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PubMed1980

An analysis of population growth rates within typological categories of small southern cities.

"The research reported here presents a typology of small cities, as well as an analysis of the causes of population growth within city types. For this research eighty-eight incorporated cities and towns in the South Atlantic and East South Central census divisions [of the United States] were chosen for investigation, all having 1960 populations between 10,000 and 50,000." Path models are constructed for each city class using the decennial rate of population growth between 1960 and 1970 as the endogenous variable and net migration and employment changes as intermediate variables.

Americas↗
PubMed2001

[Joggers live longer. The Osterbro study].

INTRODUCTION: Jogging is one of the most popular forms of vigorous exercise, but its effect on longevity has not been documented. METHOD: This analysis comprise a random sample of 4658 men aged 20-79 years with no prior myocardial infarction, who participated in the first (1976-1978) and second (1981-1983) examination of the Copenhagen City Heart Study. They were entered in the mortality analysis at the second examination and were followed up until 30 November 1998. The influence of jogging on time to death was analysed by Cox regression, with age as the time axis. In addition to jogging, the model included diabetes, smoking, household income, education, and alcohol consumption as potential confounding variables, and systolic blood pressure, total cholesterol, HDL cholesterol, and BMI as intermediate variables. RESULTS: At the first examination, 217 men (4.7%) reported active jogging. Of these, 96 (2.1%) were still joggers five years later. Overall, 4335 men were non-joggers at both examinations. A significant effect of jogging was found only for the group that were joggers at both examinations, relative risk 0.37 (95% confidence interval, 0.19 to 0.71; p = 0.003). DISCUSSION: We have found that regular joggers have a significantly lower mortality than have non-joggers. This could also be due to other lifestyle factors, but numerous studies have pointed towards a beneficial effect of physical activity on health. The optimal intensity, frequency, and duration of physical activity has yet to be established.

Adult↗
PubMed1993

Confounding or intermediate effect? An appraisal of iatrogenic bias in perinatal AIDS research.

Many epidemiological reports present estimates of exposure effect adjusted for a host of variables thought to be risk factors for the disease. The term iatrogenic bias is proposed to denote bias introduced by the analyst when inappropriately controlling for variables as though they were confounders. The focus of this commentary is iatrogenic bias resulting from the control of variables intermediate in the causal pathway between exposure and disease. Perinatal epidemiological studies are particularly vulnerable, and iatrogenic bias will typically mask or diminish the true effect of the exposure. The problem is illustrated with three examples from the field of perinatal AIDS epidemiology. It is recommended that researchers carefully scrutinize each variable considered for adjustment and use path diagrams to sort out causal pathways. In some instances, it may be most appropriate to present both adjusted and unadjusted estimates of effect.

Acquired Immunodeficiency Syndrome↗
PubMed1980

Adrenocortical responses to adrenocorticotrophin in the rat.

The time course of plasma adrenocorticotrophin (ACTH), adrenal cyclic AMP, adrenal corticosterone, and plasma corticosterone was measured in male Sprague-Dawley rats whose endogenous release of ACTH had been blocked (1) following rapid injections of 100 and 300 ng ACTH/100 g body weight, i.v., (2) during prolonged infusions at rates of 1, 2, and 4 ng ACTH/min per 100 g body weight, and (3) after termination of 30-min infusions at rates extending from 0.06 to 8 ng ACTH/min per 100 g body weight. Following injections, the time course of the variables is similar to the one simulated from our models of adrenal cortical secretion, including the simulation of an intermediate variable of our models of the adrenal cortex cell which was presumed to correspond to cyclic AMP. However, during prolonged infusions there is an unexpected overshoot of adrenal cyclic AMP content whereas adrenal and plasma corticosterone concentrations rise to a steady-state value without overshoot. The total amount of cyclic AMP gradually increases following the three increasing infusion rates of ACTH whereas similar levels of plasma corticosterone concentrations are reached at steady state; therefore the saturation of the adrenal cortical secretion is due to a step ulterior to cyclic AMP formation in the steroidogenesis. After 30-min infusions, plasma corticosterone concentration reaches its maximal value following a rate of ACTH input which evokes only a 4-fold increase in adrenal cyclic AMP content; however, there is a 250-fold increase of adrenal cyclic AMP with respect to control value following the higher rates of infusion of ACTH.

Adrenal Cortex↗
PubMed2001

The gender cycle of violence: comparing the effects of child abuse and neglect on criminal offending for males and females.

