Metafiction, historiography, and mythopoeia in the novels of John Fowles

This thesis concerns the novelist John Fowles and analyses his seven novels in the order in which they were written. The study reveals an emergent artistic trajectory, which has been variously categorized by literary critics as postmodern. However, I suggest that Fowles's work is more complex and significant than such a reductive and simplistic label would suggest. Specifically, this study argues that Fowles's work contributes to the reinvigoration of the novel form by a radical extension of the modernist project of the literary avant-garde, interrogating various conventions associated with both literary realism and the realism of the literary modernists while still managing to evade a subjective realism. Of particular interest to the study is Fowles's treatment of his female characters, which evolves over time, indicative of an emergent quasi-feminism. This study counters the claims of many contemporary literary critics that Fowles's work cannot be reconciled with any feminist ideology. Specifically, I highlight the increasing centrality of Fowles's female characters in his novels, accompanied by a growing focus on the mysterious and the uncanny. Fowles's work increasingly associates mystery with creativity, femininity, and the mythic, suggests that mystery is essential for growth and change, both in society and in the novel form itself, and implies that women, rather than men, are naturally predisposed to embrace it. Fowles's novels reflect a worldview that challenges an over-reliance on the empirical and rational to the exclusion of the mysterious and the intuitive. I suggest that Fowles's novels evince an increasingly mythopoeic realism, constantly testing the limits of what can be apprehended and articulated in language, striving towards a realism that is universal and transcendent.EThOS - Electronic Theses Online ServiceFranklin University via the Pete Giuliani AwardGBUnited Kingdo

Why is advance care planning underused in oncology settings? A systematic overview of reviews to identify the benefits, barriers, enablers, and interventions to improve uptake

BackgroundAdvance care planning (ACP) centres on supporting people to define and discuss their individual goals and preferences for future medical care, and to record and review these as appropriate. Despite recommendations from guidelines, rates of documentation for people with cancer are considerably low.AimTo systematically clarify and consolidate the evidence base of ACP in cancer care by exploring how it is defined; identifying benefits, and known barriers and enablers across patient, clinical and healthcare services levels; as well as interventions that improve advance care planning and are their effectiveness.MethodsA systematic overview of reviews was conducted and was prospectively registered on PROSPERO. PubMed, Medline, PsycInfo, CINAHL, and EMBASE were searched for review related to ACP in cancer. Content analysis and narrative synthesis were used for data analysis. The Theoretical Domains Framework (TDF) was used to code barriers and enablers of ACP as well as the implied barriers targeted by each of the interventions.ResultsEighteen reviews met the inclusion criteria. Definitions were inconsistent across reviews that defined ACP (n=16). Proposed benefits identified in 15/18 reviews were rarely empirically supported. Interventions reported in seven reviews tended to target the patient, even though more barriers were associated with healthcare providers (n=40 versus n=60, respectively).ConclusionTo improve ACP uptake in oncology settings; the definition should include key categories that clarify the utility and benefits. Interventions need to target healthcare providers and empirically identified barriers to be most effective in improving uptake.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42021288825

The Challenge of Transparency and Validation in Health Economic Decision Modelling:A View from Mount Hood

Transparency in health economic decision modelling is important for engendering confidence in the models and in the reliability of model-based cost-effectiveness analyses. The Mount Hood Diabetes Challenge Network has taken a lead in promoting transparency through validation with biennial conferences in which diabetes modelling groups meet to compare simulated outcomes of pre-specified scenarios often based on the results of pivotal clinical trials. Model registration is a potential method for promoting transparency, while also reducing the duplication of effort. An important network initiative is the ongoing construction of a diabetes model registry (https://www.mthooddiabeteschallenge.com). Following the 2012 International Society for Pharmacoeconomics and Outcomes Research and the Society of Medical Decision Making (ISPOR-SMDM) guidelines, we recommend that modelling groups provide technical and non-technical documentation sufficient to enable model reproduction, but not necessarily provide the model code. We also request that modelling groups upload documentation on the methods and outcomes of validation efforts, and run reference case simulations so that model outcomes can be compared. In this paper, we discuss conflicting definitions of transparency in health economic modelling, and describe the ongoing development of a registry of economic models for diabetes through the Mount Hood Diabetes Challenge Network, its objectives and potential further developments, and highlight the challenges in its construction and maintenance. The support of key stakeholders such as decision-making bodies and journals is key to ensuring the success of this and other registries. In the absence of public funding, the development of a network of modellers is of huge value in enhancing transparency, whether through registries or other means

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Supporting physical activity through co-production in people with severe mental ill health (SPACES): protocol for a randomised controlled feasibility trial.

