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Biomedical subjects

Stephen MacMahon

Publications and source records attributed to Stephen MacMahon.

At least 19 recordsLinked to original sources
PubMed2006

Safety and efficacy of routine postoperative ibuprofen for pain and disability related to ectopic bone formation after hip replacement surgery (HIPAID): randomised controlled trial.

OBJECTIVES: To determine the benefits and risks of a non-steroidal anti-inflammatory drug (NSAID) as prophylaxis for ectopic bone formation in patients undergoing total hip replacement (or revision) surgery. DESIGN: Double blind randomised placebo controlled clinical trial, stratified by treatment site and surgery (primary or revision). SETTING: 20 orthopaedic surgery centres in Australia and New Zealand. PARTICIPANTS: 902 patients undergoing elective primary or revision total hip replacement surgery. INTERVENTION: 14 days' treatment with ibuprofen (1200 mg daily) or matching placebo started within 24 hours of surgery. MAIN OUTCOME MEASURES: Changes in self reported hip pain and physical function 6 to 12 months after surgery (Western Ontario and McMaster University Arthritis index). RESULTS: There were no significant differences between the groups for improvements in hip pain (mean difference -0.1, 95% confidence interval -0.4 to 0.2, P = 0.6) or physical function (-0.1, -0.4 to 0.2, P = 0.5), despite a decreased risk of ectopic bone formation (relative risk 0.69, 0.56 to 0.83) associated with ibuprofen. There was a significantly increased risk of major bleeding complications in the ibuprofen group during the admission period (2.09, 1.00 to 4.39). CONCLUSIONS: These data do not support the use of routine prophylaxis with NSAIDs in patients undergoing total hip replacement surgery. TRIAL REGISTRATION: NCT00145730.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Prior events predict cerebrovascular and coronary outcomes in the PROGRESS trial.

BACKGROUND AND PURPOSE: The relationship between baseline and recurrent vascular events may be important in the targeting of secondary prevention strategies. We examined the relationship between initial event and various types of further vascular outcomes and associated effects of blood pressure (BP)-lowering. METHODS: Subsidiary analyses of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial that established the benefits of BP-lowering in 6105 patients (mean age 64 years, 30% female) with cerebrovascular disease, randomly assigned to either active treatment (perindopril for all, plus indapamide in those with neither an indication for, nor a contraindication to, a diuretic) or placebo(s). RESULTS: Stroke subtypes and coronary events were associated with 1.5- to 6.6-fold greater risk of recurrence of the same event (hazard ratios, 1.51 to 6.64; P=0.1 for large artery infarction, P<0.0001 for other events). However, 46% to 92% of further vascular outcomes were not of the same type. Active treatment produced comparable reductions in the risk of vascular outcomes among patients with a broad range of vascular events at entry (relative risk reduction, 25%; P<0.0001 for ischemic stroke; 42%, P=0.0006 for hemorrhagic stroke; 17%, P=0.3 for coronary events; P homogeneity=0.4). CONCLUSIONS: Patients with previous vascular events are at high risk of recurrences of the same event. However, because they are also at risk of other vascular outcomes, a broad range of secondary prevention strategies is necessary for their treatment. BP-lowering is likely to be one of the most effective and generalizable strategies across a variety of major vascular events including stroke and myocardial infarction.

Aged↗
PubMed2006

Blood pressure and the global burden of disease 2000. Part 1: estimates of blood pressure levels.

OBJECTIVE: To provide global estimates of blood pressure by age and sex for adults aged > or = 30 years, by WHO subregion. DESIGN AND METHODS: Data were obtained from studies identified in a literature review of population-based surveys. These were complemented by data from MONICA and INTERSALT studies. Estimates of the shape of the age-systolic blood pressure (SBP) association were made from survey data utilizing parametric and non-parametric analyses. A linear sex-specific association of SBP with age was demonstrated from 30 to 70 years in females and 20 to 70 years for males in each subregion. Mean age- and sex-specific estimates of SBP were estimated for each WHO subregion separately, based on study and country-weighted SBP data. RESULTS: Analyses were based on data from about 230 surveys and over 660 000 participants. Age-specific mean SBP values ranged from 114 to 164 mmHg for females, and 117-153 mmHg for males. Females typically had lower SBP levels than males in the 30-44-year age groups, but in all subregions, SBP levels rose more steeply with age for females than males. Therefore, SBP levels in those aged > or = 60 years tended to be higher in females. Subregions with consistently high mean SBP levels included parts of eastern Europe and Africa. Mean SBP levels were lowest in south-east Asia and parts of the western Pacific. CONCLUSIONS: These global estimates of blood pressure by age, sex and subregion show considerable variation in estimated levels. The lack of data in developing countries is substantial, and this is an important limitation given the role of blood pressure in increasing cardiovascular disease levels.

