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Purpose: Preoperative radiosurgery (SRS) of brain metastases (BM) aims to achieve cavity local control with a reduction in leptomeningeal relapse (LMD) and without additional radionecrosis compared to postoperative SRS. We present the final results of a prospective feasibility trial of linac-based stereotactic radiosurgery (SRS) prior to neurosurgical resection of a brain metastasis (PREOP-1). Methods: Eligibility criteria included a BM up to 4 cm in diameter for elective resection. The primary endpoint was the feasibility of delivering linac-based preoperative SRS in all patients prior to anticipated gross tumour resection. Secondary endpoints included rates of LMD, local control and overall survival. Exploratory endpoints were the level of expression of immunological and proliferative markers. Results: Thirteen patients of median age 65 years (range 41–77) were recruited. Twelve patients (92 %) received preoperative radiosurgery and metastasectomy and one patient went directly to surgery and received postoperative SRS, thus the primary endpoint was not met. The median time between referral and preoperative SRS was 6.5 working days (1–10) and from SRS to neurosurgery was 1 day (0–5). The median prescribed dose was 16 Gy (14–19) to a median planning target volume of 12.7 cm3 (5.9–26.1). Five patients completed 12-month follow-up after preoperative SRS without local recurrence or leptomeningeal disease. The patient who received postoperative FSRT developed LMD after six months. There was one transient toxicity (grade 2 alopecia) and nine patients have died from extracranial causes. Patients reported significant improvement in motor weakness at 6 months (P = 0.04). No pattern in changes of marker expression was observed. Conclusion: In patients with large brain metastasis without raised intracranial pressure, linac-based preoperative SRS was feasible in 12/13 patients and safe in 12/12 patients without any surgical delay or intracranial complications.

Background and purpose: This study evaluated translational and rotational intra-fractional patient movement during spinal stereotactic body radiotherapy (SBRT) using 6D positioning based on 3D cone beam computerized tomography (CBCT) and stereoscopic kilovoltage imaging (ExacTrac). The aim was to determine whether additional intra-fractional image verification reduced intra-fractional motion without significantly prolonging treatment time, whilst maintaining acceptable imaging related dose. Materials and methods: A retrospective analysis of 38 patients with 41 primary tumour volumes treated with SBRT between September 2018 and May 2021 was performed. Three different image-guided radiotherapy (IGRT) workflows were assessed. The translational and rotational positioning errors for the different imaging workflows, 3D translational vectors and estimates of imaging dose delivered for the different imaging workflows were evaluated. Results: As the frequency of intra-fractional imaging increased from workflow 1 to 3, the mean intra-fraction 3D translational vector improved from 0.91 mm (±0.52 mm), to 0.64 (±0.34 mm). 85 %, 83 % and 97 % of images were within a tolerance of 1 mm/1° for workflows 1, 2 and 3 respectively, based on post treatment CBCT images. The average treatment time for workflow 3 was 13 min, as compared to 12 min for workflows 1 and 2. The effective dose per treatment for IGRT workflows 1, 2 and 3 measured 0.6 mSv, 0.95 mSv and 1.8 mSv respectively. Conclusion: The study demonstrated that the use of additional intra-fractional stereoscopic kilovoltage image-guidance during spinal SBRT, reduced the number of measurements deemed “out of tolerance” and treatment delivery could be optimized within a standard treatment timeslot without applying substantial additional radiation dose.

