Efficacy and safety of oral ivermectin in the treatment of mild to moderate Covid-19 patients: a multi-centre double-blind randomized controlled clinical trial.

BACKGROUND: Evidence on ivermectin as a treatment for Covid-19 is controversial. A Cochrane review concluded that the efficacy and safety of ivermectin is uncertain (evidence up to April 2022) and WHO recommended its use only in the setting of clinical trials. This study aimed to assess the efficacy and safety of oral ivermectin in hospitalized patients with mild to moderate Covid-19. TRIAL DESIGN AND METHODS: A double-blind, randomized placebo-controlled clinical trial was conducted among RT-PCR-confirmed, adults, hospitalised within the first four days of symptoms. Patients received oral ivermectin 24 mg or placebo daily for five days. RT-PCR was repeated on days five and ten. Clinical progression was monitored using the World Health Organization Clinical Progression Scale. Serum ivermectin levels were measured on days three, five, and seven. The primary outcome was the difference in the viral load between day zero and ten in the two groups. RESULTS: Out of 1699 patients screened, 249 underwent randomization and 127 received ivermectin, and 122 placebo. D10 median viral load for E gene (IQR) was 2,000 copies/mL (100 - 20,500) with ivermectin (n = 80) and 4,100 copies/mL (1,000-65,600) with placebo (n = 81, p = 0.028), per protocol analysis. The difference in Log viral load between day zero and ten between ivermectin and placebo was 3.72 and 2.97 respectively (p = 0.022). There was no significant difference in the WHO clinical progression scale or the adverse effects. Ivermectin blood levels taken before or with meals were not significantly different. Only 7 and 17 patients achieved blood levels above 160ng/ML and 100ng/ML respectively and they did not achieve a significantly lower viral load. CONCLUSION: Although ivermectin resulted in statistically significant lower viral load in patients with mild to moderate Covid-19, it had no significant effect on clinical symptoms. TRIAL REGISTRATION NUMBER: SLCTR/2021/020, Sri Lanka Clinical Trials Registry. 19/07/2021.

Incidence and prevalence of alcoholic fatty liver disease: a prospective, community-based study among adult Sri Lankans.

Background: Data on the alcoholic fatty liver (AFL) is limited. Therefore, we investigated alcohol use and AFL patterns among urban, adult Sri Lankans. Methods: The study population (selected by age-stratified random sampling) was screened in 2007 (35-64 years) and re-evaluated in 2014. They were assessed by structured interviews, anthropometric measurements, liver-ultrasound, and biochemical and serological tests. AFL was diagnosed on ultrasound criteria, 'unsafe' alcohol consumption (Asian standards: males>14units, females>7units per week) and absence of hepatitis B/C markers. Controls were unsafe alcohol consumers who had no fatty liver on ultrasound. Results: 2985/3012 (99%) had complete data for analysis. 272/2985 (9.1%) were unsafe-drinkers in 2007 [males-270; mean-age-51.9, SD-8.0 years]. 86/272 (31.6%) had AFL [males-85; mean-age-50.2, SD-8.6 years]. Males [p<0.001], increased waist circumference (WC) [OR 4.9, p<0.01] and BMI>23kg/m2 [OR 3.5, p<0.01] and raised alanine aminotransferase (ALT) [OR 2.8, p<0.01] were independently associated with AFL. 173/272 (63.6%) unsafe alcohol consumers from 2007 were re-evaluated in 2014. 134/173 had either had AFL or had changed to 'safe' or no alcohol consumption. 21/39 (53.8%) [males-21 (100%), mean-age-57.9, SD-7.9 years] who remained 'unsafe' alcohol users who had no fatty liver in 2007 developed AFL after 7-years (annual incidence 7.7%). On bivariate analysis, only males were associated with new-onset AFL. Of the 42 who had AFL at baseline but changed their drinking status from unsafe to safe or no alcohol, 6 had resolution of fatty liver in 2014. Conclusion: In conclusion, in this community-based study among urban Sri Lankan adults, the annual incidence of AFL among unsafe alcohol users was 7.7%. Furthermore, new-onset AFL was associated with males.

