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T Colton

Publications and source records attributed to T Colton.

At least 19 recordsLinked to original sources
PubMed2001

Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy.

From 1940 through the 1960s, diethylstilbestrol (DES), a synthetic oestrogen, was given to pregnant women to prevent pregnancy complications and losses. Subsequent studies showed increased risks of reproductive tract abnormalities, particularly vaginal adenocarcinoma, in exposed daughters. An increased risk of breast cancer in the DES-exposed mothers was also found in some studies. In this report, we present further follow-up and a combined analysis of two cohorts of women who were exposed to DES during pregnancy. The purpose of our study was to evaluate maternal DES exposure in relation to risk of cancer, particularly tumours with a hormonal aetiology. DES exposure status was determined by a review of medical records of the Mothers Study cohort or clinical trial records of the Dieckmann Study. Poisson regression analyses were used to estimate relative risks (RR) and 95% confidence intervals (CI) for the relationship between DES and cancer occurrence. The study results demonstrated a modest association between DES exposure and breast cancer risk, RR = 1.27 (95% CI = 1.07-1.52). The increased risk was not exacerbated by a family history of breast cancer, or by use of oral contraceptives or hormone replacement therapy. We found no evidence that DES was associated with risk of ovarian, endometrial or other cancer.

Breast Neoplasms↗
PubMed2001

Cancer risk at sites other than the breast following augmentation mammoplasty.

PURPOSE: There has been limited investigation of cancer risk other than breast cancer among patients with breast implants, despite some clinical and laboratory evidence suggesting links with certain cancer sites, including hematopoietic and connective tissue malignancies. METHODS: A retrospective cohort study of 13,488 patients who received cosmetic breast implants at 18 plastic surgery practices in six geographic areas was conducted to assess long-term health effects. After an average of 12 years of follow-up, questionnaires were administered to subjects located and alive (78% of eligible population). Attempts were made to obtain death certificates for deceased subjects and medical verification for all reported cancers. Expected numbers of cancers were derived using general population cancer incidence rates and an internal comparison series of 3936 patients who received other types of plastic surgery at the same practices as the implant patients. RESULTS: A total of 359 malignancies was observed versus 295.95 expected based on general population rates, resulting in a standardized incidence ratio (SIR) of 1.21 [95% confidence interval (CI) 1.1-1.4]. Individual malignancies for which incidence was significantly elevated included cancers of the stomach (SIR = 2.65), cervix (SIR = 3.18), vulva (SIR = 2.51), brain (SIR = 2.16), and leukemia (SIR = 2.19). No excess risks were observed for other hematopoietic malignancies, including multiple myeloma. The internal analyses, however, based on cancer rates derived among the comparison patients, showed no increased cancer risk among the implant patients [relative risk (RR) = 1.00, 95% CI 0.8-1.2], as well as no statistically significant elevations for most individual sites. Cervical cancer continued to be elevated (RR = 1.78), although to a lesser extent than in the external analyses, while the risk for respiratory cancers was higher (RR = 2.40). Non-significant elevations in risk persisted in this analysis for liver cancer (RR = 2.65), brain cancer (RR = 2.83), and leukemia (RR = 1.83). Many of the cancers showing excesses were defined on the basis of death certificates, requiring caution in interpretation. The histologies of the leukemias were quite varied, which makes a biologic relationship appear unlikely. However, respiratory cancers showed some evidence of increasing risk with follow-up time and both respiratory and brain cancers were elevated in the mortality analyses. CONCLUSIONS: Although excesses of cervical and vulvar cancer among implant patients might be attributable to lifestyle factors, reasons for excesses of respiratory and brain cancers were less apparent.

Brain Neoplasms↗
PubMed2001

Early discharge after coronary artery bypass graft surgery: are patients really going home earlier?

