Search

Introduction: Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) is being increasingly used as a screening tool to predict varices. Our aim was to test the utility of Baveno VII criteria and other combinations of LSM, platelet count (PC), and splenic stiffness measurement (SSM) to predict the presence of varices in a cohort of Sri Lankan patients with compensated advanced liver cell disease (cALCD)., Methods: Consecutive patients with newly diagnosed Child-Pugh class A cALCD (non-viral, BMI<30) were recruited prospectively. They underwent gastroscopy. LSM and SSM were taken using vibration-controlled transient elastography (VCTE) (Echosens FibroScan 502 Touch; Echosens SA, Paris, France) by a single operator who was unaware of endoscopy findings. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of different Baveno VII criteria to predict the varices and different combinations of LSM, SSM, and PC were also explored., Results: One hundred and seventy-four individuals were recruited. The mean age was 61.4 ((95% CI: 59.7-62.8) years. A total of 110 individuals were males, and 106 had varices. Our results indicated that the three Baveno VII criteria had sensitivities of 61%, 63%, and 42%, and specificities of 79%, 77%, and 87% to predict varices. SSM>30kPa alone and in combination with LSM>15kPa had sensitivities of 81 and 75%, specificities of 72 and 83%, PPVs of 82 and 87%, NPVs of 71% and 67%, and accuracies of 78 and 78%, respectively, to predict varices., Conclusion: Baveno VII criteria had a low sensitivity but high specificity in predicting the presence of varices. However, SSM>30kPa alone or in combination with LSM>15kPa had better sensitivity, specificity, PPV, NPV, and accuracy in predicting varices., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics review Committee, Faculty of Medicine, University of Kelaniya, Sri Lanka issued approval P188/11/2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, de Silva et al.)

Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Iron is the leading cause of liver damage in patients with transfusion-dependent thalassaemia (TDT), and data on the contribution of NAFLD to liver damage in TDT is lacking. Forty-five heavily transfused TDT patients who did not have biochemical or ultrasonic evidence of liver cirrhosis were evaluated for effects of iron overload, including the presence of diabetes mellitus, hypogonadism, serum ferritin, R2-MRI-liver, and liver enzymes alanine aminotransferase and aspartate aminotransferase. Liver fibrosis and steatosis were estimated using transient elastography (TE). Nine (20%) patients had significant steatosis (S1), and their body mass index (BMI) and liver fibrosis scores were higher than in patients without significant steatosis (S0) (p = 0.03 and p = 0.004, respectively). On regression analysis, the controlled attenuation parameter (CAP) score (i.e., degree of liver steatosis) was associated only with increasing BMI. The TE score (i.e., degree of liver fibrosis) was associated with increasing age, CAP score, male gender, and presence of diabetes. Neither liver steatosis nor fibrosis showed significant association with the liver iron concentration or iron-related organ damage (hypogonadism). In this cohort of TDT patients, steatosis of the liver, which is associated with increasing BMI, appeared to increase the risk of liver fibrosis., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Coronavirus disease 2019 (COVID-19) may cause clinical manifestations that last for weeks or months after hospital discharge. The manifestations are heterogeneous and vary in their frequency. Their multisystem nature requires a holistic approach to management. There are sparse data from the South Asian region on the outcomes of hospital-discharged COVID-19 patients. We assessed the posthospital discharge outcomes of a cohort of Sri Lankan COVID-19 patients and explored the factors that influenced these outcomes., Methods: Data were prospectively collected from patients who were discharged following an admission to the Nawaloka Hospital, Sri Lanka with COVID-19 from March to June 2021. At discharge, their demographic, clinical and laboratory findings were recorded. The patients were categorised as having mild, moderate and severe COVID-19, based on the Sri Lanka Ministry of Health COVID-19 guidelines. Following discharge, information on health status, complications and outcomes was collected through clinic visits and preplanned telephone interviews. A validated (in Sri Lanka) version of the Short Form 36 health survey questionnaire (SF-36) was used to assess multi-item dimensions health status of the patients at 1, 2 and 3 mo postdischarge., Results: We collected data on 203 patients (male, n=111 [54.7%]). The level of vaccination was significantly associated with disease severity (p<0.001). Early recovery was seen in the mild group compared with the moderate and severe groups. At 3 mo, on average 98% of mild and 90% of moderate/severe patients had recovered. Based on the SF-36, physical functioning dimensions, role limitation due to physical and emotional health, energy/ fatigue, emotional well-being, social functioning, pain and general health were significantly different in the moderate/severe vs mild COVID-19 groups at 1, 2 and 3 mo postdischarge (p<0.05). Twenty-three patients developed complications, of which the most common were myocardial infarction with heart failure (n=6/23; 26.1%), cerebrovascular accident (n=6/23; 26.1%) and respiratory tract infections (n=3/23; 13.01%) and there were six deaths., Conclusions: In our cohort, receiving two doses of the COVID-19 vaccine was associated with reduced disease severity. Those with mild disease recovered faster than those with moderate/severe disease. At 3 mo posthospital discharge, >90% had recovered., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Objective: To evaluate the performance of the fibrosis-4 (FIB-4) score as a screening tool to detect significant liver fibrosis (F2) compared with transient elastography (TE), among chronic transfusion-dependent beta-thalassaemia (TDT) patients in a resource-poor setting., Design: A cross-sectional study., Setting: Adolescent and Adult Thalassaemia Care Centre (University Medical Unit), Kiribathgoda, Sri Lanka., Participants: 45 TDT patients who had undergone more than 100 blood transfusions with elevated serum ferritin >2000 ng/mL were selected for the study. Patients who were serologically positive for hepatitis C antibodies were excluded., Outcome Measures: TE and FIB-4 scores were estimated at the time of recruitment in all participants. Predefined cut-off values for F2, extracted from previous TE and FIB-4 scores studies, were compared. A new cut-off value for the FIB-4 score was estimated using receiver operating characteristics curve analysis to improve the sensitivity for F2 prediction., Results: Of the selected 45 TDT patients, 22 (49%) were males. FIB-4 score showed a significant linear correlation with TE (r=0.52;p<0.0003). The FIB-4 score was improbable to lead to a false classification of TDT patients to have F2 when the FIB-4 cut-off value was 1.3. On the other hand, it had a very low diagnostic yield in missing almost all (except one) of those who had F2. Using a much-lowered cut-off point of 0.32 for FIB-4, we improved the pick-up rate of F2 to 72%., Conclusions: Regardless of the cut-off point, the FIB-4 score cannot be used as a good screening tool to pick up F2 in patients with TDT, irrespective of their splenectomy status. On the contrary, at a 1.3 cut-off value, though FIB-4 is a very poor detector for F2 fibrosis, it will not erroneously diagnose F2 fibrosis in those who do not have it., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is currently no clinically validated biomarker to predict respiratory compromise in sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cycle threshold time (Ct), absolute lymphocyte count (AL) and neutrophil:lymphocyte ratio (NLR) have been previously evaluated for this purpose. We hypothesized that the combination of these parameters at presentation may be predictive of hypoxia (oxygen saturation <92%)., Methods: Data were collected on 118 patients with SARS-CoV-2 infection between May 2020 and April 2021. Demographics, clinical parameters and laboratory and radiological investigation results were recorded. Respiratory compromise (RC) was defined based on symptoms and signs, hypoxia and chest X-ray abnormalities., Results: RC occurred in 61 (51.7%) of patients. The Ct, AL and NLR at median day 3 of illness were significantly different between patients with and without RC (Ct, RC vs not: 19.46±2.64 vs 22.62±3.37, p=0.0001; AL, RC vs not: 531.49±289.09 vs 764.69±481.79, p=0.0001; NLR, RC vs not: 3.42±0.75 vs 2.59±0.55, p=0.0001). Receiver operating characteristics analysis showed that a Ct <19.9, AL <630.8×103/μL and NLR >3.12 at median day 3 of symptoms was predictive of hypoxia on day 7 of illness (area under the curve 0.805, sensitivity 96.7%, specificity 69.1%). The predictive value for the parameters combined was significantly superior to their individual predictive power., Conclusions: Ct, AL and NLR used in combination on day 3 of symptoms are predictive of hypoxia on day 7 of SARS-CoV-2 illness., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Childhood obesity is a global problem associated with metabolic abnormalities. The gut-liver axis is thought to play a major role in its pathogenesis. Probiotics are known to alter the gut microbiota and, therefore, could be a therapeutic option in the management of childhood obesity-related complications., Purpose: This double-blind randomized placebo-controlled trial evaluated the effects of probiotics on metabolic derangement in obese children with nonalcoholic fatty liver disease/ nonalcoholic steatohepatitis (NAFLD/NASH)., Methods: Obese children with NAFLD/NASH treated at the nutrition clinic of the University Paediatric Unit at Lady Ridgeway Hospital, Colombo, were recruited. Anthropometry, body fat, metabolic derangement, and liver ultrasound scan (USS) results were evaluated at baseline and after 6 months. Transient elastography (FibroScan) was performed on a subsample of these patients. Eighty-four patients were recruited and randomized into the probiotics (n=43) and placebo (n= 41) groups. The mean age was 11.3±1.9 versus 12.1±1.5 years in the probiotic and placebo groups, respectively. Baseline parameters including liver disease stage on USS, body fat percentage, fasting blood sugar, lipid profile, liver function, and C-reactive protein showed no significant intergroup differences., Results: In the probiotic group, a statistically significant reduction in body mass index was noted from the baseline value. However, the reduction was not significant compared with the placebo group. There was a significant reduction in triglycerides, aspartate transaminase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and alkaline phosphatase in the placebo group over the treatment period. Although the liver disease stage on USS improved from stage II-III to stage I in a small number of patients in the probiotic-treated group, transient elastography performed in a subsample did not demonstrate significant improvement in either group., Conclusion: Our results indicate that probiotics have no advantage over lifestyle modification for improving obesityassociated metabolic derangement in children.

