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Abstract Background Catharanthus roseus, a Madagascar native flowering plant, is known for its glossy leaves and vibrant flowers, and its medicinal significance due to its alkaloid compounds. As a source of vinblastine and vincristine used in chemotherapy, Catharanthus roseus is also employed in traditional medicine with its flower and stalks in dried form. Its toxicity can lead to various adverse effects. We report a case of Catharanthus roseus juice toxicity presenting as acute cholangitis, emphasizing the importance of healthcare providers obtaining detailed herbal supplement histories. Case presentation A 65-year-old woman presented with abdominal pain, fever, anorexia, and lower limb numbness. Initial diagnosis of acute cholangitis was considered, but imaging excluded common bile duct stones. Further investigation revealed a history of ingesting Catharanthus roseus juice for neck pain. Laboratory findings showed leukocytosis, elevated liver enzymes, and hyperbilirubinemia. The patient developed gastric ulcers, possibly due to alkaloids in Catharanthus roseus. No bacterial growth was noted in blood cultures. The patient recovered after discontinuing the herbal extract. Conclusions Catharanthus roseus toxicity can manifest as fever, hepatotoxicity with cholestatic jaundice, and gastric ulcers, mimicking acute cholangitis. Awareness of herbal supplement use and potential toxicities is crucial for healthcare providers to ensure prompt diagnosis and appropriate management. This case emphasizes the need for public awareness regarding the possible toxicity of therapeutic herbs and the importance of comprehensive patient histories in healthcare settings.

Background The objective of this study was to investigate the inter-relationship between psychosocial variables and their impact on symptom severity and quality of life (QoL) concerning abdominal bloating. Methods The study adopted a cross-sectional design with purposive sampling. Participants who consented and met the criteria for bloating based on the Rome IV classification completed designated questionnaires. Independent variables comprised health beliefs, intentions, health-promoting behaviors, social support, depression, and anxiety, while dependent variables included bloating severity (general and within 24 h) and QoL. Structural Equation Modeling (SEM) was conducted utilizing Mplus 8.0 to analyze the relationships between these factors. Results A total of 323 participants, with a mean age of 27.69 years (SD = 11.50), predominantly females (64.7%), volunteered to participate in the study. The final SEM model exhibited good fit based on various indices (CFI = 0.922, SRMR = 0.064, RMSEA (95% CI) = 0.048 (0.041–0.054), p-value = 0.714), with 15 significant path relationships identified. The model explained 12.0% of the variance in severity within 24 h, 6% in general severity, and 53.8% in QoL. Conclusion The findings underscore the significant influence of health beliefs, intentions, behaviors, social support, depression, and anxiety on symptom severity and QoL in individuals experiencing abdominal bloating.

Abstract Background Systematic reviews and meta-analyses of randomized clinical trials (RCTs) have reported the benefits of ketogenic diets (KD) in various participants such as patients with epilepsy and adults with overweight or obesity. Nevertheless, there has been little synthesis of the strength and quality of this evidence in aggregate. Methods To grade the evidence from published meta-analyses of RCTs that assessed the association of KD, ketogenic low-carbohydrate high-fat diet (K-LCHF), and very low-calorie KD (VLCKD) with health outcomes, PubMed, EMBASE, Epistemonikos, and Cochrane database of systematic reviews were searched up to February 15, 2023. Meta-analyses of RCTs of KD were included. Meta-analyses were re-performed using a random-effects model. The quality of evidence per association provided in meta-analyses was rated by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria as high, moderate, low, and very low. Results We included 17 meta-analyses comprising 68 RCTs (median [interquartile range, IQR] sample size of 42 [20–104] participants and follow-up period of 13 [8–36] weeks) and 115 unique associations. There were 51 statistically significant associations (44%) of which four associations were supported by high-quality evidence (reduced triglyceride (n = 2), seizure frequency (n = 1) and increased low-density lipoprotein cholesterol (LDL-C) (n = 1)) and four associations supported by moderate-quality evidence (decrease in body weight, respiratory exchange ratio (RER), hemoglobin A1c, and increased total cholesterol). The remaining associations were supported by very low (26 associations) to low (17 associations) quality evidence. In overweight or obese adults, VLCKD was significantly associated with improvement in anthropometric and cardiometabolic outcomes without worsening muscle mass, LDL-C, and total cholesterol. K-LCHF was associated with reduced body weight and body fat percentage, but also reduced muscle mass in healthy participants. Conclusions This umbrella review found beneficial associations of KD supported by moderate to high-quality evidence on seizure and several cardiometabolic parameters. However, KD was associated with a clinically meaningful increase in LDL-C. Clinical trials with long-term follow-up are warranted to investigate whether the short-term effects of KD will translate to beneficial effects on clinical outcomes such as cardiovascular events and mortality.

Elevated liver enzyme levels are a frequent incidental finding in primary care, and non-alcoholic fatty liver disease is the main cause of incidental elevation of liver enzymes worldwide. The features of the disease vary from simple steatosis, characterized by a benign prognosis, to non-alcoholic steatohepatitis and cirrhosis, increasing morbidity and mortality. In this case report, abnormal liver activity was incidentally detected during other medical assessments. The patient was treated with silymarin 140 mg three times daily, resulting in decreased serum liver enzyme levels over treatment with a good safety profile. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series

Abstract Helicobacter pylori is one of the most common chronic bacterial infections in humans and responsible for 90% of duodenal ulcers and 70–90% of gastric ulcers. Despite this, many misconceptions regarding the appropriate diagnostic method and treatment strategies still exist in the Malaysian clinical practice. Under the initiative of the steering committee, an expert panel consisting of nine key opinion leaders in the field of gastroenterology convened to develop a set of consensus statements that are relevant to the Malaysian healthcare practice. The panel members reviewed the current evidence on the management of H. pylori infection, focusing on the best practices that are relevant to the Malaysian population based on clinical experience and published clinical evidence. Using the modified Delphi method, the panel achieved consensus in three areas of H. pylori infection management: indications for testing, diagnosis, and treatment. The panel proposed a set of 19 consensus statements, which were synthesized via two rounds of blinded voting and group discussions. The recommendations provided are relevant to the Malaysian population and can be used as a guide by physicians across various healthcare settings to facilitate appropriate diagnostic testing and treatment of H. pylori infection.

