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When Korf (2014) recently invited (critical) geographers to come to terms with the problematic heritage of our discipline, especially with respect to spatial political thought, he first of all drew our attention to the intellectual contributions of Martin Heidegger and Carl Schmitt. While he urges us to rethink our ongoing references to these key thinkers, especially in light of the rather strict avoidance of politically problematic figures within our own discipline, such as Haushofer and Ratzel, this article now wishes to address geography's (dis)engagement with its politically problematic heritage from the opposite angle: focusing on Friedrich Ratzel, it asks if we might have been too radical in condemning his work as only poison? What if the neglect of Ratzel has actually led to a moment where his ideas feature prominently in current geographical debates without us even noticing it? By drawing on his contributions to cultural geography and, in particular, the establishment of the cultural historical method and German diffusionism, this article takes up on this question and reflects on the (imagined/actual) role of Ratzel's scholarship in contemporary geography. By pointing out striking similarities to more recent discussions about mobility, materiality and relational space, it illustrates the contemporary, though widely unnoticed, (re)appearance of Ratzel's ideas, and uses this example to emphasize the need for more critical reflection concerning the history of our discipline as well as the complex ways in which political ideologies and intellectual reasoning relate to each other.

This editorial provides the intellectual background for a themed issue that argues for a (re)consideration of human geography as a "Geisteswissenschaft". Engaging with the question of how a geography anchored in the arts and humantities might look like today, it tries to unsettle the kind of "theory-driven", post-structuralist research that has come to dominate human geography following the "cultural turn". In proposing a more thorough engagement with the potential of intrepretative, hermeneutic and phenomenological approaches, we conceptualise a "geisteswissenschaftliche" human geography as a much-needed irritation of the social scientific mainstream.

The aim of this article is to show the difference between an interpretative-hermeneutic ethnographic approach deeply embedded in the history of anthropology and ethnographic methods introduced as part of a social science repertoire. Taking the classical "network" as an example, it contrasts the way this concept is generally used in studies on translocal mobility with interpretations of ethnographic research. This not only opens up critical reflections on the role of "networks" when it comes to understanding translocality as a lived experience, but also illustrates what it actually means to follow an interpretative-hermeneutic approach in which ethnographic material is seen to serve as a way to ground, question and refine abstract concepts. The article thus argues that it is through ethnographies and their inherent openness towards the field that a more enriching and creative engagement with theories and methodologies can be achieved than qualitative social science approaches usually allow for.

For their glucose supply, ruminants are highly dependent on the endogenous synthesis in the liver, but despite the numerous studies that evaluated hepatic glucose production, very few simultaneously measured hepatic glucose production and uptake of all precursors. As a result, the variability of precursor conversion into glucose in the liver is not known. The present study aimed at investigating by meta-analysis the relationships between hepatic glucose net release and uptake of precursors. We used the FLuxes of nutrients across Organs and tissues in Ruminant Animals database, which gathers international results on net nutrient fluxes at splanchnic level measured in catheterized animals. Response equations were developed for intakes up to 41 g DM intake/kg BW per day of diets varying from 0 to 100 g of concentrate/100 g DM in the absence of additives. The net hepatic uptake of propionate, α-amino-N and l-lactate was linearly and better related to their net portal appearance (NPA) than to their afferent hepatic flux. Blood flow data were corrected for lack of deacetylation of the para-aminohippuric acid, and this correction was shown to impact the response equations. To develop response equations between the availability of precursors (portal appearance and hepatic uptake) and net glucose hepatic release, missing data on precursor fluxes were predicted from dietary characteristics using previously developed response equations. Net hepatic release of glucose was curvilinearly related to hepatic supply and uptake of the sum of precursors, suggesting a lower conversion rate of precursors at high precursor supply. Factors of variation were explored for the linear portion of this relationship, which applied to NPA of precursors ranging from 0.99 to 9.60 mmol C/kg BW per h. Hepatic release of glucose was shown to be reduced by the portal absorption of glucose from diets containing bypass starch and to be increased by an increased uptake of β-hydroxybutyrate indicative of higher body tissue mobilization. These relationships were affected by the physiological status of the animals. In conclusion, we established equations that quantify the net release of glucose by the liver from the net availability of precursors. They provide a quantitative overview of factors regulating hepatic glucose synthesis in ruminants. These equations can be linked with the predictions of portal absorption of nutrients from intake and dietary characteristics, and provide indications of glucose synthesis from dietary characteristics.

