266 results on '"Simes, RJ"'
Search Results
2. Approaches to prioritising research for clinical trial networks: a scoping review.
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Morton, RL, Tuffaha, H, Blaya-Novakova, V, Spencer, J, Hawley, CM, Peyton, P, Higgins, A, Marsh, J, Taylor, WJ, Huckson, S, Sillett, A, Schneemann, K, Balagurunanthan, A, Cumpston, M, Scuffham, PA, Glasziou, P, Simes, RJ, Morton, RL, Tuffaha, H, Blaya-Novakova, V, Spencer, J, Hawley, CM, Peyton, P, Higgins, A, Marsh, J, Taylor, WJ, Huckson, S, Sillett, A, Schneemann, K, Balagurunanthan, A, Cumpston, M, Scuffham, PA, Glasziou, P, and Simes, RJ
- Abstract
BACKGROUND: Prioritisation of clinical trials ensures that the research conducted meets the needs of stakeholders, makes the best use of resources and avoids duplication. The aim of this review was to identify and critically appraise approaches to research prioritisation applicable to clinical trials, to inform best practice guidelines for clinical trial networks and funders. METHODS: A scoping review of English-language published literature and research organisation websites (January 2000 to January 2020) was undertaken to identify primary studies, approaches and criteria for research prioritisation. Data were extracted and tabulated, and a narrative synthesis was employed. RESULTS: Seventy-eight primary studies and 18 websites were included. The majority of research prioritisation occurred in oncology and neurology disciplines. The main reasons for prioritisation were to address a knowledge gap (51 of 78 studies [65%]) and to define patient-important topics (28 studies, [35%]). In addition, research organisations prioritised in order to support their institution's mission, invest strategically, and identify best return on investment. Fifty-seven of 78 (73%) studies used interpretative prioritisation approaches (including Delphi surveys, James Lind Alliance and consensus workshops); six studies used quantitative approaches (8%) such as prospective payback or value of information (VOI) analyses; and 14 studies used blended approaches (18%) such as nominal group technique and Child Health Nutritional Research Initiative. Main criteria for prioritisation included relevance, appropriateness, significance, feasibility and cost-effectiveness. CONCLUSION: Current research prioritisation approaches for groups conducting and funding clinical trials are largely interpretative. There is an opportunity to improve the transparency of prioritisation through the inclusion of quantitative approaches.
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- 2022
3. Role of prognostic and predictive markers in cancer
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Simes, RJ, Lord, S, and Lee, C
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- 2008
4. Are clinical trial eligibility criteria representative of older patients with lung cancer? A population-based data linkage study
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Tang, M, Pearson, SA, Schaffer, AL, Lewis, CR, John, T, Simes, RJ, Lee, CK, Tang, M, Pearson, SA, Schaffer, AL, Lewis, CR, John, T, Simes, RJ, and Lee, CK
- Abstract
Objectives: Older adults constitute the majority of patients with lung cancer. However, they are under-represented in clinical trials as eligibility criteria often restrict enrolment based on comorbidities that are common with aging. We aimed to describe comorbidities relating to trial exclusion criteria in older adults with lung cancer, determine the proportion that would typically be excluded from trials, and examine the impact on treatment uptake. Materials and Methods: We conducted a population-based study of people aged ≥65 years diagnosed with metastatic lung cancer using linked data for clients of the Australian Government Department of Veterans' Affairs (2005–2015). We defined trial-typical patients based on the absence of comorbidities related to the following: inadequate organ (cardiac, renal, hepatic, marrow) function; cognitive dysfunction; poor performance status (PS); prior malignancy within 5 years. We report systemic therapy uptake within 3 months of diagnosis. Results: Our study included 677 patients (median age 84). Over half (53.4%) were not trial-typical, with the most common reasons being poor PS (37.5%), cardiac disease (19.2%), and prior cancer (12.9%). Eighty-two (12.1%) received systemic therapy. Patients with poor PS, cardiac disease, and dementia had lower treatment uptake rates. However, there was no significant difference in treatment uptake between trial-typical and non-trial-typical patients (13.4 vs 11.0%). Conclusion: More than half of older adults with advanced lung cancer would be typically excluded from trial participation. Future clinical trials of older adults need to consider broader eligibility criteria to better reflect this population to gain the best evidence for their care.
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- 2021
5. Cardiac assessment in Australian patients receiving (neo)adjuvant trastuzumab for HER2-positive early breast cancer: a population-based study
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Tang, M, Schaffer, AL, Kiely, BE, Daniels, B, Lee, CK, Simes, RJ, Pearson, SA, Tang, M, Schaffer, AL, Kiely, BE, Daniels, B, Lee, CK, Simes, RJ, and Pearson, SA
- Abstract
Purpose: Cardiac function assessment is important for detecting and managing trastuzumab-associated cardiotoxicity. Our study estimates rates and predictors of cardiac assessment among patients receiving trastuzumab for HER2-positive early breast cancer (HER2+EBC) in Australia. Methods: We conducted a retrospective cohort study of Australians initiating (neo)adjuvant trastuzumab for HER2+EBC between 1 January 2015 and 15 April 2019. We used administrative claims to determine the number of patients receiving guideline-recommended assessment, i.e. evidence of baseline cardiac assessment (between 120 days before and 30 days after trastuzumab initiation) and regular on-treatment cardiac assessments (at least every 120 days). We examined factors associated with baseline and regular on-treatment cardiac assessment. Results: Our study includes 5621 patients (median age 56 years), of whom 4984 (88.7%) had a baseline cardiac function test. Among 4280 patients with at least 12 months of follow-up, 2702 (63.1%) had guideline-recommended cardiac assessment. Rates of guideline-recommended assessment increased with later year of diagnosis (60.9% in 2015 vs 68.3% in 2018, OR 1.34, 95% CI 1.06–1.69). Patients with higher baseline comorbidities and greater socioeconomic disadvantage were less likely to have guideline-recommended cardiac assessment. Cardiac assessment practices varied by State/Territory. There was no association between baseline cardiac risk or anthracycline use and the likelihood of receiving guideline-recommended cardiac assessment. Conclusion: The majority of patients receiving (neo)adjuvant trastuzumab had guideline-recommended baseline and on-treatment cardiac assessment. Variations in cardiac assessment predominantly related to system-level factors, such as year of diagnosis and geography, rather than individual patient factors.
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- 2021
6. Relationship of low molecular weight fluorophore levels with clinical factors and fenofibrate effects in adults with type 2 diabetes
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Januszewski, AS, Chen, D, Scott, RS, O'Connell, RL, Aryal, NR, Sullivan, DR, Watts, GF, Taskinen, M-R, Barter, PJ, Best, JD, Simes, RJ, Keech, AC, Jenkins, AJ, Januszewski, AS, Chen, D, Scott, RS, O'Connell, RL, Aryal, NR, Sullivan, DR, Watts, GF, Taskinen, M-R, Barter, PJ, Best, JD, Simes, RJ, Keech, AC, and Jenkins, AJ
- Abstract
People with diabetes are at risk of chronic complications and novel biomarkers, such as Advanced glycation end-products (AGEs) may help stratify this risk. We assessed whether plasma low-molecular weight AGEs, also known as LMW-fluorophores (LMW-F), are associated with risk factors, predict complications, and are altered by fenofibrate in adults with type 2 diabetes. Plasma LMW-F were quantified at baseline, after six weeks fenofibrate, and one year post-randomisation to fenofibrate or placebo. LMW-F associations with existing and new composite vascular complications were determined, and effects of fenofibrate assessed. LMW-F correlated positively with age, glycated haemoglobin (HbA1c), pulse pressure, kidney dysfunction and inflammation; and negatively with urate, body mass index, oxidative stress and leptin, albeit weakly (r = 0.04-0.16, all p < 0.01). Independent determinants of LMW-F included smoking, diastolic blood pressure, prior cardiovascular disease or microvascular complications, Caucasian ethnicity, kidney function, HbA1c and diabetes duration (all p ≤ 0.01). Baseline LMW-F tertiles correlated with on-trial macrovascular and microvascular complications (trend p < 0.001) on univariate analyses only. Six weeks of fenofibrate increased LMW-F levels by 21% (p < 0.001). In conclusion, LMW-F levels correlate with many risk factors and chronic diabetes complications, and are increased with fenofibrate. LMW-F tertiles predict complications, but not independently of traditional risk factors.