Non-alcoholic fatty liver disease is one of the main causes of elevated liver enzymes and chronic liver disease worldwide. It ranges from steatosis to steatohepatitis, leading to cirrhosis and related liver dysfunction. Silymarin is a herbal medicine, mostly used for liver disorders owing to its supposed hepatoprotective action. This report recommends silymarin in a patient with diabetes and grade II non-alcoholic steatohepatitis, confirming significant hepatoprotective effects as shown by the reduction of liver enzyme activities. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series

Tuberculosis (TB) is a chronic infection of global-health concern because of its high incidence, costly medical treatment, drug resistance and risk of co-infections. Anti-TB treatment involves a combination of drugs with high degree of liver toxicity, leading to drug-induced liver injury in 2–28% of patients who receive anti-TB treatment. In this case report, a patient with TB experienced drug-induced liver injury, and the initiation of treatment with silymarin 140 mg three-times daily resulted in a significant hepatoprotective effects as shown by the decreased liver enzyme activity. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/ current-clinical-use-of-silymarin-in-the-treatmentof- toxic-liver-diseases-a-case-series

Background The significance of the current study was to determine normative levels of PIVKA-II and AFP in patients with unresectable HCC and healthy participants. The second goal was to assess the roles of PIVKA-II and AFP in predicting radiological response after loco-regional therapy. Methods This prospective cohort study enrolled consecutive samples of HCC patients and healthy controls. Venous blood samples were obtained at baseline and after interventions to determine serum levels of PIVKA-II and AFP using the chemiluminescent microparticle immunoassay method. Radiologic responses were determined based on the WHO criteria. Results Fifty-four HCC patients (mean age 58.9 years, 49 males) and 40 healthy controls (mean age 33.5 years, 26 males) were recruited. The median serum levels of PIVKA-II and AFP in HCC vs. healthy controls were 988.4 vs. 24.2 mAU/ml and 13.6 vs. 1.7 ng/ml, respectively (both p

Abstract Clinical benefits and safety of carbohydrate loading pre-gastroscopy remain unclear. We aimed to determine the effects of a commercial carbohydrate-rich whey protein beverage versus plain water given pre-gastroscopy on gastric residual volume and well-being, and to determine adverse events. This was a single centre, single-blinded, parallel-group, sex-stratified randomized controlled trial. Participants were randomized either to carbohydrate-rich whey protein beverage group (Resource®, Nestle Health Science) or control group (250 ml plain water) given pre-gastroscopy. Gastric contents were aspirated into a suction reservoir bottle to determine the gastric residual volume (GRV). Visual analogue scale (VAS) of well-being (anxiety, hunger, thirst, tiredness, and weakness) was compared before and after the intervention. Adverse events were also evaluated post-intervention. Of 369 screened, 78 participants (36 males, mean age 49 ± 14.3 years) were randomized. Compared with the control group, carbohydrate beverage was associated with significantly higher GRV (p

Abstract The milk fat globule membrane (MFGM) has been recognized as a milk component for more than 60 years, but its exact benefits remain unknown. Research on human MFGM has revealed that the membrane holds a host of bioactive components with potential benefits for the brain–immune–gut (BiG) axis in early life. Gangliosides and sphingomyelin, components within the MFGM, have been included in infant formulas for many years. Recent advancements in dairy milk processing have allowed the successful separation of MFGM from bovine milk, enabling it to be used for supplementing infant formulas. Evidence indicates the potential benefits of MFGM in early life supplementation, including better cognitive development, reduction of infection risks, and modulation of the gut microbiome. However, larger and more robust randomized trials are needed, in addition to long‐term outcome data beyond the infancy period.

Abstract Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections. Together, the World Society of Emergency Surgery, the Global Alliance for Infections in Surgery, the Surgical Infection Society-Europe, The World Surgical Infection Society, and the American Association for the Surgery of Trauma have jointly completed an international multi-society document to promote global standards of care in SSTIs guiding clinicians by describing reasonable approaches to the management of SSTIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting evidence was shared by an international task force with different clinical backgrounds.

For a long time, the role of an extensive neurological network in the gut (the little-brain) has been under-recognized because the enteric nervous system (ENS) is thought to have little impact beyond digestion. More recently, there has been a paradigm shift in understanding interactions between the gut and brain, i.e., the gut-brain axis, especially in clinical disorders termed functional gastrointestinal disorders (FGIDs). In a global epidemiology study commissioned by the Rome Foundation, among 70,000 adults, at least one FGID wasdiagnosed in 40.3% of internet surveys and 20.7% of household survey. FGIDs are perhaps the second most common consults in gastroenterology practice in Asia (the first being chronic liver disorders largely due to a high burden of viral hepatitis). These disorders include functional dyspepsia (FD) and irritable bowel syndrome (IBS). During the recent fourth iteration of the Rome diagnostic criteria, FGIDs have been relabeled as disorders of gut-brain interactions (DGBIs)

Abstract Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries with different clinical backgrounds. The aim of the document is to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs.

