Exposure estimation, uncertainty and variability in occupational hygiene retrospective assessment

This thesis reports on a quantitative exposure assessment and on an analysis of the attributes of the data used in the estimations, in particular distinguishing between its uncertainty and variability. A retrospective assessment of exposure to benzene was carried out for a case control study of leukaemia in the Australian petroleum industry. The study used the mean of personal task-based measurements (Base Estimates) in a deterministic algorithm and applied factors to model back to places, times etc for which no exposure measurements were available. Mean daily exposures were estimated, on an individual subject basis, by summing the task-based exposures. These mean exposures were multiplied by the years spent on each job to provide exposure estimates in ppm-years. These were summed to provide a Cumulative Estimate for each subject. Validation was completed for the model and key inputs. Exposures were low, most jobs were below TWA of 5 ppm benzene. Exposures in terminals were generally higher than at refineries. Cumulative Estimates ranged from 0.005 to 50.9 ppm-years, with 84 percent less than 10 ppm-years. Exposure probability distributions were developed for tanker drivers using Monte Carlo simulation of the exposure estimation algorithm. The outcome was a lognormal distribution of exposure for each driver. These provide the basis for alternative risk assessment metrics e.g. the frequency of short but intense exposures which provided only a minimal contribution to the long-term average exposure but may increase risk of leukaemia. The effect of different inputs to the model were examined and their significance assessed using Monte Carlo simulation. The Base Estimates were the most important determinant of exposure in the model. The sources of variability in the measured data were examined, including the effect of having censored data and the between and within-worker variability. The sources of uncertainty in the exposure estimates were analysed and consequential improvements in exposure assessment identified. Monte Carlo sampling was also used to examine the uncertainties and variability associated with the tanker drivers' exposure assessment, to derive an estimate of the range and to put confidence intervals on the daily mean exposures. The identified uncertainty was less than the variability associated with the estimates. The traditional approach to exposure estimation typically derives only point estimates of mean exposure. The approach developed here allows a range of exposure estimates to be made and provides a more flexible and improved basis for risk assessment.

Physical activity, sedentary behavior and depression among disadvantaged women

This study investigated associations between components of physical activity (PA; e.g. domain and social context) and sedentary behaviors (SBs) and risk of depression in women from disadvantaged neighborhoods. A total of 3645 women, aged 18–45 years, from disadvantaged neighborhoods, self-reported their PA, SB and depressive symptoms. Crude and adjusted odds ratios and 95% confidence intervals were calculated for each component of PA, SB and risk of depression using logistic regression analyses, adjusting for clustering by women's neighborhood of residence. Being in a higher tertile of leisure-time PA and transport-related PA was associated with lower risk of depression. No associations were apparent for domestic or work-related PA. Women who undertook a small proportion of their leisure-time PA with someone were less likely to be at risk of depression than those who undertook all leisure-time PA on their own. Women reporting greater time sitting at the computer, screen time and overall sitting time had higher odds of risk of depression compared with those reporting low levels. The domain and social context of PA may be important components in reducing the risk of depression. Reducing time spent in SB may be a key strategy in the promotion of better mental health in women from disadvantaged neighborhoods.

Estimating process capability index Cpm using a bootstrap sequential sampling procedure

Construction of a confidence interval for process capability index CPM is often based on a normal approximation with fixed sample size. In this article, we describe a different approach in constructing a fixed-width confidence interval for process capability index CPM with a preassigned accuracy by using a combination of bootstrap and sequential sampling schemes. The optimal sample size required to achieve a preassigned confidence level is obtained using both two-stage and modified two-stage sequential procedures. The procedure developed is also validated using an extensive simulation study.

The incidence of all stroke and stroke subtype in the United Kingdom, 1985 to 2008 : a systematic review

Background : There is considerable geographic variation in stroke mortality around the United Kingdom (UK). Whether this is due to geographical differences in incidence or case-fatality is unclear. We conducted a systematic review of high-quality studies documenting the incidence of any stroke and stroke subtypes, between 1985 and 2008 in the UK. We aimed to study geographic and temporal trends in relation to equivalent mortality trends.

Methods : MEDLINE and EMBASE were searched, reference lists inspected and authors of included papers were contacted. All rates were standardised to the European Standard Population for those over 45, and between 45 and 74 years. Stroke mortality rates for the included areas were then calculated to produce rate ratios of stroke mortality to incidence for each location.