Despite ample evidence of the relationship between childhood maltreatment and offending, the ways in which the cycle of violence operates remain unclear. For example, feminist researchers contend that female victims are more likely to become offenders, compared to male victims, but more research is needed to substantiate this claim. Moreover, the contradictions in research findings-with retrospective research demonstrating that most offenders have histories of abuse, and prospective work indicating that the majority of victims do not become involved in crime-highlight the importance of identifying the intermediating variables that lead from maltreatment to criminality. This review summarizes investigations related to the cycle of violence, discusses the intermediating circumstances that may affect the cycle, and identifies whether or not these processes are similar for women and men.

Child↗
PubMed2001

Thymidine kinase and thymidylate synthase in advanced breast cancer: response to tamoxifen and chemotherapy.

Thymidylate synthase (TS) is a crucial target for 5-fluorouracil (5-FU) in the de novo pathway of pyrimidine synthesis, which is necessary for DNA synthesis. Thymidine kinase (TK) plays a key role in the complementary or alternative salvage pathway of pyrimidine synthesis in acute or pathological tissue stress. In the present study, the activity levels of TS and TK were determined in 257 primary breast tumors of patients who received tamoxifen as first-line systemic therapy after diagnosis of advanced disease. In 155 (60%) responding patients, the median response duration was 23 months for tumors with low TK activity, 15 months for tumors with intermediate TK activity, and 13 months for tumors with high TK activity (P = 0.003). In Cox multivariate analysis corrected for classical predictive factors including estrogen receptor and progesterone receptor, patients with intermediate and high levels of TK activity in their tumors showed a rapid disease progression (P = 0.0002) and an early death (P = 0.002) after start of tamoxifen treatment. Tumor TS activity levels were not significantly associated with the efficacy of tamoxifen treatment. In 121 patients who became resistant to tamoxifen or additional endocrine treatments and who received 5-FU-containing polychemotherapy, tumor TK activity was not significantly related to the efficacy of chemotherapy. Of the 13 patients with low tumor TS activity, only 1 (8%) responded favorably, whereas 46% (43 of 93) of those with intermediate and 73% (11 of 15) of those with high TS activity responded (P = 0.001). In Cox multivariate regression analysis in which TS was the only significant variable, intermediate and high TS activities were associated with a slow disease progression (P = 0.005) and prolonged survival (P = 0.016) on chemotherapy. In conclusion, for patients with recurrent breast cancer, high tumor TK activity is a significant marker of poor clinical outcome on tamoxifen therapy. Elevated tumor TS activity predicts a favorable outcome for 5-FU-containing polychemotherapy when applied after tumor progression on endocrine therapy.

Adult↗
PubMed2001

[Clinical diagnosis of acute aortic dissection].

Despite the availability of modern imaging technology, 35% of aortic dissections remain undiagnosed in vivo because clinical criteria for aortic dissection are not available to date. The present study analyzed 250 patients with acute chest and/or back pain, absence of an established differential diagnosis of the pain syndrome and clinical suspicion of acute aortic dissection for presence of 26 clinical variables. Multivariate analysis identified an aortic pain syndrome with immediate onset and/or tearing or ripping character (P < 0.0001), mediastinal and/or aortic widening on chest radiography (P < 0.0002) and pulse- and/or blood pressure differentials (P < 0.0001) as predictors of acute aortic dissection. Probability of dissection was low (7%) with absence of all three variables, intermediate (31 and 39%, respectively) with isolated findings of "aortic pain" or "mediastinal widening", and high (> 83%) with either isolated "pulse- and/or blood pressure differentials" or any combination of the three variables. This model appears useful to improve selection of patients for emergency imaging of the thoracic aorta.

Acute Disease↗
PubMed1995

Fasting serum insulin levels and coronary heart disease in a Danish cohort: 17-year follow-up.

AIM: Our objective was to examine the association between the fasting serum insulin level and coronary heart disease (CHD) and cardiovascular disease in 40-year-old men and women. METHODS: In 1976, all of the men and women born in 1936 living in four municipalities in the County of Copenhagen were invited for a health examination. The participation rate was 87% (504 men and 548 women). All of the participants were followed through the Danish register of deaths and the register of hospital admissions until 1993. RESULTS: After controlling for relevant risk factors (sex, fasting glucose, total cholesterol, high density lipoprotein cholesterol, systolic blood pressure, smoking, triglycerides, body mass index, physical activity and alcohol consumption) the P value for the association between the insulin level and CHD or cardiovascular disease was found to be 0.002; the above risk factors did not appear to be intermediate variables in a causal chain from insulin level to the development of CHD or cardiovascular disease. The significant association between body mass index and CHD disappeared when the fasting insulin level was controlled for, and insulin seemed to be an intermediate factor between body mass index and CHD. CONCLUSION: The fasting serum insulin level in both men and women is a very good predictor of the development of CHD and cardiovascular disease even after controlling for relevant confounding factors.