Background: 90% of glioblastomas (GBM) relapse within two years of diagnosis. In contrast to the initial setting, there is no standard management for recurrent disease and options include hypofractionated stereotactic re-irradiation (re-mHSRT). The aims of this study were to investigate re-mHSRT practice in Swiss neuro-oncology centres., Methods: A survey of 18 questions regarding re-irradiation for GBM was created and distributed electronically (SurveyMonkey, USA) to 11 radiation oncologists in Switzerland specialising in brain tumours. We evaluated the clinical outcomes of a multicentre series of patients treated with an established re-mHSRT schedule to benchmark these against the literature and investigated the radiological patterns of relapse after re-mHSRT., Results: 8 of 11 (73%) radiation oncologists responded to the survey and re-irradiation practice was heterogeneous. The 10 × 3.5 Gy schedule (RTOG 1205, BRIOChe trials) was used by 5/8 respondents and 47/50 patients with recurrent GBM treated with re-mHSRT with this schedule in daily practice were included in the analysis. The median time to re-mHSRT following completion of adjuvant RT was 23.3 (7-224) months. The median PTV at re-mHSRT was 22.0 cm 3 (0.9-190). Combined CTV + PTV margins ranged from 0 to 10 mm and median prescription isodose was 80% (67-100). 14/47 (30%) patients received temozolomide and four (8.5%) continued bevacizumab concomitantly. On multivariable analysis, concomitant systemic therapy predicted for progression-free survival (PFS), HR 2.87 (95% CI 1-03-7.96), p = 0.042. Median PFS following re-mHSRT was 6.6 (0.2-92.5) months and 26/47 patients (55%) received subsequent systemic therapy. The median overall survival (OS) following recurrence was 11.8 months (1.5-92.5), similar to the 10.8 months in the literature with the same schedule. The six-month OS rate was 37/47 (79%), which compares well with the 73% reported in a meta-analysis of 50 publications employing various schedules. In a subgroup analysis of 36/47 (79%) patients with MR follow-up after re-mHSRT, 8/36 (22%) had no radiological evidence of tumour progression at a median follow-up of 9.4 months. 21/28 (75%) radiological relapses were in-field, two were marginal and five were out of field., Conclusions: Re-mHSRT with 10 × 3.5 Gy can achieve local control in selected patients with recurrent GBM., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics committee approval for the multicentre analysis was obtained from the Ethikkommission Nordwest und Zentral Schweiz (EKNZ 2023 − 00414). Patients provided informed consent for both medical therapy and consent for use of anonymised data in ethics-approved future research projects. Patients treated prior to introduction of this consent form in 2018 could not be asked. Consent for publication: Covered by the consent obtained. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Preoperative radiosurgery (SRS) of brain metastases (BM) aims to achieve cavity local control with a reduction in leptomeningeal relapse (LMD) and without additional radionecrosis compared to postoperative SRS. We present the final results of a prospective feasibility trial of linac-based stereotactic radiosurgery (SRS) prior to neurosurgical resection of a brain metastasis (PREOP-1)., Methods: Eligibility criteria included a BM up to 4 cm in diameter for elective resection. The primary endpoint was the feasibility of delivering linac-based preoperative SRS in all patients prior to anticipated gross tumour resection. Secondary endpoints included rates of LMD, local control and overall survival. Exploratory endpoints were the level of expression of immunological and proliferative markers., Results: Thirteen patients of median age 65 years (range 41-77) were recruited. Twelve patients (92 %) received preoperative radiosurgery and metastasectomy and one patient went directly to surgery and received postoperative SRS, thus the primary endpoint was not met. The median time between referral and preoperative SRS was 6.5 working days (1-10) and from SRS to neurosurgery was 1 day (0-5). The median prescribed dose was 16 Gy (14-19) to a median planning target volume of 12.7 cm 3 (5.9-26.1). Five patients completed 12-month follow-up after preoperative SRS without local recurrence or leptomeningeal disease. The patient who received postoperative FSRT developed LMD after six months. There was one transient toxicity (grade 2 alopecia) and nine patients have died from extracranial causes. Patients reported significant improvement in motor weakness at 6 months (P = 0.04). No pattern in changes of marker expression was observed., Conclusion: In patients with large brain metastasis without raised intracranial pressure, linac-based preoperative SRS was feasible in 12/13 patients and safe in 12/12 patients without any surgical delay or intracranial complications., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [SR has received Speaker's Honoraria from Brainlab.]., (© 2024 The Authors.)