Place of cardiovascular risk prediction models in South Asians; agreement between Framingham risk score and WHO/ISH risk charts.

INTRODUCTION AND OBJECTIVES: There are no cardiovascular risk prediction models developed in South Asian cohorts. Therefore, different risk models not validated in South Asians are being used. We aimed to compare cardiovascular risk predictions of Framingham risk score (FRS) and World Health Organization/International Society of Hypertension (WHO/ISH) charts for agreement in a sample of South Asians. METHODS: Ten-year cardiovascular risk predictions of patients without previous cardiovascular diseases attending a non-communicable disease clinic were calculated using FRS (with BMI and with cholesterol) and WHO/ISH charts (with and without cholesterol). Patients were categorised into low (<20%) and high (≥20%) cardiovascular risk groups on risk predictions. Agreement in risk categorisation with different prediction models was compared using Cohen's kappa coefficient (κ). RESULTS: One hundred sixty-nine patients (females 130 (81.1%)) mean age 65 ± 6.9 years were studied. Of the participants, 80 (47.3%), 62 (36.7%), 18 (10.7%), 16 (9.5%), were predicted high risk by FRS BMI-based, FRS cholesterol-based, WHO/ISH without-cholesterol and WHO/ISH with-cholesterol models, respectively. Agreement between the two FRS models (κ = 0.736, P < .0001) and the two WHO/ISH models (κ = 0.804, P < .0001) in stratifying patients into high and low-risk groups, was "good." However, the agreements between FRS BMI-based and WHO/ISH without-cholesterol models (κ = 0.234, P < .0001) and FRS cholesterol-based and WHO/ISH with-cholesterol models (κ = 0.306, P < .0001) were only "fair." CONCLUSION: Cardiovascular risk predictions of FRS were higher than WHO/ISH charts and the agreement in risk stratification was not satisfactory in Sri Lankans. Therefore, different cardiovascular risk prediction models should not be used interchangeably in the follow-up of South Asians.

Metabolic syndrome, but not non-alcoholic fatty liver disease, increases 10-year mortality: A prospective, community-cohort study.

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.

Clinicopathological characteristics and oncological outcomes of patients with renal cell carcinoma.

ABSTRACT: Although certain characteristics of renal cell carcinoma (RCC) seen in Sri lanka are different to the developed world and incidence is rising, no data on oncological outcome and patient survival are avaialble. A hospital-based cohort study was done in a tertiary referral centre over a period of eight years (2012-2019). A total of 285 newly diagnosed RCC had a mean follow-up period of 28.3 months. Radical nephrectomy was performed in 189 patients while 91 patients had partial nephrectomy. Clear cell RCC which was seen in 231 (81.1%) patients while papillary RCC was seen in 43 (15.1%). There were 54 deaths during the follow-up. The 30-day postoperative mortality was 2.1%. Thirty (10.5%) patients developed metastases while three patients developed local recurrences. The overall five -year survival rate was 72.8% (95%CI=65.9-80.5). Five-year survival of papillary RCC (60.5%) was lower than clear cell RCC (74.1%). Tumour stage, presence of metastases and histological grade of the tumour influenced the survival. Gender (p= 0.3), histological type (p= 0.5) or type of surgery (p=0.2) had no statistically significant effect on survival.

Headache: an important symptom possibly linked to white matter lesions in thalassaemia.

Neurological manifestations are reported only occasionally in patients with thalassaemia and are given much less prominence than the complications related to anaemia and iron overload. White matter changes (WMCs) on magnetic resonance imaging (MRI) in patients with thalassaemia were first reported two decades ago but the significance of these lesions remains unclear. We studied the neurological and cognitive manifestations in 82 older patients with thalssaemia [25 Thalassaemia major (TM), 24 thalassaemia intermedia (TI) and 33 haemaglobin E ß thalassaemia (EBT)] and 80 controls, and found that headaches were more common in thalassaemia patients (50/82, 61%) than in controls (18/80, 22·5%: P < 0·001). WMCs on MRI were found in 20/82 (24·3%) patients and 2/29 (6·9%) controls had (P = 0·078). WMC were more common among those with headaches (17/50: 34%) than in those without headache (3/32; 9·3%) (P = 0·023). WMCs were not associated with reduction of cognition. Nevertheless, cognition was lower in the TI and EBT groups compared with those with TM (P = 0·002). The association of headache with WMC in thalassaemia has not been reported before and warrants further study.