Adult↗
PubMed2006

Blood pressure and the global burden of disease 2000. Part II: estimates of attributable burden.

OBJECTIVES: To provide estimates of the global burden of disease attributable to non-optimal blood pressure by age and sex for adults aged > or = 30 years, by WHO subregion. METHODS: Estimates of attributable burden were made using population impact fractions, which used data on mean systolic blood pressure levels, disease burden [in deaths and/or disability-adjusted life years (DALYs)] and relative risk corrected for regression dilution bias. Estimates were made of burden attributable to a population distribution of blood pressure with a mean systolic blood pressure of greater than 115 mmHg. RESULTS: Globally, approximately two-thirds of stroke and one-half of ischaemic heart disease were attributable to non-optimal blood pressure. These proportions were highest in the more developed parts of the world. Worldwide, 7.1 million deaths (approximately 12.8% of the global total) and 64.3 million DALYs (4.4% of the global total) were estimated to be due to non-optimal blood pressure. Overall approximately, two-thirds of the attributable burden of disease occurred in the developing world, approximately two-thirds in the middle age groups (45-69 years) and approximately one-half occurred in those with systolic blood pressure levels between 130 and 150 mmHg. CONCLUSIONS: The burden of non-optimal blood pressure is almost double that of the only previous global estimates, which is largely explained by the correction for regression dilution adopted in these analyses. High blood pressure is a leading cause of global burden of disease, and most of it occurs in the developing world.

Blood Pressure↗
PubMed2005

Comparison of B-type natriuretic peptides for assessment of cardiac function and prognosis in stable ischemic heart disease.

UNLABELLED: In 1,049 patients with stable ischemic heart disease (IHD), brain natriuretic peptide (BNP) and amino terminal pro-brain natriuretic peptide (NTproBNP) correlated closely (r = 0.09, p < 0.001) and were similarly related to left ventricular ejection fraction (LVEF) (r = -0.50 and -0.46, respectively), age (0.44 and 0.47), and creatinine clearance (-0.51 and -0.51). Receiver-operating characteristic curves for detection of LVEF <30% were similar (area under the curves = 0.83 and 0.80, both p < 0.001), and both peptides had strong negative predictive value (95% and 94%). Both independently predicted all-cause mortality and/or heart failure with closely overlapping event-free survival curves; BNP and NTproBNP display strong, near-identical test performance in ruling about severely reduced LVEF and in prediction of all-cause mortality or heart failure in stable IHD. OBJECTIVES: The aim of this work was to test B-type natriuretic peptides for assessment of function and prognosis in stable ischemic heart disease (IHD) and to compare brain natriuretic peptide (BNP) with amino terminal pro-brain natriuretic peptide (NTproBNP), including the relative effects of age and renal function on test performance. BACKGROUND: Brain natriuretic peptide and NTproBNP are emerging diagnostic and prognostic markers in heart failure and acute coronary syndromes. Their performance in assessing function and prognosis in stable IHD is unknown. Whether one marker is superior and the relative effects of age and renal function on test performance are uncertain. METHODS: In 1,049 patients with stable IHD, left ventricular ejection fraction (LVEF) was measured by radionuclide scanning and creatinine clearance estimated by the Cockroft-Gault equation. Age, gender, and body mass index were recorded. Twelve-month all-cause mortality or admission with heart failure was prospectively recorded; BNP and NTproBNP were measured by radioimmunoassay. RESULTS: Brain natriuretic peptide and NTproBNP correlated closely (r = 0.90, p < 0.001) and had similar relationships to LVEF (r = -0.50 and -0.46, respectively, both p < 0.001), age (0.44 and 0.47, both p < 0.001), and creatinine clearance (-0.51 and -0.51, both p < 0.001). Areas under receiver-operating characteristic curves for detection of LVEF <30% were similar (0.83 and 0.80, both p < 0.001) with strong negative predictive values for both (95% and 94%). Both markers independently predicted the clinical end point with closely overlapping event-free survival curves. CONCLUSIONS: In stable IHD, BNP and NTproBNP display strong and near-identical test performance in ruling out severely reduced LVEF and in prediction of all-cause mortality or heart failure despite significant effects of age, gender, and renal function on levels of both markers.