Abstract Background Individuals with advanced colorectal adenomas (ACAs) are at high risk for colorectal cancer (CRC), and it is unclear which chemopreventive agent (CPA) is safe and cost-effective for secondary prevention. We aimed to determine, firstly, the most suitable CPA using network meta-analysis (NMA) and secondly, cost-effectiveness of CPA with or without surveillance colonoscopy (SC). Methods Systematic review and NMA of randomised controlled trials were performed, and the most suitable CPA was chosen based on efficacy and the most favourable risk–benefit profile. The economic benefits of CPA alone, 3 yearly SC alone, and a combination of CPA and SC were determined using the cost-effectiveness analysis (CEA) in the Malaysian health-care perspective. Outcomes were reported as incremental cost-effectiveness ratios (ICERs) in 2018 US Dollars ($) per quality-adjusted life-year (QALY), and life-years (LYs) gained. Results According to NMA, the risk–benefit profile favours the use of aspirin at very-low-dose (ASAVLD, ≤ 100 mg/day) for secondary prevention in individuals with previous ACAs. Celecoxib is the most effective CPA but the cardiovascular adverse events are of concern. According to CEA, the combination strategy (ASAVLD with 3-yearly SC) was cost-saving and dominates its competitors as the best buy option. The probability of being cost-effective for ASAVLD alone, 3-yearly SC alone, and combination strategy were 22%, 26%, and 53%, respectively. Extending the SC interval to five years in combination strategy was more cost-effective when compared to 3-yearly SC alone (ICER of $484/LY gain and $1875/QALY). However, extending to ten years in combination strategy was not cost-effective. Conclusion ASAVLD combined with 3-yearly SC in individuals with ACAs may be a cost-effective strategy for CRC prevention. An extension of SC intervals to five years can be considered in resource-limited countries.

Abstract Background Fructose plays an important role in the complex metabolism of uric acid in the human body. However, high blood uric acid concentration, known as hyperuricemia, is the main risk factor for development of gout. Therefore, we conducted an updated meta-analysis on the prevalence and geographical distribution of hyperuricemia among the general population in mainland China using systematic literature search. Methods Five electronic databases were used to search for relevant articles published until 2019. All calculations were conducted using the Comprehensive Meta-Analysis (CMA) software. We included 108 eligible articles (172 studies by sex, 95 studies by regions, and 107 studies by study type) and an overall sample size of > 808,505 participants. Results The pooled prevalence of hyperuricemia among the general population in mainland China was 17.4% (95% CI: 15.8–19.1%). Our subgroup analysis indicated that the pooled prevalence by regions ranged from 15.5 to 24.6%. Those living Northeast region and being males had the highest prevalence (P 20%), particularly in males. An increasing prevalence was reported since 2005–2009 until 2015–2019. No publication of bias was observed as indicated by a symmetrical funnel plot and Begg and Mazumdar rank correlation (P = 0.392). Conclusion Prevalence of hyperuricemia is increasing in China, and future studies should investigate the association between the prevalence of hyperuricemia and its risk factors in order to tackle the issue, particularly among the vulnerable groups. Also, our study was the first comprehensive study to investigate the overall prevalence of hyperuricemia in mainland China covering the six different regions.

Planar scintigraphy with 99m Tc-pertechnetate or Meckel scan is the gold standard in the diagnosis of a bleeding Meckel’s diverticulum (MD) for pediatrics. However, several setbacks may occur during the interpretation of a scintigram, especially in cases of an atypical MD presentation. In this report, we highlight the importance of functional and anatomical image co-registration using a hybrid SPECT/CT scanner to precisely localize a MD lesion. An 18-month-old boy presented with severe hematochezia over 4 days with declining hemoglobin levels. He underwent a conventional 60-min dynamic planar imaging of the Meckel scan. Upon review of the Meckel scan, a suspicious increase in the 99m Tc-pertechnetate uptake was observed at the right upper quadrant of the abdomen. Due to its atypical location at the right kidney, we could not differentiate between a physiological uptake of the right kidney or an ectopic gastric mucosa. The patient was imaged again using single-photon emission computed tomography (SPECT) and low-dose CT protocol with a hybrid SPECT/CT scanner, and the co-registration of both SPECT and CT images was able to confirm the MD, which was located anterior to the right kidney at the right hepatic flexure region. An exploratory laparotomy was then ensued to remove the bleeding MD. The patient was discharged after 3 days with no complications. In summary, this case illustrates that hybrid imaging modality and co-registration allow for a more definitive diagnosis, as well as a more precise localization of MD.

Mind-body techniques, including Guided Imagery (GI) or Progressive Muscle Relaxation (PMR), may effectively manage bloating. The current study aimed to develop and validate (psychometric and psychological responses) audio-based GI and PMR techniques for bloating. Audio scripts were first developed from literature reviews and in-depth interviews of participants with bloating diagnosed based on the Rome IV criteria. Scripts were validated using psychometric (content & face validity index) and physiological approaches (brain event-related potentials & heart rate variability). 45/63 participants completed the in-depth interview, and ‘balloon’ emerged as the synonymous imagery description for bloating, of which inflation correlated with a painful sensation. The final tools consisted of narrated audio scripts in the background of a validated choice of music. Overall, the content and face validity index for PMR and GI ranged from 0.92 to 1.00. For ERP and HRV, 17/20 participants were analyzed. For ERP, there was a significant difference between GI and PMR for alpha waves (p = 0.029), delta waves (p = 0.029), and between PMR and control for delta waves (p = 0.014). For HRV, GI and PMR exhibited similar autonomic responses over controls (overall p

Abstract Background It is unclear if the 99mTc-sodium phytate (99mTc-SP) is as reliable as the gold-standard 99mTc-sulfur colloid (99mTc-SC) for gastric emptying scintigraphy (GES). This study is aimed to compare the emptying rates of both radiotracers in a prospective, randomized cross-over trial and to determine the normative data of a healthy multi-ethnic Asian population. Methods Out of the 44 healthy individuals screened, 31 (14 females; mean age: 28.4 ± 7.0 years) were enrolled and underwent GES using the standardized egg-white meal. All participants were randomly assigned to either 99mTc-SP or 99mTc-SC on the first GES session before crossed over to the other formulation after 2 weeks. Results Both kits achieved the radiochemical purities of > 95%. The median rate (95th upper normative limit) of gastric emptying, reported as total gastric meal retention between 99mTc-SP and 99mTc-SC, was found to be comparable at all measured time points: 0.5 h [85.0% (96.6%) vs. 82.0% (94.0%)], 1 h [70.0% (86.4%) vs. 65.0% (86.6%)], 2 h [31.0% (55.8%) vs. 25.0% (64.4%)], 3 h [7.0% (26.3%) vs. 5.0% (29.9%)], and 4 h [3.0% (10.3%) vs. 2.0% (9.9%)]; P > 0.05. In addition, both radiotracers correlated well (Kendall’s Tau (τ) coefficient = 0.498, P