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- 2021
7. Correction: Treatment patterns and survival in HER2-positive early breast cancer: a whole-of-population Australian cohort study (2007–2016) (British Journal of Cancer, (2019), 121, 11, (904-911), 10.1038/s41416-019-0612-5)
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Tang, M, Schaffer, A, Kiely, BE, Daniels, B, Simes, RJ, Lee, CK, Pearson, SA, Tang, M, Schaffer, A, Kiely, BE, Daniels, B, Simes, RJ, Lee, CK, and Pearson, SA
- Abstract
Since the publication of this paper the authors noticed that an error was made in coding some trastuzumab doses as being dispensed for metastatic disease, when they were actually dispensed for early stage disease. This affected the calculation of the overall recurrence rate and yearly disease-free survival rates, but does not alter the conclusions of the paper. The adjusted numbers differ from the published results by 0.1–0.2%. This has been corrected below. Recurrence By 30 June 2016, 1027 patients (7.0%) received at least one dispensing of trastuzumab for metastatic HER2-positive breast cancer. Figure 1 describes annual RFS rates for patients commencing trastuzumab between 2007 and 2016. (Figure presented.).
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- 2020
8. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial
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Keech, AC, Mitchell, P, Summanen, PA, O'Day, J, Davis, TME, Moffitt, MS, Taskinen, M-R, Simes, RJ, Tse, D, Williamson, E, Merrifield, A, Laatikainen, LT, d'Emden, MC, Crimet, DC, O'Connell, RL, and Colman, PG
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- 2007
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9. Treatment patterns and survival in HER2-positive early breast cancer: a whole-of-population Australian cohort study (2007–2016)
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Tang, M, Schaffer, A, Kiely, BE, Daniels, B, Simes, RJ, Lee, CK, Pearson, SA, Tang, M, Schaffer, A, Kiely, BE, Daniels, B, Simes, RJ, Lee, CK, and Pearson, SA
- Abstract
Background: Randomised clinical trials (RCTs) demonstrate that trastuzumab improves survival in patients with human epidermal growth factor 2-positive early breast cancer (HER2 + EBC), but real-world patients and clinical practice often differ from RCTs. We examine real-world treatment patterns and outcomes associated with trastuzumab for HER2 + EBC. Methods: We identified all Australians dispensed trastuzumab for HER2 + EBC between 1/1/2007 and 30/6/2016. We estimated the proportion of patients completing 12 months of treatment (defined as ≥350 days of exposure within 540 days of initiation). We estimated overall survival (OS) and recurrence-free survival (RFS) by using trastuzumab dispensing for metastatic breast cancer as a surrogate for recurrence. Results: Our study included 14,644 patients. Among patients with ≥540 days of follow-up (n = 11,903), 67.4% completed 12 months of trastuzumab. OS rates at 5 and 9 years were 92.7 and 87.9%, and RFS rates at 5 and 9 years were 86.8 and 81.4%, respectively. Patients who completed 12 months of trastuzumab had a 9-year OS rate of 90.2% compared with 86.2% among patients receiving <12 months of therapy (adjusted HR 0.71, 95% CI 0.62–0.81). Conclusions: Real-world HER2 + EBC patients are less likely to complete 12 months of trastuzumab than some clinical trial counterparts but have survival outcomes comparable to those reported in landmark RCTs.
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- 2019
10. Challenges of international oncology trial collaboration-a call to action.
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Tang, M, Joensuu, H, Simes, RJ, Price, TJ, Yip, S, Hague, W, Sjoquist, KM, Zalcberg, J, Tang, M, Joensuu, H, Simes, RJ, Price, TJ, Yip, S, Hague, W, Sjoquist, KM, and Zalcberg, J
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International collaboration in oncology trials has the potential to enhance clinical trial activity by expediting the recruitment of large patient populations, testing treatments in diverse populations and facilitating the study of rare tumours or specific molecular subtypes. However, a number of challenges continue to hinder the efficient and productive conduct of both commercial and non-commercial international clinical trials. These challenges include complex and burdensome regulatory requirements, the high cost of conducting trials, and logistical challenges associated with ethics review, drug supply and biospecimen collection and management. We propose solutions to promote oncology trial collaboration, such as regulatory reform, harmonisation of trial initiation and management processes and greater recognition and funding of academic (non-commercial) clinical trials. It is only through coordinated effort and leadership from researchers, regulators and those responsible for health systems that the full potential of international trial collaboration can be realised.
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- 2019
11. Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial
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Toner, GC, Stockler, MR, Boyer, MJ, Jones, M, Thomson, DB, Harvey, VJ, Olver, IN, Dhillon, H, McMullen, A, Gebski, VJ, Levi, JA, and Simes, RJ
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- 2001
- Full Text
- View/download PDF
12. Primary coronary angioplasty compared with intravenous thrombolytic therapy for acute myocardial infarction
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Grines, C, Patel, A, Zijlstra, F, Weaver, WD, Granger, C, Simes, RJ, Ellis, S, Betriu, A, Garcia, E, Grinfeld, L, Gibbons, R, Ribeiro, E, Ribichini, F, Akhras, F, Jones, M, Topol, E, Califf, R, Van der Werf, F, Ardissino, D, Armstrong, PW, Aylward, P, Bates, E, Beatt, K, Cheseboro, J, Col, J, Emanuelsson, H, Fuster, [No Value], Gibler, WB, Gore, J, Guerci, A, Hochman, J, Holmes, D, Kleiman, N, Morris, D, Neuhaus, K, Ohman, M, Pfisterer, M, Phillips, H, Rutsch, W, Vahanian, A, White, H, Stone, G, Browne, K, Marco, J, Rothbaum, D, O'Keefe, DRJ, Overlie, P, Donohue, B, and O'Neill, W
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Blood Loss, Surgical ,Myocardial Infarction ,Context (language use) ,law.invention ,Randomized controlled trial ,Fibrinolytic Agents ,RUPTURE ,law ,Recurrence ,Risk Factors ,Internal medicine ,medicine ,Humans ,REPERFUSION ,Myocardial infarction ,Angioplasty, Balloon, Coronary ,Coronary Artery Bypass ,Survival rate ,Stroke ,METAANALYSIS ,Aged ,Randomized Controlled Trials as Topic ,IMMEDIATE ANGIOPLASTY ,OLDER ,RISK ,OUTCOMES ,business.industry ,Mortality rate ,MORTALITY ,DEATH ,Thrombolysis ,Middle Aged ,medicine.disease ,TIME ,Survival Rate ,Treatment Outcome ,Relative risk ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Background Overviews of trials suggest that percutaneous transluminal coronary angioplasty (PTCA) may be more effective than thrombolysis. However, whether these effects are sustained beyond hospital discharge, and the extent to which the results are applicable to a broad cross section of patients and the wider community are unknown. We compared the effectiveness of primary PTCA and thrombolysis in acute myocardial infarction during a 6-month follow-up period.Methods Detailed individual patient data were collected from randomized trials commenced from 1989 to 1996 that compared primary PTCA with thrombolysis. Data were combined to produce estimates of relative reduction in events at 30 days and 6 months for the group and for predefined clinical subgroups. Treatment effects were also assessed in relation to several study-related factors.Results Eleven trials were identified. The mortality rate at 30 days was 4.3% for 1348 patients randomized to undergo PTCA, and 6.9% for 1377 patients assigned to thrombolytic therapy (relative risk [RR] 0.62, 95% Cl 0.44-0.86, P = .004). At 6 months, the mortality rate was 6.2% for PTCA and 8.2% for thrombolysis (RR 0.73, 95% Cl 0.55-0.98, P = .04). Combined death and reinfarction rates at 30 days were 7.0% for PTCA and 12.9% for thrombolysis, with a sustained effect at 6 months (RR 0.60, 95% Cl 0.48-0.75, P Conclusion In the context of these trials, primary PTCA was more effective than thrombolytic therapy in reducing death, reinfarction, and stroke, with the greatest absolute benefit in patients who were at the highest risk. These benefits appear to be sustained for 6 months. The effect of treatment varied significantly across the trials, and this raises issues about how widely the results can be applied.