Challenges of Costing a Surgical Procedure in a Lower-Middle-Income Country.

BACKGROUND: It is vital to enquire into cost of health care to ensure that maximum value for money is obtained with available resources; however, there is a dearth of information on cost of health care in lower-middle-income countries (LMICs). Our aim was to develop a reproducible costing method for three routes of hysterectomy in benign uterine conditions: total abdominal (TAH), non-descent vaginal (NDVH) and total laparoscopic hysterectomy (TLH). METHODS: A societal perspective with a micro-costing approach was applied to find out direct and indirect costs. A total of 147 patients were recruited from a district general hospital (Mannar) and a tertiary care hospital (Ragama). Costs incurred from preoperative period to convalescence included direct costs of labour, equipment, investigations, medications and utilities, and indirect costs of out-of-pocket expenses, productivity losses, carer costs and travelling. Time-driven activity-based costing was used for labour, and top-down micro-costing was used for utilities. RESULTS: The total cost [(interquartile range), number] of TAH was USD 339 [(308-397), n = 24] versus USD 338 [(312-422), n = 25], NDVH was USD 315 [(316-541), n = 23] versus USD 357 [(282-739), n = 26] and TLH was USD 393 [(338-446), n = 24] versus USD 429 [(390-504), n = 25] at Mannar and Ragama, respectively. The direct cost of TAH, NDVH and TLH was similar between the two centres, whilst indirect cost was related to the setting rather than the route of hysterectomy. CONCLUSIONS: The costing method used in this study overcomes logistical difficulties in a LMIC and can serve as a guide for clinicians and policy makers in similar settings. TRIAL REGISTRATION: The study was registered in the Sri Lanka clinical trials registry (SLCTR/2016/020) and the International Clinical Trials Registry Platform (U1111-1194-8422) on 26 July 2016.

Increase in premature mortality due to non-communicable diseases in Sri Lanka during the first decade of the twenty-first century.

BACKGROUND: Globally, non-communicable diseases (NCD) are the leading cause of death and more than 40% of NCD deaths are premature occurring before the age of 70 years. In 2012, World Health Assembly declared its commitment to reduce premature NCD mortality by 25% from 2010 to 2025. The trend of premature NCD deaths in Sri Lanka has not been assessed and thus this study was done to assess it between 2001 to 2010. METHODS: Deaths due to cardiovascular diseases, cancers, chronic respiratory diseases and diabetes were studied. Premature NCD mortality was assessed using unconditional probability of dying (UPoD) due to NCDs among those aged 30 to 70 years. Number of relevant premature NCD deaths that occurred in each 5-year age interval and the respective mid-year population was used to calculate UPoD. RESULTS: During the period of 2001 to 2010, premature NCD mortality in Sri Lanka increased from 15·8% to 19·1% and males showed higher mortality compared to females throughout the period. Highest mortality was due to cardiovascular diseases followed by cancer and diabetes and all three showed an increasing trend. Chronic respiratory diseases showed an increase until 2004 and dropped thereafter. Among the four NCDs, diabetes revealed the most marked increasing trend in premature mortality during this period. CONCLUSIONS: The data revealed an increasing trend of premature NCD mortality in Sri Lanka between 2001 and 2010 although it has a relatively lower premature NCD mortality rate in the South-East Asian Region. Therefore, reducing premature NCD mortality by 25% from 2010 to 2025 is likely to be a rather challenging task in Sri Lanka and policy level changes need to be taken to achieve this target.

Incidence and risk factors for non-alcoholic fatty liver disease: A 7-year follow-up study among urban, adult Sri Lankans.

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.

Non-alcoholic fatty liver disease and its associations among adolescents in an urban, Sri Lankan community.

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.

Validation of the International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS) in two south- Asian languages.