Background and Aim: Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce., Methods: We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita., Results: Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year., Conclusions: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Chronic nausea and vomiting (CNV) are commonly encountered symptoms in medical practice. CNV is the presenting symptom in a variety of gastrointestinal and non-gastrointestinal disorders. However, in a significant percentage of patients without an obvious underlying cause, CNV poses a significant diagnostic challenge to the evaluating physician., Areas Covered: A comprehensive clinical history and physical examination form the foundation for further diagnostic work-up. In the present review, we discuss the diagnostic approach to CNV, highlighting the epidemiology, pathophysiology, causes, and modes of evaluation of this condition. Specific investigations, carefully guided by clinical assessment and tailored for each patient, would be more beneficial in diagnosing CNV than empirically performing a blanket of investigations., Expert Opinion: Whilst CNV remains a historically challenging diagnostic and therapeutic dilemma, research into this topic is limited. Hence, there is a growing call for more research into diagnostic modalities for CNV. With scientific advancement and further research, it is hoped that easy-to-use, cheap, noninvasive novel diagnostic modalities for CNV will be available soon.

Introduction: One of the main issues in the novel coronavirus 2019 (COVID-19) pandemic has been the lack of uniformity of recommendations for the usage of face masks., Areas Covered: While Asian countries started using masks early during the epidemic, most Western countries were slow to do so. To avoid such situations, clear guidelines, need to be established, not only regarding the use of masks but also the type of mask to suit different situations. In this article, we will examine the types of masks and review the recommendations for their use based on the available evidence for each type of mask., Expert Opinion: We explore future needs in research-related mask use in COVID-19 pandemic, improvements to be made in mask design, adopting guidelines for the use of masks and the psycho-social aspects of widespread and prolonged mask use.

Background: The first case of a coronavirus 2019 (COVID-19) infection in a Sri Lankan was reported on March 11, 2020. The situation in Sri Lanka changed with the rapid increase of personnel contracting COVID-19 in a naval base camp that housed more than 4000 people. This provided a unique opportunity to study the effectiveness of hydroxychloroquine (HCQ) for post-exposure prophylaxis (PEP), while taking stringent, non-pharmacologic, public health measures to prevent spread. Our aim is to study the effectiveness and safety of HCQ for PEP among naval personnel with exposure to COVID-19-positive patients., Methods/design: This is a placebo-controlled, randomized, clinical trial carried out in the naval base camp and quarantine centers of the Sri Lanka Navy, Ministry of Defense, Sri Lanka. Navy personnel who are exposed to a patient with confirmed COVID-19 infection but test negative for the virus on reverse real-time polymerase chain reaction (rRT-PCR) at recruitment will be randomized, 200 to each arm, to receive HCQ or placebo and monitored for the development of symptoms or rRT-PCR positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus for 14 days., Discussion: This trial will provide high-quality evidence of the effectiveness and safety of HCQ as PEP for COVID-19. The study design is unique due to the circumstances of the outbreak in a confined area among otherwise healthy adults, at a relatively early stage of its spread., Trial Registration: Sri Lanka Clinical Trials Registry (SLCTR) SLCTR/2020/011 . Registered on 04 May 2020.

