Comparative Risk Assessment Study Research Articles

Neurotoxicity Evaluation of Rutin Trihydrate vs. Metformin in Zebrafish Larvae: A Comparative Risk Assessment Study

To examine the neurotoxicity induced by the novel drug Rutin trihydrate and metformin in the zebrafish larvae model. Test solutions for the exposure groups were prepared by diluting the stock solution with egg water. These solutions contained 30 µM metformin in combination with 9.5 µM of the innovative drug rutin trihydrate. Maintenance of zebrafish and egg collection: Breeding groups were chambered in a specific spawning tank in a male-to-female ratio of 1:1. The spawning tank is provided with a box and with mesh as the bottom base to collect the zebrafish embryos and to protect the zebrafish embryos from the adult fish. Embryotoxicity assay: This work includes 2 groups and a total sample size of 30. Group 1 underwent examination using the novel drug Rutin trihydrate, which exhibits solubility in 0.01% of Dimethyl sulfoxide (DMSO), while Group 2 was subjected to examination using metformin, soluble in 100µl of DMSO (Dimethyl sulfoxide) combined with 99% water, both assessments conducted on larval zebrafish. Embryos were segregated for each exposure in groups in petri plates with n= 15 embryos per plate and were exposed to the novel drug Rutin trihydrate from 4 - 96 hpf (Hours Post Fertilization). Other conditions required for the validation of this study were maintained as stated by the OECD (Organization for Economic All the experiments were carried out in triplicate. Statistical analysis: SPSS software facilitated the determination of statistical significance between the two groups. The parameters adhered to a confidential ratio of 95%, a threshold of 0.05, G power at 80%, and an enrolment ratio of 1. Results indicated a significant neuroprotective effect of rutin trihydrate-treated larvae (27.77±1.15) compared to metformin-treated larvae (18.0±0.68), displaying a statistical significance of p = 0.000 (p < 0.05).

Estimating the changing burden of disease attributable to alcohol use in South Africa for 2000, 2006 and 2012.

Alcohol use was one of the leading contributors to South Africa (SA)'s disease burden in 2000, accounting for 7% of deaths and disability-adjusted life years (DALYs) in the first South African Comparative Risk Assessment Study (SACRA1). Since then, patterns of alcohol use have changed, as has the epidemiological evidence pertaining to the role of alcohol as a risk factor for infectious diseases, most notably HIV/AIDS and tuberculosis (TB). To estimate the burden of disease attributable to alcohol use by sex and age group in SA in 2000, 2006 and 2012. The analysis follows the World Health Organization (WHO)'s comparative risk assessment methodology. Population attributable fractions (PAFs) were calculated from modelled exposure estimated from a systematic assessment and synthesis of 17 nationally representative surveys and relative risks based on the global review by the International Model of Alcohol Harms and Policies. PAFs were applied to the burden of disease estimates from the revised second South African National Burden of Disease Study (SANBD2) to calculate the alcohol-attributable burden for deaths and DALYs for 2000, 2006 and 2012. We quantified the uncertainty by observing the posterior distribution of the estimated prevalence of drinkers and mean use among adult drinkers (≥15 years old) in a Bayesian model. We assumed no uncertainty in the outcome measures. The alcohol-attributable disease burden decreased from 2000 to 2012 after peaking in 2006, owing to shifts in the disease burden, particularly infectious disease and injuries, and changes in drinking patterns. In 2012, alcohol-attributable harm accounted for an estimated 7.1% (95% uncertainty interval (UI) 6.6 - 7.6) of all deaths and 5.6% (95% UI 5.3 - 6.0) of all DALYs. Attributable deaths were split three ways fairly evenly across major disease categories: infectious diseases (36.4%), non-communicable diseases (32.4%) and injuries (31.2%). Top rankings for alcohol-attributable DALYs for specific causes were TB (22.6%), HIV/AIDS (16.0%), road traffic injuries (15.9%), interpersonal violence (12.8%), cardiovascular disease (11.1%), cancer and cirrhosis (both 4%). Alcohol remains an important contributor to the overall disease burden, ranking fifth in terms of deaths and DALYs. Although reducing overall alcohol use will decrease the burden of disease at a societal level, alcohol harm reduction strategies in SA should prioritise evidence-based interventions to change drinking patterns. Frequent heavy episodic (i.e. binge) drinking accounts for the unusually large share of injuries and infectious diseases in the alcohol-attributable burden of disease profile. Interventions should focus on the distal causes of heavy drinking by focusing on strategies recommended by the WHO's SAFER initiative.