Introduction: Dopamine receptor D2 (DRD2) is one of the dopamine receptors that have been studied in relation to opioid dependence. It is possible, therefore, that DRD2 gene (DRD2) polymorphisms influence treatment outcomes of patients with opioid dependence. The objective of this study was to investigate the influence of DRD2 polymorphisms on the clinical outcomes of opioid-dependent patients on methadone maintenance therapy (MMT). Materials and Methods: Patients with opioid dependence (n = 148) were recruited from MMT clinics. Pain sensitivity, severity of the opiate withdrawal syndrome, and sleep quality were assessed using cold pressor test (CPT), Subjective Opiate Withdrawal Scale (SOWS-M), and Pittsburgh Sleep Quality Index (PSQI)-Malay, respectively. Deoxyribonucleic acid (DNA) was extracted from whole blood, and then was used for genotyping of Val96Ala, Leu141Leu, Val154Ile, Pro310Ser, Ser311Cys, TaqI A, -141C Ins/Del, and A-241G polymorphisms. Results: Among 148 patients, 8.1% (n = 12), 60.8% (n = 90), 27.7% (n = 41), and 29.1% (n = 43) had at least one risk allele for Ser311Cys, TaqI A, -141C Ins/Del, and A-241G polymorphisms, respectively. There were no significant differences in pain responses (pain threshold, tolerance, and intensity), SOWS, and PSQI scores between DRD2 polymorphisms. Conclusion: The common DRD2 polymorphisms are not associated with pain sensitivity, severity of the opiate withdrawal syndrome, and sleep quality in patients with opioid dependence on MMT. However, this may be unique for Malays. Additional research should focus on investigating these findings in larger samples and different ethnicity.

Background: This study aimed to investigate the prevalence, symptoms, and factors associated with chronic constipation among community-dwelling older people in the East Coast region of Peninsular Malaysia. Methods: A cross-sectional study was conducted in four selected health clinics using stratified cluster sampling. A face-to-face interview was carried out among the elderly outpatients, in order to complete a structured questionnaire. Results: A total of 400 participants were included in the study. The mean age was 68.7 ± 6.4 years, and 55% of the cohort were women. The prevalence of chronic constipation was 32.3% among the sample population. The most common symptom was “sensation of incomplete evacuation” (63.6%), and none of the participants reported having “less than three defecations per week,” “straining,” or “lumpy or hard stool.” Educational level (p = 0.005), number of defecations per week, stool form, time spent for defecation, and abdominal bloating were significantly associated with chronic constipation (p < 0.001). Conclusion: Chronic constipation was common in older people and associated with a low educational level. Recognition of symptoms was predominantly based on clinical features of constipation and will require the healthcare providers to consider these factors in their routine assessment of older people.

The association between emphysematous pyelonephritis (EPN) and diabetes mellitus is well known. EPN as the cause of sepsis in hepatocellular carcinoma (HCC) is rare and unreported. We report a case of EPN in a non-diabetic HCC patient, in which the clinical features of decompensated chronic liver disease masked the more sinister urological emergency to a certain degree. A computed tomography scan of the abdomen revealed a mixture of gas and fluid in the left retrorenal space, in keeping with left EPN. Nevertheless, the course of clinical deterioration was rather rapid that any surgical intervention was not feasible.

Introduction Regardless of having effective vaccines against COVID-19, containment measures such as enhanced physical distancing and good practice of personal hygiene remain the mainstay of controlling the COVID-19 pandemic. Countries across Asia have imposed these containment measures to varying extents. However, residents in different countries would have a differing degree of compliance to these containment measures potentially due to differences in the level of awareness and motivation in the early phase of pandemic.Objectives In our study, we aimed to describe and correlate the level of knowledge and attitude with the level of compliance with personal hygiene and physical distancing practices among Asian countries in the early phase of pandemic.Methods A multinational cross-sectional study was carried out using electronic surveys between May and June 2020 across 14 geographical areas. Subjects aged 21 years and above were invited to participate through social media, word of mouth and electronic mail.Results Among the 2574 responses obtained, 762 (29.6%) participants were from East Asia and 1812 (70.4%) were from Southeast Asia (SEA). A greater proportion of participants from SEA will practise physical distancing as long as it takes (72.8% vs 60.6%). Having safe distancing practices such as standing more than 1 or 2 m apart (AdjOR 5.09 95% CI (1.08 to 24.01)) or more than 3 or 4 m apart (AdjOR 7.05 95% CI (1.32 to 37.67)), wearing a mask when they had influenza-like symptoms before the COVID-19 pandemic, preferring online news channels such as online news websites/applications (AdjOR 1.73 95% CI (1.21 to 2.49)) and social media (AdjOR 1.68 95% CI (1.13 to 2.50) as sources of obtaining information about COVID-19 and high psychological well-being (AdjOR 1.39 95% CI (1.04 to 1.87)) were independent factors associated with high compliance.Conclusions We found factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic and it will be useful to consider them in risk assessment, communication and pandemic preparedness.

The aims of gastroesophageal reflux disease (GERD) treatment are symptom relief and healing of oesophagitis. Besides proton pump inhibitors (PPIs), prokinetic agents are also commonly prescribed to treat GERD. Domperidone, a well-known antiemetic, is an example of a prokinetic agent. It is a dopaminergic blocker that increases lower oesophagus sphincter pressure and activates gastric motility. We carried out a systematic review and meta-analysis to explore the benefits of domperidone in addition to PPI therapy for GERD. We searched for publications comparing PPI plus domperidone to PPI monotherapy in terms of symptom improvement in GERD (until 21 April 2022) on PubMed, Scopus, Google Scholar, Web of Science, Cochrane Library, WHO’s International Clinical Studies Registry Platform, and ClinicalTrials.gov without restricting date, language, or study design. The protocol was registered in PROSPERO (CRD42021242076). This meta-analysis incorporated 11 studies with a total of 841 participants (419 in the PPI plus domperidone group and 422 in the PPI monotherapy group). The combination of a PPI and domperidone resulted in a significant reduction in global GERD symptoms. Adverse events associated with PPI plus domperidone treatment were similar to those associated with PPI monotherapy. In conclusion, the combination of domperidone and a PPI is generally safe and effective in treating GERD as compared with that of PPI alone.

