Environmental fluoride exposure and implications on potential pediatric kidney health risks: an approach with urinary biomarkers.

BACKGROUND: Environmental fluoride exposure at elevated levels is potentially linked to kidney injury, and may contribute to chronic kidney disease of uncertain etiology (CKDu) as a risk factor. However, this link remains unclear, and examining the risk of kidney damage from early life fluoride exposure may provide important insights. Hence, this study aimed to investigate associations of fluoride exposure with pediatric kidney health in CKDu impacted and unimpacted communities in Sri Lanka. METHODS: Considering the geographical variations in environmental fluoride, climate, and prevalence of CKDu, four study groups were established within selected education zones in CKDu-endemic dry zone regions (D-En), and CKDu-nonendemic regions within the dry (D-NE), wet (W-NE), and intermediate (I-NE) climatic zones. The study population included 922 school students (11-18 years of age). Participants in each group were divided into four subgroups based on quartiles of respective urinary fluoride (UF) distribution for comparison of urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and albumin-creatinine ratio (ACR). RESULTS: UF levels in participants particularly in CKDu endemic dry zone regions were significantly high compared to the other regions. Significantly high median urinary NGAL (in D-NE) and ACR (in D-EN, and W-NE) levels were observed in subgroups of higher UF quartiles. Albuminuria was not particularly identified in subjects with high UF excretion. Urinary KIM-1 showed no significant variation across the UF quartile subgroups. Linear regression identified weak associations of UF with kidney injury biomarkers. CONCLUSIONS: Fluoride exposure is particularly high in CKDu-endemic dry zone communities. As implied by kidney injury biomarkers, a strong link between fluoride exposure and pediatric kidney health was not evident at the observed exposure levels in the study regions.

Frequency of Consumption of Food Groups and Cardio-Metabolic Risk Factors: A Genetically Informative Twin Study in Sri Lanka.

Low- and middle-income countries (LMICs) globally have undergone rapid urbanisation, and changes in demography and health behaviours. In Sri Lanka, cardio-vascular disease and diabetes are now leading causes of mortality. High prevalence of their risk factors, including hypertension, dysglycaemia and obesity have also been observed. Diet is a key modifiable risk factor for both cardio-vascular disease and diabetes as well as their risk factors. Although typically thought of as an environmental risk factor, dietary choice has been shown to be genetically influenced, and genes associated with this behaviour correlate with metabolic risk indicators. We used Structural Equation Model fitting to investigate the aetiology of dietary choices and cardio-metabolic phenotypes in COTASS, a population-based twin and singleton sample in Colombo, Sri Lanka. Participants completed a Food Frequency Questionnaire (N = 3934) which assessed frequency of intake of 14 food groups including meat, vegetables and dessert or sweet snacks. Anthropometric (N = 3675) and cardio-metabolic (N = 3477) phenotypes were also collected including weight, blood pressure, cholesterol, fasting plasma glucose and triglycerides. Frequency of consumption of most food items was found to be largely environmental in origin with both the shared and non-shared environmental influences indicated. Modest genetic influences were observed for some food groups (e.g. fruits and leafy greens). Cardio-metabolic phenotypes showed moderate genetic influences with some shared environmental influence for Body Mass Index, blood pressure and triglycerides. Overall, it seemed that shared environmental effects were more important for both dietary choices and cardio-metabolic phenotypes compared to populations in the Global North.

The Effect of Salacia Reticulata Extract Biscuits on Blood Sugar Control of Type 2 Diabetes Mellitus Patients: A Two-Period, Two-Sequence, Crossover, Randomized, Triple-Blind, Placebo-Controlled, Clinical Trial.

