Overall Survival of Elderly Patients Having Surgery for Colorectal Cancer Is Comparable to Younger Patients: Results from a South Asian Population

Introduction. There has been a continuous debate on whether elderly patients with colorectal cancer (CRC) fair worse. The aim of this study is to assess the thirty-day mortality (TDM) and overall survival (OS) of elderly patients undergoing surgery for CRC. Method. OS between two groups (≥70 versus <70 years) having surgery for CRC was analyzed. Demographics, tumour characteristics, and serological markers were considered as independent factors. Multivariable analysis was done using the Cox proportional hazard model. We also compared overall survival in the elderly versus those <60 and <50 years. Results. 477 patients, 160 elderly (55% male; median age 75, range 70–89) and 317 younger patients (49% male; median age 55, range 16 to 69), were studied. Overall survival in CRC patients ≥70 is comparable to <70 (P=0.45) and <60 years (P=0.08). Poor OS was observed in the ≥70 versus <50 years (P=0.03). TDM in the elderly was poor (P<0.05). Postoperative cardiac complication was the only determinant affecting survival in the elderly (P=0.01). Conclusion. OS in elderly CRC patients having surgery is not worse compared to <70 and <60 years although the TDM was higher. Postoperative cardiac complications significantly affected OS in those ≥70 compared to those <50 years. Chronological age alone should not negatively influence surgical decision-making in the elderly

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

Integrating human behavior and snake ecology with agent-based models to predict snakebite in high risk landscapes.

Snakebite causes more than 1.8 million envenoming cases annually and is a major cause of death in the tropics especially for poor farmers. While both social and ecological factors influence the chance encounter between snakes and people, the spatio-temporal processes underlying snakebites remain poorly explored. Previous research has focused on statistical correlates between snakebites and ecological, sociological, or environmental factors, but the human and snake behavioral patterns that drive the spatio-temporal process have not yet been integrated into a single model. Here we use a bottom-up simulation approach using agent-based modelling (ABM) parameterized with datasets from Sri Lanka, a snakebite hotspot, to characterise the mechanisms of snakebite and identify risk factors. Spatio-temporal dynamics of snakebite risks are examined through the model incorporating six snake species and three farmer types (rice, tea, and rubber). We find that snakebites are mainly climatically driven, but the risks also depend on farmer types due to working schedules as well as species present in landscapes. Snake species are differentiated by both distribution and by habitat preference, and farmers are differentiated by working patterns that are climatically driven, and the combination of these factors leads to unique encounter rates for different landcover types as well as locations. Validation using epidemiological studies demonstrated that our model can explain observed patterns, including temporal patterns of snakebite incidence, and relative contribution of bites by each snake species. Our predictions can be used to generate hypotheses and inform future studies and decision makers. Additionally, our model is transferable to other locations with high snakebite burden as well

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

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

Budget impact and cost-effectiveness analyses of the COBRA-BPS multicomponent hypertension management programme in rural communities in Bangladesh, Pakistan, and Sri Lanka.

BACKGROUND: COBRA-BPS (Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka), a multi-component hypertension management programme that is led by community health workers, has been shown to be efficacious at reducing systolic blood pressure in rural communities in Bangladesh, Pakistan, and Sri Lanka. In this study, we aimed to assess the budget required to scale up the programme and the incremental cost-effectiveness ratios. METHODS: In a cluster-randomised trial of COBRA-BPS, individuals aged 40 years or older with hypertension who lived in 30 rural communities in Bangladesh, Pakistan, and Sri Lanka were deemed eligible for inclusion. Costs were quantified prospectively at baseline and during 2 years of the trial. All costs, including labour, rental, materials and supplies, and contracted services were recorded, stratified by programme activity. Incremental costs of scaling up COBRA-BPS to all eligible adults in areas covered by community health workers were estimated from the health ministry (public payer) perspective. FINDINGS: Between April 1, 2016, and Feb 28, 2017, 11 510 individuals were screened and 2645 were enrolled and included in the study. Participants were examined between May 8, 2016, and March 31, 2019. The first-year per-participant costs for COBRA-BPS were US$10·65 for Bangladesh,$10·25 for Pakistan, and $6·42 for Sri Lanka. Per-capita costs were$0·63 for Bangladesh, $0·29 for Pakistan, and$1·03 for Sri Lanka. Incremental cost-effectiveness ratios were $3430 for Bangladesh,$2270 for Pakistan, and $4080 for Sri Lanka, per cardiovascular disability-adjusted life year averted, which showed COBRA-BPS to be cost-effective in all three countries relative to the WHO-CHOICE threshold of three times gross domestic product per capita in each country. Using this threshold, the cost-effectiveness acceptability curves predicted that the probability of COBRA-BPS being cost-effective is 79·3% in Bangladesh, 85·2% in Pakistan, and 99·8% in Sri Lanka. INTERPRETATION: The low cost of scale-up and the cost-effectiveness of COBRA-BPS suggest that this programme is a viable strategy for responding to the growing cardiovascular disease epidemic in rural communities in low-income and middle-income countries where community health workers are present, and that it should qualify as a priority intervention across rural settings in south Asia and in other countries with similar demographics and health systems to those examined in this study. FUNDING: The UK Department of Health and Social Care, the UK Department for International Development, the Global Challenges Research Fund, the UK Medical Research Council, Wellcome Trust

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

BACKGROUND Worldwide, haemoglobin E β-thalassaemia is the most common genotype of severe β-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

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

Abstract 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

Risk of low birth weight on adulthood hypertension - evidence from a tertiary care hospital in a South Asian country, Sri Lanka: a retrospective cohort study

Abstract Background Although low birth weight (LBW) is common in South Asian region there are not many studies being done to evaluate LBW and adulthood hypertension association in this region, including in Sri Lanka. Although this association has been studied in other regions, most studies have not evaluated this association in the presence of socioeconomic and lifestyle factors. This study was conducted to investigate whether low birth weight (LBW) is associated with adulthood hypertension after adjusting for other potential risk factors of hypertension. Methods Nearly 15,000 individuals born during 1950 to 1965 were selected and invitations were sent to their original addresses. Out of them 217 individuals responded and among them birth weight was recovered for 122 individuals. Separate linear logistic models were fitted to model high systolic blood pressure (SBP: systolic blood pressure > 140 mmHg), high diastolic blood pressure (DBP: diastolic blood pressure > 90 mmHg) and hypertension (either SBP > 140 mmHg or DBP > 90 mmHg). Results Separate linear logistic model fitting revealed LBW having a significant association with high SBP (OR = 2.89; 95% CI: 1.01 to 8.25; P = 0.04), and hypertension (OR = 3.15; 95% CI: 1.17 to 9.35; P = 0.03), but not with high DBP (OR = 0.75; 95% CI: 0.22 to 2.16; P = 0.62), when effect of LBW was studied after adjusting for all other potential risk factors. Conclusions LBW has a tendency to cause high adult blood pressure in South Asian region, and the findings are consistent with previous work on LBW and adulthood hypertension association in other regions of the world