Results : Five papers were included in this review. Geographic variation was narrow but incidence appeared to largely mirror mortality rates for all stroke. For men over 45, incidence (and confidence intervals) per 100,000 ranged from 124 (109-141) in South London, to 185 (164-208) in Scotland. For men, premature (45-74 years) stroke incidence per 100,000 ranged from 79 (67-94) in the North West, to 112 (95-132) in Scotland. Stroke subtype data was more geographically restricted, but did suggest there is no sizeable variation in incidence by subtype around the country. Only one paper, based in South London, had data on temporal trends. This showed that there has been a decline in stroke incidence since the mid 1990 s. This could not be compared to any other locations in this review.

Conclusions : Geographic variations in stroke incidence appear to mirror variations in mortality rates. This suggests policies to reduce inequalities in stroke mortality should be directed at risk factor profiles rather than treatment after a first incident event. More high quality stroke incidence data from around the UK are needed before this can be confirmed.

An examination of the health and wellbeing of childless women : A cross-sectional exploratory study in Victoria, Australia

Background
Childlessness among Australian women is increasing. Despite this, little is known about the physical and mental health and wellbeing of childless women, particularly during the reproductive years. The aims of this exploratory study were to: 1) describe the physical and mental health and wellbeing and lifestyle behaviours of childless women who are currently within the latter part of their reproductive years (30 – 45 years of age); and 2) compare the physical and mental health and wellbeing and lifestyle behaviours of these childless women to Australian population norms.
Methods
A convenience sample of 50 women aged between 30 and 45 years were recruited to participate in a computer assisted telephone interview. The SF-36 Health Survey v2 and lifestyle indicators were collected in regards to women’s health and wellbeing. Data were analysed using descriptive statistics, t-tests for independent sample means and 95% confidence intervals for the difference between two independent proportions.
Results
Childless women in this study reported statistically significant poorer general health, vitality, social functioning and mental health when compared to the adult female population of Australia. With the exception of vegetable consumption, lifestyle behaviours were similar for the childless sample compared to the adult female population in Australia.
Conclusions
Childless women may be at a greater risk of experiencing poor physical and mental health when compared to the Australian population. A woman’s health and wellbeing during her reproductive years may have longer term health consequences and as such the health and wellbeing of childless women requires further investigation to identify and address implications for the provision of health (and other social) services for this growing population group.

Socio-demographic characteristics of children experiencing socioeconomic disadvantage who meet physical activity and screen-time recommendations : the READI study

Objective - To identify socio-demographic characteristics of children from socioeconomically disadvantaged neighbourhoods who meet physical activity and screen recommendations.
Method - Children aged 5–12 years (n = 373; 45% boys) were recruited in 2007 from socioeconomically disadvantaged urban and rural areas of Victoria, Australia. Children's physical activity, height and weight were objectively measured. Mothers reported their highest level of education, and proxy-reported their child's usual screen-time. Odds ratios (OR) and 95% confidence intervals (95% CI) examined odds of meeting physical activity (> 60 minutes/day) and screen (≤ 120 minutes/day) recommendations according to socio-demographic characteristics.
Results - Approximately 84% of children met physical activity and 43% met screen recommendations. Age was inversely associated with odds of meeting physical activity and screen recommendations, and overweight/obese status was associated with lower odds of meeting screen recommendations (boys: OR = 0.39, 95%CI = 0.16–0.95; girls: OR = 0.47, 95%CI = 0.26–0.83). Among boys, living in a rural area was positively associated with meeting screen recommendations (OR = 3.08, 95%CI = 1.42–6.64). Among girls, high levels of maternal education were positively associated with meeting screen recommendations (OR = 2.76, 95%CI = 1.33–5.75).
Conclusion - Specific socio-demographic characteristics were associated with odds of meeting physical activity and screen recommendations. Identifying factors associated with such ‘resilience’ among this group may provide important learnings to inform future physical activity promotion initiatives.

Fruit and vegetable consumption and the risk of proximal colon, distal colon and rectal cancers in a case-control study in Western Australia

Background Fruits and vegetables (F/V) have been examined extensively in nutrition research in relation to colorectal cancer (CRC). However, their protective effect is subject to debate, possibly because of different effects on different subsites of the large bowel.

Objective To determine whether any association between F/V consumption and risk of CRC differed by subsite of the bowel (proximal colon, distal colon, and rectum).