Estimating the changing burden of disease attributable to interpersonal violence in South Africa for 2000, 2006 and 2012.

South Africa (SA)'s high rate of interpersonal violence persists as a leading public health problem for the country. The first South African Comparative Risk Assessment Study (SACRA1) in 2000 quantified the long-term mental and physical health burden attributable to interpersonal violence by supplementing the direct injury burden of disease attributable to interpersonal violence injuries with the substantial contribution of mental health, behavioural and reproductive health consequences accruing from exposure to intimate partner violence (IPV) and child sexual abuse. To revise and improve these estimates by including the additional burden from other forms of child maltreatment, community violence, sexual violence by non-partners, and bullying victimisation in SA for 2000, 2006 and 2012, and trends over time. We used comparative risk assessment methods to calculate population attributable fractions (PAFs) for interpersonal violence. This method requires inputs on the prevalence of exposure to the interpersonal violence risk factor subtypes, namely child maltreatment, bullying, IPV, sexual violence by non-partners and other community violence; the burden of related health outcomes (mortality and morbidity); and relative risks of health outcomes in individuals exposed to the risk factor v. those unexposed. We estimated the PAF for the combinations of all interpersonal violence subtypes together to estimate the burden attributable to interpersonal violence overall for 2000, 2006 and 2012. Between 2000 and 2012, there was a decrease in interpersonal violence age-standardised attributable death rates from 100 to 71 per 100 000. In the second South African Comparative Risk Assessment Study (SACRA2), estimates of the attributable disability-adjusted life years (DALYs) for interpersonal violence for the year 2000 were revised, from 1.7 million to 2 million DALYs, taking into account attributable mortality and disability from additional forms of violence. There was a decrease in DALYs attributable to interpersonal violence from 2 million in 2000 to 1.75 million in 2012, accounting for 8.5% of the total burden for SA, ranking second highest, after unsafe sex, among 18 risk factors evaluated in 2012. Overall, interpersonal violence-attributable DALYs decreased substantially but remain high. The reduction in age-standardised attributable death rates indicates that some policy and social intervention aspects are effective. Further strengthening of existing laws pertaining to interpersonal violence, and other prevention measures, are needed to intensify the prevention of violence, particularly gender-based violence. Additional forms of violence included in this analysis have improved our understanding of the interpersonal violence burden, but the attributable burden in males, although exceedingly high, remains an underestimate. There is a need to improve the epidemiological data on prevalence and risks for the different types of interpersonal violence, particularly for males.

Synthesis and characterization of palladium nanoparticles by varying size, shape and synthetic approach: A comparative risk assessment study in-vitro as a step towards the development of safe and sustainable nanotechnology

The vigorous growth in the equipment of palladium in the autocatalytic converters for mitigating air pollution has led to the release of airborne palladium micro- and nano-particulates in the environment, thus, consequently exposing the occupational workers and urban population to Pd particles, in both fine and ultra-fine fractions. Pd-NPs have been shown to exert cytotoxic and pro-inflammatory effects on the in-vitro and in-vivo models, however, the influence of size, shape and synthetic route on the immunotoxic potential of Pd-NPs is not known yet. Therefore, in this first report, we synthesized Pd microparticles (Pd-MPs), spherical-shaped Pd-NPs via the chemical route (reverse micelle/microemulsion method) and green route using Cannabissativa L. leaf extract (CS–Pd-NPs) and Pd nanorods (Pd-NRs). Characterization techniques such as UV-VIS spectroscopy, TEM, size distribution analysis and FT-IR spectroscopy were used. Further, synthesized particles of environment-relevant concentration were exposed to macrophage cell lines and their cytotoxicity was assessed by MTT assay, Annexin V FITC apoptosis assay and ELISA. Results showed dose-dependent cytotoxicity exerted by all particles when exposed to macrophage cell lines. Among these, Pd-MPs of size ⁓218 nm were found to have the highest cell viability whereas spherical-shaped Pd-NPs of size ⁓4 nm were found to be the least viable as compared to other particles at all concentrations. Apoptosis induced by all the particles was not found to be significant (<3%). ELISA studies showed a minimal rise in TNF-α and IL-6 cytokine levels as compared to control whereas Pd-MPs and CS-Pd-NPs had an insignificant effect on the markers. Through this study, we also gain an insight into the exact size and shape that have the least toxicity for their future applicability in biomedical, industrial and environmental fields to ensure safe and sustainable nanotechnology and environmental safety from their use.

