The impact of the National Programme to Eliminate Lymphatic Filariasis on filariasis morbidity in Sri Lanka: Comparison of current status with retrospective data following the elimination of lymphatic filariasis as a public health problem.

INTRODUCTION: Sri Lanka implemented the National Programme for Elimination of Lymphatic Filariasis (NPELF) in its endemic regions in 2002. Five annual rounds of mass drug administration using the two-drug combination diethylcarbamazine (DEC) and albendazole led to sustained reductions in infection rates below threshold levels. In 2016, WHO validated that Sri Lanka eliminated lymphatic filariasis as a public health problem. OBJECTIVE: To explore the impact of the NPELF on lymphatic filariasis morbidity in Sri Lanka. METHODS: Passive Case Detection (PCD) data maintained in filaria clinic registries from 2006-2022 for lymphoedema and hospital admission data for managing hydroceles/spermatoceles from 2007-2022 were analyzed. The morbidity status in 2022 and trends in overall and district-wise PCD rates were assessed. Poisson log-linear models were used to assess the trends in PCD for endemic regions, including district-wise trends and hospital admissions for the management of hydroceles/spermatoceles. RESULTS: In 2022, there were 566 new lymphoedema case visits. The mean (SD) age was 53.9 (16.0) years. The staging was done for 94% of cases, of which 79% were in the early stages (57.3% and 21.4% in stages two and one, respectively). Western Province had the highest caseload (52%), followed by the Southern (32%) and Northwestern (16%) Provinces, respectively. The reported lymphoedema PCD rate in 2022 was 0.61 per 10,000 endemic population. The overall PCD rate showed a decline of 7.6% (95%CI: 4.9% - 10.3%) per year (P < 0.0001) from 2007 to 2022. A steady decline was observed in Colombo, Gampaha and Kurunegala districts, while Kalutara remained static and other districts showed a decline in recent years. Further, admissions for inpatient management of hydroceles/spermatoceles showed a declining trend after 2015. CONCLUSIONS: The PCD rates of lymphoedema and hydroceles/spermatoceles showed a declining trend in Sri Lanka after the implementation of the NPELF.

Effects of global change on snakebite envenoming incidence up to 2050: a modelling assessment.

BACKGROUND: Human activities are driving climate, land cover, and population change (global change), and shifting the baseline geographical distribution of snakebite. The interacting effects of global change on snakes and communities at risk of snakebite are poorly understood, limiting capacity to anticipate and manage future changes in snakebite risk. METHODS: In this modelling study, we projected how global change will affect snakebite envenoming incidence in Sri Lanka, as a model system that has a high incidence of snakebite. We used the shared socioeconomic pathway (SSP) scenario analysis framework to integrate forecasts across the domains of: climate change (historical trend from WorldClim plus three underlying regional circulation models [RCMs] in the Coordinated Regional Downscaling Experiment-South Asia repository, with two emissions pathways [representative concentration pathways RCP4.5 and RCP8.5]); land cover change (Dyna-CLUE model); and human population density change (based on Gridded Population of the World data) from Jan 1, 2010 to Dec 31, 2050. Forecasts were integrated under three different development scenarios: a sustainability pathway (SSP1 and no further emissions), a middle-of-the-road pathway (SSP2 and RCP4.5), and a fossil-fuelled pathway (SSP5 and RCP8.5). For SSP2 and SSP5, we nested three different RCMs (CNRM-CM5, GFDL-CCM3, and MPI-ESM-LR; mean averaged to represent consensus) to account for variability in climate predictions. Data were used as inputs to a mechanistic model that predicted snakebite envenoming incidence based on human-snake contact patterns. FINDINGS: From 2010 to 2050, at the national level, envenoming incidence in Sri Lanka was projected to decrease by 12·0-23·0%, depending on the scenario. The rate of decrease in envenoming incidence was higher in SSP5-RCP8.5 than in SSP1 and SSP2-RCP4.5. Change in envenoming incidence was heterogenous across the country. In SSP1, incidence decreased in urban areas expected to have population growth, and with land cover changes towards anthropised classes. In SSP2-RCP4.5 and SSP5-RCP8.5, most areas were projected to have decreases in incidence (SSP5-RCP8.5 showing the largest area with incidence reductions), while areas such as the central highlands and the north of the country showed localised increases. In the model, decreases occurred with human population growth, land use change towards anthropised classes (potentially shifting occupational risk factors), and decreasing abundance of some snake species, potentially due to global warming and reduced climatic and habitat suitability, with displacement of some snake species. INTERPRETATION: Snakebite envenoming incidence was projected to decrease overall in the coming decades in Sri Lanka, but with an apparent emerging conflict with sustainability objectives. Therefore, efforts to mitigate snakebite envenoming incidence will need to consider the potential impacts of sustainability interventions, particularly related to climate and land use change and in areas where increases in incidence are projected. In view of global change, neglected tropical diseases and public health issues related to biodiversity, such as snakebite, should be managed collaboratively by both environment and health stakeholders. FUNDING: UK Medical Research Council.

