Showing papers by "John F. Forbes published in 2005"
TL;DR: The 10-year and 15-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival are reported and it is found that the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.
6,309 citations
TL;DR: In patients presenting with severe limb ischaemia due to infra-inguinal disease and who are suitable for surgery and angioplasty, a bypass-surgery-first and a balloon-angioplastic-first strategy are associated with broadly similar outcomes in terms of amputation-free survival, and in the short-term, surgery is more expensive than angiopLasty.
1,612 citations
TL;DR: In postmenopausal women with endocrine-responsive breast cancer, adjuvant treatment with letrozole, as compared with tamoxifen, reduced the risk of recurrent disease, especially at distant sites.
Abstract: Background The aromatase inhibitor letrozole is a more effective treatment for metastatic breast cancer and more effective in the neoadjuvant setting than tamoxifen. We compared letrozole with tamoxifen as adjuvant treatment for steroid-hormone-receptor-positive breast cancer in postmenopausal women. Methods The Breast International Group (BIG) 1-98 study is a randomized, phase 3, double-blind trial that compared five years of treatment with various adjuvant endocrine therapy regimens in postmenopausal women with hormone-receptor-positive breast cancer: letrozole, letrozole followed by tamoxifen, tamoxifen, and tamoxifen followed by letrozole. This analysis compares the two groups assigned to receive letrozole initially with the two groups assigned to receive tamoxifen initially; events and follow-up in the sequential-treatment groups were included up to the time that treatments were switched. Results A total of 8010 women with data that could be assessed were enrolled, 4003 in the letrozole group and 4007 in the tamoxifen group. After a median follow-up of 25.8 months, 351 events had occurred in the letrozole group and 428 events in the tamoxifen group, with five-year disease-free survival estimates of 84.0 percent and 81.4 percent, respectively. As compared with tamoxifen, letrozole significantly reduced the risk of an event ending a period of disease-free survival (hazard ratio, 0.81; 95 percent confidence interval, 0.70 to 0.93; P=0.003), especially the risk of distant recurrence (hazard ratio, 0.73; 95 percent confidence interval, 0.60 to 0.88; P=0.001). Thromboembolism, endometrial cancer, and vaginal bleeding were more common in the tamoxifen group. Women given letrozole had a higher incidence of skeletal and cardiac events and of hypercholesterolemia. Conclusions In postmenopausal women with endocrine-responsive breast cancer, adjuvant treatment with letrozole, as compared with tamoxifen, reduced the risk of recurrent disease, especially at distant sites. (ClinicalTrials.gov number, NCT00004205.)
1,532 citations
TL;DR: This study provided support for the use of total hip replacement to treat displaced intracapsular hip fractures in fit, older patients and suggested that total hip replacements has long-term advantages over bipolar hemiarthroplasty.
Abstract: OBJECTIVES To compare internal fixation, bipolar hemiarthroplasty and total hip arthroplasty for the management of displaced subcapital fracture of the hip in previously fit patients of 60 years or older. DESIGN A prospective randomised clinical trial. SETTING This multicentre trial was carried out in 11 Scottish hospitals with acute orthopaedic trauma units. PARTICIPANTS The participants were 298 previously fit patients of 60 years or older with displaced subcapital hip fractures. INTERVENTIONS The three surgical interventions for comparison were reduction and fixation, bipolar hemiarthroplasty and total arthroplasty (total hip replacement). Participating surgeons elected to randomise patients either among all three types of operation (three-way randomisation) or just between fixation and hemiarthroplasty (two-way randomisation). MAIN OUTCOME MEASURES Clinical outcomes were mortality rates, reoperation rates and the complication rates associated with each procedure. Functional outcome was measured using a hip specific questionnaire [Johanson Hip Rating Questionnaire (HRQ)] and a general health status questionnaire [EuroQol 5 Dimensions (EQ-5D)]. Economic analysis compared the costs in the randomised groups of hospital treatment for the initial and subsequent admissions for up to 2 years. RESULTS Altogether, 207 patients were randomised among all three trial operations, and 91 between just fixation and bipolar hemiarthroplasty. There were no statistically significant differences in clinical outcomes, but confidence intervals (CIs) were wide. At 2 years fixation failure reached 37% among those allocated fixation and 39% had undergone further surgery. Further surgery rates after hemiarthroplasty and total hip replacement were 5% and 9%, respectively. The group allocated fixation had significantly worse HRQ and EQ-5D scores than both arthroplasty groups at 4 and 12 months. At 24 months the results still favoured arthroplasty, but the overall HRQ and EQ-5D scores were no longer