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PubMed1985

Birth-cohort trends in rates of major depressive disorder among relatives of patients with affective disorder.

As part of the National Institute of Mental Health-Clinical Research Branch Collaborative Program on the Psychobiology of Depression Clinical Study, 2,289 relatives of 523 probands with affective disorder were interviewed with the Schedule for Affective Disorders and Schizophrenia and diagnosed for major depressive disorder by the Research Diagnostic Criteria. Data were analyzed using life-table and survival methods. The findings suggest a progressive increase in rates of depression in successive birth cohorts through the 20th century and an earlier age at onset of depression in each birth cohort. A predominance of female depressives was found in all birth cohorts but the magnitude of female-male differences fluctuated over the decades. The existence of these trends is reported to stimulate further research. These findings are discussed in terms of possible gene-environment interactions. However, no conclusive causal inferences can be drawn pending further investigation.

Actuarial Analysis↗

PubMed2004

Relationship between atherosclerosis and late-life depression: the Rotterdam Study.

CONTEXT: Depression in late life has been associated with vascular abnormalities. Several studies have demonstrated that persons with brain infarcts are more likely to have depressive disorders. Furthermore, depression is related to the subsequent development of ischemic heart disease. OBJECTIVE: To investigate the relationship between atherosclerosis at different locations and depression in the general population. DESIGN: Cross-sectional population-based study. SETTING: The Rotterdam Study, a population-based cohort study. PARTICIPANTS: In 4019 men and women 60 years and older, we assessed atherosclerosis at different locations, including common carotid intima-media thickness, plaques in the carotid arteries, the ankle-brachial blood pressure index, and aortic atherosclerosis. An overall measure of extracoronary atherosclerosis was obtained in 3747 persons by computing the principal component of these extracoronary atherosclerosis measures. In a subgroup of 1986 persons, we additionally measured coronary calcifications. MAIN OUTCOME MEASURE: All subjects were screened for depressive symptoms. Screen-positive subjects had a psychiatric interview to diagnose depressive disorder. RESULTS: More severe extracoronary atherosclerosis was associated with a higher prevalence of depressive disorders. For every 1-standard deviation increase, the prevalence increased by 30%. Furthermore, we found a strong relationship of severe coronary and aortic calcifications with depressive disorders (odds ratio, 3.89; 95% confidence interval, 1.55-9.77; and odds ratio, 2.00; 95% confidence interval, 1.02-3.96, respectively). CONCLUSIONS: Atherosclerosis and depression are associated in the elderly. This finding is compatible with the vascular depression hypothesis. However, the cross-sectional nature of the study does not allow causal inferences. In particular, earlier depressive episodes may have contributed to the development of atherosclerosis.

Age of Onset↗

PubMed2002

Diuretics, mortality, and nonrecovery of renal function in acute renal failure.

CONTEXT: Acute renal failure is associated with high mortality and morbidity. Diuretic agents continue to be used in this setting despite a lack of evidence supporting their benefit. OBJECTIVE: To determine whether the use of diuretics is associated with adverse or favorable outcomes in critically ill patients with acute renal failure. DESIGN: Cohort study conducted from October 1989 to September 1995. PATIENTS AND SETTING: A total of 552 patients with acute renal failure in intensive care units at 4 academic medical centers affiliated with the University of California. Patients were categorized by the use of diuretics on the day of nephrology consultation and, in companion analyses, by diuretic use at any time during the first week following consultation. MAIN OUTCOME MEASURES: All-cause hospital mortality, nonrecovery of renal function, and the combined outcome of death or nonrecovery. RESULTS: Diuretics were used in 326 patients (59%) at the time of nephrology consultation. Patients treated with diuretics on or before the day of consultation were older and more likely to have a history of congestive heart failure, nephrotoxic (rather than ischemic or multifactorial) origin of acute renal failure, acute respiratory failure, and lower serum urea nitrogen concentrations. With adjustment for relevant covariates and propensity scores, diuretic use was associated with a significant increase in the risk of death or nonrecovery of renal function (odds ratio, 1.77; 95% confidence interval, 1.14-2.76). The risk was magnified (odds ratio, 3.12; 95% confidence interval, 1.73-5.62) when patients who died within the first week following consultation were excluded. The increased risk was borne largely by patients who were relatively unresponsive to diuretics. CONCLUSIONS: The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function. Although observational data prohibit causal inference, it is unlikely that diuretics afford any material benefit in this clinical setting. In the absence of compelling contradictory data from a randomized, blinded clinical trial, the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.

