Wilson Disease: A Case Report of Psychosis Preceding Parkinsonism.

BACKGROUND A first psychotic episode requires the exclusion of toxic-metabolic, inflammatory, infective, and neoplastic causes. Wilson disease is a rare, autosomal recessive disorder of copper metabolism and can present with neuropsychiatric symptoms secondary to copper accumulation in the brain. CASE REPORT We describe the case of a 48-year-old man with parkinsonism on a background of longstanding schizophrenia and psychotic depression in the setting of previously undiagnosed Wilson disease. The common history of neuropsychiatric disturbance and neuroleptic use complicated the assessment of parkinsonism. However, close attention to the temporal appearance of symptoms and signs differentiated his case from drug-induced parkinsonism, which commonly develops hours to weeks after commencement or uptitration of antipsychotic medication. The early features of sialorrhea and dysarthria were also atypical for idiopathic Parkinson disease. The diagnosis was confirmed by serum copper testing and supported by Kayser-Fleischer rings on bedside ophthalmological examination. Magnetic resonance imaging (MRI) of the brain demonstrated copper accumulation in the basal ganglia and pons, contributing to the characteristic neurological manifestations of an akinetic-rigid syndrome with dysarthria. CONCLUSIONS Serum copper testing is easily obtained and should be considered as part of the first-line investigations for new neuropsychiatric disturbances. Although rare, Wilson disease, if diagnosed early, is a potentially treatable and reversible cause of psychosis. With advanced disease, extrapyramidal findings on examination correlate with MRI brain changes, aiding the clinical assessment in differentiating the disease from drug-induced parkinsonism.

Supporting anticoagulant treatment decision making to optimise stroke prevention in complex patients with atrial fibrillation: a cluster randomised trial.

BACKGROUND: Anticoagulation for preventing stroke in atrial fibrillation is under-utilised despite evidence supporting its use, resulting in avoidable death and disability. We aimed to evaluate an intervention to improve the uptake of anticoagulation. METHODS: We carried out a national, cluster randomised controlled trial in the Australian primary health care setting. General practitioners received an educational session, delivered via telephone by a medical peer and provided information about their patients selected either because they were not receiving anticoagulation or for whom anticoagulation was considered challenging. General practitioners were randomised to receive feedback from a medical specialist about the cases (expert decisional support) either before or after completing a post-test audit. The primary outcome was the proportion of patients reported as receiving oral anticoagulation. A secondary outcome assessed antithrombotic treatment as appropriate against guideline recommendations. RESULTS: One hundred and seventy-nine general practitioners participated in the trial, contributing information about 590 cases. At post-test, 152 general practitioners (84.9%) completed data collection on 497 cases (84.2%). A 4.6% (Adjusted Relative Risk = 1.11, 95% CI = 0.86-1.43) difference in the post-test utilization of anticoagulation between groups was not statistically significant (p = 0.42). Sixty-one percent of patients in both groups received appropriate antithrombotic management according to evidence-based guidelines at post-test (Adjusted Relative Risk = 1.0; 95% CI = 0.85 to 1.19) (p = 0.97). CONCLUSIONS: Specialist feed-back in addition to an educational session did not increase the uptake of anticoagulation in patients with AF. TRIAL REGISTRATION: ANZCTRN12611000076976 Retrospectively registered.

Population-based stroke surveillance using big data: state-wide epidemiological trends in admissions and mortality in New South Wales, Australia.