Objectives: Quantifying area-level inequalities in population health can help to inform policy responses. We describe an approach for estimating quality-adjusted life expectancy (QALE), a comprehensive health expectancy measure, for local authorities (LAs) in Great Britain (GB). To identify potential factors accounting for LA-level QALE inequalities, we examined the association between inclusive economy indicators and QALE., Setting: 361/363 LAs in GB (lower tier/district level) within the period 2018-2020., Data and Methods: We estimated life tables for LAs using official statistics and utility scores from an area-level linkage of the Understanding Society survey. Using the Sullivan method, we estimated QALE at birth in years with corresponding 80% CIs. To examine the association between inclusive economy indicators and QALE, we used an open access data set operationalising the inclusive economy, created by the System Science in Public Health and Health Economics Research consortium., Results: Population-weighted QALE estimates across LAs in GB were lowest in Scotland (females/males: 65.1 years/64.9 years) and Wales (65.0 years/65.2 years), while they were highest in England (67.5 years/67.6 years). The range across LAs for females was from 56.3 years (80% CI 45.6 to 67.1) in Mansfield to 77.7 years (80% CI 65.11 to 90.2) in Runnymede. QALE for males ranged from 57.5 years (80% CI 40.2 to 74.7) in Merthyr Tydfil to 77.2 years (80% CI 65.4 to 89.1) in Runnymede. Indicators of the inclusive economy accounted for more than half of the variation in QALE at the LA level (adjusted R 2 females/males: 50%/57%). Although more inclusivity was generally associated with higher levels of QALE at the LA level, this association was not consistent across all 13 inclusive economy indicators., Conclusions: QALE can be estimated for LAs in GB, enabling further research into area-level health inequalities. The associations we identified between inclusive economy indicators and QALE highlight potential policy priorities for improving population health and reducing health inequalities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

To help health economic modelers respond to demands for greater use of complex systems models in public health. To propose identifiable features of such models and support researchers to plan public health modeling projects using these models. A working group of experts in complex systems modeling and economic evaluation was brought together to develop and jointly write guidance for the use of complex systems models for health economic analysis. The content of workshops was informed by a scoping review. A public health complex systems model for economic evaluation is defined as a quantitative, dynamic, non-linear model that incorporates feedback and interactions among model elements, in order to capture emergent outcomes and estimate health, economic and potentially other consequences to inform public policies. The guidance covers: when complex systems modeling is needed; principles for designing a complex systems model; and how to choose an appropriate modeling technique. This paper provides a definition to identify and characterize complex systems models for economic evaluations and proposes guidance on key aspects of the process for health economics analysis. This document will support the development of complex systems models, with impact on public health systems policy and decision making., (© 2023 The Authors. Health Economics published by John Wiley & Sons Ltd.)

The global COVID-19 pandemic brought considerable public and policy attention to the field of infectious disease modelling. A major hurdle that modellers must overcome, particularly when models are used to develop policy, is quantifying the uncertainty in a model's predictions. By including the most recent available data in a model, the quality of its predictions can be improved and uncertainties reduced. This paper adapts an existing, large-scale, individual-based COVID-19 model to explore the benefits of updating the model in pseudo-real time. We use Approximate Bayesian Computation (ABC) to dynamically recalibrate the model's parameter values as new data emerge. ABC offers advantages over alternative calibration methods by providing information about the uncertainty associated with particular parameter values and the resulting COVID-19 predictions through posterior distributions. Analysing such distributions is crucial in fully understanding a model and its outputs. We find that forecasts of future disease infection rates are improved substantially by incorporating up-to-date observations and that the uncertainty in forecasts drops considerably in later simulation windows (as the model is provided with additional data). This is an important outcome because the uncertainty in model predictions is often overlooked when models are used in policy., (© 2023. The Author(s).)

Background and Purpose: This study evaluated translational and rotational intra-fractional patient movement during spinal stereotactic body radiotherapy (SBRT) using 6D positioning based on 3D cone beam computerized tomography (CBCT) and stereoscopic kilovoltage imaging (ExacTrac). The aim was to determine whether additional intra-fractional image verification reduced intra-fractional motion without significantly prolonging treatment time, whilst maintaining acceptable imaging related dose., Materials and Methods: A retrospective analysis of 38 patients with 41 primary tumour volumes treated with SBRT between September 2018 and May 2021 was performed. Three different image-guided radiotherapy (IGRT) workflows were assessed. The translational and rotational positioning errors for the different imaging workflows, 3D translational vectors and estimates of imaging dose delivered for the different imaging workflows were evaluated., Results: As the frequency of intra-fractional imaging increased from workflow 1 to 3, the mean intra-fraction 3D translational vector improved from 0.91 mm (±0.52 mm), to 0.64 (±0.34 mm). 85 %, 83 % and 97 % of images were within a tolerance of 1 mm/1° for workflows 1, 2 and 3 respectively, based on post treatment CBCT images. The average treatment time for workflow 3 was 13 min, as compared to 12 min for workflows 1 and 2. The effective dose per treatment for IGRT workflows 1, 2 and 3 measured 0.6 mSv, 0.95 mSv and 1.8 mSv respectively., Conclusion: The study demonstrated that the use of additional intra-fractional stereoscopic kilovoltage image-guidance during spinal SBRT, reduced the number of measurements deemed "out of tolerance" and treatment delivery could be optimized within a standard treatment timeslot without applying substantial additional radiation dose., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.J. Rogers has received speaker's honoraria from BrainLab., (© 2022 The Author(s).)

