Industrial toxic waste and health: a practical case study

The objective of this thesis is to develop a standard, simple methodology for the assessment of health in areas near sources of pollution. This methodology should make use of readily available data and computing facilities. A literature review on previous studies on the subject was carried out in order to draw from existing experience. A total of twenty-five studies on health near sources of pollution were reviewed. These studies were carried out between 1982 and 1991, most of them in Britain, two in France. The types of pollution sources studied ranged from waste dumps to incinerators, to nuclear power stations. Each study was described, stressing on their respective backgrounds, building on geographical (study) areas, data, analysis and results. Brief synopses of the studies were next grouped, according to those using conventional epidemiological methods and more innovative ones. Finally, it was concluded from the review that the methodology intended should be descriptive, making use of routinely collected data, with a study area based on small geographical divisions (small areas) and taking into account socio-economic differences over its study area. In the absence of accurate data on pollution levels, and from the previous experience of one of the studies reviewed, circular study areas centred on the source of pollution and subdivided into rings were used, with distance of each ring to the centre as a proxy indicator of levels of pollution. The new methodology was found valid and the objective of the study was met. It compared favourably with previously reviewed methodologies. The methodology is intended to be used as a descriptive, exploratory tool, whose findings may warrant further analytic studies, which the method is not designed to, and can not, replace. The use of routinely collected data greatly facilitated the study, although caveats for future studies exist on them. Distance as a surrogate for exposure is seen as a simplistic approach, but in the absence of reliable exposure data it is a useful one. Standardization by Deprivation category has also been found useful to account for factors for which little data exist

The Health Impact of Pesticide Exposure in a Cohort of Outdoor Workers

This thesis describes a study undertaken between 1992 and 2001 to explore the possible health impacts of human exposure to pesticides. The study followed the health outcomes of approximately 4000 outdoor workers over a period of up to sixty-one years. These workers comprised two subcohorts of approximately even size, one composed of agricultural workers with high insecticide exposures, and the other made up of outdoor staff from local councils in the same area with little or no occupational exposure to insecticides. Mortality and morbidity were compared between the two groups, and with the general Australian community. The study identifies significantly increased mortality among both exposed and control subjects when compared to the Australian population. The major cause of this increase was mortality from smoking related diseases. The study also identifies significant increases in mortality among exposed subjects for a number of conditions that do not appear to be the result of smoking patterns, both when compared to the control group and the Australian population. These include pancreatic cancer in some DDT exposed subjects and asthma, diabetes, and leukaemia in subjects working with more modern chemicals. There was also an increase in self reported chronic illness and asthma, and lower neuropsychological functioning scores among surviving exposed subjects when compared to controls. Diabetes was also reported more commonly by subjects reporting occupational use of herbicides

CANCER BURDEN AMONG HIV-INFECTED PERSONS ON ANTIRETROVIRAL THERAPY IN MALAWI: A RECORD LINKAGE STUDY

Sub-Saharan Africa represents 70% of the global number of people living with HIV. The regional HIV epidemic is reflected in the cancer burden, where AIDS-defining cancers are among the most common malignancies in the region. Early access and continued adherence to antiretroviral therapy (ART) may reduce the risk of certain cancers among the HIV population. Local epidemiological data are needed to characterize the cancer burden among African HIV populations during the ART era. In the Malawi HIV-Cancer Match Study, we used algorithms to link cancer cases from the population-based cancer registry of Malawi with electronic medical records from two high volume HIV clinics. We constructed a clinical cohort of 29,000 people who initiated ART from 2000 to 2010 at Lighthouse Trust and Queen Elizabeth Central Hospital. We described implementation of a healthcare data linkage in a resource-constrained setting, common analytical barriers, and solutions. We used Poisson regression to estimate cancer incidence rates and describe the timing of new cancer diagnoses after starting ART. Missing data and misreporting of patient identifiers resulted in a substantial proportion of potential cancer cases being discarded from analysis. Consequently, missing data on potential cancer cases may have diminished sensitivity of the linkage algorithms. Sensitivity analysis of incidence rates was used to address scenarios of uncertainty in the linkage process. Two AIDS-defining malignancies, Kaposi sarcoma (KS) and cervical cancer, were the most common cancers in this young population of ART users who tend to present to care with severe immunosuppression. Most incident KS occurred within the first two years of starting ART, and elevated incidence rates persisted over the course of follow-up in spite of therapy. AIDS-associated non-Hodgkin lymphomas and a heterogeneous spectrum of NADC were also observed, but at low incidence rates. Our study is a baseline against which to monitor the contemporary burden of cancer among people who are now starting ART at earlier stages of HIV, when therapy likely to have a substantial impact on cancer incidence. Descriptive epidemiological data on people living with HIV is important for public health decision makers in Malawi to develop evidence-based cancer control plans targeting high-risk HIV populations.Doctor of Philosoph

