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The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy).DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0-2 or return to baseline at 90 days, with a non-inferiority margin of -0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants.Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference -0·051, two-sided 95% CI -0·160 to 0·059; per-protocol risk difference -0·062, two-sided 95% CI -0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22-13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46-1·84).We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment.Australian National Health and Medical Research Council and Stryker USA.

Objective: This study aimed to develop an understanding of the implementation of the Leading Better Value Care (LBVC) initiatives at a Local Health District (LHD). Methods: The study used a mixed method including literature reviews, survey and semi-structured interviews of the stakeholders who participated in the implementation of the state-wide LBVC program within a LHD. All information used in this study was de-identified and anonymous. Results: Twenty-two stakeholders responded to the survey reviewing the implementation process. Fifty-one percent of the participants reported that there was very good sharing of information and ideas within the LHD, where clinicians were provided with data to support better decision making (77%). The stakeholders were overall moderately to very satisfied (60%) with how the program was implemented within the LHD. A total of 10 interviews were conducted. Analysis of the transcripts identified four core themes linking different aspects of the implementation of the LBVC initiatives: 1) Engagement; 2) Understanding of implementation process; 3) Challenges; and, 4) Future strategies for implementation. This local learning will provide valuable information to develop strategies so as to improve the LBVC program and support the LHD in continuing to embed, scale and sustain the initiatives. Conclusion: This study has provided the experience of the stakeholders participating in the implementation of the LBVC program and how it was being implemented across the LHD. It has identified factors which contribute to improvement of future implementation of similar programs.

PurposeThis study has demonstrated how technology may contribute to integrated care solutions by comparing conventional ward telemetry (WT) to a wearable ECG monitor (S-Patch) to detect atrial fibrillation (AF) in patients with stroke.Design/methodology/approach51 patients admitted for stroke workup were recruited across two major tertiary centres to compare WT monitoring for two days versus S-Patch for four days in the detection of AF. The efficacy to detect AF using both technologies was assessed via data extractions and medical officer review. A matrix was used to measure nursing/patient satisfaction and setup/resource times were assessed.FindingsPatients (84–94%) and nursing staff (75–95%) preferred the S-Patch wearable technology. Non-parametric tests indicated significant time saving for removal of S-Patch versus WT [2.2 min vs 5.1 min (p = 0.00)]. Efficacy of S-Patch to detect AF following medical officer review was greater than WT, with seven patients identified with AF by S-Patch versus one using WT. The S-patch had a false positive rate of 78%.Research limitations/implicationsThe S-Patch is sensitive in the detection of AF; however, it showed a high false-positive rate with automated reporting. This study has provided insight into the details of delivery of integrated healthcare using wearable technology.Originality/valueThe technology and partnership were the first-in-kind in Australia. The S-Patch had a higher detection rate of AF compared to WT which allows patients to be anti-coagulated appropriately for the prevention of further stroke. The results of this study will be ideally placed to inform future policy in integrated healthcare using new technologies.

Introduction: Culturally and linguistically diverse (CALD) communities are growing globally. Understanding patterns of cerebrovascular disease in CALD communities may improve health outcomes through culturally specific interventions. We compared rates of transient ischaemic attack (TIA)/stroke (ischaemic stroke, intracerebral haemorrhage) and stroke risk factor prevalence in overseas and Australian-born people in South Western Sydney (SWS) and New South Wales (NSW). Methods: This was a 10-year retrospective analysis (2011–2020) of SWS and NSW age-standardized rates per 100,000 person-years of TIA/stroke. Data were extracted from Health Information Exchange and Secure Analytics for Population Health Research and Intelligence systems. Rates of hypertension, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), smoking, and obesity were also calculated. Results: The SWS and NSW age-standardized rate of TIA/stroke for people born in Australia was 100 per 100,000 person-years (100/100,000/year). In SWS, 56.6% of people were overseas-born compared to 29.8% for NSW. The age-standardized rate of TIA/stroke for Polynesian-born people was more than double that of Australian-born people (p < 0.001). Hypertension (33 [SWS] vs. 27/100,000/year [NSW]) and T2DM (36 [SWS] vs. 26/100,000/year [NSW]) were the most common risk factors with rates >50/100,000/year (hypertension) and >80/100,000/year (T2DM) for people born in Polynesia, Melanesia, and Central America. Rates of T2DM, AF, and obesity for Polynesian-born people were over threefold greater than people born in Australia. Discussion/Conclusion: Greater rates of TIA/stroke were observed in specific CALD communities, with increased rates of cerebrovascular risk factors. Culturally specific, targeted interventions may bridge health inequalities in cerebrovascular disease.

Purpose The purpose of this paper is to appraise the development, implementation and acceptance of HealthPathways (HP), specifically in Type 2 Diabetes Mellitus (T2DM), at different levels of the health system in a large metropolitan Local Health District in Australia. Design/methodology/approach This study used a programmatic approach and mixed methods including literature reviews, site visits, semi-structured interviews of stakeholders and General Practitioners (GPs), and surveys (GPs and patients) to better understand the development, implementation and acceptance of T2DM pathways. Findings Results from this study indicate that 63 percent (n=37) of all survey respondents use HP and nearly half (47 percent) use HP in caring for a patient with diabetes. More than 80 percent of the health professionals found HP a useful tool, which has improved the quality of care, keeps them informed and supports diagnostics process. The use of website has led to an improvement in referral quality (69 percent), has assisted in the provision of more healthcare in the community (87 percent) and made their job easier. Thematic analysis from stakeholder interviews (n=12) emphasizes the importance of established collaborations and the need for standardized tools with common priorities and transparency in processes. Practical implications This study has provided insight into the details of delivery of integrated healthcare using HP. It provides a preliminary analysis of the lessons learnt for the implementation of HP. Originality/value The results of this study will be ideally placed to inform future policy amendments in the area of integrated healthcare as well as serving as a guide on implementing HP in the future.

