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Biomedical subjects

S MacMahon

Publications and source records attributed to S MacMahon.

At least 19 recordsLinked to original sources
PubMed2005

Chronic suppurative osteomyelitis of the mandible: case report.

BACKGROUND: Osteomyelitis of the maxillofacial skeleton is rare in developed countries such as Australia. This case report describes the successful surgical treatment of chronic suppurative osteomyelitis (CSO) of the mandible in a 75 year old man. The precipitant factor was thought to be a retained tooth root in the (right) posterior body of the mandible. METHODS: Treatment included a pre-surgical course of antibiotics (clindamycin 300mg, p.o. q.i.d. for two weeks) followed by removal of the retained root, surgical débridement of the affected bone, the intra-oral draining sinus, and resection of the cutaneous sinus tract. Specimens were taken for bacterial cultures and antibiotic sensitivity testing, and the resected tissue sent for histopathological review. RESULTS: On clinical and radiographic review at three months, the patient was well, completely symptom free and the osteomyelitis had fully resolved. CONCLUSION: This case report demonstrates the typical features of CSO. The combination of antibiotic therapy and surgical débridement was effective in the treatment of chronic suppurative osteomyelitis of the mandible utilizing intravenous sedation, and so averting the need for a general anaesthetic.

Aged↗
PubMed2004

Motor vehicle driver injury and marital status: a cohort study with prospective and retrospective driver injuries.

OBJECTIVE: To investigate the association of marital status with risk of motor vehicle driver injury. DESIGN: A cohort study with prospective and retrospective outcomes. SETTING: New Zealand. PARTICIPANTS: A total of 10,525 adults (a volunteer sample of a multi-industry workforce, n = 8008; and a random sample of urban electoral rolls, n = 2517). EXPOSURE VARIABLE: Self reported marital status, assessed from a questionnaire administered in 1992-93 (baseline). MAIN OUTCOME MEASURE: Motor vehicle driver injury resulting in admission of the driver to hospital and/or the driver's death, during the period 1988-98; hospitalisation and mortality data were obtained by record linkage to national health databases. RESULTS: During 108 741 person-years of follow up, 139 driver injury cases occurred (85 before baseline, 54 after). After adjustment for age, sex, and study cohort, never married participants had twice the risk of driver injury (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.35 to 3.16) as married participants (HR 1.00). The relative risk for never married participants was slightly higher (HR 2.29), though less precise (95% CI 1.39 to 3.76), after further adjustment for alcohol intake, driving exposure, area of residence, body mass index, and occupational status. CONCLUSIONS: After taking age, sex, and other variables into account, never married people had a substantially higher risk of driver injury than married people. While requiring corroboration, these findings imply that it may be appropriate for driver injury countermeasures to be targeted to never married people.

Accidents, Traffic↗
PubMed2003

Effects of a perindopril-based blood pressure-lowering regimen on the risk of recurrent stroke according to stroke subtype and medical history: the PROGRESS Trial.

BACKGROUND AND PURPOSE: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) showed that blood pressure lowering reduced stroke risk in patients with a history of cerebrovascular events. Here, we report the consistency of treatment effects across different stroke subtypes and among major clinical subgroups. METHODS: PROGRESS was a randomized, double-blind trial among 6105 people with a prior history of cerebrovascular events. Participants were assigned to 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). RESULTS: During a mean of 3.9 years of follow-up, active treatment reduced the absolute rates of ischemic stroke from 10% to 8% (relative risk reduction [RRR], 24%; 95% confidence interval [CI], 10 to 35) and the absolute rates of intracerebral hemorrhage from 2% to 1% (RRR, 50%; 95% CI, 26 to 67). The relative risk of any stroke during follow-up was reduced by 26% (95% CI, 12 to 38) among patients whose baseline cerebrovascular event was an ischemic stroke and by 49% (95% CI, 18 to 68) among those whose baseline event was an intracerebral hemorrhage. There was no evidence that treatment effects were modified by other drug therapies (antiplatelet or other antihypertensive agents), residual neurological signs, atrial fibrillation, or the time since the last cerebrovascular event. CONCLUSIONS: Beneficial effects of a perindopril-based treatment regimen were observed for all stroke types and all major clinical subgroups studied. These data suggest that effective blood pressure-lowering therapy should be routinely considered for all patients with a history of cerebrovascular events.

