Search PubMed⌕ Search

Biomedical subjects

Geoffrey A Donnan

Publications and source records attributed to Geoffrey A Donnan.

At least 19 recordsLinked to original sources
PubMed2026

Polygenic Risk Identifies Older Adults Who May Benefit From Aspirin for the Primary Prevention of Ischemic Stroke.

BACKGROUND: Low-dose aspirin is no longer recommended for routine primary prevention in older adults due to bleeding risks outweighing vascular benefits. We hypothesized that an integrative polygenic score (iPGS) could identify a subgroup of older individuals who derive net benefit from aspirin for the primary prevention of ischemic stroke. METHODS: We performed post hoc analysis of the ASPREE randomized, placebo-controlled trial (Aspirin in Reducing Events in the Elderly) of daily 100-mg aspirin, in 12 031 genotyped participants of European ancestry aged >70 years without prior cardiovascular disease. The iPGS was derived from >1.2 million variants and evaluated both continuously and by quintiles. Cox models assessed associations between polygenic risk, ischemic stroke, and major bleeding events, and tested the interaction between the iPGS and treatment allocation, with adjustment for baseline lifestyle and clinical covariates. RESULTS: The mean age of participants was 75.1 years, and 54.9% were women. Over a median of 4.6 years, 187 ischemic strokes and 373 major bleeds occurred, including 101 intracranial bleeds (46 hemorrhagic strokes). Each 1-SD increase in the iPGS was associated with higher incident ischemic stroke risk (hazard ratio, 1.39 [95% CI, 1.20-1.62]). An interaction between the continuous iPGS and aspirin allocation was observed for ischemic stroke (P=0.04) but not major bleeding. In the highest iPGS quintile, aspirin reduced ischemic stroke by 51% (hazard ratio, 0.49 [95% CI, 0.28-0.85]) without significantly increasing major bleeding (hazard ratio, 1.15 [95% CI, 0.71-1.88]). No benefit was observed in the overall cohort or in lower-risk quintiles. CONCLUSIONS: Among older adults, high polygenic risk identifies individuals who may experience substantial stroke reduction with aspirin, with no excess bleeding. These findings raise the possibility that genomic risk stratification may enable targeted aspirin use for the primary prevention of ischemic stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.

Humans↗
PubMed2003

Lifetime cost of stroke subtypes in Australia: findings from the North East Melbourne Stroke Incidence Study (NEMESIS).

BACKGROUND AND PURPOSE: Little is known about any variations in resource use and costs of care between stroke subtypes, especially nonhospital costs. The purpose of this study was to describe the patterns of resource use and to estimate the first-year and lifetime costs for stroke subtypes. METHODS: A cost-of-illness model was used to estimate the total first-year costs and lifetime costs of stroke subtypes for all strokes (subarachnoid hemorrhages excluded) that occurred in Australia during 1997. For each subtype, average cost per case during the first year and the present value of average cost per case over a lifetime were calculated. Resource use data obtained in the North East Melbourne Stroke Incidence Study (NEMESIS) were used. RESULTS: The present value of total lifetime costs for all strokes was Aus 1.3 billion dollars (US 985 million dollars). Total lifetime costs were greatest for ischemic stroke (72%; Aus 936.8 million dollars; US 709.7 million dollars), followed by intracerebral hemorrhage (26%; Aus 334.5 million dollars; US 253.4 million dollars) and unclassified stroke (2%; Aus 30 million dollars; US 22.7 million dollars). The average cost per case during the first year was greatest for total anterior circulation infarction (Aus 28 266 dollars). Over a lifetime, the present value of average costs was greatest for intracerebral hemorrhage (Aus 73 542 dollars), followed by total anterior circulation infarction (Aus 53 020 dollars), partial anterior circulation infarction (Aus 50 692 dollars), posterior circulation infarction (Aus 37 270 dollars), lacunar infarction (Aus 34 470 dollars), and unclassified stroke (Aus 12 031 dollars). CONCLUSIONS: First-year and lifetime costs vary considerably between stroke subtypes. Variation in average length of total hospital stay is the main explanation for differences in first-year costs.

Acute Disease↗
PubMed2003

Risk of ischemic stroke among users of the oral contraceptive pill: The Melbourne Risk Factor Study (MERFS) Group.

