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At least 19 recordsLinked to original sources

Comparison of the prediction by 27 different factors of coronary heart disease and death in men and women of the Scottish Heart Health Study: cohort study.

OBJECTIVE: To compare prediction by 27 different factors in men and women of coronary heart disease events, coronary deaths, and deaths from all causes. DESIGN: Cohort study. SETTING: Scottish population study. SUBJECTS: In 1984-7 random sampling of residents aged 40-59 produced 11,629 men and women who generated survey clinic questionnaires, examination findings, and blood and urine specimens. MAIN OUTCOME MEASURES: Subsequent death, coronary artery surgery, and myocardial infarction. Risks were calculated for each category of factor or fifth of continuous variables. 27 factors were ranked by descending age adjusted hazard ratio of the top to bottom class in each factor, by sex and end point. RESULTS: Follow up averaged 7.6 years, during which the 5754 men had 404 coronary events, 159 coronary deaths, and 383 deaths and the 5875 women 177, 47, and 208 respectively. The rankings for factors for the three end points were mainly similar in men and women, although hazard ratios were often higher in women. Classical risk factors ranked better for predicting coronary risk than newer ones. Yet strong prediction of coronary risk was no guarantee of significant prediction of all cause mortality. Findings included an anomalous coronary protective role for type A behaviour in women; raised plasma fibrinogen as a strong predictor of all end points; and an unexpectedly powerful protective relation of dietary potassium to all cause mortality. CONCLUSIONS: These initial unifactorial rankings and comparisons must be interpreted with caution until potential interaction, confounding, and problems of measurement and causation are further explored.

Adult↗

Influence of personal characteristics of individual women on sensitivity and specificity of mammography in the Million Women Study: cohort study.

OBJECTIVES: To examine how lifestyle, hormonal, and other factors influence the sensitivity and specificity of mammography. METHODS: Women recruited into the Million Women Study completed a questionnaire about various personal factors before routine mammographic screening. A sample of 122,355 women aged 50-64 years were followed for outcome of screening and incident breast cancer in the next 12 months. Sensitivity and specificity were calculated by using standard definitions, with adjustment for potential confounding factors. RESULTS: Breast cancer was diagnosed in 726 (0.6%) women, 629 in screen positive and 97 in screen negative women; 3885 (3.2%) were screen positive but had no subsequent diagnosis of breast cancer. Overall sensitivity was 86.6% and specificity was 96.8%. Three factors had an adverse effect on both measures: use of hormone replacement therapy (sensitivity: 83.0% (95% confidence interval 77.4% to 87.6%), 84.7% (73.9% to 91.6%), and 92.1% (87.6% to 95.0%); specificity: 96.8% (96.6% to 97.0%), 97.8% (97.5% to 98.0%), and 98.1% (98.0% to 98.2%), respectively, for current, past, and never use); previous breast surgery v no previous breast surgery (sensitivity: 83.5% (75.7% to 89.1%) v 89.4% (86.5% to 91.8%); specificity: 96.2% (95.8% to 96.5%) v 97.4% (97.3% to 97.5%), respectively); and body mass index < 25 v > or = 25 (sensitivity: 85.7% (81.2% to 89.3%) v 91.0% (87.5% to 93.6%); specificity: 97.2% (97.0% to 97.3%) v 97.4% (97.3% to 97.6%), respectively). Neither sensitivity nor specificity varied significantly according to age, family history of breast cancer, parity, past oral contraceptive use, tubal ligation, physical activity, smoking, or alcohol consumption. CONCLUSIONS: The efficiency, and possibly the effectiveness, of mammographic screening is lower in users of hormone replacement therapy, in women with previous breast surgery, and in thin women compared with other women.

Body Mass Index↗

Body mass index and mortality in a prospectively studied cohort of Scandinavian women: the women's lifestyle and health cohort study.

