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; P<0.01), indicating 6750 fewer bed days a year. The number of patients treated in a hyperacute stroke unit increased from 39% in 2010-12 to 86% in 2015/16. In London, the 90 day mortality rate was sustained (P>0.05), 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.

Patient experience of centralized acute stroke care pathways.

BACKGROUND: In 2010, Greater Manchester (GM) and London centralized acute stroke care services into a reduced number of hyperacute stroke units, with local stroke units providing on-going care nearer patients' homes. OBJECTIVE: To explore the impact of centralized acute stroke care pathways on the experiences of patients. DESIGN: Qualitative interview study. Thematic analysis was undertaken, using deductive and inductive approaches. Final data analysis explored themes related to five chronological phases of the centralized stroke care pathway. SETTING AND PARTICIPANTS: Recruitment from 3 hospitals in GM (15 stroke patients/8 family members) and 4 in London (21 stroke patients/9 family members). RESULTS: Participants were impressed with emergency services and initial reception at hospital: disquiet about travelling further than a local hospital was allayed by clear explanations. Participants knew who was treating them and were involved in decisions. Difficulties for families visiting hospitals a distance from home were raised. Repatriation to local hospitals was not always timely, but no detrimental effects were reported. Discharge to the community was viewed less positively. DISCUSSION AND CONCLUSIONS: Patients on the centralized acute stroke care pathways reported many positive aspects of care: the centralization of care pathways can offer patients a good experience. Disadvantages of travelling further were perceived to be outweighed by the opportunity to receive the best quality care. This study highlights the necessity for all staff on a centralized care pathway to provide clear and accessible information to patients, in order to maximize their experience of care.

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.

Patient, carer and public involvement in major system change in acute stroke services: The construction of value.

BACKGROUND: Patient and public involvement is required where changes to care provided by the UK National Health Service are proposed. Yet involvement is characterized by ambiguity about its rationales, methods and impact. AIMS: To understand how patients and carers were involved in major system changes (MSCs) to the delivery of acute stroke care in 2 English cities, and what kinds of effects involvement was thought to produce. METHODS: Analysis of documents from both MSC projects, and retrospective in-depth interviews with 45 purposively selected individuals (providers, commissioners, third-sector employees) involved in the MSC. RESULTS: Involvement was enacted through consultation exercises; lay membership of governance structures; and elicitation of patient perspectives. Interviewees' views of involvement in these MSCs varied, reflecting different views of involvement per se, and of implicit quality criteria. The value of involvement lay not in its contribution to acute service redesign but in its facilitation of the changes developed by professionals. We propose 3 conceptual categories-agitation management, verification and substantiation-to identify types of process through which involvement was seen to facilitate system change. DISCUSSION: Involvement was seen to have strategic and intrinsic value. Its strategic value lay in facilitating the implementation of a model of care that aimed to deliver evidence-based care to all; its intrinsic value was in the idea of citizen participation in change processes as an end in its own right. The concept of value, rather than impact, may provide greater traction in analyses of contemporary involvement practices.

Potential of high-dose cefepime/tazobactam against multiresistant Gram-negative pathogens.

BACKGROUND: Early ß-lactamase inhibitors were combined with established penicillins, but different combinations may be more appropriate to counter current ß-lactamase threats, with development facilitated by the US Generating Antibiotic Incentives Now (GAIN) Act. Cefepime/tazobactam is especially attractive, combining an AmpC-stable cephalosporin with a clinically established inhibitor, active against ESBLs and suitable for high-dose administration. METHODS: Organisms (n = 563) were clinical isolates submitted to the UK national reference laboratory. MICs were determined by CLSI agar dilution with tazobactam at 4 mg/L and, for a subset, at 8 mg/L. RESULTS: Cefepime/tazobactam 8 + 4 mg/L achieved coverage of 96%-100% of Enterobacteriaceae with penicillinases, AmpC, ESBL, K1 or OXA-48 ß-lactamases. Even at 1 + 4 mg/L, the combination inhibited >94% of isolates with penicillinases, AmpC enzymes or ESBLs. Most Enterobacteriaceae with KPC and NDM carbapenemase were resistant at current cefepime breakpoints but 80% of those with VIM types were susceptible at 8 + 4 mg/L. Tazobactam did little to potentiate cefepime against non-fermenter groups, though gains were seen against AmpC-producing Acinetobacter spp. and Stenotrophomonas maltophilia. Increasing the tazobactam concentration to 8 mg/L gave further small increases in activity against Enterobacteriaceae groups. CONCLUSIONS: High-dose cefepime/tazobactam, justifying an 8 + 4 or 8 + 8 mg/L breakpoint, can achieve a carbapenem-like spectrum, with some additional coverage of OXA-48 (and maybe VIM) Enterobacteriaceae. Clinical evaluation is warranted.

