Patient outcomes up to 15 years after stroke: survival, disability, quality of life, cognition and mental health

BACKGROUND: The global epidemiological shift of disease burden towards long-term conditions means understanding long-term outcomes of cardiovascular disease is increasingly important. More people are surviving stroke to experience its long-term consequences, but outcomes in people living more >10 years after stroke have not been described in detail. METHODS: Data were collected for the population-based South London Stroke Register, with participants followed up annually until death. Outcomes were survival, disability, activity, cognitive impairment, quality of life, depression and anxiety. FINDINGS: Of 2625 people having first-ever stroke, 262 (21%) survived to 15 years. By 15 years, 61% (95% CI 55% to 67%) of the survivors were male, with a median age of stroke onset of 58 years (IQR 48-66). 87% of the 15-year survivors were living at home and 33.8% (26.2% to 42.4%) had mild disability, 14.3% (9.2% to 21.4%) moderate disability and 15.0% (9.9% to 22.3%) severe disability. The prevalence of disability increased with time but 1 in 10 of the 15-year survivors had lived with moderate-severe disability since their stroke. At 15 years, the prevalence of cognitive impairment was 30.0% (19.5% to 43.1%), depression 39.1% (30.9% to 47.9%) and anxiety 34.9% (27.0% to 43.8%), and survivors reported greater loss of physical than mental quality of life. CONCLUSIONS: One in five people live at least 15 years after a stroke and poor functional, cognitive and psychological outcomes affect a substantial proportion of these long-term survivors. As the global population of individuals with cardiovascular long-term conditions grows, research and health services will need to increasingly focus on preventing and managing the long-term consequences of stroke

Effectiveness of a clinical pathway for acute stroke care in a district general hospital: an audit

BACKGROUND: Organised stroke care saves lives and reduces disability. A clinical pathway might be a form of organised stroke care, but the evidence for the effectiveness of this model of care is limited. METHODS: This study was a retrospective audit study of consecutive stroke admissions in the setting of an acute general medical unit in a district general hospital. The case-notes of patients admitted with stroke for a 6-month period before and after introduction of the pathway, were reviewed to determine data on length of stay, outcome, functional status, (Barthel Index, BI and Modified Rankin Scale, MRS), Oxfordshire Community Stroke Project (OCSP) sub-type, use of investigations, specific management issues and secondary prevention strategies. Logistic regression was used to adjust for differences in case-mix. RESULTS: N = 77 (prior to the pathway) and 76 (following the pathway). The median (interquartile range, IQR) age was 78 years (67.75–84.25), 88% were European NZ and 37% were male. The median (IQR) BI at admission for the pre-pathway group was less than the post-pathway group: 6 (0–13.5) vs. 10 (4–15.5), p = 0.018 but other baseline variables were statistically similar. There were no significant differences between any of the outcome or process of care variables, except that echocardiograms were done less frequently after the pathway was introduced. A good outcome (MRS<4) was obtained in 66.2% prior to the pathway and 67.1% after the pathway. In-hospital mortality was 20.8% and 23.1%. However, using logistic regression to adjust for the differences in admission BI, it appeared that admission after the pathway was introduced had a significant negative effect on the probability of good outcome (OR 0.29, 95%CI 0.09-0.99). CONCLUSION: A clinical pathway for acute stroke management appeared to have no benefit for the outcome or processes of care and may even have been associated with worse outcomes. These data support the conclusions of a recent Cochrane review

The potential role of cost-utility analysis in the decision to implement major system change in acute stroke services in metropolitan areas in England

