[Types of epidemiological study. Cohort studies].
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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.
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.
Since 1984, the Multicenter AIDS Cohort Study (MACS) has utilized four flow cytometry laboratories to measure T-lymphocyte subset levels semiannually in a large cohort of homosexual men. This report summarizes the steps taken in the MACS laboratories to attain comparability of lymphocyte subset determinations across the centers and over time. Identical flow cytometers, monoclonal antibodies, and analytic procedures have been used, and over a period of time, the procedure for sample preparation was also standardized. Interlaboratory proficiency testing utilizing identical specimens analyzed in the four laboratories was performed to evaluate the comparability of the data among the laboratories. Our results verify that such testing can identify technical bias in flow cytometric evaluations performed at different laboratories. Temporal laboratory consistency in flow cytometric measurements was evaluated using data from each site's HIV-seronegative homosexual reference group. Both sequential 95% confidence intervals (mean +/- 2 x SEM) and the within-person standard deviations of the immune measurements were considered. Significant variation in CD3, CD4, and CD8 lymphocyte subset percentages over time in the seronegative reference population was observed. Our observations indicate that the lymphocyte subset values of this seronegative group should be used to adjust those obtained on the seropositive study participants during a particular time period, thereby allowing improved discrimination of the effects of HIV on T cells in infected individuals. The data presented are of use for designing epidemiologic and intervention studies in HIV-1-infected individuals, especially for calculating sample sizes. The methods we have used to assess the quality of data in the MACS have general application to quality control programs in flow cytometry laboratories. In particular, comparison of sequential confidence intervals and within-person standard deviations for lymphocyte subset determinations on control populations are essential to a comprehensive proficiency testing program because they permit assessment of consistency within a laboratory over time.
Retrospective cohort studies are increasingly being applied in occupational health. To describe and investigate further this type of study 179 retrospective cohort studies published in six scientific journals between 1975 and 1985 inclusive were reviewed. A description of the 179 reviewed articles was made and relations between investigator orientated variables, design characteristics, and the outcome of the study were investigated. Retrospective cohort studies focusing on exposures in the chemical industry appeared to yield most negative findings, which is partly explained by the relation between the affiliation of the investigator and the outcome of the study. Studies requiring a minimal latency period, an occupational reference group, and a low percentage of lost to follow up tended to have a higher chance of a positive finding. Study size, however, did not appear to be related to the outcome.
Cohort and case-control studies are two standard approaches for investigating the etiology of occupational diseases. This paper, which is the first of a four-part series, contains a review of the design features of occupational cohort studies. Topics discussed include the basic features of prospective and historical cohort studies, options for defining the cohort, disease incidence ascertainment, and considerations involved in planning an occupational cohort study. Subsequent papers in this series will focus on data analysis of occupational cohort studies and the design and analysis of occupational case-control studies.
Recruitment of disease-free subjects into cohort studies and measurement of their time from exposure/infection to disease selectively excludes individuals (the unseen sample) who had earlier exposure and who have shorter times to disease. The unseen and observed samples may differ in other characteristics in addition to incubation period and exposure/infection time. For data with known truncation times, we develop non-parametric maximum likelihood estimates of the size, exposure/infection dates and distribution of incubation time in the unseen sample. We provide procedures to estimate and compensate for the biasing effects due to exclusion of the unseen sample in descriptive and survival analysis. We give consistency properties of these estimates and assess variability using bootstrap methods. One can use imputation to derive the above estimates from data with unknown truncation times that have been estimated parametrically. Application is made to an AIDS cohort study of over 5000 homosexual men. Important estimates obtained from this application are the annual seroconversion rates from 1978 to 1983, not otherwise obtainable in this study population.
The relation between the abdominal accumulation of body fat, total-body adiposity, and blood glucose level and the risk of non-insulin-dependent diabetes mellitus was evaluated prospectively among 1,972 male participants in the Department of Veterans Affairs Normative Aging Study cohort. The risk of non-insulin-dependent diabetes mellitus was assessed by means of the proportional hazards model; 226 cases of diabetes occurred among the 1,972 men (mean age at entry, 41.9 years; range, 22-80 years) over 35,496 person-years of observation. The relation of body mass index to diabetes risk was partly explained by body fat distribution; after adjusting for age, the ratio of abdominal circumference to hip breadth, and cigarette smoking, men in the top tertile for body mass index had a 1.3-fold greater risk of diabetes than did men in the lowest tertile (95% confidence interval 0.9-1.8). Moreover, after adjusting for age, body mass index, and cigarette smoking, men in the top tertile for the ratio of abdominal circumference to hip breadth had a 2.4-fold greater risk of diabetes than did men in the lowest tertile (95% confidence interval 1.7-3.7). When blood glucose was analyzed as a continuous outcome variable, the findings were consistent, i.e., a positive association with abdominal fat independent of total-body adiposity. These results confirm previous reports of a prospective relation between abdominal adiposity and the risk of diabetes and provide prospective evidence of a relation between blood glucose levels and both body fat distribution and obesity.