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- 2003
13. Clinical trials and 'real‐world' medicine
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Simes Rj
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Clinical trial ,medicine.medical_specialty ,business.industry ,Family medicine ,Alternative medicine ,medicine ,General Medicine ,business - Published
- 2002
14. Low cholesterol and risk of non-coronary mortality
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Simes Rj
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Male ,medicine.medical_specialty ,Heart disease ,Poison control ,Coronary Disease ,Disease ,Cohort Studies ,Sex Factors ,Risk Factors ,Neoplasms ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Mortality ,Risk factor ,Randomized Controlled Trials as Topic ,business.industry ,Mortality rate ,Confounding ,Absolute risk reduction ,Confounding Factors, Epidemiologic ,medicine.disease ,Surgery ,Cholesterol ,Wounds and Injuries ,Female ,business ,Cohort study - Abstract
Based on a systematic review of over 20 cohort studies, a clear association exists, for both men and women, between particularly low cholesterol levels and the rate of non-coronary mortality. The excess in women appears mainly confined to non-cancer causes, particularly respiratory and digestive diseases, while there is also an excess of deaths from cancer seen in men with low cholesterol levels. Higher mortality rates from trauma, haemorrhagic stroke and cirrhosis have also been observed. Much of this association is known to be as a consequence of the disease with a fall in cholesterol levels seen after developing a variety of inflammatory diseases. However, the excess risk of non-coronary heart disease deaths is still apparent by excluding deaths within five years suggesting that effect-cause is not the only explanation. Confounding still remains the most likely explanation for the association with an underlying chronic disease or risk factor causing both the low cholesterol and the fatal event. However, there is still the possibility that some of the increased risk is due to the low cholesterol. This makes it important that appropriately controlled trials of both drug and dietary interventions demonstrate net clinical benefit among those with low levels of coronary risk before cholesterol-lowering strategies are adopted more widely in these groups.
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- 1994
15. Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer
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Jonker, DJ, Karapetis, CS, Harbison, C, O'Callaghan, CJ, Tu, D, Simes, RJ, Malone, DP, Langer, C, Tebbutt, N, Price, TJ, Shapiro, J, Siu, LL, Wong, RPW, Bjarnason, G, Moore, MJ, Zalcberg, JR, Khambata-Ford, S, Jonker, DJ, Karapetis, CS, Harbison, C, O'Callaghan, CJ, Tu, D, Simes, RJ, Malone, DP, Langer, C, Tebbutt, N, Price, TJ, Shapiro, J, Siu, LL, Wong, RPW, Bjarnason, G, Moore, MJ, Zalcberg, JR, and Khambata-Ford, S
- Abstract
BACKGROUND: Anti-EGFR antibody, cetuximab, improves overall survival (OS) in K-ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor receptor ligand epiregulin (EREG) gene expression may further predict cetuximab benefit. METHODS: Tumour samples from a phase III clinical trial of cetuximab plus best supportive care (BSC) vs BSC alone (CO.17) were analysed for EREG mRNA gene expression. Predictive effects of high vs low EREG on OS and progression-free survival (PFS) were examined for treatment-biomarker interaction. RESULTS: Both EREG and K-ras status were ascertained in 385 (193 cetuximab, 192 BSC) tumour samples. Within the high EREG and K-ras wild-type status ('co-biomarker')-positive group (n=139, 36%), median PFS was 5.4 vs 1.9 months (hazard ratio (HR) 0.31; P<0.0001), and median OS was 9.8 vs 5.1 months (HR 0.43; P<0.001) for cetuximab vs BSC, respectively. In the rest (n=246, 64%), PFS (HR 0.82; P=0.12) and OS (HR 0.90; P=0.45) were not significantly different. Test for treatment interaction showed a larger cetuximab effect on OS (HR 0.52; P=0.007) and PFS (HR 0.49; P=0.001) in the co-biomarker-positive group. CONCLUSION: In pre-treated K-ras wild-type status colorectal cancer, patients with high EREG gene expression appear to benefit more from cetuximab therapy compared with low expression. Epiregulin as a selective biomarker requires further evaluation.
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- 2014
16. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients
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Pignon, Jean-Pierre, le Maître, Aurélie, Maillard, Emilie, Bourhis, Jean, Amand, C, Armand, JP, Luboinski, B, Lefebvre, JL, Syz, N, Bernier, J, Budach, V, Forastiere, AA, Stewart, AA, Vokes, EE, Adelstein, DJ, Audry, H, Bachaud, JM, Bartelink, HG, Bezwoda, WR, Buffoli, A, Bhowmik, KT, Browman, GP, Calais, G, Campbell, BH, Carugati, A, Chalkidou, S, Clark, JR, Cohen, E, Collette, L, Dal Canton, O, Dalley, D, Despondt, J, Désigné, L, Deszcz-Thomas, A, Di Blasio, B, Dobrowsky, W, Domenge, C, Eschwege, F, Evensen, JF, Fallai, C, Fischer, JJ, Forastière, AA, Fountzilas, G, Fu, KK, Gedouin, D, Guérin, S, Geara, F, Giglio, R, Gupta, NK, Haddad, E, Haffy, BG, Hasegawa, Y, Hill, C, Horiot, JC, Horiuchi, M, Houghton, J, Huguenin, P, Jan, P, Jaulerry, Ch, Jeremic, B, Jouffroy, T, Jortay, A, Kapstad, B, Kowalski, LP, Kramer, S, Krishnamurthi, KS, Kumar, S, Laramore, G, Lartigau, E, Leong, T, Lewin, F, Luboinski, M, Maipang, T, Martin, M, Mazeron, JJ, Merlano, M, Metha, S, Molinari, R, Monson, K, Morita, K, Mueller, RP, Murias, A, Mosseri, V, Numico, G, Olmi, P, O'Sullivan, B, Overgaard, Jens, Paccagnella, A, Pajak, T, Parvinen, LM, Pearlman, NW, Rao, RS, Richard, JM, Rufibach, K, Sanchiz, F, Sancho-Garnier, H, Schuller, DE, Shanta, V, Simes, RJ, Smid, L, Stewart, LA, Staar, S, Strojan, P, Stuetzer, H, Szpirglas, H, Schwaab, G, Takaku, S, Taylor, SG, Tobias, JS, Toohill, RJ, Volling, P, Weissler, MC, Wendt, T, Wernecke, KD, Widder, J, Wolf, GT, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Antineoplastic Agents ,Meta-Analysis as Topic ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Randomized Controlled Trials as Topic ,Chemotherapy ,business.industry ,Carcinoma ,Hazard ratio ,Head and neck cancer ,Induction chemotherapy ,Hematology ,medicine.disease ,Head and neck squamous-cell carcinoma ,Combined Modality Therapy ,Radiation therapy ,DAHANCA ,Treatment Outcome ,Squamous Cell ,Head and Neck Neoplasms ,Concomitant ,Carcinoma, Squamous Cell ,business - Abstract
BACKGROUND: Our previous individual patient data (IPD) meta-analysis showed that chemotherapy improved survival in patients curatively treated for non-metastatic head and neck squamous cell carcinoma (HNSCC), with a higher benefit with concomitant chemotherapy. However the heterogeneity of the results limited the conclusions and prompted us to confirm the results on a more complete database by adding the randomised trials conducted between 1994 and 2000.METHODS: The updated IPD meta-analysis included trials comparing loco-regional treatment to loco-regional treatment+chemotherapy in HNSCC patients and conducted between 1965 and 2000. The log-rank-test, stratified by trial, was used to compare treatments. The hazard ratios of death were calculated.RESULTS: Twenty-four new trials, most of them of concomitant chemotherapy, were included with a total of 87 trials and 16,485 patients. The hazard ratio of death was 0.88 (pCONCLUSION: The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.
