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T A Stukel

Publications and source records attributed to T A Stukel.

At least 19 recordsLinked to original sources

Mortality associated with low plasma concentration of beta carotene and the effect of oral supplementation.

OBJECTIVE: To examine the relationship between beta carotene plasma concentration and beta carotene supplementation and risk of death from major disease causes. DESIGN: Cohort study of plasma concentrations; randomized, controlled clinical trial of supplementation. SETTING: Medical school-affiliated dermatology practices. PATIENTS: A total of 1188 men and 532 women with mean age of 63.2 years, who had enrolled in a randomized clinical trial of beta carotene supplementation to prevent nonmelanoma skin cancer. INTERVENTION: Oral beta carotene, 50 mg per day for a median of 4.3 years. MAIN OUTCOME MEASURES: All-cause mortality and mortality from cardiovascular disease and cancer. RESULTS: During a median follow-up period of 8.2 years, there were 285 deaths. Persons whose initial plasma beta carotene concentrations were in the highest quartile (>0.52 micromol/L [27.7 microg/dL]) had a lower risk of death from all causes (adjusted relative rate [RR], 0.52; 95% confidence interval [CI] 0.44 to 0.87) and from cardiovascular diseases (adjusted RR, 0.57; 95% CI, 0.34 to 0.95) compared with persons with initial concentrations in the lowest quartile (<0.21 micromol/L [11.2 microg/dL]). Patients randomly assigned to beta carotene supplementation showed no reduction in relative mortality rates from all causes (adjusted RR, 1.03; 95% CI, 0.82 to 1.30) or from cardiovascular disease (adjusted RR, 1.16; 95% CI, 0.82 to 1.64). There was no evidence of lower mortality following supplementation among patients with initial beta carotene concentrations below the median for the study group. CONCLUSIONS: These analyses provide no support for a strong effect of supplemental beta carotene in reducing mortality from cardiovascular disease or other causes. Although the possibility exists that beta carotene supplementation produces benefits that are too small or too delayed to have been detected in this study, noncausal explanations should be sought for the association between plasma concentrations of beta carotene and diminished risk of death.

Administration, Oral

Utility of a risk assessment questionnaire in identifying children with lead exposure.

OBJECTIVE: To evaluate the utility of the Centers for Disease Control and Prevention (CDC) Risk Questionnaire and a behavioral risk factor questionnaire in identifying children with blood lead concentrations of 0.48 mumol/L (10 micrograms/dL) or more. DESIGN: Cross-sectional study of 463 urban Massachusetts children (6 to 72 months of age) screened for lead with venous blood. RESULTS: Twenty-two percent of the children had elevated blood lead concentrations. Of the five CDC questions, only one was significantly associated with an increased adjusted odds ratio for elevated blood lead: having a sibling, housemate, or playmate who was followed up or treated for lead poisoning (odds ratio, 2.7; 95% confidence interval, 1.7 to 4.2; P < .001). Children who had at least one positive or equivocal response to any of the five CDC questions (n = 318 [68.7%]) were not at higher risk than were children who displayed a negative response to all five questions (odds ratio, 1.1; 95% confidence interval, 0.7 to 1.8; P = .69). Of nine behaviors surveyed, two were associated with an increased adjusted odds for elevated blood lead: use of a pacifier (odds ratio, 2.4; 95% confidence interval, 1.3 to 4.4; P = .01) and playing near the outside of the home (odds ratio, 3.4; 95% confidence interval, 2.0 to 5.8; P < .001). CONCLUSIONS: In this population of children, the CDC risk questionnaire did not identify a group at higher risk for lead exposure. We suggest that practitioners in urban communities screen all children according to the same schedule. We conclude that risk factors differ by community and no risk questionnaire developed at the national level should be applied across communities to target screening.

Centers for Disease Control and Prevention, U.S.

Iron deficiency in Massachusetts communities: Socioeconomic and demographic risk factors among children.