Aged↗
PubMed2005

Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy.

BACKGROUND: The prevalence of white matter hyperintensities (WMHs) detected on cerebral MRI is associated with hypertension, but it is not known whether blood pressure lowering can arrest their progression. We report here the results of an MRI substudy of PROGRESS (Perindopril Protection Against Recurrent Stroke Study), a randomized trial of blood pressure lowering in subjects with cerebrovascular disease. METHODS AND RESULTS: The substudy comprised 192 participants who had a cerebral MRI both at baseline and after a mean follow-up time of 36 months (SD=6.0 months). At the first MRI, WMHs were graded with a visual rating scale from A (no WMH) to D (severe WMH). Participants were assigned to a combination of perindopril plus indapamide (or their placebos; 58%) or to single therapy with perindopril (or placebo). At the time of the second MRI, the blood pressure reduction in the active arm compared with the placebo arm was 11.2 mm Hg for systolic blood pressure and 4.3 mm Hg for diastolic blood pressure. Twenty-four subjects (12.5%) developed new WMHs at follow-up. The risk of new WMH was reduced by 43% (95% CI -7% to 89%) in the active treatment group compared with the placebo group (P=0.17). The mean total volume of new WMHs was significantly reduced in the active treatment group (0.4 mm3 [SE=0.8]) compared with the placebo group (2.0 mm3 [SE=0.7]; P=0.012). This difference was greatest for patients with severe WMH at entry, 0.0 mm3 (SE=0) in the active treatment group versus 7.6 mm3 (SE=1.0) in the placebo group (P<0.0001). CONCLUSIONS: These results indicate that an active blood pressure-lowering regimen stopped or delayed the progression of WMHs in patients with cerebrovascular disease.

Aged↗
PubMed2005

Perindopril-based blood pressure-lowering reduces major vascular events in patients with atrial fibrillation and prior stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Patients with atrial fibrillation have a high risk of stroke and other vascular events even if anticoagulated. The primary objective here is to determine whether routine blood pressure-lowering provides additional protection for this high-risk patient group. METHODS: This study was a subsidiary analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS)--a randomized, placebo-controlled trial that established the beneficial effects of blood pressure--lowering in a heterogeneous group of patients with cerebrovascular disease. A total of 6105 patients were randomly assigned to either active treatment (2 to 4 mg perindopril for all participants plus 2.0 to 2.5 mg indapamide for those without an indication for or a contraindication to a diuretic) or matching placebo(s). Outcomes are total major vascular events, cause-specific vascular outcomes, and death from any cause. RESULTS: There were 476 patients with atrial fibrillation at baseline, of whom 51% were taking anticoagulants. In these patients, active treatment lowered mean blood pressure by 7.3/3.4 mm Hg and was associated with a 38% (95% confidence interval [CI], 6 to 59) reduction in major vascular events and 34% (95% CI, -13 to 61) reduction in stroke. The benefits of blood pressure-lowering in patients with atrial fibrillation were achieved irrespective of the use of anticoagulant therapy (P homogeneity=0.8) or the presence of hypertension (P homogeneity=0.4). CONCLUSIONS: For most patients with atrial fibrillation, routine blood pressure-lowering is likely to provide protection against major vascular events additional to that conferred by anticoagulation.

Aged↗
PubMed2005

Plasma lipids predict myocardial infarction, but not stroke, in patients with established cerebrovascular disease.

AIMS: To evaluate the role of plasma lipids in recurrent vascular events, including stroke, among individuals with established cerebrovascular disease. METHODS AND RESULTS: Plasma total cholesterol, HDL cholesterol, and triglycerides were measured at baseline among individuals participating in the Perindopril Protection Against Recurrent Stroke (PROGRESS) study, a randomized clinical trial of blood pressure lowering among patients with previous stroke or transient ischaemic attack. A series of nested case-control studies were used to investigate the association between each of these lipid variables and the risk of subsequent haemorrhagic stroke, ischaemic stroke, myocardial infarction (MI), and heart failure. A total of 895 patients were selected as cases (83 haemorrhagic stroke, 472 ischaemic stroke, 206 MI, and 258 heart failure) and each was matched with one to three controls. After adjustment for other major cardiovascular risk factors, none of the lipid variables was associated with the risk of either stroke subtype. There were significant positive and negative associations for total cholesterol and HDL, respectively, with the risk of MI; the odds ratio comparing the highest and lowest thirds of each of these lipid variables was 2.00 (95% CI: 1.30-3.09) for total cholesterol and 0.58 (95% CI: 0.37-0.90) for HDL. HDL was inversely associated with the risk of heart failure; however, this result was of borderline statistical significance (P=0.05). CONCLUSION: Lipid variables are associated with the risk of MI, but not recurrent stroke, in patients with established cerebrovascular disease.