A nested case-control study is a case-control study performed with a cohort study. The nested case-control design is useful because the number of study subjects for whom risk factor information is needed is smaller than in the original cohort study. The approach is especially helpful when collection of data is expensive or time consuming, as when it is necessary to contact subjects or next of kin. Selection of controls in nested case-control studies is best performed with a method called "incidence density" sampling. An approach to incidence density sampling that yields a valid estimate of the rate ratio is sampling without replacement from noncases at the time of case occurrence. To implement this approach, a system of computer programs was written that randomly selects a user defined number of controls for each case. The case-control data produced by this program can be analyzed by conditional logistic regression.
A cohort study is under way in New York City to evaluate how levels of endogenous reproductive hormones influence the risk of breast cancer. The study, in which approximately 15,000 women are being recruited, utilizes a prospective design in which volunteers are asked to provide repeated specimens of serum during the period 1985-1992. A case-control study nested within the cohort is planned by which specimens from all cases arising in the population and from a randomly selected sample of time-matched controls will be analyzed and compared. As of December 31, 1989, 13,609 volunteers had donated blood specimens, about 50% of whom had already donated more than once. Of the 187 incident breast cancer cases who are expected to arise in the cohort before the end of 1992, 77 have been detected thus far.
A cohort study on female sterilization has been carried out to compare the safety of field-based procedures with hospital-based procedures. A total of 217 women were recruited, consisting of 103 field-based and 114 hospital-based acceptors. Married and healthy women 20-45 years of age, having at least two living children, not obese, no history of major abdominal surgery, no signs of acute pelvic inflammatory disease, and no contraindication to ketamin were included in the study. Women with severe pelvic adhesions encountered during surgery were excluded from the study. The ambulatory procedure was used for all acceptors except those who were sterilized in hospital immediately after delivery. They were asked to come to th Sarjito Hospital (hospital-based) or Puskesmas (primary health care center or field-based), after fasting the night before. Ketamin, 50-100 mg, was used intravenously for general anesthesia. Minilaparotomy followed by the Pomeroy method was used for standard female tubal sterilization. Tetracycline, 3 x 500 mg was given for five days prophylactically. Follow-up was carried out one and six weeks after the day of operation. Data were processed with an IBM-compatible PC, using version 3.0 SPSS program. Students t-test, chi-square test and relative risk (95% confidence limit (CL)) were used for statistical analysis. Both groups were comparable in terms of age, parity, body weight, and body height. The duration of operation in the field was somewhat longer than that in the hospital, i.e. 24.58 vs 21.14 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
To examine the relationship between psychosocial job stress and major depression, a prospective cohort study was conducted of 3066 male workers in two factories of an electrical company in Japan. The workers were observed for 3 years; 15 workers newly developed major depression. The effects of six job stress variables, depressive symptoms, and other possible confounders were assessed by means of self-administered questionnaires once a year. Five workers without apparent psychiatric disorder were matched for each patient by gender (all male), age (within 5 years), marital status, factory, and occupation; the 15 cases and the 75 controls were compared. Proportions of perceived stress due to unsuitable jobs and human relations were significantly higher in the cases than in the controls. Results of the conditional multiple logistic regression analysis indicated that stress due to unsuitable jobs was significantly associated with occurrence of major depression after depressive symptoms were controlled for. It is suggested that stress due to unsuitable jobs is a possible risk factor for major depression in industry.
OBJECTIVE: To determine the retrospective yield of prenatal exome sequencing (PES) by establishing the proportion of children with a postnatal monogenic diagnosis that could have been diagnosed prenatally if PES had been available. METHODS: The study cohort comprised a sample of children in Northern Ireland, born between January 2010 and January 2018 (predating routine availability of PES), who received a monogenic diagnosis postnatally via next generation sequencing as part of either of two UK-wide studies (the 100 000 Genomes Project (2015-2018) or the Deciphering Developmental Disorders study (2011-2015)). Clinical data were collected retrospectively and correlated with the current UK National Health Service PES protocol, including the phenotypic eligibility criteria for PES and the associated fetal anomalies gene panel. Cases were considered retrospective diagnoses if the fetal phenotype would have been eligible for PES and the diagnostic gene was included on the test panel, meaning prenatal diagnosis in this current era could have been feasible. RESULTS: Of 101 children, 17.8% (95% CI, 10.3-25.3%) had both an eligible fetal structural anomaly (FSA) (i.e. high-risk FSA) and a diagnostic gene on the associated test panel, meaning that they could have been diagnosed prenatally in the current clinical landscape. The median length of the diagnostic odyssey for this subgroup of children was 3.7 years (1354 (range, 822-2450) days). Moreover, 58.4% (n = 59) of cases had no anomalies detected prenatally and 19.8% (n = 20) had a FSA that would not meet the eligibility criteria for PES (low-risk FSA). Although these cases would have been ineligible for PES under the current clinical pathway, 89.9% (n = 71/79) were affected by severe or profound syndromes. Postnatally, the most common functional anomalies were neurodevelopmental delay/intellectual disability and/or behavioral abnormality, which were observed in 80.2% (n = 81) of the included children. However, 80.2% (n = 65/81) of these affected children did not present with fetal anomalies eligible for PES. CONCLUSIONS: Almost one-fifth of children with a monogenic condition included in this study could have received a diagnosis via modern PES, avoiding a diagnostic odyssey lasting almost 4 years. However, despite having a monogenic condition, over half of the children did not present with any structural anomalies in utero. This demonstrates the degree to which fetal imaging is limited in its ability to reassure parents of the absence of a fetal genetic syndrome. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
A prospective study was conducted of 2,646 employees who worked three months or more during the period January, 1957, through July, 1983, in a manufacturing plant that used trichlorethylene as a degreasing agent throughout the study period. Ninety-eight percent of the study cohort were traced; they accounted for 16,388 person-years of employment and 38,052 person-years of follow-up. Mortality experience was found to be generally more favorable than that of the comparable segment of the U.S. population over the same period of time. For the white male cohort there were fewer deaths than expected from heart disease, cancer, and trauma (standard mortality rate for all causes = 0.79, p less than .01). Reports by current and former employees of health problems requiring medical treatment showed that there were only one third as many persons with heart disease or hypertension as were reported in a comparable reference population studied over the past five years.
