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Rationale Stroke and poststroke depression are common and have a profound and ongoing impact on an individual's quality of life. However, reliable biological correlates of poststroke depression and functional outcome have not been well established in humans. Aims Our aim is to identify biological factors, molecular and imaging, associated with poststroke depression and recovery that may be used to guide more targeted interventions. Design In a longitudinal cohort study of 200 stroke survivors, the START – STroke imAging pRevention and Treatment cohort, we will examine the relationship between gene expression, regulator proteins, depression, and functional outcome. Stroke survivors will be investigated at baseline, 24 h, three-days, three-months, and 12 months poststroke for blood-based biological associates and at days 3–7, three-months, and 12 months for depression and functional outcomes. A sub-group ( n = 100), the PrePARE: Prediction and Prevention to Achieve optimal Recovery Endpoints after stroke cohort, will also be investigated for functional and structural changes in putative depression-related brain networks and for additional cognition and activity participation outcomes. Stroke severity, diet, and lifestyle factors that may influence depression will be monitored. The impact of depression on stroke outcomes and participation in previous life activities will be quantified. Study Outcomes Clinical significance lies in the identification of biological factors associated with functional outcome to guide prevention and inform personalized and targeted treatments. Evidence of associations between depression, gene expression and regulator proteins, functional and structural brain changes, lifestyle and functional outcome will provide new insights for mechanism-based models of poststroke depression.

Summary Background The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes. Methods To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16 851 cases with state-of-the-art phenotyping data and 32 473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20 941 cases and 364 736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis. Findings We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13–1·30, p=4·50 × 10 −8 ; joint OR 1·19, 1·12–1·26, p=1·30 × 10 −9 ). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29–1·49, p=3·26 × 10 −19 ; joint OR 1·37, 1·30–1·45, p=2·79 × 10 −32 ) and ZFHX3 (first stage OR 1·19, 1·11–1·27, p=2·93 × 10 −7 ; joint OR 1·17, 1·11–1·23, p=2·29 × 10 −10 ) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18–1·42, p=3·50 × 10 −8 ; joint OR 1·24, 1·15–1·33, p=4·52 × 10 −9 ) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2 , which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12–1·28, p=6·82 × 10 −8 ; joint OR 1·17, 1·11–1·23, p=2·92 × 10 −9 ). Other loci associated with stroke in previous studies, including NINJ2 , were not confirmed. Interpretation Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke. Funding US National Institute of Neurological Disorders and Stroke, National Institutes of Health.

Background One in three patients experience depression after stroke. An effective strategy to prevent depression after stroke that could be economically delivered to most patients with a low likelihood of adverse events is needed. Methods In a randomized trial conducted in New South Wales, Australia, a postcard was sent monthly to participants ( n = 100) for five-months following hospital discharge after stroke (plus usual care) and compared with usual care ( n = 101). Ethical approval was obtained to withhold information about the intervention and primary outcome from participants during the consent process. Results No significant difference was seen in the proportion of participants with depression in the intervention group (1/88) vs. the control group (3/76) (relative risk 0·29, 95% confidence interval 0·03–2·71) at six-months. No significant differences were seen on Hospital Anxiety Depression Scale (HADS) depression and anxiety sub-scale scores, quality of life, or activities of daily living; however, many (47/100) responded positively to the postcards. Conclusions Although this simple postcard intervention did not significantly reduce the proportion of participants experiencing high HADS depression sub-scale scores after stroke, it may be an effective way to engage with people after stroke following hospital discharge.