Background Health management strategies may help patients with abdominal bloating (AB), but there are currently no tools that measure behaviour and awareness. This study aimed to validate and verify the dimensionality of the newly-developed Health Promoting Behaviour for Bloating (HPB-Bloat) scale. Methods Based on previous literature, expert input, and in-depth interviews, we generated new items for the HPB-Bloat. Its content validity was assessed by experts and pre-tested across 30 individuals with AB. Construct validity and dimensionality were first determined using exploratory factor analysis (EFA) and Promax rotation analysis, and then using confirmatory factor analysis (CFA). Results During the development stage, 35 items were generated for the HPB-Bloat, and were maintained following content validity assessment and pre-testing. One hundred and fifty-two participants (mean age of 31.27 years, 68.3% female) and 323 participants (mean age of 27.69 years, 59.4% male) completed the scale for EFA and CFA, respectively. Using EFA, we identified 20 items that we divided into five factors: diet (five items), health awareness (four items), physical activity (three items), stress management (four items), and treatment (four items). The total variance explained by the EFA model was 56.7%. The Cronbach alpha values of the five factors ranged between 0.52 and 0.81. In the CFA model, one problematic latent variable (treatment) was identified and three items were removed. In the final measurement model, four factors and 17 items fit the data well based on several fit indices (root mean square error of approximation (RMSEA) = 0.044 and standardized root mean squared residual (SRMR) = 0.052). The composite reliability of all factors in the final measurement model was above 0.60, indicating acceptable construct reliability. Conclusion The newly developed HPB-Bloat scale is valid and reliable when assessing the awareness of health-promoting behaviours across patients with AB. Further validation is needed across different languages and populations.

Background: Non-cardiac chest pain is common with two-thirds due to gastroesophageal reflux disease (GERD).Objective: To evaluate the effectiveness and safety of guided vs. empirical therapy in non-cardiac chest pain.Methods: Adults with normal angiogram or stress test were randomized into either a guided or empirical group. In the guided group, after the ambulatory pH-impedance test, if GERD then dexlansoprazole 30 mg/day for 8 weeks, but if functional or hypersensitive chest pain, then theophylline SR 250 mg/day for 4 weeks. In the empirical group, dexlansoprazole 60 mg/day was given for 2 weeks. The primary outcome was global chest pain visual analog score (VAS) and secondary outcomes were Quality of Life in Reflux and Dyspepsia (QOLRAD), GERD questionnaire (GERDQ), and pH parameters, all determined at baseline, 2nd and 8th weeks.Results: Of 200 screened patients, 132 were excluded, and of 68 randomized per-protocol, 33 were in the guided group and 35 in the empirical group. For between-group analysis, mean global pain scores were better with guided vs. empirical group at 8th week (P = 0.005) but not GERDQ or QOLRAD or any of pH measures (all P > 0.05). For within-group analysis, mean QOLRAD improved earliest at 8th week vs. baseline (P = 0.006) in the guided group and 2nd week vs. baseline (P = 0.011) in the empirical group but no differences were seen in other secondary outcomes (P > 0.05). No serious adverse events were reported.Conclusions: Guided approach may be preferred over short-term empirical therapy in symptom response, however QOLRAD, acid-related symptoms, or pH measures are not significantly different (trial registration ID no. NCT03319121).

ImportanceKnowledge and attitude influence compliance and individuals' practices. The risk and protective factors associated with high compliance to these preventive measures are critical to enhancing pandemic preparedness.ObjectiveThis survey aims to assess differences in mental health, knowledge, attitudes, and practices (KAP) of preventive measures for COVID-19 amongst healthcare professionals (HCP) and non-healthcare professionals.DesignMulti-national cross-sectional study was carried out using electronic surveys between May-June 2020.SettingMulti-national survey was distributed across 36 countries through social media, word-of-mouth, and electronic mail.ParticipantsParticipants ≥21 years working in healthcare and non-healthcare related professions.Main outcomeRisk factors determining the difference in KAP towards personal hygiene and social distancing measures during COVID-19 amongst HCP and non-HCP.ResultsHCP were significantly more knowledgeable on personal hygiene (AdjOR 1.45, 95% CI -1.14 to 1.83) and social distancing (AdjOR 1.31, 95% CI -1.06 to 1.61) compared to non-HCP. They were more likely to have a positive attitude towards personal hygiene and 1.5 times more willing to participate in the contact tracing app. There was high compliance towards personal hygiene and social distancing measures amongst HCP. HCP with high compliance were 1.8 times more likely to flourish and more likely to have a high sense of emotional (AdjOR 1.94, 95% CI (1.44 to 2.61), social (AdjOR 2.07, 95% CI -1.55 to 2.78), and psychological (AdjOR 2.13, 95% CI (1.59-2.85) well-being.Conclusion and relevanceWhile healthcare professionals were more knowledgeable, had more positive attitudes, their higher sense of total well-being was seen to be more critical to enhance compliance. Therefore, focusing on the well-being of the general population would help to enhance their compliance towards the preventive measures for COVID-19.

Background Clinician burnout is an important occupational hazard that may be exacerbated by the novel COVID-19 pandemic. Within Southeast Asia, burnout in gastroenterology is understudied. The primary objective of this study is to estimate the prevalence of burnout symptoms within gastroenterology, in member states of the Associations of Southeast Asian Nations (ASEAN), during and after the COVID-19 pandemic. The secondary objective is to identify work-related stressors that contribute to burnout in ASEAN gastroenterologists.Methods and analysis This is an observational study that will use anonymised online surveys to estimate the prevalence of burnout symptoms at two time points: during the COVID-19 pandemic in 2020 and in 2022 (assumed to be after the pandemic). Gastroenterologists from Singapore, Malaysia, Thailand, Indonesia, Philippines and Brunei will be invited to participate in the online survey through their national gastroenterology and endoscopy societies. Burnout will be assessed using the Maslach Burnout Inventory-Human Services Survey tool. Supplementary questions will collect demographic and qualitative data. Associations between demographic characteristics and burnout will be tested by multiple regression.Results The prevalence of burnout symptoms in gastroenterology during the COVID-19 pandemic, and the baseline prevalence after COVID-19, will be established in the above-mentioned countries. Work-related stressors commonly associated with burnout will be identified, allowing the introduction of preventative measures to reduce burnout in the future.Ethics and dissemination Ethical approval was granted by the Singhealth Centralised Institutional Review Board (2020/2709). Results will be submitted for publication.