Background: The role of steroids in dengue infection (DI) remains uncertain., Methods: A retrospective chart review was conducted on patients ≥18 y of age diagnosed with DI based on positivity for dengue non-structural antigen 1 or immunoglobulin M between October 2017 and November 2018., Results: Hydrocortisone was administered to 106 of 406 patients. DI with warning signs occurred in nine patients (9.5%) in the steroid cohort and eight patients (2.5%) in the non-steroid group. The incidence of severe DI, bleeding and admission duration were similar between the groups., Conclusions: Our study shows no significant benefit of empirical steroids in DI., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background and Aim: Melatonin is used to treat sleep disturbances (SDs). The aim of this study was to investigate the safety and efficacy of low-dose melatonin for SDs in early-stage cirrhosis., Methods: In a single-center, randomized, double-blind, placebo-controlled, cross-over clinical trial, patients with early-stage (Child-Turcotte-Pugh [CTP] class A or B) cirrhosis with SDs, without hepatic encephalopathy, were randomized to placebo or 3 mg of melatonin for 2 weeks. After 2 weeks, the patients were given a washout period of 1 week and crossed over to melatonin or placebo for a further 2 weeks. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to measure sleep quality and daytime sleepiness, respectively. Analysis of results was based on intention to treat, and linear mixed-effect models were used to evaluate the effect of melatonin. Analysis was conducted using R-programming language 3.5.1., Results: Seventy one patients were recruited (mean age: 61.9 ± 8.7 years, males: 46 [64.8%], and CTP Class A = 52 [73.2%] and Class B = 19 [26.8%]). Sixty patients completed the study (mean age: 61.7 ± 8.8 years, males: 40 [66.6%], and CTP Class A = 45 [75.0%] and Class-B = 15 [25.0%]). Two patients dropped out due to adverse events. Nine patients were lost to follow up. Patients given melatonin had a significantly lower PSQI and ESS compared to both pretreatment ( P  < 0.001) and postplacebo scores ( P  < 0.001). Incidence of adverse events was similar (two each of abdominal pain, one each of headache, one each of dizziness) in both groups., Conclusion: Melatonin seems safe and effective for use in patients with SDs in early-stage cirrhosis in the short term. However, larger and longer-term studies to assess efficacy and safety are required before its clinical use can be recommended., (© 2020 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Data on outcomes of non-alcoholic fatty liver disease (NAFLD) from South Asia are lacking. We compared mortality, among those with- and without-NAFLD, after 10-years follow-up among urban, adult Sri Lankans., Method: Participants (aged 35-64 years), selected by age-stratified random sampling, were screened by structured-interview in 2007. Anthropometric measurements, liver ultrasonography and biochemical/serological tests were done. NAFLD was diagnosed on ultrasound criteria, safe-alcohol consumption (Asian-standards) and absence of hepatitis B/C. Subjects without NAFLD were those without any ultrasound criteria of fatty liver, safe-alcohol consumption and absence of hepatitis B/C. The cohort was re-evaluated to assess mortality in 2017. Participants or their households were contacted by telephone/post, and deaths confirmed by home-visits and death certificate review. Cox-regression was used to determine predictors of all-cause mortality (ACM) and cardiovascular mortality (CVM) in those with- and without-NAFLD., Results: 2724 (91.2%) of 2985 original participants were contacted (851-with NAFLD and 1072-without NAFLD). Overall there were 169 (6.2%) deaths [41-deaths among NAFLD (17-cardiovascular; 9-cancer-related; 4-liver-specific; 11-other) and 79-deaths among no-NAFLD (28-cardiovascular; 17-cancer-related; 1-liver-specific; 33-other)]. Metabolic syndrome (MetS), low-education level, higher age and male-gender independently predicted ACM. MetS, increasing age and male-gender independently predicted CVM. NAFLD did not predict either ACM or CVM. In those with NAFLD, MetS and age >55-years were independently associated with ACM, while MetS and male-gender were associated with CVM., Conclusion: In this community-based study, increasing age, male-gender and MetS, but not NAFLD, predicted 10-year ACM and CVM. Among those with NAFLD, only those metabolically abnormal were at a higher risk for mortality., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy., Methods: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years., Findings: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (-28·67 to 5714·24) per DALY averted over a 10-year period., Interpretation: Compared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension management in Sri Lanka should be supported to address the high population burden of cardiovascular disease., Funding: Australian National Health and Medical Research Council., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The metabolic syndrome (MetS) is a clustering of abdominal obesity, diabetes and prediabetes, high cholesterol and high blood pressure, that confers an increased risk of cardiovascular disease. There is limited data on incidence of MetS from South Asia. This study investigated incidence and risk factors for new onset MetS in an urban adult Sri Lankan population., Methods: Subjects (selected by age-stratified random sampling from the Ragama Medical Officer of Health area) were screened initially in 2007 (35-64 years) and re-evaluated in 2014 (42-71 years). On both occasions they were assessed by structured interview, anthropometric measurements, liver ultrasound, and biochemical/serological tests. MetS was diagnosed on International Diabetes Federation (IDF-2006) criteria. Total body fat (TBF) and visceral fat percentage (VFP) were measured in 2014, using body impedance method. Incidence and factors at baseline, associated with new onset MetS, were investigated among those who presented for re-evaluation., Results: 2985 (99.1%) [1636 (54.8%) women (54.8%); median age (IQR) 53 (47-59) years] from the initial cohort in 2007 had complete data. 2148 (71.9%) [1237 (57.6%) women; median age (IQR) 60 (54-66) years] attended follow-up. 949 of them [701 (73.9%) women; median age (IQR) 60 (54-65) years] had MetS (prevalence 47.2%, 95% CI 45.0-49.4%). Of 1246 who did not have MetS in 2007, 265 [178 (67.1%) women, median age (IQR) 57 (51-64) years] had developed MetS after 7 years (annual incidence 3.5% (95% CI 2.4-4.5%). Females (OR = 4.9, 95% CI 3.4-7.4), BMI > 23 kg/m 2 in 2007 (OR = 1.6 per unit increase, 95% CI 1.5-1.7), weight gain (by 2-5% OR = 2.0, 95% CI 1.1-3.5; by > 5% OR = 2.2, 95% CI 1.4-3.4), and increase in waist circumference (by 2-5% OR = 7.0, 95% CI 4.0-12.2; by > 5% OR = 13.4, 95% CI 8.3-22.4) from baseline and presence of non-alcoholic fatty liver disease (NAFLD) in 2007 (OR = 1.70, 95% CI 1.04-2.76) were associated new onset MetS. Those with MetS had abnormal VFP and TBF in 2014 [P < 0.001]., Conclusion: In this study, annual incidence of MetS was 3.5%. Female gender, BMI > 23 kg/m 2 and NAFLD in 2007 and increase in weight and waist circumference from baseline were significantly associated with new onset MetS. Obesity was the best predictor of future MetS., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Importance: Poorly controlled hypertension is a leading global public health problem requiring new treatment strategies., Objective: To assess whether a low-dose triple combination antihypertensive medication would achieve better blood pressure (BP) control vs usual care., Design, Setting, and Participants: Randomized, open-label trial of a low-dose triple BP therapy vs usual care for adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg; or in patients with diabetes or chronic kidney disease: >130 mm Hg and/or >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017., Interventions: A once-daily fixed-dose triple combination pill (20 mg of telmisartan, 2.5 mg of amlodipine, and 12.5 mg of chlorthalidone) therapy (n = 349) or usual care (n = 351)., Main Outcomes and Measures: The primary outcome was the proportion achieving target systolic/diastolic BP (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes or chronic kidney disease) at 6 months. Secondary outcomes included mean systolic/diastolic BP difference during follow-up and withdrawal of BP medications due to an adverse event., Results: Among 700 randomized patients (mean age, 56 years; 58% women; 29% had diabetes; mean baseline systolic/diastolic BP, 154/90 mm Hg), 675 (96%) completed the trial. The triple combination pill increased the proportion achieving target BP vs usual care at 6 months (70% vs 55%, respectively; risk difference, 12.7% [95% CI, 3.2% to 22.0%]; P < .001). Mean systolic/diastolic BP at 6 months was 125/76 mm Hg for the triple combination pill vs 134/81 mm Hg for usual care (adjusted difference in postrandomization BP over the entire follow-up: systolic BP, -9.8 [95% CI, -7.9 to -11.6] mm Hg; diastolic BP, -5.0 [95% CI, -3.9 to -6.1] mm Hg; P < .001 for both comparisons). Overall, 419 adverse events were reported in 255 patients (38.1% for triple combination pill vs 34.8% for usual care) with the most common being musculoskeletal pain (6.0% and 8.0%, respectively) and dizziness, presyncope, or syncope (5.2% and 2.8%). There were no significant between-group differences in the proportion of patient withdrawal from BP-lowering therapy due to adverse events (6.6% for triple combination pill vs 6.8% for usual care)., Conclusions and Relevance: Among patients with mild to moderate hypertension, treatment with a pill containing low doses of 3 antihypertensive drugs led to an increased proportion of patients achieving their target BP goal vs usual care. Use of such medication as initial therapy or to replace monotherapy may be an effective way to improve BP control., Trial Registration: anzctr.org.au Identifier: ACTRN12612001120864; slctr.lk Identifier: SLCTR/2015/020.

