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A comparative study of two methods for the measurement of alcohol consumption in the general population.

BACKGROUND: One of the major methodological problems in measuring alcohol consumption in a general population and in selected groups is underreporting. METHODS: The present study is based on a general health questionnaire survey of a random sample of about 4000 adults aged 20-74 years in an inner-city area in each of two major Swedish cities in 1991. The questionnaire included items both about alcohol consumption frequency and the usual amount of intake--the commonly used quantity-frequency (QF) method--and other questions about the consumption during work-days and weekends during a 'normal week'--the period-specific normal week (PSNW) method. RESULTS: With a few exceptions, the reported mean consumption and the proportion of high consumers was higher with the latter approach, irrespective of sex, age, socio-demographic factors, smoking and health status, i.e. for variables which are commonly used as confounders or effect modifiers. The differences between the methods was greater among women. The internal non-response rate was higher with the PSNW method but the non-responders had a comparatively low consumption, when measured with the QF method. CONCLUSION: The PSNW method has higher validity and greater precision for the measurement of alcohol consumption and, thus, is superior to the QF method. The sex differences are notable and warrant further studies focusing on sex-related modes of answering.

Adult↗

Confounding and effect modification: possible explanation for variation in the results on the association between oral and systemic diseases.

OBJECTIVES: There is large variation in the results of studies on the association between periodontitis and systemic diseases. The variation might be explained by the fact that the association between periodontitis and systemic diseases is confounded, or the association might be modified by extraneous factors. In this article, we show, using simple examples, how confounding and effect modification may cause variation in results. In addition, these examples show that uncontrolled or partially controlled confounders can induce spurious associations. CONCLUSION: Confounding and effect modification may explain the variation in the results of studies on the association between periodontitis and systemic diseases.

Cardiovascular Diseases↗

Healthy volunteer effect in industrial workers.

Volunteers for epidemiological research, have lower mortality rates than non-volunteers, thereby producing a bias referred to as the "healthy volunteer effect" (HVE). Occupationally active persons have been similarly shown to have a reduced mortality relatively to the general population (the "healthy worker effect"). To determine whether a HVE exists in occupationally active persons, we followed for 8 years a cohort of Israeli male industrial employees, of whom 71.6% agreed to participate in 1985 in screening examinations for cardiovascular disease. We calculated standardized mortality ratios (SMRs) of the entire cohort relative to the general population, and compared the mortality among participants with that of the non-participants. Over 8 years follow up, SMRs were 78% for the entire cohort, 71% for participants and 99% for non-participants. Participants were older than non-participants and worked more commonly in smaller factories. A proportional hazard model indicated that after adjusting for these variables, the all cause mortality hazard ratio among participants and non-participants was 0.69 (95% CI = 0.51-0.94). During the first and last two years of the 8-year follow-up there were 39.6 and 30.0 age-adjusted deaths per 10,000 person-years among participants, and 58.6 and 51.5 respectively among non-participants. We conclude that the HVE occurs in occupationally active persons, and that it may persist for up to 8 years follow-up.

Adult↗

Nonspecific medication side effects and the nocebo phenomenon.

Patients taking active medications frequently experience adverse, nonspecific side effects that are not a direct result of the specific pharmacological action of the drug. Although this phenomenon is common, distressing, and costly, it is rarely studied and poorly understood. The nocebo phenomenon, in which placebos produce adverse side effects, offers some insight into nonspecific side effect reporting. We performed a focused review of the literature, which identified several factors that appear to be associated with the nocebo phenomenon and/or reporting of nonspecific side effects while taking active medication: the patient's expectations of adverse effects at the outset of treatment; a process of conditioning in which the patient learns from prior experiences to associate medication-taking with somatic symptoms; certain psychological characteristics such as anxiety, depression, and the tendency to somatize; and situational and contextual factors. Physicians and other health care personnel can attempt to ameliorate nonspecific side effects to active medications by identifying in advance those patients most at risk for developing them and by using a collaborative relationship with the patient to explain and help the patient to understand and tolerate these bothersome but nonharmful symptoms.

