Explaining how medical doctors learn about and understand the approach to the end-of-life in the workplace

Background For patients approaching the end-of-life, treatments with life-prolonging intent can be futile, wasteful, and harmful. Equally, harm may be caused by prematurely treating patients as if they are dying. In order to provide a high standard of care, and align with clinical guidance, doctors must appropriately discern when a patient is approaching the end-of-life. This thesis takes the necessary and novel step of developing an explanation for how medical doctors learn about and understand the approach to the end-of-life in the workplace. Research aims 1. To examine how the approach to the end-of-life is conceptualised by medical doctors; 2. To explore experiences and understandings of doctors learning to care for patients at the approach to the end-of-life, including factors which provide barriers to learning; 3. To develop a theoretical explanation of the learning of doctors about the approach to the end-of-life. Methodology and methods Taking a critical realist ontological position, this thesis considers what causal mechanisms influence doctors learning about and understanding the approach to the end-of-life. Data were generated through complementary methods: • Scoping study and qualitative content analysis (QCA) of medical literature (2006- 2016) to examine established conceptions about the approach to the end-of-life among UK medical doctors; • Thematic analysis (TA) of data from semi-structured interviews with newly graduated (foundation) doctors to explore development of understandings of the approach to the end-of-life, and influences on this development and learning; • Examination of the findings through the lens of a socio-material epistemological framework – Cultural Historical Activity Theory (CHAT) – to theorise how interacting factors influence the learner/practitioner in a complex environment. Results QCA of two hundred and sixty-nine included documents identified that there is no single shared understanding of the approach to the end-of-life among doctors. TA of data from fifteen interviews with foundation doctors indicates that care of the patient approaching the end-of-life is a central aspect of their role and is learned about after leaving medical school, beginning practice, becoming integrated into the workplace. Both the literature and interview data indicate the approach to the end-of-life is not understood as a discrete entity but is constructed dynamically in relation to the patient, their disease, potential treatments and implications of these treatments, from the perspective of the practicing doctor. CHAT allowed for consideration of this practice-based learning as systems of activity, and identification of where contradictions within and between each activity system act as barriers to learning and practice. Discussion and conclusions The results have significant implications for educators and policy makers: understandings of the approach to the end-of-life are not gained in advance of practice (i.e. in medical schools). Instead, understandings are dynamically constructed by doctors in their practice. Improving the doctor’s workplace by overcoming tensions and challenges identified in this thesis should be focuses for intervention to improve learning and care for these patients in the future

Online forums support palliative and bereavement care: machine learning and natural language processing analysis of qualitative data from the internet

Palliative public health policy emphasises the value of sustainable community-led palliative care and psychosocial support. However, there are significant challenges to adequate palliative and bereavement care provision including precarious funding, inconsistent availability, and recent challenges presented by the COVID-19 pandemic. Minority groups and those at the greatest socioeconomic disadvantage are among those least likely to receive the care they need. Digital services may circumvent these challenges, allowing people to self-manage their needs. This research aimed to investigate how community-led online forums are used to support people facing life-limiting illness, their caregivers, and bereaved peopl

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

Harnessing citizen science through mobile phone technology to screen for immunohistochemical biomarkers in bladder cancer

Background: Immunohistochemistry (IHC) is often used in personalisation of cancer treatments. Analysis of large data sets to uncover predictive biomarkers by specialists can be enormously time-consuming. Here we investigated crowdsourcing as a means of reliably analysing immunostained cancer samples to discover biomarkers predictive of cancer survival. Methods: We crowdsourced the analysis of bladder cancer TMA core samples through the smartphone app ‘Reverse the Odds’. Scores from members of the public were pooled and compared to a gold standard set scored by appropriate specialists. We also used crowdsourced scores to assess associations with disease-specific survival. Results: Data were collected over 721 days, with 4,744,339 classifications performed. The average time per classification was approximately 15 s, with approximately 20,000 h total non-gaming time contributed. The correlation between crowdsourced and expert H-scores (staining intensity × proportion) varied from 0.65 to 0.92 across the markers tested, with six of 10 correlation coefficients at least 0.80. At least two markers (MRE11 and CK20) were significantly associated with survival in patients with bladder cancer, and a further three markers showed results warranting expert follow-up. Conclusions: Crowdsourcing through a smartphone app has the potential to accurately screen IHC data and greatly increase the speed of biomarker discovery