This study aimed to examine outcome in low risk transient ischaemic attack (TIA) patients presenting to emergency departments (ED) in a regional Australian setting discharged on antiplatelet therapy with expedited neurology review. All patients presenting to Gosford or Wyong Hospital ED with TIA, for whom faxed referrals to the neurology department were received between October 2008 and July 2010, were included in this prospective cohort study. Classification of low risk was based on an age, blood pressure, clinical features, duration of symptoms and diabetes (ABCD2) score4 and the absence of high risk features, including known carotid disease, crescendo TIA, or atrial fibrillation. Patients with ABCD2 scoresor =4 or with high risk features were discussed with the neurologist on call (a decision regarding discharge or admission was then made at the neurologist's discretion). Patients were investigated with a brain CT scan and/or CT angiography, routine pathology, and an electrocardiogram. All discharged patients were commenced on antiplatelet therapy and asked to follow up with their local medical officer within 7 days. The patients were contacted by the neurology department to arrange follow-up. Our primary outcome was the number of subsequent strokes occurring within 90 days. Of 200 discharged patients for whom referrals were received, three patients had a stroke within 90 days. None of these would have been prevented through hospitalisation. In conclusion, medical assessment, expedited investigation with immediate commencement of secondary prevention and outpatient neurology review may be a reasonable alternative to admission for low risk patients presenting to the ED with TIA.

Background and Purpose— Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS. Methods— Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. Results— Despite having power to detect odds ratio of 1.09–1.14 for overall IS and 1.20–1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. Conclusions— Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.

Loss of role as a driver significantly affects community participation; therefore, we aimed to explore the impact of driving issues post-stroke in community-dwelling stroke survivors.A longitudinal qualitative study of community-dwelling stroke survivors, using semi-structured interviews.Twenty-two participants took part in 84 interviews over a 1-year period post-stroke. The majority of participants was independent and experienced few major depressive symptoms. ages ranged from 50 to 92 years. Emergent key themes included impact on quality of life, personal impacts, change to role performance and knowledge. Participants received inconsistent advice regarding return to driving. Confidence and availability determined public transport use.Driving advice should be standard practice prior to discharge. Allied health professionals can play an essential role in interventions addressing community participation, driver re-training and alternative transport use. Therapists have an important role in assisting stroke survivors to work through feelings of loss and in providing education concerning new skills to support this life transition.

Rationale One in three patients experience depression after stroke and this risk is consistent over time. A strategy to prevent depression that could be economically delivered to most stroke patients and ideally which also has a low likelihood of adverse events needs to be developed and evaluated. Aims POST aims to determine whether a simple intervention (postcards) prevents depression (Hospital Anxiety and Depression rating Scale, HADS depression subscale score ≥8) in patients with a recent stroke. Secondary end-points include reduced anxiety (HADS anxiety subscale score ≥8) and improved health-related quality of life in patients with a recent stroke. Design A single-centre randomised, double-blind, pilot trial to prevent depression in patients with a recent (within 8 weeks) stroke presenting to hospital. Patients will be enrolled over 12 months and randomised to receive three trial-specific assessments (baseline, 3- and 6-month assessments of mood, HRQoL and social functioning), or three trial-specific assessments plus a postcard sent centrally in a sealed envelope at 1, 2, 3, 4 and 5 months after discharge from hospital. Blinded follow-up telephone assessments will be conducted for both groups. Study outcomes and sample size For the primary end-point the POST trial will have 80% power to detect a relative risk of 0·4 given an incidence of depression of 30%. For the secondary aims POST has 90% power to detect a difference of 3 points on the HADS depression subscale (assuming a standard deviation of 6 points) between randomised groups. This includes an inflation factor of 15% to account for patients lost to follow-up. Discussion Evidence of efficacy will determine whether a multi-centre, international trial is warranted.

Article abstract Gelastic seizures are the hallmark of the epilepsy syndrome associated with hypothalamic hamartomas. Patients typically develop cognitive deterioration and refractory seizures. The authors describe three patients with small hypothalamic hamartomas without these features and thus identify a mild end to the clinical spectrum. All had the unusual symptom of “pressure to laugh,” often without actual laughter. This symptom could be dismissed as psychogenic but should be recognized as a clue to the presence of this unusual lesion.