Background Traditional physicians in Sri Lanka and India use extracts from the plant Salacia reticulata,or Kothala Himbutu (KH) to treat diabetes. The effect of a KH biscuit, taken as a snack, on glycemic control was investigated in patients with type 2 diabetes. Methodology This triple-blind, randomized, placebo-controlled, two-period, two-sequence, crossover study was conducted in the Internal Medical Clinic, Teaching Hospital Anuradhapura. A research assistant opened computer-generated random numbers enclosed in a sealed envelope and performed treatment allocation. The group outcome was masked from the researchers, patients, and analysts. Both the placebo and the KH biscuit were identical. The primary outcome measure was HbA1c. Intention to treat analyses was used. Glycemic stability was assured in the run-in period, and patients with severe renal, liver, or heart disease were excluded. If patients needed insulin, they were withdrawn from the trial. Results From January 2014 to May 2016, 230 patients were screened, and 136 were randomized. Of them, 62 were allocated, 58 completed the placebo biscuit, 71 were allocated, and 69 completed the KH biscuit. After the washout period and crossover, 57 completed the KH and 65 completed the placebo biscuit. The baseline mean HbA1c level was 8.45% (68.9 mmol/mol) and 8.65% (71.0 mmol/mol) for the placebo-KH biscuit and KH-placebo biscuit groups. At the end of the trial, the HbA1c levels in the placebo-KH biscuit group and the KH-placebo biscuit group were 8.23% (66.4 mmol/mol) and 8.53% (69.3 mmol/mol), respectively. The unadjusted mean HbA1c reduced from the baseline with 0.10% (95% CI = -0.12, 0.32) after the placebo biscuit and 0.35% (95% CI = 0.10, 0.60) after the KH biscuit. After the placebo and KH biscuits, the HbA1c values were 8.46% (95% CI = 8.19, 8.73) (69 mmol/mol with 95% CI = 66, 72) and 8.19% (95% CI = 7.90, 8.48) (66 mmol/mol with 95% CI = 63, 69), respectively. The paired sample t-test shows that the reduction was not significant for placebo biscuits (p = 0.324), while it is significant for KH biscuits (p = 0.003). Analysis with multiple imputations confirmed a significant difference between the placebo and KH biscuit in reducing the HbA1c level. Conclusions KH biscuit taken as a snack reduces HbA1c by 0.25% compared to placebo without serious renal or liver adverse effects. The biscuit can be safely recommended as a snack to patients with type 2 diabetes.

Approach to Study the Efficacy and Safety of New Complementary and Alternative Medicine Formulations: Lesson during COVID-19 from Sri Lanka.

COVID-19 affected Sri Lanka from early 2020, a time of considerable ignorance accompanied by wide media coverage of a devastating epidemic in Italy and Europe. Many were attracted to complementary and alternative medicine (CAM) or traditional medicine (TM) in this desperate situation. Several preparations were claimed to be effective against COVID-19 globally. Dammika Bandara Syrup© was one such preparation promoted for preventing and treating SARS-CoV-2 infection. It was based on bees' honey, pericarp and mace of Myristica fragrans (nutmeg), the seed of Foeniculum vulgare and fresh rhizome of Zingiber officinale, all believed to have anti-viral properties. Following an unpublished clinical study claiming efficacy, Dammika Bandara Syrup© gained wide media publicity and political patronage. The producer claimed of Goddess Kali revealing the formula added an anthropological, cultural, and religious complexity to the issue. The demand for the product increased rapidly as a debate raged both in public and in the parliament on utilizing such products in combating COVID-19. The Department of Ayurveda, which is statutorily responsible for regulating CAM/TM had to respond to the situation. The legislation to regulate such indigenous medicinal products was weak, and the crisis deepened as thousands converged to the production facility, defying mobility restrictions introduced to control COVID-19. This led to the Ministry of Health requesting academics to form a team and conduct a clinical trial to prove its efficacy. This paper outlines the process and issues faced during the regulatory approval for the trial in a polarized political environment. Some health professionals accused the researchers of bowing to political pressure and questioned the scientific justification for the trial. However, the team considered this as an opportunity to streamline a path for research into CAM/TM therapies in situations such as COVID-19. Several processes were identified and addressed, such as the provisional registration of CAM preparations, assessing the potential efficacy of a CAM product, confirmation of authenticity and safety, standardization and supervision of production respecting cultural identities, obtaining approval for human use, choice of comparators, and ethical issues. We believe the study has helped set standards and a benchmark for CAM and TM research in Sri Lanka.

Associations between socioeconomic factors and depression in Sri Lanka: The role of gene-environment interplay.