For energy feeding systems for ruminants to evolve towards a nutrient-based system, dietary energy supply has to be determined in terms of amount and nature of nutrients. The objective of this study was to establish response equations of the net hepatic flux and net splanchnic release of acetate, butyrate and β-hydroxybutyrate to changes in diet and animal profiles. A meta-analysis was applied on published data compiled from the FLuxes of nutrients across Organs and tissues in Ruminant Animals database, which pools the results from international publications on net splanchnic nutrient fluxes measured in multi-catheterized ruminants. Prediction variables were identified from current knowledge on digestion, hepatic and other tissue metabolism. Subsequently, physiological and other, more integrative, predictors were obtained. Models were established for intakes up to 41 g dry matter per kg BW per day and diets containing up to 70 g concentrate per 100 g dry matter. Models predicted the net hepatic fluxes or net splanchnic release of each nutrient from its net portal appearance and the animal profile. Corrections were applied to account for incomplete hepatic recovery of the blood flow marker, para-aminohippuric acid. Changes in net splanchnic release (mmol/kg BW per hour) could then be predicted by combining the previously published net portal appearance models and the present net hepatic fluxes models. The net splanchnic release of acetate and butyrate were thus predicted from the intake of ruminally fermented organic matter (RfOM) and the nature of RfOM (acetate: residual mean square error (RMSE)=0.18; butyrate: RMSE=0.01). The net splanchnic release of β-hydroxybutyrate was predicted from RfOM intake and the energy balance of the animals (RMSE=0.035), or from the net portal appearance of butyrate and the energy balance of the animals (RMSE=0.050). Models obtained were independent of ruminant species, and presented low interfering factors on the residuals, least square means or individual slopes. The model equations highlighted the importance of considering the physiological state of animals when predicting splanchnic metabolism. This work showed that it is possible to use simple predictors to accurately predict the amount and nature of ketogenic nutrients released towards peripheral tissues in both sheep and cattle at different physiological status. These results provide deeper insight into biological processes and will contribute to the development of improved tools for dietary formulation.

This work set out to establish the response equations for hepatic blood flows in sheep and the contribution of hepatic arterial flow to hepatic venous blood flow due to changes in intake levels at constant diet composition. The FLORA (FLuxes across Organs and tissues in Ruminant Animals) database was used, and meta-analysis performed. The meta-analysis involved selection of published papers, identification of studies, description and coding of the selected dataset and statistical analysis using a covariance model. Meta-analyses were carried out using a within-study approach. To ensure absence of bias, the analysis incorporated interfering variables and factors studied in between-study comparisons. Variables concerned diet composition; qualitative factors concerned the physiological state of the animals and the methods used to measure blood flow. The results obtained showed that hepatic blood flows were positively related to intake in sheep. The magnitude of the response (as indicated by the slope) varied with the level of intake and the blood vessel (portal, hepatic venous or arterial). Nine linear relationships were established for the portal, hepatic venous and arterial blood flows as a function of dry matter intake (DMI) with below- and above-maintenance levels considered separately. Data obtained at below- and above-maintenance levels were considered together and four quadratic relationships were established for hepatic blood flows as a function of DMI. These relationships expressed a strong effect of intake on hepatic blood flows. The contribution of hepatic arterial to hepatic venous blood flow averaged 18.2%, with a wide variability. It did not vary significantly with level of intake. Although in between-study comparisons the arterial/venous blood flow was positively influenced by the organic matter digestibility of the diet, the relationships we obtained were robust. They can be used in models of net hepatic nutrient fluxes to predict variations and absolute values of hepatic blood flows from variations and absolute values of DMI.

Algunas reflexiones sobre el uso islámico del chador, comparándolo con el uso cristiano del velo: en la práctica actual no parece preceptivo sino voluntario.

Background: Advance care planning has been advocated as a way for people to have their wishes recorded and respected in relation to types of treatment and place of care. However, uptake in England remains low., Aims: To examine the views of older, well, adults towards Advance Care Plans (ACPs) and planning for end-of-life care, in order to inform national policy decisions., Methods: A mixed methods approach was adopted, involving individual and mini-group qualitative interviews (n = 76, ages 45-85), followed by a quantitative survey (n = 2294, age 55+). The quantitative sample was based on quotas in age, gender, region, socio-economic grade, and ethnicity, combined with light weighting to ensure the findings were representative of England., Results: Knowledge and understanding of advance care planning was low, with only 1% of survey respondents reporting they had completed an ACP for themselves. Common reasons for not putting wishes into writing were not wanting/needing to think about it now, the unpredictability of the future, trusting family/friends to make decisions, and financial resources limiting real choice., Conclusion: Whilst advance care planning is seen as a good idea in theory by older, well, adults living in the community, there is considerable reticence in practice. This raises questions over the current, national policy position in England, on the importance of written ACPs. We propose that policy should instead focus on encouraging ongoing conversations between individuals and all those (potentially) involved in their care, about what is important to them, and on ensuring there are adequate resources in community networks and health and social care systems, to be responsive to changing needs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Spear et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Globally, the COVID-19 pandemic has caused unprecedented strain in healthcare systems, but little is known about how it affected patients requiring palliative and end-of-life care from GPs., Aim: To evaluate the impact of the pandemic on primary care service use in the last 3 months of life, including consultations and prescribing, and to identify associated factors., Design and Setting: A retrospective cohort study in UK, using data from the Clinical Practice Research Datalink., Method: The study cohort included those who died between 2019 and 2020. Poisson regression models using generalised estimation equations were used to examine the association between primary care use and patient characteristics. Adjusted rate ratios (aRRs) and 95% confidence intervals (95% CIs) were estimated., Results: A total of 44 534 patients died during the study period. The pandemic period was associated with an 8.9% increase in the rate of consultations from 966.4 to 1052.9 per 1000 person-months, and 14.3% longer telephone consultation duration (from 10.1 to 11.5 minutes), with a switch from face-to-face to telephone or video consultations. The prescription of end-of-life care medications increased by 6.3%, from 1313.7 to 1396.3 per 1000 person-months. The adjusted rate ratios for consultations (aRR = 1.08, 95% CI = 1.06 to 1.10, P <0.001) and prescriptions (aRR 1.05: 95% CI = 1.03 to 1.07, P <0.001) also increased during the pandemic., Conclusion: The pandemic had a major impact on GP service use, leading to longer consultations, shifts from face-to-face to telephone or video consultations, and increased prescriptions. GP workload-related issues must be addressed urgently to ease the pressure on GPs., (Copyright © 2024, The Authors.)