Climate change, malaria and neglected tropical diseases: a scoping review.

To explore the effects of climate change on malaria and 20 neglected tropical diseases (NTDs), and potential effect amelioration through mitigation and adaptation, we searched for papers published from January 2010 to October 2023. We descriptively synthesised extracted data. We analysed numbers of papers meeting our inclusion criteria by country and national disease burden, healthcare access and quality index (HAQI), as well as by climate vulnerability score. From 42 693 retrieved records, 1543 full-text papers were assessed. Of 511 papers meeting the inclusion criteria, 185 studied malaria, 181 dengue and chikungunya and 53 leishmaniasis; other NTDs were relatively understudied. Mitigation was considered in 174 papers (34%) and adaption strategies in 24 (5%). Amplitude and direction of effects of climate change on malaria and NTDs are likely to vary by disease and location, be non-linear and evolve over time. Available analyses do not allow confident prediction of the overall global impact of climate change on these diseases. For dengue and chikungunya and the group of non-vector-borne NTDs, the literature privileged consideration of current low-burden countries with a high HAQI. No leishmaniasis papers considered outcomes in East Africa. Comprehensive, collaborative and standardised modelling efforts are needed to better understand how climate change will directly and indirectly affect malaria and NTDs.

Prevalence and associated factors for non-alcoholic fatty liver disease among adults in the South Asian Region: a meta-analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease worldwide. We estimated the prevalence and predefined associated factors for NAFLD among South-Asian adults. Methods: We searched PubMed and included descriptive, epidemiological studies with satisfactory methodology, reporting the prevalence of NAFLD with ultrasound. Two authors screened and extracted data independently. Gender, urban/rural settings, general population and individuals with metabolic diseases (MetD) stratified the analysis. In addition, a random-effects meta-analysis of the prevalence and effect sizes of associations of NAFLD was performed. Findings: Twenty-two publications were included after the quality assurance process. The difference in the NAFLD prevalence between the general population and people with MetD was found to be statistically significant (Q = 15.8, DF = 1, P < 0.001). The pooled overall prevalence of NAFLD in the general population was 26.9% (95% CI: 18.9-35.8%) with high heterogeneity. The prevalence was similar among men and women (Q = 0.06, DF = 1, P = 0.806). The NAFLD prevalence in the rural communities was 22.6% (95% CI: 13.6-33.1%), and the prevalence in urban communities was 32.9% (95% CI: 22.8-43.8%) and the difference was not statistically significant (Q = 1.92, DF = 1, P = 0.166). The pooled overall prevalence of NAFLD in patients with MetD was 54.1% (95% CI: 44.1-63.9%) with high heterogeneity. The pooled overall prevalence of NAFLD in the non-obese population was 11.7% (95% CI: 7.0-17.3%). The pooled prevalence of non-obese NAFLD in the NAFLD population was 43.4% (95% CI: 28.1-59.4%). Meta-analysis of binary variables showed that NAFLD in the South Asian population was associated with diabetes mellitus, hypertension, dyslipidaemia, general obesity, central obesity and metabolic syndrome. Gender was not associated with NAFLD. Interpretation: The overall prevalence of NAFLD among adults in South Asia is high, especially in those with MetD, and a considerable proportion is non-obese. In the South Asian population, NAFLD was associated with diabetes mellitus, hypertension, dyslipidaemia, general obesity, central obesity, and metabolic syndrome. Funding: None.

Lymphatic filariases and soil-transmitted helminthiases in Sri Lanka: the challenge of eliminating residual pockets of transmission.