Changes over 15\u2009years in the contribution of adiposity and smoking to deaths in England and Scotland

BackgroundFor many years smoking has been the major threat to public health in developed countries. However, smoking prevalence has declined over a period when adiposity has increased. The aim of this study was to determine whether adiposity now accounts for more deaths than smoking in the general population as a whole or sub-groups of it.MethodsThis is a comparative risk assessment study using Health Surveys for England and Scottish Health Surveys from 2003 to 2017. Annual prevalence of overweight, obesity, current and former smoking were obtained and combined using population-based weights. Sex-specific risk ratios for all-cause mortality were obtained from the most recently published meta-analyses. Population attributable fractions across yeas were then estimated.FindingsOverall, deaths attributable to current/former smoking declined from 23.1% (95% CI 20.6–25.8%) in 2003 to 19.4% (95% CI 17.3–21.6%) in 2017, whilst those attributable to adiposity (overweight or obesity) increased from 17.9% (95% CI 17.3–18.4%) in 2003 to 23.1% (95% CI 22.3–23.8%) in 2017 with cross-over occurring in 2013. Cross-over occurred earlier in men (2011) than women (2014). It occurred in 2006 for those aged over 65 years of age and in 2012 for those aged 45–64 years. Below 45 years, smoking remained the larger contributor to mortality.InterpretationAdiposity now accounts for more deaths in England and Scotland than smoking among people in middle- and old-age. National strategies to address adiposity should be a public health priority.

National, regional, and global burdens of disease from 2000 to 2016 attributable to alcohol use: a comparative risk assessment study

Alcohol use has increased globally, with varying trends in different parts of the world. This study investigates gender, age, and geographical differences in the alcohol-attributable burden of disease from 2000 to 2016. This comparative risk assessment study estimated the alcohol-attributable burden of disease. Population-attributable fractions (PAFs) were estimated by combining alcohol exposure data obtained from production and taxation statistics and from national surveys with corresponding relative risks obtained from meta-analyses and cohort studies. Mortality and morbidity data were obtained from the WHO Global Health Estimates, population data were obtained from the UN Population Division, and human development index (HDI) data were obtained from the UN Development Programme. Uncertainty intervals (UIs) were estimated using a Monte Carlo-like approach. Globally, we estimated that there were 3·0 million (95% UI 2·6-3·6) alcohol-attributable deaths and 131·4 million (119·4-154·4) disability-adjusted life-years (DALYs) in 2016, corresponding to 5·3% (4·6-6·3) of all deaths and 5·0% (4·6-5·9) of all DALYs. Alcohol use was a major risk factor for communicable, maternal, perinatal, and nutritional diseases (PAF of 3·3% [1·9-5·6]), non-communicable diseases (4·3% [3·6-5·1]), and injury (17·7% [14·3-23·0]) deaths. The alcohol-attributable burden of disease was higher among men than among women, and the alcohol-attributable age-standardised burden of disease was highest in the eastern Europe and western, southern, and central sub-Saharan Africa regions, and in countries with low HDIs. 52·4% of all alcohol-attributable deaths occurred in people younger than 60 years. As a leading risk factor for the burden of disease, alcohol use disproportionately affects people in low HDI countries and young people. Given the variations in the alcohol-attributable burden of disease, cost-effective local and national policy measures that can reduce alcohol use and the resulting burden of disease are needed, especially in low-income and middle-income countries. None.