Background: There are a range of policies and guidelines focused on meat consumption which aim to tackle health and environmental issues. Policies are often siloed in nature and propose universal limits on consumption. Despite this, there will be a number of conflicts and trade-offs between interest groups. This study explores secondary impacts associated with guidelines issued by the World Cancer Research Fund and assesses the utility of a targeted policy intervention strategy for reducing red meat consumption., Methods: We used highly detailed consumption data of over 5,000 individuals from the National Diet and Nutrition Survey. We firstly compared individual consumption against the policy guidelines to identify demographic groups most likely to consume above recommended levels. We then synthetically modified the food diary data to investigate the secondary impacts of adherence to the recommendations by all individuals. We assessed changes in overall consumption, nutrient intake (iron, zinc, vitamin B12, vitamin B3, fat and saturated fat) and global warming potential. We also projected future impacts under various population projections., Results: We found that certain demographic groups are much more likely to exceed the recommendations and would therefore benefit from a targeted intervention approach. Our results provide a baseline for which the impacts of any meat substitute diets can be assessed against. Whilst secondary health benefits may be realised by reducing intake of certain nutrients (e.g. fats), negative impacts may occur due to the reduced intake of other nutrients (e.g. iron, zinc). Reduced overall consumption is likely to have implications for the wider meat industry whilst complementary impacts would occur in terms of reduced greenhouse gas emissions. Impacts will be counteracted or maybe even reversed by any substitute products, highlighting the need to carefully consider the suitability and impacts of meat-replacements., Conclusion: The future structure of the meat industry will depend on how conflicts and trade-offs are addressed and how more holistic policy ideas are implemented. This research provides a framework for using demographic and consumption data to reduce negative trade-offs and improve policy effectiveness., (© 2022. The Author(s).)

Purpose: Stereotactic radiosurgery (SRS) is now mainstream for patients with 1-4 brain metastases however the management of patients with 5 or more brain metastases remains controversial. Our aim was to evaluate the clinical outcomes of patients with 5 or more brain metastases and to compare with published series as a benchmarking exercise., Methods: Patients with 5 or more brain metastases treated with a single isocentre dynamic conformal arc technique on a radiosurgery linac were identified from the institutional database. Endpoints were local control, distant brain failure, leptomeningeal disease and overall survival. Dosimetric data were extracted from the radiosurgery plans. Series reporting outcomes following SRS for multiple brain metastases were identified by a literature search., Results: 36 patients, of whom 35 could be evaluated, received SRS for 5 or more brain metastases between February 2015 and October 2021. 25 patients had 5-9 brain metastases (group 1) and 10 patients had 10-15 brain metastases (group 2). The mean number of brain metastases in group 1 was 6.3 (5-9) and 12.3 (10-15) in group 2. The median cumulative irradiated volume was 4.6 cm 3 (1.25-11.01) in group 1 and 7.2 cm 3 (2.6-11.1) in group 2. Median follow-up was 12 months. At last follow-up, local control rates per BM were 100% and 99.8% as compared with a median of 87% at 1 year in published series. Distant brain failure was 36% and 50% at a median interval of 5.2 months and 7.4 months after SRS in groups 1 and 2 respectively and brain metastasis velocity at 1 year was similar in both groups (9.7 and 11). 8/25 patients received further SRS and 7/35 patients received whole brain radiotherapy. Median overall survival was 10 months in group 1 and 15.7 months in group 2, which compares well with the 7.5 months derived from the literature. There was one neurological death in group 2, leptomeningeal disease was rare (2/35) and there were no cases of radionecrosis., Conclusion: With careful patient selection, overall survival following SRS for multiple brain metastases is determined by the course of the extracranial disease. SRS is an efficacious and safe modality that can achieve intracranial disease control and should be offered to patients with 5 or more brain metastases and a constellation of good prognostic factors., Competing Interests: SR has received Speaker’s Honoraria from Brainlab. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rogers, Lomax, Alonso, Lazeroms and Riesterer.)