Design The Western Australian Bowel Health Study is a population-based, case-control study conducted between June 2005 and August 2007. Complete food frequency questionnaire data were analysed from 834 CRC cases and 939 controls. Logistic regression analysis was used to estimate the effects of quartiles of F/V intake on risk of CRC at different subsites. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for CRC overall and for the three separate subsites.

Results Risk of proximal colon cancer and rectal cancer was not associated with intakes of total F/V, total vegetable, or total fruit. Brassica vegetable intake was inversely related with proximal colon cancer (Q4 vs Q1 OR 0.62; 95% CI 0.41 to 0.93). For distal colon cancer, significant negative trends were seen for total F/V, and total vegetable intake. Distal colon cancer risk was significantly decreased for intake of dark yellow vegetables (Q4 vs Q1 OR 0.61; 95% CI 0.41 to 0.92) and apples (Q4 vs Q1 OR 0.51; 95% CI 0.34 to 0.77). An increased risk for CRC was found to be associated with intake of fruit juice (Q4 vs Q1 OR 1.74; 95% CI 1.24 to 2.45).

Conclusions Our results suggest that different F/V may confer different risks for cancer of the proximal colon, distal colon, or rectum. Future studies might consider taking into account the location of the tumor when examining the relation between F/V consumption and risk of CRC.

Increased cardiometabolic risk is associated with increased TV viewing time

Purpose: Television viewing time, independent of leisure time physical activity, has cross-sectional relationships with the metabolic syndrome and its individual components. We examined whether baseline and 5-yr changes in self-reported television viewing time are associated with changes in continuous biomarkers of cardiometabolic risk (waist circumference, triglycerides, HDL-cholesterol, systolic and diastolic blood pressure, fasting plasma glucose, and a clustered cardiometabolic risk score) in Australian adults.


Methods: The Australian Diabetes, Obesity and Lifestyle Study (AusDiab) is a prospective, population-based cohort study with biological, behavioral, and demographic measures collected in 1999-2000 and 2004-2005. Noninstitutionalized adults aged >=25 yr were measured at baseline (11,247; 55% of those completing an initial household interview); 6400 took part in the 5-yr follow-up biomedical examination, and 3846 met the inclusion criteria for this analysis. Multiple linear regression analysis was used, and unstandardized B coefficients (95% confidence intervals (CI)) are provided.


Results: Baseline television viewing time (10 h·wk-1 unit) was not significantly associated with change in any of the biomarkers of cardiometabolic risk. Increases in television viewing time over 5 yr (10 h·wk-1 unit) were associated with increases in waist circumference (men: 0.43 cm, 95% CI = 0.08-0.78 cm, P = 0.02; women: 0.68 cm, 95% CI = 0.30-1.05, P < 0.001), diastolic blood pressure (women: 0.47 mm Hg, 95% CI = 0.02-0.92 mm Hg, P = 0.04), and the clustered cardiometabolic risk score (women: 0.03, 95% CI = 0.01-0.05, P = 0.007). These associations were independent of baseline television viewing time and baseline and change in physical activity and other potential confounders.


Conclusions: These findings indicate that an increase in television viewing time is associated with adverse cardiometabolic biomarker changes. Further prospective studies using objective measures of several sedentary behaviors are required to confirm causality of the associations found.

Utility-based quality of life associated with overweight and obesity : the Australian diabetes, obesity, and lifestyle study

This study aimed to estimate utility-based quality of life (UQoL) differences between healthy body weight and excess body weight categories. Cross-sectional analysis of 10,959 adults, participating in baseline data collection of the nationally representative Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study was undertaken. Height and weight were measured by trained personnel. Body weight categories were assigned as healthy weight, overweight, and obesity subclasses I, II and III. UQoL was assessed using the SF-6D, which captures physical functioning, role limitation, social functioning, pain, mental health, and vitality on a score of 0.00–1.00 (worst-best). The relationship between body weight categories and UQoL was assessed using linear regression, adjusting for age, sex, education, and smoking. Relative to the healthy weight group (mean UQoL score 0.77), mean adjusted UQoL differences (95% confidence intervals) were 0.001 (−0.008, 0.010) for overweight, −0.012 (−0.022, −0.001) for class-I obese, −0.020 (−0.041, 0.001) for class-II obese, and −0.069 (−0.099, −0.039) for class-III obese groups. Adding metabolic syndrome markers to the covariates had little impact on these differences. Results confirmed an inverse dose–response relationship between body weight and UQoL in this study of Australian adults. This highlights the need to incorporate UQoL measures which are sensitive to the subclasses of obesity when evaluating obesity interventions.