Attitude to Health↗

Depression after stroke and lesion location: a systematic review.

BACKGROUND: There is conflicting evidence on the hypothesis that the risk of depression after stroke is influenced by the location of the brain lesion. We undertook a systematic review to examine the hypotheses that depression is more commonly associated with left-hemisphere strokes than with right-hemisphere strokes and with lesions of the left anterior brain than with other regions. METHODS: We did a computer-aided search of MEDLINE, BIDS ISI, and PsychLit databases supplemented by hand searches of key journals. We included all reports on the association of depression after stroke with the location of the brain lesion. Studies were systematically and independently examined by two investigators. Fixed-effects and random-effects meta-analyses were done. FINDINGS: 143 reports were identified by the search strategy. 48 were eligible for inclusion. Not all reports included original data. Only two reports of original data supported the hypotheses and seven clearly did not. The pooled (random-effects) relative risk of depression after a left-hemisphere stroke, compared with a right-hemisphere stroke, was 0.95 (95% CI 0.83-1.10). For depression after a left anterior lesion compared with all other brain areas the pooled (random-effects) relative risk was 1-17 (0.87-1.62). Restriction of the analyses to reports from high-quality studies or major depressive disorder did not substantially affect the findings. Nor were they affected by stratification of the time between stroke and the assessment of depression. Multiple publications from the same samples of patients were apparent. INTERPRETATION: This systematic review offered no support for the hypothesis that the risk of depression after stroke is affected by the location of the brain lesion.

Aphasia↗

Uses of ecologic studies in the assessment of intended treatment effects.

Because of the potential for confounding by indication (disease severity) in individual-level observational studies of intended treatment effects, a treatment designed to prevent an adverse event may appear to cause it. We use a hypothetical example to show that despite substantial variation in the frequency of treatment among patients residing in different geographic areas, a constant area-specific mortality rate can be observed, indicating the absence of confounding by indication at the ecologic level. The advantage of ecologic over individual-level observational studies in the assessment of intended treatment effects holds even if variations in disease severity, socioeconomic status, and other unmeasured factors are taken into account, as long as treatment utilization is influenced by practice style in the local medical community independently of disease severity. Ecologic studies can suggest the need for changes in practice, help resolve ethical issues, and indicate priorities for randomized trials.

Bias↗

Equivalence of the mediation, confounding and suppression effect.

This paper describes the statistical similarities among mediation, confounding, and suppression. Each is quantified by measuring the change in the relationship between an independent and a dependent variable after adding a third variable to the analysis. Mediation and confounding are identical statistically and can be distinguished only on conceptual grounds. Methods to determine the confidence intervals for confounding and suppression effects are proposed based on methods developed for mediated effects. Although the statistical estimation of effects and standard errors is the same, there are important conceptual differences among the three types of effects.

Bias↗

An introduction to instrumental variables for epidemiologists.

Instrumental-variable (IV) methods were invented over 70 years ago, but remain uncommon in epidemiology. Over the past decade or so, non-parametric versions of IV methods have appeared that connect IV methods to causal and measurement-error models important in epidemiological applications. This paper provides an introduction to those developments, illustrated by an application of IV methods to non-parametric adjustment for non-compliance in randomized trials.

Bias↗

Nutritional impact of supplementation in the INCAP longitudinal study: analytic strategies and inferences.