Background Chronic constipation is a common symptom among the elderly, and it may affect their quality of life (QoL). A lack of available research focused on the elderly means that this effect is not well understood. This study aimed to develop and validate a new scale (Elderly-Constipation Impact Scale (E-CIS)) to measure the impact of chronic constipation on QoL among the elderly. Methods A pool of items was generated from a qualitative study, literature reviews, and expert reviews. Exploratory factor analysis (EFA) was performed on the original 40 items of the E-CIS and followed by 27 items for confirmatory factor analysis (CFA). A total of 470 elderly people with chronic constipation were involved. Results The mean age of the participants was 68.64 ± 6.57. Finally, only 22 items were indicated as appropriately representing the E-CIS, which were grouped into seven subscales: ‘daily activities’, ‘treatment satisfaction’, ‘lack of control of bodily function’, ‘diet restriction’, ‘symptom intensity’, ‘anxiety’ and ‘preventive actions’. The scale was confirmed as valid (root mean square error of approximation (RMSEA) = 0.04, comparative fit index (CFI) = 0.961, Tucker-Lewis index (TLI) = 0.952 and chi-square/degree of freedom (chiSq/df) = 1.44) and reliable (Cronbach’s alpha: 0.66–0.85, composite reliability (CR) = 0.699–0.851) to assess the impact of chronic constipation on the elderly’s QoL. Conclusions The E-CIS is useful to measure the impact of chronic constipation on the elderly’s QoL. A further test is needed to determine the validity and reliability of this scale in other elderly population.

Excessive alcohol consumption is the cause of several diseases and thus is of a major concern for society. Worldwide alcohol consumption has increased by many folds over the past decades. This urgently calls for intervention and relapse counteract measures. Modern pharmacological solutions induce complete alcohol self-restraint and prevent relapse, but they have many side effects. Natural products are most promising as they cause fewer adverse effects. Here we discuss in detail the medicinal plants used in various traditional/folklore medicine systems for targeting alcohol abuse. We also comprehensively describe preclinical and clinical studies done on some of these plants along with the possible mechanisms of action.

Background Vasoactive drugs are frequently used in combination with endoscopic variceal ligation (EVL) in treatment of acute esophageal variceal bleeding (EVB). The aim of study was to assess physicians’ preference of vasoactive agents in acute EVB, their reasons of preference and efficacy and safety of these short course regimens. Methods Cirrhotic patients with suspected EVB were screened (n = 352). Eligible patients were assigned based on the physician’s preference to either somatostatin (group S) or terlipressin (group T) followed by EVL. In group S, intravenous bolus (250 µg) of somatostatin followed by 250 µg/hour was continued for three days. In group T, 2 mg bolus injection of terlipressin was followed by 1 mg infusion every 6 h for three days. Results A total of 150 patients were enrolled; 41 in group S and 109 in group T. Reasons for physician preference was convenience in administration (77.1%) for group T and good safety profile (73.2%) for group S. Very early rebleeding within 49–120 h occurred in one patient in groups S and T (p = 0.469). Four patients in group S and 14 patients in group T have variceal rebleeding episodes within 6–42 d (p = 0.781). Overall treatment-related adverse effects were compatible in groups S and T (p = 0.878), but the total cost of terlipressin and somatostatin differed i.e., USD 621.32 and USD 496.43 respectively. Conclusions Terlipressin is the preferred vasoactive agent by physicians in our institution for acute EVB. Convenience in administration and safety profile are main considerations of physicians. Safety and hemostatic effects did not differ significantly between short-course somatostatin or terlipressin, although terlipressin is more expensive.

Biologics are large complex molecules that are produced in living systems. They have revolutionised the treatment of patients suffering from various diseases, including inflammatory bowel disease. However, in many parts of the world, patient access to biologics has been hampered, mainly because of the high costs associated with these therapies. Since the patent expiration of several of these biologics, biosimilars have emerged, promising equal effectiveness and safety for patients but at a more affordable price. Despite this, concerns remain regarding the use of biosimilars as replacements for biologics. This review discusses the issues and controversies surrounding the development and applicability of biosimilars in the field of gastroenterology.

Abstract Background After an environmental disaster, the affected community is at increased risk for persistent abdominal pain but mechanisms are unclear. Therefore, our study aimed to determine association between abdominal pain and poor water, sanitation and hygiene (WaSH) practices, and if small intestinal bacterial overgrowth (SIBO) and/or gut dysbiosis explain IBS, impaired quality of life (QOL), anxiety and/or depression after a major flood. Results New onset abdominal pain, IBS based on the Rome III criteria, WaSH practices, QOL, anxiety and/or depression, SIBO (hydrogen breath testing) and stools for metagenomic sequencing were assessed in flood victims. Of 211 participants, 37.9% (n = 80) had abdominal pain and 17% (n = 36) with IBS subtyped diarrhea and/or mixed type (n = 27 or 12.8%) being the most common. Poor WaSH practices and impaired quality of life during flood were significantly associated with IBS. Using linear discriminant analysis effect size method, gut dysbiosis was observed in those with anxiety (Bacteroidetes and Proteobacteria, effect size 4.8), abdominal pain (Fusobacteria, Staphylococcus, Megamonas and Plesiomonas, effect size 4.0) and IBS (Plesiomonas and Trabulsiella, effect size 3.0). Conclusion Disturbed gut microbiota because of environmentally-derived organisms may explain persistent abdominal pain and IBS after a major environmental disaster in the presence of poor WaSH practices.

