Biomedical subjects

W D Finkle

Publications and source records attributed to W D Finkle.

16 recordsLinked to original sources

PubMed2000

Problems due to small samples and sparse data in conditional logistic regression analysis.

Conditional logistic regression was developed to avoid "sparse-data" biases that can arise in ordinary logistic regression analysis. Nonetheless, it is a large-sample method that can exhibit considerable bias when certain types of matched sets are infrequent or when the model contains too many parameters. Sparse-data bias can cause misleading inferences about confounding, effect modification, dose response, and induction periods, and can interact with other biases. In this paper, the authors describe these problems in the context of matched case-control analysis and provide examples from a study of electrical wiring and childhood leukemia and a study of diet and glioma. The same problems can arise in any likelihood-based analysis, including ordinary logistic regression. The problems can be detected by careful inspection of data and by examining the sensitivity of estimates to category boundaries, variables in the model, and transformations of those variables. One can also apply various bias corrections or turn to methods less sensitive to sparse data than conditional likelihood, such as Bayesian and empirical-Bayes (hierarchical regression) methods.

Bias↗

PubMed2000

A retrospective cohort study of implanted medical devices and selected chronic diseases in Medicare claims data.

PURPOSE: Several case-control studies have observed associations of implanted medical devices and certain connective-tissue and neurologic diseases. We reexamined these and other associations using cohort comparisons. METHODS: We compared the incidence of 52 diseases in several retrospective cohorts constructed from Medicare claims data. Six cohorts were defined by implantation of medical devices (silicone, metal bone or joint implants, breast implants, penile implants, pacemakers, artificial heart valves), and four comparison cohorts were defined by surgeries not involving implants. RESULTS: We observed associations that were generally consistent with previous reports, including associations of bone and joint implants with connective-tissue diseases, and an association of penile implants with idiopathic progressive neuropathy. We also observed associations of breast implants and pacemakers with connective-tissue diseases. CONCLUSIONS: For the most part, our study confirms our previous case-control results. Although confounding by presurgical conditions (such as diabetes) remains a plausible explanation of the findings, several associations are worthy of more detailed research.

Chronic Disease↗

PubMed2000

Can sustained weight loss in overweight individuals reduce the risk of diabetes mellitus?

Although rates of adult-onset diabetes mellitus increase with increasing obesity, there is little evidence that weight loss in overweight individuals can reduce their risk of developing diabetes. Using data from the Framingham Study, we examined the effects of sustained and nonsustained weight loss on risk of diabetes mellitus among 618 overweight (body mass index > or =27) subjects 30-50 years of age. To separate sustained from nonsustained weight loss, we examined weight change in two consecutive 8-year periods. Subjects who had stable weight (+/- 1 lb per year) during both periods served as the referent group for all analyses. Sustained weight loss led to a 37% lower risk of diabetes [relative risk (RR) = 0.63; 95% confidence interval = 0.34-1.2], and this effect was stronger for more obese (body mass index > or =29) subjects (RR = 0.38; 95% confidence interval = 0.18-0.81). Those who lost 8.1-15 lb had a 33% reduction in diabetes risk, whereas those losing more had a 51% reduction in risk. Regardless of the amount of weight lost, those who regained the lost weight had no reduction in diabetes risk (RR = 1.1 and 1.2 for those who lost 8.1-15 and >15 lb, respectively). We conclude that a modest amount of sustained weight loss can substantially reduce the risk of diabetes mellitus in overweight individuals.

Adult↗

PubMed1998

Decline in incidence of endometrial cancer following increase in prescriptions for opposed conjugated estrogens in a prepaid health plan.

During the 1980s, the ecologic association of conjugated estrogens with endometrial cancer changed from positive to negative in a prepaid health plan. During the same period, use of progestins increased dramatically. We investigated whether the latter increase could explain the reversal of the estrogen-cancer association. Endometrial cancer incidence was estimated from cases recorded in the health plan registry divided by the number of women over age 45 years. Conjugated estrogens usage was measured as milligrams prescribed per woman per year and progestin was measured as tablets per woman per year, both based upon pharmacy records. Graphical and regression methods were used to analyze the resulting ecologic data. In a log-linear regression of incidence on conjugated estrogens and medroxyprogesterone usage, estrogen usage had a strong positive association with incidence, while medroxyprogesterone had a strong negative association with incidence. The change in the direction of the ecologic association between estrogen and endometrial cancer that occurred in 1984 continued until 1993, suggesting that the decline in endometrial cancer incidence and concomitant increase in conjugated estrogens usage since 1984 is explained by the increasing use of progestins. The data are entirely consistent with the hypothesis that progestins can protect against most of the excess risk conferred by conjugated estrogens, although the ecologic nature of the data prohibits drawing further inferences.