BACKGROUND: Low socioeconomic status is a risk factor for depression. The nature and magnitude of associations can differ cross-culturally and is influenced by a range of contextual factors. We examined the aetiology of socioeconomic indicators and depression symptoms and investigated whether socioeconomic indicators moderate genetic and environmental influences on depression symptoms in a Sri Lankan population. METHODS: Data were from a population-based sample of twins (N = 2934) and singletons (N = 1035) in Colombo, Sri Lanka. Standard of living, educational attainment, and financial strain were used to index socioeconomic status. Depression symptoms were assessed using the Revised Beck Depression Inventory. Structural equation modelling explored genetic and environmental influences on socioeconomic indicators and depression symptoms and moderation of aetiological influences on depression symptoms by socioeconomic status. RESULTS: Depression symptoms were associated with lower standard of living, lower educational attainment, and financial strain. Sex differences were evident in the aetiology of standard of living, with a small contribution of genetic influences in females. Educational attainment was moderately heritable in both males and females. Total variance in depression was greater among less socioeconomically advantaged individuals. Modest evidence of moderation of the aetiology of depression by standard of living and education was observed. LIMITATIONS: While the sample is representative of individuals living in Colombo District, it may not be representative of different regions of Sri Lanka. CONCLUSIONS: The aetiology of depression varies across socioeconomic contexts, suggesting a potential mechanism through which socioeconomic disadvantage increases the risk for depression in Sri Lanka. Findings have implications for cross-cultural investigations of the role of socioeconomic factors in depression and for identifying targets for social interventions.

Incidence of serum sickness following Indian polyvalent antivenom therapy in a cohort of snake-envenomed patients in rural Sri Lanka.

INTRODUCTION: Serum sickness is a poorly reported delayed adverse reaction following snake antivenom therapy. We aimed to assess the frequency of serum sickness associated with administering Indian polyvalent antivenom in Sri Lanka. METHODS: We recruited patients from the Anuradhapura snakebite cohort who were admitted to a rural tertiary care hospital in Sri Lanka over one year period. Patients were interviewed over the phone 21 to 28 days post-envenoming to collect data on clinical effects: fever/chills, arthralgia/myalgia, rash, malaise, headache, abdominal pain, and nausea/vomiting. The presence of three or more symptoms between the 5th to 20th days after snake envenoming was defined as serum sickness. RESULTS: We were able to contact 98/122 (80%) patients who received antivenom and 423/588 (72%) who did not receive antivenom during the study period. The treated patients received a median dose of 20 vials (interquartile range: 20-30) of Indian polyvalent antivenom and of them, 92 (92%) received premedication. However, 67/98 (68%) developed acute adverse reactions to antivenom, including 19/98 (19%) developing anaphylaxis. Only 4/98 (4%) who received antivenom met the criteria for serum sickness, compared to none who did not receive antivenom therapy. All patients who developed serum sickness were envenomed by Russell's vipers, were premedicated, and received VINS Bioproducts antivenom. Three of them were treated with hydrocortisone in the acute stage, as premedication or as a treatment for acute adverse reactions of antivenom. Although all four patients sought medical advice for their symptoms, only one was clinically suspected to be serum sickness and treated, while the others were treated for infections. CONCLUSIONS: We confirmed that Indian polyvalent antivenom use in Sri Lanka is associated with high rates of acute adverse reactions. In contrast to studies of other antivenoms only a small proportion of patients developed serum sickness.

Community-based alcohol education intervention (THEATRE) study to reduce harmful effects of alcohol in rural Sri Lanka: design and adaptation of a mixed-methods stepped wedge cluster randomised control trial.

INTRODUCTION: Alcohol consumption is a leading cause of mortality, morbidity and adverse social sequelae in Sri Lanka. Effective community-based, culturally adapted or context-specific interventions are required to minimise these harms. We designed a mixed-methods stepped wedge cluster randomised control trial of a complex alcohol intervention. This paper describes the initial trial protocol and subsequent modifications following COVID-19. METHODS AND ANALYSIS: We aimed to recruit 20 villages (approximately n=4000) in rural Sri Lanka. The proposed intervention consisted of health screening clinics, alcohol brief intervention, participatory drama, film, and public health promotion materials to be delivered over 12 weeks.Following disruptions to the trial resulting from the Easter bombings in 2019, COVID-19 and a national financial crisis, we adapted the study in two main ways. First, the interventions were reconfigured for hybrid delivery. Second, a rolling pre-post study evaluating changes in alcohol use, mental health, social capital and financial stress as the primary outcome and implementation and ex-ante economic analysis as secondary outcomes. ETHICS AND DISSEMINATION: The original study and amendments have been reviewed and granted ethical approval by Rajarata University of Sri Lanka (ERC/2018/21-July 2018 and February 2022) and the University of Sydney (2019/006). Findings will be disseminated locally in collaboration with the community and stakeholders.The new hybrid approach may be more adaptable, scalable and generalisable than the planned intervention. The changes will allow a closer assessment of individual interventions while enabling the evaluation of this discontinuous event through a naturalistic trial design. This may assist other researchers facing similar disruptions to community-based studies. TRIAL REGISTRATION: The trial is registered with the Sri Lanka Clinical Trials Registry; https://slctr.lk/trials/slctr-2018-037.

