Incidence, risk factors and estimates of a woman's risk of developing secondary lower limb lymphedema and lymphedema-specific supportive care needs in women treated for endometrial cancer

Objectives: Few studies have assessed the risk and impact of lymphedema among women treated for endometrial cancer. We aimed to quantify cumulative incidence of, and risk factors for developing lymphedema following treatment for endometrial cancer and estimate absolute risk for individuals. Further, we report unmet needs for help with lymphedema-specific issues. Methods: Women treated for endometrial cancer (n = 1243) were followed-up 3–5 years after diagnosis; a subset of 643 completed a follow-up survey that asked about lymphedema and lymphedema-related support needs. We identified a diagnosis of secondary lymphedema from medical records or self-report. Multivariable logistic regression was used to evaluate risk factors and estimates. Results: Overall, 13% of women developed lymphedema. Risk varied markedly with the number of lymph nodes removed and, to a lesser extent, receipt of adjuvant radiation or chemotherapy treatment, and use of nonsteroidal anti-inflammatory drugs (pre-diagnosis). The absolute risk of developing lymphedema was > 50% for women with 15 + nodes removed and 2–3 additional risk factors, 30–41% for those with 15 + nodes removed plus 0–1 risk factors or 6–14 nodes removed plus 3 risk factors, but ≤ 8% for women with no nodes removed or 1–5 nodes but no additional risk factors. Over half (55%) of those who developed lymphedema reported unmet need(s), particularly with lymphedema-related costs and pain. Conclusion: Lymphedema is common; experienced by one in eight women following endometrial cancer. Women who have undergone lymphadenectomy have very high risks of lymphedema and should be informed how to self-monitor for symptoms. Affected women need greater levels of support.

The unequal distribution of road trauma in China : understanding risk factors to improve public health

The World Health Organization identifies road trauma as a major public health issue in every country; most notably among low-to-middle income countries. More than 90% of all road fatalities occur in these countries, although they have only 48% of all registered vehicles [1]. Unprecedented focus has been placed on reducing the global road trauma burden through the United Nations Decade of Action for Road Safety (2011-2020). China is rapidly transitioning from a nation of bicycle riders and pedestrians to one where car ownership and use is increasing. This transition presents important public health, mobility, and safety challenges. Rapid motorisation has resulted in an increased road trauma burden, shouldered disproportionately among the population. Vulnerable road users (bicyclists, pedestrians, and motorcyclists) are of particular concern, representing 70% of all road-related fatalities [1]. Furthermore, those at greatest risk of sustaining a crash-related disability are: male, older, less educated, and earning a lower income [2] and residing in urban areas [3], with higher fatality rates in north-western poorer provinces [3]. Speeding is a key factor in road crashes in China [1, 4] and is one of two risk factors targeted in the Bloomberg Philanthropies-funded Global Road Safety Program operating in two Chinese cities over five year [5] to which the first author has provided expert advice. However, little evidence exists to help understand the factors underpinning speeding behaviour. Previous research conducted by the authors in Beijing and Hangzhou explored personal, social, and legal factors relating to speeding to assist in better understanding the motivations for non-compliance with speed limits. Qualitative and quantitative research findings indicated that speeding is relatively common, including self-reported travel speeds of greater than 30 km/hour above posted speed limits [6], and that the road safety laws and enforcement practices may, in some circumstances, contribute to this [7]. Normative factors were also evident; the role of friends, family members and driving instructors were influential. Additionally, using social networks to attempt to avoid detection and penalty was reported, thereby potentially reinforcing community perceptions that speeding is acceptable [8, 9]. The authors established strong collaborative links with the Chinese Academy of Sciences and Zhejiang Police College to conduct this research. The first author has worked in both institutions for extended time periods and recognises that research must include an understanding of culturally-relevant issues if road safety is to improve in China. Future collaborations to assist in enhancing our understanding of such issues are welcomed. References [1] World Health Organization. (2009). Global status report on road safety: Time for action; Geneva. [2] Chen, H., Du, W., & Li, N. (2013). The socioeconomic inequality in traffic-related disability among Chinese adults: the application of concentration index. Accident Analysis & Prevention, 55(101-106). [3] Wang, S. Y., Li, Y. H., Chi, G. B., Xiao, S. Y., Ozanne-Smith, J., Stevenson, M., & Phillips, M. (2008). Injury-related fatalities in China: an under-recognised public-health problem. The Lancet (British edition), 372(9651), 1765-1773. [4] He, J., King, M. J., Watson, B., Rakotonirainy, A., & Fleiter, J. J. (2013). Speed enforcement in China: National, provincial and city initiatives and their success. Accident Analysis & Prevention, 50, 282-288. [5] Bhalla, K., Li, Q., Duan, L., Wang, Y., Bishai, D., & Hyder, A. A. (2013). The prevalence of speeding and drink driving in two cities in China: a mid project evaluation of ongoing road safety interventions. Injury, 44, 49-56. doi:10.1016/S0020-1383(13)70213-4. [6] Fleiter, J. J., Watson, B., & Lennon, A. (2013). Awareness of risky behaviour among Chinese drivers. Peer-reviewed paper presented at 23rd Canadian Multidisciplinary Road Safety Conference, Montréal, Québec. [7] Fleiter, J. J., Watson, B., Lennon, A., King, M. J., & Shi, K. (2009). Speeding in Australia and China: A comparison of the influence of legal sanctions and enforcement practices on car drivers. Peer-reviewd paper presented at Australasian Road Safety Research Policing Education Conference, Sydney. [8] Fleiter, J. J., Watson, B., Lennon, A., King, M. J., & Shi, K. (2011). Social influences on drivers in China. Journal of the Australasian College of Road Safety, 22(2), 29-36. [9] Fleiter, J. J., Watson, B., Guan, M. Q., Ding, J. Y., & Xu, C. (2013). Characteristics of Chinese Drivers Attending a Mandatory Training Course Following Licence Suspension. Peer-reviewed paper presented at Road Safety on Four Continents, Beijing, China.