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- 2009
17. Fenofibrate intervention and event lowering in diabetes (FIELD) study: baseline characteristics and short-term effects of fenofibrate [ISRCTN64783481]
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Scott, R, Best, J, Forder, P, Taskinen, M-R, Simes, J, Barter, P, Keech, A, Colman, P, D'Emden, M, Davis, T, Drury, P, Ehnholm, C, Glasziou, P, Hunt, D, Kesaniemi, YA, Laakso, M, Simes, RJ, Sullivan, D, Whiting, M, Ansquer, J-C, Fraitag, B, Anderson, N, Hankey, G, Lehto, S, Mann, S, Romo, M, Li, LP, Hennekens, C, MacMahon, S, Pocock, S, Tonkin, A, Wilhelmsen, L, Akauola, H, Alford, F, Beinart, I, Bohra, S, Boyages, S, Connor, H, Darnell, D, Davoren, P, Lepre, F, De Looze, F, Duffield, A, Fassett, R, Flack, J, Fulcher, G, Grant, S, Hamwood, S, Harmelin, D, Jackson, R, Jeffries, W, Kamp, M, Kritharides, L, Mahar, L, McCann, V, McIntyre, D, Moses, R, Newnham, H, Nicholson, G, O'Brien, R, Park, K, Petrovsky, N, Phillips, P, Pinn, G, Simmons, D, Stanton, K, Stuckey, B, Sullivan, DR, Suranyi, M, Suthers, M, Tan, Y, Templer, M, Topliss, D, Waites, JH, Watts, G, Welborn, T, Wyndham, R, Haapamaki, H, Kesaniemi, A, Lahtela, J, Levanen, H, Saltevo, J, Sodervik, H, Taskinen, M, Vanhala, M, Baker, J, Burton, A, Dixon, P, Doran, J, Dunn, P, Graham, N, Hamer, A, Hedley, J, Lloyd, J, Manning, P, McPherson, I, Morris, S, Renner, C, Smith, R, Wackrow, M, Young, S, Alard, F, Alcoe, J, Allan, C, Amerena, J, Anderson, R, Arnold, N, Arsov, T, Ashby, D, Atkinson, C, Badhni, L, Balme, M, Barton, D, Batrouney, B, Beare, C, Beattie, T, Beggs, J, Bendall, C, Benz, A, Bond, A, Bradfield, R, Bradshaw, J, Brearley, S, Bruce, D, Burgess, J, Butler, J, Callary, M, Campbell, J, Chambers, K, Chow, J, Chow, S, Ciszek, K, Clifton, P, Clifton-Bligh, P, Clowes, V, Coates, P, Cocks, C, Cole, S, Colquhoun, D, Correcha, M, Costa, B, Coverdale, S, Croft, M, Crowe, J, Dal Sasso, S, Davis, W, Dunn, J, Edwards, S, Elder, R, El-Kaissi, S, Emery, L, England, M, Farouque, O, Fernandez, M, Fitzpatrick, B, Francis, N, Freeman, P, Fuller, A, Gale, D, Gaylard, V, Gillzan, C, Glatthaar, C, Goddard, J, Grange, V, Greenaway, T, Griffin, J, Grogan, A, Guha, S, Gustafson, J, Hamblin, PS, Hannay, T, Hardie, C, Harper, A, Hartl, G, Harvey, A, Havlin, S, Haworth, K, Hay, P, Hay, L, Heenan, B, Hesketh, R, Heyworth, A, Hines, M, Hockings, G, Hodge, A, Hoffman, L, Hoskin, L, Howells, M, Hunt, A, Inder, W, Jackson, D, Jovanovska, A, Kearins, K, Kee, P, Keen, J, Kilpatrick, D, Kindellan, J, Kingston-Ray, M, Kotowicz, M, Lassig, A, Layton, M, Lean, S, Lim, E, Long, F, Lucas, L, Ludeman, D, Ludeman-Robertson, C, Lyall, M, Lynch, L, Maddison, C, Malkus, B, Marangou, A, Margrie, F, Matthiesson, K, Matthiesson, J, Maxwell, S, McCarthy, K, McElduff, A, Mckee, H, McKenzie, J, McLachan, K, McNair, P, Meischke, M, Miller, AMC, Morrison, B, Morton, A, Mossman, W, Mowat, A, Muecke, J, Murie, P, Murray, S, Nadorp, P, Nair, S, Nairn, J, Nankervis, A, Narayan, K, Nattrass, N, Ngui, J, Nicholls, S, Nicholls, V, Nye, JA, Nye, E, O'Neal, D, O'Neill, M, O'Rourke, S, Pearse, J, Pearson, C, Phillips, J, Pittis, L, Playford, D, Porter, L, Portley, R, Powell, M, Preston, C, Pringle, S, Quinn, WA, Raffaele, J, Ramnath, G, Ramsden, J, Richtsteiger, D, Roffe, S, Rosen, S, Ross, G, Ross, Z, Rowe, J, Rumble, D, Ryan, S, Sansom, J, Seymour, C, Shanahan, E, Shelly, S, Shepherd, J, Sherman, G, Siddall, R, Silva, D, Simmons, S, Simpson, R, Sinha, A, Slobodniuk, R, Smith, M, Smith, P, Smith, S, Smith-Orr, V, Snow, J, Socha, L, Stack, T, Steed, K, Steele, K, Stephensen, J, Stevens, P, Stewart, G, Stewart, R, Strakosch, C, Sullivan, M, Sunder, S, Sunderland, J, Tapp, E, Taylor, J, Thorn, D, Tolley, A, Torpy, D, Truran, G, Turner, F, Turner, J, Van de Velde, J, Varley, S, Wallace, J, Walsh, J, Walshe, J, Ward, G, Watson, B, Watson, J, Webb, A, Werner, F, White, E, Whitehouse, A, Whitehouse, N, Wigg, S, Wilkinson, J, Wilmshurst, E, Wilson, D, Wittert, G, Wong, B, Wong, M, Worboys, S, Wright, S, Wu, S, Yarker, J, Yeo, M, Young, K, Youssef, J, Yuen, R, Zeimer, H, Ziffer, RW, Aura, A, Friman, A, Hanninen, J, Henell, J, Hyvarinen, N, Ikonen, M, Itkonen, A, Jappinen, J, Jarva, A, Jerkkola, T, Jokinen, V, Juutilainen, J, Kahkonen, H, Kangas, T, Karttunen, M, Kauranen, P, Kortelainen, S, Koukkunen, H, Kumpulainen, L, Laitinen, T, Laitinen, M, Lehto, R, Leinonen, E, Lindstron-Karjalainen, M, Lumiaho, A, Makela, J, Makinen, K, Mannermaa, L, Mard, T, Miettinen, J, Naatti, V, Paavola, S, Parssinen, N, Ripatti, J, Ruotsalainen, S, Salo, A, Siiskonen, M, Soppela, A, Starck, J, Suonranta, I, Ukkola, L, Valli, K, Virolainen, J, Allan, P, Arnold, W, Bagg, W, Balfour, K, Ball, T, Ballantine, B, Ballantyne, C, Barker, C, Bartley, F, Berry, E, Braatvedt, G, Campbell, A, Clarke, T, Clarke, R, Claydon, A, Clayton, S, Cresswell, P, Cutfield, R, Daffurn, J, Delahunt, J, Dissnayake, A, Eagleton, C, Ferguson, C, Florkowski, C, Fry, D, Giles, P, Gluyas, M, Grant, C, Guile, P, Guolo, M, Hale, P, Hammond, M, Healy, P, Hills, M, Hinge, J, Holland, J, Hyne, B, Ireland, A, Johnstone, A, Jones, S, Kerr, G, Kerr, K, Khant, M, Krebs, J, Law, L, Lydon, B, MacAuley, K, McEwan, R, McGregor, P, McLaren, B, McLeod, L, Medforth, J, Miskimmin, R, Moffat, J, Pickup, M, Prentice, C, Rahman, M, Reda, E, Ross, C, Ryalls, A, Schmid, D, Shergill, N, Snaddon, A, Snell, H, Stevens, L, Waterman, A, Watts, V, Jayne, K, Keirnan, E, Newman, P, Ritchie, G, Rosenfeld, A, Beller, E, Gebski, V, Pillai, A, Anderson, C, Blakesmith, S, Chan, S-Y, Czyniewski, S, Dobbie, A, Doshi, S, Dupuy, A, Eckermann, S, Edwards, M, Fields, N, Flood, K, Ford, S, French, C, Gillies, S, Greig, C, Groshens, M, Gu, J, Guo, Y, Hague, W, Healy, S, Hones, L, Hossain, Z, Howlett, M, Lee, J, Li, L-P, Matthews, T, Micallef, J, Martin, A, Minns, I, Nguyen, A, Papuni, F, Patel, A, Pike, R, Pena, M, Pinto, K, Schipp, D, Schroeder, J, Sim, B, Sodhi, C, Sourjina, T, Sutton, C, Taylor, R, Vlagsma, P, Walder, S, Walker, R, Wong, W, Zhang, J, Zhong, B, Kokkonen, A, Narva, P, Niemi, E-L, Syrjanen, A-M, Lintott, C, Tirimacco, R, Kajosaari, M, Raman, L, Sundvall, J, Tukianen, M, Crimet, D, Sirugue, I, and Aubonnet, P
- Subjects
Male ,Cardiac & Cardiovascular Systems ,Endocrinology, Diabetes and Metabolism ,Atorvastatin ,Coronary Disease ,Fibrate ,SECONDARY PREVENTION ,ATORVASTATIN ,law.invention ,Placebos ,Randomized controlled trial ,Fenofibrate ,law ,Myocardial infarction ,1102 Cardiorespiratory Medicine and Haematology ,Finland ,Original Investigation ,Hypolipidemic Agents ,PLASMA ,CHOLESTEROL ,Middle Aged ,INSULIN ,CARDIOVASCULAR-DISEASE ,Cardiovascular Diseases ,Female ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,medicine.drug ,medicine.medical_specialty ,medicine.drug_class ,Diabetes Complications ,Endocrinology & Metabolism ,Double-Blind Method ,Internal medicine ,Diabetes mellitus ,Intervention (counseling) ,medicine ,Humans ,CORONARY-HEART-DISEASE ,Obesity ,Triglycerides ,Aged ,Apolipoproteins B ,Bezafibrate ,Science & Technology ,business.industry ,Cholesterol, HDL ,Australia ,Cholesterol, LDL ,medicine.disease ,BEZAFIBRATE ,FIELD Study Investigators ,MYOCARDIAL-INFARCTION ,Diabetes Mellitus, Type 2 ,Cardiovascular System & Hematology ,Cardiovascular System & Cardiology ,business ,HIGH-DENSITY-LIPOPROTEIN ,New Zealand - Abstract
Objective The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study is examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates in patients with diabetes mellitus. This article describes the trial's run-in phase and patients' baseline characteristics. Research design and methods FIELD is a double-blind, placebo-controlled trial in 63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus. Patients were to have no indication for lipid-lowering therapy on randomization, but could start these or other drugs at any time after randomization. Follow-up in the study was to be for a median duration of not less than 5 years and until 500 major coronary events (fatal coronary heart disease plus nonfatal myocardial infarction) had occurred. Results About 2100 patients (22%) had some manifestation of cardiovascular disease (CVD) at baseline and thus high risk status. Less than 25% of patients without CVD had a (UKPDS determined) calculated 5-year CHD risk of 30), most were men, two-thirds were aged over 60 years, and substantial proportions had NCEP ATP III features of the metabolic syndrome independent of their diabetes, including low HDL (60%), high blood pressure measurement or treatment for hypertension (84%), high waist measurement (68%), and raised triglycerides (52%). After a 6-week run-in period before randomisation with all participants receiving 200 mg comicronized fenofibrate, there were declines in total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL cholesterol (6.5%). Conclusion The study will show the effect of PPAR-alpha agonist action on CHD and other vascular outcomes in patients with type 2 diabetes including substantial numbers with low to moderate CVD risk but with the various components of the metabolic syndrome. The main results of the study will be reported in late 2005.