Mortality disparities between geographic regions : results from a risk percentiles model for coronary heart disease

Background: Planning of disease prevention strategies requires information regarding the distribution of absolute risk in the population to allow targeting of people at high disease risk. It is well known that death rates from coronary heart disease (CHD) are higher in remote areas of Australia compared with major cities. Less well understood is the distribution of the absolute risk of CHD death within the different geographic regions. We present a mathematical model of CHD which projects the lifetime risk of death among individuals in different percentiles of CHD risk. We apply this to model the distribution of CHD risk within different geographic regions.

Methods: Using information from the Framingham1, MRFIT2 and AusDiab3 studies, the Australian population was divided into percentiles of CHD risk within age and gender groups by geographic location. Absolute mortality risk was determined at each percentile using current Australian mortality data. Survival curves were generated for each percentile using these risk estimates. Approximate confidence intervals were derived using bootstrap methods.

Conclusions: The difference in life expectancy at age 25 between those in the lowest decile of CHD risk compared to the highest was 5.8 years (95%CI:4.7,6.7) in major cities compared to 8.5 years (95%CI:7.6,9.7) in remote areas. The difference in risk of premature death (before age 75) was 12% (95%CI:10%,14%) in major cities compared to 33% (95%CI:28%,38%) in remote areas.

The impact of test medium on use of visual analogue scales

Objectives: Visual analog scales are frequently used as a means of allowing participants to rate symptoms during clinical trials. The accuracy and reproducibility of these scales play an important role in determining the experimental value of the data they provide. This study was initiated to compare the data collected using paper- and computer-based (Tablet PC) analog scales to better understand the variability in data provided by a visual analog scale.

Methods: Thirty participants rated ocular comfort, redness, and clarity of vision (right and left eyes) on a nondemarcated horizontal line on both paper and a Tablet PC. Measurements were taken in the morning between the hours of 8:30 and 10:30 am and again the same day between 2:30 and 4:30 pm.

Results: The mean difference between the measures recorded in the morning for the 2 media was 2.6 ± 0.9 (confidence intervals, 2 standard errors of the differences) units on a 100 unit scale, with the Tablet PC having the higher mean measure. The limits of agreement (2 standard deviations of the differences) was 9.4 units. Comparing the difference of the differences (1.0 ± 1.3) between the 2 methods of measure (morning vs. afternoon) the visual analog scales on the Tablet PC seemed to have good reproducibility of agreement in comparison with the paper version.

Conclusions: Discrepancy analysis yielded no significant difference and slight bias between paper- and computer-based analog scales. Repeatability of measures using the Tablet PC was also demonstrated. These results suggest that the choice of medium does not significantly influence the outcome for subjective analog scales.

Impact of depression treatment on mental and physical health-related quality of life of cardiac patients : a meta-analysis

PURPOSE: To conduct a meta-analysis evaluating the effectiveness of depression treatment on mental and physical health-related quality of life (HRQOL) of cardiac patients.

METHODS: Studies were identified using medical, health, psychiatry, psychology, and social sciences databases. Inclusion criteria were (1) 1 or more control conditions, (2) random assignment to condition after admission for myocardial infarction (MI)/acute coronary syndrome, after recording positive results on a depression screener, (3) documentation of depression symptoms at baseline, (4) depression management as a component of the rehabilitation/intervention, (5) validated measure of HRQOL as an outcome, at minimum 6-month followup. For meta-analysis, mental and physical HRQOL were the end points studied, using standardized mean differences for continuous outcome measures, with 95% confidence intervals. Heterogeneity was explored by calculating I2 statistic.

RESULTS: Five randomized controlled trials included in the analysis represented 2105 participants (1058 intervention vs 1047 comparator). Compared with a comparator group at 6 months, a test for overall effect demonstrated statistically significant improvements in mental HRQOL in favor of the intervention (standardized mean differences = −0.29 [−0.38 to −0.20], [P < .00001]; I2 = 0%). Depression treatment had a modest yet significant impact on physical HRQOL (standardized mean differences = −0.14 [−0.24 to −0.04] [P = .009]; I2 = 15%).

