Showing papers by "Bruce Neal published in 2002"

Incidence of heterotopic bone formation after major hip surgery.

Abstract: Background: Heterotopic bone formation is a well-established complication of major hip surgery, but traditional reviews of the published literature may have underestimated its frequency. Methods: A systematic overview of all the relevant studies was performed to determine reliably the incidence of any heterotopic bone formation and the incidence of each Brooker equivalent grade. Separate estimates were made for patients with total hip replacement and patients with acetabular fracture repair. Results: A computer-based search identified 218 studies with data on the incidence of heterotopic bone formation after either hip replacement or acetabular fracture repair. These studies included data from an estimated 59 121 operated hips among patients that received total hip replacement and an estimated 998 hips among patients that underwent acetabular fracture repair. In these studies, the incidence of any heterotopic bone formation was 43% after total hip replacement and 51% after acetabular fracture repair. The incidence of severe heterotopic bone formation was 9% and 19%, respectively. Conclusions: These results suggest that heterotopic bone formation occurs more frequently after total hip replacement than is generally believed. It is possible that heterotopic bone formation is a more important cause of postoperative disability than has previously been recognized and that effective prophylactic regimens might improve outcome in substantial numbers of patients.

Managing the global burden of cardiovascular disease

Abstract: There is a large and increasing global burden of cardiovascular disease. Approximately 14 million individuals died of cardiovascular disease in 1990, and this is projected to rise to about 25 million by 2020. In large part, this increase can be explained on the basis of major ongoing sociodemographic changes in developing countries, and associated effects on the numbers of individuals at risk and the levels of cardiovascular risk factors. Developing countries now experience a much greater burden of cardiovascular disease than do developed countries. In addition, developing countries are expected to experience the greatest rise in cardiovascular disease burden over the next few years. Cardiovascular disease prevention programmes designed and implemented primarily in developed countries have most likely averted much premature cardiovascular disease in those countries over the past few decades. However, cardiovascular disease prevention programmes designed for developed countries are unlikely to be directly transferable to developing countries. Reliable information to inform the design and implementation of cardiovascular disease prevention programmes, tailored to the socioeconomic circumstances of developing countries, is now required. Such programmes have great potential to impact on the current and projected global epidemic of cardiovascular disease.

Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease

Abstract: Aims To determine the effects on homocysteine levels of two doses of folic acid compared to placebo, where the high dose is typical of that provided by pharmacological intervention and the low dose approximates that provided by dietary supplementation. Methods and results The PACIFIC study was a double-blind, placebo-controlled, factorial randomized trial. Seven hundred and twenty-three individuals with a history of myocardial infarction or unstable angina were recruited from 28 clinical cardiology centres in Australia and New Zealand and randomized to folic acid 2.0 mg daily, folic acid 0.2 mg daily or placebo. The primary outcome, homocysteine, was measured using a fluorescence polarization immunoassay. Compared to placebo, 2.0 mg folic acid reduced homo-cysteine by 1.8 micromol x 1(-1) [95% confidence interval (CI) 1.3-2.3] and 0.2 mg reduced homocysteine by 1.2 micromol x 1(-1) [95% CI 0.8-1.7). The higher dose reduced homocysteine significantly more than the lower dose (P=001). Conclusions Both doses of folic acid reduced homocysteine, but the effects of the 2.0 mg dose were about one third greater than the 0.2 mg dose. Fortification of foods with folic acid should result in population-wide lower levels of homocysteine but high-dose pharmacological supplementation would produce greater reductions for high-risk individuals.

Effects of the vasopeptidase inhibitor, omapatrilat, in 723 patients with coronary heart disease.

Abstract: Introduction Among individuals with a history of myocardial infarction (MI), higher levels of blood pressure (BP) are associated with increased long-term risks of death from coronary heart disease. Treatment with a BP-lowering regimen, based on omapatrilat may result in greater clinical benefits than treatment with a regimen based on a regular angiotensin-converting enzyme (ACE) inhibitor because of more favourable effects on the renin-angiotensin-aldosterone system. Methods Seven hundred and twenty-three clinically stable patients with a history of MI or unstable angina, and a mean entry BP of 134/77 mmHg, were randomised to six months treatment with omapatrilat 40 mg, omapatrilat 20 mg, or matching placebo. Results After six months, mean BP levels (systolic/diastolic) in the omapatrilat 40 mg group were reduced by 4.3/ 2.9 mmHg (95% confidence interval 1.3 to 7.2/1.2 to 4.6). Mean BP levels in the omapatrilat 20 mg group were reduced by 4.6/1.0 mmHg (1.6 to 7.6/-0.7 to 2.6) in comparison with the placebo group. Both doses of omapatrilat also produced significant decreases in plasma ACE activity and significant increases in levels of plasma renin activity, atrial natriuretic peptide, endothelin and homocysteine (p<0.05 for all). Premature discontinuations were more frequent with omapatrilat than with placebo (p<0.001 for 20 mg and 40 mg). Conclusions Omapatrilat produced changes in BP, neurohormone and biochemical parameters that were similar for the two doses. The long-term clinical implications of the observed effects are uncertain and a large-scale randomised trial would be required to reliably establish the effects of omapatrilat on the risks of major vascular disease events among patients with coronary heart disease.