On 15 April 1989, Liverpool FC played Nottingham Forest in an FA Cup semi-final at the Hillsborough Stadium in Sheffield in northern England. Catastrophic errors by the police and other organisations led to the deaths of 96 Liverpool supporters, crushed against the perimeter fences on the Leppings Lane terrace. Though the horrific facts of the disaster were quickly and widely known, they were lost beneath another narrative, promoted by the police, numerous politicians, and large sections of the media. This narrative blamed the disaster on “tanked up yobs”: drunk and aggressive Liverpool supporters, who turned up late and forced their way into the ground. Over the subsequent years and decades, as Hillsborough campaigners vainly sought justice for the disaster’s victims in a series of trials and inquests, the destructive allegation remained in the public realm. It was reinforced by establishment dismissal of Liverpool as a “self-pity city”, home to a community incapable of accepting official verdicts or of leaving the past in the past. This essay uncovers the history of the myths of the Hillsborough disaster. It first shows how these myths were established - how false narratives, with powerful backers, shifted responsibility for the disaster from the police to supporters, despite overwhelming evidence to the contrary. It then examines how these myths were embedded in public discourse - how Liverpool was demonised as an aggressively sentimental city where people refused to admit to “killing their own”. It finally analyses how these myths were overturned through research, media mobilisation, and grassroots activism, a process that culminated in the 2016 inquest verdict, which ruled that the 96 Hillsborough victims were unlawfully killed. In doing so, the essay shows how Hillsborough became a key event in modern British history, influencing everything from stadium design to government legislation.

Introduction: HealthPathways (HPW) is an online health information portal which provides General Practitioners (GPs), guidance on the assessment, management, and referral of a range of conditions linked to local resources. It has been adopted as an aid to improve the integration of patient care across the health system. However, there is a lack of understanding of the acceptance of pathways within primary health. Theory/Methods This qualitative study identified baseline factors that promote the successful implementation of HPW in a major Local Health District (LHD) in Australia. The development, implementation and acceptance of Diabetes HPW was evaluated using semi-structured interviews with purposive samples. Interviews were digitally recorded, transcribed, and analysed qualitatively using a thematic analysis approach. Results A total of 16 interview transcripts were analysed. Four core themes were identified in relation to the processing of implementing the HPW: 1. The importance of creating & maintaining collaborative partnerships through the development of the pathways (engagement); 2. the process promoted trust and understanding between organisations and made their individual aims, processes and values clearer to one another (transparency); 3. HPW implementation was also seen as means of committing individual organisations to provide standardised and consistent care across the Local Health District (accountability); and, 4. the importance of providing adequate funding and resources to support the ongoing development and revision of HPW (Sustainability). Discussions This process evaluation provides additional, qualitative evidence about what facilitates the successful implementation of HPW and identifies barriers that hinder its success. Researchers anticipated the interview protocol would elicit an overall discussion about the strengths and limitations of HPW, as opposed to only about the Type 2 DM pathways; in particular its usability and utility, and suggested improvements or factors that might contribute to its success. An inductive approach was employed to conduct an analysis that extracted common themes amongst the qualitative data. Conclusions: This study provides an insight into the development and implementation of Type 2 Diabetes Mellites HPW across different levels of the health system in the LHD. The feedback and experiences from implementation and utilisation of the HPW across different levels of the health system and program implementation, provides the GP with an overall informed perspective on the acceptability of the pathways, what the general consensus is on its applicability and a transparent view on the impacts that the HPW may have on its day-to-day use. Lessons learned Collaboration between individuals and organisations has strengthened the development and implementation of the HPW. Engagement and transparency have demonstrated the significance of establishing collaborative partnerships to implement HPW. Limitations Despite a number of strategies to encourage the participation of GPs, the recruitment of GPs to take part in interviews was a challenge for the research team. Suggestions for future research Further research would be useful to investigate and explore the health outcomes and impact of HPW on the community including broader scope for evaluation of multiple pathways to identify the best ways of ensuring sustainability and uptake of the program.

ObjectiveTo assess the impact of interhospital transfer on the interplay between functional outcome, mortality, reperfusion rates and workflow time metrics in patients undergoing endovascular thrombectomy (EVT) for acute ischaemic stroke due to large vessel occlusion (LVO) in the anterior cerebral circulation.Design, setting and participantsThis is an analysis of a prospective database of consecutive patients undergoing EVT for LVO presenting between January 2017 and December 2018 at a single Australian comprehensive stroke centre (CSC). Patients presented directly or were transferred to the CSC from 21 sites across New South Wales and the Australian Capital Territory.Main outcome measuresThe main outcome measures were rate of good 90-day functional outcome (modified Rankin Scale 0–2), successful reperfusion (Thrombolysis in Cerebral Infarction scale grade 2b or 3), symptomatic intracerebral haemorrhage (sICH) and 90-day mortality. Key workflow time metric milestones were examined.Results154 of 213 (72%) patients were interhospital transfers. There was no significant difference in baseline characteristics including age, National Institutes of Health Stroke Scale score, intravenous thrombolysis administration or procedure time between transferred and direct presenters (all p>0.05). Transferred patients had worse 90-day functional outcome (39.6% vs 61.0%, OR 0.42, 95% CI 0.23 to 0.78), higher mortality (25.3% vs 6.8%, OR 4.66, CI 1.59 to 13.70) and longer stroke onset to treatment (groin puncture) time (298 min vs 205 min, pConclusionInterhospital transfer is associated with longer stroke onset to treatment, worse 90-day functional outcome and higher mortality compared with patients presenting directly to the CSC.