BACKGROUND: The economic implications of major system change are an important component of the decision to implement health service reconfigurations. Little is known about how best to report the results of economic evaluations of major system change to inform decision-makers. Reconfiguration of acute stroke care in two metropolitan areas in England, namely London and Greater Manchester (GM), was used to analyse the economic implications of two different implementation strategies for major system change. METHODS: A decision analytic model was used to calculate difference-in-differences in costs and outcomes before and after the implementation of two major system change strategies in stroke care in London and GM. Values in the model were based on patient level data from Hospital Episode Statistics, linked mortality data from the Office of National Statistics and data from two national stroke audits. Results were presented as net monetary benefit (NMB) and using Programme Budgeting and Marginal Analysis (PBMA) to assess the costs and benefits of a hypothetical typical region in England with approximately 4000 strokes a year. RESULTS: In London, after 90 days, there were nine fewer deaths per 1000 patients compared to the rest of England (95% CI -24 to 6) at an additional cost of £770,027 per 1000 stroke patients admitted. There were two additional deaths (95% CI -19 to 23) in GM, with a total costs saving of £156,118 per 1000 patients compared to the rest of England. At a £30,000 willingness to pay the NMB was higher in London and GM than the rest of England over the same time period. The results of the PBMA suggest that a GM style reconfiguration could result in a total greater health benefit to a region. Implementation costs were £136 per patient in London and £75 in GM. CONCLUSIONS: The implementation of major system change in acute stroke care may result in a net health benefit to a region, even one functioning within a fixed budget. The choice of what model of stroke reconfiguration to implement may depend on the relative importance of clinical versus cost outcomes

Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

Temporal variations in quality of acute stroke care and outcomes in London hyperacute stroke units: a mixed-methods study

This is the final version. Available from the NIHR Journals Library via the DOI in this recordBackground Seven-day working in hospitals is a current priority of international health research and policy. Previous research has shown variability in delivering evidence-based clinical interventions across different times of the day and week. We aimed to identify factors influencing such variations in London hyperacute stroke units. Objectives To investigate variations in quality of acute stroke care and outcomes by day and time of admission in London hyperacute stroke units, and to identify factors influencing such variations. Design This was a prospective cohort study using anonymised patient-level data from the Sentinel Stroke National Audit Programme. Factors influencing variations in care and outcomes were studied through interview and observation data. Setting The setting was acute stroke services in London hyperacute stroke units. Participants A total of 7094 patients with a primary diagnosis of stroke took part. We interviewed hyperacute stroke unit staff (n = 76), including doctors, nurses, therapists and administrators, and 31 patients and carers. We also conducted non-participant observations of delivery of care at different times of the day and week (n = 45, ≈102 hours). Intervention Hub-and-spoke model for care of suspected acute stroke patients in London with performance standards was designed to deliver uniform access to high-quality hyperacute stroke unit care across the week. Main outcome measures Indicators of quality of acute stroke care, mortality at 3 days after admission, disability at the end of the inpatient spell and length of stay. Data sources Sentinel Stroke National Audit Programme data for all patients in London hyperacute stroke units with a primary diagnosis of stroke between 1 January and 31 December 2014, and nurse staffing data for all eight London hyperacute stroke units for the same period. Results We found no variation in quality of care by day and time of admission across the week in terms of stroke nursing assessment, brain scanning and thrombolysis in London hyperacute stroke units, nor in 3-day mortality nor disability at hospital discharge. Other quality-of-care measures significantly varied by day and time of admission. Quality of care was better if the nurse in charge was at a higher band and/or there were more nurses on duty. Staff deliver ‘front-door’ interventions consistently by taking on additional responsibilities out of hours, creating continuities between day and night, building trusting relationships and prioritising ‘front-door’ interventions. Limitations We were unable to measure long-term outcomes as our request to the Sentinel Stroke National Audit Programme, the Healthcare Quality Improvement Partnership and NHS Digital for Sentinel Stroke National Audit Programme data linked with patient mortality status was not fulfilled. Conclusions Organisational factors influence 24 hours a day, 7 days a week (24/7), provision of stroke care, creating temporal patterns of provision reflected in patient outcomes, including mortality, length of stay and functional independence. Future work Further research would help to explore 24/7 stroke systems in other contexts. We need a clearer understanding of variations by looking at absolute time intervals, rather than achievement of targets. Research is needed with longer-term mortality and modified Rankin Scale data, and a more meaningful range of outcomes.National Institute for Health Research (NIHR