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- 2005
18. The need for a large-scale trial of fibrate therapy in diabetes: The rationale and design of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. [ISRCTN64783481]
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Barter, P, Best, J, Colman, P, d'Emden, M, Davis, T, Drury, P, Ehnholm, C, Glasziou, P, Hunt, D, Keech, A, Laakso, M, Scott, R, Simes, RJ, Sullivan, D, Taskinen, M-R, Whiting, M, Ansquer, J-C, Fraitag, B, Anderson, N, Hankey, G, Lehto, S, Mann, S, Romo, M, Li, LP, Akauola, H, Alford, F, Beinart, I, Bohra, S, Boyages, S, Connor, H, Darnell, D, Davoren, P, Lepre, F, De Looze, D, Duffield, A, Fassett, R, Flack, J, Fulcher, G, Grant, S, Hamwood, S, Harmelin, D, Jackson, R, Jeffries, W, Kamp, M, Kritharides, L, Mahar, L, McCann, V, McIntyre, D, Moses, R, Newnham, H, Nicholson, G, O'Brien, R, Park, K, Petrovsky, N, Phillips, P, Pinn, G, Simmons, D, Stanton, K, Stuckey, B, Sullivan, DR, Suranyi, M, Suthers, M, Tan, Y, Templer, M, Topliss, D, Waites, JH, Watts, G, Welborn, T, Wyndham, R, Haapamaki, H, Kesaniemi, A, Lahtela, J, Levanen, H, Saltevo, J, Sodervik, H, Taskinen, M, and Vanhala, M
- Abstract
Background: Fibrates correct the typical lipid abnormalities of type 2 diabetes mellitus, yet no study, to date, has specifically set out to evaluate the role of fibrate therapy in preventing cardiovascular events in this setting. Methods: Subjects with type 2 diabetes, aged 50-75 years, were screened for eligibility to participate in a long-term trial of comicronized fenofibrate 200 mg daily compared with matching placebo to assess benefits of treatment on the occurrence of coronary and other vascular events. People with total cholesterol levels 3.0-6.5 mmol/L plus either a total-to-HDLc ratio >4.0 or triglyceride level >1.0 mmol /L with no clear indication for lipid-modifying therapy were eligible. Results: A total of 9795 people were randomized into the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. All received dietary advice, followed by a 6-week single-blind placebo run-in, then a 6-week active run-in period before randomization. Participants are being followed up every 6 months for outcome events and safety assessments. The study is designed to yield at least 500 coronary events (primary endpoint: first nonfatal myocardial infarction or coronary death) over 5 years, to have 80% power to identify as statistically significant at 2P = 0.05 a 22% reduction in such events, using intention-to-treat methods. Conclusions: Type 2 diabetes is the most common endocrine disorder worldwide, and its prevalence is increasing. The current evidence about use of fibrates in type 2 diabetes, from around 2000 people treated, will increase with FIELD to evidence from around 12000. FIELD will establish the role of fenofibrate treatment in reducing cardiovascular risk in people with type 2 diabetes. The main results are expected to be available in late 2005. © 2004 The FIELD Study Investigators; licensee BioMed Central Ltd.
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- 2004
19. Prognostic impact and the relevance of PTEN copy number alterations in patients with advanced colorectal cancer (CRC) receiving bevacizumab
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Price, TJ, Hardingham, JE, Lee, CK, Townsend, AR, Wrin, JW, Wilson, K, Weickhardt, A, Simes, RJ, Murone, C, Tebbutt, NC, Price, TJ, Hardingham, JE, Lee, CK, Townsend, AR, Wrin, JW, Wilson, K, Weickhardt, A, Simes, RJ, Murone, C, and Tebbutt, NC
- Abstract
Loss of phosphatase and tensin homologue (PTEN) expression may be prognostic in colorectal cancer (CRC) and may have a correlation with vascular endothelial growth factor (VEGF) expression via hypoxia-inducible factor 1 (HIF-1) alpha, and the PI3K/mTOR pathways. We therefore have explored the prognostic association of PTEN loss and the potential that PTEN loss may be predictive of outcome with bevacizumab. Patients enrolled in the AGITG MAX trial, a randomized Phase III trial of capecitabine (C) +/- bevacizumab (B) (+/- mitomycin C [M]) with available tissues were analyzed for PTEN expression (loss vs. no loss) as assessed using a Taqman® copy number assay (CNA). Of the original 471 patients enrolled, tissues from 302 (64.1%) patients were analyzed. PTEN loss was observed in 38.7% of patients. There was no relationship between PTEN loss and KRAS or BRAF mutation. PTEN status was not prognostic for progression-free survival (PFS) or overall survival (OS) in multivariate analyses adjusting for other baseline factors; loss versus no loss PFS hazard ratio (HR) 0.9 (0.7-1.16), OS HR 1.04 (0.79-1.38). PTEN was not prognostic when assessed by KRAS and BRAF status. By using the comparison of C versus CB+CBM, PTEN status was not significantly predictive of the effectiveness of B for PFS or OS. PTEN status was not prognostic for survival in advanced colorectal cancer, irrespective of KRAS or BRAF status. PTEN status did not significantly predict different benefit with bevacizumb therapy.
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- 2013
20. Clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction
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Zijlstra, F, Patel, A, Jones, M, Grines, Cl, Ellis, S, Garcia, E, Grinfeld, L, Gibbons, Rj, Ribeiro, Ee, Ribichini, Flavio Luciano, Granger, C, Akhras, F, Weaver, Wd, and Simes, Rj
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- 2002
21. Cholesterol-lowering therapy with pravastin in patients with average cholesterol levels and established ischaemic heart disease: is it cost-effective?