OBJECTIVE: This study was undertaken to determine whether early discharge after coronary artery bypass grafting allows patients to return home earlier or merely increases the use of outpatient nursing and inpatient rehabilitation services. METHODS: Patterns of discharge were analyzed in 407 patients undergoing bypass grafting in 1990, when there were no early extubations or fast track protocols, and compared with 379 patients in 1998, when these protocols were used. RESULTS: Patients in 1998 had a higher prevalence of class IV angina (35.3% vs 22.8%; P =.006), urgent/emergency surgery (58.3% vs 44.9%; P =.015), and lower ejection fractions (48.9% +/- 16.4% vs 52.9% +/- 13.5%; P =.0002). Despite these increased risk factors, 1998 patients spent less time receiving ventilatory support (10.2 +/- 9.2 vs 26.7 +/- 15.7 hours; P <.001) and had a shorter length of stay (5.4 +/- 2.5 vs 9.2 +/- 4.3 days; P <.001). However, fewer 1998 patients were discharged home (56.7% vs 97.0%; P <.0001). A higher percentage of 1998 patients (43.3% vs 2.9%; P <.00001) were discharged to extended care facilities where their average length of stay was 10.6 +/- 15.1 days. Readmission to the Boston Medical Center was also more common in 1998 patients (5.3% vs 0.5%; P <.0001). CONCLUSIONS: Early extubation and fast track protocols have resulted in earlier discharge from acute care facilities. However, the anticipated earlier return to home has been offset by the increased use of outpatient nursing services, discharges to extended care facilities, and hospital readmissions.

Coronary Artery Bypass↗
PubMed2001

Mortality among augmentation mammoplasty patients.

Much attention has focused on disease risks among women receiving silicone breast implants, but there has been little evaluation of their mortality experience. We undertook a retrospective cohort study of 13,488 women receiving cosmetic implants and 3,936 patients with other types of plastic surgery at 18 plastic surgery practices. After an average of 13 years of follow-up, deficits in overall mortality were found as compared with the general population (U.S. rates) for both implant [255 deaths; standardized mortality ratio (SMR) = 0.69, 95% confidence interval (CI) = 0.6-0.8] and comparison subjects (125 deaths; SMR = 0.58, 95% CI = 0.5-0.7). These findings indicate that patients seeking plastic surgery are in general healthier than their peers. Implant patients, however, experienced excess risks of death compared with the general population for brain cancer (SMR = 2.45) and suicide (SMR = 1.54). Internal analyses showed a higher overall mortality among the implant than among the comparison patients (relative risk = 1.27, 95% CI = 1.0-1.6). This overall excess reflected increases for respiratory tract (SMR = 3.03) and brain (SMR = 2.25) cancers and for suicide (SMR = 4.24).

Adult↗
PubMed2000

Effects of early inhaled beclomethasone therapy on tracheal aspirate inflammatory mediators IL-8 and IL-1ra in ventilated preterm infants at risk for bronchopulmonary dysplasia.

We tested the hypothesis that inhaled beclomethasone therapy for prevention of bronchopulmonary dysplasia (BPD) reduces pulmonary inflammation. As part of a randomized, placebo-controlled trial, interleukin-8 (IL-8) and interleukin-1 receptor antagonist (IL-1ra) concentrations in tracheal aspirates were measured as markers of pulmonary inflammation. On study days 1 (baseline), 8, 15, and day 28 of age, samples were obtained from enrolled infants (birth weights <1,251 g, gestational age <33 week, 3 to 14 days of age) who remained ventilated and had not received systemic glucocorticoid therapy. Cytokine levels (pg/microg of free secretory component of immunoglobulin A) were compared between groups. We determined whether baseline cytokine levels modified treatment effect regarding subsequent need for systemic glucocorticoid therapy or occurrence of BPD (age 28 days). Tracheal aspirates were obtained from 161 infants (77 receiving beclomethasone, 84 receiving placebo). Median IL-8 levels were lower in beclomethasone versus placebo infants on study days 8 (82.9 vs. 209.2, P < 0.01) and 15 (37.4 vs. 77.4, P < 0.03) after controlling for antenatal glucocorticoid therapy and maternal race. Median IL-1ra levels were lower in beclomethasone versus placebo infants only on study day 8 (86.5 vs. 153.3, P < 0.01). Fewer beclomethasone infants with baseline IL-8 levels in the interquartile range required systemic glucocorticoid therapy (beclomethasone 30.6% vs. placebo 65.8%, P < 0.01) or developed BPD (beclomethasone 42.4% vs. placebo 69.4%, P < 0.03). We conclude that early-inhaled beclomethasone therapy was associated with a reduction in pulmonary inflammation after 1 week of therapy. Beclomethasone-treated infants with moderately elevated baseline IL-8 levels received less subsequent systemic glucocorticoid therapy and had a lower incidence of BPD than nontreated infants.