Introduction: Observational studies have shown conflicting data on safety and efficacy of carotid stenting in the setting of acute ischemic stroke. We evaluated our stent patency, functional outcomes and symptomatic intracranial haemorrhage rates in acute strokes with tandem occlusions treated with endovascular thrombectomy and concurrent carotid stenting. Methods: Prospectively maintained EVT databases at two comprehensive stroke centres were interrogated for patients with anterior circulation tandem occlusion stroke who were treated with EVT and extracranial carotid artery stenting. Intracranial haemorrhage on post-operative CT & MRI brain was assessed on European Cooperative Acute Stroke Study II criteria. Stent patency was assessed on CTA 12-24 hours post-operatively. Clinical and neuroimaging endpoints were modified treatment in cerebral ischaemia (mTICI) score, stent patency, any intracranial haemorrhage, symptomatic intracranial haemorrhage (sICH), and 90-day modified Rankin Scale (mRS). Results: Between 2016 and 2019, 105 patients were identified (mean age 70 years, 78% male, median NIHSS 15). Median time to reperfusion was 9.26 hours, with 97.1% achieving mTICI 2b/3. Immediate dual antiplatelet therapy was used in 102 (97.1%) patients. Good functional outcomes (mRS 0-2) were achieved in 53 (51%) patients. Acute stent thrombosis occurred in 12 (11.4%) patients with 7 (58.3%) still achieving good functional outcomes. Any intracranial haemorrhage occurred in 46 (44%) of all patients. Symptomatic intracranial haemorrhage occurred in 8 (7.6%). All sICH patients had 90-day mRS of 3-6. Conclusion: Acute tandem occlusion stroke patients present complex management challenges. Despite immediate dual antiplatelet therapy, acute stent occlusions may still occur. Symptomatic intracranial haemorrhage rates are acceptable in these complex patients, however, all patients with sICH had poorer outcomes.

Introduction: Recent data suggests stenting of symptomatic intracranial atherosclerotic disease (ICAD) in the hyper-acute period (< 8 days of symptom onset) is associated with a high incidence of early postoperative morbidity and mortality. We assessed the efficacy and safety of this select group of patients at our institutions. Methods: Between December 2017 to May 2019, anterior circulation stroke patients who underwent acute stenting of symptomatic intracranial atherosclerotic disease with the Atlas stent (Stryker) were identified from a prospectively maintained database of stroke patients at two comprehensive stroke centres. Baseline characteristics, imaging, and clinical outcomes are reported. Results: Nine cases were identified (mean age 71years, 44.4% male, median NIHSS 9 (range 5-18)). All patients had baseline mRS of 3 or less. Median time from symptom onset to groin puncture was 10hours (range 4-96hours). All patients received dual-antiplatelet therapy with Aspirin and Prasugrel(DAPT) either immediately before or after the procedure. In patients who did not receive pre-procedure loading with DAPT (55.6%), a single intravenous dose of Abciximab (mean 9mg +/- 4mg) or Tirofiban (1mg) was given intra-operatively. No thromboembolic complications or mortality occurred in the early postoperative period (within 72hours). All patients showed improvement in target vessel perfusion on day-one CT-perfusion. At 90-days, 7 (77.8%) patients were either functionally independent (mRS 0-2) or at their pre-operative baseline. No symptomatic intracranial haemorrhage occurred. No recurrent target vessel strokes were recorded. One patient died of medical complications unrelated to intracranial stenting and one patient was mRS 3 at 90-days. Conclusion: Hyper-acute stenting of symptomatic ICAD may be safe and effective. Antiplatelet treatment strategies and advances in stent devices may be critical in the success of this approach.

Introduction: Endovascular thrombectomy (EVT) is beneficial in late time window stroke. However, patients with tandem extracranial carotid and intracranial occlusions are under-represented in previous trials. We analysed our acute anterior circulation strokes with tandem occlusions treated with EVT and extracranial internal carotid artery stenting. Methods: A prospectively maintained database of EVT patients treated in two Australian comprehensive stroke centres between January 2016 and May 2019 was screened for acute anterior circulation ischaemic stroke patients treated with EVT and extracranial internal carotid artery stenting. The cohort was divided into patients treated in early ( < 6 hours from symptom onset) and late (>6 hours from symptom onset) time windows. Results: Endovascular thrombectomy with acute carotid stenting was performed in 96 patients (mean age 71years, 78.3% male, mean time to reperfusion 13.5 +/- 10.1 hours, median NIHSS 15). Treatment >6hours after symptom onset occurred in 61 (63.5%) patients. No significant difference was seen between the two groups with respect to age, sex, presenting NIHSS, or mTICI score. At 90-day follow-up, good functional outcome (mRS 0-2) was similar for patients treated in the late versus early time windows, 19 (54.3%) vs 34 (55.7%), p=0.89 respectively. No difference was seen for symptomatic intracranial haemorrhage, 5 (7.2%) vs 3 (8.1%) p=0.87, or mortality at 90-day follow-up, 15 (24.6%) vs 6 (17.1%) p=0.40. Conclusion: Carotid stenting in late time window has comparable safety and efficacy to early time window stroke.

One club towered above all others in the final decade of East German football. Berliner FC Dynamo (BFC), the team sponsored by the secret police (Stasi), won the league title for ten straight seasons between 1979 and 1988, often in highly controversial circumstances. BFC’s success triggered unprecedented nationwide protests. This essay examines these protests, situating BFC’s hegemony in the complex web of domestic club rivalries and the transnational framework of Cold War sport. The BFC problem symbolized a deep popular disillusionment with “existing socialism” and ultimately prefaced the demise of Communist rule in 1989.