INTRODUCTION: The multifaceted nature of pelvic floor disorders means that a systematic evaluation is required for optimal treatment outcome. It is also generally acknowledged that a valid tool is necessary to objectively assess symptoms reported by affected women. METHODS: The International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS) questionnaire was translated to Sinhala and Tamil and a validation study carried out among women attending gynecology clinics at North Colombo Teaching Hospital, Ragama, and the district general hospitals Mannar and Vavuniya. RESULTS: Content validity was assessed by the level of missing answers, which was < 4% and 2% for each item in Sinhala and Tamil, respectively. Construct validity was assessed by the ability of the questionnaire to differentiate between patients and controls. Both differentiated patients from controls on vaginal symptoms score (VSS) (p < 0.001), sexual symptoms score (SSS) (p < 0.01), and quality of life (QoL) (p < 0.001). There was a strong positive correlation between Pelvic Organ Prolapse Quantification (POP-Q) scores and VSS (Sinhala r s = 0.64, p < 0.001, Tamil r s = 0.65, p < 0.001), and QoL (Sinhala r s = 0.49, p < 0.001, Tamil r s = 0.60, p < 0.001). Internal consistency as assessed using Cronbach's coefficient alpha: 0.78 (0.76-0.78) and 0.83 (0.80-0.84) in Sinhala and Tamil, respectively. Test-retest reliability was assessed by weighted kappa scores (Sinhala 0.58-0.88 and Tamil 0.76-0.90). Both questionnaires were sensitive to change and showed that VSS and QoL improved following surgery (Wilcoxon matched-pairs signed-rank test p < 0.001). CONCLUSION: The validated Sinhala and Tamil translations of ICIQ-VS will be useful for assessing vaginal and sexual symptoms among women speaking Sinhala and Tamil.

Translation and validation of ICIQ-FLUTS for Tamil-speaking women.

AIMS: Research in to lower urinary tract symptoms (LUTS) in women in South Asia is hampered by lack of validated tools. Our aim was to validate the International Consultation on Incontinence Modular Questionnaire on Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) from English to Tamil. METHOD: After translation to Tamil, a validation study was carried out among women attending the gynecology clinic at District General Hospital-Mannar. RESULTS: Content validity assessed by the level of missing data was <2%. Construct validity was assessed by the ability of the questionnaire to identify patients with incontinence (n = 45) from controls (n = 93) using the incontinence score [patients = 7.7 standard deviation (SD) = 4.7, controls = 1.4 SD = 2.2, p < 0.001] and those with symptomatic anterior wall prolapse (n = 16) from controls (n = 93) using voiding symptoms score (patients = 4.8 SD = 2.3, controls = 0.3 SD = 0.8, p < 0.001). Internal consistency was assessed using Cronbach's coefficient alpha score [0.80 (0.77-0.81)]. Test-retest reliability assessed by weighted kappa (κ) ranged from 0.73 to 0.87. Patients with incontinence (n = 30, pretreatment incontinence score = 7.9, SD = 4.9 versus posttreatment incontinence score = 3.3, SD = 3.1) and symptomatic anterior wall prolapse (n = 14, preoperative voiding symptoms score = 4.9 SD = 2.5 versus postoperative voiding symptoms score = 0.9 SD = 1.5) showed an improvement with treatment (Wilcoxon matched--pairs signed-rank test p < 0.001 and p < 0.01, respectively). An incontinence score ≥ 3 (sensitivity = 86.7%, specificity = 78.4%) and a voiding symptoms score ≥ 3 (sensitivity = 87.5%, specificity = 96.2%) detected any form of incontinence and symptomatic anterior wall prolapse, respectively. CONCLUSION: Tamil translation of ICIQ-FLUTS retained the psychometric properties of the original English questionnaire and will be an invaluable tool to detect LUTS among Tamil-speaking women.

Epidemiology of irritable bowel syndrome in children and adolescents in Asia.