Sri Lanka has successfully met the challenge of controlling both lymphatic filariasis (LF) and soil-transmitted helminthiases (STH) as public health problems. The primary public health strategy for combatting both conditions has been preventive chemotherapy. The national programme for the elimination of LF implemented five annual rounds of mass chemotherapy in the endemic districts from 2002 to 2006 using a combination of diethylcarbamazine and albendazole. The overall microfilaria rate declined from 0.21% in 2001 before the mass chemotherapy, to 0.06% in 2016, at declaration of elimination of LF as a public health problem by the World Health Organization. Currently Sri Lanka is in the phase of post-validation surveillance. Achieving control of STH has been more difficult. Mass deworming programmes have been implemented for nearly a century, and national-level surveys reported prevalence rates declining from 6.9% in 2003 to 1% in 2017. However, neither of these infections has been completely eliminated. A situation analysis indicates continued transmission of both among high-risk communities. This paper explores the reasons for persistence of transmission of both LF and STH in residual pockets and the measures that are required to achieve long-term control, or perhaps even interrupt transmission in Sri Lanka. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Neoadjuvant Chemoradiation for Rectal Cancer Achieves Satisfactory Tumour Regression and Local Recurrence - Result of a Dedicated Multi-disciplinary Approach from a South Asian Centre.

BACKGROUND: Pre-operative long-course chemoradiotherapy (CRT) for rectal cancer has resulted in improvement in rates of restorative rectal resection and local recurrence by inducing tumour downstaging and downsizing. Total mesorectal excision (TME) is a standardised surgical technique of low anterior resection aimed at the prevention of local tumour recurrence. The purpose of this study was to evaluate tumour response following CRT in a standardised group of patients with rectal cancer. METHODS: One hundred and thirty-one patients (79 male; 52 female, median age 57; interquartile range 47-62 years) of 153 with rectal cancer who underwent pre-operative long-course CRT were treated by standardised open low anterior resection at a median of 10 weeks post-CRT. Sixteen of 131 (12%) were 70 years or older. Median follow-up at the time of analysis was 15 months (interquartile range 6-45 months). Pathology reports were analysed based on AJCC-UICC classification using the TNM system. Data recorded were overall/subgrades of tumour regression; good, moderate or poor, lymph node harvest, local recurrence, disease-free and overall survival using standard statistical methods. RESULTS: 78% showed tumour regression post-CRT; 43% displayed good tumour regression/response while 22% had poor tumour regression/response. All patients had a pre-operative T-stage of either T3 or T4. Post-operation, good responders had a median T stage of T2 vs. T3 in poor responders (P = 0.0002). Overall, the median lymph node harvest was < 12. There was no difference in the number of nodes harvested in good vs. poor responders (Good/moderate-6 nodes vs. Poor- 8; P = 0.31). Good responders tended to have a lesser number of malignant nodes vs. poor responders (P = 0.31). Overall, local recurrence was 6.8% and the anal sphincter preservation rate was 89%. Predicted 5-year disease-free and overall survival were similar between good and poor responders. CONCLUSION: Long-course CRT resulted in satisfactory tumour regression and enabled consideration for safe, sphincter-saving resection in rectal cancer. A dedicated multi-disciplinary team approach achieved a global benchmark for local recurrence in a resource-limited setting.

Clinical Exome Gene Panel Analysis of a Cohort of Urothelial Bladder Cancer Patients from Sri Lanka.

BACKGROUND: Bladder cancer has a high rate of recurrence and high mortality rates in those who progress to muscle invasive disease. Biomarkers and molecular sub classification of tumours beyond standard histopathology has been proposed to address therapeutic dilemmas. The Cancer Genome Atlas project and other studies have contributed to the enhanced knowledge base of the mutational landscape of urothelial bladder cancer. Once again, these are mostly from Caucasian and Chinese patients, with data from the rest of Asia and Sri Lanka being sparse. The objective of this study was to assess the genomic variations of a cohort of urothelial bladder cancer patients in Sri Lanka. METHODS: The molecular genetic study was conducted on formalin fixed paraffin embedded tumour samples of 24 patients, prospectively enrolled from 2013 to 2017. The samples were sequenced and variant distribution performed based on a 70-gene panel. RESULTS: Total number of filtered mutations in the 24 patients was 10453. Median mutations per patient were 450 (range 22-987). The predominant mutational change was C>T and G>A. The top 5 mutated genes in our cohort were SYNE1, SYNE2, KMT2C, LRP2, and ANK2. The genes were clustered into 3 groups dependent on the number of mutations per patient per gene. The genes of cluster 1 and 2 mapped to Chromatin modifying enzymes and Generic Transcription Pathway. The chromatin remodelling pathway accounted for the largest proportion (22%) of mutations. CONCLUSIONS: Clinical exome sequencing utilising a gene panel yielded a high mutation rate in our patients. The predominant mutational change was C>T and G>A. Three clusters of genes were identified. SYNE1 was the gene with the most mutations. The mutations comprised predominantly of genes of the chromatin remodelling pathway.