Background Severe mental ill health (SMI) includes schizophrenia, bipolar disorder and schizoaffective disorder and is associated with premature deaths when compared to people without SMI. Over 70% of those deaths are attributed to preventable health conditions, which have the potential to be positively affected by the adoption of healthy behaviours, such as physical activity. People with SMI are generally less active than those without and face unique barriers to being physically active. Physical activity interventions for those with SMI demonstrate promise, however, there are important questions remaining about the potential feasibility and acceptability of a physical activity intervention embedded within existing NHS pathways. Method This is a two-arm multi-site randomised controlled feasibility trial, assessing the feasibility and acceptability of a co-produced physical activity intervention for a full-scale trial across geographically dispersed NHS mental health trusts in England. Participants will be randomly allocated via block, 1:1 randomisation, into either the intervention arm or the usual care arm. The usual care arm will continue to receive usual care throughout the trial, whilst the intervention arm will receive usual care plus the offer of a weekly, 18-week, physical activity intervention comprising walking and indoor activity sessions and community taster sessions. Another main component of the intervention includes one-to-one support. The primary outcome is to investigate the feasibility and acceptability of the intervention and to scale it up to a full-scale trial, using a short proforma provided to all intervention participants at follow-up, qualitative interviews with approximately 15 intervention participants and 5 interventions delivery staff, and data on intervention uptake, attendance, and attrition. Usual care data will also include recruitment and follow-up retention. Secondary outcome measures include physical activity and sedentary behaviours, body mass index, depression, anxiety, health-related quality of life, healthcare resource use, and adverse events. Outcome measures will be taken at baseline, three, and six-months post randomisation. Discussion This study will determine if the physical activity intervention is feasible and acceptable to both participants receiving the intervention and NHS staff who deliver it. Results will inform the design of a larger randomised controlled trial assessing the clinical and cost effectiveness of the intervention. Trial registration ISRCTN: ISRCTN83877229. Registered on 09.09.2022

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Advancing economic evaluation methods for better medical decision making through real-world, longitudinal data

© 2020 Michelle Siew Ping TewHealth economic evaluation is a fundamental component in helping inform health care providers and policy makers in making decisions on priorities in health care. This is particularly relevant in today’s tight budgetary climate and in response to continued calls for sustainable health care systems. Economic evaluation evidence has influenced and contributed to many areas of health policy making, at all levels of the health care system – from shaping guidelines that guide clinical care to informing decision for subsidy of pharmaceuticals and medical services. For these evaluations to be useful to decisions makers, they need to provide useful and reliable information and to achieve this, methodological guidelines should be followed, and robust evidence of effectiveness and cost is paramount. With recent advances in information technology, data and statistical methods and implementation of electronic health records, health decision makers are increasingly seeking real-world, generalisable evidences to complement and support policy and clinical decisions. This thesis aims to demonstrate the usefulness and practicality of applying real-world longitudinal data in health economics research and applications. It features six individual health economics studies which explore longitudinal data and show their value and contribution towards advancing economic evaluation methodologies and better decision making. Each of the studies answer specific research questions and contribute to the research literature through methodological research to improve consistency in extrapolating costs, utility inputs and modelling long-term outcomes, generating robust evidence for resource allocation decisions, promoting a better understanding of real-world heterogeneity and approaches to optimise patient outcomes. Collectively, these studies highlight important variations in the cost and outcomes of health care delivery in real-world settings, provide useful insights into the implications of such variations and demonstration of translating research findings to implementation

An Economic Model for Estimating Trial Costs with an Application to Placebo Surgery Trials

Background and Objective: Waste in clinical trials remains rife. We developed an economic model to predict the cost of trials based on input costs, duration, power, number of sites, recruitment eligibility and consenting rates. Methods: We parameterised the model for three proxy placebo-controlled surgical trials using data from a systematic review, a bespoke cost survey, and from the literature. We used the model to compare target and actual trial performance for (i) a trial that was completed on time but with more sites, (ii) a trial that completed after a time extension, and (iii) an incomplete trial. Results: Successful trials more accurately anticipated the true recruitment rate that they achieved and those that overestimated this were most likely to fail. The costs of overestimating recruitment rates were dramatic: all proxy trials had significantly higher costs than planned, with additional funding of at least AUD$600,000 (50$2 million (260% above budget) for incomplete trials. Conclusions: This model shows the trade-offs between time and cost, or both, when recruitment is lower than anticipated. Greater consideration is needed to improve trial planning, reviewing, and funding of these trials to avoid costly overruns and incomplete trials