Guillain-Barré Syndrome Following the First Dose of Inactivated SARS-CoV-2 Vaccine, BBIBP-CorV.

We present a case report of Guillain-Barré syndrome (GBS) following inactivated whole virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, BBIBP-CorV. A man presented with paresthesia in both upper and lower limbs with bifacial weakness, onset 18 days after receiving the first BBIBP-CorV vaccine. A bifacial palsy with a paresthesia variant of GBS was diagnosed, and the patient was treated with intravenous immunoglobulin, arresting the progression of neurological symptoms. Clinicians need to be aware of the possibility of GBS following vaccination with BBIBP-CorV, an inactivated SARS-CoV-2 vaccine.

Environmental heat exposure and implications on renal health of pediatric communities in the dry climatic zone of Sri Lanka: An approach with urinary biomarkers.

Prolonged heat exposure during outdoor physical exertion can result in adverse renal health outcomes, and it is also supposed to be a driver of chronic kidney disease of uncertain etiology (CKDu) in tropical regions. School students are more likely to experience high heat exposure during outdoor sports practices, and the current knowledge on potential renal health outcomes associated with heat exposure carries many knowledge gaps. Hence, the present study aimed to perform biomarker-based assessment of the likelihood of pediatric renal injury focusing the communities in the dry climatic zone in Sri Lanka, where it prevails relatively harsh climate and high prevalence of CKDu. School students who engaged in regular outdoor sports practices (high-heat exposure), and an age-matched control of students who did not engage in sports practices (low-heat exposure) from four educational zones: Padavi Sripura (N = 159) and Medirigiriya (N = 171), Uhana (N = 165) and Thanamalwila (N = 169) participated in this cross-sectional study representing CKDu endemic and non-endemic regions. Effective temperature (ET), wet-bulb globe temperature (WBGT), heat index (HI) and humidex were used for comparison of thermal comfort in the environment. The intensity of environmental heat measured by thermal comfort indices showed no significant difference (p > 0.05) among the study regions. Urinary kidney injury molecule (KIM-1) and albumin-creatinine ratio (ACR) in participants with high heat exposure did not differ significantly from those in the control groups in the four study zones, where urinary neutrophil gelatinase-associated lipocalin showed substantial differences in some groups. Irrespective of heat exposure, increased KIM-1 excretion was observed (p < 0.01) in participants of CKDu endemic regions compared to those in non-endemic areas. Within the context of our findings, there is no plausibly strong evidence to establish potential association of heat exposure with the likelihood of developing renal injury or abnormal renal outcomes in dry zone school students in Sri Lanka.

Does snake envenoming cause chronic kidney disease? A cohort study in rural Sri Lanka.

BACKGROUND: There is limited information on the risk of chronic kidney disease (CKD) following snakebite and its relationship with chronic interstitial nephritis in agricultural communities (CINAC). We aimed to investigate CKD in patients with a confirmed snakebite in rural Sri Lanka. METHODS: Patients prospectively recruited to the Anuradhapura snakebite cohort with authenticated bites were followed up. Two groups of patients were followed up: 199 patients in group I with a snakebite (August 2013-October 2014), reviewed after 4 years, and 168 patients in group II with a snakebite (May 2017-August 2018), reviewed after one year, with serum creatinine (estimated glomerular filtration rate [eGFR]) and urinary albumin to creatinine ratio (ACR). RESULTS: There were 12/199 (6%) in group I and 9/168 (5%) in group II with AKI following snakebite; 3/12 in group I and 2/9 in group II had haemodialysis. On review after 1 and 4 years, no patient had CKD and all had an eGFR ≥60 mL/min/1.73m2. Of 234 patients with a creatinine measured on discharge, 17/140 in group I and 11/94 in group II had a low eGFR (<60mL/min/1.73m2). In group I, 14/17 had a normal eGFR after four years, including 11/12 who had AKI following snakebite, and the 3/17 with a low eGFR on review had CKD or co-morbidities for CKD. In group II, 10/11 had a normal eGFR after one year, including all nine patients with AKI following snakebite, and the one patient with a low eGFR on review had CKD. Fifty patients (25%) in group I and 43 (26%) in group II had a high urinary ACR on review, all but two in each group had microalbuminuria. Multivariate logistic regression showed in group I that only comorbidities for CKD were associated with high urinary ACR, and in group II comorbidities for CKD, snakebite associated AKI and snake type were associated with high urinary ACR. All nine patients from both groups with a low eGFR (CKD stages 3-5) had CKD prior to the snakebite or treatment for hypertension or diabetes. CONCLUSION: There was no significant association between snakebite-associated AKI and CKD in patients followed up from a snakebite cohort post-bite. Microalbuminuria was common in these patients but likely associated with hypertension, diabetes mellitus and CINAC in this rural farming population.