Road Traffic Noise - Factors modifying its relation to annoyance and cardiovascular disease

Traffic noise causes annoyance and sleep disturbance and has been linked with several other adverse effects on life quality and health, including increased risk of hypertension and myocardial infarction. Conservative estimates assume that at least one million healthy life years are lost every year from traffic related noise in the western part of Europe. We know from earlier studies that the adverse effects of environmental noise may be modified by social, demographic and individual factors. However, there is a need to better evaluate exposure-response in susceptible groups. The aim of this thesis was to test a number of factors hypothesised to modify the association between road traffic noise, annoyance and cardiovascular disease. Paper I-III are cross-sectional, while paper IV is a cohort study. The four different study populations in this thesis were selected through stratified random sampling of men and women aged 18-80 years old in the county of Skåne and its major city Malmö in southern Sweden. Exposures of road traffic and railway noise as well as air pollution were modelled using geographic information system (GIS) for the survey participants’ residential addresses. Possible confounding and modifying factors were mainly drawn from survey responses while outcomes were based on both self-reporting and inpatient registers. We were not able to show a relation between current and medium-term noise exposure to road traffic noise and incident myocardial infarction or ischemic heart disease in the general population. Air-pollution at low levels did not modify this effect. An association was however found between road traffic noise and hypertension in a cross-sectional study >60dB(A). We also found strong and positive relations between road traffic noise and annoyance. Railway noise was found to be less annoying at intermediate levels, but not >55dB(A). Access to quiet side had a protective effect and decreased the risk of annoyance, sleep and concentration problems equal to a 5dB(A) decrease in noise exposure. Generally middle-aged persons were found to be more susceptible to noise. Higher socioeconomic status and educational level were related to noise annoyance. With regard to sex, findings were less consistent. We also found that results in our studies might be biased due to selective participation, that noise sensitive individuals were likely to have a higher response rate and that inter-study comparison may be difficult since different annoyance scales can produce very different results. In conclusion, the health effects of noise are modified by noise source, co-exposures, environmental and socio-demographic factors (as well as personal traits) and research methodology. To develop better policies for residential noise environment, future research should focus on combined exposures and stressors as well as further explaining age differences and developing better ways to account for social class