Overweight and obesity increase the risk of numerous chronic diseases, including several forms of cancer. However, the association between excess body weight and all-cause mortality among young and middle-aged women is incompletely known, and the impact of menopausal status on the association has hardly been investigated. We studied prospectively a cohort comprising a population sample of 102,446 women from Norway and Sweden aged 30-50 years when they answered an extensive questionnaire in 1991/1992. During follow-up through year 2000, 1187 women in the cohort died. We used Cox proportional hazard models to estimate multivariate Hazard rate ratios (HRR) with 95% confidence intervals (CI) of death in relation to body mass index (BMI, weight (kg)/height (m(2))) at start of follow-up. Both in age-adjusted models and in models adjusting for several variables (including smoking and physical activity) mortality increased with increasing BMI among premenopausal women, whereas a U-shaped relationship was seen among the postmenopausal women. Among premenopausal women obesity (BMI 30.0) doubled the mortality (HRR = 2.2, 95% CI: 1.7-3.0) when compared to women of normal weight (BMI 18.5-24.9), whilst the association was modest after menopause. Although we had limited power to analyze women who were underweight (BMI<18.5), an excess mortality of about 50% was seen among postmenopausal women. No excess risk was found for underweight premenopausal women. The data indicate that the rapidly growing prevalence of obesity in many Western countries will substantially increase premature deaths among young women.

Adult↗

Types of clinical studies. II. Cohort studies.

Cohort studies include groups of patients that are followed over time to determine the incidence or natural history of a disease, together with the risk factors for specific outcomes. These studies can be used to determine disease characteristics as well as the causal relationship between exposure and disease. They are, however, very expensive, because they need large patient samples. Cohort studies can be classified as prospective (the investigator defines the sample and measures predictive variables before outcomes arise) or retrospective (the investigator defines the sample and measures predictive variables after outcomes arise). Cohort studies are susceptible to various types of bias (systematic errors) that must be eliminated in order to ensure the validity of the results. To increase the validity of cohort studies the investigator has to consider exposure, outcome, sample selection and the statistical analysis (risk ratios and/or differences, absolute and relative risks, etc.).

Cohort Studies↗

Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study.

The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4(+) T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele (CKR5Delta32) was identified that is present at a frequency of approximately0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Delta32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.

Acquired Immunodeficiency Syndrome↗

Avoidance of bias in cohort studies.

Cohort studies have particular advantages in confirming results of retrospective or case-control studies in those situations in which case-control studies are no longer feasible. In circumstances, the cohort study may involve randomization, thus reducing selection bias, but ordinarily there will have been self-selection by individuals as to the group in which they will fall. Investigators should analyze data from a cohort study so as to take the passage of time into account. Variables anticipated to have effects should be accounted for by stratification, if feasible, or by mathematical modeling, if necessary. Results should be interpreted with care, and qualifications should be made on any interpretations, including qualifications relating to the propriety of the mathematical model used. When long latencies are a factor, and particularly when exposure is initiated late in life, establishment of a positive role for the exposure can be difficult. Case-control and other epidemiologic studies are biased toward identification of exposures leading to outcomes of a unique nature but fail to identify more serious exposures with adverse outcomes which are more commonplace.

Clinical Trials as Topic↗

Cohort studies.

Cohort studies generally provide more definitive evidence regarding causality than do other types of observational epidemiologic studies, but the high cost usually associated with them limits their use to special situations. Retrospective cohort studies and combined cohort/case-control studies are suggested as modifications of the traditional prospective cohort study which retain certain of their advantages but which are considerably less expensive.

Arthritis, Rheumatoid↗

Bias in cohort studies.

Cohort studies allow an exploration of patient change over time. They can provide information on the incidence of disease, prognosis (including patient satisfaction) and likely health-care resource use. Nonetheless, bias can be present in cohort studies in the way patients are selected and followed-up, the way measures are taken, or the way data are analysed. This short paper explores ways in which such flaws can be uncovered in published studies, so that their findings can be interpreted appropriately.

Cohort Studies↗

Selection factors in cohort studies.

Cohort studies play an important role in the quantitation of cancer risk among occupationally exposed individuals. Properly conducted cohort studies can develop important data on the age, time, and exposure dependence of cancer risk. Such information allows identification of possible selection effects which may be present and allows generalization of risk estimates to other exposure circumstances.

Adult↗

Multisite time-series studies versus cohort studies: methods, findings, and policy implications.

Time-series and cohort studies of air pollution on human health have advanced greatly our understanding of the effects of air pollution on health since the earliest studies. Availability of large national databases and progress in computational tools and statistical methods have made possible the estimation of national average pollution effects and the exploration of potential sources of heterogeneity in the effects of air pollution across countries or regions. Interpretation of the findings needs to account for several challenges, including confounding and the resolution of seemingly conflicting results from time-series and cohort studies. This article presents an overview of the time-series and cohort studies' approaches for estimating the relative risk of mortality from particulate air pollution and discusses the statistical issues and challenges inherent in each of these studies. We also discuss policy relevant summaries in air pollution epidemiology, approaches for estimating the impact of particulate matter on mortality from time-series and cohort studies, and research opportunities under the National Medicare Cohort Study (NMCS).