Background: The benefit of palliative care referral for severe stroke patients on endof-life care pathway (EOLCP) is increasingly recognised. Palliative care provides assistance with symptom management and transition to end-of-life care. Advance care planning (ACP) may help accommodate patient/family expectations and guide management. Methods: This is a retrospective study of all stroke deaths (2014–2015) at Liverpool Hospital, Sydney, Australia. Data examined included age, comorbidities, living arrangements, pre-existing ACP, palliative care referral rates and ‘survival time’. Results: In total, 123 patient (mean age SD = 76 13 years) deaths were identified from 1067 stroke admissions (11.5% mortality); 64 (52%) patients had ischaemic stroke and 59 (48%) intracerebral haemorrhage (ICH), and 40% suffered a prior stroke, and 43% required a carer at home or were in an aged care facility. Survival time from admission was significantly longer in patients with ischaemic stroke compared to intracerebral haemorrhage (median, interquartile range [IQR]: 9.5 [18] vs 2 [4] days, P < 0.001). Only two patients had pre-existing ACP; 44% of patients were referred to palliative care and 41% were commenced on dedicated EOLCP. Palliative care referral was less likely in patients who died under neurosurgery. EOLCP were significantly less likely to be commenced in patients who underwent acute intervention or were not referred to palliative care. Conclusion: In this cohort, palliative care referral and EOLCP were commenced in less than 50% of patients, highlighting significant variations in clinical care. These data support the need to promote awareness of ACP, particularly in patients with prior stroke or significant comorbidities. This may help reduce potentially futile invasive investigations and treatment.

Background: Failure to recognise acute stroke may result in worse outcomes due to missed opportunity for acute stroke therapies. Our study examines factors associated with stroke misdiagnosis in patients admitted to a large comprehensive stroke centre. Methods: Retrospective review comparing 156 consecutive stroke patients misdiagnosed in emergency department (ED) with 156 randomly selected stroke controls matched for age, gender, language spoken and stroke subtype for the period 2014–2016. Results: There were 141 ischemic and 15 hemorrhagic misdiagnosed strokes (median age: 77 years, male:female = 1.3: 1). Symptom resolution, altered mental status, nausea/vomiting, dizziness and vertigo favored misdiagnosis (p < 0.05). Hemiparesis and dysarthria favored an accurate diagnosis (p < 0.05). Misdiagnosed patients were more commonly triaged into a lower ED category (62 vs. 42%, p = 0.001), clinically assessed as Face, Arm, Speech and Time (FAST) – negative (78 vs. 22%, p < 0.001) and underwent delayed CT imaging (median 4.1 vs. 1.5 h, p < 0.001). Misdiagnosed patients were more likely to have posterior circulation stroke (PCS; 39 vs. 22%, p = 0.01) and be admitted under non-neurological services (35 vs. 11%, p < 0.001) with worse discharge outcomes including increased mortality. Conclusions: Patients with stroke misdiagnosis were commonly FAST-negative with nonspecific symptoms including altered mental status, dizziness and nausea/vomiting often associated with PCS. Improved diagnostic accuracy may increase access to acute therapies.

Background and Aims: Endovascular Thrombectomy (EVT) for anterior circulation large vessel occlusion(LVO) in late time windows (over 6 hours) has been validated. Studies utilised advanced neuroimaging to select patients with small ischaemic cores. We have evaluated if routine imaging with non-contrast CT (NCCT) is inferior to CT Perfusion (CTP) to select patients for EVT in late time windows. Method: A prospectively maintained database of all EVT patients at two tertiary referral centres was retrospectively interrogated to identify anterior circulation LVO patients, with groin puncture times over 6 hours from symptom onset or time last seen well. Subjects were divided into those that underwent CTP in addition to routine NCCT and CT angiography (CTA) and those that were selected by NCCT/CTA alone. Results: A total of 85 patients were included, 39 (46%) had CTP (CTP+). No significant difference between baseline characteristics of CTP+ vs CTP- groups such as age (mean 66 vs 74, p=0.26), gender (male 49% vs 59%, p=0.36), median ASPECT (8 vs 8, p=0.84) and median NIHSS (13 vs 13, p=0.42) were observed. The two groups were also well matched with respect to time metrics including onset to imaging time (mean 519 vs 477 mins, p=0.41), time to groin puncture (mean 733 vs 690 mins, p=0.90) and procedure time (mean 41 vs 38 mins, p=0.94). No significant difference between early neurological recovery (36% vs 44%, p=0.48), 90 day mean utility weighted mRS (6.2, 95% CI [5.1, 7.4] vs 6.4, 95% CI [5.2, 7.5] p=0.75), rates of functional independence at 90 days (60% vs 64%, p=0.76), and rates of symptomatic haemorrhage (8 vs 9%, p=0.41) was observed between the groups. Conclusion: In late time windows, anterior circulation LVO patients selected for EVT based on routine imaging had non-inferior outcomes to those who underwent CTP. Our data suggests that late time window patients who do not have access to advanced neuroimaging should not be excluded from EVT.

