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B Langholz

Publications and source records attributed to B Langholz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Statistical methods for epidemiologic studies of the health effects of air pollution.

We describe two statistical designs that can provide efficient estimates of the health effects of exposure to air pollutants in epidemiologic studies. We also evaluate the effects of measurement error in exposure assessment on the accuracy of estimated health effects. The bidirectional case-crossover design is a variant of a method proposed by Maclure (1991). Our version of the method takes advantage of the fact that in epidemiologic studies involving environmental exposure, accurate information about past exposure is more readily available, and that levels of exposure are generally unaffected by the response of the subject. It differs from other case-crossover methods in that control information is assessed both before and after failure, thus avoiding confounding due to time trends in exposure. The multilevel analytic design provides a method of combining estimates of health effects made on the individual level with those made at the group level. It has great potential value in situations where variations in exposure within groups may not be great enough to provide adequate power to detect health effects, as is often the case in air pollution studies where exposure levels are similar within a geographic community. Measurement errors in exposure assessment can have substantial impact on the accuracy of estimated health effects. When the microenvironmental approach is used to estimate exposure, a standard error of 30% in estimating indoor/outdoor ratios can increase the standard error of a relative risk estimate by 50%, and introduce bias as well. Similar results hold when exposure is estimated with personal samplers. When the microenvironmental approach is used, errors in estimating indoor/outdoor ratios have more influence on the accuracy of risk estimation than do errors in estimating the time spent in microenvironments.

Absenteeism↗
PubMed1998

Radical prostatectomy and postoperative irradiation in patients with pathological stage C (T3) carcinoma of the prostate.

PURPOSE: Adenocarcinoma of the prostate is the most common human cancer of internal organs. Radical surgery is regarded by many to be the treatment of choice for capsule confined disease. Since accurate preoperative assessment of tumor stage is difficult to define, many patients are subsequently found to have pathological stage C (T3) disease. These patients should be considered for adjuvant radiotherapy. METHODS AND MATERIALS: A group of 201 PS C (T3) unselected patients, treated with radical prostatectomy and limited pelvic lymphadenectomy, received postoperative irradiation to the prostate bed. This radiotherapy was given between 42-90 days after surgery and consisted of a median dose of 48 Gy. Patient survival, disease free survival, time to clinical and chemical relapse and the incidence of local and systemic relapse were analyzed. The influence of multiple parameters on the treatment outcome including patient age, treatment period, clinical stage, pathological stage, Gleason's score, prostate specific antigen (PSA), radiotherapy techniques and radiation dose were examined using univariate and multivariate analysis. Follow-up ranged from 3 to 15 years, with a median of 5 years. RESULTS: The overall 5- and 10-year actuarial survival was 92% and 83% (median > 10 years), respectively and the 5- and 10-year disease-free survival (clinical and PSA) was 67% and 53% (median > 10 years), respectively. A total of 61 (30%) patients had a recurrence, including 23 (11%) patients who had clinical and 38 (19%) who had PSA recurrence. Of the 23 patients with clinical recurrence, 10 (5%) had local recurrence, including two patients who had local and systemic recurrence. Pathological stage and Gleason's score were independently predictive of recurrence (each with p < 0.001 after controlling for the other). Patients in the worst prognostic category with pathological stage C3 and Gleason's score 8-10 were predicted to be at 7.2 times the risk of recurrence, compared to stage C1 or C2 and Gleason's score 2-7 patients. Preoperative PSA level (> 25 ng/ml) was also an important independent factor predicting tumor recurrence, p = 0.05. All other investigated parameters were not significant in predicting tumor recurrence. This treatment program was very well tolerated by the study patients, with seven (3.5%) recorded with major and 18 (9%) with minor surgical complications, while 65% of patients had minor and clinically insignificant radiation complications. CONCLUSION: Surgery followed by moderate dose radiotherapy in patients with PS C (T3) prostatic carcinoma was well tolerated and resulted in excellent overall and disease free survival, with a low incidence of local recurrence. New treatment strategies need to be developed for patients with C3 tumors and those with high (8-10) Gleason's score and those with high (> 25 ng/ml) PSA level at diagnosis.

Aged↗
PubMed1997

Estimation of excess risk from case-control data using Aalen's linear regression model.