OBJECTIVES: Several cross-sectional surveys have been conducted to study the prevalence of irritable bowel syndrome (IBS) in children. The aim of the present study was to conduct a systematic review and a meta-analysis of published literature to estimate the prevalence of IBS among Asian children. METHOD: A computer-assisted search of MEDLINE, EMBASE, PsycINFO, and regional databases of Asia was carried out. Selected articles were reviewed in depth and data were extracted. Pooled prevalence, sex differences, and 95% confidence intervals were calculated. Heterogeneity of the studies was assessed using the I(2) test. RESULTS: A total of 16 cross-sectional studies that reported prevalence of IBS (in children and adolescents) and qualified to be included were taken into the final analysis containing 38,076 patients. Selected studies are from China, Korea, Japan, Iran, Sri Lanka, and Saudi Arabia. Studies showed a marked heterogeneity with I(2) of 98.59 (P < 0.0001). Prevalence of IBS ranges from 2.8% to 25.7%, with a pooled prevalence of 12.41% (95% confidence interval 9.87-14.95). Prevalence risk ratio of girl:boy is 1.39. Prevalence of subtypes is diverse and varies between studies. CONCLUSIONS: The published data indicate that IBS is a significant problem among Asian children and adolescents. Female sex predisposes children and adolescents to develop IBS.

Role of red cell distribution width in screening for Hb E trait in population screening for hemoglobin disorders.

The national screening policy for hemoglobinopathies uses the cutoffs for red cell indices mean corpuscular volume >80 and mean corpuscular hemoglobin >27, a strategy known to miss some individuals with Hb E trait (EBT), the most common abnormal hemoglobin in Sri Lanka. We wanted to determine if red cell distribution width (RDW) cutoff values would help in increasing the sensitivity of screening for Hb E trait. High-performance liquid chromatography was carried out as the gold standard to detect hemoglobinopathies and red blood cell parameters with colter counter. Receiver operating characteristic curve was drawn to determine the cutoff value for EBT against ß-trait (BTT) and other anemias. Of the 504 patients, 246 had BTT, 110 had EBT, and 151 had other types of anemias. Mean (SD) RDW among patients with BTT was 16 (2.8), with EBT 14.5 (2.9), and with other anemias 15.8 (4.2) (P>0.001). With 14.45 as the cutoff for RDW and considering accepted values for mean corpuscular volume >80 and mean corpuscular hemoglobin >27, it gave a predictive sensitivity of 98.2% for EBT. By using RDW cutoff at 14.45 in addition to the accepted screening indices, sensitivity of Hb E trait detection went up to 98.2% from 86.6%. This study highlights the importance of taking RDW into consideration for screening.

Antenatal oral glucose tolerance test abnormalities in the prediction of future risk of postpartum diabetes in women with gestational diabetes: Results from the LIVING study.

OBJECTIVES: To explore associations between type and number of abnormal glucose values on antenatal oral glucose tolerance test (OGTT) with postpartum diabetes in South Asian women diagnosed with gestational diabetes (GDM) using International Association of the Diabetes and Pregnancy Study Groups criteria. METHODS: This post-hoc evaluation of the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, a randomized controlled trial, was conducted among women with GDM in the index pregnancy, across 19 centers in Bangladesh, India, and Sri Lanka. Postpartum diabetes (outcome) was defined on OGTT, using American Diabetes Association (ADA) criteria. RESULTS: We report data on 1468 women with GDM, aged 30.9 (5.0) years, and with median (interquartile range) follow-up period of 1.8 (1.4-2.4) years after childbirth following the index pregnancy. We found diabetes in 213 (14.5%) women with an incidence of 8.7 (7.6-10.0)/100 women-years. The lowest incidence rate was 3.8/100 women years, in those with an isolated fasting plasma glucose (FPG) abnormality, and highest was 19.0/100 women years in participants with three abnormal values. The adjusted hazard ratios for two and three abnormal values compared to one abnormal value were 1.73 (95% confidence interval [CI], 1.18-2.54; p = .005) and 3.56 (95% CI, 2.46-5.16; p < .001) respectively. The adjusted hazard ratio for the combined (combination of fasting and postglucose load) abnormalities was 2.61 (95% CI, 1.70-4.00; p < .001), compared to isolated abnormal FPG. CONCLUSIONS: Risk of diabetes varied significantly depending upon the type and number of abnormal values on antenatal OGTT. These data may inform future precision medicine approaches such as risk prediction models in identifying women at higher risk and may guide future targeted interventions.