From 1969 to 1977 a supplementation trial was conducted in Guatemala to ascertain the effects on physical and behavioral outcomes of improved nutrition in pregnant women and in preschool children. This paper reviews different strategies to analyze the effect of the intervention on physical growth. One strategy compares outcomes in two villages that were randomly allocated to receive Atole, a supplement containing high amounts of protein and energy, with values in two other villages that received Fresco, a beverage containing no protein and little energy. Both supplements contained micronutrients. This comparison of village means gives a probability significance statement (P < 0.005) that the difference in growth was because of the supplement intervention, although it does not specify the aspect of the intervention that caused the effect. Complementary strategies increase the credibility that the effect of the supplement was nutritional. Thus, analysis of the dose response with increasing supplement intake within the villages excludes the possibility that the above findings were the result of knowing which villages received which supplement (i.e., measuring biases). A greater effect in those most likely to respond nutritionally also increases the credibility that the mechanism was nutritional. In studying other behavioral and biomedical impacts of this supplementation intervention, analyses for credibility should always be included.

Child Nutrition Disorders↗

Confounding and effect-modification. 1974.

Confounding and effect-modification--both very central to epidemiologic thinking and research on causality--are closely related but distinctly separate concepts and phenomena. Both of them involve considerable subleties, with implications for problem conceptualization, study design, data analysis and inference. Some of these subtleties and their implications may warrant greater appreciation in the practice of epidemiologic research, while others require further conceptual development.

Confounding Factors, Epidemiologic↗

Estimating causal effects from epidemiological data.

In ideal randomised experiments, association is causation: association measures can be interpreted as effect measures because randomisation ensures that the exposed and the unexposed are exchangeable. On the other hand, in observational studies, association is not generally causation: association measures cannot be interpreted as effect measures because the exposed and the unexposed are not generally exchangeable. However, observational research is often the only alternative for causal inference. This article reviews a condition that permits the estimation of causal effects from observational data, and two methods -- standardisation and inverse probability weighting -- to estimate population causal effects under that condition. For simplicity, the main description is restricted to dichotomous variables and assumes that no random error attributable to sampling variability exists. The appendix provides a generalisation of inverse probability weighting.

Causality↗

Challenges in interpreting study results: the conflict between appearance and reality.

BACKGROUND: Many studies investigating the relationship between periodontal disease and systemic diseases have been reported; the majority of these have been epidemiologic (or observational) studies. The purpose of this article is to help readers understand the strengths and limitations of epidemiology for the purpose of being better able to interpret these studies. FINDINGS: Epidemiologic studies include retrospective case-control studies and prospective cohort studies. While these studies cannot prove causality, they can provide strong evidence for and show the strength of an association between a disease and putative causative factors. Randomized controlled trials (RCTs) are used to test therapeutic and preventive measures and can provide presumptive evidence of disease causation in certain circumstances. Each of these study types has limitations that can distort the study results and, therefore, should be considered in study design and analysis. CONCLUSIONS AND CLINICAL IMPLICATIONS: Epidemiologic studies conducted to date suggest an association between periodontal disease and a number of systemic diseases. However, the strength and nature of this association are not yet clear, because in some cases it might result from confounding by smoking or other variables. Additional well-designed observational studies and future RCTs should increase our understanding of the actual relationship between periodontal and systemic diseases.

Bias↗

Deriving treatment recommendations from evidence within randomized trials. The role and limitation of meta-analysis.

Meta-analysis is commonly used in reviews of the effectiveness of medical technologies, but this approach has not been used in direct support of guidelines development groups. This paper describes the approach of the North of England Guidelines Development Project in describing the evidence using meta-analyses that were conducted explicitly to address questions on the choice of therapy raised by the guidelines development groups. Particular emphasis is placed on the context within which the contributing trials were conducted and the extent to which systematic differences between trials (heterogeneity) was observed, described, and explained. There is a trade-off between internal and external validity for different metrics when presenting the results of trials. More interpretable metrics, such as risk differences or weighted mean differences, are confounded by study design issues and strong assumptions. More robust measures such as odds ratios or standardized weighted mean differences are difficult to interpret physically. Individual patient data may prove particularly helpful in addressing pivotal questions on the magnitude of effects of interventions, though accessing and reanalyzing these data requires a substantial investment in time and other resources.

Bias↗