Administration, Inhalation↗
PubMed2000

Fraud in medical research: an international survey of biostatisticians. ISCB Subcommittee on Fraud.

The characteristics of scientific fraud and its impact on medical research are in general not well known. However, the interest in the phenomenon has increased steadily during the last decade. Biostatisticians routinely work closely with physicians and scientists in many branches of medical research and have therefore unique insight into data. In addition, they have methodological competence to detect fraud and could be expected to have a professional interest in valid results. Biostatisticians therefore are likely to provide reliable information on the characteristics of fraud in medical research. The objective of this survey of biostatisticians, who were members of the International Society for Clinical Biostatistics, was to assess the characteristics of fraud in medical research. The survey was performed between April and July 1998. The participation rate was only 37%. We report the results because a majority (51%) of the participants knew about fraudulent projects, and many did not know whether the organization they work for has a formal system for handling suspected fraud or not. Different forms of fraud (e.g., fabrication and falsification of data, deceptive reporting of results, suppression of data, and deceptive design or analysis) had been observed in fairly similar numbers. We conclude that fraud is not a negligible phenomenon in medical research, and that increased awareness of the forms in which it is expressed seems appropriate. Further research, however, is needed to assess the prevalence of different types of fraud, as well as its impact on the validity of results published in the medical literature.

Biometry↗
PubMed2000

Breast cancer following augmentation mammoplasty (United States).

OBJECTIVE: Although clinical reports have raised concern that breast implants may either increase the risk of breast cancer or delay its diagnosis, epidemiologic studies have generally shown implant recipients to be at a reduced risk of subsequent breast cancer. A large retrospective cohort study was undertaken to clarify effects of cosmetic breast implantation. METHODS: Medical records of 13,488 women receiving cosmetic implants at 18 plastic surgery practices and a group of 3936 patients who received other types of plastic surgery at the same practices were reviewed and information abstracted. Questionnaires were sent to all subjects located as alive, with 71% being completed. Attempts were made to obtain medical verification for all reported cancers and to obtain death certificates for deceased subjects. RESULTS: A total of 136 breast cancers were observed among the breast implant patients. External analyses, using general population rates from the Surveillance, Epidemiology and End Results (SEER) program, resulted in 152.2 cases expected and a standardized incidence ratio (SIR) of 0.9 (95% CI 0.8-1.1). A comparable SIR was found for the other plastic surgery patients (SIR =1.0, 95% CI 0.7-1.2). Internal analyses, directly comparing the implant patients with the other plastic surgery patients, showed a RR of 0.8 (95% CI 0.6-1.1). In neither the external nor internal analyses was there any systematic variation in risk by age or calendar year of initial implant. Risk also did not vary by years of follow-up or by type of implant. Risk was not affected by exclusion of patients who received their implants following surgery for benign breast disease. Although breast tumors tended to be detected at a somewhat later stage among the breast implant than the comparison patients, the difference was not statistically significant, nor was there any significant difference in breast cancer mortality between the two groups. CONCLUSIONS: Breast implants do not appear to alter the risk of subsequent breast cancer.

Adult↗
PubMed2000

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Journal Article↗
PubMed2000

Characteristics of a population of women with breast implants compared with women seeking other types of plastic surgery.