Kufs disease is the major adult form of neuronal ceroid lipofuscinosis, but is rare and difficult to diagnose. Diagnosis was traditionally dependent on the demonstration of characteristic storage material, but distinction from normal age-related accumulation of lipofuscin can be challenging. Mutation of CLN6 has emerged as the most important cause of recessive Kufs disease but, remarkably, is also responsible for variant late infantile ceroid lipofuscinosis. Here we provide a detailed description of Kufs disease due to CLN6 pathogenic variants. We studied 20 cases of Kufs disease with CLN6 pathogenic variants from 13 unrelated families. Mean age of onset was 28 years (range 12-51) with bimodal peaks in teenage and early adult life. The typical presentation was of progressive myoclonus epilepsy with debilitating myoclonic seizures and relatively infrequent tonic-clonic seizures. Patients became wheelchair-bound with a mean 12 years post-onset. Ataxia was the most prominent motor feature. Dementia appeared to be an invariable accompaniment, although it could take a number of years to manifest and occasionally cognitive impairment preceded myoclonic seizures. Patients were usually highly photosensitive on EEG. MRI showed progressive cerebral and cerebellar atrophy. The median survival time was 26 years from disease onset. Ultrastructural examination of the pathology revealed fingerprint profiles as the characteristic inclusions, but they were not reliably seen in tissues other than brain. Curvilinear profiles, which are seen in the late infantile form, were not a feature. Of the 13 unrelated families we observed homozygous CLN6 pathogenic variants in four and compound heterozygous variants in nine. Compared to the variant late infantile form, there was a lower proportion of variants that predicted protein truncation. Certain heterozygous missense variants in the same amino acid position were found in both variant late infantile and Kufs disease. There was a predominance of cases from Italy and surrounding regions; this was partially explained by the discovery of three founder pathogenic variants. Clinical distinction of type A (progressive myoclonus epilepsy) and type B (dementia with motor disturbance) Kufs disease was supported by molecular diagnoses. Type A is usually caused by recessive pathogenic variants in CLN6 or dominant variants in DNAJC5. Type B Kufs is usually associated with recessive CTSF pathogenic variants. The diagnosis of Kufs remains challenging but, with the availability of genetic diagnosis, this will largely supersede the use of diagnostic biopsies, particularly as biopsies of peripheral tissues has unsatisfactory sensitivity and specificity.

IgLON5 antibodies are typically associated with the insidious onset of sleep disorder, parasomnia, gait disturbance and abnormal movements, with variable response to immunosuppressive therapy. We describe a case of a 50-year-old man who presented with acute speech difficulties, headache and focal seizures followed by well-formed visual hallucinations, and later, musical hallucinations of mainstream popular music. MRI of the brain demonstrated right temporal lobe changes with corresponding epileptiform activity seen on electroencephalogram. Subsequently, IgLON5 antibodies were detected in the serum. The patient was treated with anticonvulsants, as well as azathioprine with a tapering oral prednisone course with a complete resolution of the symptoms. Our case demonstrates an unusual presentation of the rare but increasingly described anti-IgLON5 disease, with musical hallucinations. The case highlights the variable and evolving clinical phenotypes that can be seen in autoimmune central nervous system disorders.

In communist East Germany, football was far more popular than the Olympic sports on which the country based its formidable sporting reputation. Very few of the films made by the state film studio Deutsche Film-Aktiengesellschaft (DEFA), though, took football as their subject matter – and those that did have been all but ignored by scholars of East German cinema. Focusing on two little-known works, the children's film Der neue Fimmel/The New Craze (1960) and the comedy Verzeihung, Sehen Sie Fusball?/Excuse Me, Are You Watching Football? (1983), this article examines the football film's evolving role as a marker of socialist values in East Germany. By analysing key themes in the two films, it argues that they chronicle a story of declining public faith in the cause of state socialism. DEFA's football films reflect and represent broad shifts in East German society in this period, charting transitions from the collective to the individual, from playing the game to watching it, and from an engagement w...

Turning away from star players and secret police surveillance, this article provides a history of East German football from below, examining the role of the people's game in shaping everyday life in the socialist state. Analyzing issues of class, gender, and youth culture as they related to three aspects of recreational football culture—men's workplace teams, women's football, and fan clubs—it argues that the sport, like few other leisure pursuits, illustrates the complex relationship between politics and pleasure in a one-party dictatorship. Football was an unusually visible, versatile, regular, and unpredictable means of giving voice and agency to ordinary East Germans, a place of multiple networks (both formal and informal) from which communist power was often excluded.

Background Tuberculous meningitis (TBM) accounts for 1–4% of all tuberculosis (TB) presentations. Paradoxical deterioration in non-HIV patients is a common manifestation of anti-tuberculosis therapy, characterised by clinico-radiological deterioration. We report a case series of TBM admissions to our institution including one case with paradoxical deterioration refractory to corticosteroids who responded to adjuvant cyclosporine. Methods Retrospective review of 12 HIV-negative patients admitted to Liverpool Hospital, Sydney (2005–2016) with laboratory and/or radiologically confirmed TBM. Results Median patient age was 40 (range 22–81 years), M:F = 7:5. Eleven patients (92%) were of Asia-Pacific origin. Eleven initially presented with central nervous system manifestations and one had preceding miliary TB. Nine patients had extra-cranial TB involvement including eight with past or current pulmonary disease. Cerebrospinal fluid (CSF) TB PCR/culture was positive in 10 patients. Paradoxical deterioration developed in three patients despite concomitant corticosteroids in two. One patient with paradoxical deterioration was refractory to corticosteroids: A 22-year-old Vietnamese male with TBM developed worsening headaches and altered mentation after seven weeks concomitant anti-TB and corticosteroid treatment. Interval MRI brain demonstrated increased size and number of tuberculomas as well as hydrocephalus. Cyclosporine was added with gradual improvement and ultimately good outcome. Conclusion Our case series highlights the seriousness of paradoxical deterioration in TBM and the potential role of adjuvant cyclosporine in patients refractory to corticosteroids.

In 1954 the football association of the German Democratic Republic (GDR) became one of UEFA's founding members. With Germany divided, and Cold War tensions at their peak, football provided one of the few cultural outlets that consistently breached the Iron Curtain. East German clubs participated regularly in UEFA competitions. The national team entered the inaugural European Championship in 1960. GDR administrators and referees became respected figures within the European game. This paper examines the history of early East German involvement in European football competitions, and the tensions that surrounded the GDR's dialogue with the European football community. Analysing the experiences of players and spectators, it focuses on the East German game as a multi-layered site of cultural transfer. Allied to the Soviet Union, GDR football primarily looked east for inspiration and opponents. At the same time, it sought contacts with the West, home of Europe's best football teams, in order to raise sta...