Climate change maladaptation for health: Agricultural practice against shifting seasonal rainfall affects snakebite risk for farmers in the tropics.

Snakebite affects more than 1.8 million people annually. Factors explaining snakebite variability include farmers' behaviors, snake ecology and climate. One unstudied issue is how farmers' adaptation to novel climates affect their health. Here we examined potential impacts of adaptation on snakebite using individual-based simulations, focusing on strategies meant to counteract major crop yield decline because of changing rainfall in Sri Lanka. For rubber cropping, adaptation led to a 33% increase in snakebite incidence per farmer work hour because of work during risky months, but a 17% decrease in total annual snakebites because of decreased labor in plantations overall. Rice farming adaptation decreased snakebites by 16%, because of shifting labor towards safer months, whereas tea adaptation led to a general increase. These results indicate that adaptation could have both a positive and negative effect, potentially intensified by ENSO. Our research highlights the need for assessing adaptation strategies for potential health maladaptations.

The association between steatosis and liver damage in transfusion-dependent beta thalassaemia patients.

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.

Prevalence and correlates of cognitive impairment in schizophrenia: a cross-sectional study from a teaching hospital southern Sri Lanka.

INTRODUCTIONS: This study assessed the prevalence of cognitive impairment, the degree of impairment in individual cognitive domains and sociodemographic and clinical correlates among patients attending to psychiatry clinics at Teaching Hospital, Karapitiya, Sri Lanka. METHODS: A cross-sectional study was carried out at the psychiatry outpatient clinics of Teaching Hospital, Karapitiya, Sri Lanka. Their cognitive functions were assessed using the culturally validated Sinhala version of Addenbrooke's Cognitive Examination - III (ACE-III-S). ACE-III-S score below 85.5 was considered as significant cognitive impairment. Linear regression analysis was used to assess the factors associated with cognitive impairment. A P value of 0.05 is considered significant. RESULTS: One hundred forty patients with schizophrenia were assessed. Of this, 125 patients had significant cognitive impairment with a prevalence of 89.3% (95% CI:84.1-94.5). Impairment in each cognitive domain was as follows: 60% in attention, 65.7% in memory, 55% in fluency, 61.4% in language, and 63.6% in visuospatial skills. Impairment was not different between cognitive domains. Advancing age (P < 0.001), shorter duration of formal education (P = < 0.001), longer duration of illness (P = < 0.001) and not having a full-time employment (P = 0.020) showed a positive association with cognitive impairment. CONCLUSIONS: Nine out of ten patients with schizophrenia experienced significant cognitive impairment. Patients showed more than 50% impairment in all cognitive domains. The cognitive domains did not show disproportionate impairment. This study highlights the importance of introducing routine cognitive assessment protocols in patients with schizophrenia.

Geographically regulated designs of incidence surveys can match the precision of classical survey designs whilst requiring smaller sample sizes: the case of snakebite envenoming in Sri Lanka.

BACKGROUND: Snakebite envenoming is a neglected tropical disease. Data from the worst affected countries are limited because conducting epidemiological surveys is challenging. We assessed the utility of inhibitory geostatistical design with close pairs (ICP) to estimate snakebite envenoming incidence. METHODS: The National Snakebite Survey (NSS) in Sri Lanka adopted a multistage cluster sampling design, based on population distribution, targeting 1% of the country's population. Using a simulation-based study, we assessed predictive efficiency of ICP against a classical survey design at different fractions of the original sample size of the NSS. We also assessed travel distance, time taken to complete the survey, and sensitivity and specificity for detecting high-risk areas for snake envenoming, when using these methods. RESULTS: A classical survey design with 33% of the original NSS sample size was able to yield a similar predictive efficiency. ICP yielded the same at 25% of the NSS sample size, a 25% reduction in sample size compared with a classical survey design. ICP showed >80% sensitivity and specificity for detecting high-risk areas of envenoming when the sampling fraction was >20%. When ICP was adopted with 25% of the original NSS sample size, travel distance was reduced by >40% and time to conduct the survey was reduced by >75%. CONCLUSIONS: This study showed that snakebite envenoming incidence can be estimated by adopting an ICP design with similar precision at a lower sample size than a classical design. This would substantially save resources and time taken to conduct epidemiological surveys and may be suited for low-resource settings.

