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John Lynch

Publications and source records attributed to John Lynch.

At least 37 records · Page 2Linked to original sources
PubMed2005

The mediation proportion: a structural equation approach for estimating the proportion of exposure effect on outcome explained by an intermediate variable.

It is often of interest to assess how much of the effect of an exposure on a response is mediated through an intermediate variable. However, systematic approaches are lacking, other than assessment of a surrogate marker for the endpoint of a clinical trial. We review a measure of "proportion explained" in the context of observational epidemiologic studies. The measure has been much debated; we show how several of the drawbacks are alleviated when exposures, mediators, and responses are continuous and are embedded in a structural equation framework. These conditions also allow for consideration of several intermediate variables. Binary or categorical variables can be included directly through threshold models. We call this measure the mediation proportion, that is, the part of an exposure effect on outcome explained by a third, intermediate variable. Two examples illustrate the approach. The first example is a randomized clinical trial of the effects of interferon-alpha on visual acuity in patients with age-related macular degeneration. In this example, the exposure, mediator and response are all binary. The second example is a common problem in social epidemiology-to find the proportion of a social class effect on a health outcome that is mediated by psychologic variables. Both the mediator and the response are composed of several ordered categorical variables, with confounders present. Finally, we extend the example to more than one mediator.

Adult↗
PubMed2005

A brief conceptual tutorial of multilevel analysis in social epidemiology: linking the statistical concept of clustering to the idea of contextual phenomenon.

STUDY OBJECTIVE: This didactical essay is directed to readers disposed to approach multilevel regression analysis (MLRA) in a more conceptual than mathematical way. However, it specifically develops an epidemiological vision on multilevel analysis with particular emphasis on measures of health variation (for example, intraclass correlation). Such measures have been underused in the literature as compared with more traditional measures of association (for example, regression coefficients) in the investigation of contextual determinants of health. A link is provided, which will be comprehensible to epidemiologists, between MLRA and social epidemiological concepts, particularly between the statistical idea of clustering and the concept of contextual phenomenon. DESIGN AND PARTICIPANTS: The study uses an example based on hypothetical data on systolic blood pressure (SBP) from 25,000 people living in 39 neighbourhoods. As the focus is on the empty MLRA model, the study does not use any independent variable but focuses mainly on SBP variance between people and between neighbourhoods. RESULTS: The intraclass correlation (ICC = 0.08) informed of an appreciable clustering of individual SBP within the neighbourhoods, showing that 8% of the total individual differences in SBP occurred at the neighbourhood level and might be attributable to contextual neighbourhood factors or to the different composition of neighbourhoods. CONCLUSIONS: The statistical idea of clustering emerges as appropriate for quantifying "contextual phenomena" that is of central relevance in social epidemiology. Both concepts convey that people from the same neighbourhood are more similar to each other than to people from different neighbourhoods with respect to the health outcome variable.

Adult↗
PubMed2005

A brief conceptual tutorial on multilevel analysis in social epidemiology: investigating contextual phenomena in different groups of people.

STUDY OBJECTIVE: (1) To provide a didactic and conceptual (rather than mathematical) link between multilevel regression analysis (MLRA) and social epidemiological concepts. (2) To develop an epidemiological vision of MLRA focused on measures of health variation and clustering of individual health status within areas, which is useful to operationalise the notion of "contextual phenomenon". The paper shows how to investigate (1) whether there is clustering within neighbourhoods, (2) to which extent neighbourhood level differences are explained by the individual composition of the neighbourhoods, (3) whether the contextual phenomenon differs in magnitude for different groups of people, and whether neighbourhood context modifies individual level associations, and (4) whether variations in health status are dependent on individual level characteristics. DESIGN AND PARTICIPANTS: Simulated data are used on systolic blood pressure (SBP), age, body mass index (BMI), and antihypertensive medication (AHM) ascribed to 25 000 subjects in 39 neighbourhoods of an imaginary city. Rather than assessing neighbourhood variables, the paper concentrated on SBP variance between individuals and neighbourhoods as a function of individual BMI. RESULTS: The variance partition coefficient (VPC) showed that clustering of SBP within neighbourhoods was greater for people with a higher BMI. The composition of the neighbourhoods with respect to age, AHM use, and BMI explained about one fourth of the neighbourhood differences in SBP. Neighbourhood context modified the individual level association between BMI and SBP. Individual level differences in SBP within neighbourhoods were larger for people with a higher BMI. CONCLUSIONS: Statistical measures of multilevel variations can effectively quantify contextual effects in different groups of people, which is a relevant issue for understanding health inequalities.