SY23-3 * DEVELOPMENT OF RESEARCH IN SUBSTANCE USE DISORDERS IN THE DEPARTMENT OF PSYCHIATRY, SIRIRAJ HOSPITAL

According to the comparative risk assessment study in 2009, alcohol abuse and smoking are the top two-ranked risk behaviors among Thai males, with an uprising trend for both genders since 2004. Overall, the number of patients with substance use disorders increased continuously. This emphasizes the dire need for the development of services and research focusing on substance use disorders. Addiction is one of the areas of research excellence in our department. The psychiatric and special clinics for substance use problems of the psychiatric department has set up research teams and performed various studies, including analysis of services provided, prevalence survey studies, validation of instruments and controlled trial. In this symposium, I will highlight the progress of research projects related to alcohol, tobacco and amphetamine use disorders that has been carried out in the department of psychiatry in our hospital. Albeit limited resources, we aim to develop more advance research in addiction, including biological research and genetic association studies, with various inter-departmental and multi-center collaboration. Furthermore, we hope that we can apply the knowledge obtained from these studies to continuously improve our services for the management of addiction.

Global burden of tuberculosis and lower respiratory infections attributable to alcohol consumption in 2004

Shield, K. D., Samokhvalov, A. V. &amp; Rehm, J. (2013). Global burden of tuberculosis and lower respiratory infections attributable to alcohol consumption in 2004. International Journal of Alcohol and Drug Research, 2(1), 11-18. doi: 10.7895/ijadr.v2i1.49 (http://dx.doi.org/10.7895/ijadr.v2i1.49)Aim: To quantify the extent to which alcohol contributes to the global burden of tuberculosis (TB) and lower respiratory infections (LRI).Design: TB and LRI deaths and disability-adjusted life years (DALYs) lost due to alcohol consumption were calculated from alcohol-attributable fractions (AAFs) using various data sources.Measures: Deaths and DALYs lost were obtained from the World Health Organization (2004 revision of the Global Burden of Disease study). Alcohol consumption indicators were obtained from the ongoing Comparative Risk Assessment study. Relative risks were obtained from meta-analyses, and confidence intervals (CIs) for the AAFs were obtained using Monte Carlo simulations.Findings: In 2004 alcohol was responsible for 381,000 deaths (95% CI: 209,000–560,000), 215,000 from TB (95% CI: 135,000–295,000) and 167,000 from LRI (95% CI: 74,000–264,000); and 6,101,000 DALYs lost (95% CI: 3,463,000–8,777,000), 4,581,000 due to TB (95% CI: 2,835,000 to 6,326,000) and 1,152,000 due to LRI (95%CI: 954,000–566,000). This represents 0.65% of all deaths (95% CI: 0.36%–0.95%) and 0.40% of all DALYs lost (95% CI: 0.23%–0.23%) for people aged 15 years and older.Conclusions: The global burden of alcohol-attributable TB and LRI is substantial, and significant attention should be paid to monitoring it. Future research should focus on quantifying alcohol’s role in (1) the risk for infection, (2) disease progression, and (3) adherence to medication regimens, in order to ensure accurate descriptions of the resulting global burden attributable to alcohol consumption.

Global burden of tuberculosis and lower respiratory infections attributable to alcohol consumption in 2004

Shield, K. D., Samokhvalov, A. V. &amp; Rehm, J. (2013). Global burden of tuberculosis and lower respiratory infections attributable to alcohol consumption in 2004. International Journal of Alcohol and Drug Research, 2(1), 11-18. doi: 10.7895/ijadr.v2i1.49 (http://dx.doi.org/10.7895/ijadr.v2i1.49)Aim: To quantify the extent to which alcohol contributes to the global burden of tuberculosis (TB) and lower respiratory infections (LRI).Design: TB and LRI deaths and disability-adjusted life years (DALYs) lost due to alcohol consumption were calculated from alcohol-attributable fractions (AAFs) using various data sources.Measures: Deaths and DALYs lost were obtained from the World Health Organization (2004 revision of the Global Burden of Disease study). Alcohol consumption indicators were obtained from the ongoing Comparative Risk Assessment study. Relative risks were obtained from meta-analyses, and confidence intervals (CIs) for the AAFs were obtained using Monte Carlo simulations.Findings: In 2004 alcohol was responsible for 381,000 deaths (95% CI: 209,000–560,000), 215,000 from TB (95% CI: 135,000–295,000) and 167,000 from LRI (95% CI: 74,000–264,000); and 6,101,000 DALYs lost (95% CI: 3,463,000–8,777,000), 4,581,000 due to TB (95% CI: 2,835,000 to 6,326,000) and 1,152,000 due to LRI (95%CI: 954,000–566,000). This represents 0.65% of all deaths (95% CI: 0.36%–0.95%) and 0.40% of all DALYs lost (95% CI: 0.23%–0.23%) for people aged 15 years and older.Conclusions: The global burden of alcohol-attributable TB and LRI is substantial, and significant attention should be paid to monitoring it. Future research should focus on quantifying alcohol’s role in (1) the risk for infection, (2) disease progression, and (3) adherence to medication regimens, in order to ensure accurate descriptions of the resulting global burden attributable to alcohol consumption.

