients presenting to gastroenterology clinics across a sampling of Asian cities.

    METHODS: From March 2011 to October 2013, adult patients presenting to hospital-based gastroenterology outpatient clinics in 11 cities across Asia, who fulfilled screening criteria for any functional gastrointestinal disorder, were asked to complete a validated culturally adapted translation of the Rome III diagnostic questionnaire, a checklist of medications received in the preceding 3 months and questions on treatment satisfaction.

    RESULTS: A total of 1376 patients (female 755, male 621, 41.36 ± 13.25 years) comprising irritable bowel (621, 45.1%), unspecified functional bowel disorder (372, 27.8%), functional constipation (202, 14.7%), functional bloating (144, 10.5%), and functional diarrhea (56, 4.1%) completed the study. Of 1105 patients with a previous consultation, 509 (46.1%) were dissatisfied with their treatment, with ineffective treatment being the commonest reason. Satisfaction with previous consultation was lowest by diagnosis for functional constipation (29.2%), and the most bothersome symptom was straining (37.5%). Of 1046 patients who had taken medications for their gastrointestinal symptoms in the last 3 months, 793 (75.8%) had received two or more drugs. For irritable bowel syndrome patients, treatment with proton pump inhibitors and antispasmodics was recorded in 57% and 31%, with overlapping epigastric pain and heartburn predicting proton pump inhibitors use.

    CONCLUSIONS: More attention should be given to treatment gaps with regards to possible under-treatment with antispasmodics in irritable bowel syndrome and to critically evaluating the efficacy of constipation management.
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  15. Tan HJ, Mahadeva S, Menon J, Ng WK, Zainal Abidin I, Chan FK, et al.
    J Dig Dis, 2013 Jan;14(1):1-10.
    PMID: 23134105 DOI: 10.1111/1751-2980.12000
    The working party statements aim to provide evidence and guidelines to practising doctors on the use of antiplatelet therapy and proton pump inhibitors (PPIs) in patients with cardiovascular risk as well as those at risk of gastrointestinal (GI) bleeding. Balancing the GI and cardiovascular risk and benefits of antiplatelet therapy and PPIs may sometimes pose a significant challenge to doctors. Concomitant use of anti-secretory medications has been shown to reduce the risk of GI bleeding but concerns have been raised on the potential interaction of PPIs and clopidogrel. Many new data have emerged on this topic but some can be confusing and at times controversial. These statements examined the supporting evidence in four main areas: rationale for antiplatelet therapy, risk factors of GI bleeding, PPI-clopidogrel interactions and timing for recommencing antiplatelet therapy after GI bleeding, and made appropriate recommendations.
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  16. Damanhuri NS, Kumolosasi E, Omar MS, Razak AFA, Mansor AH
    Daru, 2021 Jun;29(1):13-22.
    PMID: 33405191 DOI: 10.1007/s40199-020-00377-2
    BACKGROUND: P-glycoprotein (P-gp) is an Adenosine triphosphate (ATP) dependent drug-efflux pump which is located abundantly in the stomach and protects the gut mucosa from xenobiotic.

    OBJECTIVE: The purpose of this study was to investigate the influence of P-gp modulation on the efficacy of treatment regimen.

    METHOD: P-gp modulation in rats was performed by using P-gp inducer (150 mg/kg rifampicin) and P-gp inhibitor (10 mg/kg cyclosporine A) for 14 days prior to be infected with Helicobacter pylori (H. pylori). The rats were further divided into groups, which were normal control, vehicle control, antibiotics and omeprazole, antibiotics only and omeprazole only for another 2 weeks of treatment. The ulcer formation and P-gp expression were determined by using macroscopic evaluation and western blot analysis, respectively.

    RESULTS: The highest P-gp expression was shown in the induced P-gp rats (2.00 ± 0.68) while the lowest P-gp expression was shown in the inhibited P-gp rats (0.45 ± 0.36) compared to the normal P-gp rats. In all groups, the rats which were infected with H. pylori, had a significant increase (p proton pump inhibitor (omeprazole) have shown to effectively eradicate the H. pylori infection. Thus, P-gp expression influenced the effectiveness of the treatment.

    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
  17. Goh KL, Choi MG, Hsu WP, Chun HJ, Mahachai V, Kachintorn U, et al.
    J Gastroenterol Hepatol, 2014 Dec;29(12):1969-75.
    PMID: 24990817 DOI: 10.1111/jgh.12655
    Data on patient satisfaction with proton pump inhibitor (PPI) therapy for gastroesophageal reflux disease (GERD) are scarce in Asia. The perspectives of Asian patients with GERD and their satisfaction with PPI therapy were investigated.
    Matched MeSH terms: Proton Pump Inhibitors/therapeutic use*
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