Aged↗
PubMed2003

Effects of a perindopril-based blood pressure-lowering regimen on disability and dependency in 6105 patients with cerebrovascular disease: a randomized controlled trial.

BACKGROUND AND PURPOSE: We sought to quantify the effects of blood pressure lowering on long-term disability and dependency among patients with cerebrovascular disease. METHODS: We performed a randomized, double-blind, placebo-controlled trial. A total of 6105 participants with a history of stroke or transient ischemic attack in the past 5 years were recruited from 172 hospital outpatient clinics in 10 countries. Subjects were randomly assigned to the following groups: active treatment (angiotensin-converting enzyme inhibitor perindopril [4 mg/d] for all patients, with the diuretic indapamide added at the discretion of treating physicians) or matching placebo(s). Measurements were disability (defined as a Barthel Index score < or =99/100) and dependency (a positive response to the following question: "In the last 2 weeks has the patient required regular help with everyday activities?"). RESULTS: The median duration of follow-up was 4 years. At the last available assessment, 19% of the active treatment group and 22% of the placebo group were disabled (adjusted odds ratio, 0.76; 95% CI, 0.65 to 0.89; P<0.001). Twelve percent of the active treatment group and 14% of the placebo group were dependent (adjusted odds ratio, 0.84; 95% CI, 0.71 to 0.99; P=0.04). The effects of treatment appeared to be mediated primarily through the prevention of disability and dependency associated with recurrent stroke. Four-year treatment with the study drug regimen would be expected to result in the avoidance of 1 case of long-term disability for every 30 (95% CI, 19 to 79) patients. CONCLUSIONS: Among individuals with cerebrovascular disease, a perindopril-based blood pressure-lowering regimen not only reduced the risk of stroke and major vascular events but also substantially reduced the risks of associated long-term disability and dependency.

Activities of Daily Living↗
PubMed2003

Cholesterol, coronary heart disease, and stroke in the Asia Pacific region.

BACKGROUND: Cholesterol levels in many Asian countries are rising. Predictions of the likely effects of this on the incidence of cardiovascular diseases have mostly relied on data from Western populations. Whether the associations between total cholesterol and cardiovascular diseases are similar in Asia is not established. METHODS: The Asia Pacific Cohort Studies Collaboration (APCSC) is an individual-participant data meta-analysis of prospective studies from the Asia-Pacific region. Cox models were applied to the combined data from 29 cohorts to estimate the region-, sex-, and age-specific hazard ratios of major cardiovascular diseases by the fifths of total cholesterol. RESULTS: At baseline, the age/sex-adjusted mean value of total cholesterol was higher in Australia and New Zealand (ANZ) (5.52 +/- 1.05 mmol/l) than in Asia (4.87 +/- 1.05 mmol/l). During 2 million person-years of follow-up among 352 033 individuals, 4841 cardiovascular deaths were recorded. The association of total cholesterol with coronary heart disease and stroke was similar in Asian and ANZ cohorts. Overall, each 1-mmol/l higher level of total cholesterol was associated with 35% (95% CI: 26-44%) increased risk of coronary death, 25% (95% CI: 13-40%) increased risk of fatal or non-fatal ischaemic stroke, and 20% (95% CI: 8-30%) decreased risk of fatal haemorrhagic stroke. CONCLUSIONS: In both Asian and non-Asian populations in the Asia-Pacific region, total cholesterol is similarly strongly associated with the risk of CHD and ischaemic, but not haemorrhagic, stroke. Rising population-wide levels of cholesterol would be expected to contribute to a substantial increase in the overall burden of cardiovascular diseases in this region.