Abstract Background In clinical practice, assessment of constipation depends on reliability, consistency and frequency of several commonly reported or core symptoms. It is not known if frequency patterns of constipation symptoms in adults are different between the West and the East. This review aimed to describe core constipation symptoms and their frequency patterns among the Asian adults. Methods Articles published in PubMed, MEDLINE, CINAHL and Science Direct from 2005 to 2015 were searched systematically. Studies were included if constipation satisfied the Rome II and or III criteria. Study populations consisted of Asian adults above 18 years old and with sample size above 50. Results Of 2812 articles screened, 11 met the eligibility criteria. Constipation among Asian adults was characterized by three core symptoms of ‘straining’ at 82.8%, ‘lumpy and hard stool’ at 74.2% and ‘sensation of incomplete evacuation’ at 68.1% and the least frequent symptom was ‘manual maneuver to facilitate defecation’ at 23.3%. There was heterogeneity in frequency patterns of core symptoms between different Asian studies but also differences in core symptoms between constipation subtypes of functional constipation and irritable bowel syndrome with constipation. Conclusions In general, Asian adults perceive constipation symptoms in a similar but not equivalent manner to the West. Recognition of core symptoms will increase the diagnostic confidence of constipation and its subtypes but more studies of the various specific Asian populations are needed to address their differences.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Proton pump inhibitors (PPI) are one of the most widely prescribed drugs worldwide. They are the mainstay for treatment of most gastric acid-related disorders. PPIs are often used for inappropriate indications and unnecessarily prolonged durations. Initially thought to be a very safe class of drugs, concerns have been raised with regard to an increased risk of adverse events thought to be related to the long-term use of PPIs. PPIs are now known to be associated with increased risk of osteoporotic fractures, nutritional deficiencies (vitamin B12, magnesium, and iron), myocardial infarction, Clostridium difficile infection, community-acquired pneumonia, and gastric neoplasia. More recent evidence has shown that PPI use is also associated with renal impairment and dementia. Although these associations do not necessarily imply a causal link, PPIs should be used for the correct indications and for an appropriate duration. Prolonged use should be discouraged unless the benefits of treatment clearly outweigh the associated risks. More studies are needed to further explore these associations and to establish causality if present.

Irritable bowel syndrome (IBS), a common gastrointestinal disorder involving the gut-brain axis, and inflammatory bowel disease (IBD), a chronic relapsing inflammatory disorder, are both increasing in incidence and prevalence in Asia. Both have significant overlap in terms of symptoms, pathophysiology, and treatment, suggesting the possibility of IBS and IBD being a single disease entity albeit at opposite ends of the spectrum. We examined the similarities and differences in IBS and IBD, and offer new thoughts and approaches to the disease paradigm.

Background: The new coronavirus disease (COVID-19) has high infection and mortality rates, and has become a pandemic. The infection and mortality rates are lower in Asian countries than in European countries. This study aimed to conduct a survey on the effects of COVID-19 on the capacity to perform gastrointestinal motility tests in Asian countries compared with European countries. Methods: We used the questionnaire previously established by our team for researchers in European countries. The correlation between the decreased rate of gastrointestinal motility and function tests, and the infection/mortality rates of COVID-19 and stringency of a government’s interventions in each country was analysed and protective measures were assessed. Results: In total, 58 gastroenterologists/motility experts in Asian countries responded to this survey. The infection/mortality rates of COVID-19 and Stringency Index had a significant impact on the testing capacity of oesophageal manometry and catheter-based pH monitoring. In European countries, most facilities used filtering facepiece 2/3 (FFP2/3) masks during oesophageal motility studies. Meanwhile, in Asian countries, most facilities used surgical masks. Conclusion: The total infection and mortality rates of COVID-19 can affect the rate of gastrointestinal motility testing and the type of protective equipment that must be used.

In many developing countries, jaundice is the common symptom of hepatic diseases which are a major cause of mortality. The use of natural product-based therapies is very popular for such hepatic disorders. A great number of medicinal plants have been utilized for this purpose and some facilitated the discovery of active compounds which helped the development of new synthetic drugs against jaundice. However, more epidemiological studies and clinical trials are required for the practical implementation of the plant pharmacotherapy of jaundice. The focus of this second part of our review is on several of the most prominent plants used against jaundice identified in the analysis performed in the first part of the review viz. Andrographis paniculata (Burm.f.) Nees, Silybum marianum (L.) Gaertn., Terminalia chebula Retz., Glycyrrhiza glabra L. and some species of genus Phyllanthus. Furthermore, we discuss their physiological effects, biologically active ingredients, and the potential mechanisms of action. Some of the most important active ingredients were silybin (also recommended by German commission), phyllanthin and andrographolide, whose action leads to bilirubin reduction and normalization of the levels of relevant serum enzymes indicative for the pathophysiological status of the liver.

