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At least 469 records · Page 26Linked to original sources
PubMed1997

Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer.

BACKGROUND: The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed about 90% of the worldwide epidemiological evidence on the relation between risk of breast cancer and use of hormone replacement therapy (HRT). METHODS: Individual data on 52,705 women with breast cancer and 108,411 women without breast cancer from 51 studies in 21 countries were collected, checked, and analysed centrally. The main analyses are based on 53,865 postmenopausal women with a known age at menopause, of whom 17,830 (33%) had used HRT at some time. The median age at first use was 48 years, and 34% of ever-users had used HRT for 5 years or longer. Estimates of the relative risk of breast cancer associated with the use of HRT were obtained after stratification of all analyses by study, age at diagnosis, time since menopause, body-mass index, parity, and the age a woman was when her first child was born. FINDINGS: Among current users of HRT or those who ceased use 1-4 years previously, the relative risk of having breast cancer diagnosed increased by a factor of 1.023 (95% CI 1.011-1.036; 2p=0.0002) for each year of use; the relative risk was 1.35 (1.21-1.49; 2p=0.00001) for women who had used HRT for 5 years or longer (average duration of use in this group 11 years). This increase is comparable with the effect on breast cancer of delaying menopause, since among never-users of HRT the relative risk of breast cancer increases by a factor of 1.028 (95% CI 1.021-1.034) for each year older at menopause. 5 or more years after cessation of HRT use, there was no significant excess of breast cancer overall or in relation to duration of use. These main findings did not vary between individual studies. Of the many factors examined that might affect the relation between breast cancer risk and use of HRT, only a woman's weight and body-mass index had a material effect: the increase in the relative risk of breast cancer associated with long durations of use in current and recent users was greater for women of lower than of higher weight or body-mass index. There was no marked variation in the results according to hormonal type or dose but little information was available about long durations of use of any specific preparation. Cancers diagnosed in women who had ever used HRT tended to be less advanced clinically than those diagnosed in never-users. In North America and Europe the cumulative incidence of breast cancer between the ages of 50 and 70 in never-users of HRT is about 45 per 1000 women. The cumulative excess numbers of breast cancers diagnosed between these ages per 1000 women who began use of HRT at age 50 and used it for 5, 10, and 15 years, respectively, are estimated to be 2 (95% CI 1-3), 6 (3-9), and 12 (5-20). Whether HRT affects mortality from breast cancer is not known. INTERPRETATION: The risk of having breast cancer diagnosed is increased in women using HRT and increases with increasing duration of use. This effect is reduced after cessation of use of HRT and has largely, if not wholly, disappeared after about 5 years. These findings should be considered in the context of the benefits and other risks associated with the use of HRT.

Adult↗
PubMed2000

Reanalysis of stone manipulation prior to extracorporeal shock wave lithotripsy for management of upper ureteral calculi.

BACKGROUND: In situ extracorporeal shock wave lithotripsy (ESWL) for upper ureteral stones is controversial, in contrast to ESWL treatment of the majority of other renal calculi. Some urologists recommend retrograde mobilization of the calculi into the renal pelvis prior to ESWL as a routine procedure, while others report little advantage in manipulating a ureteral stone into the kidney before treatment by ESWL. To better understand this controversial issue, we reanalyzed clinical studies and the mechanism of stone disintegration in ESWL. METHODS: We performed a computerized MEDLINE search and manual bibliographic review of relevant peer reviewed reports from 1980 to 1998. Ten reports were analyzed with respect to stone-free rate and the important findings are summarized. RESULTS: Two of 10 data sets are statistically significant (p < 0.05) to verify a higher stone-free rate and another five reports also revealed that higher stone-free rates could be expected with retrograde stone manipulation into the renal collecting system before treatment by ESWL. CONCLUSIONS: Higher stone-free rates with retrograde stone manipulation into the renal collecting system before treatment by ESWL is statistically significant and theoretically supported by the mechanism of stone disintegration.