OBJECTIVES: Epidemiological trends for major causes of death and disability, such as stroke, may be monitored using administrative data to guide public health initiatives and service delivery. METHODS: We calculated admissions rates for ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage between 1 January 2005 and December 31st, 2013 and rates of 30-day mortality and 365-day mortality in 30-day survivors to 31 December 2014 for patients aged 15 years or older from New South Wales, Australia. Annual Average Percentage Change in rates was estimated using negative binomial regression. RESULTS: Of 81,703 eligible admissions, 64,047 (78.4%) were ischaemic strokes and 13,302 (16.3%) and 4,778 (5.8%) were intracerebral and subarachnoid haemorrhages, respectively. Intracerebral haemorrhage admissions significantly declined by an average of 2.2% annually (95% Confidence Interval = -3.5% to -0.9%) (p < 0.001). Thirty-day mortality rates significantly declined for ischaemic stroke (Average Percentage Change -2.9%, 95% Confidence Interval = -5.2% to -1.0%) (p = 0.004) and subarachnoid haemorrhage (Average Percentage Change = -2.6%, 95% Confidence Interval = -4.8% to -0.2%) (p = 0.04). Mortality at 365-days amongst 30-day survivors of ischaemic stroke and intracerebral haemorrhage was stable over time and increased in subarachnoid haemorrhage (Annual Percentage Change 6.2%, 95% Confidence Interval = -0.1% to 12.8%), although not significantly (p = 0.05). DISCUSSION: Improved prevention may have underpinned declining intracerebral haemorrhage rates while survival gains suggest that innovations in care are being successfully translated. Mortality in patients surviving the acute period is unchanged and may be increasing for subarachnoid haemorrhage warranting investment in post-discharge care and secondary prevention.

Noninvasive Monitoring of Dynamic Cerebrovascular Autoregulation and 'Optimal Blood Pressure' in Normal Adult Subjects.

BACKGROUND: Cerebrovascular autoregulation can be continuously monitored from slow fluctuations of arterial blood pressure (ABP) and regional cerebral oxygen saturation (rSO2). The purpose of this study was to evaluate the index of dynamic cerebrovascular autoregulation (TOx) and the associated 'optimal' ABP in normal adult healthy subjects. METHODS: Twenty-eight healthy volunteers were studied. TOx was calculated as the moving correlation coefficient between spontaneous fluctuations of ABP and rSO2. ABP was measured with the Finometer photoplethysmograph. The ABP with optimal autoregulation (ABPOPT) was also determined as the ABP level with the lowest associated TOx (opt-TOx). RESULTS: Average rSO2 and TOx was 72.3 ± 2.9% and 0.05 ± 0.18, respectively. Two subjects had impaired autoregulation with a TOx > 0.3. The opt-TOx was - 0.1 ± 0.26. ABPOPT was 87.0 ± 16.7 mmHg. The difference between ABP and ABPOPT was - 0.3 ± 7.5 mmHg. In total, 44% of subjects had a deviation of ABP from ABPOPT exceeding 5 mmHg. ABPOPT ranged from 57 to 117 mmHg. CONCLUSIONS: TOx in healthy volunteers on average displays intact autoregulation and ABP close to ABPOPT. However, some subjects have possible autoregulatory dysfunction or a significant deviation of ABP from ABPOPT, which may confer a susceptibility to neurological injury.

Prevalence of positive syphilis serology and meningovascular neurosyphilis in patients admitted with stroke and TIA from a culturally diverse population (2005-09).

The study aims were to determine the prevalence of positive syphilis serology and meningovascular neurosyphilis (NS) in patients admitted with transient ischaemic attack (TIA) and stroke to a tertiary hospital serving a culturally diverse community. A retrospective cohort analysis was conducted using routinely collected administrative data and medical records to identify patients admitted with TIA, stroke and other conditions, with positive syphilis serology, between 2005 and 2009. Direct medical record review confirmed diagnoses of meningovascular NS. Syphilis serology was requested in 27% (893/3270) of all patients with TIA and stroke (2005-09) of whom 4% (38/893) were positive. Thirty-seven patients with positive serology had clinical characteristics consistent with meningovascular NS. Their mean age was 72±13 years; 65% were male and 68% had a recorded place of birth in South-East Asia or the Pacific Islands. One of 12 patients with suspected meningovascular NS with cerebrospinal fluid (CSF) analysis had a positive CSF Venereal Disease Research Laboratory (VDRL) test. Three patients (8%) met diagnostic criteria for "definite or probable" meningovascular NS. All three patients with a "definite or probable" meningovascular NS and 15 (44%) of the remainder who had positive serology without confirmation of NS were treated with intravenous or intramuscular penicillin. Lumbar puncture (LP) and penicillin were underutilised in patients with TIA and stroke with positive serology. In conclusion, syphilis testing should be considered part of the diagnostic work-up of TIA and stroke, particularly in ethnically diverse populations. In patients with TIA and stroke with positive syphilis serology, it would seem appropriate to further pursue diagnosis and treatment and in patients unable to undergo LP, empiric treatment for NS should be considered.