Background: Good end-of-life care is essential to ensure dignity and comfort in death. To our knowledge, there has not been a national population-based study in England of community prescribing of all drugs used in end-of-life care for patients with cancer., Methods: 57 632 people who died from malignant cancer in their own home or in a care home in 2017 in England were included in this study. National routinely collected data were used to examine community prescriptions dispensed for drugs for symptom control and anticipatory prescribing by key sociodemographic factors in the last 4 months of life., Results: 94% of people who died received drugs to control their symptoms and 65% received anticipatory prescribing. Prescribing increased for the symptom control drug group (53% to 75%) and the anticipatory prescribing group (4% to 52%) over the 4-month period to death., Conclusions: Most individuals who died of cancer in their own home or a care home were dispensed drugs commonly used to control symptoms at the end of life, as recommended by best-practice guidance. Lower prescribing activity was found for those who died in a care home, highlighting a potential need for improved end-of-life service planning., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: The World Health Assembly recommends integration of palliative care into treatment of patients with any life-limiting condition, yet patients with non-malignant disease are less likely to receive specialist palliative care (SPC). This study compares SPC offered to patients with hepatocellular carcinoma (HCC) versus patients with chronic liver disease without HCC (CLD without HCC)., Methods: Patients who died from CLD or HCC over 5 years (2013-2017) in England were identified using a dataset linking national data on all hospital admissions (Hospital Episode Statistics - HES) with national mortality data from the Office for National Statistics (HES - ONS). The primary outcome was the proportion of patients who received inpatient SPC in their last year of life (LYOL). Secondary outcomes were (1) early inpatient SPC input and (2) the proportion dying in a hospice. The outcomes were compared between patients with HCC and CLD without HCC., Results: 29 669 patients were identified, 8143 of whom had HCC. Patients with HCC were significantly more likely to receive inpatient SPC input-adjusted OR 3.74 (95% CI 3.52-3.97) and early inpatient SPC input-adjusted OR 7.26 (95% CI 6.38-8.25) and die in a hospice OR 8.23 (95% CI 7.33-9.24) than patients with CLD without HCC., Conclusions: These data highlight the stark inequity in access to SPC services between patients with HCC and patients with CLD without HCC in England. Addressing these inequities will improve end-of-life care for patients with CLD., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Introduction: Liver disease deaths are rising, but specialist palliative care services for hepatology are limited. Expansion across the NHS is required., Methods: We surveyed clinicians, patients and carers to design an 'ideal' service. Using standard NHS tariffs, we calculated the cost of this service. In hospitals where specialist palliative care was available for liver disease, patient-level costs and bed utilisation in last year of life (LYOL) were compared between those seen by specialist palliative care before death and those not., Results: The 'ideal' service was described. Costs were calculated as whole time equivalent for a minimal service, which could be scaled up. From a hospital with an existing service, patients seen by specialist palliative care had associated costs of £14 728 in LYOL, compared with £18 558 for those dying without. Savings more than balanced the costs of introducing the service. Average bed days per patient in LYOL were reduced (19.4 vs 25.7) also intensive care unit bed days (1.1 vs 1.8). Despite this, time from first admission in LYOL to death was similar in both groups (6 months for the specialist palliative care group vs 5 for those not referred)., Conclusions: We have produced a template business case for an 'ideal' advanced liver disease support service, which self-funds and saves many bed days. The model can be easily adapted for local use in other trusts. We describe the methodology for calculating patient-level costs and the required service size. We present a financially compelling argument to expand a service to meet a growing need., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: People with severe mental illness (SMI) are 2.5 times more likely to die prematurely from cancer in England. Lower participation in screening may be a contributing factor., Methods: Clinical Practice Research Datalink data for 1.71 million, 1.34 million and 2.50 million adults were assessed (using multivariate logistic regression) for possible associations between SMI and participation in bowel, breast and cervical screening, respectively., Results: Screening participation was lower among adults with SMI, than without, for bowel (42.11% vs. 58.89%), breast (48.33% vs. 60.44%) and cervical screening (64.15% vs. 69.72%; all p < 0.001). Participation was lowest in those with schizophrenia (bowel, breast, cervical: 33.50%, 42.02%, 54.88%), then other psychoses (41.97%, 45.57%, 61.98%), then bipolar disorder (49.94%, 54.35%, 69.69%; all p-values < 0.001, except cervical screening in bipolar disorder; p-value > 0.05). Participation was lowest among people with SMI who live in the most deprived quintile of areas (bowel, breast, cervical: 36.17%, 40.23%, 61.47%), or are of a Black ethnicity (34.68%, 38.68%, 64.80%). Higher levels of deprivation and diversity, associated with SMI, did not explain the lower participation in screening., Conclusions: In England, participation in cancer screening is low among people with SMI. Support should be targeted to ethnically diverse and socioeconomically deprived areas, where SMI prevalence is greatest., (© 2023. The Author(s).)

