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PubMed1997

Multicollinearity may lead to artificial interaction: an example from a cross sectional study of biomarkers.

Collinearity is the situation which arises in multiple regression when some or all of the explanatory variables are so highly correlated with one another that it becomes very difficult, if not impossible, to disentangle their influences and obtain a reasonably precise estimate of their effects. Suppressor variable is one of the extreme situations of collinearity that one variable can substantially increase the multiple correlation when combined with a variable that is only modestly correlated with the response variable. In this study, we describe the process by which we disentangled and discovered multicollinearity and its consequences, namely artificial interaction, using the data from cross-sectional quantification of several biomarkers. We showed how the collinearity between one biomarker (blood lead level) and another (urinary trans, trans-muconic acid) and their interaction (blood lead level* urinary trans, trans-muconic acid) can lead to the observed artificial interaction on the third biomarker (urinary 5-aminolevulinic acid).

Biomarkers↗
PubMed1998

[Interviewer effects in assessing subjective quality of life and satisfaction with care in sheltered housing].

The impact of interviewer-effects on subjective evaluative criteria was examined in a randomized control group design (n = 26 x 2) of clients of sheltered living in Berlin-Spandau. The assessment of care and subjective quality of life showed that clients were more satisfied if they had been interviewed by their responsible caregivers compared to interviewers from other providers of the same region--unknown to the clients. Conductibility of interviews was independent of interview conditions. A systematic overestimation of satisfaction should be taken into account if responsible caregivers interview their own clients. Such data should not be used comparing different settings.

Adult↗
PubMed1995

[Epidemiologic research on the environment and health: some methodologic aspects].

Research in environmental epidemiology deals with physical, chemical and biological agents whose presence--or relative absence--within the different media coming into contract with human beings (air, water, soil, food, etc...) may be harmful to human health. Some "major" environmental risk factors are well known. In a number of situations, however, environment-disease associations are "weak". This does not rule out the possibility that the exposures involved have a significant impact on human health, considering their prevalence which is frequently high. However, this complicates their study owing to the potential importance of biases as well as that of sampling fluctuations. Although increasing study size is of crucial importance, it is not sufficient to establish a clearcut distinction between "weak" associations and "diluted" ones. To improve our knowledge of health risks which are associated with environmental exposures, the basic methodological principles of epidemiological research--to define and adequately measure exposures, health outcomes, confounders and effect modifiers--may be very valuable to approach the study of "weak" associations: 1) identifying and quantifying the presence of the agents of interest in the environment, studying the distribution of environmental exposures among individuals and its determinants, taking into account the whole history of personal exposures and integrating adequately the short term time variability of exposures, giving special attention to the type and intensity of exposures may help in the definition and measurement of exposures; 2) carefully analyzing the interactions which may exist between the physical, chemical and biological agents of interest and the human body may greatly help in the elaboration, measurement and validation of relevant health outcomes (exposures to the target organs, early lesions and health impairments); 3) this same approach may also greatly contribute to the identification of constitutional or acquired individual characteristics which may interact with environmental agents in the development of diseases. While there is no guarantee that such approaches will successfully discriminate between "weak" and "diluted" associations, it is likely that inconclusive epidemiological evidence will be very difficult to avoid if such approaches are neglected by environmental epidemiologists.

Bias↗
PubMedDate not supplied

Cancer mortality and poverty in Argentina: a geographical correlation study.

Age-standardized mortality rates of cancer were calculated for the Argentine provinces using deaths from 7 years of registration (1980-1986). Correlations between the geographical distributions of the rates for the main causes of death by cancer were analyzed. The correlations were adjusted for socioeconomic status using an indicator of low socioeconomic level (NBI) as a third variable in a multivariate analysis or stratifying by NBI. Correlations between the distribution of the age-standardized mortality rates in males and females for the same tumor site also were analyzed. Positive intersex correlations were observed for mortality rates of cancers of the colon, liver, pancreas, esophagus, stomach, gallbladder, and bladder. Negative correlations with NBI were observed for cancers of the breast and ovary in females, colon and pancreas in both sexes, and bladder in males. Positive correlations with NBI were observed for cancer of the cervix and for all uterine cancers. After adjusting by NBI, only the correlations between the distributions of cancer of the lung and cancers of the bladder, larynx, and pancreas in males remained statistically significant. The stratified analysis showed changes in the values of many of the correlation indexes by level of NBI. It is concluded that the socioeconomic level, measured by the NBI, is a strong confounder and an effective modifier of many correlations presented.