To report Australian outcomes from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Register (SITS-ISTR).Observational study using data collected prospectively from December 2002 to December 2008.Centres administering thrombolysis for acute stroke in Australia and worldwide.All patients treated with recombinant tissue plasminogen activator for acute stroke in participating centres, regardless of stroke severity, time of treatment and other clinical factors.Thrombolysis for acute stroke, administered according to local protocol.Functional outcome as 3-month modified Rankin score (mRS), and frequency of symptomatic intracerebral haemorrhage (ICH).During the study period, a total of 32 countries participated, and confirmed baseline data were available for 581 Australian patients and 20 953 patients in the rest of the world. Australian patients were older (median age, 73 v 69 years; P 0.001), were less independent before stroke (premorbid mRS of 0-1, 87.5% v 91.2%; P 0.005), and had more comorbidities and more severe strokes. Comparing the Australian cohort with the rest of the world, the odds ratio of 3-month mRS of 0-2 was 0.98 (95% CI, 0.88-1.08; P = 0.63), the odds ratio of symptomatic ICH was 0.98 (95% CI, 0.83-1.16; P = 0.85 [by the definition used by the National Institute of Neurological Disorders]) and the odds ratio of death was 1.04 (95% CI, 0.91-1.19; P = 0.54). Good outcome in the Australian cohort was predicted by younger age, presence of hyperlipidaemia, lower premorbid mRS, absence of infarct on early brain imaging, less severe stroke, and lower baseline blood glucose level.Clinical outcomes after thrombolysis in Australia were similar to those worldwide.

We hypothesized that polymorphisms in 5 genes related to thrombolytic and inflammation pathways will independently influence occurrence, severity, and 3-month functional outcome in patients with ischemic stroke. This was a case-control design with ischemic stroke patients recruited from 4 public hospitals (n = 640) and community controls (n = 627). Baseline clinical data were collected, and follow-up telephone interviews were conducted with 520 patients at 90 days postevent to determine stroke outcome using the Barthel Index (BI), Modified Rankin Scale (mRS) and Glasgow Outcome Scale (GOS). Blood samples were collected and genotyped for polymorphisms in platelet glycoprotein Ibα (GPIbα) rs224309 and rs6065, glycoprotein IIIa (GPIIIa) rs5918, tissue plasminogen activator (tPA) rs63020761, plasminogen activating inhibitor (PAI-1) rs72578597, and cyclooxygenase-2 (COX-2) rs5275 and rs20417. COX-2 polymorphism rs5275 demonstrated a significant association with poststroke mRS, with a dominant genetic model demonstrating the best fit (CC + TC) (adjusted odds ratio [aOR] = 1.61; P = .026). The COX-2 rs20417 C allele showed an association with GOS (aOR = 1.95; P = .012), and again a dominant genetic model demonstrated the best fit (CC + GC). GPIIIa rs5918 (A1A2) was associated with poststroke BI, with a dominant model demonstrating the best fit (A1A2 + A2A2) (aOR = 0.56; P = .014). There was a significant association between stroke severity and tPA rs63020761 TT allele (aOR = 1.96; 95% CI = 1.03-3.72; P = .040). This is the first study to demonstrate associations between stroke functional outcome and 2 COX-2 variants (rs20417 and rs5275) and a GPIIIa variant (rs5918).

Background: Handicap is rarely comprehensively examined after stroke. We examined handicap among 5-year stroke survivors from an ‘ideal’ stroke incidence study. Methods: Survivors were assessed with the London Handicap Scale [LHS, score range: 0 (greatest handicap) to 100 (least handicap)]. Multivariable regression was used to examine demographic, risk and stroke-related factors associated with handicap. Results: 351 of 441 (80%) survivors were assessed. Those assessed were more often Australian born than those not assessed (p < 0.05). The mean LHS score was 73 (SD = 21). The greatest handicap was present for physical independence and occupation/leisure items. Handicap was associated with older age, manual occupations, smoking, initial stroke severity, recurrent stroke and mood disorders. Conclusion: Reducing recurrent stroke, through better risk factor management, is likely to reduce handicap. The association between handicap and mood disorders, which are potentially modifiable, warrants further investigation.