Adult↗
PubMed1997

The relationship between low family income and psychological disturbance in young children: an Australian longitudinal study.

OBJECTIVE: This study examines the relationship between low family income (LFI) experienced at different points in time, chronic low income status and its impact on child behaviour measured at 5 years of age. METHOD: Longitudinal data from the Mater University Study of Pregnancy were used to measure LFI in families at three points in time (the antenatal period, 6 months post birth and at 5 years cf age). Outcome variables were three independent groups of behaviour problems labelled as externalising, social, attentional and thought (SAT) problems, and internalising problems. These groups were developed from the Child Behaviour Checklist. An analysis based on logistic regression modelling was carried out examining the relationship between LFI and a range of intermediate variables known to be associated with child behaviour problems. RESULTS: The more often families experienced low income, the higher the rate of child behaviour problems at age 5. Low family income was still independently associated with SAT behaviour problems after controlling for smoking in the first trimester, parenting styles, maternal depression and marital dysharmony at age 5. The association between LFI and internalising and externalising behaviour problems was largely mediated by maternal depression. CONCLUSION: Low family income is a significant factor in the aetiology of a variety of child behaviour problems. The mechanisms involved in the link between LFI and childhood internalising and externalising behaviours involve the exposure of the children to maternal depression. However, the relationship between LFI and SAT behaviour problems remains to be elucidated.

Attention Deficit Disorder with Hyperactivity↗
PubMed1982

[Socio-spatial heterogeneity and differential fertility in Bolivia. Pt. 2 (author's transl)].

In this research, based on the 1976 census, the population is simultaneously disaggregated in 3 regions, 5 urbanization levels, and 5 social sectors. This 2nd part discusses the role of intermediate variables both through the differential analysis of marital fertility and a simulation exercise with the Bongaarts model. An analysis is also made of the trends of general fertility between 1963-1972, estimated through the "own children method." The findings show that the stability of fertility in the country would be the consequence of the fertility rise in the rural areas and its decrease in the urban areas, particularly in the intermediate strata. There is indirect evidence that this decrease would mainly be the result of the growing practice of birth control. The effect of education on fertility would be strongly conditioned by the urbanization level. The higher fertility in the region of "los Llanos" would be the consequence of a higher nuptiality conditioned by the sex composition of internal migrations.

Americas↗
PubMed1992

Methodological problems of time-related variables in occupational cohort studies.

In studies of long-term health effects of occupational exposures it is important that the time patterns of the study exposure and of the relevant confounders should be taken into account in the analysis. The time-related confounders that have been most frequently considered include age at risk, calendar period, duration of employment, length of follow-up, and employment status (active or retired). These factors are related to the healthy worker effect which is more pronounced among active workers, and declines with length of follow-up. Thus, these time-related factors are potential confounders in occupational cohort studies (and in nested case-control studies). It is therefore advisable to routinely control for length of follow-up and employment status, in addition to the usual confounding factors of age at risk and calendar period. However, it should be stressed that this approach will minimise, but not eliminate, confounding due to the healthy worker effect. In particular, direct control for employment status is inadvisable if this constitutes an intermediate variable in the pathway between exposure and disease, and more complex analytical procedures are necessary in such situations. It is also important that the principle exposure under study should also be analyzed in a time-related manner, taking account of the likely induction and latency periods, and the relative etiological importance of exposure intensity, exposure duration and cumulative exposure. The simplest approach is to analyse the cumulative exposure in a time-related manner, and this may suffice when the aim is merely to consider whether or not there is an effect of exposure. However, once it has been provisionally assumed that an effect exists, attention then shifts to understanding the nature of the effect. In this context, the temporal pattern of exposure and outcome can be considered by examining the effects of exposures in specific time windows while controlling for time-related confounders, and for the effects of exposures in other time windows. A more sophisticated approach is direct fitting of a theoretical model of carcinogenesis, such as the Armitage-Doll or Moolgavkar models. However, it should be emphasized that occupational cohort studies only rarely have sufficient numbers, and data of sufficient quality, to permit meaningful conclusions to be drawn from more sophisticated analyses of this type.

Age Factors↗
PubMed1990

Primitive neuroectodermal tumors of the central nervous system. Patterns of expression of neuroendocrine markers, and all classes of intermediate filament proteins.