Adolescent↗
PubMed1999

The role of perceived job stress in the relationship between smoking and the development of peptic ulcers.

Although smoking has been considered a risk factor in causing pepticulcers, no study has examined the effects of job stress on the relationship between peptic ulcers and smoking. To establish a link between gastric or duodenal ulcers over two years and a state of perceived job stress, a questionnaire, including questions on demographics, smoking, history of peptic ulcer and perceived job stress was conducted. Follow-up surveys were carried out every six months to accumulate the data for this analysis and the time span of this follow up study was two years. To examine the role of perceived job stress on the relationship between smoking and peptic ulcers, stratified analyses were performed. Some specific causes of perceived job stress such as "Too much competition," "Schedule is too tight or pressed to work too hard" had high estimated relative risks: 2.13 with 95% confidence interval (CI) of 1.09-4.16 and 2.50 with 95% CI of 0.98-6.40, respectively. Stratified analyses suggested an effect-measure modification of perceived job stress in the relationship between peptic ulcers and smoking. Multiplicative and additive models suggest positive interaction between perceived job stress and smoking. These results suggest that specific perceived job stress is an effect modifier in the relationship between the history of the peptic ulcer and smoking.

Adult↗
PubMed2004

Issues in the reporting of epidemiological studies: a survey of recent practice.

OBJECTIVES: To review current practice in the analysis and reporting of epidemiological research and to identify limitations. DESIGN: Examination of articles published in January 2001 that investigated associations between risk factors/exposure variables and disease events/measures in individuals. SETTING: Eligible English language journals including all major epidemiological journals, all major general medical journals, and the two leading journals in cardiovascular disease and cancer. MAIN OUTCOME MEASURE: Each article was evaluated with a standard proforma. RESULTS: We found 73 articles in observational epidemiology; most were either cohort or case-control studies. Most studies looked at cancer and cardiovascular disease, even after we excluded specialty journals. Quantitative exposure variables predominated, which were mostly analysed as ordered categories but with little consistency or explanation regarding choice of categories. Sample selection, participant refusal, and data quality received insufficient attention in many articles. Statistical analyses commonly used odds ratios (38 articles) and hazard/rate ratios (23), with some inconsistent use of terminology. Confidence intervals were reported in most studies (68), though use of P values was less common (38). Few articles explained their choice of confounding variables; many performed subgroup analyses claiming an effect modifier, though interaction tests were rare. Several investigated multiple associations between exposure and outcome, increasing the likelihood of false positive claims. There was evidence of publication bias. CONCLUSIONS: This survey raises concerns regarding inadequacies in the analysis and reporting of epidemiological publications in mainstream journals.

Confounding Factors, Epidemiologic↗
PubMed2007

Lipid peroxidation, oxidative stress genes and dietary factors in breast cancer protection: a hypothesis.

We have recently proposed that lipid peroxidation may be a common mechanistic pathway by which obesity and hypertension lead to increased renal cell cancer risk. During this exercise, we noted a risk factor swap between breast and kidney cancer (oophorectomy and increased parity, detrimental for kidney, beneficial for breast; high blood pressure, detrimental for kidney, beneficial for breast when it occurs during pregnancy; alcohol, beneficial for kidney, detrimental for breast, and so on). We have subsequently proposed the hypothesis that lipid peroxidation represents a protective mechanism in breast cancer, and reviewed the evidence of the role of lipid peroxidation on established hormonal and non-hormonal factors for breast cancer. Here, we review the evidence in support of lipid peroxidation playing a role in the relationships between dietary factors and breast cancer. Available evidence implicates increased lipid peroxidation products in the anti-carcinogenic effect of suspected protective factors for breast cancer, including soy, marine n-3 fatty acids, green tea, isothiocyanates, and vitamin D and calcium. We also review the epidemiological evidence supporting a modifying effect of oxidative stress genes in dietary factor-breast cancer relationships.

Breast Neoplasms↗
PubMed1996

Is self-reported pain an appropriate outcome measure in ergonomic-epidemiologic studies of work-related musculoskeletal disorders?