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Glasziou, PP, Eckermann, SD, Mulray, SE, Simes, RJ, Martin, AJ, Kirby, AC, Hall, JP, Caleo, S, White, HD, and Tonkin, AM
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General & Internal Medicine - Published
- 2002
22. Quality-adjusted survival as an end point in breast cancer trials
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Martin, AJ, primary and Simes, RJ, additional
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- 2013
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23. Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: Baseline characteristics and short-term effects of fenofibrate [ISRCTN64783481]
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Keech, AC, Scott, R, Best, J, Forder, P, Taskinen, MR, Simes, J, Barter, P, Colman, P, d'Emden, M, Davis, T, Drury, P, Ehnholm, C, Glasziou, P, Hunt, D, Kesaniemi, YA, Laakso, M, Simes, RJ, Sullivan, D, Whiting, M, Ansquer, JC, Fraitag, B, Anderson, N, Hankey, G, Lehto, S, Mann, S, Romo, M, Li, LP, Hennekens, C, MacMahon, S, Pocock, S, Tonkin, A, Wilhelmsen, L, Akauola, H, Alford, F, Beinart, I, Bohra, S, Boyages, S, Connor, H, Darnell, D, Davoren, P, Lepre, F, De Looze, F, Duffield, A, Fassett, R, Flack, J, Fulcher, G, Grant, S, Hamwood, S, Harmelin, D, Jackson, R, Jeffries, W, Kamp, M, Kritharides, L, Mahar, L, McCann, V, McIntyre, D, Moses, R, Newnham, H, Nicholson, G, O'Brien, R, Park, K, Petrovsky, N, Phillips, P, Pinn, G, Simmons, D, Stanton, K, Stuckey, B, Sullivan, DR, Suranyi, M, Suthers, M, Tan, Y, Templer, M, Topliss, D, Waites, JH, Watts, G, Welborn, T, Wyndham, R, Haapamaki, H, Kesaniemi, A, Lahtela, J, Levanen, H, Saltevo, J, Sodervik, H, Taskinen, M, Vanhala, M, Baker, J, Burton, A, Dixon, P, Doran, J, Dunn, P, Graham, N, Hamer, A, Hedley, J, Lloyd, J, Manning, P, McPherson, I, Morris, S, Keech, AC, Scott, R, Best, J, Forder, P, Taskinen, MR, Simes, J, Barter, P, Colman, P, d'Emden, M, Davis, T, Drury, P, Ehnholm, C, Glasziou, P, Hunt, D, Kesaniemi, YA, Laakso, M, Simes, RJ, Sullivan, D, Whiting, M, Ansquer, JC, Fraitag, B, Anderson, N, Hankey, G, Lehto, S, Mann, S, Romo, M, Li, LP, Hennekens, C, MacMahon, S, Pocock, S, Tonkin, A, Wilhelmsen, L, Akauola, H, Alford, F, Beinart, I, Bohra, S, Boyages, S, Connor, H, Darnell, D, Davoren, P, Lepre, F, De Looze, F, Duffield, A, Fassett, R, Flack, J, Fulcher, G, Grant, S, Hamwood, S, Harmelin, D, Jackson, R, Jeffries, W, Kamp, M, Kritharides, L, Mahar, L, McCann, V, McIntyre, D, Moses, R, Newnham, H, Nicholson, G, O'Brien, R, Park, K, Petrovsky, N, Phillips, P, Pinn, G, Simmons, D, Stanton, K, Stuckey, B, Sullivan, DR, Suranyi, M, Suthers, M, Tan, Y, Templer, M, Topliss, D, Waites, JH, Watts, G, Welborn, T, Wyndham, R, Haapamaki, H, Kesaniemi, A, Lahtela, J, Levanen, H, Saltevo, J, Sodervik, H, Taskinen, M, Vanhala, M, Baker, J, Burton, A, Dixon, P, Doran, J, Dunn, P, Graham, N, Hamer, A, Hedley, J, Lloyd, J, Manning, P, McPherson, I, and Morris, S
- Abstract
Objective: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study is examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates in patients with diabetes mellitus. This article describes the trial's run-in phase and patients' baseline characteristics. Research design and methods: FIELD is a double-blind, placebo-controlled trial in 63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus. Patients were to have no indication for lipid-lowering therapy on randomization, but could start these or other drugs at any time after randomization. Follow-up in the study was to be for a median duration of not less than 5 years and until 500 major coronary events (fatal coronary heart disease plus nonfatal myocardial infarction) had occurred. Results: About 2100 patients (22%) had some manifestation of cardiovascular disease (CVD) at baseline and thus high risk status. Less than 25% of patients without CVD had a (UKPDS determined) calculated 5-year CHD risk of <5%, but nearly all had a 5-year stroke risk of <10%. Despite this, half of the cohort were obese (BMI >30), most were men, two-thirds were aged over 60 years, and substantial proportions had NCEP ATP III features of the metabolic syndrome independent of their diabetes, including low HDL (60%), high blood pressure measurement (41%), high waist measurement (65%), and raised triglycerides (52%). After a 6-week run-in period before randomisation with all participants receiving 200 mg comicronized fenofibrate, there were declines in total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL cholesterol (6.5%). Conclusion: The study will show the effect of PPAR-alpha agonist action on CHD and other vascular outcomes in patients with type 2 diabetes including substantial numbers with low to moderate CVD risk but with the various components of the metabolic
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- 2005
24. Variations in patient management and outcomes for acute myocardial infarction in the United States and other countries. Results from the GUSTO trial. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries
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Hampton, Christopher B. Granger, Kerry L. Lee, Alan D. Guerci, Eric J. Topol, Van de Werf F, Paul W. Armstrong, Simes Rj, Gabriel I. Barbash, and Lynn H. Woodlief
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Male ,medicine.medical_specialty ,Canada ,Combination therapy ,Luxembourg ,medicine.medical_treatment ,Streptokinase ,Myocardial Infarction ,Tissue plasminogen activator ,Belgium ,Internal medicine ,Germany ,medicine ,Humans ,Thrombolytic Therapy ,Myocardial infarction ,Israel ,Survival analysis ,Aged ,Netherlands ,business.industry ,Heparin ,Australia ,General Medicine ,Thrombolysis ,Middle Aged ,medicine.disease ,Survival Analysis ,Recombinant Proteins ,United Kingdom ,United States ,Surgery ,Coronary arteries ,medicine.anatomical_structure ,Logistic Models ,Treatment Outcome ,Spain ,Tissue Plasminogen Activator ,Drug Therapy, Combination ,Female ,France ,Poland ,business ,Ireland ,Switzerland ,medicine.drug ,New Zealand - Abstract
OBJECTIVE To examine differences in outcomes and patient management between patients in the United States and outside the United States undergoing thrombolysis for acute myocardial infarction. DESIGN, SETTING, AND PATIENTS Patients in the United States (n = 23,105) and 14 other countries (n = 17,916) were randomized to receive streptokinase plus either subcutaneous or intravenous (IV) heparin, accelerated recombinant tissue-type plasminogen activator (rt-PA) plus IV heparin, or combined streptokinase and rt-PA plus IV heparin. OUTCOME MEASURES Differences in 30-day mortality and patient management were compared among treatments and between US and non-US patients. Treatment-by-country interactions were assessed by logistic regression analyses. Expected mortality of US and non-US patients was estimated using a predictive model and was compared with observed mortality. RESULTS Mortality reduction with accelerated rt-PA vs streptokinase was greater in the United States (1.2% absolute decrease vs 0.7% elsewhere), but the test for treatment-by-country interaction against streptokinase was not significant (P = .30). Benefits of accelerated rt-PA over combination therapy were observed in the United States, but not in other countries (P = .02). Despite differences in base-line characteristics and patient management, 30-day mortality was not significantly different: 6.8% in the United States vs 7.2% elsewhere (P = .09). After adjustment for baseline differences, observed vs predicted outcomes were slightly better in the United States (6.8% vs 7.0%) than elsewhere (7.2% vs 7.0%), indicating that enrollment in the United States was a marginally significant predictor of better survival (P = .047). CONCLUSIONS No significant evidence for a differentially greater benefit of accelerated rt-PA over streptokinase was found in US vs non-US patients. However, increased procedure and treatment use in the United States was associated with only a small decrease in short-term mortality. Long-term follow-up is required to clarify the relationship between survival and the more intensive US management approach.