Background: The number and proportion of home deaths in the UK increased during the Covid-19 pandemic. It is not known whether these changes were experienced disproportionately by people from different socioeconomic groups., Aim: To examine the association between home death and socioeconomic position during the Covid-19 pandemic, and how this changed between 2019 and 2020., Design: Retrospective cohort study using population-based individual-level mortality data., Setting/participants: All registered deaths in England, Wales, Scotland and Northern Ireland. The proportion of home deaths between 28th March and 31st December 2020 was compared with the same period in 2019. We used Poisson regression models to evaluate the association between decedent's area-based level of deprivation and risk of home death, as well as the interaction between deprivation and year of death, for each nation separately., Results: Between the 28th March and 31st December 2020, 409,718 deaths were recorded in England, 46,372 in Scotland, 26,410 in Wales and 13,404 in Northern Ireland. All four nations showed an increase in the adjusted proportion of home deaths between 2019 and 2020, ranging from 21 to 28%. This increase was lowest for people living in the most deprived areas in all nations, with evidence of a deprivation gradient in England., Conclusions: The Covid-19 pandemic exacerbated a previously described socioeconomic inequality in place of death in the UK. Further research to understand the reasons for this change and if this inequality has been sustained is needed.

Competing Interests: Rocket Medical are supplying the long-term drains for the REDUCe 2 study, for which SV is chief investigator. SV reports research grants and consultancy fees from Gilead Sciences; and speaker fees from Gilead Sciences, Dr Falk, and AbbVie. All other authors declare no competing interests.

The COVID-19 pandemic has had high mortality rates in the elderly and frail worldwide, particularly in care homes. This is driven by the difficulty of isolating care homes from the wider community, the large population sizes within care facilities (relative to typical households), and the age/frailty of the residents. To quantify the mortality risk posed by disease, the case fatality risk (CFR) is an important tool. This quantifies the proportion of cases that result in death. Throughout the pandemic, CFR amongst care home residents in England has been monitored closely. To estimate CFR, we apply both novel and existing methods to data on deaths in care homes, collected by Public Health England and the Care Quality Commission. We compare these different methods, evaluating their relative strengths and weaknesses. Using these methods, we estimate temporal trends in the instantaneous CFR (at both daily and weekly resolutions) and the overall CFR across the whole of England, and dis-aggregated at regional level. We also investigate how the CFR varies based on age and on the type of care required, dis-aggregating by whether care homes include nursing staff and by age of residents. This work has contributed to the summary of measures used for monitoring the UK epidemic., Competing Interests: The authors have declared that no competing interests exist.

