Analysis of case-control studies of the efficacy of screening for cancer: How should we deal with tests done in persons with symptoms?
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Case-Control Studies↗
Biomedical subjects
N S Weiss
Publications and source records attributed to N S Weiss.
Re: estrogen-progestin replacement therapy and endometrial cancer.
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Drug Administration Schedule↗
Risk factors for pediatric tuberculosis infection and disease after household exposure to adult index cases in Alaska.
OBJECTIVES: To determine risk factors for pediatric tuberculosis infection and active tuberculosis. STUDY DESIGN: We examined medical records from multiple sources for all 282 children younger than 15 years in Alaska during the period 1987 to 1994 who were household contacts of an adult with culture-positive pulmonary tuberculosis. RESULTS: Infection developed in 25% of the children and progressed to active disease in 9.6%. Risk factors for pediatric infection included exposure to a parent who had active tuberculosis and exposure to any adult with active tuberculosis who had a cough, smear positivity, or a left upper lobe (LUL) chest lesion (odds ratios, 2.1 to 2.8). Among the 71 children in whom infection developed, Alaska Natives and younger children were more likely to progress to active tuberculosis, as were children exposed to a parent who had active tuberculosis and children exposed to any adult who had a LUL chest lesion (odds ratios, 1.5 to 12). CONCLUSIONS: Although all children with household exposure to adults with active tuberculosis have a high risk of contracting the infection and disease, specific risk factors can be identified and differ for infection and disease. Alaska Natives have an increased risk of progression to disease once infected.
Adolescent↗
Risk of endometrial cancer in relation to use of low-dose, unopposed estrogens.
OBJECTIVE: To determine whether a low dosage (0.3 mg/day) of unopposed conjugated estrogens can be used without incurring an elevated risk of endometrial cancer. METHODS: In this case-control study, cases (n = 484) consisted of women diagnosed with endometrial cancer between 1985 and 1991 in three counties in Western Washington. Controls (n = 780) were identified using random digit dialing within the same three counties. Subjects were interviewed in person to obtain basic demographic and medical history information, as well as specific information about hormone use. RESULTS: Eighteen cases and eight controls had taken 0.3 mg/day of unopposed conjugated estrogens and no other dose or preparation of estrogens (risk relative to that of women who had not taken postmenopausal hormones = 5.4, 95% confidence interval [CI] 2.3, 13.0). The risk was particularly high in women whose use of this dose was both current and of more than 8 years' duration (odds ratio = 9.2, 95% CI 2.9, 29.0). The elevation in risk in users of 0.3 mg/day was similar in size to that associated with the daily unopposed use of 0.625 mg of conjugated estrogens. CONCLUSION: The results suggest that a dosage of 0.3 mg per day of unopposed conjugated estrogens is associated with an increased risk of endometrial cancer.
Aged↗
Studying injuries with case-control methods in the emergency department.
To study factors that cause or prevent injuries, it can be efficient to use a case-control study design and select both cases and controls from patients seen in the ED. Bias in case ascertainment can be reduced by studying exposures that, aside from their influence on the risk of injury, are unrelated to the use of emergency care. The ideal control group often includes persons generally not seen in an ED: for example, those who experience the injury-producing event, such as a bicycle crash, but who do not sustain serious injury. However, the exposure experience of the underlying population at risk sometimes can be closely approximated with information from selected persons seeking emergency care. With careful attention to the selection of study subjects, valid case-control studies of the causes of some injuries can be conducted in the ED.
Bias↗
Avascular necrosis following bone marrow transplantation: a case-control study.
The role of specific immunosuppressive agents in the development of avascular necrosis (AVN) following hematopoietic stem cell and solid organ transplantation remains unclear. To further explore this question, we conducted a case-control study of patients who underwent bone marrow transplantation (BMT) at the Fred Hutchinson Cancer Research Center. 96 of 1939 long-term survivors transplanted between May 1976 and October 1993 were identified as having AVN. Eight patients were excluded because AVN developed before transplant and one was excluded due to restrictions on reviewing follow-up records. The remaining 87 patients developed AVN a mean of 26.3 +/- 2 months posttransplant and were matched for age, gender, and date of transplant to other BMT recipients. Records were reviewed for corticosteroid and cyclosporine use, pretransplant conditioning with total body irradiation (TBI), and other information including disease for which the transplant was indicated, type of transplant, the occurrence of acute and chronic graft-vs.-host disease, and steroid use prior to transplant. Adjusted odds ratios (ORs) were obtained from conditional logistic regression for 87 matched pairs. Posttransplant steroid use was a risk factor for the occurrence of AVN (adjusted OR, 14.4; 95% CI, 2.8-73.2), with the greatest risk associated with those receiving steroids at the time of diagnosis of AVN (adjusted OR, 31.9; 95% CI, 4.4-248.9). There was no further increasing risk associated with increasing duration of steroid use. Conditioning with TBI was also associated with the occurrence of AVN (adjusted OR, 3.2; 95% CI, 1.1-9.7); however, cyclosporine was not a risk factor for AVN (adjusted OR, 0.5; 95% CI, 0.1-1.9). Our results support the hypothesis that AVN following BMT has a strong association with the administration of corticosteroids. TBI may be an additional risk factor, and cyclosporine does not appear to contribute to an increased incidence of AVN.