Multilevel competing risk models to evaluate the risk of nosocomial infection

Introduction Risk factor analyses for nosocomial infections (NIs) are complex. First, due to competing events for NI, the association between risk factors of NI as measured using hazard rates may not coincide with the association using cumulative probability (risk). Second, patients from the same intensive care unit (ICU) who share the same environmental exposure are likely to be more similar with regard to risk factors predisposing to a NI than patients from different ICUs. We aimed to develop an analytical approach to account for both features and to use it to evaluate associations between patient- and ICU-level characteristics with both rates of NI and competing risks and with the cumulative probability of infection. Methods We considered a multicenter database of 159 intensive care units containing 109,216 admissions (813,739 admission-days) from the Spanish HELICS-ENVIN ICU network. We analyzed the data using two models: an etiologic model (rate based) and a predictive model (risk based). In both models, random effects (shared frailties) were introduced to assess heterogeneity. Death and discharge without NI are treated as competing events for NI. Results There was a large heterogeneity across ICUs in NI hazard rates, which remained after accounting for multilevel risk factors, meaning that there are remaining unobserved ICU-specific factors that influence NI occurrence. Heterogeneity across ICUs in terms of cumulative probability of NI was even more pronounced. Several risk factors had markedly different associations in the rate-based and risk-based models. For some, the associations differed in magnitude. For example, high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with modest increases in the rate of nosocomial bacteremia, but large increases in the risk. Others differed in sign, for example respiratory vs cardiovascular diagnostic categories were associated with a reduced rate of nosocomial bacteremia, but an increased risk. Conclusions A combination of competing risks and multilevel models is required to understand direct and indirect risk factors for NI and distinguish patient-level from ICU-level factors.

Female greater wax moths reduce sexual display behavior in relation to the potential risk of predation by echolocating bats