Publisher Summary The chapter discusses the occurrence of stroke among women, ethnic groups, young adults, and children. There are a number of different groups of people among whom the incidence and etiology of stroke differ. Incidence of stroke is lower among women than men, and is lower among young adults and children. Women have a number of unique risk factors for stroke that involve their reproductive capacity, although other factors may also be involved. People aged less than 45 years with stroke require special consideration. The frequencies of underlying etiology differ from the older stroke population and a greater breadth of investigation is required. Although considered rare, stroke is more common than brain tumors in children. Arteriopathies are the most commonly identified risk factor for arterial ischemic stroke, followed by cardiac and thromboembolic disorders. Neurological sequelae are common in arterial ischemic stroke and sinovenous thrombosis.

White JH, Magin P, Attia J, Pollack MR, Sturm J, Levi CR. Exploring poststroke mood changes in community-dwelling stroke survivors: a qualitative study. Objective To explore the long-term experience of mood changes in community-dwelling stroke survivors at 1, 3, and 5 years after stroke. Design A qualitative study using a modified grounded theory approach. The primary data collection method was semi-structured interviewing. Setting Community-dwelling stroke survivors in metropolitan Newcastle, NSW, Australia. Participants Twelve community-dwelling stroke survivors (6 men, 6 women; age range 43−92y; 4 participants from each cohort) discharged from a tertiary referral hospital. Interventions Not applicable. Main Outcome Measures Qualitative outcomes were participants' perceptions using in-depth, semi-structured interviews with participants from 3 community-based cohorts of stroke survivors at 1, 3, and 5 years poststroke. Results Four main categories of mood change were described by participants including feelings of frustration, reduced self-efficacy, dependency, and loss. Factors that modulated these mood changes included the presence or absence of insight, hope for the future, faith, and support. A modified grounded theory approach was used for data analysis using a process of constant comparison. Conclusions Mood changes continued well beyond discharge and in some cases commenced after discharge in this sample of stroke survivors. Use of qualitative methodology extends our understanding of the extent and nature of low mood after stroke. There is a need for enhanced services to monitor and address low mood.

To investigate whether the 4G/5G polymorphism of plasminogen activator inhibitor type 1 (PAI-1) and the −7351 C/T polymorphism of tissue-type plasminogen activator (t-PA) are associated with ischemic stroke, we conducted a case-control study of 190 hospital cases of first-ever ischemic stroke and 185 community-based controls. Our findings do not indicate any association between the PAI-1 or t-PA polymorphisms and risk of stroke. Adding our PAI-1 results to previous studies in a meta-analysis indicated a strong association between this polymorphism and ischemic stroke ( P = .0002), with no publication bias but with extreme heterogeneity. There was evidence of stroke association with the PAI-1 4G/5G locus. Strong heterogeneity indicates the need to address other issues, including association with particular stroke subtypes or linkage disequilibrium (LD) with another causative allele. The results also sound a cautionary note that varying LD structure across populations may obscure the relationship with a causative locus, and that future meta-analyses need to look beyond a simple pooled estimate.

Background and Purpose— There are few data on the prevalence or treatment of depression from unselected populations long-term poststroke. We assessed the prevalence of depression and antidepressant use at 5-years poststroke in an unselected stroke population. Methods— Five-year survivors from a prospective community-based stroke incidence study were assessed for depression with the Irritability, Depression and Anxiety Scale. Medications indicated primarily for treatment of depression were recorded. Results— At 5-years poststroke, 441 (45%) of 978 incident cases were alive (mean age=74±15 years, 49% female). Seventeen percent of those assessed were depressed. Twenty-two percent with depression were taking an antidepressant medication. Of those taking an antidepressant, 72% were not depressed. Conclusions— Although nearly one-fifth of survivors were depressed, few were taking antidepressants. Further exploration of this low level of treatment is warranted.