Adult↗
Birthweight and blood pressure among children in Harare, Zimbabwe.
AIM: To determine whether poor uterine growth may be associated with increased blood pressure and subsequent hypertension in adulthood. METHODS: A retrospective cohort study of 756 schoolchildren (mean age 6.5 years) was carried out in six low income areas in Harare city, Zimbabwe. Indices of intrauterine growth and blood pressure were assessed. RESULTS: Adjusted for current weight, the children's systolic blood pressure was inversely related to their birthweight; for each decreasing kg of birthweight, systolic blood pressure rose by 1.73 mm Hg (95% CI; 0.181 to 3.28). After adjustment for current weight, systolic blood pressure was also inversely associated with occipito-frontal circumference, but not with birth length or gestational age. Diastolic blood pressure was not associated with any of the intrauterine indices. CONCLUSION: Fetal size may be inversely related to systolic blood pressure in childhood in an African population.
Africa↗
Case series and exposure series: the role of studies without controls in providing information about the etiology of injury or disease.
Descriptions of exposure histories in persons with the same injury or illness ("case series"), and descriptions of outcomes in persons with the same exposure ("exposure series"), have the potential to contribute knowledge relevant to disease etiology in some special situations. The case series can be thought of as a primitive form of case-control study--one in which the controls are only implied. Similarly, the exposure series is a rudimentary type of cohort study. By keeping these analogies in mind, those who author or read studies without controls can assess the design or results for selection bias, confounding, or information bias. While studies without controls cannot supplant true case-control or cohort studies, they are relatively cheap and easy to perform, and there are circumstances in which they provide valuable information. Attention to design is needed to strengthen the results they provide.
Case-Control Studies↗
Screening digital rectal examination and prostate cancer mortality: a case-control study.
BACKGROUND: Prostate cancer is the second most common cause of death from cancer in men in the United States. Digital rectal examination is the oldest and most commonly used screening test for prostate cancer, but as yet there are no studies which demonstrate its effectiveness. METHODS: A case-control study was conducted among members of a large health maintenance organisation to estimate the effect of screening digital rectal examination on mortality from prostate cancer. 150 men, aged 40-84 when cancer was diagnosed, who developed fatal prostate cancer, and 299 male controls matched for age who did not die from prostate cancer were studied. A history of screening digital rectal examination during the 10 years before the date on which cancer was-diagnosed was determined from medical records. RESULTS: A similar proportion of men who died from prostate cancer and controls had undergone at least one screening digital rectal examination during the 10 year interval (odds ratio = 0.84, 95% confidence interval 0.48 to 1.46). Similar results were obtained when a shorter interval (such as five years before diagnosis) during which screening histories were evaluated was considered, or in analyses in which men with a history of benign prostatic hypertrophy were excluded. CONCLUSIONS: The data suggest that screening digital rectal examination does not reduce mortality from prostate cancer to any appreciable degree.
Adult↗
Postmenopausal estrogens and risk of myocardial infarction in diabetic women.
OBJECTIVE: The effect of hormone replacement therapy on the risk of myocardial infarction in diabetic women has not been well studied. We conducted a case-control study of postmenopausal estrogen use and risk of incident myocardial infarction (MI) in pharmacologically treated diabetic women enrolled at Group Health Cooperative of Puget Sound, a large health maintenance organization in the state of Washington. RESEARCH DESIGN AND METHODS: Case subjects (n = 212) were all postmenopausal women with treated diabetes who sustained an incident fatal or nonfatal MI between July 1986 and December 1994. Control subjects (n = 122) were treated diabetic women drawn from a stratified random sample of postmenopausal women without prior MI. Computerized pharmacy data and medical records were used to measure use of estrogens. Cardiovascular risk factors recorded from medical records, computerized pharmacy and laboratory data, and telephone interviews were used as adjustment variables. RESULTS: In this study 8.5% of case and 13.9% of control subjects were current users of estrogens. The relative risk (RR) of MI for current estrogen users was 0.51 (95% CI 0.22-1.15) relative to never users, adjusted for age, study year, weight, angina, and duration of treated diabetes. Among current estrogen users, risk of MI tended to decline with each additional year of estrogen use (adjusted RR = 0.78, 95% CI 0.56-1.08). Of those studied, 45.3% of case and 37.7% of control subjects were past users of estrogens (adjusted RR = 1.22, 95% CI 0.71-2.09). CONCLUSIONS: This study suggests that use of postmenopausal estrogens does not increase risk of MI in diabetic women and that sustained use may be of benefit.