Utility of Atherosclerosis Imaging in the Evaluation of High-Density Lipoprotein–Raising Therapies

Decreased level of high density-lipoprotein cholesterol (HDL-C) is a rigorous predictor for future cardiovascular events. Much effort is being made to develop HDL-C–raising pharmacotherapies in the attempt to avert the pandemic of atherosclerotic disease. Important properties by which HDL-C–raising compounds are effective involve improvement of cholesterol uptake from macrophages in plaque for transport back to the liver, improvement of endothelial function, and anti-inflammatory effects. Vascular imaging can aid in the determination which HDL-C–raising compounds are effective. Ultrasound and MRI have proved suitable for assessment of structural changes of the vessel wall. Ultrasound can also be used or assessment of endothelial function. 18F-fluordeoxyglucose positron emission tomography has opened up the possibility to assess vessel wall inflammation. In this article we discuss these various imaging techniques and how they can assess efficacy as well as provide pathophysiologic information on the mechanism of action of novel HDL-C–raising drugs

Impact and sustainability of centralising acute stroke services in English metropolitan areas: retrospective analysis of hospital episode statistics and stroke national audit data

OBJECTIVES: To investigate whether further centralisation of acute stroke services in Greater Manchester in 2015 was associated with changes in outcomes and whether the effects of centralisation of acute stroke services in London in 2010 were sustained. DESIGN: Retrospective analyses of patient level data from the Hospital Episode Statistics (HES) database linked to mortality data from the Office for National Statistics, and the Sentinel Stroke National Audit Programme (SSNAP). SETTING: Acute stroke services in Greater Manchester and London, England. PARTICIPANTS: 509 182 stroke patients in HES living in urban areas admitted between January 2008 and March 2016; 218 120 stroke patients in SSNAP between April 2013 and March 2016. INTERVENTIONS: Hub and spoke models for acute stroke care. MAIN OUTCOME MEASURES: Mortality at 90 days after hospital admission; length of acute hospital stay; treatment in a hyperacute stroke unit; 19 evidence based clinical interventions. RESULTS: In Greater Manchester, borderline evidence suggested that risk adjusted mortality at 90 days declined overall; a significant decline in mortality was seen among patients treated at a hyperacute stroke unit (difference-in-differences -1.8% (95% confidence interval -3.4 to -0.2)), indicating 69 fewer deaths per year. A significant decline was seen in risk adjusted length of acute hospital stay overall (-1.5 (-2.5 to -0.4) days; P0.05), length of hospital stay declined (P<0.01), and more than 90% of patients were treated in a hyperacute stroke unit. Achievement of evidence based clinical interventions generally remained constant or improved in both areas. CONCLUSIONS: Centralised models of acute stroke care, in which all stroke patients receive hyperacute care, can reduce mortality and length of acute hospital stay and improve provision of evidence based clinical interventions. Effects can be sustained over time

Evaluation of reconfigurations of acute stroke services in different regions of England and lessons for implementation: a mixed-methods study