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

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

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Resisting the (re-)medicalisation of dying and grief in the post-digital age : Natural language processing and qualitative analysis of data from internet support forums

In the mid-twentieth century, the social movement of death revivalism sought to resist the medicalisation of dying and grief through promotion of the dying person retaining autonomy, and societal openness toward death and bereavement. Despite this advocacy, present-day dying in high income countries is largely institutionalised, with value placed on control over the body and emotions. These phenomena are at odds with the ambitions of death revivalism, and demonstrate the re-medicalisation of dying and grief. Furthermore, contemporary society is continually advancing into the post-digital age, reflected in digital technologies being a tacit part of human existence. Within this framework, this study aims to investigate how people living with life-limiting illness and their loved ones experience, negotiate, and resist medicalisation of dying and grief through online internet forums. We collected posts through web-scraping and utilised Natural Language Processing techniques to select 7048 forum posts from 2003 to 2020, and initially categorise data, before utilising Inductive Thematic Analysis, which generated two major themes. The theme of ‘Comfort’ describes online forums facilitating psychosocial support which was often used to compensate for systemic deficiencies, especially during the Covid-19 pandemic. Common sources of comfort included animal companions and spirituality, in stark contrast with the medicalised model. The theme of ‘Capability’ describes online forums acting as solutions for people facing disempowering care systems, including providing information on legal rights and benefits which may not be otherwise easily available, and facilitating collective advocacy. Our findings indicate that community-led online forums can play an effective and sustainable role in democratising care and retaining agency when facing life-limiting illness and grief. Future palliative and bereavement care research must focus on how online forums can be integrated into existing systems, made transparent and accessible, be adequately funded and structured, and be optimised, including compensating for service disruption encountered during future pandemics

Resisting the (re-)medicalisation of dying and grief in the post-digital age: natural language processing and qualitative analysis of data from internet support forums

Abstract In the mid-twentieth century, the social movement of death revivalism sought to resist the medicalisation of dying and grief through promotion of the dying person retaining autonomy, and societal openness toward death and bereavement. Despite this advocacy, present-day dying in high income countries is largely institutionalised, with value placed on control over the body and emotions. These phenomena are at odds with the ambitions of death revivalism, and demonstrate the re-medicalisation of dying and grief. Furthermore, contemporary society is continually advancing into the post-digital age, reflected in digital technologies being a tacit part of human existence. Within this framework, this study aims to investigate how people living with life-limiting illness and their loved ones experience, negotiate, and resist medicalisation of dying and grief through online internet forums. We collected posts through web-scraping and utilised Natural Language Processing techniques to select 7048 forum posts from 2003-2020, and initially categorise data, before utilising Inductive Thematic Analysis, which generated two major themes. The theme of ‘Comfort’ describes online forums facilitating psychosocial support which was often used to compensate for systemic deficiencies, especially during the Covid-19 pandemic. Common sources of comfort included animal companions and spirituality, in stark contrast with the medicalised model. The theme of ‘Capability’ describes online forums acting as solutions for people facing disempowering care systems, including providing information on legal rights and benefits which may not be otherwise easily available, and facilitating collective advocacy. Our findings indicate that community-led online forums can play an effective and sustainable role in democratising care and retaining agency when facing life-limiting illness and grief. Future palliative and bereavement care research must focus on how online forums can be integrated into existing systems, made transparent and accessible, be adequately funded and structured, and be optimised, including compensating for service disruption encountered during future pandemics