This Review, in addressing the unacceptably high mortality of patients with liver disease admitted to acute hospitals, reinforces the need for integrated clinical services. The masterplan described is based on regional, geographically sited liver centres, each linked to four to six surrounding district general hospitals-a pattern of care similar to that successfully introduced for stroke services. The plan includes the establishment of a lead and deputy lead clinician in each acute hospital, preferably a hepatologist or gastroenterologist with a special interest in liver disease, who will have prime responsibility for organising the care of admitted patients with liver disease on a 24/7 basis. Essential for the plan is greater access to intensive care units and high-dependency units, in line with the reconfiguration of emergency care due to the COVID-19 pandemic. This Review strongly recommends full implementation of alcohol care teams in hospitals and improved working links with acute medical services. We also endorse recommendations from paediatric liver services to improve overall survival figures by diagnosing biliary atresia earlier based on stool colour charts and better caring for patients with impaired cognitive ability and developmental mental health problems. Pilot studies of earlier diagnosis have shown encouraging progress, with 5-6% of previously undiagnosed cases of severe fibrosis or cirrhosis identified through use of a portable FibroScan in primary care. Similar approaches to the detection of early asymptomatic disease are described in accounts from the devolved nations, and the potential of digital technology in improving the value of clinical consultation and screening programmes in primary care is highlighted. The striking contribution of comorbidities, particularly obesity and diabetes (with excess alcohol consumption known to be a major factor in obesity), to mortality in COVID-19 reinforces the need for fiscal and other long delayed regulatory measures to reduce the prevalence of obesity. These measures include the food sugar levy and the introduction of the minimum unit price policy to reduce alcohol consumption. Improving public health, this Review emphasises, will not only mitigate the severity of further waves of COVID-19, but is crucial to reducing the unacceptable burden from liver disease in the UK., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Adults increasingly live and die with chronic progressive conditions into advanced age. Many live with multimorbidity and an uncertain illness trajectory with points of marked decline, loss of function and increased risk of end of life. Intermediate care units support mainly older adults in transition between hospital and home to regain function and anticipate and plan for end of life. This study examined the patient characteristics and the factors associated with mortality over 1 year post-admission to an intermediate care unit to inform priorities for care., Methods: A national cohort study of adults admitted to intermediate care units in England using linked individual-level Hospital Episode Statistics and death registration data. The main outcome was mortality within 1 year from admission. The cohort was examined as two groups with significant differences in mortality between main diagnosis of a non-cancer condition and cancer. Data analysis used Kaplan-Meier curves to explore mortality differences between the groups and a time-dependant Cox proportional hazards model to determine mortality risk factors., Results: The cohort comprised 76,704 adults with median age 81 years (IQR 70-88) admitted to 220 intermediate care units over 1 year in 2016. Overall, 28.0% died within 1 year post-admission. Mortality varied by the main diagnosis of cancer (total n = 3680, 70.8% died) and non-cancer condition (total n = 73,024, 25.8% died). Illness-related factors had the highest adjusted hazard ratios [aHRs]. At 0-28 days post-admission, risks were highest for non-cancer respiratory conditions (pneumonia (aHR 6.17 [95%CI 4.90-7.76]), chronic obstructive pulmonary disease (aHR 5.01 [95% CI 3.78-6.62]), dementia (aHR 5.07 [95% CI 3.80-6.77]) and liver disease (aHR 9.75 [95% CI 6.50-14.6]) compared with musculoskeletal disorders. In cancer, lung cancer showed largest risk (aHR 1.20 [95%CI 1.04-1.39]) compared with cancer 'other'. Risks increased with high multimorbidity for non-cancer (aHR 2.57 [95% CI 2.36-2.79]) and cancer (aHR 2.59 [95% CI 2.13-3.15]) (reference: lowest)., Conclusions: One in four patients died within 1 year. Indicators for palliative care assessment are respiratory conditions, dementia, liver disease, cancer and rising multimorbidity. The traditional emphasis on rehabilitation and recovery in intermediate care units has changed with an ageing population and the need for greater integration of palliative care.

Background: There is much variation in hospice use with respect to geographic factors such as area-based deprivation, location of patient's residence and proximity to services location. However, little is known about how the association between geographic access to inpatient hospice and hospice deaths varies by patients' region of settlement., Study Aim: To examine regional differences in the association between geographic access to inpatient hospice and hospice deaths., Methods: A regional population-based observational study in England, UK. Records of patients aged ≥ 25 years (n = 123088) who died from non-accidental causes in 2014, were extracted from the Office for National Statistics (ONS) death registry. Our cohort comprised of patients who died at home and in inpatient hospice. Decedents were allocated to each of the nine government office regions of England (London, East Midlands, West Midlands, East, Yorkshire and The Humber, South West, South East, North West and North East) through record linkage with their postcode of usual residence. We defined geographic access as a measure of drive times from patients' residential location to the nearest inpatient hospice. A modified Poisson regression estimated the association between geographic access to hospice, comparing hospice deaths (1) versus home deaths (0). We developed nine regional specific models and adjusted for regional differences in patient's clinical & socio-demographic characteristics. The strength of the association was estimated with adjusted Proportional Ratios (aPRs)., Findings: The percentage of deaths varied across regions (home: 86.7% in the North East to 73.0% in the South East; hospice: 13.3% in the North East to 27.0% in the South East). We found wide differences in geographic access to inpatient hospices across regions. Median drive times to hospice varied from 4.6 minutes in London to 25.9 minutes in the North East. We found a dose-response association in the East: (aPRs: 0.22-0.78); East Midlands: (aPRs: 0.33-0.63); North East (aPRs: 0.19-0.87); North West (aPRs: 0.69-0.88); South West (aPRs: 0.56-0.89) and West Midlands (aPRs: 0.28-0.92) indicating that decedents who lived further away from hospices locations (≥ 10 minutes) were less likely to die in a hospice., Conclusion: The clear dose-response associations in six regions underscore the importance of regional specific initiatives to improve and optimise access to hospices. Commissioners and policymakers need to do more to ensure that home death is not due to limited geographic access to inpatient hospice care., Competing Interests: The authors have declared that no competing interests exist.