Cluster-randomised trial of the impact of school-based deworming and iron supplementation on the cognitive abilities of schoolchildren in Sri Lanka's plantation sector.

OBJECTIVE: To assess the impact of deworming and iron supplementation on the cognitive abilities and educational achievement of school-age children in Sri Lanka. METHODS: Prospective, placebo-controlled randomised study. The treatment group received deworming and weekly iron supplementation for 6 months; the control group received placebo for both the anthelmintic and iron. A mixed effects regression model was used to answer the main research question. To increase the precision of this study's estimates, various background variables were controlled for that were not related to treatment but could have some impact on the outcome. RESULTS: The prevalence of soil-transmitted helminth (STH) infection was reduced in the treatment group (n = 615), with significant differences between treatment and control groups (n = 575) in the levels of Ascaris and Trichuris. No impact was found on haemoglobin (Hb) levels, nor any significant impact on concentration levels or on educational test scores. CONCLUSION: Decline in STH prevalence alone, in the absence of improved Hb status, produced no evidence of impact on concentration levels or educational test scores.

Response of the airways and autonomic nervous system to acid perfusion of the esophagus in patients with asthma: a laboratory study.

BACKGROUND: Gastro-esophageal reflux disease (GERD) predisposes to airway disease through a vagally-mediated esophago-bronchial reflex. This study investigates this vagal response to esophageal acid perfusion. METHODS: 40 asthmatics with mild stable asthma participated. Each subject underwent spirometry and autonomic function testing (valsalva maneuver, heart rate response to deep breathing and to standing from supine position) four times: a) before intubation, b) after intubation, and then immediately after perfusion with, in random order, c) concentrated lime juice solution (pH 2-3) and d) 0.9% saline. Subjects were blinded to the solution perfused. RESULTS: Asthmatics were of mean (SD) age 34.3 years (1.3), and 67.5% of them were females. pH monitoring demonstrated that 20 subjects had abnormal reflux and 20 did not. In each group 10 subjects had a positive GERD symptom score. Following perfusion with acid compared to saline, all subjects showed significant decreases in FEV1 and PEFR and significant increases in the mean valsalva ratio and heart rate difference on deep breathing from baseline values, but no changes in FVC or heart rate ratio on standing. There were no significant differences in any of the parameters between subjects with and without reflux. CONCLUSIONS: Acid stimulation of the distal esophagus results in increased parasympathetic activity and concomitant broncho-constriction in asthmatics irrespective of their reflux state. This strengthens the hypothesis that GER triggers asthma-like symptoms through a vagally mediated esophago-bronchial reflex and encourages a possible role for anti-cholinergic drugs in the treatment of reflux-associated asthma.

Inhaled beclomethasone in the treatment of early COVID-19: a double-blind, placebo-controlled, randomised, hospital-based trial in Sri Lanka.

OBJECTIVES: To study if early initiation of inhaled beclomethasone 1200 mcg in patients with asymptomatic, mild or moderate COVID-19 reduces disease progression to severe COVID-19. DESIGN: Double-blinded, parallel-groups, randomised, placebo-controlled trial. SETTING: A hospital-based study in Sri Lanka. PARTICIPANTS: Adults with asymptomatic, mild or moderate COVID-19, presenting within the first 7 days of symptom onset or laboratory diagnosis of COVID-19, admitted to a COVID-19 intermediate treatment centre in Sri Lanka between July and November 2021. INTERVENTIONS: All participants received inhaled beclomethasone 600 mcg or placebo two times per day, for 10 days from onset of symptoms/COVID-19 test becoming positive if asymptomatic or until reaching primary endpoint, whichever is earlier. PRIMARY OUTCOME MEASURE: Progression of asymptomatic, mild or moderate COVID-19 to severe COVID-19. SECONDARY OUTCOME MEASURES: The number of days with a temperature of 38°C or more and the time to self-reported clinical recovery. RESULTS: A total of 385 participants were randomised to receive beclomethasone(n=193) or placebo(n=192) stratified by age (≤60 or >60 years) and sex. One participant from each arm withdrew from the study. All participants were included in final analysis. Primary outcome occurred in 24 participants in the beclomethasone group and 26 participants in the placebo group (RR 0.90 ; p=0.763). The median time for self-reported clinical recovery in all participants was 5 days (95% CI 3 to 7) in the beclomethasone group and 5 days (95% CI 3 to 8) in the placebo group (p=0.5). The median time for self-reported clinical recovery in patients with moderate COVID-19 was 5 days (95% CI 3 to 7) in the beclomethasone group and 6 days (95% CI 4 to 9) in the placebo group (p=0.05). There were no adverse events. CONCLUSIONS: Early initiation of inhaled beclomethasone in patients with asymptomatic, mild or moderate COVID-19 did not reduce disease progression to severe COVID-19. TRIAL REGISTRATION NUMBER: Sri Lanka Clinical Trials Registry; SLCTR/2021/017.