Female greater wax moths Galleria mellonella display by wing fanning in response to bursts of ultrasonic calls produced by males. The temporal and spectral characteristics of these calls show some similarities with the echolocation calls of bats that emit frequency-modulated (FM) signals. Female G. mellonella therefore need to distinguish between the attractive signals of male conspecifics, which may lead to mating opportunities, and similar sounds made by predatory bats. We therefore predicted that (1) females would display in response to playbacks of male calls; (2) females would not display in response to playbacks of the calls of echolocating bats (we used the calls of Daubenton's bat Myotis daubentonii as representative of a typical FM echolocating bat); and (3) when presented with male calls and bat calls during the same time block, females would display more when perceived predation risk was lower. We manipulated predation risk in two ways. First, we varied the intensity of bat calls to represent a nearby (high risk) or distant (low risk) bat. Second, we played back calls of bats searching for prey (low risk) and attacking prey (high risk). All predictions were supported, suggesting that female G. mellonella are able to distinguish conspecific male mating calls from bat calls, and that they modify display rate in relation to predation risk. The mechanism (s) by which the moths separate the calls of bat and moth must involve temporal cues. Bat and moth signals differ considerably in duration, and differences in duration could be encoded by the moth's nervous system and used in discrimination.

Prevalence of active foot disease and foot disease risk factors in a subacute inpatient rehabilitation facility: a cross-sectional prevalence study

Background Australian subacute inpatient rehabilitation facilities face significant challenges from the ageing population and the increasing burden of chronic disease. Foot disease complications are a negative consequence of many chronic diseases. With the rapid expansion of subacute rehabilitation inpatient services, it seems imperative to investigate the prevalence of foot disease and foot disease risk factors in this population. The primary aim of this cross-sectional study was to determine the prevalence of active foot disease and foot disease risk factors in a subacute inpatient rehabilitation facility. Methods Eligible participants were all adults admitted at least overnight into a large Australian subacute inpatient rehabilitation facility over two different four week periods. Consenting participants underwent a short non-invasive foot examination by a podiatrist utilising the validated Queensland Health High Risk Foot Form to collect data on age, sex, medical co-morbidity history, foot disease risk factor history and clinically diagnosed foot disease complications and foot disease risk factors. Descriptive statistics were used to determine the prevalence of clinically diagnosed foot disease complications, foot disease risk factors and groups of foot disease risk factors. Logistic regression analyses were used to investigate any associations between defined explanatory variables and appropriate foot disease outcome variables. Results Overall, 85 (88%) of 97 people admitted to the facility during the study periods consented; mean age 80 (±9) years and 71% were female. The prevalence (95% confidence interval) of participants with active foot disease was 11.8% (6.3 – 20.5), 32.9% (23.9 – 43.5) had multiple foot disease risk factors, and overall, 56.5% (45.9 – 66.5) had at least one foot disease risk factor. A self-reported history of peripheral neuropathy diagnosis was independently associated with having multiple foot disease risk factors (OR 13.504, p = 0.001). Conclusion This study highlights the potential significance of the burden of foot disease in subacute inpatient rehabilitation facilities. One in eight subacute inpatients were admitted with active foot disease and one in two with at least one foot disease risk factor in this study. It is recommended that further multi-site studies and management guidelines are required to address the foot disease burden in subacute inpatient rehabilitation facilities. Keywords: Subacute; Inpatient; Foot; Complication; Prevalence

The contribution of major depression to the global burden of ischemic heart disease : a comparative risk assessment

Background Cardiovascular disease and mental health both hold enormous public health importance, both ranking highly in results of the recent Global Burden of Disease Study 2010 (GBD 2010). For the first time, the GBD 2010 has systematically and quantitatively assessed major depression as an independent risk factor for the development of ischemic heart disease (IHD) using comparative risk assessment methodology. Methods A pooled relative risk (RR) was calculated from studies identified through a systematic review with strict inclusion criteria designed to provide evidence of independent risk factor status. Accepted case definitions of depression include diagnosis by a clinician or by non-clinician raters adhering to Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) classifications. We therefore refer to the exposure in this paper as major depression as opposed to the DSM-IV category of major depressive disorder (MDD). The population attributable fraction (PAF) was calculated using the pooled RR estimate. Attributable burden was calculated by multiplying the PAF by the underlying burden of IHD estimated as part of GBD 2010. Results The pooled relative risk of developing IHD in those with major depression was 1.56 (95% CI 1.30 to 1.87). Globally there were almost 4 million estimated IHD disability-adjusted life years (DALYs), which can be attributed to major depression in 2010; 3.5 million years of life lost and 250,000 years of life lived with a disability. These findings highlight a previously underestimated mortality component of the burden of major depression. As a proportion of overall IHD burden, 2.95% (95% CI 1.48 to 4.46%) of IHD DALYs were estimated to be attributable to MDD in 2010. Eastern Europe and North Africa/Middle East demonstrate the highest proportion with Asia Pacific, high income representing the lowest. Conclusions The present work comprises the most robust systematic review of its kind to date. The key finding that major depression may be responsible for approximately 3% of global IHD DALYs warrants assessment for depression in patients at high risk of developing IHD or at risk of a repeat IHD event.