This final report of the Lancet Commission into liver disease in the UK stresses the continuing increase in burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions which are worsening in deprived areas. Only with comprehensive food and alcohol strategies based on fiscal and regulatory measures (including a minimum unit price for alcohol, the alcohol duty escalator, and an extension of the sugar levy on food content) can the disease burden be curtailed. Following introduction of minimum unit pricing in Scotland, alcohol sales fell by 3%, with the greatest effect on heavy drinkers of low-cost alcohol products. We also discuss the major contribution of obesity and alcohol to the ten most common cancers as well as measures outlined by the departing Chief Medical Officer to combat rising levels of obesity-the highest of any country in the west. Mortality of severely ill patients with liver disease in district general hospitals is unacceptably high, indicating the need to develop a masterplan for improving hospital care. We propose a plan based around specialist hospital centres that are linked to district general hospitals by operational delivery networks. This plan has received strong backing from the British Association for Study of the Liver and British Society of Gastroenterology, but is held up at NHS England. The value of so-called day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and, in particular, schemes to allow general practitioners to refer patients directly for elastography assessment. New funding arrangements for general practitioners will be required if these proposals are to be taken up more widely around the country. Understanding of the harm to health from lifestyle causes among the general population is low, with a poor knowledge of alcohol consumption and dietary guidelines. The Lancet Commission has serious doubts about whether the initiatives described in the Prevention Green Paper, with the onus placed on the individual based on the use of information technology and the latest in behavioural science, will be effective. We call for greater coordination between official and non-official bodies that have highlighted the unacceptable disease burden from liver disease in England in order to present a single, strong voice to the higher echelons of government., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Funding shortages and an ageing population have increased pressures on state or insurance funded end of life care for older people. Across the world, policy debate has arisen about the potential role volunteers can play, working alongside health and social care professionals in the community to support and care for the ageing and dying., Aims: The authors examined self-reported levels of care for the elderly by the public in England, and public opinions of community volunteering concepts to care for the elderly at the end of life. In particular, claimed willingness to help and to be helped by local people was surveyed., Methods: A sample of 3,590 adults in England aged 45 or more from an online access panel responded to a questionnaire in late 2017. The survey data was weighted to be representative of the population within this age band. Key literature and formative qualitative research informed the design of the survey questionnaire, which was further refined after piloting., Results: Preferences for different models of community volunteering were elicited. There was a preference for 'formal' models with increased wariness of 'informal' features. Whilst 32% of adults said they 'might join' depending on whom the group helped, unsurprisingly more personal and demanding types of help significantly reduced the claimed willingness to help. Finally, willingness to help (or be helped) by local community carers or volunteers was regarded as less attractive than care being provided by personal family, close friends or indeed health and care professionals., Conclusion: Findings suggest that if community volunteering to care for elderly people at the end of life in England is to expand it may require considerable attention to the model including training for volunteers and protections for patients and volunteers as well as public education and promotion. Currently, in England, there is a clear preference for non-medical care to be delivered by close family or social care professionals, with volunteer community care regarded only as a back-up option., Competing Interests: The authors have declared that no competing interests exist.

Background: Little is known about the role of geographic access to inpatient palliative and end of life care (PEoLC) facilities in place of death and how geographic access varies by settlement (urban and rural). This study aims to fill this evidence gap., Methods: Individual-level death data in 2014 (N = 430,467, aged 25 +) were extracted from the Office for National Statistics (ONS) death registry and linked to the ONS postcode directory file to derive settlement of the deceased. Drive times from patients' place of residence to nearest inpatient PEoLC facilities were used as a proxy estimate of geographic access. A modified Poisson regression was used to examine the association between geographic access to PEoLC facilities and place of death, adjusting for patients' socio-demographic and clinical characteristics. Two models were developed to evaluate the association between geographic access to inpatient PEoLC facilities and place of death. Model 1 compared access to hospice, for hospice deaths versus home deaths, and Model 2 compared access to hospitals, for hospital deaths versus home deaths. The magnitude of association was measured using adjusted prevalence ratios (APRs)., Results: We found an inverse association between drive time to hospice and hospice deaths (Model 1), with a dose-response relationship. Patients who lived more than 10 min away from inpatient PEoLC facilities in rural areas (Model 1: APR range 0.49-0.80; Model 2: APR range 0.79-0.98) and urban areas (Model 1: APR range 0.50-0.83; Model 2: APR range 0.98-0.99) were less likely to die there, compared to those who lived closer (i.e. ≤ 10 min drive time). The effects were larger in rural areas compared to urban areas., Conclusion: Geographic access to inpatient PEoLC facilities is associated with where people die, with a stronger association seen for patients who lived in rural areas. The findings highlight the need for the formulation of end of life care policies/strategies that consider differences in settlements types. Findings should feed into local end of life policies and strategies of both developed and developing countries to improve equity in health care delivery for those approaching the end of life.