Purpose: This study compared pain sensitivity among opioid dependent patients on methadone maintenance therapy (MMT) and opioid naive subjects. Methods: The three hundred participants comprised 152 opioid naive subjects and 148 opioid dependent patients. Opioid naive subjects had not taken any opioids including morphine and methadone to their best knowledge and were presumed so after two consecutive negative urine screenings for drugs. All opioid dependent patients were stabilized in treatment, defined as having been enrolled in the program for more than one month with no change of methadone dosage over the past one month. Excluded from the study were individuals with chronic or ongoing acute pain and individuals with a history of analgesics ingestion within 3 d before the cold pressor test (CPT). Pain tolerance to CPT was evaluated at 0 h, and at 2, 4, 8, 12, and 24 h post-methadone dose. Results: Patients exhibited a significantly shorter mean pain tolerance time of 34.17 s (95% CI 24.86, 43.49) versus 61.36 (52.23, 70.48) [p < 0.001] compared with opioid naive subjects. Time-dependent mean pain tolerance was also significantly different when naive subjects were compared to patients (p = 0.016). Conclusions: This study revealed hyperalgesia amongst patients on MMT, as manifested by their quicker hand withdrawal. The complaints of pain in this population should not be underestimated and the pain should be evaluated seriously and managed aggressively. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Aim. Poor sleep quality due to pain has been reported among opioid-dependent male patients on methadone maintenance therapy (MMT) but objective pain data are lacking. This study aimed to investigate the rate of pain-sensitivity using cold pressor test (CPT) and the relationship between pain-sensitivity and sleep quality in this population.Methods. A total of 168 male participants were included into the study. Objective pain-tolerance was evaluated at 0 h and at 24 h after the first CPT. Malay version of the Pittsburgh Sleep Quality Index (PSQI) and the subjective opiate withdrawal scale (SOWS) questionnaires were administered to evaluate the quality of sleep and withdrawal symptoms, respectively.Results. The mean age of study participants was 37.22 (SD 6.20) years old. Mean daily methadone dose was 76.64 (SD 37.63) mg/day, mean global PSQI score was 5.47 (SD 2.74) and mean averaged SOWS score was 5.43 (SD 6.91). The averaged pain-tolerance time ranged from 7 to 300 s with a mean time of 32.16 (SE 2.72) s, slightly below the cut-off score of 37.53 s. More specifically, 78.6% (n = 132) of participants were identified as pain-sensitive (averaged pain-tolerance time ≤37.53 s), and 36 (21.4%) participants were pain-tolerant (averaged pain-tolerance time >37.53 s). The pain-sensitive group reported poorer sleep quality with mean (SD) PSQI of 5.78 (2.80) compared with the pain-tolerant group with mean (SD) PSQI of 4.31 (2.18) (p = 0.005). With analysis of covariance, pain-sensitive group was found to have higher global PSQI scores (adjusted mean 5.76, 95% CI 5.29; 6.22) than pain-tolerant participants (adjusted mean 4.42, 95% CI 3.52; 5.32) (p = 0.010).Conclusions. Majority of opioid-dependent male patients on methadone treatment are pain-sensitive with CPT. Poor sleep quality is associated with cold pressor pain-sensitivity. Pain and sleep complaints in this male population should not be overlooked.

Aim. Helicobacter pylori (H. pylori) infection is exceptionally rare in population from the north-eastern region of Peninsular Malaysia. This provides us an opportunity to contemplate the future without H. pylori in acute non-variceal upper gastrointestinal (GI) bleeding.Methods. All cases in the GI registry with GI bleeding between 2003 and 2006 were reviewed. Cases with confirmed non-variceal aetiology were analysed. Rockall score > 5 was considered high risk for bleeding and primary outcomes studied were in-hospital mortality, recurrent bleeding and need for surgery.Results. The incidence of non-variceal upper GI bleeding was 2.2/100,000 person-years. Peptic ulcer bleeding was the most common aetiology (1.8/100,000 person-years). In-hospital mortality (3.6%), recurrent bleeding (9.6%) and need for surgery (4.0%) were uncommon in this population with a largely low risk score (85.2% with score ≤5). Elderly were at greater risk for bleeding (mean 68.5 years, P = 0.01) especially in the presence of duodenal ulcers (P = 0.04) despite gastric ulcers being more common. NSAIDs, aspirin and co-morbidities were the main risk factors.Conclusions. The absence of H. pylori infection may not reduce the risk of peptic ulcer bleeding in the presence of risk factors especially offending drugs in the elderly.

BACKGROUND: A few studies have indicated inverse relationships between serum ghrelin and gastric and esophageal cancers but those associations have been restricted to specific populations, including smokers and overweight individuals. We examined the association between ghrelin and gastroesophageal cancers and atrophic gastritis in a population-based setting. METHODS: In total 220 gastroesophageal cancers, comprising non-cardia and cardia gastric cancer, esophageal adenocarcinoma, esophageal squamous cell carcinoma (SCC) and age and gender-matched controls were recruited. Serum ghrelin, pepsinogen I/II ratio (PGI/II) and anti-H.pylori IgG antibodies were measured. Relationships between ghrelin and gastroesophageal cancers, after adjustment for PGI/II ratio, H.pylori status and smoking, were tested using logistic regression. Furthermore, in 125 endoscopically normal volunteers, with and without histological atrophic gastritis, the relationship with ghrelin was compared. RESULTS: Serum ghrelin (lowest vs. highest quintile) was inversely associated with gastric cancer: OR (95% CI) 8.71 (1.70-44.59) for cardia and 6.58 (1.26-34.46) for non-cardia cancer. Lower serum ghrelin was also associated with esophageal SCC: OR (95% CI) 5.69 (1.36-23.78), but not with esophageal adenocarcinoma. A similar association was observed between gastric cancer (cardia and non-cardia) and esophageal SCC when serum ghrelin was analysed as a continuous scaled variable. In endoscopically-normal volunteers, extensive atrophic gastritis was associated with low serum ghrelin [OR (95% CI) 0.25 (0.10-0.64)]. CONCLUSION: Inverse associations between ghrelin and some gastroesophageal cancers suggest a potential role for serum ghrelin as a biomarker of upper gastrointestinal cancers and atrophic gastritis. In areas with a high incidence of gastric and/or esophageal cancer, screening might be more effectively targeted to individuals with low serum ghrelin in addition to the PGI/II ratio.

We report a 33-year-old Malay woman presented with acute left dense hemiparesis and an NIHSS score of 11/15. Computed tomography (CT) scan brain showed a massive right middle cerebral artery (MCA) territory infarct. The right internal carotid artery (ICA) and right proximal MCA were shown occluded from digital substraction angiography (DSA). Carotid dissection, carotid canal anomaly, and intercavernous communication were systematically ruled out. She had no risk factors for atherosclerosis. The connective tissue screening and thrombophilic markers were negative. However, she was anaemic on admission and subsequent investigations revealed that she had alpha-thalassemia and iron deficiency anaemia. The right ICA remained occluded from a repeat CT cerebral angiogram after one year, but otherwise she was neurologically stable. This case illustrates an unusual association between intracranial vessel occlusion with iron deficiency anaemia and alpha-thalassemia trait.

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