The effects of capping the alcohol consumption distribution and relative risk functions on the estimated number of deaths attributable to alcohol consumption in the European Union in 2004

BackgroundWhen calculating the number of deaths attributable to alcohol consumption (i.e., the number of deaths that would not have occurred if everyone was a lifetime abstainer), alcohol consumption is most often modelled using a capped exposure distribution so that the maximum average daily consumption is 150 grams of pure alcohol. However, the effect of capping the exposure distribution on the estimated number of alcohol-attributable deaths has yet to be systematically evaluated. Thus, the aim of this article is to estimate the number of alcohol-attributable deaths by means of a capped and an uncapped gamma distribution and capped and uncapped relative risk functions using data from the European Union (EU) for 2004.MethodsSex- and disease-specific alcohol relative risks were obtained from the ongoing Global Burden of Disease, Comparative Risk Assessment Study. Adult per capita consumption estimates were obtained from the Global Information System on Alcohol and Health. Data on the prevalence of current drinkers, former drinkers, and lifetime abstainers by sex and age were obtained from various population surveys. Alcohol-attributable deaths were calculated using Alcohol-Attributable Fractions that were calculated using capped (at 150 grams of alcohol) and uncapped alcohol consumption distributions and capped and uncapped relative risk functions.ResultsAlcohol-attributable mortality in the EU may have been underestimated by 25.5% for men and 8.0% for women when using the capped alcohol consumption distribution and relative risk functions, amounting to the potential underestimation of over 23,000 and 1,100 deaths in 2004 in men and women respectively. Capping of the relative risk functions leads to an estimated 9,994 and 468 fewer deaths for men and for women respectively when using an uncapped gamma distribution to model alcohol consumption, accounting for slightly less than half of the potential underestimation.ConclusionsAlthough the distribution of drinkers in the population and the exact shape of the relative risk functions at large average daily alcohol consumption levels are not known, the findings of our study stress the importance of conducting further research to focus on exposure and risk in very heavy drinkers.

Mortality and Potential Years of Life Lost Attributable to Alcohol Consumption by Race and Sex in the United States in 2005

BackgroundAlcohol has been linked to health disparities between races in the US; however, race-specific alcohol-attributable mortality has never been estimated. The objective of this article is to estimate premature mortality attributable to alcohol in the US in 2005, differentiated by race, age and sex for people 15 to 64 years of age.Methods and FindingsMortality attributable to alcohol was estimated based on alcohol-attributable fractions using indicators of exposure from the National Epidemiologic Survey on Alcohol and Related Conditions and risk relations from the Comparative Risk Assessment study. Consumption data were corrected for undercoverage (the observed underreporting of alcohol consumption when using survey as compared to sales data) using adult per capita consumption from WHO databases. Mortality data by cause of death were obtained from the US Department of Health and Human Services. For people 15 to 64 years of age in the US in 2005, alcohol was responsible for 55,974 deaths (46,461 for men; 9,513 for women) representing 9.0% of all deaths, and 1,288,700 PYLL (1,087,280 for men; 201,420 for women) representing 10.7% of all PYLL. Per 100,000 people, this represents 29 deaths (29 for White; 40 for Black; 82 for Native Americans; 6 for Asian/Pacific Islander) and 670 PYLL (673 for White; 808 for Black; 1,808 for Native American; 158 for Asian/Pacific Islander). Sensitivity analyses showed a lower but still substantial burden without adjusting for undercoverage.ConclusionsThe burden of mortality attributable to alcohol in the US is unequal among people of different races and between men and women. Racial differences in alcohol consumption and the resulting harms explain in part the observed disparities in the premature mortality burden between races, suggesting the need for interventions for specific subgroups of the population such as Native Americans.