Using FIB-4 score as a screening tool in the assessment of significant liver fibrosis (F2) in patients with transfusion-dependent beta thalassaemia: a cross-sectional study.

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.

A mechanistic model of snakebite as a zoonosis: Envenoming incidence is driven by snake ecology, socioeconomics and its impacts on snakes.

Snakebite is the only WHO-listed, not infectious neglected tropical disease (NTD), although its eco-epidemiology is similar to that of zoonotic infections: envenoming occurs after a vertebrate host contacts a human. Accordingly, snakebite risk represents the interaction between snake and human factors, but their quantification has been limited by data availability. Models of infectious disease transmission are instrumental for the mitigation of NTDs and zoonoses. Here, we represented snake-human interactions with disease transmission models to approximate geospatial estimates of snakebite incidence in Sri Lanka, a global hotspot. Snakebites and envenomings are described by the product of snake and human abundance, mirroring directly transmitted zoonoses. We found that human-snake contact rates vary according to land cover (surrogate of occupation and socioeconomic status), the impacts of humans and climate on snake abundance, and by snake species. Our findings show that modelling snakebite as zoonosis provides a mechanistic eco-epidemiological basis to understand snakebites, and the possible implications of global environmental and demographic change for the burden of snakebite.

Student usage of open educational resources and social media at a Sri Lanka Medical School.

BACKGROUND: The use of Open Educational Resources (OER) and Social Media (SM) for academic information seeking is common among undergraduates nowadays. There is limited data on OER and SM use for education in Sri Lanka. This study was aimed at evaluating the OER and SM use for education among the medical students at the Faculty of Medicine, University of Kelaniya, Sri Lanka. METHODS: A cross-sectional study was conducted at the Faculty of Medicine, University of Kelaniya. Stratified random sampling was used to select students from the first year to the final year. A self-administrated questionnaire was used to collect data. RESULTS: The study included 257 responses (response rate: 89.5%), of which 185 (72.0%) were females. The OER and SM use for educational purposes at least once a month among students was 96.1% (95%CI: 93.7-98.5%) and 88.3% (95%CI: 84.4-92.3%) respectively. There was no gender difference in OER and SM use. The main reasons for accessing OER were the availability of information at any time (36.1%) and ease of information access (31.5%). Wiki sites (84.4%) and Facebook (79.8%) were the highest accessed OER and SM platforms. The majority of students were in view that the information on wiki sites (51.4%) and results of general non-specific web searches (56.0%) were reliable. Only 33.9% of students searched information from educational and government-related sources and 18.7% had accessed e-journals. Through SM, 79.0% joined educational groups and 77.0% followed the medical-related sites, pages and people. More than one-third of students (35.8%) could not find academic information from SM due to the information overload and 31.1% mentioned that SM distracted their education. CONCLUSION: The majority of the students used OER and SM for education; however, only a minority accessed reliable information. Students accepted information available in wiki sites and general non-specific web searchers without considering the credibility of sources. The majority of the students did not refer to e-journals. Distractions to academic work and the difficulty to access accurate information were major concerns of using SM. This study highlights the importance of improving information literacy among medical students.

Demographics, pathological characteristics and survival in urothelial bladder cancer in a cohort of Sri Lankan patients.