Supporting Treatment decision making to Optimise the Prevention of STROKE in Atrial Fibrillation: the STOP STROKE in AF study. Protocol for a cluster randomised controlled trial.

BACKGROUND: Suboptimal uptake of anticoagulation for stroke prevention in atrial fibrillation has persisted for over 20 years, despite high-level evidence demonstrating its effectiveness in reducing the risk of fatal and disabling stroke. METHODS: The STOP STROKE in AF study is a national, cluster randomised controlled trial designed to improve the uptake of anticoagulation in primary care. General practitioners from around Australia enrolling in this 'distance education' program are mailed written educational materials, followed by an academic detailing session delivered via telephone by a medical peer, during which participants discuss patient de-identified cases. General practitioners are then randomised to receive written specialist feedback about the patient de-identified cases either before or after completing a three-month posttest audit. Specialist feedback is designed to provide participants with support and confidence to prescribe anticoagulation. The primary outcome is the proportion of patients with atrial fibrillation receiving oral anticoagulation at the time of the posttest audit. DISCUSSION: The STOP STROKE in AF study aims to evaluate a feasible intervention via distance education to prevent avoidable stroke due to atrial fibrillation. It provides a systematic test of augmenting academic detailing with expert feedback about patient management.

No difference demonstrated between faxed or mailed prenotification in promoting questionnaire response among family physicians: a randomized controlled trial.

OBJECTIVE: Achieving high survey participation rates among physicians is challenging. We aimed to assess the effectiveness of response-aiding strategies in a postal survey of 1,000 randomly selected Australian family physicians (FPs). STUDY DESIGN AND SETTING: A two × two randomized controlled trial was undertaken to assess the effectiveness of a mailed vs. faxed prenotification letter and a mailed questionnaire sealed with a label marked attention to doctor vs. a control label. At the time of our final reminder, we randomized remaining nonresponders to receive a more or less personalized mail-out. RESULTS: Response did not significantly differ among eligible FPs receiving a prenotification letter via mail or fax. However, 25.6% of eligible FPs whose questionnaires were sealed with a label marked attention to the doctor responded before reminders were administered and compared with 18.6% of FPs whose questionnaires were sealed with a control label (P=0.008). Differences were not statistically significant thereafter. There was no significant difference in response between FPs who received a more vs. less personalized approach at the time of the final reminder (P=0.16). CONCLUSION: Mail marked attention to doctor may usefully increase early response. Prenotification letters delivered via fax are equally effective to those administered by mail and may be cheaper.

Relative survival after transient ischaemic attack: results from the Program of Research Informing Stroke Management (PRISM) study.