Global burden of injuries attributable to alcohol consumption in 2004: a novel way of calculating the burden of injuries attributable to alcohol consumption

BackgroundAlcohol consumption is a major risk factor for injuries; however, international data on this burden are limited. This article presents new methods to quantify the burden of injuries attributable to alcohol consumption and quantifies the number of deaths, potential years of life lost (PYLL), and disability-adjusted life years (DALYs) lost from injuries attributable to alcohol consumption for 2004.MethodsData on drinking indicators were obtained from the Comparative Risk Assessment study. Data on mortality, PYLL, and DALYs for injuries were obtained from the World Health Organization. Alcohol-attributable fractions were calculated based on a new risk modeling methodology, which accounts for average and heavy drinking occasions. 95% confidence intervals (CIs) were calculated using a Monte Carlo simulation method.ResultsIn 2004, 851,900 (95% CI: 419,400 to 1,282,500) deaths, 19,051,000 (95% CI: 9,767,000 to 28,243,000) PYLL, and 21,688,000 (95% CI: 11,097,000 to 32,385,000) DALYs for people 15 years and older were due to injuries attributable to alcohol consumption. With respect to the total number of deaths, harms to others were responsible for 15.1% of alcohol-attributable injury deaths, 14.5% of alcohol-attributable injury PYLL, and 11.35% of alcohol-attributable injury DALYs. The overall burden of injuries attributable to alcohol consumption corresponds to 17.3% of all injury deaths, 16.7% of all PYLL, and 13.6% of all DALYs caused by injuries, or 1.4% of all deaths, 2.0% of all PYLL, and 1.4% of all DALYs in 2004.ConclusionsThe novel methodology described in this article to calculate the burden of injuries attributable to alcohol consumption improves on previous methodology by more accurately calculating the burden of injuries attributable to one’s own drinking, and for the first time, calculates the burden of injuries attributable to the alcohol consumption of others. The burden of injuries attributable to alcohol consumption is large and is entirely avoidable, and policies and strategies to reduce it are recommended.

Interpersonal violence: an important risk factor for disease and injury in South Africa

BackgroundBurden of disease estimates for South Africa have highlighted the particularly high rates of injuries related to interpersonal violence compared with other regions of the world, but these figures tell only part of the story. In addition to direct physical injury, violence survivors are at an increased risk of a wide range of psychological and behavioral problems. This study aimed to comprehensively quantify the excess disease burden attributable to exposure to interpersonal violence as a risk factor for disease and injury in South Africa.MethodsThe World Health Organization framework of interpersonal violence was adapted. Physical injury mortality and disability were categorically attributed to interpersonal violence. In addition, exposure to child sexual abuse and intimate partner violence, subcategories of interpersonal violence, were treated as risk factors for disease and injury using counterfactual estimation and comparative risk assessment methods. Adjustments were made to account for the combined exposure state of having experienced both child sexual abuse and intimate partner violence.ResultsOf the 17 risk factors included in the South African Comparative Risk Assessment study, interpersonal violence was the second leading cause of healthy years of life lost, after unsafe sex, accounting for 1.7 million disability-adjusted life years (DALYs) or 10.5% of all DALYs (95% uncertainty interval: 8.5%-12.5%) in 2000. In women, intimate partner violence accounted for 50% and child sexual abuse for 32% of the total attributable DALYs.ConclusionsThe implications of our findings are that estimates that include only the direct injury burden seriously underrepresent the full health impact of interpersonal violence. Violence is an important direct and indirect cause of health loss and should be recognized as a priority health problem as well as a human rights and social issue. This study highlights the difficulties in measuring the disease burden from interpersonal violence as a risk factor and the need to improve the epidemiological data on the prevalence and risks for the different forms of interpersonal violence to complete the picture. Given the extent of the burden, it is essential that innovative research be supported to identify social policy and other interventions that address both the individual and societal aspects of violence.