Faculty Bibliography

BACKGROUND:Australian national biomonitoring for persistent organic pollutants (POPs) relies upon age-specific pooled serum samples to characterize central tendencies of concentrations but does not provide estimates of upper bound concentrations. This analysis compares population variation from biomonitoring datasets from the US, Canada, Germany, Spain, and Belgium to identify and test patterns potentially useful for estimating population upper bound reference values for the Australian population. METHODS:Arithmetic means and the ratio of the 95th percentile to the arithmetic mean (P95:mean) were assessed by survey for defined age subgroups for three polychlorinated biphenyls (PCBs 138, 153, and 180), hexachlorobenzene (HCB), p,p-dichlorodiphenyldichloroethylene (DDE), 2,2',4,4' tetrabrominated diphenylether (PBDE 47), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). RESULTS:Arithmetic mean concentrations of each analyte varied widely across surveys and age groups. However, P95:mean ratios differed to a limited extent, with no systematic variation across ages. The average P95:mean ratios were 2.2 for the three PCBs and HCB; 3.0 for DDE; 2.0 and 2.3 for PFOA and PFOS, respectively. The P95:mean ratio for PBDE 47 was more variable among age groups, ranging from 2.7 to 4.8. The average P95:mean ratios accurately estimated age group-specific P95s in the Flemish Environmental Health Survey II and were used to estimate the P95s for the Australian population by age group from the pooled biomonitoring data. CONCLUSIONS:Similar population variation patterns for POPs were observed across multiple surveys, even when absolute concentrations differed widely. These patterns can be used to estimate population upper bounds when only pooled sampling data are available.

Analyses of the concentrations of a given environmental compound usually show that most citizens have much lower concentrations than a certain minority, whose members have high body concentrations. Surveys of human exposure to chemicals do not usually integrate the number of chemical compounds detected per person and the concentration of each compound. This leaves untested relevant exposure situations, for example, whether individuals with low concentrations of some compounds have high concentrations of the other compounds. On scientific grounds, it is puzzling that this possibility, arithmetically and conceptually rather simple, has seldom if ever been tested in studies based on a representative sample of the general population. A study based on a representative sample of the general population of Catalonia (Spain) (Porta, Pumarega, & Gasull, 2012), which integrated the number of compounds detected per person and the concentration of each compound, found that more than half of the population had concentrations in the top quartile of 1 or more of the 19 persistent toxic substances (PTS) (pesticides and polychlorinated biphenyls) analyzed. Significant subgroups of the population accumulated PTS mixtures at high concentrations. For instance, 48% of women 60-74 years had concentrations of 6 or more PTS in the top quartile; half of the entire population had levels of 1-5 PTS above 500 ng/g, and less than 4% of citizens had all PTS in the lowest quartile. Thus, PTS concentrations appear low in most of the population only when each individual compound is looked at separately. It is not accurate to state that most of the population has low concentrations of PTS. The assessment of mixture effects must address the fact that most individuals are contaminated by PTS mixtures made of compounds at both low and high concentrations.

Scant evidence is available worldwide on the relative influence of occupational social class and educational level on body concentrations of persistent organic pollutants (POPs) in the general population. The objective was to analyse such influence in a representative sample of the general population of Catalonia, Spain. Participants in the Catalan Health Interview Survey aged 18-74 were interviewed face-to-face, gave blood, and underwent a physical exam. The role of age, body mass index (BMI), and parity was analysed with General Linear Models, and adjusted geometric means (GMs) were obtained. Crude (unadjusted) concentrations were higher in women and men with lower education, and in women, but not men, in the less affluent social class. After adjusting for age, in women there were no associations between POP levels and social class or education. After adjusting for age and BMI, men in the less affluent class had higher p,p'-DDE concentrations than men in class I (p-value=0.016), while men in class IV had lower HCB than men in the upper class (p-value<0.03). Also in contrast with some expectations, positive associations between education and POP levels were observed after adjusting for age and BMI in men; e.g., men with university studies had higher HCB concentrations than men with first stage of primary schooling (adjusted GM 153.9 and 80.5ng/g, respectively) (p-value<0.001). When education and social class were co-adjusted for, some positive associations with education in men remained statistically significant, whereas class remained associated only with p,p'-DDE. Educational level influenced blood concentrations of POPs more than occupational social class, especially in men. In women, POP concentrations were mainly explained by age/birth cohort, parity and BMI. In men, while concentrations were also mainly explained by age/birth cohort and BMI, both social class and education showed positive associations. Important characteristics of socioeconomic groups as age and BMI may largely explain crude differences among such groups in internal contamination by POPs. The absence of clear patterns of relationships between blood concentrations of POPs and indicators of socioeconomic position may fundamentally be due to the widespread, lifelong, and generally invisible contamination of human food webs. Decreasing historical trends would also partly explain crude socioeconomic differences apparently due to birth cohort effects.