Adult↗
PubMed2003

Blood pressure and cardiovascular disease in the Asia Pacific region.

OBJECTIVES: To estimate age-, sex- and region-specific associations of blood pressure with cardiovascular diseases. DESIGN: Relative risk estimates and 95% confidence intervals were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk on individual participant data from 37 cohort studies. Repeat measurements of blood pressure were used to adjust for regression dilution bias. SETTING: Studies included in the Asia Pacific Cohort Studies Collaboration from Australia, mainland China, Hong Kong, Japan, New Zealand, Singapore, South Korea, and Taiwan. PARTICIPANTS: A total of 425 325 study participants. MAIN OUTCOMES MEASURES: Stroke, ischaemic heart disease, total cardiovascular death. RESULTS: During over 3 million person-years of follow-up, 5178 strokes, 3047 ischaemic heart disease events and 6899 cardiovascular deaths were observed. Continuous log-linear associations were seen between systolic blood pressure and the risks of all three endpoints down to at least 115 mmHg. In the age groups < 60, 60-69, and > or = 70 years, a 10 mmHg lower usual systolic blood pressure was associated with 54% (95% CI 53-56%), 36% (34-38%) and 25% (22-28%) lower stroke risk, and 46% (43-49%), 24% (21-28%) and 16% (13-20%) lower ischaemic heart disease risk, respectively. All associations were similar in men and women. Blood pressure was at least as strongly associated with cardiovascular events in Asian populations compared to Australasian populations. CONCLUSIONS: About half of the world's cardiovascular burden is predicted to occur in the Asia Pacific region. Blood pressure is an important determinant of this burden, with considerable potential benefit of blood pressure lowering down to levels of at least 115 mmHg systolic blood pressure.

Aged↗
PubMed2003

Motor vehicle driver injury and socioeconomic status: a cohort study with prospective and retrospective driver injuries.

STUDY OBJECTIVE: To investigate the association between motor vehicle driver injury and socioeconomic status. DESIGN: Cohort study with prospective and retrospective outcomes. SETTING: New Zealand. PARTICIPANTS: 10 525 adults (volunteer sample of a multi-industry workforce, n=8008; and a random sample of urban electoral rolls, n=2517). OUTCOME MEASURE: Motor vehicle driver injury resulting in admission of the driver to hospital or the driver's death, or both, during the period 1988-98; hospitalisation and mortality data were obtained by record linkage to national health databases. MAIN RESULTS: After adjustment for age and sex, driver injury risk was inversely associated with both occupational status (p for linear trend <0.0001) and educational level (p for linear trend =0.007). Participants in the lowest approximate quartile of occupational status were four times as likely (HR 4.17, 95% CI 2.31 to 7.55) to have experienced a driver injury during follow up as participants in the highest approximate quartile. Participants who had been to secondary school for less than two years were twice as likely (HR 2.26, 95% CI 1.34 to 3.81) to have experienced a driver injury as those who had been to university or polytechnic. There was little evidence that driver injury risk was associated with neighbourhood income (p for linear trend =0.12) CONCLUSIONS: Occupational status and educational level seem to be important determinants of driver injury risk. Driver injury countermeasures should be targeted to people in low status occupations, as well as to people with comparatively little formal education.

Accidents, Traffic↗
PubMed2003

The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region.