Several previous studies have shown that breast implant patients demonstrate a number of differences compared with the general population. However, studies have not compared patients with breast implants with women receiving other types of plastic surgery, of interest because this latter group has been proposed as a comparison group for assessing the long-term health effects experienced by breast implant patients. Questionnaire data obtained from 7447 breast implant patients and 2203 patients with other types plastic surgery were collected during the course of a retrospective cohort study, to determine whether implant patients demonstrate different characteristics compared with a more restricted group of patients. In contrast to previous investigations that compared implant patients with the general population, distinctive differences with respect to family income, number of pregnancies, alcohol consumption, cigarette smoking, or histories of previous gynecologic operations or operations for benign breast disease were not found. However, implant patients were significantly more likely than other plastic surgery patients to be white, have low levels of education, have early ages at first birth, be thin, and be screened frequently for breast disease. Furthermore, implant patients reported somewhat greater use of exogenous hormones and familial histories of rheumatoid arthritis. These results support the notion that other plastic surgery patients are a more appropriate comparison group than women in the general population for studies of the health effects of breast implants; however, there continue to be distinctive characteristics possessed by breast implant patients, which need to be taken into account in an assessment of what disease effects can be uniquely attributed to silicone breast implants.

Adult↗
PubMed1999

The role of biostatistics in the prevention, detection and treatment of fraud in clinical trials.

Recent cases of fraud in clinical trials have attracted considerable media attention, but relatively little reaction from the biostatistical community. In this paper we argue that biostatisticians should be involved in preventing fraud (as well as unintentional errors), detecting it, and quantifying its impact on the outcome of clinical trials. We use the term 'fraud' specifically to refer to data fabrication (making up data values) and falsification (changing data values). Reported cases of such fraud involve cheating on inclusion criteria so that ineligible patients can enter the trial, and fabricating data so that no requested data are missing. Such types of fraud are partially preventable through a simplification of the eligibility criteria and through a reduction in the amount of data requested. These two measures are feasible and desirable in a surprisingly large number of clinical trials, and neither of them in any way jeopardizes the validity of the trial results. With regards to detection of fraud, a brute force approach has traditionally been used, whereby the participating centres undergo extensive monitoring involving up to 100 per cent verification of their case records. The cost-effectiveness of this approach seems highly debatable, since one could implement quality control through random sampling schemes, as is done in fields other than clinical medicine. Moreover, there are statistical techniques available (but insufficiently used) to detect 'strange' patterns in the data including, but no limited to, techniques for studying outliers, inliers, overdispersion, underdispersion and correlations or lack thereof. These techniques all rest upon the premise that it is quite difficult to invent plausible data, particularly highly dimensional multivariate data. The multicentric nature of clinical trials also offers an opportunity to check the plausibility of the data submitted by one centre by comparing them with the data from all other centres. Finally, with fraud detected, it is essential to quantify its likely impact upon the outcome of the clinical trial. Many instances of fraud in clinical trials, although morally reprehensible, have a negligible impact on the trial's scientific conclusions.

Biometry↗
PubMed1999

Early inhaled glucocorticoid therapy to prevent bronchopulmonary dysplasia.

BACKGROUND: The safety and efficacy of inhaled glucocorticoid therapy for asthma stimulated its use in infants to prevent bronchopulmonary dysplasia. We tested the hypothesis that early therapy with inhaled glucocorticoids would decrease the frequency of bronchopulmonary dysplasia in premature infants. METHODS: We conducted a randomized, multicenter trial of inhaled beclomethasone or placebo in 253 infants, 3 to 14 days old, born before 33 weeks of gestation and weighing 1250 g or less at birth, who required ventilation therapy. Beclomethasone was delivered in a decreasing dosage, from 40 to 5 microg per kilogram of body weight per day, for four weeks. The primary outcome measure was bronchopulmonary dysplasia at 28 days of age. Secondary outcomes included bronchopulmonary dysplasia at 36 weeks of postmenstrual age, the need for systemic glucocorticoid therapy, the need for bronchodilator therapy, the duration of respiratory support, and death. RESULTS: One hundred twenty-three infants received beclomethasone, and 130 received placebo. The frequency of bronchopulmonary dysplasia was similar in the two groups: 43 percent in the beclomethasone group and 45 percent in the placebo group at 28 days of age, and 18 percent in the beclomethasone group and 20 percent in the placebo group at 36 weeks of postmenstrual age. At 28 days of age, fewer infants in the beclomethasone group than in the placebo group were receiving systemic glucocorticoid therapy (relative risk, 0.6; 95 percent confidence interval, 0.4 to 1.0) and mechanical ventilation (relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0). CONCLUSIONS: Early beclomethasone therapy did not prevent bronchopulmonary dysplasia but was associated with lower rates of use of systemic glucocorticoid therapy and mechanical ventilation.