BACKGROUND AND PURPOSE: There is a lack of modern-day data quantifying the effect of transient ischemic attack (TIA) on survival, and recent data do not take into account expected survival. METHODS: Data for 22 157 adults hospitalized with a TIA from July 1, 2000, to June 30, 2007, in New South Wales, Australia, were linked with registered deaths to June 30, 2009. We estimated survival relative to the age- and sex-matched general population up to 9-years after hospitalization for TIA comparing relative risk of excess death between selected subgroups. RESULTS: At 1 year, 91.5% of hospitalized patients with TIA survived compared with 95.0% expected survival in the general population. After 5 years, observed survival was 13.2% lower than expected in relative terms. By 9 years, observed survival was 20% lower than expected. Females had higher relative survival than males (relative risk, 0.79; 95% CI, 0.69-0.90; P<0.001). Increasing age was associated with an increasing risk of excess death compared with the age-matched population. Prior hospitalization for stroke (relative risk, 2.63; 95% CI, 1.98-3.49) but not TIA (relative risk, 1.42; 95% CI, 0.86-2.35) significantly increased the risk of excess death. Of all risk factors assessed, congestive heart failure, atrial fibrillation, and prior hospitalization for stroke most strongly impacted survival. CONCLUSIONS: This study is the first to quantify the long-term effect of hospitalized TIA on relative survival according to age, sex, and medical history. TIA reduces survival by 4% in the first year and by 20% within 9 years. TIA has a minimal effect on mortality in patients <50 years but heralds significant reduction in life expectancy in those >65 years.

Outcomes for patients with ischaemic stroke and atrial fibrillation: the PRISM study (A Program of Research Informing Stroke Management).

BACKGROUND: In the past decade the prevalence of atrial fibrillation (AF) has been increasing in ageing populations while stroke prevention and management have advanced. To inform clinician practice, health service planning and further research, it is timely to reassess the burden of AF-related ischaemic stroke. METHODS: We identified patients aged 18+ years with a primary or stay diagnosis of ischaemic stroke (ICD-10-AM I63.x), from July 1, 2000 to June 30, 2006, using an administrative health dataset of all hospitalisations in New South Wales (population ∼7 million). Fact of death was determined to December 2007. RESULTS: Of the 26,960 index cases of ischaemic stroke, 25.4% had AF recorded during admission. Median age for AF and non-AF patients was 80.4 and 75.2 years, respectively (p < 0.001). Mortality was significantly higher in patients with AF at 30 days (19.4 vs. 11.5%), 90 days (27.7 vs. 15.8%) and 365 days (38.5 vs. 22.6%) (p values <0.0001). Adjusting for age and co-morbidities reduced these differences, with 90-day mortality of 20.9% in AF patients versus 14.7% in non-AF patients (p value <0.0001). The effect of AF on outcomes appears stronger in younger stroke patients relative to patients without AF (p value(interaction) <0.0001). At 30 days, the relative risk of mortality due to AF was 3.16 (95% CI 1.92-5.25) amongst those younger than 50, 1.71 (95% CI 1.32-2.22) in patients aged 50-64 years, 1.39 (95% CI 1.16-1.66) in patients aged 65-74 years, 1.29 (95% CI 1.17-1.43) in those aged 75-84 years, and 1.23 (95% CI 1.13-1.33) in those aged 85+ years. AF patients, surviving admission, spent a median of 19.2 days (95% CI 18.4-20.1) in hospital compared with 14.5 days (95% CI 13.9-15.1) for patients without AF (p < 0.001), with differences in length of stay greatest in younger patients (p value(interaction) <0.0001). 90-Day stroke survivors with AF spent an average of 21.5 days (95% CI 20.6-22.4) in hospital versus 16.6 days (95% CI 15.9-17.2) in those without AF. AF patients accessed more in-hospital rehabilitation (36.6%; 95% CI 35.0-38.2) than patients without AF (31.8%; 95% CI 31.0-32.7) (p value <0.0001), and differences in the proportion of AF versus non-AF patients accessing rehabilitation was greatest in younger patients (p value(interaction) <0.0006). CONCLUSIONS: Ischaemic stroke patients with AF have substantially worse outcomes than patients without AF, which can be partly explained by older age and greater co-morbidities. We have quantified the large effect of AF in younger patients and our results strongly argue for new antithrombotic research in young AF patients.

Study protocol: the DESPATCH study: delivering stroke prevention for patients with atrial fibrillation - a cluster randomised controlled trial in primary healthcare.