Background: Nonalcoholic fatty liver disease (NAFLD) is a common problem across the world. We aimed to determine the prevalence of NAFLD and its associations in Sri Lankan adolescents living in an urban Sri Lankan community., Method: The study population consisted of the birth cohort of the year 2000, residing in the Ragama Medical Officer of Health area. Socio-demographic and anthropometric data [anthropometric measurements, blood pressure and total body fat distribution] of these adolescents were collected by trained data collectors. Fasting blood sugar, serum insulin, fasting serum lipids and serum alanine aminotransferase (ALT) levels were measured and an abdominal ultrasound was performed. NAFLD was diagnosed on established ultrasound criteria for fatty liver and absent alcohol consumption., Results: The study sample consisted of 499 adolescents [263 (51.8%) girls]. Forty two (8.4%) had NAFLD. NAFLD was significantly associated with being breast fed for less than 4 months (33.3% vs. 17.1 in controls, p = 0.02), higher waist circumference (prevalence risk ratio 83.3/20.3, 4.1, p < 0.0001), higher body mass index (prevalence risk ratio 40.5/4.8, 8.4, p < 0/0001),higher HOMA-IR (3.7 vs. 1.9, p < 0.0001) and high triglycerides (prevalence risk ratio 14.3/5.8, 2.5, p = 0.033). Adolescents with NAFLD also had a higher amount of total body fat (p < 0.001) and subcutaneous fat (p < 0.001) than those without NAFLD. The number of children with metabolic derangements was higher among adolescents with NAFLD than those without (85.8 vs 26.3 in controls, p < 0.0001), but a family history of hypertension, diabetes, myocardial infarction or dyslipidaemia were not., Conclusion: Prevalence of NAFLD was high in Sri Lankan adolescents, and was associated with metabolic derangements, especially obesity, insulin resistance and early cessation of breast feeding.