Adult↗
PubMed2005

A brief conceptual tutorial on multilevel analysis in social epidemiology: interpreting neighbourhood differences and the effect of neighbourhood characteristics on individual health.

STUDY OBJECTIVE: Using a conceptual rather than a mathematical approach, this article proposed a link between multilevel regression analysis (MLRA) and social epidemiological concepts. It has been previously explained that the concept of clustering of individual health status within neighbourhoods is useful for operationalising contextual phenomena in social epidemiology. It has been shown that MLRA permits investigating neighbourhood disparities in health without considering any particular neighbourhood characteristic but only information on the neighbourhood to which each person belongs. This article illustrates how to analyse cross level (neighbourhood-individual) interactions, how to investigate associations between neighbourhood characteristics and individual health, and how to use the concept of clustering when interpreting those associations and geographical differences in health. DESIGN AND PARTICIPANTS: A MLRA was performed using hypothetical data pertaining to systolic blood pressure (SBP) from 25 000 subjects living in the 39 neighbourhoods of an imaginary city. Associations between individual characteristics (age, body mass index (BMI), use of antihypertensive drug, income) or neighbourhood characteristic (neighbourhood income) and SBP were analysed. RESULTS: About 8% of the individual differences in SBP were located at the neighbourhood level. SBP disparities and clustering of individual SBP within neighbourhoods increased along individual BMI. Neighbourhood low income was associated with increased SBP over and above the effect of individual characteristics, and explained 22% of the neighbourhood differences in SBP among people of normal BMI. This neighbourhood income effect was more intense in overweight people. CONCLUSIONS: Measures of variance are relevant to understanding geographical and individual disparities in health, and complement the information conveyed by measures of association between neighbourhood characteristics and health.

Antihypertensive Agents↗
PubMed2005

A life course approach to chronic disease epidemiology.

A life course approach to chronic disease epidemiology uses a multidisciplinary framework to understand the importance of time and timing in associations between exposures and outcomes at the individual and population levels. Such an approach to chronic diseases is enriched by specification of the particular way that time and timing in relation to physical growth, reproduction, infection, social mobility, and behavioral transitions, etc., influence various adult chronic diseases in different ways, and more ambitiously, by how these temporal processes are interconnected and manifested in population-level disease trends. In this review, we discuss some historical background to life course epidemiology and theoretical models of life course processes, and we review some of the empirical evidence linking life course processes to coronary heart disease, hemorrhagic stroke, type II diabetes, breast cancer, and chronic obstructive pulmonary disease. We also underscore that a life course approach offers a way to conceptualize how underlying socio-environmental determinants of health, experienced at different life course stages, can differentially influence the development of chronic diseases, as mediated through proximal specific biological processes.

Age Distribution↗
PubMed2005

Methodological issues in measuring health disparities.

OBJECTIVES: This report discusses six issues that affect the measurement of disparities in health between groups in a population: Selecting a reference point from which to measure disparity. Measuring disparity in absolute or in relative terms. Measuring in terms of favorable or adverse events. Measuring in pair-wise or in summary fashion. Choosing whether to weight groups according to group size. Deciding whether to consider any inherent ordering of the groups. These issues represent choices that are made when disparities are measured. METHODS: Examples are used to highlight how these choices affect specific measures of disparity. RESULTS: These choices can affect the size and direction of disparities measured at a point in time and conclusions about the size and direction of changes in disparity over time. Eleven guidelines for measuring disparities are presented. CONCLUSIONS: Choices concerning the measurement of disparity should be made deliberately, recognizing that each choice will affect the results. When results are presented, the choices on which the measurements are based should be described clearly and justified appropriately.

Data Collection↗
PubMed2004

Lay people's understanding of and preference against the word "mutation".