Acute Kidney Injury↗

PubMed1996

Biliary tract cancers among textile and other workers in Shanghai, China.

Using occupational data for more than 500 patients with cancers of the biliary tract (CBT) diagnosed between 1980 and 1984 in Shanghai, and employment information from the 1982 census for the Shanghai population, the associations between CBT and occupational categories were examined by standardized incidence ratios (SIR). Compared to the general population, risk was elevated by nearly 40% among textile workers (SIR for women = 137, 95% CI = 106-175 and SIR for men = 137, 95% CI = 76-217), consistent with other investigations linking CBT to textile work. Increased risks were observed also among waiters/ waitresses, male sanitation personnel and chemical workers, and female janitor and similar workers. Although causal inferences cannot be firmly drawn, our findings add to the limited evidence linking CBT to occupational exposures, especially in the textile industry.

Biliary Tract Neoplasms↗

PubMed1997

A preliminary evaluation of treatment outcomes at a veterans' hospital's inpatient psychiatry unit.

This article describes a preliminary effort to evaluate inpatient psychiatric services at the Carl Vinson DVA Medical Center in Dublin, Georgia. The facility annually treats a large number of veterans for a variety of psychiatric disorders. To determine whether these veterans improved following care, a simple pretest-posttest group design was employed, using the SCL-90-R, to assess psychiatric symptomatology before and after inpatient treatment. Both statistically significant and practically meaningful improvements in symptomatology were evident at discharge. While the research design does not permit causal inferences, low-cost evaluations such as this one simply demonstrating that patients get better are important first steps in empirically determining the efficacy of inpatient psychiatric services, and represent one means of demonstrating accountable practice.

Adult↗

PubMed2003

Association between occupational exposure to power frequency electromagnetic fields and amyotrophic lateral sclerosis: a review.

BACKGROUND: For the past two decades, there has been concern over electromagnetic exposure and human health. While most research has focused on cancer and reproductive outcomes, there is interest in the relationship between electromagnetic fields (EMF) and neurodegenerative diseases. METHODS: We review epidemiological findings and evidence regarding the association between occupational exposure to power frequency EMFs and amyotrophic lateral sclerosis (ALS). Medline was searched for citations related to occupational hazards and ALS, literature reviews and epidemiological evaluations. RESULTS: Nine out of the ten epidemiological studies that have been conducted on the risk of ALS in relation to occupational exposure to EMF show moderate to strong relative risk estimates that supported a link between them. Although data from these studies was consistent, the causal inference to a link between EMF exposure and ALS is restricted mainly due to the lack of direct information on EMF exposure and incomplete consideration of the other potential risk factors for ALS at workplaces. For instance, electric shock, in particular, is more common in electrical occupations than in any other occupations. CONCLUSIONS: This review concludes that further studies should consider investigating the separate effect of EMF exposure and electrical shocks to make more specific interpretations. On-site measurements of EMF should be conducted to include information on EMF exposure from residences as well as workplaces to improve exposure assessment.

Amyotrophic Lateral Sclerosis↗

PubMed2003

Pulmonary function abnormality and respiratory tract irritation symptoms in epichlorohydrin-exposed workers in Taiwan.