Aged↗
PubMed2005

Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials.

BACKGROUND: Blood pressure (BP) level is a major determinant of cardiovascular morbidity and mortality in individuals with diabetes mellitus. Several guidelines recommend lower BP goals and specific drug classes for these patients. The overviews reported herein were performed to formally compare the effects on cardiovascular events and death of different BP-lowering regimens in individuals with and without diabetes. METHODS: Twenty-seven randomized trials (N = 158 709 participants) that included 33 395 individuals with diabetes and 125 314 without diabetes contributed to these analyses. For each outcome and each comparison summary, estimates of effect and 95% confidence intervals were calculated for patients with and without diabetes using a random-effects model. The constancy of the effects of each treatment regimen in participants with and without diabetes was examined using chi(2) tests of homogeneity. RESULTS: Total major cardiovascular events were reduced to a comparable extent in individuals with and without diabetes by regimens based on angiotensin-converting enzyme inhibitors, calcium antagonists, angiotensin receptor blockers, and diuretics/beta-blockers (P > .19 for all by chi(2) test of homogeneity). There was limited evidence that lower BP goals produced larger reductions in total major cardiovascular events in individuals with vs without diabetes (P = .03 by chi(2) test of homogeneity). CONCLUSIONS: These overviews showed that the short- to-medium-term effects on major cardiovascular events of the BP-lowering regimens studied were broadly comparable for patients with and without diabetes. Different effects of regimens on intermediate renal outcomes not evaluated in these overviews may still provide a rationale for using specific drug classes in patients with diabetes.

Aged↗
PubMed2004

Leg ulceration and perceived health: a population based case-control study.

OBJECTIVES: To quantify the effect of leg ulceration on health-related quality of life and to estimate a health state value for leg ulceration. DESIGN: Population based case-control study. SETTING: Two New Zealand health districts (population 540,468 people). SUBJECTS: 241 people with a leg ulcer of any aetiology, and 224 controls randomly selected from the electoral roll using stratified sampling. MAIN OUTCOME MEASURES: health-related quality of life as measured by the eight domains of the Short Form 36 question Health Survey, adjusted for age, sex and confounding co-morbidities; the physical component summary and mental component summary scores of the Short Form 36 question Health Survey standardised for age and sex; preference-based health state value derived from the Short Form 36 question Health Survey. RESULTS: Completed Short Form 36 question Health Survey questionnaires were available for 230 cases (95%) and 218 controls (97%). Cases reported significantly lower mean scores than controls across all eight domains of the Short Form 36 question Health Survey (P < 0.0005). Mean domain scores for cases were also significantly lower than population norms. The mean physical component summary score for cases and controls was 45.2 versus 50.1 (P < 0.0001) and the mean mental component summary score was 48.1 for cases versus 51 for controls (P < 0.0001). The mean health state values (adjusted for age and sex) were 0.80 for cases and 0.89 for controls. CONCLUSION: Leg ulcers reduce quality of life to a similar extent as other common chronic conditions, such as arthritis and diabetes.

Adult↗
PubMed2004

Perindopril-based blood pressure lowering in individuals with cerebrovascular disease: consistency of benefits by age, sex and region.

OBJECTIVE: To assess the consistency of the benefits of blood pressure lowering on secondary stroke risk by age, sex and geographic region of recruitment. DESIGN: Randomized, placebo-controlled trial. Participants were randomized to the angiotensin-converting enzyme (ACE) inhibitor perindopril (plus the diuretic indapamide if not indicated or contraindicated) or to placebo(s) over a mean follow-up of 3.9 years. Main analyses used Cox proportional hazards models on an intention-to-treat basis. Subgroup results were standardized for the proportion (42%) taking single-drug therapy. SETTING: A total of 172 centres in Asia, Australia, New Zealand and Europe. PARTICIPANTS: Patients (n = 6105) with a history of stroke or transient ischaemic attack, of whom 50% were aged over 65 years at baseline, 30% were women and 39% were from Asia. MAIN OUTCOME MEASURES: Stroke, coronary heart disease and major vascular events. RESULTS: Overall, treatment reduced stroke by 28% [95% confidence interval (CI) 17-38%] and major vascular events by 26% (16-44%), with separately significant reductions across subgroups defined by age (< or > or = 65 years), sex and region (Asia or not). Treatment was safe and well tolerated, and the absolute benefits were large; 5 years' treatment would be expected to avert at least one major vascular event among every 20 patients in all age, sex and region subgroups. There was some evidence of particularly large benefits among younger participants and those from Asia. CONCLUSIONS: Blood pressure lowering reduces secondary stroke risk, with large absolute benefits across groups defined by age, sex and geographic region.