The burden attributable to mental and substance use disorders as risk factors for suicide : findings from the Global Burden of Disease Study 2010

Background The Global Burden of Disease Study 2010 (GBD 2010) identified mental and substance use disorders as the 5th leading contributor of burden in 2010, measured by disability adjusted life years (DALYs). This estimate was incomplete as it excluded burden resulting from the increased risk of suicide captured elsewhere in GBD 2010's mutually exclusive list of diseases and injuries. Here, we estimate suicide DALYs attributable to mental and substance use disorders. Methods Relative-risk estimates of suicide due to mental and substance use disorders and the global prevalence of each disorder were used to estimate population attributable fractions. These were adjusted for global differences in the proportion of suicide due to mental and substance use disorders compared to other causes then multiplied by suicide DALYs reported in GBD 2010 to estimate attributable DALYs (with 95% uncertainty). Results Mental and substance use disorders were responsible for 22.5 million (14.8-29.8 million) of the 36.2 million (26.5-44.3 million) DALYs allocated to suicide in 2010. Depression was responsible for the largest proportion of suicide DALYs (46.1% (28.0%-60.8%)) and anorexia nervosa the lowest (0.2% (0.02%-0.5%)). DALYs occurred throughout the lifespan, with the largest proportion found in Eastern Europe and Asia, and males aged 20-30 years. The inclusion of attributable suicide DALYs would have increased the overall burden of mental and substance use disorders (assigned to them in GBD 2010 as a direct cause) from 7.4% (6.2%-8.6%) to 8.3% (7.1%-9.6%) of global DALYs, and would have changed the global ranking from 5th to 3rd leading cause of burden. Conclusions Capturing the suicide burden attributable to mental and substance use disorders allows for more accurate estimates of burden. More consideration needs to be given to interventions targeted to populations with, or at risk for, mental and substance use disorders as an effective strategy for suicide prevention.

Epidemiology and risk factors of oral cancer in South Africa

Head and neck cancers are some of the leading cancers in the coloured and black South African male population and the perception exists that the incidence rates are rising. Aims: To determine the standardised morbidity rates and some of the risk factors for oral cancer in South Africa. Methods: Using histologically verified data from the National Cancer Registry, the age standardised incidence rates (ASIR) and life-time risks (LR) of oral cancer in South Africa were calculated for 1988-1991.2. In an ongoing case control study (1995 +) among black patients in Johannesburg/Soweto, adjusted odds ratios for developing oral cancers in relation to tobacco and alcohol consumption were calculated. Results: Coloured males vs. females: ASIR 13.13 vs. 3.5 (/100,000/year), LR 1:65 vs. 1:244. Black males vs. females: ASIR 9.06 vs. 1.75, LR 1:86 and 1:455. White males vs. females: ASIR 8.06 vs. 3.18, LR 1:104 vs. 1:278. Asian males vs. females: ASIR 5.24 vs. 6.66, LR 1:161 vs. 1:125. The odds ratio for oral cancer in black males in relation to smoking was 7.0 (95% CI 3.0-14.6) and daily alcohol consumption 1.3 (95% CI 0.6-2.8). In black females the odds ratios in relation to smoking were 3.9 (95% CI 1.7 8.9) and daily alcohol consumption 1.7(95% CI 0.7-4.1). Conclusions: The risk factors for oral cancer in South Africa are multiple and gender discrepancies in ASIR and LR signal differences in exposure to carcinogens. It is unclear whether the incidence of oral cancers will rise in the future.

Design, construction and evaluation of systems to predict risk in obstetrics

We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy. We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy.