Adenocarcinoma↗

PubMed1998

A case-control study of prosthetic implants and selected chronic diseases in Medicare claims data.

PURPOSE: In an exploratory case-control study of a private insurance-claims database, Greenland and Finkle (Ann Epidemiol. 1996;6:530-540) observed associations of certain prosthetic nonbreast implants with certain connective-tissue and neurologic conditions. We wished to test these associations using the same design with new data. METHODS: We examined these associations in a case-control analysis of Medicare claims data. To control for possible confounding effects of surgery, our analysis examined nonimplant surgeries of severity similar to implant surgeries. RESULTS: We again found associations of silicone and metal implants with connective-tissue and neurologic conditions, but we also found similar associations of carpal-tunnel surgery with those conditions. CONCLUSIONS: Possible explanations for these findings include confounding by presurgical conditions. Therefore, we recommend further studies be done in which such conditions can be measured and controlled.

Aged↗

PubMed1996

A case-control study of prosthetic implants and selected chronic diseases.

We examined the association between prosthetic nonbreast implants and selected malignant neoplasms, connective tissue disorders, and neurologic diseases. We conducted a case-control study from an insurance claims database. We selected controls who had diseases for which no association with implants have been claimed or reported. Data were analyzed using both tabular and polytomous regression analysis methods, including methods to account for the large number of comparisons. All analyses exhibited positive associations between implants (both silicone and metal) and neurologic conditions, especially idiopathic progressive neuropathy and Meniere syndrome, as well as the expected associations with arthritic conditions. There also was an unexpected negative association between metal implants and brain tumors. In conclusion, further studies of prosthetic implants and neurologic diseases appear warranted. These studies should obtain medical histories to control for possible confounding effects of drug treatments associated with implant surgery.

Adult↗

PubMed1995

A critical look at methods for handling missing covariates in epidemiologic regression analyses.

Epidemiologic studies often encounter missing covariate values. While simple methods such as stratification on missing-data status, conditional-mean imputation, and complete-subject analysis are commonly employed for handling this problem, several studies have shown that these methods can be biased under reasonable circumstances. The authors review these results in the context of logistic regression and present simulation experiments showing the limitations of the methods. The method based on missing-data indicators can exhibit severe bias even when the data are missing completely at random, and regression (conditional-mean) imputation can be inordinately sensitive to model misspecification. Even complete-subject analysis can outperform these methods. More sophisticated methods, such as maximum likelihood, multiple imputation, and weighted estimating equations, have been given extensive attention in the statistics literature. While these methods are superior to simple methods, they are not commonly used in epidemiology, no doubt due to their complexity and the lack of packaged software to apply these methods. The authors contrast the results of multiple imputation to simple methods in the analysis of a case-control study of endometrial cancer, and they find a meaningful difference in results for age at menarche. In general, the authors recommend that epidemiologists avoid using the missing-indicator method and use more sophisticated methods whenever a large proportion of data are missing.

Case-Control Studies↗

PubMed1995

The relation of gastroesophageal reflux disease and its treatment to adenocarcinomas of the esophagus and gastric cardia.

OBJECTIVE: To examine the relationship of gastrointestinal disorders and their treatment to the risk of adenocarcinomas of the esophagus and gastric cardia (AEC). DESIGN: A medical record-based case-control study, with data collected on a standardized form by a trained abstractor, blind to the case-control status. SETTING: A large prepaid health plan. SUBJECTS: Case patients were plan members newly diagnosed with histologically confirmed AEC from 1986 to 1992. For each of the 196 eligible case patients, one control was selected who matched for membership at time of diagnosis, sex, year of birth, and duration of membership. MAIN OUTCOME MEASURES: Association between AEC and history of gastroesophageal conditions and their treatment. Conditional logistic regression procedures were used for calculation of odds ratios (ORs) and corresponding 95% confidence intervals (Cls), with adjustment for race, smoking status, and body mass index. Medications were grouped into H2 antagonists (cimetidine, ranitidine, famotidine, and nizatidine) and anticholinergics (propantheline bromide, dicyclomine hydrochloride, Donnatal [combination of atropine sulfate, hyoscyamine sulfate, phenobarbital, and scopolamine hydrobromide], and Librax [combination of chlordiazepoxide hydrochloride and clidinium bromide]). RESULTS: Significant twofold or greater risks of AEC were associated with a history of esophageal reflux, hiatal hernia, esophagitis/esophageal ulcer, and difficulty swallowing. The ORs increased with increasing number of these conditions. Although a fourfold risk was linked to four or more prescriptions for H2 antagonists, the risk was reduced to 1.5 (95% Cl, 0.4 to 5.4) after adjusting for the predisposing conditions. Further analysis revealed that the excess risk was restricted to persons with a history of gastroesophageal reflux and related conditions. No association was observed for overall use of anticholinergics. However, after adjustment for predisposing conditions, ORs decreased with increasing number of prescriptions for anticholinergics (P for trend = .08) CONCLUSIONS: This study provides reassuring findings that use of H2 antagonists and anticholinergics does not increase AEC risk. It also quantifies the elevated risk of AEC associated with gastroesophageal reflux disease. Further research into reflux disease and the production of premalignant epithelial changes may help elucidate carcinogenic mechanisms and measures aimed at early detection and prevention of AEC.