Explaining outcomes in major system change: a qualitative study of implementing centralised acute stroke services in two large metropolitan regions in England.

BACKGROUND: Implementing major system change in healthcare is not well understood. This gap may be addressed by analysing change in terms of interrelated components identified in the implementation literature, including decision to change, intervention selection, implementation approaches, implementation outcomes, and intervention outcomes. METHODS: We conducted a qualitative study of two cases of major system change: the centralisation of acute stroke services in Manchester and London, which were associated with significantly different implementation outcomes (fidelity to referral pathway) and intervention outcomes (provision of evidence-based care, patient mortality). We interviewed stakeholders at national, pan-regional, and service-levels (n = 125) and analysed 653 documents. Using a framework developed for this study from the implementation science literature, we examined factors influencing implementation approaches; how these approaches interacted with the models selected to influence implementation outcomes; and their relationship to intervention outcomes. RESULTS: London and Manchester's differing implementation outcomes were influenced by the different service models selected and implementation approaches used. Fidelity to the referral pathway was higher in London, where a 'simpler', more inclusive model was used, implemented with a 'big bang' launch and 'hands-on' facilitation by stroke clinical networks. In contrast, a phased approach of a more complex pathway was used in Manchester, and the network acted more as a platform to share learning. Service development occurred more uniformly in London, where service specifications were linked to financial incentives, and achieving standards was a condition of service launch, in contrast to Manchester. 'Hands-on' network facilitation, in the form of dedicated project management support, contributed to achievement of these standards in London; such facilitation processes were less evident in Manchester. CONCLUSIONS: Using acute stroke service centralisation in London and Manchester as an example, interaction between model selected and implementation approaches significantly influenced fidelity to the model. The contrasting implementation outcomes may have affected differences in provision of evidence-based care and patient mortality. The framework used in this analysis may support planning and evaluating major system changes, but would benefit from application in different healthcare contexts.

Effects of Centralizing Acute Stroke Services on Stroke Care Provision in Two Large Metropolitan Areas in England.

BACKGROUND AND PURPOSE: In 2010, Greater Manchester and London centralized acute stroke care into hyperacute units (Greater Manchester=3, London=8), with additional units providing ongoing specialist stroke care nearer patients' homes. Greater Manchester patients presenting within 4 hours of symptom onset were eligible for hyperacute unit admission; all London patients were eligible. Research indicates that postcentralization, only London's stroke mortality fell significantly more than elsewhere in England. This article attempts to explain this difference by analyzing how centralization affects provision of evidence-based clinical interventions. METHODS: Controlled before and after analysis was conducted, using national audit data covering Greater Manchester, London, and a noncentralized urban comparator (38 623 adult stroke patients, April 2008 to December 2012). Likelihood of receiving all interventions measured reliably in pre- and postcentralization audits (brain scan; stroke unit admission; receiving antiplatelet; physiotherapist, nutrition, and swallow assessments) was calculated, adjusting for age, sex, stroke-type, consciousness, and whether stroke occurred in-hospital. RESULTS: Postcentralization, likelihood of receiving interventions increased in all areas. London patients were overall significantly more likely to receive interventions, for example, brain scan within 3 hours: Greater Manchester=65.2% (95% confidence interval=64.3-66.2); London=72.1% (71.4-72.8); comparator=55.5% (54.8-56.3). Hyperacute units were significantly more likely to provide interventions, but fewer Greater Manchester patients were admitted to these (Greater Manchester=39%; London=93%). Differences resulted from contrasting hyperacute unit referral criteria and how reliably they were followed. CONCLUSIONS: Centralized systems admitting all stroke patients to hyperacute units, as in London, are significantly more likely to provide evidence-based clinical interventions. This may help explain previous research showing better outcomes associated with fully centralized models.