Background and Purpose— Greater stroke mortality has been reported among lower socioeconomic groups. We aimed to determine whether fatal, nonfatal, and overall stroke incidence varied by socioeconomic status. Methods— All suspected strokes occurring in 22 postcodes (population of 306 631) of Melbourne, Australia, during a 24-month period between 1997 and 1999 were found and assessed. Multiple overlapping sources were used to ascertain cases with standard clinical definitions for stroke. Socioeconomic disadvantage was assigned in 4 bands from least to greatest using an area-based measure developed by the Australian Bureau of Statistics. Results— Overall stroke incidence (number per 100 000 population per year), adjusted to the European population 45 to 84 years of age, increased with increasing socioeconomic disadvantage: 200 (95% CI, 173 to 228); 251 (95% CI, 220 to 282); 309 (95% CI, 274 to 343); and 366 (95% CI, 329 to 403; χ 2 for ranks; P 2 for ranks; P Conclusions— In this population-based study, both fatal and nonfatal stroke incidence increased with increasing socioeconomic disadvantage. The greater contributor to this incidence pattern was nonfatal stroke incidence. This may have implications for service provision to those least able to afford it. Area-based identification of those most disadvantaged may provide a simple and effective way of targeting regions for stroke prevention strategies.

Patients with a spontaneous low cerebrospinal fluid pressure headache commonly present with a severe headache on assuming an upright posture which is relieved when lying flat. However, initial neuroimaging may not reveal abnormalities typically associated with a low-pressure state. A 37-year-old woman presented to Gosford Hospital with a 10 day history of severe headache associated with nausea and mild photophobia, relieved completely by recumbency. There was no history of preceding trauma, lumbar puncture, epidural anaesthesia or spinal or neurosurgical intervention. While the initial MRI of the brain was normal, symptoms persisted with conservative management. Further neuroimaging was required to confirm a diagnosis. A further MRI of the brain and spine with gadolinium was performed 12 days later demonstrating diffuse pachymeningeal thickening. An MRI of the spine using sagittal fat suppression and gradient-echo sequencing showed cerebrospinal fluid collection within the thoracic spine. Given the presence of perineural cysts at C7–T1 and T10–T11 in the spinal cord, a lumbar myelogram was performed to confirm the site of the leak at T10–T11 and a blood patch was applied. Despite initial symptom resolution, the headache returned. However, a second blood patch was effective in abolishing the headache. This patient demonstrates the importance of repeating imaging to confirm diagnosis and guide therapy when the history strongly suggests a low cerebrospinal fluid pressure headache and initial imaging is negative.

Background and Purpose— Although much is known about the long-term outcome of stroke patients in terms of mortality and disability, there has been little research on the patient-centered outcome of health-related quality of life (HRQoL). There are limited natural history data on HRQoL beyond 2 years after stroke and no data on those factors present at stroke onset that predict HRQoL beyond 2 years after stroke. For these reasons, we aimed to examine these aspects of HRQoL in an unselected population of stroke patients. Methods— All cases of first-ever stroke from a prospective community-based stroke incidence study (excluding subarachnoid hemorrhage) were assessed 5 years after stroke. HRQoL was measured with the assessment of quality of life instrument. ANOVA was used to determine baseline predictors of HRQoL. Results— In total, 978 cases were recruited, 45% were male, and the mean age (±SD) was 75.5±13.8 years. Five years after stroke, 441 (45.1%) were alive and 356 were assessed (80.7%). Those assessed were more often born in Australia and older in age (both P Conclusion— At 5 years after stroke, we found that a substantial proportion of survivors were suffering from poor HRQoL. As our population ages, the number of strokes and, thus, stroke survivors with poor HRQoL is likely to increase. Therefore, strategies to improve HRQoL should be vigorously pursued.