Age Distribution↗
PubMed2004

International collaborative study of cardiovascular disease in Asia: design, rationale, and preliminary results.

OBJECTIVES: The overall objective of the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA) was to estimate the prevalence and distribution of cardiovascular disease risk factors, including hypertension, hypercholesterolemia, diabetes, obesity, cigarette smoking, and physical inactivity, in the general population of both China and Thailand. METHODS AND RESULTS: A multistage cluster sampling method was used to select a nationally representative sample of 15,838 adults, aged 35-74 years, in China, and 5,350 similarly aged adults in Thailand. Data on medical history, cigarette smoking, alcohol consumption, diet, physical activity, and awareness and control of risk factors for cardiovascular disease, were collected. Blood pressure, body weight and height, and hip and waist circumferences, were measured using standard methods. Fasting blood specimens were collected to measure levels of total cholesterol, high-density lipoprotein cholesterol, triglycerides, glucose, and creatinine. All data were carefully collected by specially trained, experienced observers using standardized methods and a stringent level of quality control. The prevalence of self-reported cardiovascular disease in Chinese adults aged 35-74 years was 3.3% in men and 3.6% in women (representing 8,147,000 male and 8,270,000 female cases nationally). The prevalence of self-reported cardiovascular disease in Thai adults was 1.5% in men and 1.7% in women (representing 184,000 male and 226,000 female cases). CONCLUSIONS: The InterASIA study provides important information on the current prevalence and control of both cardiovascular disease and its risk factors in the region. These findings will be useful for developing national strategies to reduce the large, and increasing, burden of cardiovascular disease in China and Thailand.

Adult↗
PubMed2003

The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition.

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.

Adult↗
PubMed2003

Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease.

BACKGROUND: High blood pressure and stroke are associated with increased risks of dementia and cognitive impairment. This study aimed to determine whether blood pressure lowering would reduce the risks of dementia and cognitive decline among individuals with cerebrovascular disease. METHODS: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial conducted among 6105 people with prior stroke or transient ischemic attack. Participants were assigned to either active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). The primary outcomes for these analyses were dementia (using DSM-IV criteria) and cognitive decline (a decline of 3 or more points in the Mini-Mental State Examination score). RESULTS: During a mean follow-up of 3.9 years, dementia was documented in 193 (6.3%) of the 3051 randomized participants in the actively treated group and 217 (7.1%) of the 3054 randomized participants in the placebo group (relative risk reduction, 12% [95% confidence interval, -8% to 28%]; P =.2). Cognitive decline occurred in 9.1% of the actively treated group and 11.0% of the placebo group (risk reduction, 19% [95% confidence interval, 4% to 32%]; P =.01). The risks of the composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke were reduced by 34% (95% confidence interval, 3% to 55%) (P =.03) and 45% (95% confidence interval, 21% to 61%) (P<.001), respectively, with no clear effect on either dementia or cognitive decline in the absence of recurrent stroke. CONCLUSIONS: Active treatment was associated with reduced risks of dementia and cognitive decline associated with recurrent stroke. These findings further support the recommendation that blood pressure lowering with perindopril and indapamide therapy be considered for all patients with cerebrovascular disease.

Aged↗
PubMed2003

Leg ulceration as a long-term complication of deep vein thrombosis.