OBJECTIVE: To provide reliable age- and region-specific estimates of the associations between diabetes and major cardiovascular diseases and death in populations from the Asia-Pacific region. RESEARCH DESIGN AND METHODS: Twenty-four cohort studies from Asia, Australia, and New Zealand (median follow-up, 5.4 years) provided individual participant data from 161,214 people (58% from Asia) of whom 4,873 had a history of diabetes at baseline. The associations of diabetes with the risks of coronary heart disease, stroke, and cause-specific mortality during follow-up were estimated using time-dependent Cox models, stratified by study cohort and sex and adjusted for age at risk. RESULTS: In all, 9,277 deaths occurred (3,635 from cardiovascular disease). The hazard ratio (95% CI) associated with diabetes was 1.97 (1.72-2.25) for fatal cardiovascular disease; there were similar hazard ratios for fatal coronary heart disease, fatal stroke, and composites of fatal and nonfatal outcomes. For all cardiovascular outcomes, hazard ratios were similar in Asian and non-Asian populations and in men and women, but were greater in younger than older individuals. For noncardiovascular death, the hazard ratio was 1.56 (1.38-1.77), with separately significant increases in the risks of death from renal disease, cancer, respiratory infections, and other infective causes. The hazard ratio for all-causes mortality was 1.68 (1.55-1.84), with similar ratios in Asian and non-Asian populations, but with significantly higher ratios in younger than older individuals. CONCLUSIONS: The relative effect of diabetes on the risks of cardiovascular disease and death in Asian populations is much the same as that in the largely Caucasian populations of Australia and New Zealand. Hazard ratios were severalfold greater in younger people than older people. The rapidly growing prevalence of diabetes in Asia heralds a large increase in the incidence of diabetes-related death in the coming decades.

Age Distribution↗
PubMed2001

Synthetic approaches to a variety of covalently linked porphyrin--fullerene hybrids.

There is substantial interest in dyads in which C(60) is covalently linked to electron donors, such as porphyrins, which absorb light strongly in the visible region. We present here the details of the syntheses of such compounds, which can be broadly organized into categories depending upon the nature of the linker joining the two chromophores. The structural aspects of intramolecular electronic interaction that we have sought to explore have dictated the synthetic strategies employed to generate these classes of molecules. Flexible glycol linkers were used to allow close approach between the fullerene and porphyrin, facilitating through-space interactions. These linkers also allowed studies of the effects of metal cation complexation. Naphthalene and alkyne linkers were used to examine the possible effects a conjugated or aromatic linker might have on photophysical properties. Finally, steroids were used as linkers in dyads expected to possess a large distance between the two chromophores, in which only through-bond interactions between the fullerene and porphyrin should be possible.

Journal Article↗
PubMed2001

Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group.

OBJECTIVES: We sought to assess plasma concentrations of the amino (N)-terminal portion of pro-brain natriuretic peptide (N-BNP) and adrenomedullin for prediction of adverse outcomes and responses to treatment in 297 patients with ischemic left ventricular (LV) dysfunction who were randomly assigned to receive carvedilol or placebo. BACKGROUND: Although neurohormonal status has known prognostic significance in heart failure, the predictive power of either N-BNP or adrenomedullin in chronic ischemic LV dysfunction has not been previously reported. METHODS: Plasma N-BNP and adrenomedullin were measured in 297 patients with chronic ischemic (LV) dysfunction before randomization to carvedilol or placebo, added to established treatment with a converting enzyme inhibitor and loop diuretic (with or without digoxin). The patients' clinical outcomes, induding mortality and heart failure events, were recorded for 18 months. RESULTS: Above-median N-BNP and adrenomedullin levels conferred increased risks (all p < 0.001) of mortality (risk ratios [95% confidence intervals]: 4.67 [2-10.9] and 3.92 [1.76-8.7], respectively) and hospital admission with heart failure (4.7 [2.2-10.3] and 2.4 [1.3-4.5], respectively). Both of these predicted death or heart failure independent of age, New York Heart Association functional class, LV ejection fraction, previous myocardial infarction or previous admission with heart failure. Carvedilol reduced the risk of death or heart failure in patients with above-median levels of N-BNP or adrenomedullin, or both, to rates not significantly different from those observed in patients with levels below the median value. CONCLUSIONS: In patients with established ischemic LV dysfunction, plasma N-BNP and adrenomedullin are independent predictors of mortality and heart failure. Carvedilol reduced mortality and heart failure in patients with higher pre-treatment plasma N-BNP and adrenomedullin.