Introduction: Bladder cancer has the 9th highest incidence among Sri Lankan males. This study describes the demographic profiles and survival in bladder cancer patients at two tertiary care centres in Sri Lanka. Methods: A group of patients with urothelial bladder cancer, presenting for the first time for definitive treatment, were prospectively enrolled from 2013 to 2017. Results: There were sixty-six patients, with median age of 65 years and male to female ratio of 7:1. Histopathologically pTa 24%, pT1 47% and pT2 29%. Of the pT1 tumours 61% were low grade (LG). The majority (71%) of non-muscle invasive bladder cancer (NMIBC) patients underwent transurethral resection of bladder tumour only. For the entire cohort the 5-year overall survival was 59% and cancer specific survival (CSS) was 65%. CSS in NMIBC was 75% and 30% in muscle invasive bladder cancer (MIBC). The 5-year female CSS (22%) was significantly lower than in males (71%). Conclusion: Our cohort has a high male to female ratio. The percentage of MIBC was lower than reported in previous Sri Lankan studies. Of the pT1 tumours there is a higher percentage of pT1 LG patients in comparison to Western reports. There is low utilisation of intravesical mitomycin / bacillus Calmette-Guérin (BCG) in the treatment of NMIBC. The 5-year CSS in the Sri Lankan (lower middle-income economy) cohort lies between the values of high-income economies and upper middle-income economies in Asia. The reasons for poor CSS among Sri Lankan women with bladder cancer needs to be further investigated.

Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study.

BACKGROUND: Worldwide, haemoglobin E ß-thalassaemia is the most common genotype of severe ß-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia. METHODS: In this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality. FINDINGS: 109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14-20). Median age at recruitment was 13 years (range 8-21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45-not reached). Median survival was worse among male patients (hazard ratio [HR] 2·51, 95% CI 1·16-5·43), patients with a history of serious infections (adjusted HR 8·49, 2·90-24·84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1·03, 1·01-1·06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4·5 g/dL (vs concentration >4·5 g/dL), serum ferritin concentration more than 1300 µg/L (vs concentration ≤1300 µg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration ≤5 mg/g) were associated with poorer survival. INTERPRETATION: Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival. FUNDING: Wellcome Trust, Medical Research Council, US March of Dimes, Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal.

Addressing the global snakebite crisis with geo-spatial analyses - Recent advances and future direction.

Venomous snakebite is a neglected tropical disease that annually leads to hundreds of thousands of deaths or long-term physical and mental ailments across the developing world. Insufficient data on spatial variation in snakebite risk, incidence, human vulnerability, and accessibility of medical treatment contribute substantially to ineffective on-ground management. There is an urgent need to collect data, fill knowledge gaps and address on-ground management problems. The use of novel, and transdisciplinary approaches that take advantage of recent advances in spatio-temporal models, 'big data', high performance computing, and fine-scale spatial information can add value to snakebite management by strategically improving our understanding and mitigation capacity of snakebite. We review the background and recent advances on the topic of snakebite related geospatial analyses and suggest avenues for priority research that will have practical on-ground applications for snakebite management and mitigation. These include streamlined, targeted data collection on snake distributions, snakebites, envenomings, venom composition, health infrastructure, and antivenom accessibility along with fine-scale models of spatio-temporal variation in snakebite risk and incidence, intraspecific venom variation, and environmental change modifying human exposure. These measures could improve and 'future-proof' antivenom production methods, antivenom distribution and stockpiling systems, and human-wildlife conflict management practices, while simultaneously feeding into research on venom evolution, snake taxonomy, ecology, biogeography, and conservation.

Evaluating spatiotemporal dynamics of snakebite in Sri Lanka: Monthly incidence mapping from a national representative survey sample.

BACKGROUND: Snakebite incidence shows both spatial and temporal variation. However, no study has evaluated spatiotemporal patterns of snakebites across a country or region in detail. We used a nationally representative population sample to evaluate spatiotemporal patterns of snakebite in Sri Lanka. METHODOLOGY: We conducted a community-based cross-sectional survey representing all nine provinces of Sri Lanka. We interviewed 165 665 people (0.8% of the national population), and snakebite events reported by the respondents were recorded. Sri Lanka is an agricultural country; its central, southern and western parts receive rain mainly from Southwest monsoon (May to September) and northern and eastern parts receive rain mainly from Northeast monsoon (November to February). We developed spatiotemporal models using multivariate Poisson process modelling to explain monthly snakebite and envenoming incidences in the country. These models were developed at the provincial level to explain local spatiotemporal patterns. PRINCIPAL FINDINGS: Snakebites and envenomings showed clear spatiotemporal patterns. Snakebite hotspots were found in North-Central, North-West, South-West and Eastern Sri Lanka. They exhibited biannual seasonal patterns except in South-Western inlands, which showed triannual seasonality. Envenoming hotspots were confined to North-Central, East and South-West parts of the country. Hotspots in North-Central regions showed triannual seasonal patterns and South-West regions had annual patterns. Hotspots remained persistent throughout the year in Eastern regions. The overall monthly snakebite and envenoming incidences in Sri Lanka were 39 (95%CI: 38-40) and 19 (95%CI: 13-30) per 100 000, respectively, translating into 110 000 (95%CI: 107 500-112 500) snakebites and 45 000 (95%CI: 32 000-73 000) envenomings in a calendar year. CONCLUSIONS/SIGNIFICANCE: This study provides information on community-based monthly incidence of snakebites and envenomings over the whole country. Thus, it provides useful insights into healthcare decision-making, such as, prioritizing locations to establish specialized centres for snakebite management and allocating resources based on risk assessments which take into account both location and season.