Rapid Recovery of Acute Respiratory Distress Syndrome in Scrub Typhus, With Pulse Methylprednisolone and Therapeutic Plasma Exchange.

Acute respiratory distress syndrome (ARDS) is an atypical presentation of scrub typhus infection with associated high morbidity and mortality compared to uncomplicated scrub typhus infection. Here we report an otherwise healthy 41-year-old female patient admitted with moderate ARDS secondary to scrub typhus infection who gained comparatively rapid recovery within 72 hours following intravenous methylprednisolone pulse (MPP) therapy with therapeutic plasma exchange (TPE), suggesting a beneficial role of MPP and TPE in the treatment of ARDS secondary to scrub typhus infection. To our knowledge, this is the first case report regarding the use of MPP therapy and TPE in a patient with ARDS due to scrub typhus infection.

Cardiometabolic risk profiles in a Sri Lankan twin and singleton sample.

INTRODUCTION: Prevention of cardiovascular disease and diabetes is a priority in low- and middle-income countries, especially in South Asia where these are leading causes of morbidity and mortality. The metabolic syndrome is a tool to identify cardiometabolic risk, but the validity of the metabolic syndrome as a clinical construct is debated. This study tested the existence of the metabolic syndrome, explored alternative cardiometabolic risk characterisations, and examined genetic and environmental factors in a South Asian population sample. METHODS: Data came from the Colombo Twin and Singleton follow-up Study, which recruited twins and singletons in Colombo, Sri Lanka, in 2012-2015 (n = 3476). Latent class analysis tested the clustering of metabolic syndrome indicators (waist circumference, high-density lipoprotein cholesterol, triglycerides, blood pressure, fasting plasma glucose, medications, and diabetes). Regression analyses tested cross-sectional associations between the identified latent cardiometabolic classes and sociodemographic covariates and health behaviours. Structural equation modelling estimated genetic and environmental contributions to cardiometabolic risk profiles. All analyses were stratified by sex (n = 1509 men, n = 1967 women). RESULTS: Three classes were identified in men: 1) "Healthy" (52.3%), 2) "Central obesity, high triglycerides, high fasting plasma glucose" (40.2%), and 3) "Central obesity, high triglycerides, diabetes" (7.6%). Four classes were identified in women: 1) "Healthy" (53.2%), 2) "Very high central obesity, low high-density lipoprotein cholesterol, raised fasting plasma glucose" (32.8%), 3) "Very high central obesity, diabetes" (7.2%) and 4) "Central obesity, hypertension, raised fasting plasma glucose" (6.8%). Older age in men and women, and high socioeconomic status in men, was associated with cardiometabolic risk classes, compared to the "Healthy" classes. In men, individual differences in cardiometabolic class membership were due to environmental effects. In women, genetic differences predicted class membership. CONCLUSION: The findings did not support the metabolic syndrome construct. Instead, distinct clinical profiles were identified for men and women, suggesting different aetiological pathways.

Comparison of bedside clotting tests for detecting venom-induced consumption coagulopathy following Sri Lankan viper envenoming.