Of the various overlapping approaches used to define outcome in ergonomic-epidemiologic studies of work-related musculoskeletal disorders, the most widely used are clinical diagnostic entities, whose criteria derive either from clinical examination (consisting of clinical tests in conjunction with symptoms and clinical history) or from findings of special investigations, such as nerve conduction testing. Problems with the use of clinical diagnostic entities as surveillance tools relate to their high definitional variability, to the unknown test attributes and performance in worker populations, and to their lack of field utility. Other approaches to define outcome such as impairment and disability evaluations are seldom used; there are problems with existing instruments in disentangling multiple determinants. The use of subjective measures (self-reported pain) may be the most valuable approach to measuring outcome in population-based surveys. This approach has high capacity (can be used in large populations) and good field utility, has been supported by evidence of construct validity in some ergonomic-epidemiologic studies, and is able to assimilate the diverse and overlapping symptom patterns characteristic of some work-related musculoskeletal disorders. Traditional biases against subjective measures are evident in the literature, but these measures have also been badly used in many studies, with insufficient attention being paid to potential confounders and effect modifiers. Measurement of factors that influence pain perception and reporting need to be incorporated in ergonomic-epidemiologic studies and controlled for in analysis. Outcome definitions should be made more explicit.

Bias↗
PubMed1992

[Attributable risk percent under an effect modifier and legal causality].

Among civil trials there are cases which are influenced by evidence derived from epidemiologic studies. In such cases, causality of a factor (X) illegitimately introduced by defendants is considered to be measured with an epidemiologic measure, attributable risk percent (AR%) expressing the level of risk. This paper aims to discuss calculations and interpretations of AR% in complicated cases where plaintiffs themselves introduced an additional risk factor (Y) for the alleged health injury. When X is not an effect modifier, AR% of X adjusted for Y can be simply adopted for arriving at a judgement of causality. Where Y is an effect modifier, and is not an indispensable item in the plaintiffs' daily life (e.g., smoking), the AR% of X for those not exposed to Y and also the AR% for those exposed to Y may both need to exceed a legally determined threshold, in order for X to be legally acknowledged as being causal to the alleged injury. The role of epidemiologists for such trials is to determine the AR% of X for each level of Y, and to advise the court on a realistic range of the AR%s.

Effect Modifier, Epidemiologic↗
PubMed2000

Allelic polymorphism of GSTM1 and NAT2 genes modifies dietary-induced DNA damage in colorectal mucosa.

Typically, cancer is caused by the interaction of genetic and environmental factors. In colorectal carcinogenesis, diet and nutritional habits are the most important external risk determinants. Allelic polymorphisms of certain metabolizing enzymes may have an influence on cancer risk by modifying the concentration of active carcinogenic compounds in the body. In the present study we investigated the interaction between nutritional and genetic susceptibility factors in human colon carcinogenesis. Healthy volunteers were divided into four groups, based on allelic polymorphisms of N-acetyltransferase 2 and glutathione-S-transferase M1 enzymes. Comet assay was used to determine the level of DNA strand breaks in exfoliated colorectal mucosal cells, following a 2-day vegetarian diet, and after switching to a 2-day 'high-meat' diet. The 'high-meat' diet statistically significantly increased the amount of single-strand breaks in rapid acetylators and among individuals with a GSMT1 + genotype, while it caused only a slight and not significant increase in the other groups. Our study emphasizes the importance of using susceptibility markers in cancer epidemiology, since environmental effects are strongly modified by these genetic factors.

Alleles↗
PubMed2006

Implications of gender differences for human health risk assessment and toxicology.

This paper from The Human Health working group of SGOMSEC 16 examines a broad range of issues on gender effects in toxicology. Gender differences in toxicology begin at the gamete and embryo stage, continuing through development and maturation and into old age. Sex influences exposure, toxicokinetics, and toxicodynamics. The effects of sex have often been overlooked in both epidemiology and toxicology. In addition to the obvious modifying effects of the sex hormones and conditions affecting the male and female reproductive organs and sex roles, both genetic and hormonal effects influence many aspects of life and toxic responses. All aspects of toxicology should consider gender-balanced designs so that a more comprehensive understanding of differences and similarities can be obtained. Differential gene expression is a new frontier in toxicology. Risk assessment should account for gender and life cycle differences. The biological basis for altered sex ratios observed in several populations should be sought in animal models, and expanded to other compounds that might exert sex-selective effects. Wherever possible and feasible, toxicologic and environmental epidemiological studies should be designed and have sufficient statistical power to quantify differential gender-based exposures and outcomes.