Adrenergic beta-Antagonists↗
PubMed2001

Effect of pravastatin on frequency of fracture in the LIPID study: secondary analysis of a randomised controlled trial. Long-term Intervention with Pravastatin in Ischaemic Disease.

BACKGROUND: Statins inhibit the same biochemical pathway as aminobisphosphonates, therefore these cholesterol-lowering agents may have a beneficial effect on osteoporosis. This possibility has been supported by the finding that some statins also stimulate bone formation, and by observational studies suggesting that patients using statins have higher bone densities and lower fracture rates than controls. To assess whether statins have clinically significant effects on bone, we studied the frequency of fractures in a large randomised controlled trial of these agents. METHODS: 9014 patients (17% women, median age 62 years) with ischaemic heart disease were randomly assigned pravastatin 40 mg daily or placebo and followed up for a mean of 6.0 years. Fractures were ascertained from adverse-event reports. FINDINGS: 101 patients in the placebo group were admitted to hospital for fracture compared with 107 in the pravastatin group (hazard ratio 1.05 [95% CI 0.80-1.37]). When patients with fractures not necessitating hospital admission were added, the total number of patients having a fracture was 183 in the placebo group and 175 in the pravastatin group (0.94 [0.77-1.16]). Separate analyses for women alone and for individuals aged 65 years and over gave similar results. INTERPRETATION: These findings offer no support for the hypothesis that statins have a significant effect on fracture risk. However, this study was not of an osteoporotic population, and fracture rate, although clinically important, is an insensitive index of effects on bone. Statins should not be used to prevent osteoporosis until there is evidence for their efficacy based on randomised controlled trials.

Aged↗
PubMed2001

Reliable assessment of the effects of treatment on mortality and major morbidity, II: observational studies.

Observational studies and randomised trials can contribute complementary evidence about the effects of treatment on mortality and on major non-fatal outcomes. In particular, observational studies have an important role in the identification of large adverse effects of treatment on infrequent outcomes (ie, rare, but serious, side-effects) that are not likely to be related to the indications for (or contraindications to) the treatment of interest. Such studies can also provide useful information about the risks of death and disability in particular circumstances that can help to generalise from clinical trials to clinical practice. But, due to their inherent potential for moderate or large biases, observational studies have little role in the direct assessment of any moderate effects of treatment on major outcomes that might exist. Instead, sufficiently large-scale evidence from randomised trials is needed to assess such treatment effects appropriately reliably. Wider appreciation of the different strengths and weaknesses of these two types of epidemiological study should increase the likelihood that the most reliable evidence available informs decisions about the treatments doctors use--and patients receive--for the management of a wide range of life-threatening conditions.

Evidence-Based Medicine↗
PubMed2001

Reliable assessment of the effects of treatment on mortality and major morbidity, I: clinical trials.

This two-part review is intended principally for practising clinicians who want to know why some types of evidence about the effects of treatment on survival, and on other major aspects of chronic disease outcome, are much more reliable than others. Although there are a few striking examples of treatments for serious disease which really do work extremely well, most claims for big improvements turn out to be evanescent. Unrealistic expectations about the chances of discovering large treatment effects could misleadingly suggest that evidence from small randomised trials or from non-randomised studies will suffice. By contrast, the reliable assessment of any more moderate effects of treatment on major outcomes--which are usually all that can realistically be expected from most treatments for most common serious conditions--requires studies that guarantee both strict control of bias (which, in general, requires proper randomisation and appropriate analysis, with no unduly data-dependent emphasis on specific parts of the overall evidence) and strict control of random error (which, in general, requires large numbers of deaths or of some other relevant outcome). Past failures to produce such evidence, and to interpret it appropriately, have already led to many premature deaths and much unnecessary suffering.

Clinical Trials as Topic↗
PubMed2001

Random errors in the measurement of 10 cardiovascular risk factors.

