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Biomedical subjects

R John Simes

Publications and source records attributed to R John Simes.

At least 19 recordsLinked to original sources
PubMed2007

Psychosocial factors and patients' preferences for adjuvant chemotherapy in early breast cancer.

PURPOSE: Many women who have had adjuvant chemotherapy for early breast cancer judge small benefits sufficient to make it worthwhile despite significant side effects and inconvenience. The rationality of these preferences has been questioned. We sought to better understand such preferences by assessing associations between preferences and psychosocial factors, and by asking women who judged negligible benefits sufficient to explain why. METHODS: We recruited 83 consecutive consenting women who had completed adjuvant chemotherapy for early breast cancer 3-34 months earlier. Preferences were elicited during a structured, scripted interview using four sets of validated, hypothetical trade-off scenarios about the possible benefits of adjuvant chemotherapy on survival times (5 and 15 years) and rates (65 and 85% at 5 years). Women completed questionnaires measuring anxiety, depression, optimism, quality and quantity of social support, and illness perceptions. RESULTS: More than half the women judged benefits of 1 day or 0.1% sufficient to make adjuvant chemotherapy worthwhile. The most important factors in multivariable models were whether the woman had dependants and number of non-specific symptoms attributed to breast cancer and adjuvant chemotherapy since completing treatment. The proportion of variance explained was modest. Preferences were not associated with: scores for anxiety, optimism, and perceived quality and quantity of social support. Explanations for judging negligible benefits sufficient included minimising regret, parenting concerns, doubts about the information provided and feeling that they had no choice. CONCLUSIONS: Preferences were highly variable and influenced by women's unique circumstances and attitudes, but not by their anxiety or optimism scores.

Adult↗
PubMed2006

When is measuring sensitivity and specificity sufficient to evaluate a diagnostic test, and when do we need randomized trials?

The clinical value of using a new diagnostic test depends on whether it improves patient outcomes beyond the outcomes achieved using an old diagnostic test. When can studies of diagnostic test accuracy provide sufficient information to infer clinical value, and when do clinicians need to wait for results from randomized trials? The authors argue that accuracy studies suffice if a new diagnostic test is safer or more specific than, but of similar sensitivity to, an old test. However, if a new test is more sensitive than an old test, it leads to the detection of extra cases of disease. Results from treatment trials that enrolled only patients detected by the old test may not apply to these extra cases. Clinicians need to wait for results from randomized trials assessing treatment efficacy in cases detected by the new diagnostic test, unless they can be satisfied that the new test detects the same spectrum and subtype of disease as the old test or that treatment response is similar across the spectrum of disease.

Diagnostic Techniques and Procedures↗
PubMed2006

Statin use and sex-specific stroke outcomes in patients with vascular disease.

BACKGROUND AND PURPOSE: Although statins reduce the risk of stroke in patients with coronary heart disease, possible differing effects of statins on stroke outcomes based on sex remain uncertain. We investigated the relationships between statin use and sex-specific stroke incidence, severity, and mortality. METHODS: Data from 3 trials of oral glycoprotein IIb/IIIa inhibitors (first and second Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes [SYMPHONY] and Blockade of the glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion [BRAVO]) were pooled and stroke outcomes compared among 8191 baseline statin users versus 14,752 nonusers. Time-to-event data were modeled with proportional hazards regression. Stroke severity was assessed retrospectively with the Canadian Neurological Scale (CNS) based on records with scoreable neurological examinations. RESULTS: A total of 217 subjects had strokes (0.95%). Statin users had a lower risk of stroke in unadjusted (hazard ratio [HR], 0.69; 95% CI, 0.51 to 0.92) and risk-adjusted models (HR, 0.72; 95% CI, 0.53 to 0.97). There was no difference in stroke mortality with statin use (P=0.8). CNS scores could be assigned to 106 of the subjects, with no difference in severity among statin users and nonusers (median CNS=10.5 in users versus CNS=9.75 in nonusers; P=0.14). Women had more severe strokes than men (median CNS=10.5 in men versus 9.5 in women; Poisson regression P=0.035). Women had more severe strokes after adjustment for statin use (P=0.03) and the combination of statin use, atrial fibrillation, and age (P=0.03). CONCLUSIONS: In patients included in these clinical trials of oral glycoprotein IIb/IIIa inhibitors, statin use is associated with a reduced risk of stroke but not severity or mortality. Women had more severe strokes than men, a difference that was not explained by baseline characteristics or statin use.

Aged↗
PubMed2006

Frequency of recurrent ST-elevation myocardial infarction after fibrinolytic therapy in a different territory as a manifestation of multiple unstable coronary arterial plaques.