Bone and Bones↗
PubMed2003

Iodine deficiency, radiation dose, and the risk of thyroid cancer among children and adolescents in the Bryansk region of Russia following the Chernobyl power station accident.

BACKGROUND: Little is known about the joint effect of iodine deficiency and radiation exposure on the risk of thyroid cancer. No epidemiological studies have been published assessing the modifying effect of iodine deficiency on radiation-induced thyroid cancer following the Chernobyl accident. METHODS: A population sample of 3070 individuals (2590 ages 6-18, and 480 adults) from 75 settlements in the most highly contaminated regions of the Bryansk Oblast of Russia was identified and sampled for urinary iodine measurements in 1996, and iodine deficiency in each geopolitical unit (raion) was estimated. All cases of thyroid cancer were identified in those born 1968-1986 who were resident in the study area in May-June 1986 (34 histologically confirmed cases). The risk of thyroid cancer was examined in relation to population estimates of thyroid radiation dose and urinary iodine excretion level. RESULTS: The excess relative risk (ERR) of thyroid cancer was significantly associated with increasing thyroid radiation dose, and was inversely associated with urinary iodine excretion levels. There was a joint effect of radiation exposure and iodine deficiency. At 1 gray (Gy), the ERR in territories with severe iodine deficiency was approximately two times that in areas of normal iodine intake. CONCLUSIONS: These findings suggest that elimination of iodine deficiency in areas affected by Chernobyl may be important in reducing the effects of radiation exposure on the thyroid. If confirmed by studies based on individuals, they may have implications for the use of stable iodine in the case of population exposure to radioactive iodine.

Adolescent↗
PubMed2001

Systematic review of population-based epidemiological studies of oro-facial pain.

OBJECTIVES: To conduct a systematic review of epidemiological literature in order to determine the prevalence and associated risk factors of oro-facial pain. DATA: Population based observational studies (cohorts, cross-sectional and case-control studies) of oro-facial pain, published in the English language, prior to 1999 were included. SOURCES: Electronic databases (Medline, Embase, Cinahl, BIDS and Health CD) were searched. Reference lists of relevant articles were examined, and the journals "Pain" and "Community Dentistry and Oral Epidemiology" were handsearched for the years 1994-1998. RESULTS: The results of the search strategy were screened for relevance. A standardised checklist was used to assess the methodological quality of each study by two reviewers before an attempt was made to summarise the results. The median quality score was 70% of the maximum attainable score. Due to methodological issues, it was not possible to pool the data on the prevalence of oro-facial pain. Age, gender and psychological factors were found to be associated with OFP, however there was not enough information on other factors such as local mechanical and co-morbidities to draw any reliable conclusions. None of the factors fully fulfilled criteria for causality. CONCLUSIONS: There is a need for good quality epidemiological studies of oro-facial pain in the general population. To enable comprehensive examination of the aetiology of oro-facial pain, it is necessary to address a broad range of factors including demography and life-style, local mechanical factors, medical history and psychological factors. Future studies should recruit adequately sized samples for precise determination of the prevalence and detection of important associated factors. Data on potential confounders and effect modifiers should also be collected and adjusted for in the statistical analysis.

Adult↗
PubMedDate not supplied

The ability of disease modifying antirheumatic drugs to induce and maintain improvement in patients with rheumatoid arthritis. epidemiology of DMARDs treatment in Japan.

OBJECTIVE: The effectiveness of the disease-modifying antirheumatic drugs (DMARDs) methotrexate (MTX), bucillamine (BUC), salazosulphapyridine (SASP) and gold sodium thiomalate (GST) over two courses of treatment with a follow-up period of at least 12 months was evaluated in 425 patients with rheumatoid arthritis. METHODS: Clinical efficacy was evaluated on the basis of the numbers of painful and swollen joints, morning stiffness, grip strength, erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor levels before and after treatment. Results were evaluated on the basis of the survival rate (Kaplan-Meier method) and the incidence and types of adverse drug reactions (ADR) following single and combined therapies. RESULTS: In the first course of treatment, the survival rates for MTX, GST, BUC and SASP were 52.3%, 40.4%, 33.0% and 24.8%, respectively. The rates of development of ADR were 22.9%, 23.5%, 26.3% and 30.0% for BUC, SASP, GST and MTX, respectively. In the second course, the survival rates for MTX, BUC and SASP were 36.6%, 14.1% and 10%, respectively. CONCLUSION: DMARDs used in the first course of treatment improved the clinical parameters until the 6th month after initiation of treatment. Combination treatments showed some effectiveness, but because of the high incidence of ADR the survival rate was low. DMARDs used in the second course of treatment were not efficacious and there was no improvement in the survival rate compared to the first course of treatment.