Background: Although a number of acute stroke interventions are of proven efficacy, there is uncertainty about their community benefits. We aimed to assess this within a defined population. Methods: Eligibility for tissue plasminogen activator (tPA), aspirin, stroke unit management and neuroprotection were assessed among incident stroke cases within the community-based North East Melbourne Stroke Incidence Study. Results: Among 306,631 people, there were 645 incident strokes managed in hospital. When eligible patients were extrapolated to the Australian population, for every 1,000 cases, 46 (95% CI 17–69) could have been saved from death or dependency with stroke unit management, 6 (95% CI 1–11) by using aspirin, 11 (95% CI 5–17) or 10 (95% CI 3–16) by using tPA at 3 and 6 h, respectively. Conclusions: Although tPA is the most potent intervention, management in stroke units has the greatest population benefit and should be a priority.

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 133,816 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 100,000 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.

Although precipitation of seizures by exercise has been described, the reproducible induction of temporal lobe seizures by exercise is unusual. The authors report two patients with left temporal lobe seizures induced by exercise. In one patient the family history suggested autosomal-dominant inheritance. Prolonged hyperventilation, simple movements, and visualization of a competitive game did not produce epileptiform discharges on the interictal EEG.

Background: Patient education is a vital component of Heart Failure Management Programs (HF-MPs) and should be specifically designed to meet the needs of this patient population. Aim: To investigate the learning style and preferences for information delivery of heart failure patients for the purposesof informing thedesignofeducational resources. Methods: A purposive sample of 12 participants, diagnosed with heart failure and enrolled in a HF-MP, participated in semi-structured in-depth interviews. Results: Four themes emerged: knowledge quest (L(AIS) causes alteration to left ventricular volumes and function. We studied patients with acute ischaemic stroke using NT–pro-BNP blood assays on days 1 and 5 after admission to Gosford Hospital Stroke Unit. Patients were submitted to 3-dimentional (3-D) echocardiographic assessment using Phillips Sonos 7500 Equipment. End diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) were measured on presentation and days 3–5 following admission. The echocardiographic images were analysed using Phillips Q Lab Software. NT–pro-BNP level at presentation (mean±S.E.) was 1027± 429 pg/ml (N= 14) which was higher than day 5 (535± 215 pg/ml, N= 14, p< 0.5). Day 1 EDV, ESV and SV were 87± 6 ml, 44± 5ml and 48± 3ml, respectively (N= 21). Day 1 EFwas 55± 3 (N= 21). Days 3–5 EDV, ESV and SV were 90± 7ml, 43± 6ml and 53± 4ml, respectively (N= 21). Days 3–5 EF was 58± 4 (N= 21). The results demonstrate a trend towards a reduction in EF and SV in the acute post-AIS phase associated with evidence of neurohormonal regulation. The role of BNP in altering myocardial kinetics in early post-AIS phase deserves further investigation and needs to be viewed in the context of interaction between different neurohormones including catecholamines.

Folate status and/or genes have been linked to depression in a number of studies. This may be via a direct action (or actions) on neuronal membranes or indirect effects through the metabolism of methyl groups involved in neurotransmitter synthesis. This study examines folate and related thiol metabolism that might underpin either phenomenon.Cohort study describing the relationship between several genetic and nutritional aspects of folic acid homeostasis and depression assessed by the HADS psychometric index in an elderly cohort.New South Wales (Australia) retirement village.118 elderly participants (age 65-90 years).Stepwise multiple regression was used to determine the best statistical model to predict depression; C677T-MTHFR (p=0.0103) was found to be positively associated with depression, while the thiol dipeptide Cys-Gly was negatively associated (p=0.0403). The statistical models used accounted for the major folate related indices (genetic and biochemical) that are most often evaluated in the context of health and disease. When only genetic data were examined for interactions, C677T-MTHFR was found to be negatively associated with the HADS Depression Index Score (p=0.0191).The potential influence of Cys-Gly on this phenotype is novel, and of considerable interest given that it has been linked to altered spontaneous activity and sedation in an animal model. Cys-Gly is a recognised ligand at the N-methyl-D-aspartatic acid (NMDA) subclass of glutamate receptor, a system associated with depression. In addition, the C677T-MTHFR association adds further support to existing findings underscoring the potential role of folate in depression.