Air Pollution↗

Incidence of shoulder and neck pain in a working population: effect modification between mechanical and psychosocial exposures at work? Results from a one year follow up of the Malmö shoulder and neck study cohort.

STUDY OBJECTIVE: To assess the impact of mechanical exposure and work related psychosocial factors on shoulder and neck pain. DESIGN: A prospective cohort study. PARTICIPANTS: 4919 randomly chosen, vocationally active men and women ages 45-65 residing in a Swedish city. Neck and shoulder pain were determined by the standardised Nordic questionnaire. Mechanical exposure was assessed by an index based on 11 items designed and evaluated for shoulder and neck disorders. Work related psychosocial factors were measured by the Karasek and Theorell demand-control instrument. MAIN RESULTS: High mechanical exposure was associated with heightened risk for shoulder and neck pain among men and women during follow up. Age adjusted odds ratios (OR) were 2.17 (95% confidence intervals (CI): 1.65, 2.85) and 1.59 (95% CI: 1.22, 2.06), respectively. In women, job strain (high psychological job demands and low job decision latitude) correlated with heightened risk (OR = 1.73, 95% CI: 1.29, 2.31). These risk estimates remained statistically significant when controlled for high mechanical exposure regarding job strain (and vice versa), and for sociodemographic factors. Testing for effect modification between high mechanical exposure and job strain showed them acting synergistically only in women. CONCLUSION: Job related mechanical exposure in both sexes, and psychosocial factors in women, seem independently of each other to play a part for development of shoulder and neck pain in vocationally active people. The effect of psychosocial factors was more prominent in women, which could be the result of biological factors as well as gender issues. These results suggest that interventions aiming at reducing the occurrence of shoulder and neck pain should include both mechanical and psychosocial factors.

Aged↗

Molecular epidemiology of tuberculosis among HIV-infected persons in Switzerland: a countrywide 9-year cohort study. Swiss HIV Cohort Study.

We investigated tuberculosis transmission during a nine-year period (1988-1996) in a countrywide community-based cohort of HIV-infected persons in Switzerland (the Swiss HIV Cohort Study [SHCS]). We estimated the proportion of tuberculosis cases due to reinfection and relapse, and assessed factors which may increase the risk of tuberculosis transmission. HIV-infected persons were followed prospectively and molecular fingerprinting with insertion sequence (IS) 6110, 36-bp direct repeat, and IS6110-PCR was used to determine M. tuberculosis case clustering. Out of 7999 SHCS participants, 267 persons developed tuberculosis. 158 M. tuberculosis isolates from 138 patients were available for study. Molecular analysis identified 33 (24%) episodes of tuberculosis associated with 12 clusters including 2 to 8 patients. Two patients experienced reinfection, and nine had a relapse. Detailed contact investigation identified definite or possible epidemiological links between 21 of 33 cluster patients (64%). Multivariate logistic regression analysis did not identify any risk marker significantly associated with clustering. During a nine-year period, one fourth of tuberculosis cases were grouped in clusters within a selection of 138 HIV-infected patients. This may represent the lowest estimation of recently acquired tuberculosis infection. There were no large institutional or community outbreaks among HIV-infected participants of the Swiss HIV Cohort Study.

AIDS-Related Opportunistic Infections↗

Vegetable and fruit consumption and risks of colon and rectal cancer in a prospective cohort study: The Netherlands Cohort Study on Diet and Cancer.

The relation between vegetable and fruit consumption and colorectal cancer risk was comprehensively assessed in the Netherlands Cohort Study on Diet and Cancer using a validated 150-item food frequency questionnaire. After 6.3 years of follow-up (1986-1992), over 1,000 incident cases of colorectal cancer were registered. Using case-cohort analysis, the authors calculated rate ratios and 95% confidence intervals adjusted for age, alcohol intake, and family history of colorectal cancer. For colon cancer, no statistically significant associations with total vegetable intake or total fruit intake were found. However, among women, an inverse association was observed with vegetables and fruits combined (for the highest quintile vs. the lowest, the rate ratio was 0.66 (95% confidence interval: 0.44, 1.01)). Brassica vegetables and cooked leafy vegetables showed inverse associations for both men and women. Among women and, to a lesser extent, among men, inverse associations were stronger for distal colonic tumors than for proximal colonic tumors. For rectal cancer, no statistically significant associations were found for vegetable consumption or fruit consumption or for specific groups of vegetables and fruits; only Brassica vegetables showed a positive association in women. As in other cohort studies, the observed inverse relation between vegetable and fruit consumption and occurrence of colorectal cancer was less strong than relations reported in case-control studies.