IntroductionThere is limited research on the visual deficits found in dementia. The Queens Square Screening Test for Visual Deficits (QS test) is designed to screen for changes in visual processing. Our study aimed to validate this test and examine the types of visual processing deficits found in dementia.MethodsWe assessed the QS test in participants with dementia, mild cognitive impairment (MCI), and healthy controls. Participants were recruited from the Neurology and Geriatrics departments of a tertiary hospital over 3-months. Cognitive impairment was measured using the Rowland Universal Dementia Assessment Scale (RUDAS).ResultsTwenty-six patients were examined. There were no statistically significant differences in age, gender, English fluency, and education between the three groups. Participants with dementia (n=8, mean RUDAS 17.5/30) scored 51.4/71 on the QS test, compared to 60.7/71 in MCI (n=7, mean RUDAS 25.0/30) and 64.6/71 in controls (n=11, mean RUDAS 27.4/30). The mean scores for each subset of the QS test for dementia, MCI and normal cognition, respectively, were: early visual processing – 19.6/25, 22.4/25, 23.7/25; object perception – 5.6/11, 7.9/11, 8.7/11; space perception – 11.4/14, 11.1/14, 12.4/14; face perception – 4.4/8, 6.4/8, 7.0/8; reading – 10.4/13, 12.9/13, 12.8/13.ConclusionIn this pilot study, the QS test was markedly abnormal in dementia but did not differentiate between MCI and normal cognition. Our findings suggest that deficits in early visual processing, reading, and the perception of objects and faces are common in dementia. Understanding the types of visual difficulties may improve the care of patients with dementia.

Background: The ABCD2 stroke risk score is recommended in national guidelines for stratifying care in transient ischaemic attack (TIA) patients, based on its prediction of early stroke risk. We had become concerned about the score accuracy and its clinical value in modern TIA cohorts. Methods: We identified emergency department-diagnosed TIA at two hospitals over 3 years (2004–2006). Cases were followed for stroke occurrence and ABCD2 scores were determined from expert record review. Sensitivity, specificity and positive predictive values (PPV) of moderate–high ABCD2 scores were determined. Results: There were 827 indexed TIA diagnoses and record review was possible in 95.4%. Admitted patients had lower 30-day stroke risk (n= 0) than discharged patients (n= 7; 3.1%) (P < 0.0001). There was no significant difference in proportion of strokes between those with a low or moderate–high ABCD2 score at 30 (1.2 vs 0.8%), 90 (2.0 vs 1.9%) and 365 days (2.4 vs 2.4%) respectively. At 30 days the sensitivity, specificity and PPV of a moderate–high score were 57% (95% confidence interval (CI) 25.0–84.2), 32.2% (95% CI 29.1–35.6) and 0.75% (95% CI 0.29–1.91) respectively. Conclusions: Early stroke risk was low after an emergency diagnosis of TIA and significantly lower in admitted patients. Moderate–high ABCD2 scores did not predict early stroke risk. We suggest local validation of ABCD2 before its clinical use and a review of its place in national guidelines.

Summary Background Previous studies have suggested that any benefits of folic acid-based therapy to lower serum homocysteine in prevention of cardiovascular events might be offset by concomitant use of antiplatelet therapy. We aimed to establish whether there is an interaction between antiplatelet therapy and the effects of folic acid-based homocysteine-lowering therapy on major vascular events in patients with stroke or transient ischaemic attack enrolled in the vitamins to prevent stroke (VITATOPS) trial. Methods In the VITATOPS trial, 8164 patients with recent stroke or transient ischaemic attack were randomly allocated to double-blind treatment with one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B 6 , and 500 μg vitamin B 12 ) and followed up for a median 3·4 years (IQR 2·0–5·5) for the primary composite outcome of stroke, myocardial infarction, or death from vascular causes. In our post-hoc analysis of the interaction between antiplatelet therapy and the effects of treatment with B vitamins on the primary outcome, we used Cox proportional hazards regression before and after adjusting for imbalances in baseline prognostic factors in participants who were and were not taking antiplatelet drugs at baseline and in participants assigned to receive B vitamins or placebo. We also assessed the interaction in different subgroups of patients and different secondary outcomes. The VITATOPS trial is registered with ClinicalTrials.gov, number NCT00097669, and Current Controlled Trials, number ISRCTN74743444. Findings At baseline, 6609 patients were taking antiplatelet therapy and 1463 were not. Patients not receiving antiplatelet therapy were more likely to be younger, east Asian, and disabled, to have a haemorrhagic stroke or cardioembolic ischaemic stroke, and to have a history of hypertension or atrial fibrillation. They were less likely to be smokers and to have a history of peripheral artery disease, hypercholesterolaemia, diabetes, ischaemic heart disease, and a revascularisation procedure. Of the participants taking antiplatelet drugs at baseline, B vitamins had no significant effect on the primary outcome (488 patients in the B-vitamins group [15%] vs 519 in the placebo group [16%]; hazard ratio [HR] 0·94, 95% CI 0·83–1·07). By contrast, of the participants not taking antiplatelet drugs at baseline, B vitamins had a significant effect on the primary outcome (123 in the B-vitamins group [17%] vs 153 in the placebo group [21%]; HR 0·76, 0·60–0·96). The interaction between antiplatelet therapy and the effect of B vitamins on the primary outcome was significant after adjusting for imbalance in the baseline variables (adjusted p for interaction=0·0204). Interpretation Our findings support the hypothesis that antiplatelet therapy modifies the potential benefits of lowering homocysteine with B-vitamin supplementation in the secondary prevention of major vascular events. If validated, B vitamins might have a role in the prevention of ischaemic events in high-risk individuals with an allergy, intolerance, or lack of indication for antiplatelet therapy. Funding Australia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, and Singapore National Medical Research Council.

The molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood-onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and can require a brain biopsy or autopsy for final diagnosis. We mapped four families with Kufs disease for whom there was good evidence of autosomal-recessive inheritance and found two peaks on chromosome 15. Three of the families were affected by Kufs type A disease and presented with progressive myoclonus epilepsy, and one was affected by type B (presenting with dementia and motor system dysfunction). Sequencing of a candidate gene in one peak shared by all four families identified no mutations, but sequencing of CLN6, found in the second peak and shared by only the three families affected by Kufs type A disease, revealed pathogenic mutations in all three families. We subsequently sequenced CLN6 in eight other families, three of which were affected by recessive Kufs type A disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family affected by unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder, in which definitive identification usually requires invasive biopsy.

Introduction: In March 2014, the NSW Government announced the NSW Integrated Care Strategy to:Transform delivery of careImprove health outcomesReduce associated costs of inappropriate / fragmented care Practice change implemented: A Local Health District LHD and a Primary Health Network PHN have been working collaboratively and developing multiple projects across Sydney’s South West. From this collaboration, an Integrated Care Collaboration ICC group was established in October 2013.The ICC Research and Evaluation R&E Implementation Working Group formed early 2015 oversees and coordinates the research and evaluation strategies related to Integrated Care initiatives. Aim / theory of change: From the implementation of those initiatives and guided by the Population, Intervention, Comparator and Outcomes PICO framework, the ICC R&E group conducted a theory analysis to consolidate each projects’ aims and align the evaluation with the Integrated Care Strategy. The outcome was the development of Common Areas of Research Concepts, each with their Logic Map and Working Group:Timeliness to Diagnosis:Management of ConditionsPrevention of EscalationsSupported Self-management / CareTechnology Enabled Population and stakeholders: Membership consists of stakeholders across multiple tiers of the health system, including government state, federal, local, non-government organisations, private enterprise, and consumer and community participation; collaborating in partnership for the Sydney’s South West community. Timeline: Established 2013 - prospective long-termHighlights: The diversity of initiatives and future evaluation prospects has also encouraged identification of key stakeholders for broader collaboration across organisations.The number of research projects and external partnerships has increased from: 4 x initiatives, 3 x research projects, and 9 x partnerships in 2016; to 9 x initiatives, 18 x research projects and 18 x partnerships.Results from research projects have already proven valuable by providing insight into details of delivering integrated care, understanding of practical issues from implementation of the strategies, advising innovative models for new technologies, and allowing for expansion. Sustainability:The ICC R&E has been able to identify some of the factors crucial for its sustained development, including:Collaborative governance modelEnhanced partnerships and relationship buildingDefined responsibilities and terms of referenceWhole of system approach for resources allocation and project management Transferability: The increasing number on partnerships and initiatives is a result from the replication of the engagement model which has proven successful since the beginning of the original three projects. Conclusions: This collaborative model has provided a stable platform for co-designing enhanced service delivery across primary and secondary care. It has also assisted with streamlining methods and turnkey solutions implementation for identifying and addressing barriers within current models of care, and for research and evaluation methodology and reporting. Discussion: The foundation of Alliances and new ways of collaboration has open the ground for innovation and transference across Local Government Areas, where key stakeholders are identified and become the crucial backbone for the establishment of new partnerships. Lessons: Formulae for maintenance of momentum and drive for development of projects concept to completion has proven to be, in great part, due to the commitment and lead from the Working Groups.

Introduction: In July 2015, HealthPathways HP was implemented by a Local Health District and a Primary Health Network. Type 2 Diabetes T2DM was identified as a priority area. HealthPathways is a dynamic online health information portal aimed at General Practitioners GPs. It supports integration by bringing together general practice and hospital-based clinicians to develop agreed local pathways. It provides guidance for assessment, management, and referral of diverse conditions linked to local resources. New pathways are constantly developed and existing pathways regularly reviewed. Methods: The study used a programmatic approach and mixed-methods including literature reviews, site visits, semi-structured interviews stakeholders and GPs, and surveys GPs and patients to understand the development, implementation and acceptance of T2DM pathways. Electronic surveys were analysed using SPSS Version 20. Cronbach’s alpha was calculated to assess internal consistency of Likert scales responses. Interviews were digitally recorded, transcribed and evaluated using NVivo10 for thematic analysis. Initial codes were abstracted further to identify concepts and categories to generate final themes. Results: 57 GPs responded to the electronic survey. 86% reported awareness of HP and 30% had used diabetes pathways. Of those using diabetes pathways: Over 80% reported it improves quality of care, keeps them informed and supports diagnostic processes 93% agreed information is of high quality and practical 68% reported improvement in referral quality 87% reported assisted in providing more health care in the community and made their job easier Access, workflow and perceived utility were reported as barriers to use Patient survey data including wait times, frequency of clinic and emergency department visits and hospitalisations will form a baseline for later evaluations. **Preliminary analysis of the 12 stakeholder interviews has identified: Implementation Enablers: Key stakeholders’ commitment Seamless networks and collaboration between parties Clear processes and accountabilities Facilitating Factors: Identified as an effective and practical tool with high quality information Supports diagnostic process and patient management Improves referral and triage process for secondary care. Barriers: Longer consultations Prior knowledge and beliefs of health professionals Access difficulties i.e. username/password Increasing size and overly prescriptive nature of website Availability of other online resources Lack of content awareness and how it will add to the consultation/management of patients. Discussion: This preliminary analysis suggest that those who use HP have found it to be a practical tool that supports their diagnostic and referral processes and provides information of high quality. However, there may be a lack of awareness of the HP within general practices. Conclusions: HP is reported to be an effective tool which has improved referral and triage process for secondary care. It helps in improving patient outcomes and management. Lessons: Early evaluation of the pathways can only provide information on development and project implementation, rather than clinical outcomes. Study Limitations: Small survey sample size; Low GP recruitment Suggestions for Future: Broader scope for evaluation of multiple pathways to identify the best ways of ensuring sustainability, identify outcomes related to patient care and provide lessons for other regions. **NOTE: Currently on final stages of qualitative data analysis.