CONCLUSION: While the impact of post-MI depression interventions on physical HRQOL is modest, treatment can improve mental HRQOL in a significant way. Future research is required to develop and evaluate a program that can achieve vital improvements in overall HRQOL, and potentially cardiovascular outcomes, of cardiac patients.

Epidemiology of acute rheumatic fever in New Zealand 1996-2005

Aim: Acute rheumatic fever (ARF) and its sequela chronic rheumatic heart disease remain significant causes of morbidity and mortality in New Zealand, particularly among Māori and Pacific peoples. Despite its importance, ARF epidemiology has not been reviewed recently. The aims of this study were to assess trends in ARF incidence rates between 1996 and 2005 and the extent to which ARF is concentrated in certain populations based on age, sex, ethnicity and geographical location.

Methods: This descriptive epidemiological study examined ARF incidence rates using hospitalisation data (1996–2005) and population data from the 1996 and 2001 censuses. Rates were compared by using rate ratios and 95% confidence intervals.

Results: New Zealand's annual ARF rate was 3.4 per 100 000. ARF was concentrated in certain populations: 5- to 14-year-olds, Māori and Pacific peoples and upper North Island areas. From 1996 to 2005, the New Zealand European and Others ARF rate decreased significantly while Māori and Pacific peoples’ rates increased. Compared with New Zealand European and Others, rate ratios were 10.0 for Māori and 20.7 for Pacific peoples. Of all cases, 59.5% were Māori or Pacific children aged 5–14 years, yet this group comprised only 4.7% of the New Zealand population.

Conclusion: ARF rates in New Zealand have failed to decrease since the 1980s and remain some of the highest reported in a developed country. There are large, and now widening, ethnic disparities in ARF incidence. ARF is so concentrated by age group, ethnicity and geographical area that highly targeted interventions could be considered, based on these characteristics.

Prediction of Drug Dissolution Profiles Using Artificial Neural Networks

This paper investigates the efficacy and reliability of Artificial Neural Networks (ANNs) as an intelligent decision support tool for pharmaceutical product formulation. Two case studies have been employed to evaluate capabilities of the Multilayer Perceptron network in predicting drug dissolution/release profiles. Performances of the network were evaluated using similarity factor (&fnof[sub 2]) — an index recommended by the United States Food and Drug Administration for profile comparison in pharmaceutical research. In addition, the bootstrap method was applied to assess the network prediction reliability by estimating confidence intervals associated with the results. The Multilayer Perceptron network also demonstrated a superior performance in comparison with multiple regression models. The results reveal that the ANN system has potentials to be a decision support tool for profile prediction in pharmaceutical experimentation, and the bootstrap method could be used as a means to assess reliability of the network prediction. [ABSTRACT FROM AUTHOR].

Insulin sensitivity in response to a single resistance exercise session in apparently healthy individuals

BACKGROUND: Regular resistance exercise completed for a number of weeks has been shown to increase insulin sensitivity and reduce the risk of diabetes-related complications. However, the acute responses to resistance exercise have not been adequately investigated in relation to training frequency.
AIM: To investigate the changes to insulin sensitivity in apparently healthy individuals following a single session of unaccustomed resistance exercise.
SUBJECTS AND METHODS: Ten sedentary, apparently healthy individuals performed a baseline oral glucose tolerance test and maximal strength testing. Participants then performed a single session of moderate-high intensity resistance exercise which was followed by 4 consecutive days of oral glucose tolerance testing, for which participants replicated their initial diet. Mean estimated insulin sensitivity change scores from baseline values and their 95% confidence intervals were compared to the previously determined values for a clinically meaningful change.
RESULTS: Two participants were identified as having hyperinsulinemia and their data were therefore removed from the main analysis. There was a clinically meaningful increase in insulin response (mean >7237 pmol·l⁻¹·120 min⁻¹) on all days following the exercise session and a clinically meaningful increase in glucose response (mean >81 mmol·l⁻¹·120 min⁻¹) on only the 3rd day following exercise. These changes suggest a potentially adverse short-term effect. Additionally, the 2 individuals with hyperinsulinemia displayed more extreme results.
CONCLUSION: These results suggest that insulin sensitivity may be impaired following a single session of unaccustomed resistance exercise for approximately 4 days in healthy untrained, older individuals. Further research is required for individuals with hyperinsulinemia