Background: Low socioeconomic position (SEP) is recognized as a risk factor for worse health outcomes. How socioeconomic factors influence end-of-life care, and the magnitude of their effect, is not understood. This review aimed to synthesise and quantify the associations between measures of SEP and use of healthcare in the last year of life., Methods and Findings: MEDLINE, EMBASE, PsycINFO, CINAHL, and ASSIA databases were searched without language restrictions from inception to 1 February 2019. We included empirical observational studies from high-income countries reporting an association between SEP (e.g., income, education, occupation, private medical insurance status, housing tenure, housing quality, or area-based deprivation) and place of death, plus use of acute care, specialist and nonspecialist end-of-life care, advance care planning, and quality of care in the last year of life. Methodological quality was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). The overall strength and direction of associations was summarised, and where sufficient comparable data were available, adjusted odds ratios (ORs) were pooled and dose-response meta-regression performed. A total of 209 studies were included (mean NOS quality score of 4.8); 112 high- to medium-quality observational studies were used in the meta-synthesis and meta-analysis (53.5% from North America, 31.0% from Europe, 8.5% from Australia, and 7.0% from Asia). Compared to people living in the least deprived neighbourhoods, people living in the most deprived neighbourhoods were more likely to die in hospital versus home (OR 1.30, 95% CI 1.23-1.38, p < 0.001), to receive acute hospital-based care in the last 3 months of life (OR 1.16, 95% CI 1.08-1.25, p < 0.001), and to not receive specialist palliative care (OR 1.13, 95% CI 1.07-1.19, p < 0.001). For every quintile increase in area deprivation, hospital versus home death was more likely (OR 1.07, 95% CI 1.05-1.08, p < 0.001), and not receiving specialist palliative care was more likely (OR 1.03, 95% CI 1.02-1.05, p < 0.001). Compared to the most educated (qualifications or years of education completed), the least educated people were more likely to not receive specialist palliative care (OR 1.26, 95% CI 1.07-1.49, p = 0.005). The observational nature of the studies included and the focus on high-income countries limit the conclusions of this review., Conclusions: In high-income countries, low SEP is a risk factor for hospital death as well as other indicators of potentially poor-quality end-of-life care, with evidence of a dose response indicating that inequality persists across the social stratum. These findings should stimulate widespread efforts to reduce socioeconomic inequality towards the end of life., Competing Interests: The authors have declared that no competing interests exist.

Background: Emergency department (ED) attendance for older people towards the end of life is common and increasing, despite most preferring home-based care. We aimed to review the factors associated with older people's ED attendance towards the end of life., Methods: Systematic review using Medline, Embase, PsychINFO, CINAHL and Web of Science from inception to March 2017. Included studies quantitatively examined factors associated with ED attendance for people aged ≥65 years within the last year of life. We assessed study quality using the QualSyst tool and determined evidence strength based on quality, quantity and consistency. We narratively synthesized the quantitative findings., Results: Of 3824 publications identified, 21 were included, combining data from 1 565 187 participants. 17/21 studies were from the USA and 19/21 used routinely collected data. We identified 47 factors and 21 were included in the final model. We found high strength evidence for associations between ED attendance and palliative/hospice care (adjusted effect estimate range: 0.1-0.94); non-white ethnicity (1.03-2.16); male gender (1.04-1.83, except 0.70 in one sub-sample) and rural areas (0.98-1.79). The final model included socio-demographic, illness and service factors, with largest effect sizes for service factors., Conclusions: In this synthesis, receiving palliative care was associated with lower ED attendance in the last year of life for older adults. This has implications for service models for older people nearing the end of life. However, there is limited evidence from European countries and none from low or middle-income countries, which warrants further research.

Objective: The aim of this study was to develop a predictive model for risk of death in hospital for gynecological cancer patients specifically examining the impact of sociodemographic factors and emergency admissions to inform patient choice in place of death., Methods: The model was based on data from 71,269 women with gynecological cancer as underlying cause of death in England, January 1, 2000, to July 1, 2012, in a national Hospital Episode Statistics-Office for National Statistics database. Two thousand eight hundred eight deaths were used for validation of the model. Logistic regression identified independent predictors of a hospital death: adjusting for year of death, age group, income deprivation quintile, Strategic Health Authority, gynecological cancer site, and number of elective and emergency hospital admissions and respective total durations of stay., Results: Forty-three percent of deaths from gynecological cancer occurred in hospital. The variables significantly predicting death in hospital were less recent year of death (odds ratio [OR], 0.93; P < 0.001), increasing age (OR, 1.17; P < 0.001), increasing deprivation (OR, 1.06; P < 0. 001), increasing frequency and length of elective and emergency admissions (P < 0.001). The model correctly identified 73% of hospital deaths with a sensitivity of 75% and a specificity of 72%. The areas under the receiver operating curve were 0.78 for the predictive model and 0.71 for the validation data set. Each subsequent emergency admission in the last month of life increased the odds of death in hospital by 2.4 times (OR, 2.38; P < 0.001). Hospital deaths were significantly lower in all other regions compared with London. The model predicted a 16% reduction of deaths in hospital if 50% of emergency hospital admissions in the last month of life could be avoided by better community care., Conclusions: Our findings could enable identification of patients at risk of dying in hospital to ensure greater patient choice for place of death.