We introduce methods for statistical inference in Aalen's non-parametric linear regression model of disease incidence (Aalen, 1989, Statistics in Medicine 8, 907-925) from nested case-control data. These methods provide the basis for estimation of excess risk as a linear function of dose and absolute risk for a given exposure history. The methods are illustrated by estimating excess and absolute risks associated with radon exposure and smoking from nested case-control samples from the Colorado Plateau uranium miners cohort.

Adult↗
PubMed1997

Estimation of absolute risk from nested case-control data.

Benichou and Gail (1995, Biometrics 51, 182-194) describe methods for estimating the absolute risk of developing disease given a set of covariate values over a specified time interval from a case-control study within a cohort. The methods are most suitable for unmatched case-control studies, and are restricted to categorical covariates. Expanding on methods for estimating relative mortality from nested case-control studies presented in Borgan and Langholz (1993, Biometrics 49, 593-602), we present methods for estimating absolute risk from individually matched nested case-control data. These methods accommodate continuous and time-dependent covariate histories, the sampling of cases, and various control sampling designs.

Adult↗
PubMed1995

Variation in HLA-associated risks of childhood insulin-dependent diabetes in the Finnish population: I. Allele effects at A, B, and DR loci. DiMe Study Group. Childhood Diabetes in Finland.

Variation in the risk of insulin-dependent diabetes mellitus (IDDM) across alleles at HLA-A, B, and DR loci was investigated in a population-based study of 801 families of children with newly diagnosed IDDM in Finland nationwide. Parallel analyses assessed the relative frequencies of alleles in IDDM children compared with age-matched sibling controls and with the four possible genotypes which could have been inherited from the parents. The joint effects of DR3 and DR4 alleles were investigated under dominant, recessive, and additive models of gene expression. The additive model gave the best fit, though the relative risk for DR4 homozygotes was smaller than predicted. To investigate other alleles, we fitted the standard multiplicative model for alleles at each locus. After controlling for the correlation among alleles, significantly elevated risks were found for B13, DR3, DR4, and DR14. Subjects with these alleles have more than twice the risk of IDDM as those without. Alleles A24 and B62 incurred relative risks between one and two. DR2 and DR5 were significantly negatively associated with IDDM, incurring less than half the risk. These findings support an independent role of class I antigens in the etiology of IDDM.

Adolescent↗
PubMed1995

Variation in HLA-associated risks of childhood insulin-dependent diabetes in the Finnish population: II. Haplotype effects. DiMe Study Group. Childhood Diabetes in Finland.

We fitted models for the main effects of alleles at the HLA-A, B, and DR loci and their haplotypes on the risk of insulin-dependent diabetes mellitus (IDDM). Empirical Bayes methods were used, assuming independent exchangeable normal priors for effects at each locus separately and for haplotype effects. A pure main effects model, pure haplotype effects model, and a combined model were fitted using Gibbs sampling. The main effects model showed that the DR locus had the largest variation in risk between alleles, followed by the B locus; significance tests for each allele in this model were in general agreement with those in the companion paper [Langholz et al. (1995) Genet Epidemiol 12:441-453], although all relative risks were shrunk toward 1.0 in the empirical Bayes analysis. The variance estimate for pure haplotype effects was substantially larger than for any of the three main effects considered in this analysis, but in the combined model, the DR locus showed larger variability than the haplotype deviations. We confirmed that haplotype A2/B56/DR4 previously reported to be common in Finnish diabetics does indeed confer unusually high risk (relative risk = 7.6, P < 0.001), but found this to be only 1.9 times higher than predicted by its component main effects (P = 0.046). All of the other haplotypes could be adequately explained by their main effects. Empirical Bayes methods provide a natural means of dealing with the problems of multiple comparisons, multicolinearity, and sparse data that complicate the analysis of HLA data.

Adolescent↗
PubMed1995

Prostate cancer: trends in mortality and stage-specific incidence rates by racial/ethnic group in Los Angeles County, California (United States).