BACKGROUND: Epichlorohydrin (ECH) is a strong irritant of the eyes, respiratory tract, and skin. The aims of this study were to examine the dose-response relationship between observed abnormal pulmonary function tests and respiratory tract irritation symptoms among epichlorohydrin-exposed workers in Taiwan. METHODS: A total of 167 workers were randomly selected from a resin synthesis factory. Sixty-six air samples were taken to determine ECH concentration in the workplace. Demographic data, work history, smoking status, and respiratory tract irritation symptoms were gathered by a standard self-administered questionnaire. Pulmonary function tests were also performed. RESULTS: There were 13 of 41 (31.7%) abnormal mean mid-expiratory flow (MMEF) among the high-ECH-exposed workers, 11 of 38 (29%) among the low-ECH-exposed workers, and 4 of 59 (6.8%) among non-ECH-exposed workers. There was a significant linear trend between ECH exposure and the prevalence of small airway abnormalities (P = 0.007) after adjusting for other factors. There was also a significant dose-response relationship of respiratory tract irritation symptoms (cough, phlegm, chest tightness, and dyspnea) among the ECH-exposed workers. CONCLUSIONS: This study suggests that obstructive lung abnormalities and small airway lung damage are associated with ECH exposure. The study also suggests that exposure to very low concentrations (<0.2 ppm) causes significant higher prevalence of respiratory tract irritation symptoms. Causal inferences from the findings cannot be made from this cross-sectional study and further longitudinal studies are needed to better clarify the nature of the observed associations.

Adult↗

PubMed2003

Depressive and anxiety symptoms among housemaids.

BACKGROUND: Housemaid, the most common occupation in the female labor force in Brazil, is known to be targeted by a generalized racial and job discrimination, which can generate mental suffering such as depressive and anxiety symptoms. In this cross-sectional study, the association between being a maid and having depressive and anxiety symptoms was evaluated. METHODS: Data for this study was taken from a former survey carried out in a random sample of 470 families living in a poor area of the city of Salvador, capital of the state of Bahia, Northeast Brazil. The study population comprised all women between the ages of 14 and 69, who reported having a paid occupation (n = 335). Data was collected by trained interviewers, using questionnaires. Psychological symptoms were identified using the Questionnaire for Psychiatric Morbidity among Adults, (QMPA), from which only those related to depression and anxiety (QMPA-SAD) were analyzed. RESULTS: Logistic regression showed that being a housemaid was positively associated with "sadness/tiredness" (adjusted prevalence ratio, PR(adj) = 1.64; 95% confidence interval, CI: 1.17-2.28), "poor concentration" (PR(adj) = 1.81; 95% CI: 1.13-2.90), "palpitations" (PR(adj) = 2.22; 95% CI: 1.28-3.84), and "aggressive behavior" (PR(aj) = 1.58; 95% CI: 1.01-2.46). CONCLUSIONS: Although cross-sectional designs are limited by causal inference, these results are in accordance with those obtained in qualitative studies. Advances in the Brazilian labor legislation with respect to domestic service may help to reduce social discrimination and contribute towards minimizing a possible mental burden resulting from this occupation.

Adolescent↗

PubMed1993

Occupational risks for primary liver cancer in Shanghai, China.

Using occupational data for over 3,400 primary liver cancer cases diagnosed between 1980 and 1984 reported to the Shanghai Cancer Registry, and employment information from the 1982 census for the Shanghai population, standardized incidence ratios were computed to generate leads to occupational risks of liver cancer. Among men, a statistically significant excess number of cases was observed for chemical processors, textile workers, wood workers, blacksmiths and machine-tool operators, and material handlers and dock workers. Increased incidence of liver cancer also was observed among female transport equipment operators. These findings indicate that a number of similar occupations are associated with increased risk of primary liver cancer in western countries and China. Although causal inferences cannot be drawn from these data, our study adds to the limited evidence of the potential role of occupational exposures in liver carcinogenesis.

Adult↗

PubMed1988

Activity-induced patterns of dental abrasion in prehistoric Pakistan: evidence from Mehrgarh and Harappa.