p-Cresyl glucuronide (p-CG) is a by-product of tyrosine metabolism that accumulates in patients with end-stage renal disease. p-CG binding to human serum albumin in physiological conditions (37 °C, pH 7.40) was studied by ultrafiltration (MWCO 10 kDa) and data were analyzed assuming one binding site. The estimated value of the association constant was 2.77 × 10 3  M -1 and a maximal stoichiometry of 3.80 mol per mole. At a concentration relevant for end-stage renal patients, p-CG was 23% bound to albumin. Competition experiments, using fluorescent probes, demonstrated that p-CG did not bind to Sudlow's site I or site II. The p-CG did not interfere with the binding of p-cresyl-sulfate or indoxyl sulfate to serum albumin., (Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Background: Liver disease represents the third commonest cause of death in adults of working age and is associated with an extensive illness burden towards the end of life. Despite this, patients rarely receive palliative care and are unlikely to be involved in advance care planning discussions. Evidence addressing how existing services meet end-of-life needs, and exploring attitudes of patients and carers towards palliative care, is lacking., Aim: To explore the needs of patients and carers with liver disease towards the end of life, evaluate how existing services meet need, and examine patient and carer attitudes towards palliative care., Design: Qualitative study - semi-structured interviews analysed using thematic analysis. Settings/participants: A total of 17 participants (12 patients, 5 bereaved carers) recruited from University Hospitals Bristol., Results: Participants described escalating physical, psychological and social needs as liver disease progressed, including disabling symptoms, emotional distress and uncertainty, addiction, financial hardship and social isolation. End-of-life needs were incompatible with the healthcare services available to address them; these were heavily centred in secondary care, focussed on disease modification at the expense of symptom control and provided limited support after curative options were exhausted. Attitudes towards palliative care were mixed, however, participants valued opportunities to express future care preferences (particularly relating to avoidance of hospital admission towards the end of life) and an increased focus on symptomatic and logistical aspects of care., Conclusion: The needs of patients with liver disease and their carers are frequently incompatible with the healthcare services available to them towards the end of life. Novel strategies, which recognise the life-limiting nature of liver disease explicitly and improve coordination with community services, are required if end-of-life care is to improve.

Whereas l-3-oxo-hexanoyl homoserine lactone (OHHL) is the active enantiomer of the of LuxR-regulated quorum sensing (QS) autoinducer, its d isomer is implicitly considered as inactive. The present work aims to clarify this l-specificity and investigate whether it extends to some analogues in the acyl homoserine lactone (AHL) family. For this purpose, OHHL and a series of AHL analogs were synthesized in racemic and enantiomerically pure d and l forms and their ability to induce or attenuate bioluminescence in the LuxR-dependent QS system was evaluated. In this study, l-isomers are confirmed as either the only, or as the most active, enantiomers. However, in several cases, especially for the natural ligand of LuxR (OHHL) and the very similar AHL agonist analogue 2, the d-isomer cannot be considered as totally inactive on QS. Molecular modelling suggests that when the lactone moiety of the d-isomer is able to twist, enabling the lactone carbonyl group and the amide function to interact with the key residues in the binding site, then the d-isomer can exhibit some activity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This report contains new and follow-up metric data relating to the eight main recommendations of the Lancet Standing Commission on Liver Disease in the UK, which aim to reduce the unacceptable harmful consequences of excess alcohol consumption, obesity, and viral hepatitis. For alcohol, we provide data on alcohol dependence, damage to families, and the documented increase in alcohol consumption since removal of the above-inflation alcohol duty escalator. Alcoholic liver disease will shortly overtake ischaemic heart disease with regard to years of working life lost. The rising prevalence of overweight and obesity, affecting more than 60% of adults in the UK, is leading to an increasing liver disease burden. Favourable responses by industry to the UK Government's soft drinks industry levy have been seen, but the government cannot continue to ignore the number of adults being affected by diabetes, hypertension, and liver disease. New direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection have reduced mortality and the number of patients requiring liver transplantation, but more screening campaigns are needed for identification of infected people in high-risk migrant communities, prisons, and addiction centres. Provision of care continues to be worst in regions with the greatest socioeconomic deprivation, and deficiencies exist in training programmes in hepatology for specialist registrars. Firm guidance is needed for primary care on the use of liver blood tests in detection of early disease and the need for specialist referral. This report also brings together all the evidence on costs to the National Health Service and wider society, in addition to the loss of tax revenue, with alcohol misuse in England and Wales costing £21 billion a year (possibly up to £52 billion) and obesity costing £27 billion a year (treasury estimates are as high as £46 billion). Voluntary restraints by the food and drinks industry have had little effect on disease burden, and concerted regulatory and fiscal action by the UK Government is essential if the scale of the medical problem, with an estimated 63 000 preventable deaths over the next 5 years, is to be addressed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)