Age Factors↗
Menopausal hormone use and endometrial cancer, by tumor grade and invasion.
We analyzed data from a population-based case-control study to investigate whether combined hormone replacement therapy influences the incidence of high-grade and -stage endometrial cancer. Subjects were women with epithelial endometrial cancer (N = 730) diagnosed during 1985-1991 and controls identified through random digit dialing (N = 1,002). Relative to hormone nonusers, women who took unopposed estrogens (mostly conjugated estrogens) for 3 or more years had a fivefold increase in the risk of tumors with myometrial invasion; the corresponding relative risk associated with combined therapy (estrogen and cyclic or continuous progestogen) for 3 or more years was only 1.3 (95% confidence interval = 0.8-2.2). We found a similar pattern of association for high-grade tumors.
Aged↗
Drinking water and adverse reproductive outcomes.
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Abortion, Spontaneous↗
Accounting for time-dependent covariates whose levels are influenced by exposure status.
When measuring the association between an exposure and disease, one must decide whether to account for confounding or modifying variables whose levels are altered by the presence of the exposure. For example, to assess the impact of cessation of unopposed estrogen therapy on the occurrence of endometrial cancer, a researcher needs to consider the duration of the estrogen therapy, a strong risk factor for endometrial cancer, as a potential confounder or effect modifier. Duration of estrogen therapy, however, is itself influenced by the decision to stop the therapy (the "exposure" of interest). In such a case, two distinct approaches may be taken, depending upon the question being considered. One may wish to assess the degree to which the exposure predicts disease incidence, over and above the additional variable, at some later point in time. In this case, it is appropriate to consider the value of the other variable (for example, duration) at that later time. On the other hand, one may also wish to measure the rate of disease beginning at the time of cessation of the exposure, relative to the corresponding rate in persons with continuing exposure Here, the most appropriate analysis considers the level of the confounding variable (for example, duration) measured only until the time of exposure of interest occurs (for example, cessation of unopposed estrogen therapy). Examples are given to illustrate that the specific question being addressed dictates the handling of covariates of this type.
Confounding Factors, Epidemiologic↗
Risk of recurrence after ductal carcinoma in situ of the breast.
A cohort study was conducted to estimate the risk of breast cancer recurrence among women diagnosed with ductal carcinoma in situ (DCIS) and to identify tumor or patient characteristics that influence that risk. A population-based cancer registry was used to identify a cohort of 709 female residents of western Washington who were diagnosed with DCIS between January 1980 and June 1992 and were treated with breast-conserving surgery. Information about breast cancer recurrences, treatment, and several patient characteristics and exposures was obtained from postal questionnaires. Recurrences were confirmed using information from the cancer registry or hospital pathology reports. Approximately 15% of women experienced a recurrence within the first 5 years after diagnosis [95% confidence interval (CI), 12-18%]; 31% had a recurrence within 10 years (95% CI, 24-38%). There was a suggestion that risk was slightly elevated for women with larger tumors (> or =1.5 cm) and tumors of comedo subtype. Relative risks (RRs) were elevated for women who were premenopausal at diagnosis of DCIS (RR = 2.3; 95% CI, 1.1-5.0). Women in the upper decile of body mass index were at twice the risk of a recurrence as those women in the lower four deciles (RR = 2.3; 95% CI, 1.1-4.8). There was also a suggestion that women who used menopausal hormones for at least 2 years after their diagnosis of DCIS were at increased risk of recurrence compared to nonusers of menopausal hormones (RR = 1.8; 95% CI, 0.7-5.0). Our results suggest that the risk of recurrence may be related to some tumor characteristics as well as the hormonal milieu of the patient at or after her diagnosis of DCIS. However, larger studies are needed to more clearly document predictors of disease recurrence after DCIS.
Adult↗
Dietary risk factors for pre-eclampsia among women attending Harare Maternity Hospital, Zimbabwe.