Snap-frozen samples from 22 primitive neuroectodermal tumors (PNETs) primary in the central nervous system were studied with antibodies to synaptophysin, bombesin, somatostatin, substance P, vasoactive intestinal polypeptide, all classes of intermediate filaments, and desmoplakins I and II. Frozen sections were immunostained by the avidin-biotin peroxidase complex and indirect immunofluorescence microscopy methods. Selected cases were also studied by double and triple label immunofluorescence microscopy, and by two-dimensional gel electrophoresis and immunoblot analysis. We found that all 22 PNETs expressed synaptophysin extensively. Focal expression of 2 or more neuropeptides was noted in 10 samples studied. All PNETs expressed vimentin, 21 of 22 expressed glial filament protein (GFP), 16 of 22 expressed neurofilament proteins (NFP), 4 of 22 expressed desmin, and 3 of 22 expressed cytokeratins. In only one case were focal and questionable reactions with desmoplakin antibodies seen. Immunoblots confirmed the presence of desmin. Double and triple immunofluorescence revealed a number of antigenic coexpressions in individual cells including: synaptophysin with vimentin, GFP, NFP and desmin, vimentin-GFP, vimentin-NFP, vimentin-cytokeratin, vimentin-desmin and desmin-NFP; similarly, combinations of vimentin-GFP-NFP, vimentin-GFP-desmin, and vimentin-GFP-cytokeratin were found. The consistent expression of synaptophysin and 2 or more neuropeptides indicates that central nervous system PNETs have significant phenotypic features in common with neuroendocrine tumors. Their complex and variable intermediate filament complement patterns combined with their consistent expression of specific neuroendocrine differentiation markers, suggest that central nervous system PNETs comprise a distinct, albeit heterogeneous group of neoplasms.

Adolescent↗
PubMed2000

Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy: a 5-year cohort study.

BACKGROUND: Although human immunodeficiency virus (HIV)-related morbidity and mortality rates in patients with advanced HIV infection who are treated with combination antiretroviral drugs have declined, significant metabolic adverse effects associated with these regimens have been increasingly recognized. However, since data from patients studied before and after initiation of protease inhibitor (PI) therapy are scant, the true effect of PIs on these metabolic changes remains unknown. OBJECTIVES: To examine temporal trends in serum glucose and lipid levels after initiation of PI therapy, to assess whether changes are independent of virological response and improvement in disease severity, and to determine risk factors associated with the development of hyperglycemia, hyperlipidemia, and lipodystrophy. METHODS: A 5-year historical cohort analysis in a population of 221 HIV-infected patients observed in the Infectious Diseases Clinic of a tertiary care center from October 1, 1993, through July 31, 1998. Clinical and laboratory data were retrieved from medical records and a computerized database. The main outcome measure was the incidence of hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and lipodystrophy. Adjusted incidence rate ratios (IRRs) were estimated by means of Poisson regression. In addition, mixed regression analyses were performed to examine effects of PIs on serum lipid and glucose levels, modeled as continuous outcomes. RESULTS: The cumulative incidence of new-onset hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and lipodystrophy was 5%, 24%, 19%, and 13%, respectively. Most of these events occurred after initiation of PI therapy. Protease inhibitors were independently associated with hyperglycemia (adjusted IRR, 5.0; 95% confidence interval [CI], 1. 3-19.4), hypercholesterolemia (adjusted IRR, 2.8; 95% CI, 1.5-5.2), hypertriglyceridemia (adjusted IRR, 6.1; 95% CI, 3.1-11.7), and lipodystrophy (adjusted IRR, 5.1; 95% CI, 1.9-13.9). Anabolic steroids and psychotropic medications were also associated with lipodystrophy. Inclusion of potential intermediate variables (eg, virological suppression and increase in body weight) did not reduce the magnitude of the association with PIs. The association between hypertriglyceridemia and ritonavir was stronger than for other PIs (Wald test, P=.02). In contrast, the incidence of hyperglycemia, hypercholesterolemia, and lipodystrophy did not vary significantly across different PIs. Longitudinal mixed models confirmed that serum lipid levels were more substantially affected by antiretroviral therapy, particularly PIs, than serum glucose levels. Similarly, controlling for surrogate markers did not abolish the strong association between PIs and increase in serum lipid levels. CONCLUSION: We found an independent association between PI use and hyperglycemia, hyperlipidemia, and lipodystrophy that is not explained by the antiviral and therapeutic effect of PIs.

Adult↗
PubMedDate not supplied

Event history analysis and inference from observational epidemiology.