A detailed investigation of worn teeth should reveal a record of past activity patterns including information regarding diet, food preparation methods, and craft or occupational activities. Anthropological studies of the extensive dental samples from Neolithic (MR 3) and Chalcolithic (MR 2) levels at Mehrgarh, Baluchistan, and Bronze Age Harappa, Punjab, yielded several interesting examples of unusual dental abrasion. This paper provides macro- and microscopic (scanning electron microscope) descriptions of three types of activity-induced dental abrasion: 1) interproximal tooth grooving and interproximal abrasion patches, 2) facial abrasion of maxillary anterior teeth, and 3) lingual abrasion of maxillary incisors in association with rounded wear of lower incisors. The gross size and shape of abrasion features, the orientation of microscopic wear striae, and ethnographic parallels are employed in inferring causal factors involved in their formation. Behavioral activities and dietary explanations possibly associated with each type of dental wear are considered and their implications for reconstructing prehistoric activity patterns discussed. The need for extensive ethno-anthropology research into variations of tooth use among living people with different diets, subsistence bases, and craft specializations is essential to further progress in this field.

Female↗

PubMed2026

Multi-Omics Integration Identifies a Five-Gene Metabolic Signature With Experimental Validation in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is hallmarked by profound metabolic reprogramming; however, its intricate crosstalk with the tumor immune microenvironment (TIME) and its clinical ramifications remain inadequately elucidated. This study aims to systematically decipher the metabolic-immune interplay in ccRCC through multi-omics integration, with the goal of identifying robust prognostic biomarkers and actionable therapeutic vulnerabilities. AIMS: This study aims to systematically decipher the metabolic-immune interplay in clear cell renal cell carcinoma (ccRCC) through multi‑omics integration, and to identify robust prognostic biomarkers and actionable therapeutic vulnerabilities that can inform precision risk stratification and individualized treatment strategies. METHODS: We integrated bulk transcriptomic, genomic, and clinical data from multiple ccRCC cohorts. Differential expression and functional enrichment analyses were performed to characterize metabolic pathway alterations. Mendelian randomization (MR) was employed to infer causal relationships between metabolic disorders and ccRCC risk. A machine learning-based prognostic framework, incorporating SHAP (SHapley Additive exPlanations) for feature interpretability, was constructed and rigorously validated. TIME heterogeneity was dissected using deconvolution algorithms, while drug sensitivity, tumor mutation burden (TMB), and TIDE scores were utilized to assess therapeutic responses and immune evasion. Candidate gene function was evaluated through in vitro gain- and loss-of-function assays, with expression validated via TCGA, HPA, western blot, and qRT-PCR. RESULTS: Enrichment analysis identified coordinated dysregulation in lipid metabolism, energy homeostasis, and hypoxia response pathways. MR analysis confirmed lipid metabolism disorders as a causal risk factor for ccRCC. Our machine-learning model, centered on five core SHAP-identified features (SUCLA2, ACAT1, PC, SUCLG1, and HMGCS2), demonstrated superior predictive accuracy over conventional clinical staging. Immune profiling unveiled dichotomous TIME states: the low-risk group retained active immune surveillance, whereas the high-risk group was enriched with immunosuppressive subsets. Drug sensitivity screening pinpointed LY2109761 and carmustine as high-risk-specific candidate agents. Furthermore, TMB and TIDE analyses stratified high-risk patients displaying genomic instability and immune evasion phenotypes. Functionally, SUCLA2 knockdown significantly enhanced ccRCC cell proliferation and invasion, while its overexpression suppressed these malignant phenotypes, corroborating its tumor-suppressive role. Expression patterns of the hub genes were consistently validated across multi-level datasets and experimental assays. CONCLUSION: This study establishes a precision oncology framework for ccRCC by functionally linking metabolic biomarkers, immunophenotypes, and stratified therapeutic strategies. Importantly, we identify SUCLA2 as a potential functional tumor suppressor and a promising target for further mechanistic and translational investigation.