Reason of state and a new notion of fortune : Historicising the risk society

Since the 1980s the concept of risk has produced a large and diverse volume of sociological research. Ulrich Beck’s groundbreaking risk society thesis provides a particularly engaging contribution, since it seems that nearly every sociological account of risk engages with this work. For Beck, we are living in second modernity – a new epoch that breaks with pre-modernity and industrial society due to the centrality, incalculability and reflexivity of globalised risk. While Beck’s theory is compelling, a reading of other theorists such as Foucault (2007[1978]) and Hacking (1975,1990) suggests that a difficulty with Beck’s work is that in attempting to explain what is novel about risk in contemporary times, he too quickly passes over the complexities and ruptures of historical change that impact on the history and contingency of risk. This paper begins by presenting a brief analysis of the present state of risk by introducing Beck’s historical narrative of risk from pre-modernity to the risk society; it then outlines the challenges with the “risk as epoch” argument by considering a range of literature, which suggests risk has a more complex history than proposed by Beck; and finally it highlights the value in examining strategies of statecraft in early modern Europe, specifically Machiavelli’s The Prince (2008[1513]) and Giovanni Botero’s political treatise, Della Ragion di Stato (1956[1589]) – as a means of more thoroughly understanding how our current concept of risk emerges. In doing so, this paper seeks to open up new trajectories in the historicisation of risk for other interested scholars.

Is there a potential relationship between prior h amstring strain injury and increased risk for future a nterior cruciate ligament injury?

Hamstring strain injuries (HSIs) are the most prevalent injury in a number of sports, and while anterior cruciate ligament (ACL) injuries are less common, they are far more severe and have long-term implications, such as an increased risk of developing osteoarthritis later in life. Given the high incidence and severity of these injuries, they are key targets of injury preventive programs in elite sport. Evidence has shown that a previous severe knee injury (including ACL injury) increases the risk of HSI; however, whether the functional deficits that occur after HSI result in an increased risk of ACL injury has yet to be considered. In this clinical commentary, we present evidence that suggests that the link between previous HSI and increased risk of ACL injury requires further investigation by drawing parallels between deficits in hamstring function after HSI and in women athletes, who are more prone to ACL injury than men athletes. Comparisons between the neuromuscular function of the male and female hamstring has shown that women display lower hamstring-to-quadriceps strength ratios during isokinetic knee flexion and extension, increased activation of the quadriceps compared with the hamstrings during a stop-jump landing task, a greater time required to reach maximal isokinetic hamstring torque, and lower integrated myoelectrical hamstring activity during a sidestep cutting maneuver. Somewhat similarly, in athletes with a history of HSI, the previously injured limb, compared with the uninjured limb, displays lower eccentric knee flexor strength, a lower hamstrings-to-quadriceps strength ratio, lower voluntary myoelectrical activity during maximal knee flexor eccentric contraction, a lower knee flexor eccentric rate of torque development, and lower voluntary myoelectrical activity during the initial portion of eccentric contraction. Given that the medial and lateral hamstrings have different actions at the knee joint in the coronal plane, which hamstring head is previously injured might also be expected to influence the likelihood of future ACL. Whether the deficits in function after HSI, as seen in laboratory-based studies, translate to deficits in hamstring function during typical injurious tasks for ACL injury has yet to be determined but should be a consideration for future work.

Risk perception and the public acceptance of drones

Unmanned aircraft, or drones, are a rapidly emerging sector of the aviation industry. There has been limited substantive research, however, into the public perception and acceptance of drones. This paper presents the results from two surveys of the Australian public designed to investigate (a) whether the public perceive drones to be riskier than existing manned aviation, (b) whether the terminology used to describe the technology influences public perception, and (c) what the broader concerns are that may influence public acceptance of the technology. We find that the Australian public currently hold a relatively neutral attitude towards drones. Respondents did not consider the technology to be overly unsafe, risky, beneficial, or threatening. Drones are largely viewed as being of comparable risk to that of existing manned aviation. Further, terminology had a minimal effect on the perception of the risks or acceptability of the technology. The neutral response is likely due to a lack of knowledge about the technology, which was also identified as the most prevalent public concern as opposed to the risks associated with its use. Privacy, military use and misuse (e.g., terrorism) were also significant public concerns. The results suggest that society is yet to form an opinion of drones. As public knowledge increases, the current position is likely to change. Industry communication and media coverage will likely influence the ultimate position adopted by the public, which can be difficult to change once established.