Multiple unstable plaques have been demonstrated by various imaging techniques in culprit and nonculprit arteries in patients with acute coronary syndromes, but the frequency with which clinical manifestations of multiple unstable plaques occur is unclear. To estimate this frequency in patients who present within 6 hours with ST-elevation myocardial infarction, we studied electrocardiograms and cardiac marker levels of 722 patients with suspected reinfarction in the HERO-2 trial of 17,073 patients; this trial compared intravenous bivalirudin with unfractionated heparin before administration of streptokinase. Twenty-six patients (3.6%) developed recurrent ST elevation in a different territory. Of all the patients who developed ST elevation in a different territory, 50% (13 of 26) did so during the 48 hours of randomized antithrombin therapy compared with 29% (140 of 487) of those who developed recurrent ST elevation in the index territory (p = 0.046). Recurrent index territory ST elevation occurred in 392 of 552 patients (71%) with confirmed reinfarction, and ST elevation in a new territory occurred in 21 patients (3.8%) with confirmed reinfarction (2.3% and 0.12% of all HERO-2 enrollees, respectively). These data suggest that clinical manifestation of multiple unstable plaques of recurrent ST elevation and reinfarction in a territory different from that of the index ST elevation myocardial infarction after intravenous fibrinolytic and antithrombin therapies is rare.

Aged↗
PubMed2005

Patients with prolonged ischemic chest pain and presumed-new left bundle branch block have heterogeneous outcomes depending on the presence of ST-segment changes.

OBJECTIVES: The purpose of this research was to examine the prognostic value of ST-segment changes (concordant ST-segment elevation and/or precordial V1 to V3 ST-segment depression) during presumed-new left bundle branch block (LBBB) in patients receiving fibrinolytic therapy. BACKGROUND: These patients are often considered high-risk, but their outcome is not well-defined. METHODS: The Hirulog and Early Reperfusion or Occlusion (HERO)-2 trial compared bivalirudin with heparin in patients receiving streptokinase for ST-segment elevation or presumed-new LBBB. Each patient with LBBB was matched with a control (with normal intraventricular conduction) for age, gender, pulse rate, systolic blood pressure, Killip class, and region. RESULTS: A total of 300 patients had LBBB (92 with and 208 without ST-segment changes) and 15,340 had normal conduction. Acute myocardial infarction (AMI) occurred in 80.7% of LBBB patients and 88.7% of controls (p = 0.006). ST-segment changes were specific (96.6%) but not sensitive (37.8%) for enzymatic diagnosis of AMI. Mortality at 30 days was similar in LBBB patients with ST-segment changes (21.7%) and controls (25.0%, p = 0.563), but lower in LBBB patients without ST-segment changes than in controls (13.5% vs. 21.6%, p = 0.022). In the whole HERO-2 cohort, the LBBB patients with ST-segment changes had higher mortality than patients with normal conduction (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.78 to 2.42). The LBBB patients without ST-segment changes had lower mortality than patients with normal conduction (OR 0.52, 95% CI 0.33 to 0.80). CONCLUSIONS: ST-segment changes during LBBB are specific for the diagnosis of AMI and predict 30-day mortality; LBBB patients without ST-segment changes have lower adjusted 30-day mortality than those with normal conduction. Trials are required to determine the best treatment for high-risk and low-risk patients with LBBB.

Aged↗
PubMed2005

White blood cell count predicts reduction in coronary heart disease mortality with pravastatin.

BACKGROUND: Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment. METHODS AND RESULTS: We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1x10(9)/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P=0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2x10(9)/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (P=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased (by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively). CONCLUSIONS: These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.

Aged↗
PubMed2005

Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial.

BACKGROUND: Resection remains the best treatment for carcinoma of the oesophagus in terms of local control, but local recurrence and distant metastasis remain an issue after surgery. We aimed to assess whether a short preoperative chemoradiotherapy regimen improves outcomes for patients with resectable oesophageal cancer. METHODS: 128 patients were randomly assigned to surgery alone and 128 patients to surgery after 80 mg/m(2) cisplatin on day 1, 800 mg/m(2) fluorouracil on days 1-4, with concurrent radiotherapy of 35 Gy given in 15 fractions. The primary endpoint was progression-free survival. Secondary endpoints were overall survival, tumour response, toxic effects, patterns of failure, and quality of life. Analysis was done by intention to treat. FINDINGS: Neither progression-free survival nor overall survival differed between groups (hazard ratio [HR] 0.82 [95% CI 0.61-1.10] and 0.89 [0.67-1.19], respectively). The chemoradiotherapy-and-surgery group had more complete resections with clear margins than did the surgery-alone group (103 of 128 [80%] vs 76 of 128 [59%], p=0.0002), and had fewer positive lymph nodes (44 of 103 [43%] vs 69 of 103 [67%], p=0.003). Subgroup analysis showed that patients with squamous-cell tumours had better progression-free survival with chemoradiotherapy than did those with non-squamous tumours (HR 0.47 [0.25-0.86] vs 1.02 [0.72-1.44]). However, the trial was underpowered to determine the real magnitude of benefit in this subgroup. INTERPRETATION: Preoperative chemoradiotherapy with cisplatin and fluorouracil does not significantly improve progression-free or overall survival for patients with resectable oesophageal cancer compared with surgery alone. However, further assessment is warranted of the role of chemoradiotherapy in patients with squamous-cell tumours.