Background: This study investigated incidence and risk factors for NAFLD among an adult cohort with 7-year follow-up., Methods: The study population (age-stratified random sampling, Ragama MOH area) was screened initially in 2007 (aged 35-64 years) and re-evaluated in 2014 (aged 42-71 years). On both occasions assessed by structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. NAFLD was diagnosed on ultrasound criteria, safe alcohol consumption and absence of hepatitis B/C markers. Non-NAFLD controls did not have any ultrasound criteria for NAFLD. An updated case-control genetic association study for 10 selected genetic variants and NAFLD was also performed., Results: Out of 2985 of the original cohort, 2148 (72.0%) attended follow-up (1238 [57.6%] women; mean-age 59.2 [SD-7.6] years) in 2014, when 1320 (61.5%) were deemed NAFLD subjects. Out of 778 who initially did not have NAFLD and were not heavy drinkers throughout follow-up, 338 (43.4%) (221 [65.4%] women, mean-age 57.8 [SD-8.0] years) had developed NAFLD after 7-years (annual incidence-6.2%). Central obesity (OR=3.82 [95%-CI 2.09-6.99]), waist increase >5% (OR=2.46 [95%-CI 1.20-5.05]) overweight (OR=3.26 [95%-CI 1.90-5.60]), weight gain 5%-10% (OR=5.70 [95%-CI 2.61-12.47]), weight gain >10% (OR=16.94 [95%-CI 6.88-41.73]), raised plasma triglycerides (OR=1.96 [95%-CI 1.16-3.29]) and diabetes (OR=2.14 [95%-CI 1.13-4.06]), independently predicted the development of incident NAFLD in multivariate analysis. The updated genetic association study (1362-cases, 392-controls) showed replicated association (P=.045, 1-tailed) with NAFLD at a candidate locus: PNPLA3 (rs738409)., Conclusions: In this community cohort study, the annual incidence of NAFLD was 6.2%. Incident NAFLD was associated with general and central obesity, raised triglycerides and diabetes, and showed a tendency of association with PNPLA3 gene polymorphisms., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Crohn disease has low prevalence in Sri Lanka while compared to the West, while intestinal tuberculosis is common in the region. Since clinical, endoscopic and investigation features of Crohn disease overlap with intestinal tuberculosis, differentiating these two conditions becomes a dilemma for the clinician in the intestinal tuberculosis endemic setting. An 18-year old Sri Lankan Muslim female presented with chronic abdominal pain and weight loss. Colonoscopy revealed an ulcerated ileocaecal valve and a terminal ileal stricture. Biopsy confirmed Crohn disease with no supportive features to suggest intestinal tuberculosis. Despite treatment with adequate immunosuppression she failed to improve and underwent a limited right hemicolectomy and terminal ileal resection. Histology confirmed intestinal tuberculosis and she made full recover with 6 months of anti-tuberculosis treatment., Conclusion: This case illustrates the importance of reviewing the diagnosis to include intestinal tuberculosis in an endemic setting, when already diagnosed Crohn disease is treatment refractory.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is linked to metabolic syndrome, and is known to be associated with impaired fasting glycemia and diabetes mellitus. This prospective community-based study was conducted to determine the association between NAFLD and incidence of diabetes mellitus in an urban adult population in Sri Lanka., Methods: Participants of the Ragama Health Study cohort were assessed for NAFLD using established ultrasound criteria in 2007. Those who were free of diabetes at baseline were followed up for 3 years. Incidence rates of diabetes mellitus were compared between subjects with and without NAFLD at baseline., Results: Out of 2984 subjects, 926 had NAFLD and 676 had diabetes in 2007. Of the 2276 subjects who were free of diabetes in 2007, 1914 were re-assessed in 2010. After 3 years, 104 out of 528 subjects with NAFLD and 138 out of 1314 subjects without NAFLD had developed diabetes mellitus de novo. Incidence rates of diabetes were respectively 64.2 and 34 per 1000 person-years of follow up for those with and without NAFLD. NAFLD was an independent predictor of developing diabetes mellitus. Other independent predictors were impaired fasting glycemia and dyslipidemia., Conclusions: Subjects with ultrasonically diagnosed NAFLD have an increased risk of developing diabetes mellitus. Intervention for NAFLD through lifestyle modification may prevent progression of the current diabetes epidemic., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background: Asthmatics are known to have esophageal hypomotility. Vagal hypofunction and prolonged intra-esophageal acidification cause esophageal hypomotility. The contribution of gastroesophageal reflux (GER) and vagal function to esophageal motility in asthmatics is unclear. We studied the relationship between esophageal motility, GER and vagal function in a cohort of adult asthmatics., Methods: Thirty mild, stable asthmatics (ATS criteria) and 30 healthy volunteers underwent 24-hour ambulatory esophageal monitoring, manometry, autonomic function testing and GER symptom assessment. 27 asthmatics underwent gastroscopy. A vagal function score calculated from 3 tests (valsalva maneuver, heart rate response to deep breathing and to standing from supine position) was correlated with esophageal function parameters., Results: Asthmatics (mean age 34.8 (SD 8.4), 60% female) had more frequent GERD symptoms than controls (mean age 30.9 (SD 7.7), 50% female). 10/27 asthmatics had esophageal mucosal damage, 22 showed hypervagal response, none had a hyperadrenergic response. 14 asthmatics had ineffective esophageal motility. Higher GERD-score asthmatics had significantly fewer peristaltic and more simultaneous contractions than controls, and higher esophageal acid contact times than those with lower scores. All reflux parameters were significantly higher and acid clearance time prolonged in asthmatics than controls (p < 0.001, Mann-Whitney U test). There was no correlation between vagal function score and esophageal function parameters., Conclusions: A cohort of adult asthmatics was found to have peristaltic dysfunction and pathological GER, but otherwise normal esophageal motility. The peristaltic dysfunction seems to be associated with vagal hyperreactivity rather than vagal hypofunction.