Do twins differ from single-born children on rates of behavioral difficulty in early childhood? A study of sibling relationship risk factors

The hypothesis that twinning raises risk for behavioral difficulties in childhood is persistent, yet there is limited and inconsistent empirical evidence. Simple mean comparison without control for confounders provides data on prevalence rates but cannot provide knowledge about risk or etiology. To assess the effect of twin relationship on behavior, comparison of patterns of association with single-born siblings may be informative. Analyses of data from an Australian sample of twins and single-born children (N = 305, mean age 4 years 9 months, and a follow-up 12 months later) were undertaken. The outcome measure was the Strengths and Difficulties Questionnaire. Predictor and control measures were obtained from parent report on the sibling/co-twin relationship behavior, family demographics, and obstetric history. We assessed difference between twins and single-born children in two respects: (a) mean behavioral difficulties, and (b) patterns of association between sibling relationship and behavioral difficulties, controlling for confounders. Results showed no differences in mean levels of behavioral difficulties between twins and single-born siblings identifying the importance of statistical control for family and obstetric adversity. Differences in patterns of association were found; for twin children, conflict in their co-twin relationship predicted externalizing behaviors, while for single-born children conflict predicted internalizing behaviors. The findings of mean differences between twin and single-born children in social background, but not in behavioral difficulties, underscore the necessity of statistical control to identify risk associated with twinning compared with risk associated with family and obstetric background factors.

Interaction of erythrocyte eicosapentaenoic acid and physical activity predicts reduced risk of mild cognitive impairment

Objectives To evaluate relationships between self-reported physical activity, proportions of long-chain omega-3 polyunsaturated fatty acids (LCn3) in erythrocyte content (percentage of total fatty acids) and risk of mild cognitive impairment (MCI) in older adults. Method A cross-sectional study was conducted. Community-dwelling male and female (n = 84) participants over the age of 65 years with and without MCI were tested for erythrocyte proportions of the LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Physical activity was measured using a validated questionnaire. Results The interaction between erythrocyte EPA, but not DHA, and increased physical activity was associated with increased odds of a non-MCI classification. Conclusion An interaction between physical activity and erythrocyte EPA content (percentage of fatty acids) significantly predicted MCI status in older adults. Randomised control trials are needed to examine the potential for supplementation with EPA in combination with increased physical activity to mitigate the risk of MCI in ageing adults.

Estimating the burden of disease attributable to four selected environmental risk factors in South Africa

INTRODUCTION: The first South African National Burden of Disease study quantified the underlying causes of premature mortality and morbidity experienced in South Africa in the year 2000. This was followed by a Comparative Risk Assessment to estimate the contributions of 17 selected risk factors to burden of disease in South Africa. This paper describes the health impact of exposure to four selected environmental risk factors: unsafe water, sanitation and hygiene; indoor air pollution from household use of solid fuels; urban outdoor air pollution and lead exposure. METHODS: The study followed World Health Organization comparative risk assessment methodology. Population-attributable fractions were calculated and applied to revised burden of disease estimates (deaths and disability adjusted life years, [DALYs]) from the South African Burden of Disease study to obtain the attributable burden for each selected risk factor. The burden attributable to the joint effect of the four environmental risk factors was also estimated taking into account competing risks and common pathways. Monte Carlo simulation-modeling techniques were used to quantify sampling, uncertainty. RESULTS: Almost 24 000 deaths were attributable to the joint effect of these four environmental risk factors, accounting for 4.6% (95% uncertainty interval 3.8-5.3%) of all deaths in South Africa in 2000. Overall the burden due to these environmental risks was equivalent to 3.7% (95% uncertainty interval 3.4-4.0%) of the total disease burden for South Africa, with unsafe water sanitation and hygiene the main contributor to joint burden. The joint attributable burden was especially high in children under 5 years of age, accounting for 10.8% of total deaths in this age group and 9.7% of burden of disease. CONCLUSION: This study highlights the public health impact of exposure to environmental risks and the significant burden of preventable disease attributable to exposure to these four major environmental risk factors in South Africa. Evidence-based policies and programs must be developed and implemented to address these risk factors at individual, household, and community levels.