statistically significant. Total hip replacement had the best patient-assessed outcome scores. At 24 months the overall HRQ and EQ-5D scores for total hip replacement were significantly better than for hemiarthroplasty. The mean costs for the initial episode ranged from 6384 pounds Sterling for fixation to 7633 pounds Sterling for total hip replacement. The cost differences were largely due to differences in theatre costs and the cost of prostheses and hardware. The cumulative cost over 2 years of hemiarthroplasty was around 3000 pounds Sterling lower than for fixation (95% CI 1227 pounds Sterling to 7192 pounds Sterling). Compared with total hip replacement, both fixation and hemiarthroplasty were characterised by increased costs arising from hip-replacement admissions. When total (initial episode and subsequent hip-related admissions) hip-related costs are compared, total hip replacement conferred a cost advantage of around 3000 pounds Sterling per patient (versus hemiarthroplasty, 95% CI -pounds Sterling 1400 to 7420 pounds Sterling). CONCLUSIONS In fit, older patients the results of the study show a clear advantage for arthroplasty over fixation; arthroplasty was more clinically effective and probably less costly over a 2-year period postsurgery. The results suggest that total hip replacement has long-term advantages over bipolar hemiarthroplasty, but these findings are less definite. This study provided support for the use of total hip replacement to treat displaced intracapsular hip fractures in fit, older patients. A larger trial comparing total versus hemiarthroplasty for these fractures could help to verify these findings. It would also be useful to know whether the findings of this study apply to patients aged 60 years or less who are usually treated with reduction and fixation. A clinical trial comparing arthroplasty versus fixation in patients older than 40 years would be a logical extension of the current study.
148 citations
TL;DR: This work has shown that L has been shown to be active in postmenopausal women with endocrine-responsive breast cancer for whom prior treatment with anti-estrogens has failed, as first-line treatment for metastatic breast cancer, and in patients who remain disease-free after five years of T.
Abstract: 511 Background: L has been shown to be active in postmenopausal women with endocrine-responsive breast cancer for whom prior treatment with anti-estrogens has failed, as first-line treatment for metastatic breast cancer, and in patients who remain disease-free after five years of T. The Primary Core Analysis (PCA) of BIG 1–98 comparing L (2.5 mg/d) vs. T (20 mg/d), both for 5 years, is planned for January 2005. Methods: 8,028 postmenopausal women with endocrine-responsive breast cancer were randomized to A:Tx5 years, B:Lx5, C:Tx2→Lx3, D:Lx2→Tx3; 1,835 to the 2-arm option (A or B March 1998 to March 2000) and 6,193 to the 4-arm option (April 1999 to May 2003). Planned sample size was 7,935 to provide 80% power to detect a 20% reduction in the risk of recurrence/relapse at the 5% (2-sided) significance level. The PCA was planned after 647 disease-free survival (DFS) events (counting events in arms C and D only up to the treatment switch + 30 days), with 2 interim analyses at 261 and 430 events. Results: The...
118 citations
TL;DR: The SBSS crude incidence rate is one of the highest in the world but age-adjusted rates, case fatality and relative risk for all stroke and stroke subtypes were not significantly different from the majority of previous studies.
Abstract: Background and Purpose— The purpose of this study was to determine the incidence and case fatality of stroke in a geographically defined region of Scotland, a nation with a high cardiovascular risk. Methods— All strokes occurring in residents of the Scottish Borders (population 106 352) were identified during a 24-month period from 1998 to 2000 using multiple overlapping methods of case-ascertainment. Standard criteria were used to define stroke and case fatality. Stroke subtypes were determined by computer tomography (CT) scan, MRI, or autopsy. Results— 790 strokes were identified; 596 were first-ever-in-a-lifetime strokes (FES). 91.1% of FES underwent CT scan and/or autopsy. The crude annual incidence rate per 100 000 per year was: 280 (95% CI, 258 to 304) overall, 197 (95% CI 179–217) cerebral infarction, 24 (95% CI 17–31) intracerebral haemorrhage, 11 (95% CI 7–16) subarachnoid haemorrhage and 49 (95% CI 40–59) undetermined stroke. 28 day FES case fatality was 15.9% (95% CI, 13.2 to 19.1) increasing to 26.3% (95% CI, 23.0 to 30.0) at 1 year. Comparing 18 previous worldwide incidence studies with the SBSS showed a similar relative risk of stroke incidence and case fatality for FES and FES subtypes. Conclusions— The SBSS crude incidence rate is one of the highest in the world but age-adjusted rates, case fatality and relative risk for all stroke and stroke subtypes were not significantly different from the majority of previous studies. Unlike cardiovascular disease, the Scottish risk of stroke would appear to be similar to other populations worldwide.