BACKGROUND AND PURPOSE: Use of oral contraceptives has increased, and there is uncertainty about the stroke risk associated with their use. Our aim was to investigate this issue. METHODS: Using case-control techniques, we identified consecutive women with ischemic stroke from 4 Melbourne hospitals. All patients were between 15 and 55 years of age and had no prior stroke. Neighborhood-based control subjects were individually age-matched (+/-5 years) and geographically matched to subject cases. A questionnaire administered to participants elicited information about prior exposure to various potential risk factors, including the oral contraceptive pill (OCP). RESULTS: We included 234 cases and 234 controls (mean age, 42 years). Compared with noncurrent use, current use of the OCP, in doses of 20 cigarettes per day (OR, 3.68; 95% CI, 1.22 to 11.09). CONCLUSIONS: There was no evidence for an association between ischemic stroke and use of the OCP in low doses (<or=50 microg estrogen) in young Australian women. Other modifiable risk factors such as hypertension, diabetes mellitus, and smoking are important.

Adolescent↗
PubMed2003

Increased risk of cognitive impairment 3 months after mild to moderate first-ever stroke: a Community-Based Prospective Study of Nonaphasic English-Speaking Survivors.

BACKGROUND AND PURPOSE: Results of hospital-based studies indicate a high risk of cognitive impairment 3 months after stroke. There are no comprehensive data on this issue from prospective community-based studies comparing first-ever stroke patients with stroke-free subjects. METHODS: We administered a comprehensive neuropsychological battery to 99 community-based nonaphasic survivors of first-ever stroke at 3 months and 99 age- and sex-matched (1:1) stroke-free individuals. Domain-specific cognitive deficits were identified by blinded neuropsychological consensus. METHODS: Stroke patients were more likely to suffer any cognitive impairment (relative risk [RR], 1.5; 95% CI, 1.1 to 2.1) attributable mainly to a greater risk of single-domain cognitive impairment (RR, 2.8; 95% CI, 1.5 to 5.3) but not multiple-domain cognitive impairment (RR, 1.2; 95% CI, 0.8 to 1.9). CONCLUSIONS: In this community-based study, a first-ever stroke of mild to moderate severity was associated with a significant risk of cognitive impairment at 3 months, even in the absence of clinical aphasia. This was due primarily to an increased risk of solitary deficits rather than generalized deficits.

Adult↗
PubMed2003

Evidence-based care and outcomes of acute stroke managed in hospital specialty units.

OBJECTIVES: To assess the use of evidence-based investigations and treatments in patients with acute stroke in selected Australian hospitals and to compare management and outcomes between stroke and other types of hospital specialty unit. DESIGN: Retrospective, multicentre audit of hospital case files. SETTING: Eight metropolitan tertiary-care hospitals from five Australian States. SUBJECTS: 300 consecutive patients from each hospital admitted between 17 September 1999 and 23 May 2001 and having a discharge diagnosis of stroke or transient ischaemic attack. MAIN OUTCOME MEASURES: Use of investigations and treatments supported by best available evidence; comparison of management and outcomes between stroke, neurology, general medical and geriatric units. RESULTS: 2383 patients were audited (median age, 72.7 years; 52% men); 72% had ischaemic events, and 28% haemorrhagic events. Use of investigations and treatments varied between hospitals and types of unit. Stroke units or teams cared directly for 23% of patients (range across hospitals, 0-100%). Although 47% of patients with ischaemic events presented within 3 hours of symptom onset (when thrombolysis might provide benefit), only nine (2%) received thrombolysis. Angiotensin-converting enzyme (ACE) inhibitors were given to 28% of survivors at discharge (range, 14%-38%). Stroke units were more likely to use diagnostic tests, while neurology units were more likely to prescribe heparin acutely for patients with ischaemic stroke (not recommended for patients in general), and geriatric units were less likely to discharge patients with atrial fibrillation on anticoagulation therapy. Outcomes also varied significantly between types of unit. In-hospital survival rates were 90% (stroke units), 91% (neurological units), 82% (general medical units) and 79% (geriatric units) (P < 0.001). Stroke units and neurological units sent more patients home than the other units. Stroke units also sent fewer patients to rehabilitation and had longer mean length of stay. CONCLUSIONS: Acute stroke care varies between Australian tertiary-care hospitals and types of specialty unit, with suboptimal use of many evidence-based interventions.