Administration, Inhalation↗
PubMed1999

Adrenal function in premature infants during inhaled beclomethasone therapy.

OBJECTIVE: We tested the hypothesis that inhaled beclomethasone therapy for prevention of bronchopulmonary dysplasia does not cause adrenal suppression. STUDY DESIGN: Infants receiving ventilatory support with birth weights </=1250 g and born at <33 weeks' gestation, age 3 to 14 days, were enrolled in a multicenter randomized trial to study the efficacy and safety of beclomethasone therapy versus placebo for prevention of bronchopulmonary dysplasia. Adrenal function was assessed on study day 21 (+/- 2 days) by determination of basal and stimulated plasma cortisol levels. Initially, cortisol response was assessed with insulin-induced hypoglycemia test (IIHT) (n = 63) until an interim analysis revealed insignificant cortisol response in both study groups. Thereafter, cosyntropin stimulation was used (n = 85). RESULTS: Beclomethasone therapy was associated with lower median basal cortisol levels (5 microg/dL beclomethasone, 6 microg/dL placebo, P =.04). IIHT revealed insignificant change in cortisol response within each group. Cortisol response to cosyntropin stimulation was similar for each group (17 microg/dL beclomethasone, 18 microg/dL placebo, P =.86). CONCLUSION: Beclomethasone therapy was associated with a small decrease in basal cortisol levels. There was no evidence of adrenal suppression in response to cosyntropin stimulation during beclomethasone therapy. Lack of cortisol response to hypoglycemia may reflect missed timing and/or decreased response of the premature infants' hypothalamic-pituitary-adrenal axis to hypoglycemia.

Administration, Inhalation↗
PubMed1999

Risk factors for a decline in upper body function following treatment for early stage breast cancer.

PURPOSE: To identify risk factors for a decline in upper body function following treatment for early stage breast cancer. METHODS: We conducted a cross-sectional observational study of 213 women > 55 years of age newly diagnosed with early stage breast cancer interviewed three to five months following their definitive surgery. Patients were classified as having impaired upper body function related to their breast cancer treatment if: 1) they reported having no difficulty in performing any of three tasks requiring upper body function (pushing or pulling large objects; lifting objects weighing more than 10 pounds; and reaching or extending arms above shoulder level) prior to treatment, but reported that any of these tasks were somewhat or very difficult in the four weeks prior to interview, or 2) they reported that performing any of the three tasks requiring upper body function was somewhat difficult prior to treatment, but reported that any of these tasks were very difficult in the four weeks prior to interview. RESULTS: In multiple logistic regression models, both the extent and type of primary tumor therapy and cardiopulmonary comorbidity were significantly associated with a decline in upper body function following breast cancer treatment. CONCLUSION: Given the critical importance of upper body function in maintaining independent living, clinicians should consider the functional consequences of treatment when they discuss treatment options and post-operative care with older women who have early stage breast cancer.