Background: Ileal intubation is the gold standard for a complete colonoscopy. However, despite evidence of clinical benefit ileoscopy is not always attempted due to perceived technical difficulty. Our aim was to compare time taken for ileal intubation using a new position-the prone 12 o'clock position (PP) with the standard method (left lateral 6 o'clock position-LLP)., Methods: We performed a pilot study using fluoroscopy to determine the best patient position for ileal intubation. This was the prone 12 o'clock position. Patients were colonoscoped in the left lateral position and then randomized to ileal intubation in the 6 o'clock position(LL) or the 12 o'clock (PP) position., Results: 202 consecutive patients were referred for colonoscopy. Colonoscopy was performed on 150 patients [82 females, mean (SD) age 53 (16) years]. 75 patients were randomized for ileal intubation in the PP and 75 patients in the LLP. Overall, the ileum was successfully intubated in 145 (96%) patients [74 (98.7%) in the PP and 71 (94.7%) in the LLP]. The median (Interquartile Range) ileal intubation time was 12 (10) seconds in the PP and 87 (82) seconds in the LLP (p < 0.0001; Mann-Whitney U test). The ileum was abnormal in 11 (7.5%) patients., Conclusions: During colonoscopy, the prone 12 o'clock position gives a more direct approach to the ileo-caecal valve and significantly reduces ileal intubation time., Trial Registry: Sri Lanka Clinical Trial Registry Clinical trial registry number: SLCTR/2009/002.

Background: Insulin resistance (IR) plays a major role in the pathogenesis of metabolic syndrome. Acanthosis nigricans (AN) is an easily detectable skin condition that is strongly associated with IR. The aims of this study were, firstly, to investigate the prevalence of AN among adults in an urban Sri Lankan community and secondly, to describe its utility to detect metabolic syndrome., Findings: In a community based investigation, 35-64 year adults who were selected using stratified random sampling, underwent interview, clinical examination, liver ultrasound scanning, and biochemical and serological tests. Metabolic syndrome was diagnosed on revised ATP III criteria for Asian populations. AN was identified by the presence of dark, thick, velvety skin in the neck.2957 subjects were included in this analysis. The prevalence of AN, metabolic syndrome and type 2 diabetes mellitus were 17.4%, 34.8% and 19.6%, respectively. There was a strong association between AN and metabolic syndrome. The sensitivity, specificity, positive predictive value and negative predictive value of AN to detect metabolic syndrome were 28.2%, 89.0%, 45.9% and 79.0% for males, and 29.2%, 88.4%, 65.6% and 62.3% for females, respectively., Conclusions: AN was common in our study population, and although it did not have a high enough sensitivity to be utilized as a screening test for metabolic syndrome, the presence of AN strongly predicts metabolic syndrome.

Objective: Rice is the staple diet in many Asian countries. Current endoscopic guidelines advice a 6 h fast for solids and a 4 h fast for liquids before the procedure. However, these guidelines focus on a Western type diet. The aim of the study was to determine if a 6 h fast for rice is sufficient prior to upper gastrointestinal endoscopy (UGIE)., Patients and Methods: After informed consent, 212 patients referred for UGIE, who had no alarm symptoms, were randomized into two groups in preparation for UGIE. Fasting 6 h after a rice meal (R6) or fasting 10 h after a rice meal (R10). All meals contained lentils and an egg, and were isocaloric. Endoscopic vision was graded as poor, average, or good., Results: In the R10 group (n = 107) vision was poor in 2 (1.9%), average in 7 (6.5%), and good in 98 (91.6%). While in the R6 group (n = 105) vision was poor in 30 (28.6%), average in 19 (18.1%), good in 56 (53.3%). The observed difference of percentages among the two groups for endoscopic vision was significant (M-H Chi-Square for trend = 25.67; df = 1; p < 0.001)., Conclusions: Fasting for 6 h after a rice based meal seems inadequate for UGIE. Fasting for 10 h significantly improves endoscopic vision. Current guidelines need to be re-evaluated for populations where rice is the staple diet.

Background: There is a need for a practical instrument to screen for gastro-oesophageal reflux disease (GORD) in epidemiological studies., Objectives: To develop a practical score to detect GORD and compare assessment of both symptom frequency and severity with frequency alone., Methods: One hundred patients with upper gastrointestinal symptoms and 150 volunteers with no such past history faced an interviewer-administered questionnaire assessing seven symptoms, graded for frequency and severity. Two scores were generated. Score 1, the sum of frequency of symptoms and score 2, the sum of products of frequency and severity of each. Internal consistency, test-retest reliability and criterion validity against 24-h pH monitoring were assessed. Cut-off scores were generated by receiver operating characteristic curves using scores of half the volunteers and patients selected randomly and validated on the other half., Results: Cut-off scores and area under the curve for score 1 were >/=10.5 and 0.93, and score 2 were >/=12.5 and 0.93, respectively. The sensitivity and specificity of diagnosing the disease in the remaining participants using score 1 was 89.7 and 92.4% and score 2 was 93.8 and 94.0%, respectively. The instrument had good internal consistency (Cronbach alpha = 0.73) and reliability (intraclass correlation coefficient of scores 1 and 2 were 0.94 and 0.95, respectively). Score 2 showed better correlation with 24-h pH monitoring parameters (Spearman's rank correlation, P = 0.01)., Conclusion: Our score is valid, reliable and can detect GORD with high sensitivity and specificity. A score assessing both frequency and severity of symptoms correlates better to an objective measure of GORD.