Impact of centralising acute stroke services in English metropolitan areas on mortality and length of hospital stay: difference-in-differences analysis.

OBJECTIVE: To investigate whether centralisation of acute stroke services in two metropolitan areas of England was associated with changes in mortality and length of hospital stay. DESIGN: Analysis of difference-in-differences between regions with patient level data from the hospital episode statistics database linked to mortality data supplied by the Office for National Statistics. SETTING: Acute stroke services in Greater Manchester and London, England. PARTICIPANTS: 258,915 patients with stroke living in urban areas and admitted to hospital in January 2008 to March 2012. INTERVENTIONS: "Hub and spoke" model for acute stroke care. In London hyperacute care was provided to all patients with stroke. In Greater Manchester hyperacute care was provided to patients presenting within four hours of developing symptoms of stroke. MAIN OUTCOME MEASURES: Mortality from any cause and at any place at 3, 30, and 90 days after hospital admission; length of hospital stay. RESULTS: In London there was a significant decline in risk adjusted mortality at 3, 30, and 90 days after admission. At 90 days the absolute reduction was -1.1% (95% confidence interval -2.1 to -0.1; relative reduction 5%), indicating 168 fewer deaths (95% confidence interval 19 to 316) during the 21 month period after reconfiguration in London. In both areas there was a significant decline in risk adjusted length of hospital stay: -2.0 days in Greater Manchester (95% confidence interval -2.8 to -1.2; 9%) and -1.4 days in London (-2.3 to -0.5; 7%). Reductions in mortality and length of hospital stay were largely seen among patients with ischaemic stroke. CONCLUSIONS: A centralised model of acute stroke care, in which hyperacute care is provided to all patients with stroke across an entire metropolitan area, can reduce mortality and length of hospital stay.

Phase I study of lapatinib in combination with chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck.

PURPOSE: This study (EGF100262) sought to establish the recommended phase II dose of lapatinib with chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). PATIENTS AND METHODS: Patients were enrolled onto cohorts of escalating lapatinib dose (500, 1,000, and 1,500 mg/d). Patients received 1 week of lapatinib alone followed by 6.5 to 7 weeks of the same dose of lapatinib plus radiotherapy 66 to 70 Gy and cisplatin 100 mg/m(2) on days 1, 22, and 43 of radiotherapy. End points included safety/tolerability and clinical activity. RESULTS: Thirty-one patients were enrolled (seven patients in each of the 500- and 1,000-mg cohorts and three in the 1,500-mg cohort; an additional 14 patients were enrolled at 1,500 mg in a safety cohort). Dose-limiting toxicities (DLTs) included perforated ulcer in one patient in the 500-mg cohort and transient elevation of liver enzymes in one patient in the 1,000-mg cohort. No DLTs were observed in the 1,500-mg cohort. Therefore, the recommended phase II dose was defined as lapatinib 1,500 mg/d with chemoradiotherapy. The most common grade 3 to 4 adverse events were radiation mucositis, radiation dermatitis, lymphopenia, and neutropenia. No patients experienced drug-related symptomatic cardiotoxicity, and no interstitial pneumonitis was reported. The overall response rate was 81% (65% at the recommended phase II dose). CONCLUSION: The recommended phase II dose is lapatinib 1,500 mg/d with chemoradiotherapy in patients with LA SCCHN; this regimen is associated with an acceptable tolerability profile. Given these findings, randomized phase II and III studies of lapatinib plus chemoradiotherapy have been initiated.