Between 1976 and 1988 in the United States, the secular trends to age-adjusted incidence rates of prostate cancer were significantly different by racial/ethnic group (P < 0.001), and increased significantly only among non-Hispanic Whites at a rate of 2.7 percent (95 percent confidence interval [CI] = 2.3-3.1%) annually. While incidence rates of regional disease increased significantly (7.7 percent to 11.3 percent annually) among all racial/ethnic groups during this period, localized disease increased significantly only among non-Hispanic Whites, by 1.8 percent (CI = 1.4-2.3%) annually. Prostate cancer mortality in Los Angeles County (California) remained constant among Hispanics, non-Hispanic Whites, and Asians, but increases 1.6 percent (CI = 0-3.2%) annually among Blacks. While the increase in localized disease rates of non-Hispanic Whites may be due to increased detection of asymptomatic disease, this apparently has not occurred among other racial/ethnic groups in Los Angeles County. The secular increase in regional disease rates among all racial/ethnic groups without a concurrent increase in mortality (except Blacks), suggests increased accuracy of staging rather than a true increase in incidence may account for these trends. Adjusted for socioeconomic status, year and age at diagnosis, Black and Hispanic men were at significantly higher risk of being diagnosed with non-localized disease (odds ratio = 1.39 and 1.24, respectively) than were non-Hispanic Whites.

Black or African American↗
PubMed1995

Initial brachytherapy in the breast conservation approach to breast cancer.

The outcome of 100 consecutive newly diagnosed breast cancer patients treated between 1975 and 1985 within a protocol of planned segmental mastectomy and radiation therapy that included an initial brachytherapy boost is reported. Margins were not routinely inked in this study and the tumor bed was determined with the operating surgeon at the time of brachytherapy. There were 30 T1 tumors, 61 T2, and 9 T3. Segmental mastectomy was followed 2 weeks later by an interstitial implant with iridium-192 sources given as initial boost dose to the tumor bed, at the time of axillary dissection. All patients received at least 20 Gy as boost dose followed by external beam radiation to a total dose of 45-50 Gy to the breast and regional nodes delivered over a period of 4-5 weeks. With a median follow-up of 7 years a total of 3 (3%) breast recurrences were detected (1/30 in T1 tumors, 2/61 in T2 tumors). Only one of the three recurrences was at the initial tumor bed. None of the nine T3 patients included in this series recurred locally. There were 4 severe complications (2 soft tissue necroses and 2 osteonecroses) occurring in 2/30 T1 and in 2/61 T2. Cosmetic results were good to excellent in 77% of the cases and fair to poor in 23%. The actuarial local control and survival probability rate were, respectively, 95% and 85% at 5 years and 93% and 73% at 10 years. Initial brachytherapy boost to a target volume accurately determined with the operating surgeon followed by subsequent external beam radiotherapy achieved excellent local control in the breast even for lesions larger than 2 cm (70% of the reported cases).

Adult↗
PubMed1994

Temporal modifiers of the radon-smoking interaction.

Data on lung cancer mortality in a cohort of 3,347 Colorado Plateau uranium miners was reanalyzed to investigate the role of time-related modifiers of the radon-smoking interaction. A nested case-control sample of the cohort was drawn, matching each of the 258 lung cancer deaths with 15 controls drawn at random from the subjects who were born in the same year and still alive at the time the case died. As reported earlier, the dose response was sublinear for both total radon and total smoking, and their joint effect was approximately multiplicative. We fitted linear multiplicative models to these data, transforming the radon and smoking variables to improve their fit, and then added variables testing various temporal modifying effects and interactions. The strongest modifiers of the main effects of each variable taken separately were latency and duration of exposure. The strongest modifier of the interaction effect was the timing of radon and smoking exposures: Exposure to radon followed by smoking produced a significantly more-than-multiplicative effect, whereas the reverse sequence produced a significantly less-than-multiplicative effect. These findings suggest that smoking may act as a promoter of radon-initiated cells.

Air Pollutants, Radioactive↗
PubMed1994

Sampling strategies in nested case-control studies.