BACKGROUND: The whole blood clotting test (WBCT) is commonly used for diagnosing venom-induced consumption coagulopathy (VICC) in resource-poor settings. We aimed to investigate the diagnostic accuracy of the WBCT and capillary blood clotting test (CBCT) for detecting VICC in viper envenoming in Sri Lanka. METHODS: All confirmed snakebites admitted to Teaching Hospital Anuradhapura from July 2020 to June 2021 were included. On admission, WBCTs after 15, 20 and 25 min observation times (WBCT-15, WBCT-20 and WBCT-25) and CBCT observed in 30 s intervals (CBCT-t), 5 and 10 min CBCT (CBCT-5 and CBCT-10) were done. Blood was collected simultaneously for prothrombin time (PT)/international normalized ratio (INR) and plasma fibrinogen. We defined VICC as an INR >1.5 (Incomplete VICC = INR>1.5 and complete VICC = ≥3.0). RESULTS: A total of 272 confirmed snakebites (Russell's viper[76], hump-nosed viper[89], non-venomous snakes[51] and unidentified bites[56]) were recruited (median age: 42 y [interquartile range: 30- 53 y]; 189 males [69%]). On admission, 82 (30%) had incomplete VICC (INR >1.5 and <3) and 77 (28%) had complete VICC (INR ≥3). Sixteen (6%) developed clinically apparent bleeding. The WBCT-15 had the best sensitivity of 47% for detecting VICC and 68% for complete VICC. The sensitivities of the WBCT-20, WBCT-25, CBCT-5 and CBCT-10 was 30-35%. The sensitivities of all tests were better in detecting complete VICC, VICC in Russell's viper bites and more than 2 h post-bite. The WBCT-15 test had a sensitivity of 76% for VICC in confirmed Russell's viper bites. For detection of VICC, CBCT-t had an an excellent sensitivity of 97%, but a poor specificity of 35% for an optimal cut-off of >6.25 min. CONCLUSION: WBCTs are poorly diagnostic for VICC in Russell's viper and hump-nosed viper envenoming, missing up to two-thirds of patients for some tests. The WBCT-15 was the best test, improving for more severe VICC and greater than 2 h post-bite.

Long-term health effects perceived by snakebite patients in rural Sri Lanka: A cohort study.

The acute effects of snakebite are often emphasized, with less information on long-term effects. We aimed to describe the long-term health effects perceived by patients followed up after confirmed snakebites. Two groups of snakebite patients (>18y) from the Anuradhapura snakebite cohort were reviewed: Group I had a snakebite during August 2013-October 2014 and was reviewed after 4 years, and group II had a snakebite during May 2017-August 2018, and was reviewed after one year. Patients were invited by telephone, by sending letters, or doing home visits, including 199 of 736 patients (27%) discharged alive from group I and 168 of 438 patients (38%) from group II, a total of 367 followed up. Health effects were categorised as musculoskeletal, impact on daily life, and medically unexplained. Health issues were attributed to snakebite in 107/199 patients (54%) from group I and 55/168 patients (33%) from group II, suggesting the proportion with health issues increases with time. Sixteen patients (all viperine bites) had permanent musculoskeletal problems, none with a significant functional disability affecting daily routine. 217/367 reported being more vigilant about snakes while working outdoors, but only 21/367 were using protective footwear at review. Of 275 farmers reviewed, only six (2%) had restricted farming activities due to fear of snakebite, and only one stopped farming. 104/199 (52%) of group I and 42/168 (25%) of group II attributed non-specific symptoms (fatigue, body aches, pain, visual impairment) and/or oral cavity-related symptoms (avulsed teeth, loose teeth, receding gums) to the snakebite, which cannot be explained medically. In multivariate logistic regression, farming, type of snake, antivenom administration, and time since snakebite were associated with medically unexplained symptoms. The latter suggests medically unexplained effects increased with time. Based on two groups of snakebite patients reviewed one and four years post-bite, we show that long-term musculoskeletal disabilities are uncommon and not severe in snakebite survivors in rural Sri Lanka. However, a large portion of patients complain of various non-specific general and oral symptoms, not explainable based on the known pathophysiology of snakebite. These perceived effects of snakebite were more common in patients with systemic envenoming, and were more frequent the longer the time post-bite.

Demographic, exposure, clinical, biochemical and diagnostic data of febrile patients recruited for the largest field study on leptospirosis in Sri Lanka.

This dataset includes data from febrile patients recruited for a large hospital-based study in Sri Lanka from 2016 to 2019. The variables include primary socio-demographic data, exposure data, clinical data, biochemical and investigation data. Some of these data are available as serial data from admission to discharge daily. Microscopic agglutination test, quantitative PCR of whole blood, urine and serum and culture isolation was performed to diagnose the patients with leptospirosis.