Diagnostic accuracy may be overestimated when using certain study designs; thus, the inclusion of studies using different designs in meta-analyses may have important effects on their results, and influence clinical decision making. The main aim of this study was to explore the influence of heterogeneity (based on the inclusion of different study designs) on diagnostic accuracy in a sample of published meta-analyses of diagnostic accuracy studies. We identified 30 systematic reviews which included 95 separate meta-analyses combining the results from a total of 976 individual studies. We classified each individual study according to the study design (case-control studies, clinically relevant patient series or other), and each meta-analysis according to the heterogeneity of the included studies. Furthermore, we registered how the methodological quality of the individual studies was assessed. Finally, for each meta-analysis, the summary measure of diagnostic accuracy was categorised as Good, Fair or Poor. We used logistic regression to assess the relationship between reporting good diagnostic accuracy and heterogeneity. Meta-analyses with heterogeneous populations were over three times more likely to report good diagnostic accuracy compared to meta-analyses that included only clinically relevant patient series (adjusted odds ratio 3.07 95% CI 1.16-8.11). The combination of studies that use different designs, within the same meta-analysis, may lead to higher estimates of diagnostic accuracy.

OBJECTIVES/OBJECTIVE:To analyze whether differences between the interval from suspicion or clinical diagnosis to treatment onset (IClinDT) and the interval from certainty diagnosis to treatment onset (ICertDT) varied by tumor site, stage, and mode of hospital admission. STUDY DESIGN AND SETTING/METHODS:From our hospital cancer registry, we selected all 8,814 patients with breast, colorectal, lung, prostate, or cervical cancer diagnosed between 1992 and 2006. We compared IClinDT and ICertDT with density plots and logistic regression. RESULTS:IClinDT was up to three times higher than ICertDT. There were very large differences among stages and within each stage in IClinDT and ICertDT. Tumor stage significantly influenced the difference between the two intervals in three of the five locations (breast, lung, and prostate cancer); as stage worsened, the difference between IClinDT and ICertDT became smaller. In all tumor sites, the difference was larger in scheduled than in emergency admissions. Overall, therapeutic delays--even when measured by ICertDT--were disturbingly common for important subgroups of patients. CONCLUSION/CONCLUSIONS:The difference between IClinDT and ICertDT varied highly by tumor site, stage, and mode of hospital admission. More standardized definitions and procedures to calculate time intervals between cancer diagnosis and treatment onset are needed.

There is increasing evidence that environmental factors play an important role in the development of type 2 diabetes. Several persistent organic pollutants are suspected to contribute to the increasing prevalence and risk of type 2 diabetes. The aim of this study was to investigate the association of the body burden of three organochlorine pesticides and three polychlorinated biphenyls and the overall estrogenic activity with the risk of type 2 diabetes in a sample of adults from Southern Spain. Samples of adipose tissue and serum were obtained from 386 subjects undergoing non-cancer-related surgery and were extracted using validated methodologies. Residues of persistent organic pollutants were analyzed by means of high-resolution gas chromatography with a mass spectrometry detector in tandem mode. The overall estrogenicity of the adipose tissue extracts was measured by using the total effective xenoestrogen burden (TEXB) biomarker. Data on lifestyle, dietary habits, and health status were gathered from face-to-face interviews and clinical records. Statistical analyses were performed with unconditional logistic regression and different adjustment levels. In the models adjusted for adipose tissue origin, sex, age, and body mass index, the 2nd and 3rd tertiles of adipose tissue concentrations of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were positively associated with the risk of diabetes [odds ratios (95% confidence interval)=3.6 (0.8-17.3) and 4.4 (1.0-21.0), respectively]. A positive association with β-hexachlorocyclohexane was also found when body mass index and adipose tissue origin were removed from the models, with odds ratios (95% confidence interval) of 3.3 (1.0-10.4) and 5.5 (1.7-17.3), for the 2nd and 3rd tertiles of exposure, respectively. In addition, a statistically significant interaction was observed between p,p'-DDE and body mass index, such that the risk of diabetes increased with tertiles of exposure in a linear manner in non-obese subjects but not in the obese, in whom an inverted U-shape pattern was observed.