Cardiovascular and metabolic effects of long-term traffic noise exposure

Traffic noise is an increasingly common environmental exposure affecting large parts of the European population. Since the auditory system is directly linked to the sympathetic nervous and the endocrine systems, noise may induce a stress response, influencing several physiological, metabolic and immunological processes. Previous epidemiological studies suggest harmful effects of traffic noise on the cardiovascular system; however, the overall picture is inconclusive. The primary aim of this thesis was to investigate the long-term effects of traffic noise on cardiovascular and metabolic outcomes. A secondary aim was to apply and evaluate digital noise maps produced in Sweden in accordance with the European Environmental Noise Directive (END) for assessments of residential traffic noise exposure. The long-term effects of aircraft noise on hypertension, obesity and Type 2 diabetes were investigated using questionnaire and clinical data from a cohort within the Stockholm Diabetes Prevention Program. Aircraft noise exposure was assessed by Geographic Information Systems and based on the participants’ residential history. After exclusion of subjects who used tobacco prior to the clinical examinations, the risk of hypertension related to aircraft noise exposure was increased in males (RR per 5 dB(A) Lden 1.21; 95% CI 1.05-1.39) but not in females (RR 0.97; 0.83-1.13). Stronger associations were seen among noise annoyed (RR 1.42; 1.11-1.82). Regardless of sex, long-term exposure to aircraft noise also showed statistically significant associations with waist circumference: 0.62 cm (0.54-0.70) per 1 dB(A) Lden. Also, females exposed at ≥50 dB(A) Lden had a twofold increased risk of Type 2 diabetes, although adjustments for contextual confounding reduced the estimates. A sub-population of the National Environmental Health Survey 2007 (NEHS07) was used to evaluate the Swedish END maps of road traffic and railway noise. The observed proportion of annoyed subjects was plotted as a function of noise exposure and compared to already established exposure-response functions. Generally, there was a good agreement between observed and predicted proportions of annoyed, suggesting that the noise maps are useful for assessments of residential traffic noise exposure. The best agreement was found when the noise estimates derived from the maps were adjusted for how the dwellings were located within the buildings. Cross-sectional analyses were performed based on the NEHS07 of associations between neighborhood traffic load, Lden levels of road traffic and railway noise, respectively, and prevalence of self-reported hypertension and cardiovascular disease. Neither traffic load nor road traffic noise was associated with the cardiovascular outcomes; however, there was a borderline significant association between railway noise and cardiovascular disease. Methodological limitations make these results difficult to interpret. In conclusion, our findings suggest adverse effects of long-term traffic noise exposure on cardiovascular as well as metabolic outcomes. Thus, traffic noise may have detrimental public health effects and research in this area should be prioritized

Exploring The Association Between Antidepressants and Colorectal Cancer in Administrative Data: Negative Controls, Active Comparators and Algorithms

Some antidepressants, especially Selective Serotonin Reuptake Inhibitors (SSRIs), may prevent colorectal cancer (CRC), but these effects may be drug rather than class specific. Previous epidemiological studies have only examined class-level effects, and all studies used non-user comparisons, which are susceptible to several biases. Examining specific SSRI-CRC associations requires a large sample size and precise prescription records, which are features of administrative data; however, these data do not generally contain pathology confirmed cases and algorithms are required to identify probable cases. The goals of this dissertation were: 1) to examine the class-level associations between three antidepressant classes, including SSRIs, and CRC compared to a negative control, antihypertensive initiators (AHT), 2) to examine the association between specific SSRIs and CRC, and 3) to re-evaluate claims-based CRC-identification algorithms in a contemporary population. To examine the first two goals, we performed a new-user, cohort study using a 20% random sample of Medicare beneficiaries (2007-2013), aged ≥66. We estimated hazard ratios (HRs) and 95% confidence intervals (CI), and controlled measured confounding using a propensity score weighting approach. SSRI initiators had lower CRC rates compared with AHT initiators (aHR=0.85, 95% CI: 0.70-1.02). Paroxetine and fluoxetine initiators had lower CRC rates compared with citalopram users (aHR: 0.78, 95% CI: 0.56-1.06; aHR: 0.74, 95% CI: 0.52-1.05, respectively). Estimates were consistent across sensitivity analyses. We re-evaluated CRC-identification algorithm performance in a ≥65, 2006-2009 North Carolina Medicare population, a proportion of which were cancer registry identified CRC cases. We employed a novel cohort creation strategy, whereby cases contribute information from both their pre-diagnostic non-case and case states to accurately capture CRC incidence. Specificity was lower (98.3-99.4% versus 98.5-99.6%) and Positive Predictive Value (PPV) substantially lower (18-37% versus 45-71%) in this population compared to the original population. Results from the first two goals warrant further investigation into the SSRI-CRC association, including incorporating additional part D data as it becomes available. Algorithms are a necessity when performing a drug-cancer study in administrative data, but should be used cautiously, because they are population and time specific. These CRC-identification algorithms need to be updated to reflect a more contemporary and economically diverse population. Future validation studies should employ strategies to accurately ascertain incidence to avoid overestimating PPV.Doctor of Philosoph

Causal inference methods in environmental epidemiology: different approaches to evaluate the health effects of industrial air pollution.