Lay understandings of the term "mutation" are explored using three methodologies and three population bases. A community based sample (n = 848) employing a written survey to assess knowledge and understanding indicated good lay understanding of the basic concept of mutation. However, lay people associated mutation with reproductive outcomes, but not with changes in genes across the life span. A student sample (n = 241) employed a written survey to assess connotations of the term mutation. It showed a strong negative response to mutation. A community based sample (n = 120) employing focus groups also showed strong negative reactions to the term mutation and rejection of use of the term mutation in public service announcements (PSAs). The term variation had better response and is recommended as an alternative in genetic counseling and public media.

Alcohol Drinking↗
PubMed2004

Ibuprofen inhibits survival of bladder cancer cells by induced expression of the p75NTR tumor suppressor protein.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to reduce inflammation and as analgesics by inhibition of cyclooxygenase-2. At higher concentrations, some NSAIDs inhibit proliferation and induce apoptosis of cancer cells. Although several molecular mechanisms have been postulated to explain the anticancer effects of NSAIDs, they do not involve merely the inhibition of cyclooxygenase-2, and a more proximate initiator molecule may be regulated by NSAIDs to inhibit growth. The p75 neurotrophin receptor (p75NTR) is a proximate cell membrane receptor glycoprotein that has been identified as a tumor and metastasis suppressor. We observed that NSAID treatment of cell lines from bladder and other organs induced expression of the p75NTR protein. Of the different types of NSAIDs examined, ibuprofen was more efficacious than aspirin and acetaminophen and comparable with (R)-flurbiprofen and indomethacin in induction of p75NTR protein expression. This rank order NSAID induction of the p75NTR protein correlated with the ability of these NSAIDs to reduce cancer cell survival. To examine a mechanistic relationship between ibuprofen induction of p75NTR protein and inhibition of survival, bladder cancer cells were transfected with ponasterone A-inducible vectors that expressed a death domain-deleted (DeltaDD) or intracellular domain-deleted (DeltaICD) p75NTR product that acts as a dominant negative antagonist of the intact p75NTR protein. Expression of DeltaDD and DeltaICD rescued cells from ibuprofen inhibition of growth. These observations suggest that p75NTR is an important upstream modulator of the anticancer effects of NSAIDs and that ibuprofen induction of the p75NTR protein establishes an alternate mechanism by which ibuprofen may exert an anticancer effect.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Population effects on individual systolic blood pressure: a multilevel analysis of the World Health Organization MONICA Project.

Individuals from the same population share a number of contextual circumstances that may condition a common level of blood pressure over and above individual characteristics. Understanding this population effect is relevant for both etiologic research and prevention strategies. Using multilevel regression analyses, the authors quantified the extent to which individual differences in systolic blood pressure (SBP) could be attributed to the population level. They also investigated possible cross-level interactions between the population in which a person lived and pharmacological (antihypertensive medication) and nonpharmacological (body mass index) effects on individual SBP. They analyzed data on 23,796 men and 24,986 women aged 35-64 years from 39 worldwide Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study populations participating in the final survey of this World Health Organization project (1989-1997). SBP was positively associated with low educational achievement, high body mass index, and use of antihypertensive medication and, for women, was negatively associated with smoking. About 7-8% of all SBP differences between subjects were attributed to the population level. However, this population effect was particularly strong (i.e., 20%) in antihypertensive medication users and overweight women. This empirical evidence of a population effect on individual SBP emphasizes the importance of developing population-wide strategies to reduce individual risk of hypertension.

Adult↗
PubMed2004

Can we disentangle life course processes of accumulation, critical period and social mobility? An analysis of disadvantaged socio-economic positions and myocardial infarction in the Stockholm Heart Epidemiology Program.

The accumulation hypothesis would propose that the longer the duration of exposure to disadvantaged socio-economic position, the greater the risk of myocardial infarction. However there may be a danger of confounding between accumulation and possibly more complex combinations of critical periods of exposure and social mobility. The objective of this paper is to investigate the possibility of distinguishing between these alternatives. We used a population based case-control study (Stockholm Heart Epidemiology Programme) of all incident first events of myocardial infarction among men and women, living in the Stockholm region 1992-94. The analyses were restricted to men 53-70 years, 511 cases and 716 controls. From a full occupational history each subject was categorized as manual worker or non-manual at three stages of the life course, childhood (from parent's occupation), at the ages 25-29 and 51-55, resulting in 8 possible socio-economic trajectories. We found a graded response to the accumulation of disadvantaged socio-economic positions over the life course. However, we also found evidence for effects of critical periods and of social mobility. A conceptual analysis showed that there are, for theoretical reasons, only a limited number of trajectories available, too small to form distinct empirical categories of each hypothesis. The empirical task of disentangling the life course hypotheses of critical period, social mobility and accumulation is therefore comparable to the problem of separating age, period, and cohort effects. Accordingly, the interpretation must depend on prior knowledge of more specific causal mechanisms.