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- 1995
25. Sustained ventricular arrhythmias among patients with acute coronary syndromes with no ST-segment elevation - Incidence, predictors, and outcomes
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Al-Khatib, SM, Granger, CB, Huang, Y, Lee, KL, Califf, RM, Simoons, Maarten, Armstrong, PW, van der Werf, F, White, HD, Simes, RJ, Moliterno, DJ, Topol, EJ, Harrington, RA, Al-Khatib, SM, Granger, CB, Huang, Y, Lee, KL, Califf, RM, Simoons, Maarten, Armstrong, PW, van der Werf, F, White, HD, Simes, RJ, Moliterno, DJ, Topol, EJ, and Harrington, RA
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- 2002
26. Fenofibrate and diabetic retinopathy – Authors' reply
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Keech, AC, primary, Mitchell, PM, additional, Summanen, PA, additional, Davis, TME, additional, and Simes, RJ, additional
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- 2008
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27. CN2 DEVELOPMENT ANDVALIDATION OF OPTIMALLYWEIGHTED MEASURES OF GLOBAL HEALTH-RELATED QUALITY OF LIFE (QOL) AND UTILITY BASED ON A CANCER-SPECIFIC QOL INSTRUMENT
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Grimison, PS, primary, Simes, RJ, additional, and Stockler, MR, additional
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- 2007
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28. The FIELD study – Authors' reply
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Keech, A, primary, Simes, RJ, additional, Barter, P, additional, Best, J, additional, Scott, R, additional, and Taskinen, M-R, additional
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- 2006
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29. Post-operative radiotherapy for ductal carcinoma in situ of the breast
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Ghersi, D, primary, Simes, RJ, additional, and Lockwood, S, additional
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- 2004
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30. Absolute and relative truth in clinical trials
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White, HD, primary, Armstrong, PW, additional, Califf, RM, additional, Simes, RJ, additional, and Van de Verf, FJ, additional
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- 2002
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31. Post-operative radiotherapy for ductal carcinoma in situ of the breast
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Ghersi, D, primary, Simes, RJ, additional, Lockwood, S, additional, and Weir, L, additional
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- 2001
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32. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis.
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Boekholdt SM, Arsenault BJ, Mora S, Pedersen TR, LaRosa JC, Nestel PJ, Simes RJ, Durrington P, Hitman GA, Welch KM, DeMicco DA, Zwinderman AH, Clearfield MB, Downs JR, Tonkin AM, Colhoun HM, Gotto AM Jr, Ridker PM, Kastelein JJ, and Boekholdt, S Matthijs
- Abstract
Context: The associations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (apoB) levels with the risk of cardiovascular events among patients treated with statin therapy have not been reliably documented.Objective: To evaluate the relative strength of the associations of LDL-C, non-HDL-C, and apoB with cardiovascular risk among patients treated with statin therapy.Design: Meta-analysis of individual patient data from randomized controlled statin trials in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.Data Sources: Relevant trials were identified by a literature search updated through December 31, 2011. Investigators were contacted and individual patient data were requested and obtained for 62,154 patients enrolled in 8 trials published between 1994 and 2008.Data Extraction: Hazard ratios (HRs) and corresponding 95% CIs for risk of major cardiovascular events adjusted for established risk factors by 1-SD increase in LDL-C, non-HDL-C, and apoB.Results: Among 38,153 patients allocated to statin therapy, 158 fatal myocardial infarctions, 1678 nonfatal myocardial infarctions, 615 fatal events from other coronary artery disease, 2806 hospitalizations for unstable angina, and 1029 fatal or nonfatal strokes occurred during follow-up. The adjusted HRs for major cardiovascular events per 1-SD increase were 1.13 (95% CI, 1.10-1.17) for LDL-C, 1.16 (95% CI, 1.12-1.19) for non-HDL-C, and 1.14 (95% CI, 1.11-1.18) for apoB. These HRs were significantly higher for non-HDL-C than LDL-C (P = .002) and apoB (P = .02). There was no significant difference between apoB and LDL-C (P = .21).Conclusion: Among statin-treated patients, on-treatment levels of LDL-C, non-HDL-C, and apoB were each associated with risk of future major cardiovascular events, but the strength of this association was greater for non-HDL-C than for LDL-C and apoB. [ABSTRACT FROM AUTHOR]- Published
- 2012
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33. Benefits and safety of long-term fenofibrate therapy in people with type 2 diabetes and renal impairment: the FIELD Study.
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Ting RD, Keech AC, Drury PL, Donoghoe MW, Hedley J, Jenkins AJ, Davis TM, Lehto S, Celermajer D, Simes RJ, Rajamani K, Stanton K, FIELD Study Investigators, Ting, Ru-Dee, Keech, Anthony C, Drury, Paul L, Donoghoe, Mark W, Hedley, John, Jenkins, Alicia J, and Davis, Timothy M E
- Abstract
Objective: Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m(2)) are at particular cardiovascular risk. Fenofibrate's safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate's effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study.Research Design and Methods: Type 2 diabetic patients (aged 50-75 years) with eGFR ≥30 mL/min/1.73 m(2) were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30-59, 60-89, and ≥90 mL/min/1.73 m(2)). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine >400 μmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat.Results: Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80-0.99]; P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30-59 mL/min/1.73 m(2): 0.68 [0.47-0.97], P = 0.035; eGFR ≥90 mL/min/1.73 m(2): 0.85 [0.70-1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment.Conclusions: Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive. [ABSTRACT FROM AUTHOR]- Published
- 2012
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34. Linking the evidence: intermediate outcomes in medical test assessments.
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Staub LP, Dyer S, Lord SJ, and Simes RJ
- Published
- 2012
35. Capecitabine versus classical cyclophosphamide, methotrexate, and Fluorouracil as first-line chemotherapy for advanced breast cancer.
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Stockler MR, Harvey VJ, Francis PA, Byrne MJ, Ackland SP, Fitzharris B, Van Hazel G, Wilcken NR, Grimison PS, Nowak AK, Gainford MC, Fong A, Paksec L, Sourjina T, Zannino D, Gebski V, Simes RJ, Forbes JF, and Coates AS
- Published
- 2011
36. Early decline in cancer antigen 125 as a surrogate for progression-free survival in recurrent ovarian cancer.
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Lee CK, Friedlander M, Brown C, Gebski VJ, Georgoulopoulos A, Vergote I, Pignata S, Donadello N, Schmalfeldt B, Delva R, Mirza MR, Sauthier P, Pujade-Lauraine E, Lord SJ, and Simes RJ
- Published
- 2011
37. Monitoring cholesterol levels: measurement error or true change?
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Glasziou PP, Irwig L, Heritier S, Simes RJ, Tonkin A, LIPID Study Investigators, Glasziou, Paul P, Irwig, Les, Heritier, Stephane, Simes, R John, and Tonkin, Andrew
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Background: Cholesterol level monitoring is a common clinical activity, but the optimal monitoring interval is unknown and practice varies.Objective: To estimate, in patients receiving cholesterol-lowering medication, the variation in initial response to treatment, the long-term drift from initial response, and the detectability of long-term changes in on-treatment cholesterol level ("signal") given short-term, within-person variation ("noise").Design: Analysis of cholesterol measurement data in the LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) study.Setting: Randomized, placebo-controlled trial in Australia and New Zealand (June 1990 to May 1997).Patients: 9014 patients with past coronary heart disease who were randomly assigned to receive pravastatin or placebo.Measurements: Serial cholesterol concentrations at randomization, 6 months, and 12 months, and then annually to 5 years.Results: Both the placebo and pravastatin groups showed small increases in within-person variability over time. The estimated within-person SD increased from 0.40 mmol/L (15 mg/dL) (coefficient of variation, 7%) to 0.60 mmol/L (23 mg/dL) (coefficient of variation, 11%), but it took almost 4 years for the long-term variation to exceed the short-term variation. This slow increase in variation and the modest increase in mean cholesterol level, about 2% per year, suggest that most of the variation in the study is due to short-term biological and analytic variability. Our calculations suggest that, for patients with levels that are 0.5 mmol/L or more (> or =19 mg/dL) under target, monitoring is likely to detect many more false-positive results than true-positive results for at least the first 3 years after treatment has commenced.Limitations: Patients may respond differently to agents other than pravastatin. Future values for nonadherent patients were imputed.Conclusion: The signal-noise ratio in cholesterol level monitoring is weak. The signal of a small increase in cholesterol level is difficult to detect against the background of a short-term variability of 7%. In annual rechecks in adherent patients, many apparent increases in cholesterol level may be false positive. Independent of the office visit schedule, the interval for monitoring patients who are receiving stable cholesterol-lowering treatment could be lengthened. [ABSTRACT FROM AUTHOR]- Published
- 2008
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38. Initial aspirin dose and outcome among ST-elevation myocardial infarction patients treated with fibrinolytic therapy.