Humans↗

PubMed2003

Depressive symptoms at two months after miscarriage: interpreting study findings from an epidemiological versus clinical perspective.

We identify two study designs used to investigate psychiatric symptoms following reproductive loss. One design examines psychiatric outcomes in a single cohort of bereaved women; the other compares psychiatric outcomes in bereaved and non-bereaved cohorts. We employ the findings from one study of depressive symptoms following miscarriage to exemplify these designs and inferential differences in causal inferences that can be drawn. We interviewed a cohort of 114 women at 6-8 weeks after miscarriage and a cohort of 318 community women not recently pregnant. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression (CES-D) Scale. Among miscarrying women, the mean level of depressive symptoms was substantially elevated above that in the community cohort (adjusted difference in means between cohorts, 4.9, 95% confidence interval [CI] 2.3-7.4). Among miscarrying women, 20.2% were highly symptomatic (CES-D 30+), as compared with 10.1% among community women (adjusted odds ratio [OR] 2.8, 95% CI 1.4-5.6). However, in contrast to findings from the same study concerning depressive reactions at 2 weeks after loss, the impact of miscarriage on depressive symptoms at 6-8 weeks was markedly greater for younger women and possibly for women with a history of prior reproductive loss, but otherwise did not vary with number of living children, marital status, ethnicity or educational level. We conclude that miscarrying women first seen at their 6- to 8-week post miscarriage gynecologic visit are likely to be more depressed on average than otherwise comparable women who have not experienced a recent reproductive loss. Factors that moderate the impact of miscarriage may vary with time since loss. Enhanced recognition of the implications of study design for research inferences may help bring greater clarify and uniformity to findings from future investigations in this field.

Abortion, Spontaneous↗

PubMed2001

Accounting for correlation and compliance in cluster randomized trials.

This paper discusses causal inference with survival data from cluster randomized trials. It is argued that cluster randomization carries the potential for post-randomization exposures which involve differentially selective compliance between treatment arms, even for an all or nothing exposure at the individual level. Structural models can be employed to account for post-randomization exposures, but should not ignore clustering. We show how marginal modelling and random effects models allow to adapt structural estimators to account for clustering. Our findings are illustrated with data from a vitamin A trial for the prevention of infant mortality in the rural plains of Nepal.

Cluster Analysis↗

PubMed2004

Statistical assessment of mediational effects for logistic mediational models.

The concept of mediation has broad applications in medical health studies. Although the statistical assessment of a mediational effect under the normal assumption has been well established in linear structural equation models (SEM), it has not been extended to the general case where normality is not a usual assumption. In this paper, we propose to extend the definition of mediational effects through causal inference. The new definition is consistent with that in linear SEM and does not rely on the assumption of normality. Here, we focus our attention on the logistic mediation model, where all variables involved are binary. Three approaches to the estimation of mediational effects-Delta method, bootstrap, and Bayesian modelling via Monte Carlo simulation are investigated. Simulation studies are used to examine the behaviour of the three approaches. Measured by 95 per cent confidence interval (CI) coverage rate and root mean square error (RMSE) criteria, it was found that the Bayesian method using a non-informative prior outperformed both bootstrap and the Delta methods, particularly for small sample sizes. Case studies are presented to demonstrate the application of the proposed method to public health research using a nationally representative database. Extending the proposed method to other types of mediational model and to multiple mediators are also discussed.

Adolescent↗

PubMed1994

Inconsistency between workplace and spousal studies of environmental tobacco smoke and lung cancer.