This study aims at implementing different causal inference approaches for the first time in a longitudinal cohort analysis with a continuous exposure, to assess the causal effect of industrial air pollution on health. A first review of the literature on the addressed causal inference methods is conducted, focusing on the main assumptions and suggested applications. Then the main longitudinal study, from which the causal inference methods originate, is described. A standard time-to-event analysis is performed to assess the relationship between exposure to air pollution (PM10 and SO2 from industrial origin) and mortality, as well as morbidity, in the cohort of residents around a large steel plant in the Taranto area (Apulia region, Italy). The Difference-in difference (DID) approach as well as three methods using the generalized propensity score (Propensity Function-PF of Imai and van Dyk, the Dose-response Function DRF by Hirano and Imbens, and the Robins’ Importance sampling-RIS using the GPS) were implemented in a Cox Proportional Hazard model for mortality. The main study demonstrated a negative effect of exposure to industrial air pollution on mortality and morbidity, after controlling for occupation, age, time period, and socioeconomic position index. The health effects were confirmed in all the causal approaches applied to the cohort, and the concentration-response curves showed increasing risk of natural and cause-specific mortality for higher levels of PM10 and SO2. We conclude that the health effects estimated are causal and that the adjustment for socioeconomic index already takes into account other, not measured, individual factors

Adult Changes in Weight and Physical Activity in Association with the Risk of Pancreatic Cancer: In the Vital Cohort

Significance. Pancreatic cancer is the fourth most common cancer-related death in the United States (U.S.); by 2030 this lethal disease is projected to be the second leading cause of cancer-related mortality. Thus, identifying modifiable risk factors for pancreatic cancer is of public health importance. Innovation. Two modifiable factors that impact pancreatic cancer are obesity and, perhaps, physical activity. Obesity is among the few risk factors that have been consistently associated with pancreatic cancer incidence, whereas the association with physical activity is inconsistent. However, whether age-specific exposures, or adult changes in exposure, are associated with pancreatic cancer is unclear for both exposures. Identification of age-specific risk factors, or adult changes in exposure, could lead to age-specific targeted prevention strategies. Dissertation Goals. My hypothesis was that age-specific weight and physical activity, and perhaps adult changes, may modulate pancreatic cancer risk. These exposures could plausibly act through several biologic mechanisms, including influencing circulating endogenous hormones, which may in turn impact pancreatic carcinogenesis. Thus, my objectives were to prospectively examine the associations of age-specific weight and physical activity, and adult changes, with pancreatic cancer risk. Methods. I used the National Cancer Institute-funded VITamins And Lifestyle (VITAL) study. This cohort of ~77,000 men and women in Washington state was recruited in 2000-2002, when participants were aged 55-76 years. Data collection included assessment of baseline, age-specific, and changes in adult weight and physical activity. Incident pancreatic cancer events (n=280) were identified through linkage to state and national registries after ~10 years of follow-up. Multi-variable Cox proportional hazards models were used to obtain estimates for the pancreatic cancer risk associations. Results. Pancreatic cancer risk was reduced by ~30-40% in association with adult physical activity undertaken in the 10 years prior to study recruitment, and with physical activity undertaken most days of the week during mid-life. In addition, mid-life adult obesity and weight gain, were associated with ~30-80% elevation in pancreatic cancer risk. Study Impact. If my results are replicated, targeting middle-aged adult Americans to engage in physical activity most days of the week, and avoid weight gain may be possible risk reduction strategies for this lethal cancer.Doctor of Philosoph