IntroductionTuberculous meningitis (TBM) accounts for MethodsRetrospective review of 12 HIV-negative patients admitted to Liverpool Hospital, Sydney (2005–2017) with laboratory and/or radiologically confirmed TBM.ResultsMedian age 40 (range 22–81 years), 7 males. Eleven patients were of Asia-Pacific origin. All eleven presented with central nervous system manifestations and 1 had preceding miliary TB. Nine patients had extra-cranial TB involvement, including 8 with past or current pulmonary disease. Cerebrospinal fluid (CSF) TB PCR/culture was positive in 10 patients. One patient had multi-resistant TB. PR of TBM developed in 5 patients despite concomitant corticosteroids in 4. Two cases had refractory PR.Case 1. 22 year old Vietnamese male presented with 6 week history of progressive headache and neck stiffness. CSF demonstrated 61 WCC (75% neutrophils), protein 2.67 g/L (nCase 2. 47 year old Filipino male presented with 3 week history of headache and neck stiffness and 3 day history of fever, dysarthria and diplopia. MRI brain showed basal meningitis, hydrocephalus and left putaminal infarction. CSF demonstrated 245 WCC (35% neutrophils), protein 0.68 g/L, glucose 1.8 mmol/L. Despite concomitant anti-tuberculosis and corticosteroid treatment, the patient developed PR-induced worsening hydrocephalus necessitating ventriculo-peritoneal shunting. Cyclosporin was added with gradual PR resolution.ConclusionOur case series highlights the importance of concomitant corticosteroids in TBM and the potential role of cyclosporin in refractory PR.

Introduction : HealthPathways is an integrated care approach that brings together general practice and hospital-based clinicians to develop agreed local management streams and pathways, and document these on an easily accessible website. It provides general practice teams with clinically relevant guidance on the assessment, management, and referral of a range of conditions, which are linked to locally relevant resources. In July 2015, HealthPathways was implemented by a Local Health District (LHD) and a Primary Health Network (PHN). Type 2 Diabetes (T2DM) was identified as a priority area. Methods : This is a programmatic evaluation on the development, implementation and acceptance of T2DM pathways, with qualitative and quantitative data being collected and analysed from a range of sources to better understand the pathways implications and applications. This study uses data from: HealthPathways working groups Online survey responses from General Practitioners (GPs) Semi-structured interviews of: Stakeholders (e.g., LHD and PHN staff) GPs who use the T2DM pathways Anonymous surveys of patients at diabetes clinics HealthPathways web server utilisation data Interviews are digitally recorded and transcripts analysed using a thematic analysis approach – with initial codes generated directly from the participant’s words. These codes will be abstracted further to identify concepts and categories to generate final themes. Results : NOTE: This project is currently recruiting participants and undergoing analysis. Current results indicate that 68% of GP respondents use HealthPathways, with 39% on a daily to weekly basis and nearly half (47%) use HealthPathways in caring for a patient with DM. Thematic analysis from stakeholder interviews emphasise the importance of established collaborations and the need for standardized tools with common priorities and transparency in processes. Discussion : This preliminary analysis suggest that those who use HealthPathways have found it to be a practical tool that supports their diagnostics process and provides information of high quality. However, it also highlights that there is a lack of awareness of the HealthPathways within general practices. Conclusions : HealthPathways has been live for 18 months and is still under development Due to early evaluation of the pathways, clinical outcomes data is not in the scope Lessons : Early evaluation of the pathways can only provide information on development and project implementation, rather than clinical outcomes Implementation Enablers : Key stakeholders’ commitment Seamless networks and collaboration with steering committee and working party rapport Clear processes and accountabilities for project management and implementation Study Limitations : Analysis of only one specific pathway has proven to be a barrier for GP recruitment Project design dependent on volunteer participation for two arms of the study Extent of dynamic engagement Access to Diabetes Clinics Suggestions for Future : Broader scope for evaluation of multiple pathways Further enquiry into the experiences and practical implementation of the HealthPathways within the general practice business model (including referral to specialised services) Evaluation of clinical outcomes and patient experience Cost analysis for impacts on lower duplication of pathology/imaging studies and hospitalisations Potential impact on streamlining patient flow through the health system and decrease on avoidable hospitalisations due to early identification and timely management of targeted conditions

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.

In Soviet-occupied East Germany during the mid- to late 1940s, a remarkable but scarcely remarked-upon transition took place. Hundreds of thousands of young Germans who had previously been members of the Nazi youth organizations, the Hitler Youth (HJ) and the League of German Girls (BDM) flocked to join the Communist-led Free German Youth (FDJ), a unisex ‘united youth organization’ founded under Soviet auspices in March 1946. This paper examines the experiences of this ‘twice betrayed’ generation, whose members rapidly—though with varying degrees of enthusiasm—switched allegiance from Nazism to Communism after the Second World War and ultimately exchanged life in one authoritarian youth organization for life in another. Drawing on archival and interview material, it first seeks to outline Communist attitudes towards denazification among the young in the postwar period, before going on to examine from a grass-roots perspective the experiences, motivations, and attitudes of those who exchanged their HJ or BDM membership books for those of the FDJ. Despite, or perhaps because of, East Germany's strongly-espoused and rigidly dogmatic ‘anti-fascism’, open discussion of the Nazi past was—for a variety of reasons—taboo during the immediate postwar period, particularly among the young. This paper concludes by discussing the reasons behind this ‘pact of silence’ between the Communists and the ‘Hitler Youth generation’—and how it impacted upon subsequent generations of young people ‘born into socialism’.