A stratified version of nested case-control sampling which we call "countermatching" is presented. This design uses data available for all cohort members to obtain a sample for collecting additional information in a case-control substudy. Hitherto the only stratified sampling design for such studies has involved matching of controls to cases with respect to confounding variables. However, in some situations, rather than sampling to make controls as similar as possible to cases, we might wish to make them as different as possible. This is achieved by the counter-matched design. Statistical analysis of counter-matched studies is straightforward using existing computer software. We investigate the use of the design when a surrogate measure of exposure is available for the full cohort, but accurate exposure data is to be collected only in a nested case-control study, and when exposure data are available for the whole cohort but data concerning important confounders are not. Asymptotic relative efficiency calculations indicate that a substantial efficiency gain relative to simple random sampling of controls can be expected in these situations. We also illustrate how the design might be implemented in practice.

Bias↗
PubMed1993

Early introduction of dairy products associated with increased risk of IDDM in Finnish children. The Childhood in Diabetes in Finland Study Group.

Associations between infant-feeding patterns and risk of IDDM were investigated in a nationwide Finnish case-control study of 690 IDDM children < 15 yr of age. Each child was matched by date of birth and sex to a randomly selected population-based control child. Univariate analysis revealed that the risk of IDDM was increased by approximately 1.5 in children for whom breast-feeding was terminated at < 2 mo of age, doubled in those who were exclusively breast-fed for < 2 mo, and doubled in those who were introduced to dairy products at < 2 mo of age. In further multivariate analyses of these factors, it was found that introduction of dairy products at an early age was the most important risk factor, and the observed univariate effects of duration of breast-feeding variables were explained by their correlation with this factor. This is the first observational study to show that early introduction of dairy products is independently associated with an increased risk of IDDM. Adjustment for mother's education and age, child's birth order, or birth weight did not affect the results.

Adolescent↗
PubMed1993

Nonparametric estimation of relative mortality from nested case-control studies.

Andersen et al. (1985, Biometrics 41, 921-932) gave an estimator of the cumulative relative mortality comparing rates of death in an epidemiologic cohort to an external population as a function of time when covariate information is available on all cohort members. We present an analogous estimator when covariate information is known only on a nested case-control sample. Counting process techniques are used to show that this estimator is almost unbiased and an estimator of its variance is derived. Estimators of the relative mortality function, using kernel smoothing methods, and the average relative mortality over grouped time intervals are also presented. The methods are illustrated by comparing rates of lung cancer mortality in a cohort of Montana smelter workers to that in the United States population.

Case-Control Studies↗
PubMed1992

DDT and related compounds and risk of pancreatic cancer.

BACKGROUND: A cohort mortality study among 5886 chemical manufacturing workers was completed in 1987 and showed increased mortality due to pancreatic cancer. PURPOSE: We conducted a nested case-control study of pancreatic cancer among these chemical manufacturing workers to identify risk factors for this disease. METHODS: Twenty-eight verified cases of pancreatic cancer and 112 matched controls were studied. Next of kin of each subject were interviewed to determine lifestyle factors, including tobacco, alcohol, and coffee consumption. Written work records and interviews with co-workers were used to determine chemical exposures at the plant under study. RESULTS: DDT was associated with pancreatic cancer (risk ratio [RR] for ever exposed compared with never exposed = 4.8; 95% confidence interval = 1.3-17.6). Among subjects who had a mean exposure to DDT of 47 months, the risk was 7.4 times that among subjects with no exposure. Two DDT derivatives, Ethylan and DDD, were additionally associated with pancreatic cancer (RR = 5.0 and 4.3, respectively); exposures to these two chemicals were correlated, and it was not possible to determine whether each acted independently of the other. Smoking was identified as an independent risk factor, but controlling for smoking (and other potential confounders) in the analyses did not appreciably alter the risks seen for DDT, DDD, or Ethylan. CONCLUSIONS: Exposure to DDT was associated with pancreatic cancer. The association was not explained by exposure to lifestyle factors or other chemicals, and risk increased with both duration of exposure and latency since first exposure. IMPLICATIONS: These results may indicate that DDT can cause pancreatic cancer in humans under circumstances of heavy and prolonged exposure.

Case-Control Studies↗
PubMed1992

Episcleral plaque thermoradiotherapy in patients with choroidal melanoma.