OBJECTIVE: To identify specific foods that predispose Zimbabwean women to a higher or lower risk of pre-eclampsia and/or eclampsia. DESIGN: A case control study was implemented. Participants were asked by questionnaire to recall the specific amounts of meats, poultry, fruits, fish, vegetables and dairy products they had consumed in the month prior to giving birth. SETTING: Harare Maternity Hospital, Harare, Zimbabwe between June of 1995 and April of 1996. SUBJECTS: 180 women clinically diagnosed with pre-eclampsia (144) or eclampsia (36), and 194 normotensive women without these conditions. MAIN OUTCOME MEASURES: Pre-eclampsia/eclampsia. RESULTS: There were few associations between consumption of specific food items and the occurrence of pre-eclampsia/eclampsia. Meat and fruit were the only foods found to be significantly associated with pre-eclampsia. Women who consumed 12 or more servings of meat per month were more likely to have pre-eclampsia/eclampsia when compared to women eating 11 servings of meat or less per month. While intake of bananas and mangos was unrelated to risk, women who consumed other fruits (i.e. apples, oranges, grapes, peaches, apricots, paw paw, and plums), were 1.7 (95% CI = 1.0 to 3.1) times more likely to develop pre-eclampsia/eclampsia as women who ate none of these fruits. However, women who consumed relatively large quantities of these fruits were not at a particularly high risk. Increased consumption of kapenta was modestly associated with a decrease in disease risk, but this finding was well within the limits of chance and no association was present with intake of other types of fish. CONCLUSIONS: Our findings suggest that variation in consumption of specific foods do not have a strong effect on the incidence of pre-eclampsia in this population. However, further research involving the use of a more comprehensive dietary measure, biochemical measurements of nutrients, pre-pregnancy assessment and ascertainment of dietary intake prior to the development of pre-eclampsia are needed.
Adult↗
Facilitating patient-specific decisions regarding hormone replacement therapy.
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Coronary Disease↗
Duration of estrogen replacement therapy in relation to the risk of incident myocardial infarction in postmenopausal women.
BACKGROUND: There is little information about whether an increasing duration of estrogen replacement therapy is associated with a declining risk for myocardial infarction in postmenopausal women. OBJECTIVE: To conduct a population-based, case-control study among enrollees of the Group Health Cooperative (GHC) of Puget Sound, Seattle, Wash. SUBJECTS AND METHODS: Case subjects were all post-menopausal women who were enrolled in the GHC with an incident fatal or nonfatal myocardial infarction from July 1986 through December 1993. Control subjects were a stratified random sample of postmenopausal women who were enrolled in the GHC without myocardial infarction and matched to case subjects by age and calendar year. We reviewed the medical records of the 850 case subjects and 1974 control subjects and conducted telephone interviews with consenting survivors. Use of estrogen or estrogen and progestin was assessed using GHC's computerized pharmacy database. RESULTS: Among women who were currently using estrogen, a longer duration of use was inversely associated with a risk for myocardial infarction after adjustment for age, year of identification, diabetes mellitus, angina, and smoking. For categories of increasing duration of estrogen use (never, > 0-< 1.8 years, 1.8-< 4.2 years, 4.2-< 8.2 years, and > or = 8.2 years), the odds ratios for myocardial infarction were 1.00 (reference), 0.91, 0.70, 0.65, and 0.55 (for trend among the current users, P = .05). Among women who had used estrogen in the past, there was no evidence of decreasing risk with increasing duration of estrogen use. CONCLUSION: In this study, a long duration of hormone replacement therapy among women currently using estrogen was associated with a reduced risk for first myocardial infarction.
Adult↗
Characteristics of women with and without breast augmentation.
OBJECTIVE: To compare selected characteristics of women with and without augmentation mammaplasty to identify differences between these 2 groups of women. DESIGN AND STUDY PARTICIPANTS: White women identified as controls in previously conducted population-based, case-control studies formed the study population for the present cross-sectional analysis (N=3570). MAIN OUTCOME MEASURE: Interview information on selected characteristics was compared between women who had received augmentation mammaplasty (n=80) and other women (n=3490) using the prevalence odds ratio (pOR) as the measure of association. RESULTS: Women with breast implants were more likely to drink a greater average number of alcoholic drinks per week (for > or =7 drinks vs 0 drinks: pOR=2.9, 95% confidence interval [CI]=1.5-5.5), be younger at first pregnancy (for age <20 years vs age 20-29 years: pOR=1.6, 95% CI=1.0-2.7), be younger at first birth (for age <20 years vs age 20-29 years: pOR=1.9, 95% C1=1.1-3.3), have a history of terminated pregnancies (for > or =1 termination vs 0 terminations: pOR=2.0, 95% CI=1.2-3.4), have ever used oral contraceptives (pOR=2.2, 95% CI=1.0-4.7), have ever used hair dyes (pOR=4.5, 95% CI=1.3-15.4), and have had a greater lifetime number of sexual partners (for > or =14 partners vs < or =4 partners: pOR=8.9, 95% CI=3.1-25.5) than other women. A history of smoking, lactation, high blood pressure, or thyroid disorders, as well as the number of pregnancies, full-term births, or miscarriages, differed little between women with and without implants. Women with breast augmentation were much less likely to be heavy than other women (for > or =74 kg vs <56 kg: pOR=0.1, 95% CI=0.03-0.3). CONCLUSION: The differences we found between women with and without breast implants suggest that consideration and evaluation of confounding factors in future studies will help to clarify some of the long-term health consequences of having breast implants.
Adult↗