BACKGROUND: Compelling evidence shows that appropriate use of anticoagulation in patients with nonvalvular atrial fibrillation reduces the risk of ischaemic stroke by 67% and all-cause mortality by 26%. Despite this evidence, anticoagulation is substantially underused, resulting in avoidable fatal and disabling strokes. METHODS: DESPATCH is a cluster randomised controlled trial with concealed allocation and blinded outcome assessment designed to evaluate a multifaceted and tailored implementation strategy for improving the uptake of anticoagulation in primary care. We have recruited general practices in South Western Sydney, Australia, and randomly allocated practices to receive the DESPATCH intervention or evidence-based guidelines (control). The intervention comprises specialist decisional support via written feedback about patient-specific cases, three academic detailing sessions (delivered via telephone), practice resources, and evidence-based information. Data for outcome assessment will be obtained from a blinded, independent medical record audit. Our primary endpoint is the proportion of nonvalvular atrial fibrillation patients, over 65 years of age, receiving oral anticoagulation at any time during the 12-month posttest period. DISCUSSION: Successful translation of evidence into clinical practice can reduce avoidable stroke, death, and disability due to nonvalvular atrial fibrillation. If successful, DESPATCH will inform public policy, providing quality evidence for an effective implementation strategy to improve management of nonvalvular atrial fibrillation, to close an important evidence-practice gap. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12608000074392.

Validation of emergency and final diagnosis coding in transient ischemic attack: South Western Sydney transient ischemic attack study.

BACKGROUND: It is important to establish the validity of diagnostic coding in administrative datasets used in stroke and transient ischemic attack (TIA) research. This study examines the accuracy of emergency department (ED) TIA diagnosis and final diagnostic coding after hospital admission. METHODS: Using administrative datasets, we identified all patients with an ED TIA diagnosis (435.9; ICD-9) admitted to Liverpool Hospital from January 2003 to December 2007. ED and hospital admission records were matched and final diagnosis codes (ICD-10-AM) recorded. All records were expertly reviewed to determine coding validity. RESULTS: 570 patients were admitted with an ED TIA diagnosis. According to ICD-10-AM coding, 46% had TIA, 29% stroke and 25% TIA mimic diagnoses. Expert review determined final diagnoses of TIA in 51.4%, stroke in 26.1% and TIA mimic in 22.5% of the patients. The positive predictive value of a final TIA diagnosis (ICD-10-AM) was 88.2% when subjected to expert review. TIA mimic disorders diagnosed after admission included serious conditions. CONCLUSIONS: Half of the emergency diagnoses retained a TIA diagnosis after hospital admission. In the setting of neurological admission there were small percentage differences between coded final diagnosis for TIA, stroke and mimic and diagnoses at expert review. Admission of ED TIA cases permitted identification of TIA mimics with serious conditions requiring non-TIA management.

Decreasing presentations of seizures to emergency departments in a large Australian population.

This study was designed (1) to compare the prevalence of emergency department (ED) presentations in Western Zone Sydney South West Area Health Service (WZS) between 1998-2002 and 2003-2007 for epilepsy (including status epilepticus (SE) and convulsions), hospital admission rates, and proportion of first seizure presentations; and (2) to compare these data with those for New South Wales (NSW) and Australia-wide figures. Using health department data sets, we found 19,834 presentations to WZS EDs between 1998 and 2007 (24.85/10,000 population/year). When the periods 2003-2007 and 1998-2002 in WZS are compared, ED presentations fell by 3% (P=0.03) and hospital admissions fell by 6% (P=0.001). The prevalence of ED presentations for seizures in NSW did not change (P=0.92), but hospital admissions fell by 3% (P<0.0001). When 1999/2000-2002/2003 was compared with 2003/2004-2006/2007, the prevalence of hospital admissions in Australia fell by 1% (P=0.0002). Rates of presentation for epilepsy in WZS have fallen over the last decade. Most presentations were first seizures rather than recurrences. The reason for this is speculative, but may reflect improved levels of education and health care delivery.

The management of non-valvular atrial fibrillation (NVAF) in Australian general practice: bridging the evidence-practice gap. A national, representative postal survey.