Background and Purpose: Incidence rates of stroke subtypes may be imprecise when samples are small. We aimed to determine the incidence of stroke subtypes in a large geographically defined population. Methods: Multiple overlapping sources were used to ascertain all strokes occurring in 22 postcodes (population of 306,631) of Melbourne, Australia, between 1997 and 1999. Stroke subtypes were defined by CT, MRI and autopsy. The Mantel-Haenszel age-adjusted rate ratio (MH RR) was used to compare incidence rates between men and women. Results: We identified 1,421 strokes among 1,337 residents, 1,035 (72.8%) being first-ever strokes. Incidence (number/100,000 population/year), adjusted to the European population 45–84 years, was 197 (95% confidence interval, CI, 169–224) for ischemic stroke (IS), 47 (95% CI 33–60) for intracerebral haemorrhage (ICH) and 19 (95% CI 10–27) for subarachnoid haemorrhage (SAH). Compared with women, men in this age group had a greater incidence of IS (MH RR 1.65, 95% CI 1.39–1.96, p < 0.0001) and ICH (MH RR 1.46, 95% CI 1.01–2.10, p = 0.0420), but lesser rates of SAH (MH RR 0.34, 95% CI 0.16–0.69, p = 0.0031). Conclusions: In this population-based study, the incidence of IS and ICH was greater among men than women, while women had a greater incidence of SAH. More effort may need to be directed at modifying risk factors for IS and ICH in men.

Background Stroke-specific outcome measures and descriptive measures of health-related quality of life (HRQoL) are unsuitable for informing decision-makers of the broader consequences of increasing or decreasing funding for stroke interventions. The quality-adjusted life year (QALY) provides a common metric for comparing interventions over multiple dimensions of HRQoL and mortality differentials. There are, however, many circumstances when – because of timing, lack of foresight or cost considerations – only stroke-specific or descriptive measures of health status are available and some indirect means of obtaining QALY-weights becomes necessary. In such circumstances, the use of regression-based transformations or mappings can circumvent the failure to elicit QALY-weights by allowing predicted weights to proxy for observed weights. This regression-based approach has been dubbed 'Transfer to Utility' (TTU) regression. The purpose of the present study is to demonstrate the feasibility and value of TTU regression in stroke by deriving transformations or mappings from stroke-specific and generic but descriptive measures of health status to a generic preference-based measure of HRQoL in a sample of Australians with a diagnosis of acute stroke. Findings will quantify the additional error associated with the use of condition-specific to generic transformations in stroke. Methods We used TTU regression to derive empirical transformations from three commonly used descriptive measures of health status for stroke (NIHSS, Barthel and SF-36) to a preference-based measure (AQoL) suitable for attaching QALY-weights to stroke disease states; based on 2570 observations drawn from a sample of 859 patients with stroke. Results Transformations from the SF-36 to the AQoL explained up to 71.5% of variation in observed AQoL scores. Differences between mean predicted and mean observed AQoL scores from the 'severity-specific' item- and subscale-based SF-36 algorithms and from the 'moderate to severe' index- and item-based Barthel algorithm were neither clinically nor statistically significant when 'low severity' SF-36 transformations were used to predict AQoL scores for patients in the NIHSS = 0 and NIHSS = 1–5 subgroups and when 'moderate to severe severity' transformations were used to predict AQoL scores for patients in the NIHSS ≥ 6 subgroup. In contrast, the difference between mean predicted and mean observed AQoL scores from the NIHSS algorithms and from the 'low severity' Barthel algorithms reached levels that could mask minimally important differences on the AQoL scale. Conclusion While our NIHSS to AQoL transformations proved unsuitable for most applications, our findings demonstrate that stroke-relevant outcome measures such as the SF-36 and Barthel Index can be adequately transformed to preference-based measures for the purposes of economic evaluation.