Humans↗
PubMed2001

Temperature, routine activities, and domestic violence: a reanalysis.

It was hypothesized that base rate differences in the number of complaints made during daylight and nighttime hours were responsible for a previously reported, nonlinear relationship between temperature and domestic violence. This hypothesis was tested by subjecting calls for service in 1987 and 1988 in Minneapolis, to moderator-variable regression analyses with controls for time of day, day of the week, season, and their interactions as well as linear trend, major holidays, public school closings, the first day of the month, and other weather variables. Temporal variables explained 75% of the variance in calls for service. As hypothesized, the base rate artifact was responsible for an apparent downturn in violence at high temperatures: Fewer complaints were received during afternoon hours, because they happen to be the warmest time of the day. The results were interpreted in terms of routine activity theory.

Adult↗
PubMed2001

Thyroid cancer following scalp irradiation: a reanalysis accounting for uncertainty in dosimetry.

In the 1940s and 1950s, over 20,000 children in Israel were treated for tinea capitis (scalp ringworm) by irradiation to induce epilation. Follow-up studies showed that the radiation exposure was associated with the development of malignant thyroid neoplasms. Despite this clear evidence of an effect, the magnitude of the dose-response relationship is much less clear because of probable errors in individual estimates of dose to the thyroid gland. Such errors have the potential to bias dose-response estimation, a potential that was not widely appreciated at the time of the original analyses. We revisit this issue, describing in detail how errors in dosimetry might occur, and we develop a new dose-response model that takes the uncertainties of the dosimetry into account. Our model for the uncertainty in dosimetry is a complex and new variant of the classical multiplicative Berkson error model, having components of classical multiplicative measurement error as well as missing data. Analysis of the tinea capitis data suggests that measurement error in the dosimetry has only a negligible effect on dose-response estimation and inference as well as on the modifying effect of age at exposure.

Biometry↗
PubMedDate not supplied

Reanalysis of carbamazepine and carbamazepine-epoxide pharmacokinetics after multiple dosing of extended release formulation.

PURPOSE: To model and re-evaluate the pharmacokinetics of carbamazepine (CBZ) and CBZ-10, 11-epoxide (CBZ-E) after 5 day b.i.d. dosing with either Carbatrol (extended-release beads) or Tegretol-XR (an osmotic pump tablet, an Oros tablet) using compartmental method. METHODS: Plasma concentration time profile data from 15 normal healthy adults received, in a randomized crossover fashion, Carbatrol (2 x 200 mg capsules), b.i.d. for 5 days and Tegretol-XR (400 mg), b.i.d. for 5 days were available for analysis from previous study. The compartmental kinetic parameters of CBZ and CBZ-E were simultaneously fitted by assuming: i) one compartment open model with zero order absorption with lag time, and first order elimination for CBZ and ii) one compartment open model with Michaelis-Menten formation with a sigmoidity factor, and first order elimination for CBZ-E. Time to 50% of CBZ plateau concentrations (TC50) was estimated and statistically compared between the two products. RESULTS: There was a good agreement between simulated and observed plasma concentrations. For CBZ, the fitted parameters were: the first order elimination rate constant (K(10)) 0.024 and 0.022 hr(-1), t(1/2) 27.3 and 30.3 hr, volume of central compartment (V(1) ) 1.119 and 1.160 L/kg, for Carbatrol and Tegretol-XR, respectively. For CBZ-E, the fitted parameters were: the first order elimination rate constant (K (30) ) 0.128 and 0.157 hr (-1), t (1/2) 6.1 and 5.1 hr, volume of central compartment (V (3) ) 0.728 and 0.644 L/kg, V (max) 0.085 and 0.076 mg/hr/kg, K (m) 28.639 and 33.138 mg/mL, for Carbatrol and Tegretol-XR, respectively. The fitted pharmacokinetic parameters of CBZ and CBZ-E were generally consistent with published values from previous studies. A minimal rise in CBZ-E concentrations was observed during the first 12 hours, the finding of which has not been reported before. Consequently, the CBZ-E plasma profiles appear as sigmoid curves and have a different shape compared to those of the CBZ profiles. The inclusion of the sigmoidity factor allowed flexibility in the fitting and optimized the simulation results. When compared to published literature of single dose data, the investigation of CBZ and CBZ-E pharmacokinetics from this study suggested that autoinduction might occur by the fifth day of dosing and might partly contribute to the sigmoidal shape of CBZ-E profiles. CONCLUSION: The fitted model well described the plasma profiles of both CBZ and CBZ-E. Carbatrol and Tegretol-XR were similar in their pharmacokinetics based on compartmental analysis.