Adenocarcinoma↗

PubMed1995

Endometrial cancer risk after discontinuing use of unopposed conjugated estrogens (California, United States).

To examine the decline in risk of endometrial cancer after discontinuation of use of conjugated estrogens, we conducted a case-control study in a prepaid health plan. We identified 318 patients who had endometrial cancer but had no history of bilateral oophorectomy and had been in the Southern California (United States) Kaiser Foundation Health Plan for more than 10 years. For each patient, one or two control members were selected, 599 in all, matched for age and duration of membership at the time of cancer detection and who had had neither hysterectomy nor bilateral oophorectomy. A history of prescriptions for conjugated estrogens and of potential confounders was obtained for each subject by reviewing outpatient medical records. Rate ratios (RR) contrasting users with nonusers were estimated by time of latest prescription. We found that estrogen-induced risk of endometrial cancer decreases rapidly as the estrogen-free interval increases. The RR estimates, adjusted for duration of use and potential confounding factors, declined from 5.0 for those receiving their latest prescription within 24 months (95 percent confidence limits [CL] = 2.6-9.8), to 1.8 for those receiving their latest prescription within 24 to 48 months (CL = 0.9-3.7), to values near one for each latest prescription interval earlier than 48 months ago (P for trend = 0.00004). For those who used conjugated estrogens extensively (five or more prescriptions, five to 10 years ago), the RR estimate declined from 5.1 for those whose latest prescription was within two years to 0.6 yr for those whose latest prescription was four to five years previously (P for trend = 0.05).

Adenocarcinoma↗

PubMed1993

Increased risk of renal cell cancer among women using diuretics in the United States.

Use of prescription diuretics and incidence of renal cell cancer have increased in the United States in the past 25 years. Recent interview-based epidemiologic studies have reported an association between diuretic use and renal cell cancer risk. Our study evaluated this hypothesis using, for the first time, medical records as the source of the information on prescription diuretic use. Using medical records of women from a prepaid health plan, we identified 191 cases and 191 controls matched on age, membership duration, and membership at diagnosis. Diuretics use and history of potential confounding factors were ascertained by a standardized review of the medical records of each subject, without reference to case or control status. There was a strong and statistically significant association between renal cell cancer and prescription diuretics (odds ratio [OR] adjusted for hypertension, smoking, and obesity = 2.9, 95 percent confidence interval [CI] = 1.7-4.7). Risk tended to increase with dose, measured by number of prescriptions. Since renal cancer can induce hypertension, which is treated by diuretics, and thereby confound the association with diuretics, we examined diuretic use 10 or more years prior to diagnosis when secondary hypertension would be unlikely. The OR for prescriptions 10 or more years before diagnosis was 3.5 (CI = 1.7-7.4). Our results support earlier reports of an excess risk of renal cell cancer among users of prescription diuretics and indicate need for further study to evaluate this relationship, especially due to the extensive use of diuretics and the increasing incidence of this cancer.

Carcinoma, Renal Cell↗

PubMed1981

Conjugated estrogens and breast cancer risk in women.

The relationship between conjugated estrogen(s) (CE) and breast cancer was investigated by the examination of the records of 345 women with newly diagnosed breast cancer and 611 healthy controls belonging to a prepaid health plan. Use of CE was associated with a 40% elevation in risk [relative risk (RR) = 1.4; 95% confidence interval-1.0-2.0]. The RR was 1.3 for menopausal women with intact ovaries and 1.5 for those with ovaries removed. There was statistically significant evidence of a dose-response relationship with the three measures of dose evaluated. RR's rose to about twofold for women with 10 or more CE prescriptions noted in their charts, for those with 5 years or more between their first and last prescription, and for those with a usual daily dose of 1.25 mg or more. The RR associated with having ever used CE and with long-term use was highest among those women with a family history of breast cancer. These data support the hypothesis that long-term use of CE is associated with increased breast cancer risk.