BACKGROUND:Nearly 13 million new cancer cases and 7.6 million cancer deaths occur worldwide each year; 63% of cancer deaths occur in low- and middle-income countries. A substantial proportion of all cancers are attributable to carcinogenic exposures in the environment and the workplace. OBJECTIVE:We aimed to develop an evidence-based global vision and strategy for the primary prevention of environmental and occupational cancer. METHODS:We identified relevant studies through PubMed by using combinations of the search terms "environmental," "occupational," "exposure," "cancer," "primary prevention," and "interventions." To supplement the literature review, we convened an international conference titled "Environmental and Occupational Determinants of Cancer: Interventions for Primary Prevention" under the auspices of the World Health Organization, in Asturias, Spain, on 17-18 March 2011. DISCUSSION/CONCLUSIONS:Many cancers of environmental and occupational origin could be prevented. Prevention is most effectively achieved through primary prevention policies that reduce or eliminate involuntary exposures to proven and probable carcinogens. Such strategies can be implemented in a straightforward and cost-effective way based on current knowledge, and they have the added benefit of synergistically reducing risks for other noncommunicable diseases by reducing exposures to shared risk factors. CONCLUSIONS:Opportunities exist to revitalize comprehensive global cancer control policies by incorporating primary interventions against environmental and occupational carcinogens.

OBJECTIVE:To describe the time trend in atmospheric lead concentrations in Spain, from before lead was banned as a gasoline additive to the present, and to determine the trend in lead body burden in the Spanish child population. METHODS:We obtained the annual average for atmospheric lead levels in several Spanish cities from the 1980s to the present. A literature search was conducted to identify published studies on lead concentrations in populations of Spanish children. RESULTS:Overall, atmospheric lead levels decreased, particularly between 1991 and 1999. This downward trend was related to a decrease in lead concentrations in Spanish children from 1989, the year in which the first study of childhood lead exposure was published, until the present. The decreased concentrations in both air and in children was most probably a result of legislative measures regulating the maximum amount of lead in gasoline in 1987 until a complete ban in August 2001. CONCLUSIONS:From a public health point of view, the banning of leaded gasoline has significantly increased health protection in the Spanish population.

BACKGROUND:There are no analyses of citations to books on epidemiological and statistical methods in the biomedical literature. Such analyses may shed light on how concepts and methods changed while biomedical research evolved. Our aim was to analyze the number and time trends of citations received from biomedical articles by books on epidemiological and statistical methods, and related disciplines. METHODS AND FINDINGS/RESULTS:The data source was the Web of Science. The study books were published between 1957 and 2010. The first year of publication of the citing articles was 1945. We identified 125 books that received at least 25 citations. Books first published in 1980-1989 had the highest total and median number of citations per year. Nine of the 10 most cited texts focused on statistical methods. Hosmer & Lemeshow's Applied logistic regression received the highest number of citations and highest average annual rate. It was followed by books by Fleiss, Armitage, et al., Rothman, et al., and Kalbfleisch and Prentice. Fifth in citations per year was Sackett, et al., Evidence-based medicine. The rise of multivariate methods, clinical epidemiology, or nutritional epidemiology was reflected in the citation trends. Educational textbooks, practice-oriented books, books on epidemiological substantive knowledge, and on theory and health policies were much less cited. None of the 25 top-cited books had the theoretical or sociopolitical scope of works by Cochrane, McKeown, Rose, or Morris. CONCLUSIONS:Books were mainly cited to reference methods. Books first published in the 1980s continue to be most influential. Older books on theory and policies were rooted in societal and general medical concerns, while the most modern books are almost purely on methods.