Adult↗
PubMed2002

Bioinformatics and reanalysis of subtracted expressed sequence tags from the human ciliary body: Identification of novel biological functions.

PURPOSE: The ciliary body is largely known for its major roles in the regulation of aqueous humor secretion, intraocular pressure, and accommodation of the lens. In this review article we applied bioinformatics to re-examine hundreds of expressed sequence tags (ESTs) previously isolated by subtractive hybridization from a human ciliary body library [1]. The DNA sequences of these clones have been recently added to the web site of NEIBank. METHODS: DNA sequence comparisons of subtracted ESTs were performed against all entries in the last available release of the non-redundant database containing GenBank, EMBL, DDBJ and PDB sequences using the BlastN program accessed through NCBI's BLAST services on the internet (NCBI). Sequences were also compared and mapped using the Blast search program provided through the Internet by the Human Genome Project (UCSC). RESULTS: A total number of 284 independent ESTs were classified in 17 functional groups. Analysis of their relationships allowed to define the expression of five major groups of known genes: (i) protein synthesis, folding, secretion and degradation (20%); (ii) energy supply and biosynthesis (12%); (iii) contractility and cytoskeleton structure (6%); (iv) cellular signaling and cell cycle regulation (7%); and (v) nerve cell related tasks (2%), including neuropeptide processing and putative non-visual phototransduction and circadian rhythm control. The largest group contain unidentified sequences, a total of 105 sequences, accounting for 37% of ESTs. The unidentified sequences show similarity to genomic non-coding regions, or genes of unknown function. CONCLUSIONS: The most highly represented EST, correspond to myocilin, a gene involved in glaucoma. The data also confirms the secretory functions of the ciliary epithelium, and its high metabolism; the presence of a neuroendocrine peptidergic system presumably involved in the regulation of the intraocular pressure and/or aqueous humor secretion. Additional genes may be related to a non-visual phototransduction cascade and/or to circadian rhythms. Overall this initial group of subtracted ESTs can lead to uncover novel physiological functions of the ciliary body in normal and in disease, as well as novel candidate genes for ocular diseases.

Ciliary Body↗
PubMed2003

A randomized double blind, placebo controlled trial of topical Tripterygium wilfordii in rheumatoid arthritis: reanalysis using logistic regression analysis.

OBJECTIVE: To assess the efficacy of topical Tripterygium wilfordii (TW), a Chinese herbal therapy, in rheumatoid arthritis (RA). METHODS: A 6 week randomized double blind placebo controlled study of 61 patients with RA meeting American College of Rheumatology (ACR) criteria was conducted in China. The primary outcome was a modified ACR-20 response rate, analyzed by logistic regression analysis. RESULTS: The modified ACR-20 response rate differed significantly (topical TW 58% vs placebo 20%; p = 0.002). There was an 8.1-fold (95% CI 1.9-35.4) increase in the modified ACR-20 response for the TW compared to the placebo group, adjusted for age and erythrocyte sedimentation rate. CONCLUSION: Topical TW appears efficacious for the treatment of RA, but larger studies are needed.

Adult↗