Urinary biomarkers indicate pediatric renal injury among rural farming communities in Sri Lanka.

Pediatric renal injury is an emerging health concern in communities affected by chronic kidney disease of uncertain etiology (CKDu). Early detection of susceptibilities through highly sensitive and specific biomarkers can lead to effective therapeutic and preventive interventions against renal diseases. Here, we aimed to investigate the utility of kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in early detection of renal abnormalities in selected pediatric communities in Sri Lanka. The study areas were stratified as CKDu endemic, emerging, and non-endemic based on the prevalence of CKDu, and a total of 804 school students (10-18 years of age) participated in the study. The median (IQR) urinary KIM-1 levels of the participants were 0.193 (0.026-0.338), 0.082 (0.001-0.220) and 0.040 (0.003-0.242) ng/mgCr for CKDu endemic, emerging and non-endemic regions respectively. Participants from CKDu endemic regions reported elevated (p < 0.0001) urinary KIM-1 expression compared to those from the other regions. The median (IQR) NGAL levels in participants from CKDu endemic (2.969; 1.833-5.641), emerging (3.374; 1.766-6.103), and non-endemic (3.345; 1.742-5.128 ng/mgCr) regions showed no significant difference. Also, urinary albumin-creatinine ratio (UACR) showed no significant differences across gender or residency. The prevalence of albuminuria was 1-2% in the locations irrespective of CKDu burden. Albuminuric participants reported higher (p < 0.05) urinary KIM-1 levels in comparison to normoalbuminuric participants. Significantly elevated urinary KIM-1 expression in a pediatric population from CKDu affected regions, especially in the presence of albuminuria, may indicate low-grade early renal damage supporting the utility of KIM-1 as a quantifiable biomarker.

Indian Polyvalent Antivenom Accelerates Recovery From Venom-Induced Consumption Coagulopathy (VICC) in Sri Lankan Russell's Viper (Daboia russelii) Envenoming.

Background: Venom-induced consumption coagulopathy (VICC) is an important clinical consequence of Russell's viper (Daboia russelii) envenoming. There is limited evidence for antivenom effectiveness in resolving VICC. We aimed to compare the recovery of VICC in patients who received and did not receive antivenom following Russell's viper envenoming. Patients and Methods: This was a non-randomized observational study comparing patients with VICC from Russell's viper envenoming given antivenom for systemic envenoming and those not given antivenom. Antivenom administration was decided by the treating physicians. We included 44 patients with confirmed Russell's viper bites with one or more International Normalized Ratio (INR) value ≥ 1.5 (VICC). We compared five patients who did not receive antivenom with 39 patients who did receive antivenom. The primary outcome was the proportion of patients with an INR < 1.5 by 48 h post-bite. Results: The antivenom group had higher peak serum venom concentrations [median (IQR) = 272 (96-1,076) ng/mL versus 21 (8-58) ng/mL] and more severe VICC compared to the no antivenom group. Twenty seven of 39 patients (69%) in the antivenom group had an INR < 1.5 at 48 h post-bite compared to none of the five patients (0%) in the no antivenom group (absolute difference: 69%; 95%CI: 13 to 83%; p = 0.006; Fisher's exact test). The fibrinogen recovered in 32 of 39 patients (82%) in the antivenom group compared to one of five patients (20%) in the no antivenom group (absolute difference 62%; 95% CI: 28 to 95%; p = 0.001; Fisher's exact test). Both INR and fibrinogen were significantly improved between 24 and 48 h post-bite in the antivenom group compared to the no antivenom group. Conclusion: Antivenom accelerated the recovery of VICC in patients with Russell's viper envenoming, compared to no recovery in a smaller group of patients with milder VICC not receiving antivenom. This supports the efficacy of antivenom in patients with VICC.

The aetiological relationship between depressive symptoms and health-related quality of life: A population-based twin study in Sri Lanka.