Random errors in the measurement of 10 commonly investigated cardiovascular risk factors (systolic and diastolic blood pressure, blood cholesterol, blood glucose, pulse rate, body mass index (BMI), cigarette consumption, passive smoking, alcohol intake and physical exercise) were assessed in a general population cohort (n = 2517) and a workforce cohort (n = 8008). Random errors were estimated from regression dilution ratios (lower ratios imply greater random error, and a ratio of one implies no random error). All of the risk factors, except for BMI (which had regression dilution ratios of 0.93 and 0.98 in the two cohorts), were measured with substantial levels of random error. Particularly low regression dilution ratios were observed for physical exercise (0.28 and 0.39) and pulse rate (0.47 and 0.56). For each of these risk factors, with the possible exception of BMI, associations with long-term average values could be importantly biased toward the null unless appropriate corrections are made.

Bias↗
PubMed2001

Blood pressure lowering in diabetes: a brief review of the current evidence and description of a new trial.

1. Diabetes is a major global public health problem. The prevalence of this disease is predicted to increase sharply in the coming decades, particularly in less-developed regions of the world. 2. Most premature morbidity and mortality associated with diabetes relates to markedly increased risks of major cardiovascular diseases, such as myocardial infarction and stroke (macrovascular events), as well as microvascular complications, such as nephropathy and retinopathy. 3. Hypertension is a prevalent and important risk factor for vascular events in these patients. However, observational data demonstrate a continuous relationship between blood pressure and risk of vascular events, suggesting that even those individuals considered normotensive may benefit from blood pressure lowering. 4. Trials of blood pressure lowering among mostly hypertensive individuals with diabetes have demonstrated benefit of intervention on macrovascular and microvascular outcomes. Recent data may suggest additional effects of angiotensin- converting enzyme inhibitors independent of blood pressure lowering. 5. Issues where data are lacking with respect to blood pressure lowering in diabetes include the effects of blood pressure lowering among non-hypertensive individuals and the effects of blood pressure lowering regimens based on different classes of drug. 6. Data expected to address some of these issues are being collected. These include a prospective meta-analysis of blood pressure-lowering trials with large numbers of patients with diabetes. A new large-scale randomised trial, ADVANCE (Action in Diabetes and Vascular Disease), is also described.

Antihypertensive Agents↗
PubMed2000

Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials.

OBJECTIVES: To obtain reliable estimates of the effects of neuraxial blockade with epidural or spinal anaesthesia on postoperative morbidity and mortality. DESIGN: Systematic review of all trials with randomisation to intraoperative neuraxial blockade or not. STUDIES: 141 trials including 9559 patients for which data were available before 1 January 1997. Trials were eligible irrespective of their primary aims, concomitant use of general anaesthesia, publication status, or language. Trials were identified by extensive search methods, and substantial amounts of data were obtained or confirmed by correspondence with trialists. MAIN OUTCOME MEASURES: All cause mortality, deep vein thrombosis, pulmonary embolism, myocardial infarction, transfusion requirements, pneumonia, other infections, respiratory depression, and renal failure. RESULTS: Overall mortality was reduced by about a third in patients allocated to neuraxial blockade (103 deaths/4871 patients versus 144/4688 patients, odds ratio=0.70, 95% confidence interval 0.54 to 0.90, P=0. 006). Neuraxial blockade reduced the odds of deep vein thrombosis by 44%, pulmonary embolism by 55%, transfusion requirements by 50%, pneumonia by 39%, and respiratory depression by 59% (all P<0.001). There were also reductions in myocardial infarction and renal failure. Although there was limited power to assess subgroup effects, the proportional reductions in mortality did not clearly differ by surgical group, type of blockade (epidural or spinal), or in those trials in which neuraxial blockade was combined with general anaesthesia compared with trials in which neuraxial blockade was used alone. CONCLUSIONS: Neuraxial blockade reduces postoperative mortality and other serious complications. The size of some of these benefits remains uncertain, and further research is required to determine whether these effects are due solely to benefits of neuraxial blockade or partly to avoidance of general anaesthesia. Nevertheless, these findings support more widespread use of neuraxial blockade.

Anesthesia, Epidural↗