In a risk assessment released at the end of 1992, the U.S. Environmental Protection Agency (EPA) concluded that environmental tobacco smoke (ETS) is a known human lung carcinogen. The Agency reached that conclusion primarily on the basis of epidemiologic studies of self-reported never-smoking women, in which the exposure index was marriage to a smoker. However, the use of the spousal smoking exposure surrogate introduces many potential confounding factors. Such confounding and bias due to denial of active smoking are likely explanations for weak and inconsistent reported ETS-lung cancer associations. This contention is supported by the results of 14 worldwide studies of lung cancer and ETS exposure in the workplace, which in combination indicated no risk elevation. Workplace ETS-lung cancer studies are not subject to the bias and confounding introduced by the spousal smoking exposure surrogate. The EPA ignored the workplace studies in its risk assessment and extrapolated the results of spousal smoking studies to workplace and other sources of ETS exposure. In its estimate of ETS-attributable lung cancer deaths in the United States, the EPA ascribed over 70% of the deaths to nonspousal ETS exposure, primarily workplace exposure. Considered in their entirety, the ETS-lung cancer epidemiologic data do not support a causal inference or provide a scientific basis for government regulation of smoking in the workplace.

Bias↗

PubMed1998

Complications of severe mental illness related to alcohol and drug use disorders.

In this chapter we review research on the relationships between substance use disorder and 11 domains of adjustment for people with severe mental illness. Studies are divided into correlational research and prospective, longitudinal research, with greater weight given to those in the latter category. The weight of the evidence indicates that substance abuse severely complicates severe mental illness in the following domains: relapse of psychiatric illness, hospitalization, disruptive behavior, familial problems, residential instability, decreased functional status, HIV infection, and medication noncompliance. We discuss the limits of causal inference in these studies and the possible mechanisms that relate substance abuse to various complications.

Alcoholism↗

PubMed2004

Evolution of epidemiologic methods and concepts in selected textbooks of the 20th century.

Textbooks are an expression of the state of development of a discipline at a given moment in time. By reviewing eight epidemiology textbooks published over the course of a century, we have attempted to trace the evolution of five epidemiologic concepts and methods: study design (cohort studies and case-control studies), confounding, bias, interaction and causal inference. Overall, these eight textbooks can be grouped into three generations. Greenwood (1935) and Hill (first edition 1937; version reviewed 1961)'s textbooks belong to the first generation, "early epidemiology", which comprise early definitions of bias and confounding. The second generation, "classic epidemiology", represented by the textbooks of Morris (first edition 1957; version reviewed 1964), MacMahon & Pugh (first edition 1960; version reviewed 1970), Susser (1973), and Lilienfeld & Lilienfeld (first edition 1976; version reviewed 1980), clarifies the properties of cohort and case-control study designs and the theory of disease causation. Miettinen (1985) and Rothman (1986)'s textbooks belong to a third generation, "modern epidemiology", presenting an integrated perspective on study designs and their measures of outcome, as well as distinguishing and formalizing the concepts of confounding and interaction. Our review demonstrates that epidemiology, as a scientific discipline, is in constant evolution and transformation. It is likely that new methodological tools, able to assess the complexity of the causes of human health, will be proposed in future generations of textbooks.

Epidemiologic Methods↗

PubMed2003

A short history of pathology registries, with emphasis on cancer registries.

In the 1950s, major technical problems for ensuring quality and effectiveness of population based registration of cancer and other conditions had been faced and solved. Nevertheless, the classical epidemiological texts published in the 1960s and the 1970s gave little attention to and showed limited enthusiasm for population-based registries of pathology. The latter, in fact, have been marginal to the dramatic evolution of basic conceptual issues such as study design and causal inference. This perspective may change with the use of registries in order to assess quality of care in a public health perspective. In looking retrospectively, marked changes occurred since the 1960s in distribution between countries and continents of cancer registries to the dataset known as "Cancer Incidence in Five Continents" (where worldwide data from cancer registries of quality converge). The number of countries with cancer registries approximately doubled vs. a fivefold increase in both the number of active cancer registries and the total population served by registration. Nevertheless the increases were concentrated in developed countries whereas in developing countries there was a substantial decrease in registration, attributable to the political and economical situation.

Cross-Cultural Comparison↗