OBJECTIVE: Depression often co-occurs with poor health-related quality of life (HRQL). Twin studies report genetic and individual-level environmental underpinnings in the aetiology of both depression and HRQL, but there is limited twin research exploring this association further. There is also little evidence on sex differences and non-Western populations are underrepresented. In this paper we explored the phenotypic and aetiological relationship between depressive symptoms and HRQL and possible sex differences in a low-middle-income Sri Lankan population. METHOD: Data for 3,948 participants came from the Colombo Twin and Singleton Follow-up Study (CoTaSS-2). Using self-report measures of depressive symptoms and HRQL, we conducted univariate and bivariate sex-limitation twin analyses. RESULTS: Depressive symptoms showed moderate genetic (33%) and strong nonshared environmental influences (67%). Nonshared environment accounted for the majority of variance in all the subscales of HRQL (ranging from 68 to 93%), alongside small genetic influences (ranging from 0 to 23%) and shared environmental influences (ranging from 0 to 28%). Genetic influences were significant for emotional wellbeing (23%). Shared environmental influences were significant for four out of the eight HRQL variables (ranging from 22-28%), and they were more prominent in females than males. Depressive symptoms were significantly associated with lower HRQL scores. These correlations were mostly explained by overlapping nonshared environmental effects. For traits related to emotional functioning, we also detected substantial overlapping genetic influences with depressive symptoms. CONCLUSIONS: Our study confirmed previous findings of a negative association between depressive symptoms and HRQL. However, some of the aetiological factors of HRQL differed from Western studies, particularly regarding the effects of shared environment. Our findings highlight the importance of cross-cultural research in understanding associations between psychological wellbeing and HRQL.

Relationship between CRP and depression: A genetically sensitive study in Sri Lanka.

BACKGROUND: Previous studies have shown associations between major depression and C-reactive protein (CRP) levels. Few studies have considered the extent to which shared genetic and environmental factors contribute to this association, nor have they considered the relationship outside of European populations. We examined the association between CRP levels and depression and their aetiology in a Sri Lankan population. METHODS: Data were collected from 2577 twins and 899 singletons in Colombo, Sri Lanka. Depression symptoms were assessed using the revised Beck Depression Inventory (BDI-II). High-sensitive CRP blood levels were assessed using immunoturbidimetry. Linear regressions were performed to test the association between CRP and depression. The heritability of CRP levels was estimated using Structural Equation Modelling. RESULTS: CRP was significantly associated with BMI (p < 0.01) but not depression (p > 0.05). In males, variance in CRP levels was explained by shared environment (51% 95%CIs: 13-62) and non-shared environment (45% 95%CIs: 36-54). In contrast, in females, CRP variance was explained by genetic (41% 95%CIs: 10-52) and non-shared environment (56% 95%CIs: 47-67). A genetic correlation between CRP and BMI was observed in females only. LIMITATIONS: CRP level was based on a single data collection point, longer term data collection would give a more accurate picture of an individual's state of inflammation. CONCLUSIONS: The lack of association between depression and CRP strengthens the hypothesis that inflammation might contribute to the development of some, but not all types of depression. CRP levels were moderated by the environment, suggesting interventions aimed at reducing CRP levels and risk for inflammatory conditions, particularly in males.

Ultrasound Based Radiomics Features of Chronic Kidney Disease.

RATIONALE AND OBJECTIVES: Interstitial fibrosis, common to most chronic kidney diseases, can potentially affect the speckle patterns of kidney ultrasound (US). Here we use Radiomics features derived from US images to identify kidneys with chronic kidney disease. MATERIALS AND METHODS: B-mode US without speckle reduction was performed on a cohort of CKD patients (n = 75) and healthy subjects (n = 27). Images of the patients with renal cysts, agenesis and calculi were excluded. After background subtraction, regions of interest were selected from each kidney. Four hundred and sixty-five Radiomics features including first and second-order gray level statistics were calculated on the selected regions. Second-order features were also calculated on wavelet transformed images. A random forest model was used to identify the most important features that can differentiate healthy and diseased kidneys. The ten most important features, based on the Gini index, were used to train a support vector machine. Synthetic minority oversampling technique was used to remove over fitting. RESULTS: Wavelet transformed, Gray Level Run Length Matrix based Normalized Run Length Non-uniformity, WT (LH) (GRLN) was identified as the most significant feature in differentiating CKD and healthy kidneys (accuracy - 0.85, sensitivity - 1.0). The mean WT (LH) GRLN of healthy kidneys (0.40 ± 0.01) was significantly higher (p < 0.01) than that of the CKD kidneys (0.24 ± 0.01). According to the Gini Index, the differentiability of WT (LH) GRLN was highest when the long axis of the kidney was oriented perpendicular to the columns of the image matrix. CONCLUSION: Radiomics features based on wavelet transformation are sensitive to directionality of US speckle patters and can be successfully used to differentiate CKD and healthy US kidney images.