BACKGROUND: General practitioners (GPs) are ideally placed to bridge the widely noted evidence-practice gap between current management of NVAF and the need to increase anticoagulant use to reduce the risk of fatal and disabling stroke in NVAF. We aimed to identify gaps in current care, and asked GPs to identify potentially useful strategies to overcome barriers to best practice. METHODS: We obtained contact details for a random sample of 1000 GPs from a national commercial data-base. Randomly selected GPs were mailed a questionnaire after an advance letter. Standardised reminders were administered to enhance response rates. As part of a larger survey assessing GP management of NVAF, we included questions to explore GPs' risk assessment, estimates of stroke risk and GPs' perceptions of the risks and benefits of anticoagulation with warfarin. In addition, we explored GPs' perceived barriers to the wider uptake of anticoagulation, quality control of anticoagulation and their assessment of strategies to assist in managing NVAF. RESULTS: 596 out of 924 eligible GPs responded (64.4% response rate). The majority of GPs recognised that the benefits of warfarin outweighed the risks for three case scenarios in which warfarin is recommended according to Australian guidelines. In response to a hypothetical case scenario describing a patient with a supratherapeutic INR level of 5, 41.4% of the 596 GPs (n = 247) and 22.0% (n = 131) would be "highly likely" or "likely", respectively, to cease warfarin therapy and resume at a lower dose when INR levels are within therapeutic range. Only 27.9% (n = 166/596) would reassess the patient's INR levels within one day of recording the supratherapeutic INR. Patient contraindications to warfarin was reported to "usually" or "always" apply to the patients of 40.6% (n = 242/596) of GPs when considering whether or not to prescribe warfarin. Patient refusal to take warfarin "usually" or "always" applied to the patients of 22.3% (n = 133/596) of GPs. When asked to indicate the usefulness of strategies to assist in managing NVAF, the majority of GPs (89.1%, n = 531/596) reported that they would find patient educational resources outlining the benefits and risks of available treatments "quite useful" or "very useful". Just under two-thirds (65.2%; n = 389/596) reported that they would find point of care INR testing "quite" or "very" useful. An outreach specialist service and training to enable GPs to practice stroke medicine as a special interest were also considered to be "quite" or "very useful" by 61.9% (n = 369/596) GPs. CONCLUSION: This survey identified gaps, based on GP self-report, in the current care of NVAF. GPs themselves have provided guidance on the selection of implementation strategies to bridge these gaps. These results may inform future initiatives designed to reduce the risk of fatal and disabling stroke in NVAF.

Outcomes of patients with transient ischaemic attack after hospital admission or discharge from the emergency department.

OBJECTIVE: To compare outcomes at 28 days and 1 year between patients admitted to hospital and those discharged after presenting to the emergency department (ED) with transient ischaemic attack (TIA). DESIGN AND SETTING: All TIA presentations to EDs in a large metropolitan and rural region of Sydney and its surroundings, New South Wales, between 2001 and 2005 were extracted from state health department databases and followed up over 1 year. Admission and discharge data and subsequent TIA or stroke presentations were identified. MAIN OUTCOME MEASURES: TIA recurrence or stroke. RESULTS: Of 2535 presentations to an ED with TIA during the 5-year period, 1816 patients were admitted to hospital (71.6%) and 719 were discharged from the ED (28.4%). At 28 days, the discharged group had significantly higher rates of recurrence than the admitted group for all events (TIA or stroke) (5.3% v 2.3%, P < 0.001), stroke (2.1% v 0.7%, P = 0.002), and recurrent TIA (3.2% v 1.6%, P = 0.01). During the 29-365-day follow-up period, there was no significant difference between the discharged and admitted groups for all events (4.2% v 5.1%; P = 0.37), stroke (1.3% v 2.5%; P = 0.06) or recurrent TIA (2.9% v 2.6%; P = 0.65). CONCLUSION: Patients with an ED diagnosis of TIA may benefit from admission to hospital through a reduced risk of early stroke.