Identification of patients with type 2 diabetes with non-alcoholic fatty liver disease who are at increased risk of progressing to advanced fibrosis: a cross-sectional study.

INTRODUCTION: Identification of advanced hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD) is important as this may progress to cirrhosis and hepatocellular carcinoma. The risk of hepatic fibrosis is especially high among patients with diabetes with NAFLD. Annual screening of patients with diabetes for fatty liver and calculation of Fibrosis-4 (FIB-4) score and exclusion of significant fibrosis with vibration-controlled transient elastography (VCTE) have been recommended. However, VCTE is expensive and may not be freely available in resource-limited settings. We aim to identify predictors of significant liver fibrosis who are at increased risk of progression to advanced liver fibrosis and to develop a prediction model to prioritise referral of patients with diabetes and NAFLD for VCTE. METHODS AND ANALYSIS: This cross-sectional study is conducted among all consenting adults with type 2 diabetes mellitus with NAFLD at the Colombo North Teaching Hospital, Ragama, Sri Lanka. All patients get the FIB-4 score calculated. Those with FIB-4 ≥1.3 undergo VCTE (with FibroScan by Echosens). Risk associations for progression to advanced liver fibrosis/cirrhosis will be identified by comparing patients with significant fibrosis (liver stiffness measure (LSM) ≥8 kPa) and without significant fibrosis (LSM <8 kPa). A model to predict significant liver fibrosis will be developed using logistic regression. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (P/66/07/2021). Results of the study will be disseminated as scientific publications in reputable journals.

The incidence and risk factors of postpartum diabetes in women from Bangladesh, India and Sri Lanka (South Asia) with prior gestational diabetes mellitus: Results from the LIVING study.

AIM: To study, the incidence and risk factors for postpartum diabetes (DM), in women with gestational diabetes mellitus (GDM) from South Asia (Bangladesh, India and Sri Lanka), followed for nearly two years after delivery. METHODS: Women with prior GDM diagnosed using IADPSG criteria were invited at 19 centres across Bangladesh, India and Sri Lanka for an oral glucose tolerance test (OGTT) following childbirth, and were enrolled in a randomized controlled trial. The glycaemic category (outcome) was defined from an OGTT based on American Diabetes Association criteria. RESULTS: Participants (n = 1808) recruited had a mean ± SD age of 31.0 ± 5.0 years. Incident DM was identified, between childbirth and the last follow-up, in 310 (17.1 %) women [incidence 10.75/100 person years], with a median follow-up duration of 1.82 years after childbirth. Higher age, lower education status, higher prior pregnancy count, prior history of GDM, family history of DM, and postpartum overweight/obese status were significantly associated with incident DM. Women in Bangladesh had a higher cumulative incidence of DM [16.49/100 person years] than in Sri Lanka [12.74/100 person years] and India [7.21/100 person years]. CONCLUSIONS: A high incidence of DM was found in women with prior GDM in South Asia, with significant variation between countries. Women from Bangladesh had a significantly higher pregnancy count, family history of DM and overweight/obese status, despite having significantly lower age, which could be responsible for their higher rates of DM. Registration of this study: The study was registered with the Clinical Trials Registry of India (CTRI/2017/06/008744), Sri Lanka Clinical Trials Registry (SLCTR/2017/001), and ClinicalTrials.gov (NCT03305939).