Age Factors↗
PubMed1999

Efficacy of recombinant human erythropoietin in the critically ill patient: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine whether the administration of recombinant human erythropoietin (rHuEPO) to critically ill patients in the intensive care unit (ICU) would reduce the number of red blood cell (RBC) transfusions required. DESIGN: A prospective, randomized, double-blind, placebo-controlled, multicenter trial. SETTING: ICUs at three academic tertiary care medical centers. PATIENTS: A total of 160 patients who were admitted to the ICU and met the eligibility criteria were enrolled in the study (80 into the rHuEPO group; 80 into the placebo group). INTERVENTIONS: Patients were randomized to receive either rHuEPO or placebo. The study drug (300 units/kg of rHuEPO or placebo) was administered by subcutaneous injection beginning ICU day 3 and continuing daily for a total of 5 days (until ICU day 7). The subsequent dosing schedule was every other day to achieve a hematocrit (Hct) concentration of >38%. The study drug was given for a minimum of 2 wks or until ICU discharge (for subjects with ICU lengths of stay >2 wks) up to a total of 6 wks (42 days) postrandomization. MEASUREMENTS AND MAIN RESULTS: The cumulative number of units of RBCs transfused was significantly less in the rHuEPO group than in the placebo group (p<.002, Kolmogorov-Smirnov test). The rHuEPO group was transfused with a total of 166 units of RBCs vs. 305 units of RBCs transfused in the placebo group. The final Hct concentration of the rHuEPO patients was significantly greater than the final Hct concentration of placebo patients (35.1+/-5.6 vs. 31.6+/-4.1; p<.01, respectively). A total of 45% of patients in the rHuEPO group received a blood transfusion between days 8 and 42 or died before study day 42 compared with 55% of patients in the placebo group (relative risk, 0.8; 95% confidence interval, 0.6, 1.1). There were no significant differences between the two groups either in mortality or in the frequency of adverse events. CONCLUSIONS: The administration of rHuEPO to critically ill patients is effective in raising their Hct concentrations and in reducing the total number of units of RBCs they require.

Critical Illness↗
PubMed1998

Cancer risk in women exposed to diethylstilbestrol in utero.

CONTEXT: The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers. As many as 3 million women in the United States may have been exposed to DES in utero. OBJECTIVE: To determine whether women exposed to DES in utero have a higher risk of cancer after an average of 16 years of follow-up. DESIGN: A cohort study with mailed questionnaires and medical record review of reported cancer outcomes. PARTICIPANTS: A cohort of 4536 DES-exposed daughters (of whom 81% responded) and 1544 unexposed daughters (of whom 79% responded) who were first identified in the mid-1970s. MAIN OUTCOME MEASURES: Cancer incidence in DES-exposed daughters compared with population-based rates and compared with cancer incidence in unexposed daughters. RESULTS: To date, DES-exposed daughters have not experienced an increased risk for all cancers (rate ratio, 0.96; 95% confidence interval [CI], 0.58-1.56) or for individual cancer sites, except for CCA. Three cases of vaginal CCA occurred among the exposed daughters, resulting in a standardized incidence ratio of 40.7 (95% CI, 13.1-126.2) in comparison with population-based incidence rates. The rate ratio for breast cancer was 1.18 (95% CI, 0.56-2.49); adjustment for known risk factors did not alter this result. CONCLUSIONS: Thus far, DES-exposed daughters show no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in our study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years.

Adenocarcinoma, Clear Cell↗
PubMed1998

A longitudinal study of body mass index and lens opacities. The Framingham Studies.

OBJECTIVE: The purpose of the study was to determine whether body mass index (BMI) is an independent risk factor for the development of nuclear, cortical, or posterior subcapsular lens opacities. DESIGN: A cohort study. PARTICIPANTS AND METHODS: Eye examinations were conducted on surviving members of the Framingham Heart Study Cohort from 1973 to 1975 (Framingham Eye Study I) and again from 1986 to 1989 (Framingham Eye Study II). Data from the Framingham Heart Study, including weight measurements collected biennially from 1948, were used to examine associations between BMI (mean BMI across examinations, slope of BMI over time, and fluctuations in BMI) and the development of lens opacities. This analysis included 714 individuals, aged 52-80 years, who were free of lens opacities at the first eye examination. MAIN OUTCOME MEASURES: Development of nuclear, cortical, and posterior subcapsular lens opacities. RESULTS: A total of 444 persons developed lens opacities during the approximately 13 years between eye examinations. In logistic regression analyses that controlled for age, sex, education, diabetes, and smoking, the risk of developing cortical opacity increased with higher BMI at the time of the first eye examination (P = 0.002). Risk of cortical opacities also increased, at a borderline level of significance, with higher average BMI (P = 0.09) across examinations and increasing BMI levels over time (P = 0.10). There was a strong association between increasing BMI over time and the development of posterior subcapsular lens opacities (P = 0.002). No associations were found for nuclear lens opacities. CONCLUSIONS: Although the mechanism explaining the association is unclear, these findings suggest that BMI, a potentially modifiable characteristic, is associated with the development of cortical and posterior subcapsular lens opacities.

Aged↗