Prevalence and predictors of new onset depression in the acute phase of stroke.

INTRODUCTION: Post-stroke depression (PSD) is known to be associated with poor functional outcome and high mortality. There is limited data on the prevalence and associated factors of depression in the acute phase after stroke. OBJECTIVES: To determine the prevalence of PSD in the acute phase and its correlates among patients with stroke in a tertiary care hospital in Sri Lanka. METHOD: A cross sectional descriptive study was conducted among patients with stroke admitted to the stroke unit of a tertiary care hospital in Sri Lanka over a 3-year period. Demographic and clinical information was obtained using an interviewer administered questionnaire. Depression was diagnosed using the ICD-10 criteria. Group comparisons were performed using Pearson's Chi-square test and Mann-Whitney U test Multiple logistic regression was used to identify factors associated with PSD. RESULTS: Of 374 patients, 106 patients experienced moderate to severe PSD, with a prevalence of 28.3 % (95 % CI: 23.8 %-32.9 %). Of them, 54.7 % were females, 49 % were above the age of 60 years, and 79.9 % had ischemic strokes. Female gender (OR-2.77, 95 % CI: 1.46-5.07, P = 0.002), a longer duration of hypertension (OR-1.31, 95 % CI: 1.01-1.721, P = 0.004), strokes involving the temporal lobe (OR-7.25, 95 % CI: 2.81-20.25, P < 0.001) and post-stroke functional disability (OR- O.98, 95 % CI:0.97-0.99, P = 0.001) were associated with PSD on multivariate analysis. CONCLUSION: More than one fourth of the patients suffered from PSD in the acute phase of stroke. Female gender, longer history of hypertension, physical dependence and temporal lobe strokes were predictive of PSD.

Revisiting the ATP 30: the Factor Structure of a Scale Measuring Medical Students' Attitudes Towards Psychiatry.

OBJECTIVE: Among the scales developed for assessing medical students' attitudes regarding psychiatry, "attitude towards psychiatry-30" (ATP-30) is probably the most widely used. Although this scale was originally deemed to form a unitary dimension without any meaningful subscales, the authors sought to re-examine its factor structure and the viability of subscales. METHOD: Secondary data from a survey of 743 final-year medical students from nine medical schools in Sri Lanka were analyzed using exploratory factor analysis (EFA) with promax rotation and confirmatory factor analysis (CFA), to assess the underlying factor structure of ATP-30. Parallel analysis was used in determining the number of factors to retain. Items conceptually external to the emerging factors were discarded. RESULTS: Three models based on literature (one-, five-, and eight-factor) were disproved by CFA. A six-factor solution encompassing 18 items was supported by EFA and CFA and was gender-invariant. These factors were, namely, the image of psychiatrists, psychiatric patients and mental illness, the efficacy of treatment, psychiatric teaching, career choice, and psychiatry as an evidence-based discipline. While "the image of psychiatrists" formed the most consistent subscale (ω = 0.71), the internal consistencies of the other subscales were modest (ω = 0.55-0.67). The overall 18-item scale showed good internal consistency (ω = 0.78). CONCLUSION: The findings provide evidence of a multi-dimensional structure in medical students' attitudes towards psychiatry, endorsing six meaningful subscales of the ATP-30. Future researchers and educators can utilize these subscales in identifying specific areas where students' attitudes are more stigmatized, to be intervened during undergraduate training.