Adult↗
PubMed2005

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.

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.

Aged↗
PubMed2004

Incidence and characteristics of stroke during 90-day follow-up in patients stabilized after an acute coronary syndrome.

BACKGROUND: Stroke is a rare but serious event that complicates the course of patients with acute coronary syndromes (ACS). The type, outcome, and risk factors of stroke occurring in stabilized patients with ACS have not been previously reported. METHODS: We evaluated stroke incidence, subtypes, and outcomes, in addition to demographics and clinical risk characteristics associated with stroke among patients enrolled in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials. RESULTS: Of 15,904 stabilized patients with ACS, 113 (0.71%) had a stroke over a median follow-up of 90 days. The majority of strokes occurred within 30 days of presentation, and the time course for stroke occurrence paralleled that of myocardial (re)infarction. Most strokes were ischemic (78%), and 52% resulted in moderate or severe disability or death. Patients with stroke were older and more often had hypertension, diabetes, peripheral vascular disease, and atrial fibrillation. Among patients with stroke who had cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass grafting, stroke occurred predominantly after the procedure. No difference in occurrence or type of stroke was observed in the assigned treatment groups. In multivariable modeling age, heart failure, prior stroke, left bundle branch block, and systolic blood pressure predicted the occurrence of stroke. CONCLUSIONS: In patients stabilized after presenting with a spectrum of ACS and treated with sibrafiban and/or aspirin, stroke occurred in fewer than 1% within 90 days but carried a significant mortality and morbidity risk.

Acute Disease↗
PubMed2003

Depression and cardiovascular morbidity and mortality: cause or consequence?

BACKGROUND: Depression after myocardial infarction has been associated with increased cardiovascular mortality. This study assessed whether depressive symptoms were associated with adverse outcomes in people with a history of an acute coronary syndrome, and evaluated possible explanations for such an association. METHODS AND RESULTS: Depressive symptoms were assessed using the General Health Questionnaire at least 5 months after hospital admission for acute myocardial infarction or unstable angina in 1130 participants of the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study, a multicentre, placebo-controlled, clinical trial of cholesterol-lowering treatment. Cardiovascular symptoms, self-rated general health, cardiovascular risk factors, employment status, social support and life events were also assessed at the baseline visit. Cardiovascular death (n=114), non-fatal myocardial infarction (n=108), non-fatal stroke (n=53) and unstable angina (n=274) were documented during a median follow-up period of 8.1 years. Individuals with depressive symptoms (General Health Questionnaire score >/=5; 22% of participants) were more likely to report angina, dyspnoea, claudication, poorer general health, not being in paid employment, few social contacts and/or adverse life events (P<0.05 for all). There was a modest association between depressive symptoms and cardiovascular events (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.13-1.77), but not cardiovascular death (HR 1.12. 95% CI 0.71-1.77). After adjustment for symptoms related to cardiovascular disease, the HR for cardiovascular events was 1.22 (95% CI 0.97-1.53). After further adjustment for employment status, social support and life events, the HR was 1.13 (95% confidence interval 0.87-1.47). CONCLUSIONS: There was no significant association between depressive symptoms and fatal or non-fatal cardiovascular events after adjustment for cardiovascular symptoms associated with poorer prognosis. Previously observed associations between depression and cardiovascular mortality may not be causal.

Adult↗
PubMed2003

International variation in the use of evidence-based medicines for acute coronary syndromes.

AIMS: We sought to evaluate international patterns of use and factors influencing use of evidence-based medications early after ACS. METHODS AND RESULTS: Using a database of 15904 ACS patients enrolled in the SYMPHONY and 2nd SYMPHONY trials in 37 countries, we performed descriptive and logistic regression analyses. After controlling for other factors, region was significantly associated with the use of every class of evidence-based medication, most pronounced for intravenous unfractionated heparin (IV UFH), low-molecular-weight heparin (LMWH), angiotensin II converting enzyme inhibitors (ACEI) and discharge use of lipid-lowering agents. Latin America and Eastern Europe were among the highest users of early ACEI, yet the lowest users of discharge lipid-lowering therapy. Relative to the United States, all regions except Canada had greater use of LMWH and lower use of IV UFH. Compared with patients with acute myocardial infarction, those with unstable angina less often received aspirin, beta-blockers, ACEI, or IV UFH. Older age was associated with lower use of aspirin, beta-blockers, IV UFH, and lipid-lowering agents. CONCLUSIONS: Use of evidence-based therapies for management of ACS patients is strongly associated with region. To improve patient outcomes, more research is needed to understand this variation, and to institute appropriate solutions.