OBJECTIVES: This study examined the association between community rates of iron deficiency in children and sociodemographic characteristics of Massachusetts communities. METHODS: Between April 1990 and March 1991, 238 273 Mssachusetts children 6 through 59 months of age were screened; iron deficiency was defined as an erythrocyte protopophyrin concentration of 0.62 micromol/L or higher and a blood lead level of less than 1.2 micromol/L. Sociodemographic data were obtained from the 1990 US Census. RESULTS: Five percent of communities had iron deficiency rates greater than 13.9 per 100 children screened. Iron deficiency rate was positively associated with proportion of Southeast Asians (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.08, 1.12), proportion of Hispanics (OR = 1.008, 95% CI = 1.002, 1.013), and high school incompletion (OR = 1.028, 95% CI = 1.020, 1.035). Similarly, an examination of three Massachusetts cities indicated that the iron deficiency rate was higher for children with Southeast Asian (relative risk [RR] = 3.6, 95% CI = 3.3, 3.8) and Hispanic (RR = 1.6, 95% CI = 1.5, 1.8) surnames than for all other children. CONCLUSIONS: Wide variation exists in iron deficiency rates for children in Massachusetts communities. Community iron deficiency was associated with low socioeconomic status and high proportions of Southeast Asians and Hispanics.

Anemia, Iron-Deficiency

Long-term morbidity following jejunoileal bypass. The continuing potential need for surgical reversal.

OBJECTIVE: To review the late sequelae of jejunoileal bypass (JIB) and the potential role of late surgical reversal in ameliorating morbidity and mortality following JIB. DESIGN: Patients who underwent JIB between 1965 and 1977 were contacted and pertinent health-event information was gathered. Early sequelae were defined as disorders occurring within the first 2 years after JIB; late sequelae were those occurring after 2 years. Health events occurring between 0 and 23 years after JIB were documented. SETTING: A private, tertiary referral center. PATIENTS: Patients underwent JIB for morbid obesity that had failed medical and/or psychiatric interventions. MAIN OUTCOME MEASURES: Body mass index (BMI) (weight kilograms divided by the square of the height in meters), diarrhea, electrolyte imbalance, acute, and chronic liver disease, renal disease, JIB reversal, reason for JIB reversal, death, and cause of death. RESULTS: A total of 453 morbidity obese patients underwent JIB. By 2 years following JIB, the mean (+/- SD) BMI dropped from 49.3 +/- 8.1 to 31.1 +/- 0.8 and remained at this level until year 15, after which weight gradually increased (BMI, 35.4 +/- 3.1). The most severe early complication was acute liver failure, which occurred in 7% of patients and caused seven deaths. At 15 years, the actuarial probability of the most common serious late complications related to JIB were renal disease (37%), with two deaths; diarrhea (29%); and liver disease (10%), with three deaths. One hundred thirty-eight patients (31%) had a bypass reversal. The most common indications for reversal were diarrhea and electrolyte disturbance (29%), renal disease (19%), and liver disease (17%). Fifty-six patients died more than 30 days after JIB: 64% before JIB reversal, 13% at the time of reversal, and 23% subsequently. CONCLUSIONS: Jejunoileal bypass is associated with progressive accrual of serious, sometimes life-threatening complications. Lifelong follow-up for early diagnosis and surgical reversal before life is threatened should reduce the morbidity and mortality associated with this procedure.

Acid-Base Imbalance

Hospital readmission rates for cohorts of Medicare beneficiaries in Boston and New Haven.

BACKGROUND: Geographic variations in the use of hospital services are associated with differences in the availability of hospital beds. There continues to be uncertainty about the extent to which unmeasured case-mix differences explain these findings. Previous research showed that the number of occupied beds per capita in Boston was substantially higher than the number of occupied beds per capita in New Haven, Connecticut, and that overall rates of hospital utilization were higher for Boston residents than for New Haven residents. METHODS: We used Medicare claims data to study cohorts of Medicare beneficiaries 65 years of age or older and residing in Boston or New Haven who were initially hospitalized for one of five indications (acute myocardial infarction, stroke, gastrointestinal bleeding, hip fracture, or potentially curative surgery for breast, colon, or lung cancer). Residents of Boston or New Haven who were discharged between October 1, 1987, and September 30, 1989, were enrolled in the cohort corresponding to the earliest such admission and followed for up to 35 months. RESULTS: The relative rate of readmission in Boston as compared with New Haven was 1.64 (95 percent confidence interval, 1.53 to 1.76) for all cohorts combined, with a similarly elevated rate for each of the five clinical cohorts and each age, sex, and race subgroup examined. Hospital-specific readmission rates varied substantially among the hospitals in Boston and were higher than those in New Haven. No relation was found between mortality (during the first 30 days after discharge or over the entire study period) and either community or hospital-specific readmission rates. CONCLUSIONS: Regardless of the initial cause of the admission, Medicare beneficiaries who were initially hospitalized in Boston had consistently higher rates of readmission than did Medicare beneficiaries hospitalized in New Haven. Differences in the severity of illness are unlikely to explain these findings. One possible explanation is a threshold effect of hospital-bed availability on decisions to admit patients.