OBJECTIVE: To evaluate the role of deep vein thrombosis as a cause of leg ulcers. PATIENTS AND METHODS: A population-based, case-control study was conducted in Central and North Auckland, New Zealand. Cases comprised 241 people aged 40 to 99 years and on the electoral roll, with current leg ulcers (all types). Cases were identified by means of notification from health professionals and by self-referral. Controls were 224 people in the same age group, without leg ulcers, who were selected from the electoral roll by using a stratified random sampling process. MAIN OUTCOME MEASURES: The occurrence of leg ulceration as a consequence of exposure to deep vein thrombosis or being at high risk of deep vein thrombosis (that is, people with a family history of deep vein thrombosis, and/or a history of leg fracture and/or hip, leg, or foot surgery). RESULTS: After adjustment for age, sex, and other potential confounding factors, people who had a diagnosed thromboembolism were at almost three times higher risk of having a leg ulcer (odds ratio, 2.92; 95% confidence interval (CI), 1.47 to 6.08). In addition, people who had been at high risk of a venous thrombosis but were not diagnosed with this condition (eg, people with a history of major leg surgery) were also at increased risk of ulceration (odds ratio, 2.25; 95% CI, 1.49-3.42). Overall, 56% (95% CI, 33% - 71%) of leg ulcers were attributed to being at high risk of deep vein thrombosis. CONCLUSIONS: Deep vein thrombosis and factors that place people at high risk of deep vein thrombosis are an important cause of leg ulcers in older people. This finding strengthens the rationale for the routine and long-term use of thromboprophylaxis, particularly in high-risk patients.

Adult↗
PubMed2003

Is body mass index a risk factor for motor vehicle driver injury? A cohort study with prospective and retrospective outcomes.

OBJECTIVE: To investigate the association between risk of motor vehicle driver injury and body mass index (BMI). METHODS: In a cohort study of 10 525 New Zealand men and women, BMI was assessed in 1992-1993 (baseline), and data on deaths and hospitalizations for motor vehicle driver injury were obtained by record linkage to national health databases for the period 1988-1998. Hazard ratios (HR) and CI were estimated by Cox regression. RESULTS: During a mean 10.3 years of follow-up, 139 fatal and non-fatal driver injury cases occurred (85 before baseline and 54 after). A U-shaped association was observed between driver injury risk and BMI, both crudely and after adjustment for covariates, which included age, sex, driving exposure, and alcohol intake (P-values for quadratic trend </=0.02). Participants in the highest (>/=28.7 kg/m(2); HR = 2.00, 95% CI: 1.18-3.39) and lowest (<23.5 kg/m(2); HR = 2.17, 95% CI: 1.27-3.73) quartiles of BMI were twice as likely to have experienced a driver injury during the follow-up period as participants in the reference quartile (25.9-28.6 kg/m(2); HR = 1.00). CONCLUSION: Further research is needed to corroborate or refute the hypothesis that BMI is a risk factor for serious motor vehicle driver injury.

Accidents, Traffic↗
PubMed2003

Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS): interpretation and implementation.

OBJECTIVES: To determine the effects of a perindopril-based blood pressure lowering regimen in hypertensive and non-hypertensive patients with a history of stroke or transient ischaemic attack (TIA). DESIGN AND METHODS: 6105 subjects from 172 centres in Asia, Australasia, and Europe were randomised to receive active treatment (n = 3051) or placebo (n = 3054). Active treatment consisted of a flexible regimen based on the angiotensin-converting enzyme inhibitor perindopril (4 mg daily), with the addition of the diuretic indapamide, at the discretion of treating physicians. The primary outcome was total stroke (fatal or non-fatal). Analysis was by intention to treat. RESULTS: Active treatment reduced blood pressure by 9/4 mmHg over 4 years of follow-up. 307 (10%) individuals assigned active treatment suffered a stroke, compared with 420 (14%) assigned placebo [relative risk reduction 28% (95% confidence interval 17-38), P < 0.0001]. Active treatment also reduced the risks of total major vascular events [26% (16-34)] including non-fatal myocardial infarction [38% (14-55)], severe cognitive decline [19% (4-32)], stroke-related dementia [34% (3-55)] and disability [18% (8-28)]. There were similar reductions in the risk of stroke in hypertensive and non-hypertensive subgroups (P < 0.01). Combination therapy with perindopril plus indapamide lowered blood pressure by 12/5 mmHg and stroke risk by 43%. Single-drug therapy lowered blood pressure by 5/3 mmHg and produced no significant fall in the risk of stroke. CONCLUSIONS: The blood-pressure lowering regimen used in Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) reduced the risks of stroke and other serious events in hypertensive and non-hypertensive subjects with a history of stroke (whatever the subtype) or transient ischaemic attack. Combination therapy with perindopril and indapamide produced larger blood pressure reductions and larger stroke reductions than monotherapy with perindopril alone. Treatment with these two agents should be considered routinely for all patients with a history of previous stroke or TIA, whether hypertensive or normotensive.

Angiotensin-Converting Enzyme Inhibitors↗