Adolescent↗
PubMed2006

Temperature modifies the health effects of particulate matter in Brisbane, Australia.

A few epidemiological studies have examined whether there was an interactive effect between temperature and ambient particulate matter on cardiorespiratory morbidity and mortality, but the results were inconsistent. The present study used three time-series approaches to explore whether maximum temperature modified the impact of ambient particulate matter less than 10 microm in diameter (PM(10)) on daily respiratory hospital admissions, cardiovascular hospital admissions, respiratory emergency visits, cardiovascular emergency visits, non-external cause mortality and cardiovascular mortality in Brisbane between 1996 and 2001. The analytical approaches included a bivariate response surface model, a non-stratification parametric model and a stratification parametric model. Results show that there existed a statistically significant interaction between PM(10) and temperature on most health outcomes at various lags. PM(10) exhibited more adverse health effects on warm days than cold days. The choice of the degree of freedom for smoothers to adjust for confounders and the selection of arbitrary cut-offs for temperature affected the interaction estimates to a certain extent, but did not change the overall conclusion. The results imply that it is important to control and reduce the emission of air particles in Brisbane, particularly when temperature increases.

Air Pollutants↗
PubMed2005

Three Mile Island epidemiologic radiation dose assessment revisited: 25 years after the accident.

Over the past 25 years, public health concerns following the Three Mile Island (TMI) accident prompted several epidemiologic investigations in the vicinity of TMI. One of these studies is ongoing. This commentary suggests that the major source of radiation exposure to the population has been ignored as a potential confounding factor or effect modifying factor in previous and ongoing TMI epidemiologic studies that explore whether or not TMI accidental plant radiation releases caused an increase in lung cancer in the community around TMI. The commentary also documents the observation that the counties around TMI have the highest regional radon potential in the United States and concludes that radon progeny exposure should be included as part of the overall radiation dose assessment in future studies of radiation-induced lung cancer resulting from the TMI accident.

Body Burden↗
PubMed2001

The interaction between risk factors and self-regulation in the development of chronic diseases.

Most established risk factors for chronic disease incidence and mortality from cancer, such as cigarette smoke, alcohol drinking, occupational and environmental hazards and dietary factors, have been shown to vary in their importance in terms of relative risk. In studies which addressed the individual level of behaviour, but also coping and self-regulation, a strong modifying effect of long-lasting hopelessness and helplessness has been found to depend on personality. Autonomy and healthful self-regulation have been defined as the regulation of behaviour in those activities which are carried out in the physical and social environment and lead to stimulated feeling, pleasure, perception of inner and social security, and competence. Persons with such well-regulated behaviour are capable of coping with sources of listlessness, uncertainty and instability. Those individuals showing a well-regulated behaviour arrive at a psycho-neuro-physiological basis for better competence and defence against health hazards. The capability determined by the degree of self-regulation is measured with different instruments. The experience with a questionnaire for the assessment of self-regulation, its quantification and predictive value is presented here. The method of study is by prospective approach, which permits the demonstration of causal associations (promotion, co-causality) and facilitates the experimental approach through intervention. A causal association is likely if the effect of a modifier is not only found in a prospective (observational) follow-up but also if the (experimental) intervention shows an effect. The method of intervention by stimulation of self-regulation is the autonomy training developed by Grossarth-Maticek. Using several examples presenting the method, the modifying effect is shown by referring to four risk factors. If the risk factors are associated with an inhibited self-regulation, then the effect in terms of disease and pathological outcome is stronger. This was shown with the hazardous effects of smoking, alcohol drinking and dietary malnutrition as well as with automobile exhaust. It may be important, for example, whether a person feels self-determined when driving a car for hours but does not need to consume ethanol-containing drinks for feeling well. One's own capability to regulate well over time apparently modulates functions of the body and hence modifies the effects of physical factors. In epidemiological studies, which assess mostly only exogenous factors (so called established risk factors) this evidence has to be considered by including the pertinent data on the relevant questions in each field study.

Alcohol Drinking↗