Aged↗
PubMed2003

Recommendations for the relationship between sponsors and investigators in the design and conduct of clinical stroke trials.

BACKGROUND: As increasing numbers of clinical trials are being conducted worldwide, there has been concern about the relationship between the sponsors and investigators. Both parties need benchmarks or recommendations to act as a reference point when trials are initiated and conducted. These recommendations are designed to fulfill this role. SUMMARY OF COMMENT: A series of meetings of the International Trial Subcommittee of the International Stroke Liaison Committee, American Stroke Association, were conducted to review a series of draft recommendations that were then modified on the basis of the experience of the committee in the conduct of clinical trials. Consensus was reached on all points of the final document. The recommendations represent the opinions of the authors and do not necessarily reflect the views of the American Stroke Association. The document contains sensible recommendations concerning required sponsor company qualities, trial management structure, protocol development, trial conduct, data management, blinding, data analyses, publication, remuneration, and conflict of interest issues. CONCLUSIONS: The recommendations should provide a simple and practical benchmark for both investigators and sponsors in the conduct of clinical trials. Although designed for trials involving therapies for stroke, the framework allows generalization to other disciplines.

Clinical Trials as Topic↗
PubMed2003

PROGRESS results: implementation in stroke guidelines.

The most important issues facing clinicians is the transfer of evidence from clinical trials into practice. Physician, patient and community acceptance of the evidence are key components of this process. Although barriers to this exist, in the case of transfer of evidence from the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) into clinical practice, these are minimal. Hence, transfer of this information into clinical practice should put blood pressure lowering in place as the fourth major secondary prevention strategy for stroke.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

The role of blood pressure lowering before and after stroke.

PURPOSE OF REVIEW: Elevated blood pressure is one of the most potent risk factors for first ever and recurrent stroke as well as influencing early outcome after acute stroke. There have been a number of significant randomized controlled trials which may influence management in each of these three categories. RECENT FINDINGS: For primary prevention, the recent information from the Heart Outcomes Prevention Evaluation, Losartan Intervention for Endpoint Reduction to Hypertension, Study on Cognition and Prognosis in the Elderly and Australian National Blood Pressure Study support the view that blood pressure lowering protects against stroke regardless of baseline blood pressure level. There is some evidence that blockade of the angiotensin system may give additional protection. For secondary prevention, evidence from the Perindopril Protection against Recurrent Stroke Study shows that blood pressure lowering with perindopril based therapy reduces fatal or non-fatal stroke events, again in hypertensive or normotensive individuals. There is uncertainty about blood pressure lowering in acute stroke, although presentation of the recent Acute Candesartan Cilexetil Evaluation in Stroke Survivors trial in which there was significant protection against vascular events using candesartan suggests that further studies should be undertaken. SUMMARY: Blood pressure lowering for primary prevention of stroke should be undertaken using a variety of therapeutic agents. For secondary stroke prevention perindopril based therapy should be used based on current evidence. Uncertainty still exists as to whether blood pressure lowering in the acute stroke setting is safe or improves outcomes.

Aged↗
PubMed2003

Incidence and outcome of subtypes of ischaemic stroke: initial results from the north East melbourne stroke incidence study (NEMESIS).

Information about the incidence and outcome of stroke subtypes is necessary to understand the likely impact of stroke prevention and treatment strategies. The purpose of this study was to determine the incidence and outcome of subtypes of cerebral infarction (CI). All strokes occurring in a population of 133816 in Melbourne, Australia, during a 12-month period of 1996 and 1997 were identified and cases of CI subtyped according to the Oxfordshire Community Stroke Project classification. 276 'first-ever-in-a-lifetime' stroke cases were registered. CI accounted for 72% of cases. Annual incidence rates per 100000 persons adjusted to the 'world' population were 11 (95% CI, 4-18) for TACI, 25 (95% CI, 15-35) for PACI, 17 (95% CI, 9-25) for POCI and 18 (95% CI, 10-26) for LACI. 28-day case fatality was highest for TACI (35%; 95% CI, 19-51%) and first year recurrence rate highest for PACI (17%; 95% CI, 8-26%). TACI had the poorest functional outcome at 3 and 12 months. These findings are similar to those of two previous studies conducted in the northern hemisphere.

Adolescent↗