Breast Neoplasms↗

PubMed1980

Current experience with radioimmunoassay techniques for prostatic acid phosphatase.

Data are presented demonstrating that radioimmunoassay techniques for measurement of serum prostatic acid phosphatase are more sensitive than enzymatic methods in the detection of all stages of prostatic cancer. The possibility of using a solid phase RIA technique to screen for prostatic cancer is considered. Sixty-three hundred and twenty men over age 45 entering a clinical laboratory for any indication were evaluated using the RIA test for PAP. In this group 444 (7%) had elevated test values. Clinical recall and urologic review of the patients with elevated test results yielded 67 who were suspect for prostatic cancer, of whom 59 (88%) were confirmed by prostatic needle biopsy. These data suggest that the RIA for prostatic acid phosphatase as an isolated clinical procedure is not sufficiently specific to be used for screening due to the large number of false-positive results. However, the RIA-PAP test in combination with a follow-up urologic examination is quite specific and deserves further consideration as a screening method for prostatic malignancy.

Acid Phosphatase↗

PubMed1979

Drug evaluation after marketing.

After marketing, drugs should be evaluated for safety and for efficacy. Present national systems are inadequate for both tasks. Safety can be evaluated by means of nonexperimental research, whereas evaluation of efficacy in a variety of settings representing normal medical practice generally requires experiments, randomized and blinded. Research into safety requires the maintenance of routine, yet flexible, multipurpose data systems, different for established and newly marketed drugs. Ad hoc studies on safety and on efficacy can be mounted more swiftly and economically through the maintenance of "standby" capabilities, in addition to maximal use of resources outside the actual national system.

Drug Evaluation↗

PubMed1977

Estrogen and endometrial carcinoma. An independent pathology review supporting original risk estimate.

Initial evidence suggested that estrogen therapy increases the risk of endometrial carcinoma. It was then suggested that some studies may have exaggerated the hazard of estrogen therapy by including patients with atypical endometrial hyperplasia among those having endometrial carcinoma. Three internationally recognized pathologists reviewed the histology slides available from the Ziel and Finkle study, which originally reported a risk ratio of 7.6 for estrogen users. At least one of the pathologists concurred with the original diagnosis in all but one case. Furthermore, all pathologists aggreed that 74 per cent (66/89) were correctly diagnosed. In the 66 patients with unanimous diagnosis, 61 per cent (40/66) had used conjugated estrogens, versus 57 per cent (54/94) in the original study. On the basis of 66 patients and 132 matched controls, the revised risk-ratio estimate is 8.1 (with a one-sided 95 per cent lower confidence limit of 4.5), validating the original estimate.

Biopsy↗

PubMed1976

Association of estrone with the development of endometrial carcinoma.

Although few clinicians suspect estrogen as the prime cause of endometrial carcinoma, a retrospective study showed the following among postmenopausal women: 70 per cent of those with endometrial carcinoma and only 23 per cent of matched control subjects used estrogen systemically. Endometrial cancer developed an average of five years earlier in those taking than in those not receiving estrogen. Forty-two per cent of those with endometrial cancer had received estrogen three years or more. Most significantly, conjugated estrogens were used by 89 per cent of postmenopausal cancer patients who had received any estrogenic substance. The increased risk of endometrial cancer for all patients receiving conjugated estrogen (the risk ratio) was 7.4. This risk ratio increased with duration of conjugated estrogen exposure, from 4.6 in patients with less than three years' exposure to 9.2 in patients with three or more years' exposure.

Androstenedione↗

PubMed1975

Increased risk of endometrial carcinoma among users of conjugated estrogens.

The possibility that the use of conjugated estrogens increases the risk of endometrial carcinoma was investigated in patients and a twofold age-matched control series from the same population. Conjugated estrogens (principally sodium estrone sulfate) use was recorded for 57 per cent of 94 patients with endometrial carcinoma, and for 15 per cent of controls. The corresponding point estimate of the (instantaneous) risk ratio was 7.6 with a one-sided 95 per cent lower confidence limit of 4.7. The risk-ratio estimate increased with duration of exposure: from 5.6 for 1 to 4.9 years exposure to 13.9 for seven or more years. The estimated proportion of cases related to conjugated estrogens, the etiologic fraction, was 50 per cent with a one-sided 95 per cent lower confidence limit of 41 per cent. These data suggest that conjugated estrogens have an etiologic role in endometrial carcinoma.

Adenocarcinoma↗