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Berger JS, Stebbins A, Granger CB, Ohman EM, Armstrong PW, Van de Werf F, White HD, Simes RJ, Harrington RA, Califf RM, and Peterson ED
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- 2008
39. Biases in the identification of risk factor thresholds and j-curves.
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Marschner IC, Simes RJ, and Keech A
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For some diseases, there has been controversy about whether key risk factors are related linearly to the occurrence of disease events. This issue has important implications for strategies to modify risk factors, since nonlinear threshold or J-curve associations imply that risk factor modification is not beneficial beyond a certain level. This paper considers whether nonlinear risk factor associations can arise spuriously from selection mechanisms common in prospective cohort studies. Using theory, simulation, and cohort data, the authors show that selecting individuals based on their prior disease status leads to the primary risk factor being negatively confounded with other residual risk factors. If this confounding combines with effect modification between the primary and residual risk factors, as exists in cardiovascular disease, then the aggregate effect is nonlinear distortion of the risk factor relation. Such distortion can produce an apparent threshold or J-curve relation, even if the true underlying relation is linear. The authors conclude that nonlinear risk factor associations observed in primary or secondary prevention cohorts should be interpreted with caution because they may be consistent with an underlying linear lower-is-better relation. Randomized studies provide an important complement to prospective cohort studies when choosing between intensive and moderate risk factor modification strategies in high-risk populations. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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40. Primary ercutaneous Coronary Intervention compared with fibrinolysis for myocardial infarction in diabetes mellitus: results from the Primary Coronary Angioplasty vs Thrombolysis-2 trial.
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Timmer JR, Ottervanger JP, de Boer MJ, Boersma E, Grines CL, Westerhout CM, Simes RJ, Granger CB, Zijlstra F, and Primary Coronary Angioplasty vs Thrombolysis-2 Trialists Collaborators Group
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- 2007
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41. Statin use and sex-specific stroke outcomes in patients with vascular disease.
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Bushnell CD, Griffin J, Newby LK, Goldstein LB, Mahaffey KW, Graffagnino CA, Harrington RA, White HD, Simes RJ, Califf RM, Topol EJ, Easton JD, Bushnell, Cheryl D, Griffin, Jeffrey, Newby, L Kristin, Goldstein, Larry B, Mahaffey, Kenneth W, Graffagnino, Carmelo A, Harrington, Robert A, and White, Harvey D
- Published
- 2006
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42. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial [corrected] [published erratum appears in LANCET 2006 Oct 21-27;368(9545):1420].
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Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, Forder P, Pillai A, Davis T, Glasziou P, Drury P, Kesäniemi YA, Sullivan D, Hunt D, Colman P, d'Emden M, Whiting M, Ehnholm C, Laakso M, and FIELD study investigators
- Published
- 2005
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43. Relation of diet to cardiovascular disease risk factors in subjects with cardiovascular disease in Australia and New Zealand: analysis of the Long-Term Intervention with Pravastatin in Ischaemic Disease trial.
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Nestel PJ, Baghurst K, Colquhoun DM, Simes RJ, Mehalski K, White HD, Tonkin AM, Kirby A, Pollicino C, and Long-Term Intervention with Pravastatin in Ischaemic Disease Study Investigators
- Abstract
BACKGROUND: Comparisons of the relation of diet with coronary heart disease (CHD) between countries with similar socioeconomic environments have been few. Patients in Australia and New Zealand (n = 9014) who participated in a large secondary prevention trial had significantly different CHD mortality rates. OBJECTIVE: The objective of this study was to ascertain the effects of nutrient consumption on cardiovascular disease risk in patients from the 2 countries. DESIGN: Nutrient consumption patterns were surveyed in a subgroup of 1077 patients on 3 occasions over 4 y during an intervention trial with a statin. RESULTS: Within the entire cohort of 9014 patients, the New Zealanders had significantly (40%) more cardiovascular deaths than did the Australians. In the subgroup of 1077 patients, the New Zealanders were found at entry to have eaten significantly more total (69.34 +/- 12.35 compared with 66.45 +/- 12.9 g/d) and saturated (26.23 +/- 8.41 compared with 24.37 +/- 7.36 g/d) fat (P < 0.001 for each) and to have significantly (4%) higher concentrations of LDL cholesterol (3.96 +/- 0.74 compared with 3.8 +/- 0.76 mmol/L; P < 0.001) than did the Australians. At baseline, patients with previous coronary artery bypass grafting had diets that were significantly different from those of patients without previous coronary artery bypass grafting. Relations between nutrients and plasma lipids confirmed the direct effects of saturated fatty acids on LDL cholesterol and of alcohol on plasma triacylglycerol and HDL cholesterol. Dietary counseling throughout the trial led to significant improvements in compliance with guidelines. However, neither the baseline nor the improved 1-y nutrient intakes predicted future changes in cardiovascular events. CONCLUSION: Differences in CHD mortality and in LDL-cholesterol concentrations between 2 populations with similar socioeconomic and cultural backgrounds were consistent with the amounts and types of fats eaten. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]
- Published
- 2005
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44. White blood cell count predicts reduction in coronary heart disease mortality with pravastatin.
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Stewart RAH, White HD, Kirby AC, Heritier SR, Simes RJ, Nestel PJ, West MJ, Colquhoun DM, Tonkin AM, Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) Study Investigators, and Braunwald E
- Published
- 2005
45. Lessons learned from a clinical trial.
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Armstrong PW, Newby LK, Granger CB, Lee KL, Simes RJ, Van de Werf F, White HD, Califf RM, and Virtual Coordinating Centre for Global Collaborative Cardiovascular Research Group
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- 2004
46. Risk factors for non-haemorrhagic stroke in patients with coronary heart disease and the effect of lipid-modifying therapy with pravastatin.
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West MJ, White HD, Simes RJ, Kirby A, Watson JD, Anderson NE, Hankey GJ, Wonders S, Hunt D, Tonkin AM, West, Malcolm J, White, Harvey D, Simes, R John, Kirby, Adrienne, Watson, John D, Anderson, Neil E, Hankey, Graeme J, Wonders, Susan, Hunt, David, and Tonkin, Andrew M
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- 2002
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47. Pravastatin therapy and the risk of stroke.
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White HD, Simes RJ, Anderson NE, Hankey GJ, Watson JDG, Hunt D, Colquhoun DM, Glasziou P, MacMahon S, Kirby AC, West MJ, and Tonkin AM
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- 2000
48. Ultrastructure of Chondrosarcoma
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Simes Rj, Schajowicz F, Klein-Szanto Aj, and Rómulo L. Cabrini
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Pathology ,medicine.medical_specialty ,business.industry ,medicine ,Ultrastructure ,Orthopedics and Sports Medicine ,Surgery ,General Medicine ,Chondrosarcoma ,medicine.disease ,business - Published
- 1974
49. High-risk patients with ST-elevation myocardial infarction derive greatest absolute benefit from primary percutaneous coronary intervention: Results from the Primary Coronary Angioplasty Trialist versus Thrombolysis (PCAT)-2 Collaboration.
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de Boer SP, Barnes EH, Westerhout CM, Simes RJ, Granger CB, Kastrati A, Widimsky P, de Boer MJ, Zijlstra F, and Boersma E
- Published
- 2011
50. Historical cross-trial comparisons for competing treatments in advanced breast cancer -- an empirical analysis of bias.
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Lee CK, Lord SJ, Stockler MR, Coates AS, Gebski V, and Simes RJ
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PURPOSE: Randomised controlled trials (RCTs) provide optimal evidence to assess the benefits of new treatments. However, clinicians routinely rely on cross-trial comparisons to assess competing treatments when head-to-head randomised comparisons are unavailable. We investigate the validity of cross-trial comparisons using individual patient data (IPD) where patients received the same treatment protocol. We also examine the extent to which statistical adjustment for baseline characteristics can account for inter-trial differences in outcomes. PATIENTS AND METHODS: We used pooled IPD of 378 women with advanced breast cancer assigned to oral cyclophosphamide, intravenous methotrexate and 5-fluorouracil (CMF) in the control arms of three first-line treatment RCTs (ANZ8101, ANZ8614 and ANZ0001) conducted between 1982 and 2001. The Kaplan-Meier method was used to compare progression-free survival (PFS) and overall survival (OS) across trials. Proportional hazard models were constructed to estimate the hazard rates across trials after adjustment for baseline characteristics. RESULTS: The distribution of baseline characteristics varied across trials. There was a statistically significant difference in survival among women treated with CMF in these trials (logrank p=0.009). The median OS were 17.7, 10.3 and 10.1 months for 0001, 8101 and 8614, respectively. The hazard ratios for survival, adjusted for baseline characteristics differences, were 1.44 (8614) and 1.45 (8101) compared to 0001 (p=0.03). PFS did not differ across trials (logrank p=0.38). CONCLUSIONS: Caution should be exercised when interpreting results from historical cross-trial comparisons even if the adjustment of baseline prognostic characteristics can be performed. Cross-trial comparisons have some role in hypothesis-generating, identifying and prioritising promising treatments for further investigation; however RCTs are still essential to guide sound clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
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