Aged↗
PubMed2004

Self-esteem and mortality: prospective evidence from a population-based study.

PURPOSE: Self-esteem is considered to be importantly associated with both psychosocial states such as depression as well as physical health. There are no population-based studies that examine the association between self-esteem and mortality. The objective of this study was to assess whether low self-esteem was prospectively associated with increased risk of death in a population-based sample of Finnish men. METHODS: A sample of 2682 male residents of Kuopio, Finland were interviewed and followed prospectively as part of the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD). Characteristics of the KIHD sample at baseline included self-esteem, measured by the Rosenberg ten-item scale, socioeconomic factors, behavioral risk factors, other psychosocial characteristics, and prevalent diseases. Mortality was ascertained through linkage to the Finnish national death registry. We assessed the relationship between self-esteem and all-cause mortality using Cox proportional hazards models. RESULTS: Low self-esteem was associated with a two-fold [hazard ratio (HR)=2.0, 95% confidence interval (CI)=1.3-3.2] increase in age-adjusted mortality. This relationship was partially explained by behavioral and socioeconomic factors, and prevalent diseases, and fully explained by other psychosocial characteristics (hopelessness, depression, cynical hostility, and sullenness). When adjusted for hopelessness alone there was no increased risk associated with low self-esteem (HR=1.3, 95% CI=0.8-2.2). CONCLUSIONS: This study found no association between self-esteem and all-cause mortality after adjustment for other psychosocial characteristics, primarily hopelessness. Our understanding of the observed relationships between some psychosocial factors and mortality may be improved by simultaneous measurement of multiple psychosocial domains, thus diminishing the potential for residual confounding.

Adult↗
PubMed2004

Foucault on targets.

This paper seeks to gain an insight into the behavior of a large NHS trust, in its attempt to meet a 90 percent patient access target, in a week long national audit in March 2003. Why did individuals act in dramatically different ways to their norm over this period. The work of Michel Foucault is used to explore these issues. The discourses of power, knowledge, discipline and governmentality are identified as key foucaudian themes that offer an alternative interpretation of how individuals behave in their place of work. The importance of the historical context of discourse within the NHS cannot be underestimated in shaping the behavior of individuals and groups today. Power and knowledge permeate NHS organizations through disciplinary practices and dressage. Governmentality seeks to maintain the status quo through disciplinary processes such as national healthcare targets. The natural response of NHS organizations is therefore, to seek order and conformity rather than disorder and conflict.

Cooperative Behavior↗
PubMed2004

Is income inequality a determinant of population health? Part 1. A systematic review.

This article reviews 98 aggregate and multilevel studies examining the associations between income inequality and health. Overall, there seems to be little support for the idea that income inequality is a major, generalizable determinant of population health differences within or between rich countries. Income inequality may, however, directly influence some health outcomes, such as homicide in some contexts. The strongest evidence for direct health effects is among states in the United States, but even that is somewhat mixed. Despite little support for a direct effect of income inequality on health per se, reducing income inequality by raising the incomes of the most disadvantaged will improve their health, help reduce health inequalities, and generally improve population health.

Aged↗
PubMed2004

Is income inequality a determinant of population health? Part 2. U.S. National and regional trends in income inequality and age- and cause-specific mortality.

This article describes U.S. income inequality and 100-year national and 30-year regional trends in age- and cause-specific mortality. There is little congruence between national trends in income inequality and age- or cause-specific mortality except perhaps for suicide and homicide. The variable trends in some causes of mortality may be associated regionally with income inequality. However, between 1978 and 2000 those regions experiencing the largest increases in income inequality had the largest declines in mortality (r= 0.81, p < 0.001). Understanding the social determinants of population health requires appreciating how broad indicators of social and economic conditions are related, at different times and places, to the levels and social distribution of major risk factors for particular health outcomes.

Adolescent↗