Systematic inclusion of time in observational epidemiological studies may help strengthen the inference to be drawn, but new epidemiological challenges arise, such as time-dependent confounders - covariates which may change from being confounders to being intermediate variables. The focus of this presentation concerns two sets of tools: event history analysis and structural nested failure time models, both applied to a particularly intricate problem in observational epidemiology, of empirically assessing the graft-versus-leukaemia effect after bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1995

Poppers, Kaposi's sarcoma, and HIV infection: empirical example of a strong confounding effect?

Are there empirical examples of strong confounding effects? Textbooks usually show examples of weak confounding or use hypothetical examples of strong confounding to illustrate the paradoxical consequences of not separating out the effect of the studied exposure from that of second factor acting as a confounder. HIV infection is a candidate strong confounder of the spuriously high association reported between consumption of poppers, a sexual stimulant, and risk of Kaposi's sarcoma in the early phase of the AIDS epidemic. To examine this hypothesis, assumptions must be made on the prevalence of HIV infection among cases of Kaposi's sarcoma and on the prevalence of heavy popper consumption according to HIV infection in cases and controls. Results show that HIV infection may have confounded the poppers-Kaposi's sarcoma association. However, it cannot be ruled out that HIV did not qualify as a confounder because it was either an intermediate variable or an effect modifier of the association between popper inhalation and Kaposi's sarcoma. This example provides a basis to discuss the mechanism by which confounding occurs as well as the practical importance of confounding in epidemiologic research.

Confounding Factors, Epidemiologic↗
PubMedDate not supplied

The Kahnawake Schools Diabetes Prevention Project: intervention, evaluation, and baseline results of a diabetes primary prevention program with a native community in Canada.

OBJECTIVES: Kahnawake Schools Diabetes Prevention Project is a 3-year community-based, primary prevention program for non-insulin-dependent diabetes mellitus in a Mohawk community near Montreal, Canada. Objectives are to improve healthy eating and encourage more physical activity among elementary school children. METHODS: Intervention incorporates behavior change theory, Native learning styles, the Ottawa Charter for Health Promotion, and a health promotion planning model. Evaluation uses a mixed longitudinal and cross-sectional design to measure obesity, fitness, eating habits, and physical activity of elementary school children in the experimental and comparison communities. Intermediate variables are self-efficacy and perceived parental support. Process evaluation provides feedback to the intervention. RESULTS: During 3 years, 63 distinct interventions that included a Health Education Program reinforced by school events, a new Community Advisory Board, a recreation path, and community-based activities promoting healthy lifestyles were implemented. Baseline consent rates were 87 and 71% in the experimental and comparison schools. As expected, anthropometric data increase with age. Between 9 and 10 years there are increased weight, height, BMI, and skinfold thicknesses; decreased fitness; and increased television watching. CONCLUSIONS: Implementing a Native community-based diabetes prevention program is feasible through participatory research that incorporates Native culture and local expertise.

Child↗
PubMed1987

Factors influencing treatment outcome and patient satisfaction in a short-term psychiatric ward. A path analysis study of the importance of patient involvement in treatment planning.

Factors influencing treatment outcome and patient satisfaction in a short-term psychiatric treatment programme were analysed using a path analysis method. The programme used two models of treatment planning, one with and one without active participation of the patient in formulating a written treatment contract. A causal structural model, which explained 23% of the variance in the model, was used in the final analysis. The results indicated a positive relationship between a cooperation contract procedure and the level of expectations of improvement as well as high ratings of the importance of the patients own effort in treatment. The level of expectations of improvement were related to the symptom level at discharge and global improvement during treatment, indicating a better treatment outcome for the patients of the cooperation contract group, while the importance of own effort was not related to treatment outcome. Symptoms at discharge were mainly determined by symptoms at admission and global improvement, and also by expectations of improvement, initial psychic status and social background. The explained variance was 63%. Satisfaction with treatment was mainly determined by global improvement, symptoms at discharge and expectations of improvement. The explained variance was 60%. It is concluded that attention to patient expectations of improvement viewed as an important intermediate variable, is related to a an improvement in treatment outcome.

Adult↗
PubMed1997

Conceptualizing services research on outpatient commitment.

Issues affecting the research of outcomes of involuntary outpatient commitment (OC) of persons with serious mental illness are explored. These issues include the reliance on hospital recidivism as a primary measure of outcome, the role of family members and coercion in the process of outpatient commitment, and the conceptualization and design of studies. A conceptual framework that attempts to incorporate responses to these issues is proposed. Continued research on OC should build on conceptual models that include family role and burden, services delivered, an accounting for varied coercive mechanisms, and client-level outcomes. Rehospitalization should be conceptualized as an intermediate variable between OC and client-level outcomes rather than as an ultimate outcome.

Ambulatory Care↗