110 citations
TL;DR: CMF given concurrently (early, delayed or both) with tamoxifen was more effective than tamox ifen alone for patients with node-positive, endocrine-responsive breast cancer, supporting late administration of chemotherapy even after commencement of tamoxIFen.
19 citations
TL;DR: The availability of the new classifications in terms of their ability to explain variation and measure inequality in self-assessed health is unlikely to transform the understanding of the extent or the causes of socioeconomic inequality in health, but provides useful opportunities for sensitivity analysis.
Abstract: There is growing international interest in the choice of socioeconomic indicators for health research. This study used a combination of standard and novel methods to compare three occupation-based measures of social position in terms of their ability to explain variation and measure inequality in self-assessed health. The recently developed National Statistics Socioeconomic Classification (NS-SEC) is compared with its predecessor, the Registrar General's Social Class schema (RGSC), and with another occupation-based measure, the Cambridge Social Interaction and Stratification Scale (CAMSIS). With data from two large, independent, nationally representative samples of adults aged 16-64 living in private households in Scotland, logistic regression models are used to compare the classifications' ability to predict self-assessed health. Concentration indices are estimated to compare how well they capture inequality in self-assessed health. The study shows that all three classifications are strongly associated with self-assessed health, though the associations are heavily attenuated by adjustment for one another and for other measures of social position. Despite their differing theoretical bases, the three are closely related. No evidence is found that any of them systematically under- or overstate the extent of inequality in self-assessed health in either men or women, and the extent to which they measure independent dimensions of social inequality is questioned. It is concluded that the availability of the new classifications is unlikely to transform our understanding of the extent or the causes of socioeconomic inequality in health, but provides useful opportunities for sensitivity analysis.
15 citations
TL;DR: The proposed results unify the available results on input performance limitations and are useful for various purposes including selection of variables for the stabilizing layer, process design and formulation of the optimal controller design problem.
Abstract: In this paper, we characterize the achievable input performance for linear time invariant systems under feedback control. We provide analytical expressions for minimal input requirement for stabilization in both of the and optimal control frameworks. The achievable input performance primarily depends on the joint controllability and observability of unstable poles. These results are also extended to systems with time delay. It is shown that time delay poses no serious limitations on the achievable input performance for systems with slow instabilities and vice versa. The proposed results unify the available results on input performance limitations and are useful for various purposes including selection of variables for the stabilizing layer, process design and formulation of the optimal controller design problem.
10 citations
TL;DR: It is argued that Predefined rules can be used to trigger a debate within the Independent Data Monitoring and Safety Committee about early stopping, but the IDMC should retain the responsibility of assessing overall clinical benefit in making its recommendation.
Abstract: Early stopping of clinical trials in favour of a new treatment creates ethical and scientific difficulties, which are different from those associated with early stopping due to toxicity or futility. Two major breast cancer trials have recently taken such a decision, and the problem is relevant for several ongoing trials. Here we argue that such a decision should be taken with the utmost gravity and should be based on a clear overall clinical benefit for the new treatment, and not as an automatic response to crossing a predefined threshold. Predefined rules can be used to trigger a debate within the Independent Data Monitoring and Safety Committee (IDMC) about early stopping, but the IDMC should retain the responsibility of assessing overall clinical benefit in making its recommendation.
8 citations
08 Jun 2005
TL;DR: An approximate solution to the problem of performance assessment of decentralized controllers using a minimum variance (MV) benchmark is proposed by explicitly solving simple linear matrix equations.
Abstract: This paper deals with performance assessment of decentralized controllers using a minimum variance (MV) benchmark. The available MV benchmarks do not take the structure of the controller into account and can give overly optimistic estimates of achievable performance, when applied to systems under decentralized control. We propose an approximate solution to this problem obtained by explicitly solving simple linear matrix equations. As a special case of this general result, we also present an upper bound on the achievable performance for systems under multi-loop proportional-integral-derivative control. These results are useful for assessing the feasibility of significant performance improvement by retuning the decentralized controller and input-output pairing selection.
Journal Article•
TL;DR: The Medical Journal of Australia as mentioned in this paper conducted an analysis based on individual patient data from 14 diagnosed with early breast cancer, involved 194 tr 1995 in which chemotherapy and hormonal t evaluated alone and in combination for their effe rence, breast cancer mortality and total mortality.
Abstract: The Medical Journal of Australia ISSN: 0025729X 7 November 2005 183 9 447-448 ©The Medical Journal of Australia 2005 www.mja.com.au Editorials analysis, based on individual patient data from 14 diagnosed with early breast cancer, involved 194 tr 1995 in which chemotherapy and hormonal t evaluated alone and in combination for their effe rence, breast cancer mortality and total mortality. T with data from more trials than the earlier ove patients and more years of follow-up, provided n There is clear evidence of long-term benefits