Background: Inflammatory bowel disease (IBD) is being increasingly diagnosed in Asia. However there are few epidemiological data from the region., Methods: To determine prevalence and clinical characteristics of IBD, a hospital-based survey was performed in the Colombo and Gampaha districts (combined population 4.5 million) in Sri Lanka. Patients with established ulcerative colitis (UC) and Crohn's disease (CD), who were permanent residents of these adjoining districts, were recruited from hospital registries and out-patient clinics. Clinical information was obtained from medical records and patient interviews., Results: There were 295 cases of IBD (UC = 240, CD = 55), of which 34 (UC = 30, CD = 4) were newly diagnosed during the study year. The prevalence rate for UC was 5.3/100,000 (95% CI 5.0-5.6/100,000), and CD was 1.2/100,000 (95% CI 1.0-1.4/100,000). The incidence rates were 0.69/100,000 (95% CI 0.44-0.94/100,000) for UC and 0.09/100,000 (95% CI 0.002-0.18/100,000) for CD. Female:male ratios were 1.5 for UC and 1.0 for CD. Mean age at diagnosis was (males and females) 36.6 and 38.1y for UC and 33.4 and 36.2y for CD. Among UC patients, 51.1% had proctitis and at presentation 58.4% had mild disease. 80% of CD patients had only large bowel involvement. Few patients had undergone surgery., Conclusions: The prevalence of IBD in this population was low compared to Western populations, but similar to some in Asia. There was a female preponderance for UC. UC was mainly mild, distal or left-sided, while CD mainly involved the large bowel.

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in the Asia-Pacific region. However, its prevalence and risk factors in Asian (especially South Asian) communities is poorly studied. In this study, the aim was to determine the community prevalence and risk factors for NAFLD among adults in an urban Sri Lankan population., Methods: The study population consisted of 35-64-year-old adults, selected by stratified random sampling. NAFLD was diagnosed on established ultrasound criteria for fatty liver, safe alcohol consumption (< 14 units/week for men, < 7 units/week for females) and absence of hepatitis B and C markers. Blood pressure (BP) and anthropometric measurements were made, and fasting glucose, glycosylated hemoglobin, serum lipids, fasting serum insulin and serum alanine aminotransferase (ALT) were determined., Results: Of the 2985 study participants, 974 (32.6%) had NAFLD (605 [62.1%] women, mean age 52.8 years [standard deviation, 7.3]). On multivariate analysis, obesity, acanthosis nigricans, insulin resistance, elevated diastolic BP, fasting plasma glucose, plasma triglycerides, and ALT twice the upper limit of the reference range or more were independently associated with NAFLD., Conclusion: The prevalence of NAFLD among adults in this urban Sri Lankan community is high and is strongly associated with constituent features of the metabolic syndrome.

Background and Aim: Current guidelines for upper gastrointestinal endoscopy (UGIE) advise at least 6-8 h fasting for solids and 4-h fasting for liquids. We aimed to determine whether a 6-h fast for solids and one-hour fast for water prior to UGIE gives good endoscopic vision and less patient discomfort., Methods: 128 patients referred for UGIE were given a standard meal 6 h before endoscopy, and then randomized to either nil by mouth for 6 h (group A, n = 65) or allowed to drink water for up to one hour prior to endoscopy (group B, n = 63). Before endoscopy patients were requested to indicate discomfort due to fasting on a visual analog scale. Fluid in the gastric fundus was aspirated, when present, for volume and pH measurements, and endoscopic vision was graded., Results: 53 patients in group A and 43 patients in group B completed the study. Discomfort was significantly lower in group B than group A (P < 0.0001). Endoscopic vision was good in all 53 patients in group A and 40 in group B, and average in 3 patients in group B. Fluid in the gastric fundus was noted in 11 patients in group A and 16 in group B, but there were no significant differences in volume or pH between groups. There were no complications attributable to endoscopy in either group., Conclusions: A 6-h fast for solids and a 1-h fast for water prior to UGIE gives good endoscopic vision, and causes minimum patient discomfort.

Tumour necrosis factor-alpha (TNF) expression is increased in inflammatory bowel disease (IBD), and TNF maps to the IBD3 susceptibility locus. Transmission disequilibrium and case-control analyses, in two independent Caucasian cohorts, showed a novel association of the TNF(-857C) promoter polymorphism with IBD (overall P=0.001 in 587 IBD families). Further genetic associations of TNF(-857C) with IBD sub-phenotypes were seen for ulcerative colitis and for Crohn's disease, but only in patients not carrying common NOD2 mutations. The genetic data suggest a recessive model of inheritance, and we observed ex vivo lipopolysaccharide-stimulated whole-blood TNF production to be higher in healthy TNF(-857C) homozygotes. We show the transcription factor OCT1 binds TNF(-857T) but not TNF(-857C), and interacts in vitro and in vivo with the pro-inflammatory NF(-kappa)B transcription factor p65 subunit at an adjacent binding site. Detailed functional analyses of these interactions in gut macrophages, in addition to further genetic mapping of this gene-dense region, will be critical to understand the significance of the observed association of TNF(-857C) with IBD.