Background: Centralising acute stroke services is an example of major system change (MSC). ‘Hub and spoke’ systems, consisting of a reduced number of services providing acute stroke care over the first 72 hours following a stroke (hubs), with a larger number of services providing care beyond this phase (spokes), have been proposed to improve care and outcomes. Objective: To use formative evaluation methods to analyse reconfigurations of acute stroke services in different regions of England and to identify lessons that will help to guide future reconfigurations, by studying the following contrasting cases: (1) London (implemented 2010) – all patients eligible for Hyperacute Stroke Units (HASUs); patients admitted 24 hours a day, 7 days a week; (2) Greater Manchester A (GMA) (2010) – only patients presenting within 4 hours are eligible for HASU treatment; one HASU operated 24/7, two operated from 07.00 to 19.00, Monday to Friday; (3) Greater Manchester B (GMB) (2015) – all patients eligible for HASU treatment (as in London); one HASU operated 24/7, two operated with admission extended to the hours of 07.00–23.00, Monday to Sunday; and (4) Midlands and East of England – planned 2012/13, but not implemented. Design: Impact was studied through a controlled before-and-after design, analysing clinical outcomes, clinical interventions and cost-effectiveness. The development, implementation and sustainability of changes were studied through qualitative case studies, documentation analysis (n = 1091), stakeholder interviews (n = 325) and non-participant observations (n = 92; ≈210 hours). Theory-based framework was used to link qualitative findings on process of change with quantitative outcomes. Results: Impact – the London centralisation performed significantly better than the rest of England (RoE) in terms of mortality [–1.1%, 95% confidence interval (CI) –2.1% to –0.1%], resulting in an estimated additional 96 lives saved per year beyond reductions observed in the RoE, length of stay (LOS) (–1.4 days, 95% –2.3 to –0.5 days) and delivering effective clinical interventions [e.g. arrival at a Stroke Unit (SU) within 4 hours of ‘clock start’ (when clock start refers to arrival at hospital for strokes occurring outside hospital or the appearance of symptoms for patients who are already in-patients at the time of stroke): London = 66.3% (95% CI 65.6% to 67.1%); comparator = 54.4% (95% CI 53.6% to 55.1%)]. Performance was sustained over 6 years. GMA performed significantly better than the RoE on LOS (–2.0 days, 95% CI –2.8 to –1.2 days) only. GMB (where 86% of patients were treated in HASU) performed significantly better than the RoE on LOS (–1.5 days, 95% CI –2.5 to –0.4 days) and clinical interventions [e.g. SU within 4 hours: GMB = 79.1% (95% CI 77.9% to 80.4%); comparator = 53.4% (95%CI 53.0% to 53.7%)] but not on mortality (–1.3%, 95% CI –2.7%to 0.01%; p = 0.05, accounting for reductions observed in RoE); however, there was a significant effect when examining GMB HASUs only (–1.8%, 95% CI –3.4% to –0.2%), resulting in an estimated additional 68 lives saved per year. All centralisations except GMB were cost-effective at 10 years, with a higher net monetary benefit than the RoE at a willingness to pay for a quality-adjusted life-year (QALY) of £20,000–30,000. Per 1000 patients at 10 years, London resulted in an additional 58 QALYs, GMA resulted in an additional 18 QALYs and GMB resulted in an additional 6 QALYs at costs of £1,014,363, –£470,848 and £719,948, respectively. GMB was cost-effective at 90 days. Despite concerns about the potential impact of increased travel times, patients and carers reported good experiences of centralised services; this relied on clear information at every stage. Planning change – combining top-down authority and bottom-up clinical leadership was important in co-ordinating multiple stakeholders to agree service models and overcome resistance. Implementation – minimising phases of change, use of data, service standards linked to financial incentives and active facilitation of changes by stroke networks was important. The 2013 reforms of the English NHS removed sources of top-down authority and facilitative capacity, preventing centralisation (Midlands and East of England) and delaying implementation (GMB). Greater Manchester’s Operational Delivery Network, developed to provide alternative network facilitation, and London’s continued use of standards suggested important facilitators of centralisation in a post-reform context. Limitations: The main limitation of our quantitative analysis was that we were unable to control for stroke severity. In addition, findings may not apply to non-urban settings. Data on patients’ quality of life were unavailable nationally, clinical interventions measured changed over time and national participation in audits varied. Some qualitative analyses were retrospective, potentially influencing participant views. Conclusions: Centralising acute stroke services can improve clinical outcomes and care provision. Factors related to the service model implemented, how change is implemented and the context in which it is implemented are influential in improvement. We recommend further analysis of how different types of leadership contribute to MSC, patient and carer experience during the implementation of change, the impact of change on further clinical outcomes (disability and QoL) and influence of severity of stroke on clinical outcomes. Finally, our findings should be assessed in relation to MSC implemented in other health-care specialties. Funding: The National Institute for Health Research Health Services and Delivery Research programme