Aged

Standardized rates of recurrent outcomes.

Longitudinal studies are often concerned with estimating the rate of an event that may recur. Examples are nonmelanoma skin cancer rates, screening rates for breast cancer using mammography and hospital admission rates. We propose simple estimators for directly and indirectly standardized summary rates and relative rates of recurrent events and their variances. We also develop an estimator of the excess rate in an area if the rate in another area applied. For non-recurrent events, the estimators are identical to the usual standardized summary rates. The estimators are independent of the underlying distribution of the event of interest and allow for unequal follow-up times and event rate heterogeneity among individuals. The method is not computationally intensive and does not require specialized software. We illustrate the application of the method in a retrospective cohort study of hospital utilization patterns of Medicare enrollees in Boston and New Haven over a three and a half year period.

Boston

Steady-state serum concentration of alpha tocopherol not altered by supplementation with oral beta carotene. The Polyp Prevention Study 1 Group.

BACKGROUND: The antioxidants beta carotene and vitamin E may play a role in cancer prevention. However, some studies have suggested that oral supplements of beta carotene may cause a decrease in serum levels of alpha tocopherol (vitamin E). PURPOSE: We conducted this study to determine if beta carotene supplements affect serum levels of vitamin E and vice versa. METHODS: Five hundred five patients in a clinical trial of antioxidant vitamins, used to prevent recurrences of colonic polyps, received either a placebo, 25 mg of beta carotene per day, 1 g ascorbic acid plus 400 mg alpha tocopherol per day, or all three agents combined. Serum levels of beta carotene and vitamin E were measured before and after 9 months of supplementation, using high-performance liquid chromatography. RESULTS: Vitamin E levels changed very little among the groups receiving placebo or beta carotene and went up substantially and equally in the groups receiving vitamin E plus ascorbic acid or all three agents together. Conversely, beta carotene levels changed very little for the groups receiving placebo or ascorbic acid plus vitamin E but went up substantially and equally for the groups receiving beta carotene alone or all three agents. CONCLUSIONS: We conclude that oral supplementation with beta carotene for 9 months does not alter serum concentration of vitamin E and that supplementation with vitamin E plus ascorbic acid does not alter serum beta carotene levels.

Administration, Oral

Comparison of methods for the analysis of longitudinal interval count data.

Longitudinal studies are often concerned with estimating the recurrence rate of a non-fatal event. In many cases, only the total number of events occurring during successive time intervals is known. We compared a mixed Poisson-gamma regression method proposed by Thall and a quasi-likelihood method proposed by Zeger and Liang for the analysis of such data, in the case where the mean was correctly specified, using simulation techniques with large samples. Both methods produced similar standard errors in most situations, except in the case of time-dependent covariates with non-Poisson-gamma data where they were seriously underestimated by the Thall method. A simple method for discriminating between the variance forms of the two methods is described. The findings are applied to the analyses of clinical trials of non-melanoma skin cancer and familial polyposis. This study extends the findings of Breslow concerning variance misspecification in overdispersed Poisson and quasi-likelihood models to the longitudinal setting.

Adenomatous Polyposis Coli

Estimating the variance of standardized rates of recurrent events, with application to hospitalizations among the elderly in New England.

Usual approaches for estimating the variance of a standardized rate may not be applicable to rates of recurrent events. Where individuals are prone to repeated health events, Greenwood and Yule (J R Stat Soc [A], 1920;83:255-79) advocated use of the negative binomial distribution to account for departures from the assumption of randomness of recurrent events required by the Poisson distribution. In this paper, the authors implemented the negative binomial distribution in the computation of annual hospitalization rates within certain hospital market areas. Data used were from 1,549,915 New England residents aged 65 years or more who were enrolled in Medicare between October 1, 1988, and September 30, 1989, and who had 458,593 hospital admissions during that year. New England was partitioned into 170 hospital market areas ranging in population size from 162 to 70,821 elderly Medicare enrollees. The negative binomial distribution demonstrated substantially better fits than the Poisson distribution to the numbers of hospitalizations within hospital market areas. Estimated standard errors for indirectly standardized rates based on the negative binomial distribution were 25-51 percent higher than estimated standard errors that assumed an underlying Poisson distribution. Using regression analysis to smooth overdispersion parameters across hospital market areas produced similar results. The approach described in this paper may be useful in estimation of confidence intervals for standardized rates of recurrent events when these events do not recur randomly.