From 1988 to 1991, 21 patients with uveal melanoma were treated in a Phase I study with episcleral plaque radiotherapy (EPRT). This irradiation was combined with localized current field episcleral hyperthermia (LCFHT). Tumor stage was: T3 = 15 (71%) and T2 = 6 (29%). Follow-up ranged from 2 to 42 months (mean 9.2 months). EPRT was given using custom built I-125 gold plaques. Radiation doses to the tumor apex ranged from 13 to 123 Gy (mean dose 70.0 Gy) given at a mean dose rate of 55 cGy/hr. LCFHT was given with 500 KHz frequency for 45 min immediately before EPRT. The temperature was controlled on the scleral surface using four thermocouples. T mean ranged from 42.5 degrees C to 45 degrees C +/- 0.5 degrees C (mean 43.4 degrees C). The study patients showed rapid tumor necrosis. A 25% mean decrease of apical tumor dimension was noted, p = 0.0007. At least ambulatory vision (greater than 5/200) was maintained by 17/21 (81%) patients. Visual acuity was seen to improve greater than 6 months post-plaque therapy in 10 (48%) study patients. This was following an intermediate decrease in visual acuity. Severe complications, including large hemorrhagic retinal detachment and large vitreous hemorrhage, were seen in two (9.5%) of the early study patients. A mean scleral temperature reduction to less than or equal to 44 degrees C +/- 0.5 degrees C resulted in good treatment tolerance and a lack of serious complications in subsequently treated patients. A Phase II prospective randomized trial comparing LCFHT with 60 versus 80 Gy EPRT dose to the tumor apex is currently being activated for patients with choroidal melanoma.

Adolescent↗
PubMed1992

Episcleral plaque radiotherapy in the treatment of uveal melanomas.

During an 8-year period, 85 patients with uveal melanomas were treated with episcleral plaque radiotherapy (EPRT). The T-stage was: T1-3 (4%), T2-29 (34%) and T3-53 (62%). The mean tumor elevation was 6.1 mm. Radiation dose was prescribed at the tumor apex and at D5mm. The mean D5mm dose was 150.1 Gy (range 70.5-430 Gy) and the mean dose at the apex was 102.6 Gy (range 29.8-200 Gy). Useful vision (greater than 5/200) was maintained in 73% of patients. The 5-year actuarial survival was 88%. Metastatic disease developed in 9 (11%) patients, 6 of whom died of their disease. Basal tumor dimensions were important factors predicting metastatic disease, p = 0.002. A decrease in tumor evaluation was seen in 82%. There was a much lower incidence of decrease in tumor radial and circumferential dimensions, 47.5 and 46%, respectively, p less than 0.001. Treatment complications were common (56%), particularly in patients with large tumors (72%), p = 0.04. The incidence of complications was higher in patients treated prior to 1988 as compared to those who were treated more recently (67 vs 35%, p = 0.010). There were 13 (15%) patients who had enucleation. This included 12 treated before 1986 and 1 patient treated subsequently (46 vs 2%, p less than 0.001). In a univariate analysis, tumor height and radiation dose at D5mm were important factors predicting enucleation, p = 0.004. In a multivariate analysis, however, the most important factor predicting enucleation was treatment administration prior to 1986, p less than 0.001). A sharp decrease in the incidence of severe complications, including enucleation, as seen after 1985, is likely due to a major effort in treatment optimization.

Adult↗
PubMed1992

Stage and delay in breast cancer diagnosis by race, socioeconomic status, age and year.

Information on 23,567 Non-Hispanic White, 2,539 Black, and 2,380 Hispanic breast cancer cases diagnosed between 1977 and 1985 was used to evaluate the risk of late stage diagnosis and long duration of symptoms prior to diagnosis in relation to ethnicity, socioeconomic status, age and year of diagnosis. All data were collected by the University of Southern California Cancer Surveillance Program, the comprehensive population-based incidence registry of Los Angeles County. The results indicate that lower socioeconomic status, Black or Hispanic ethnicity, younger age, and earlier year of diagnosis are risk factors for late stage diagnosis and long duration of symptoms. The effect of ethnicity was not explained by lower SES levels among Black or Hispanic women. After controlling for duration of symptoms, race and SES remained significantly predictive of more advanced stage. More recent diagnosis across the 9 year time frame was not associated with improved stage for those of low SES. These results suggest that increased efforts are needed to reach low SES and Black and Hispanic women with campaigns to improve the stage at which breast cancer is detected.

Adult↗