Aged↗
PubMed2003

The benefits and costs of tamoxifen for breast cancer prevention.

OBJECTIVE: To estimate the effects of key uncertainties on the effectiveness and cost-effectiveness of breast cancer prevention with tamoxifen. METHODS: The incremental cost-effectiveness ratio of tamoxifen therapy relative to placebo was estimated using decision analysis with Markov modelling of health states, outcomes and costs for a simulated cohort of women at high risk for breast cancer. Relative effects of tamoxifen's benefits and harms were estimated from meta-analyses of randomised controlled trials. Cost estimates were based on Australian treatment patterns and costs. The main outcome measure was cost per quality-adjusted life year (QALY) gained with costs and effects discounted at a 5% annual rate. RESULTS: Tamoxifen therapy over five years reduces the incidence of breast cancer by approximately 1.4%, which is offset by an increase in endometrial cancer of 0.7% and pulmonary embolism of 0.2%. If the reduction is permanent (preventing new breast cancers emerging over five years and no further treatment effect thereafter), the model estimates an increase in life expectancy of 0.057 QALYs and an extra cost of $2,193; or $38,271/QALY gained. A model assuming further treatment effects of tamoxifen preventing new breast cancers emerging for up to 10 years results in an incremental cost of $19,354/QALY. However, if five years of tamoxifen therapy merely delays when these breast cancers appear (such that by 10 years there is no longer a reduced incidence), the incremental cost per QALY saved is estimated to be $199,149. CONCLUSIONS: Tamoxifen is potentially cost-effective in preventing breast cancer in women at high risk. However, its cost-effectiveness as a preventive therapy is highly sensitive to whether these cancers are permanently prevented or their clinical presentation is only delayed. Long-term follow-up in randomised controlled trials is therefore crucial in forming health policy.

Antineoplastic Agents, Hormonal↗
PubMed2003

Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose: results from the LIPID trial.

OBJECTIVE: Diabetes, a major health problem worldwide, increases the risk of cardiovascular disease and its associated mortality: The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial showed that cholesterol-lowering treatment with pravastatin reduced mortality and coronary heart disease (CHD) events in 9014 patients aged 31-75 years with CHD and total cholesterol 4.0-7.0 mmol/l. We measured the effects of pravastatin therapy, 40 mg/day over 6.0 years, on the risk of CHD death or nonfatal myocardial infarction and other cardiovascular outcomes in 1,077 LIPID patients with diabetes and 940 patients with impaired fasting glucose (IFG). RESULTS: In patients allocated to placebo, the risk of a major CHD event was 61% higher in patients with diabetes and 23% higher in the IFG group than in patients with normal fasting glucose, and the risk of any cardiovascular event was 37% higher in the diabetic group and 19% higher in the IFG group. Pravastatin therapy reduced the risk of a major CHD event overall from 15.9 to 12.3% (relative risk reduction [RRR] 24%, P < 0.001) and from 23.4 to 19.6% in the diabetic group (19%, P = 0.11); in the diabetic group, the reduction was not significantly different from the reductions in the other groups. Pravastatin reduced the risk of any cardiovascular event from 52.7 to 45.2% (21%, P < 0.008) in patients with diabetes and from 45.7 to 37.1% (26%, P = 0.003) in the IFG group. Pravastatin reduced the risk of stroke from 9.9 to 6.3% in the diabetic group (RRR 39%, CI 7-61%, P = 0.02) and from 5.4 to 3.4% in the IFG group (RRR 42%, CI -9 to 69%, P = 0.09). Pravastatin did not reduce the incidence of diabetes. Over 6 years, pravastatin therapy prevented one major CHD event (CHD death or nonfatal myocardial infarction) in 23 patients with IFG and 18 patients with diabetes. A meta-analysis of other major trials confirmed the high absolute risks of diabetes and IFG and the absolute benefits of statin therapy in these patients. CONCLUSIONS: Cholesterol-lowering treatment with pravastatin therapy prevents cardiovascular events, including stroke, in patients with diabetes or IFG and established CHD.

Adult↗
PubMed2002

Cholesterol-lowering therapy with pravastatin in patients with average cholesterol levels and established ischaemic heart disease: is it cost-effective?

OBJECTIVE: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels. DESIGN: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo. PATIENTS AND SETTING: 9014 patients aged 35-75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992. MAIN OUTCOME MEASURES: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life. RESULTS: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%-4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107 730 (95% CI, $68 626-$209 881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%). CONCLUSIONS: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.

Adult↗