Age Factors

Normal values for random urinary calcium to creatinine ratios in infancy.

OBJECTIVE: To determine normal values for the urinary calcium/creatinine ratio (UCa/Cr) in infants. To assess the impact of short-term supplementation of infant formula with calcium and phosphorus on UCa/Cr in a group of infants. DESIGN: We determined UCa/Cr in randomly collected urine samples from a group of children and adults. Short-term supplementation of infant formula with calcium glycerophosphate was carried out in 21 infants, and UCa/Cr was monitored in a before-and-after trial. SETTING: A pediatric clinic at an academic center (infants and adults), and a day-care center (older children). PARTICIPANTS: A total of 103 infants between 5 days and 7 months of age, 40 infants between 8 and 17 months of age, 41 children between 18 months and 6 years, and 31 adults. RESULTS: The 95th percentiles for molar UCa/Cr for the different age groups were as follows: less than 7 months, 2.42 (0.86 mg/mg); 7 to 18 months, 1.69 (0.60 mg/mg); 19 months to 6 years, 1.18 (0.42 mg/mg); and adults, 0.61 (0.22 mg/mg). Regression analysis indicated a statistically significant decline in average UCa/Cr with age (R2 = 0.115, p < 0.0001 for log (UCa/Cr) vs log (age)). The geometric means for the two groups of infants were significantly greater than those of the older children and the adults (p < 0.05). Values for UCa/Cr in adults in our sample were comparable to those previously reported. We detected no significant changes in mean UCa/Cr during week-long periods of calcium supplementation of up to 1.8 gm of calcium and 1.39 gm of phosphorus per liter of formula. CONCLUSION: We conclude that normal values for UCa/Cr are much higher in infants than in older children and adults; UCa/Cr is age-related and declines gradually in the first several years of life, and short-term supplementation of infant formula with calcium glycerophosphate has minimal effect on UCa/Cr.

Adult

Immunohistochemical staining for transforming growth factor beta 1 associates with disease progression in human breast cancer.

The transforming growth factor beta s (TGF-beta) comprise a family of M(r) 25,000 pluripotent growth factors which have been implicated in the development and progression of human breast cancer. Conflicting data suggest that TGF-beta has the potential to either inhibit or promote the progression of mammary neoplasia. We therefore examined a pathological library of malignant breast biopsy specimens to determine the prevalence and distribution of immunoreactivity with antibodies specific for the three mammalian isoforms of TGF-beta (beta 1, beta 2, and beta 3). We found that intense staining for TGF-beta 1 was positively associated with rate of disease progression, and that this was independent of age, stage, nodal status, or estrogen receptor status (P = 0.009).

Adult

Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer. Skin Cancer Prevention Study Group.

OBJECTIVE: The primary aims of this study were to assess risk of subsequent basal and squamous cell skin cancer among patients with a prior history of these tumors and to examine these risks in relation to patient characteristics and life-style factors. DESIGN: Follow-up of participants in a randomized trial of betacarotene as a possible skin cancer preventive agent. SETTING: Clinical centers in Los Angeles, Calif, San Francisco, Calif, Minneapolis, Minn, and Hanover, NH. PARTICIPANTS: Patients (n = 1805) who were diagnosed as having a basal or squamous cell skin cancer between January 1980 and February 1986 and were free of skin cancer at study entry. MAIN OUTCOME MEASURE: Time from study entry to first new occurrence of basal and squamous cell skin cancer. RESULTS: The estimated risk of developing one or more new skin cancers was 35% at 3 years and 50% at 5 years. New skin cancers tended to be of the same cell type as the previous skin cancers. For both basal and squamous cell skin cancer, risk was higher among patients who were male, were over the age of 60 years, had more prior skin cancers, had severe actinic skin damage, or who burned easily with sun exposure. Compared with those who had never smoked, the rate of subsequent squamous cell skin cancer was higher among current smokers (rate ratio, 2.01; 95% confidence interval, 1.21 to 3.34) and former smokers (rate ratio, 1.62; 95% confidence interval, 1.07 to 2.47) and increased with both duration and amount smoked. There was no clear relationship between smoking and basal cell skin cancer; the rate appeared lower among heavy smokers but was unrelated to duration of smoking. CONCLUSIONS: Persons with a prior nonmelanoma skin cancer had a substantial 5-year risk of developing another tumor of the same histologic type. Number of previous skin cancers, solar damage, and skin sensitivity to sun exposure were particularly related to this risk. The increased risk of squamous cell skin cancer associated with cigarette smoking merits further study.