Age Distribution↗

Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC)

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.

Acquired Immunodeficiency Syndrome↗

Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.

The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression. A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5.

Acquired Immunodeficiency Syndrome↗

Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study. Swiss HIV Cohort Study.

BACKGROUND: The efficacy of highly active antiretroviral therapy (HAART) in suppression of HIV-1 is well documented. We investigated virological and clinical outcomes of HAART in routine practice. METHODS: We analysed prospective data from the Swiss HIV Cohort Study on suppression of viral load and progression to AIDS or death in 2674 outpatients (median age 36 years, 27.3% women) who started HAART in 1995-98. Viral rebound was defined as two consecutive HIV-1-RNA measurements of more than 400 copies/mL. We analysed separately outcomes in patients with a history of antiretroviral treatment and in treatment-naïve patients. FINDINGS: An estimated 90.7% of treatment-naïve patients reached undetectable viral load (<400 copies/mL) by 12 months. Among pretreated patients, estimates ranged from 70.3% treated with one new drug to 78.7% on three new drugs. 2 years after reaching undetectable concentrations, an estimated 20.1% of treatment-naïve patients and 35.7-40.1% of pretreated patients had viral rebound. At 30 months, an estimated 6.6% (95% CI 4.6-8.6) of patients who had maintained undetectable concentrations, 9.0% (5.5-12.5) who had viral rebound, and 20.1% (15.3-24.9) who had never reached undetectable concentrations developed AIDS or died. Compared with patients who maintained undetectable viral load, the adjusted relative hazard of AIDS or death was 1.00 (0.66-1.55) for patients with viral rebound, and 2.40 (1.72-3.33) for patients who failed to reach undetectable concentrations. INTERPRETATION: The rate of virological failure of HAART was high among these patients, but the probability of clinical progression was low even in patients with viral rebound.

Adult↗

Enteric infections and diarrhea in human immunodeficiency virus-infected persons: prospective community-based cohort study. Swiss HIV Cohort Study.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are at increased risk for diarrhea and enteric infections. We studied (1) the epidemiology of enteric pathogens associated with diarrhea, (2) the diagnostic yield of stool examination and endoscopic evaluation, (3) risks to develop diarrhea, and (4) the impact of diarrhea on patients' survival. METHODS: A total of 1933 participants in the Swiss HIV Cohort Study were prospectively followed up for a median of 25.5 months. A total of 560 diarrheal episodes were evaluated by standardized stool examination. Endoscopic evaluation was performed in 25% of patients with chronic diarrhea. RESULTS: The incidence of diarrhea was 14.2 per 100 person-years (95% confidence interval, 13.0-15.4). Among patients with CD4 cell counts below 0.05 x 10(9)/L, the probability to develop diarrhea within 1, 2, and 3 years was 48.5%, 74.3%, and 95.6%, respectively. The risk to develop diarrhea was increased among patients with severe immunodeficiency, homosexual men, and patients taking antiretroviral therapy. Pneumocystis carinii chemoprophylaxis did not reduce the risk of diarrhea. Diarrhea was an independent negative predictor of survival. Enteric pathogens were detected in 16.5% of 212 acute diarrheal episodes and in 46% of 348 chronic diarrheal episodes. The sensitivity of histological and stool examination was similar except for the diagnosis of intestinal cytomegalovirus infection and leishmaniasis, which required invasive evaluation. CONCLUSIONS: Intestinal infections were diagnosed in less than 50% of chronic diarrheal episodes. The prevalence of enteric pathogens tended to decrease during the observation period, possibly because of improved antiretroviral therapy. Endoscopic evaluation did not improve the diagnostic yield compared with stool examination except for the diagnosis of cytomegalovirus enteritis and leishmaniasis.

AIDS-Related Opportunistic Infections↗