This study used epidemiologic methods to examine hearing loss in the elderly. The Framingham Heart Study Cohort was the reference population. The participants were 935 men and 1358 women, aged 57 to 89 years. Using a conservative definition of hearing loss as threshold levels greater than 20 dB above audiometric zero for at least one frequency from 0.5 to 4 kHz, the prevalence was estimated to be 83%. The majority of cases displayed a sensorineural hearing loss. There were no statistically significant differences by sex at 1 kHz and below. Women had significantly better hearing than men at 2 kHz and above. A multivariate model was constructed to determine which variables had a significant impact upon hearing loss. Under the model, age, sex, illness, family history of hearing loss, Meniere's disease, and noise exposure were significant population risk factors. Age was by far the most critical risk factor.
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BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) using hamstring tendon (HT) autografts faces persistent challenges of graft failure, especially in patients with high internal rotational tibial subluxation (IRTS). HYPOTHESIS: Patients with high IRTS who undergo HT autograft ACLR with suture tape augmentation (STA) will have lower graft failure rates and superior clinical outcomes as compared with those without STA. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective cohort study included patients with high IRTS-defined as lateral minus medial anterior tibial subluxation >5.8 mm based on prior studies-who underwent primary ACLR using HT autografts with STA and had a minimum follow-up of 3 years. Propensity score matching (1:1) was performed to identify a control group of patients with similarly high IRTS who underwent HT ACLR without STA. Postoperative outcomes were assessed by the International Knee Documentation Committee score, Lysholm score, and Tegner activity scale, as well as by return-to-sport status and graft failure. Clinically meaningful improvements were evaluated by the minimal clinically important difference, Patient Acceptable Symptom State, and substantial clinical benefit. RESULTS: This study included 62 patients with high IRTS: 31 with STA and 31 matched controls. The mean IRTS was 6.6 mm (range, 5.9-8.9) in the STA group and 6.8 mm (range, 5.8-8.7) in the control group. The mean patient age was 32.9 years (range, 20-50), and the mean follow-up was 3.8 years (range, 3.1-5.0). At final follow-up, the STA group showed significantly higher proportions of patients achieving the minimal clinically important difference (93.5% vs 74.2%; P = .038), Patient Acceptable Symptom State (96.8% vs 74.2%; P = .012), and substantial clinical benefit (54.8% vs 25.8%; P = .020). The return-to-sport rate was also higher in the STA group (74.2% vs 48.4%; P = .037). Additionally, the STA group demonstrated a lower graft failure rate (0% vs 12.9%; P = .039). CONCLUSION: For patients with high IRTS, STA in ACLR with HT autografts is associated with improved clinical outcomes, a higher return-to-sport rate, and a lower risk of graft failure at midterm follow-up.
While there have been numerous epidemiology studies of refinery workers, no studies have been done on producing and pipeline workers. This is a retrospective follow-up study of all persons who were employed for at least 6 months at a Texaco producing or pipeline location and who worked at some time during the period 1946-1980. Of the 11,098 white men in the cohort, 8,964 were alive, 1,886 were known to be dead, and the vital status of the remaining 248 as of December 31, 1980 was unknown. The standardized mortality ratio (SMR) of 63 for all causes was significantly low, on the basis of 2,976 expected deaths. Statistically significant deficits also were seen for all major causes of death. Mortality patterns were also examined for the major job categories in these departments. Similar patterns of mortality were seen, although there was a significant excess of thyroid cancer in those employed as pumper-gaugers. However, it was based on only four cases.