Adult

Childhood mortality after a high dose of vitamin A in a high risk population.

OBJECTIVES: To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme. DESIGN: Opportunistic controlled trial. SETTING: Jumla district, Nepal. SUBJECTS: All children aged under 5 years; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation. MAIN OUTCOME MEASURES: Mortality and cause of death in the five months after supplementation. RESULTS: Risk of death for children aged 1-59 months in supplemented communities was 26% lower (relative risk 0.74, 95% confidence interval 0.55 to 0.99) than in unsupplemented communities. The reduction in mortality was greatest among children aged 6-11 months: death rate (deaths/1000 child years at risk) was 133.8 in supplemented children and 260.8 in unsupplemented children (relative risk 0.51, 0.30 to 0.89). The death rate from diarrhoea was also reduced (63.5 supplemented v 97.5 unsupplemented; relative risk 0.65, 0.44 to 0.95). The extra cost per death averted was about $11. CONCLUSION: The results support a role for Vitamin A in increasing child survival. The supplementation programme was readily integrated with the ongoing community health programme at little extra cost.

Child Health Services

Diurnal and seasonal variation of five carotenoids measured in human serum.

We studied within-person variation over time in serum concentrations of five carotenoids. In a diurnal study involving 33 subjects, only the 1700 h blood samples demonstrated carotenoid concentrations different from the original 0800 values. Correlations between serum concentrations of the same carotenoids drawn 1 d apart ranged from 0.93 to 0.98. In a seasonal study involving 29 subjects, no systematic trends were observed for serum concentrations of these carotenoids. Correlations between concentrations of the same carotenoids drawn 1 y apart ranged from 0.57 to 0.82. Concentrations of different carotenoids within an individual tended to be correlated with each other. Obtaining one blood sample from subjects is a relatively imprecise way to estimate their usual serum concentrations of carotenoids. If an epidemiological study was to be based on only one determination of serum carotenoids, within-person variability in serum concentrations would attenuate true regression coefficients by 4-13% and would increase the required numbers of study subjects by 19-65%.

Adult

Predictive value of flow cytometric analyses of blast cells in assessing the phenotype of the leukemia colony-forming cell (L-CFC) population in acute myeloid leukemia.

Acute myeloid leukemia (AML) blast cells (BC) express antigens that are commonly found on their normal counterparts. The leukemia colony-forming cell (L-CFC) subpopulation, identified by its ability to form leukemia colonies in vitro, is thought to be the stem cell population that produces BC. To ascertain the association between myeloid antigens on the BC and the L-CFC from the same patient, we compared the expression of CD14, CD15, CD33, p124 and HLA class I from 17 cases of AML. These particular myeloid antigens were studied because they are suitable targets in purging bone marrow for autotransplantation. We found no significant difference in the expression of CD14, CD15, CD33, and HLA class I on the BC and L-CFC from the same patient, although we observed considerable heterogeneity among different AML cases. Analysis of the progenitor cell antigen p124 revealed significant within-patient differences on the BC and L-CFC (p = 0.007), with a greater tendency for expression on the L-CFC. This heterogeneity may be due to differences in maturation stage of the L-CFC and BC. This information is important when L-CFC phenotype is used to determine the appropriate selection of antibodies for purging of residual disease in the context of auto-transplantation.

Antigens, Differentiation

Lack of effect of chronic administration of oral beta-carotene on serum cholesterol and triglyceride concentrations.

Previous studies suggest that chronic oral administration of retinol and other retinoids causes elevation of plasma triglyceride concentrations. The effects of chronic oral administration of beta-carotene, a carotenoid partially metabolized to retinol, on plasma lipid concentrations have not been well studied; therefore, we studied 61 subjects over 12 mo while they were enrolled in a skin-cancer-prevention study in which patients were randomly assigned to receive either placebo (n = 30) or 50 mg beta-carotene/d orally (n = 31). At study entry and 1 y later, fasting blood samples were obtained for measurement of triglycerides, total cholesterol, HDL cholesterol, retinol, and beta-carotene. Retinol concentrations changed minimally in both groups; beta-carotene concentration increased an average of 12.1 +/- 47 nmol/L in the placebo group and 4279 +/- 657 nmol/L in the active-treatment group. Both groups experienced similar small increases in triglyceride and total cholesterol concentrations and small decreases in HDL cholesterol. Daily oral administration of 50 mg beta-carotene/d did not affect plasma lipid concentrations.

Administration, Oral