Background: The number of people living with obesity or who are overweight presents a global challenge, and the development of effective interventions is hampered by a lack of research which takes a joined up, whole system, approach that considers multiple elements of the complex obesity system together. We need to better understand the collective characteristics and behaviours of those who are overweight or have obesity and how these differ from those who maintain a healthy weight., Methods: Using the UK Biobank cohort we develop an obesity classification system using k-means clustering. Variable selection from the UK Biobank cohort is informed by the Foresight obesity system map across key domains (Societal Influences, Individual Psychology, Individual Physiology, Individual Physical Activity, Physical Activity Environment)., Results: Our classification identifies eight groups of people, similar in respect to their exposure to known drivers of obesity: 'Younger, urban hard-pressed', 'Comfortable, fit families', 'Healthy, active and retirees', 'Content, rural and retirees', 'Comfortable professionals', 'Stressed and not in work', 'Deprived with less healthy lifestyles' and 'Active manual workers'. Pen portraits are developed to describe the characteristics of these different groups. Multinomial logistic regression is used to demonstrate that the classification can effectively detect groups of individuals more likely to be living with overweight or obesity. The group identified as 'Comfortable, fit families' are observed to have a higher proportion of healthy weight, while three groups have increased relative risk of being overweight or having obesity: 'Active manual workers', 'Stressed and not in work' and 'Deprived with less healthy lifestyles'., Conclusions: This paper presents the first study of UK Biobank participants to adopt this obesity system approach to characterising participants. It provides an innovative new approach to better understand the complex drivers of obesity which has the potential to produce meaningful tools for policy makers to better target interventions across the whole system to reduce overweight and obesity., (© 2022. The Author(s).)

In order to understand the health outcomes for distinct sub-groups of the population or across different geographies, it is advantageous to be able to build bespoke groupings from individual level data. Individuals possess distinct characteristics, exhibit distinct behaviours and accumulate their own unique history of exposure or experiences. However, in most disciplines, not least public health, there is a lack of individual level data available outside of secure settings, especially covering large portions of the population. This paper provides detail on the creation of a synthetic micro dataset for individuals in Great Britain who have detailed attributes which can be used to model a wide range of health and other outcomes. These attributes are constructed from a range of sources including the United Kingdom Census, survey and administrative datasets. It provides a rationale for the need for this synthetic population, discusses methods for creating this dataset and provides some example results of different attribute distributions for distinct sub-population groups and over different geographical areas., (© 2022. The Author(s).)

Many researchers are beginning to adopt the use of wrist-worn accelerometers to objectively measure personal activity levels. Data from these devices are often used to summarise such activity in terms of averages, variances, exceedances, and patterns within a profile. In this study, we report the development of a clustering utilising the whole activity profile. This was achieved using the robust clustering technique of k-medoids applied to an extensive data set of over 90,000 activity profiles, collected as part of the UK Biobank study. We identified nine distinct activity profiles in these data, which captured both the pattern of activity throughout a week and the intensity of the activity: "Active 9 to 5", "Active", "Morning Movers", "Get up and Active", "Live for the Weekend", "Moderates", "Leisurely 9 to 5", "Sedate" and "Inactive". These patterns are differentiated by sociodemographic, socioeconomic, and health and circadian rhythm data collected by UK Biobank. The utility of these findings are that they sit alongside existing summary measures of physical activity to provide a way to typify distinct activity patterns that may help to explain other health and morbidity outcomes, e.g., BMI or COVID-19. This research will be returned to the UK Biobank for other researchers to use.

A 70-year old male with stage I large cell neuroendocrine carcinoma (LCNEC) of the lung underwent resection of a metachronous 5 cm brain metastasis and received postoperative hypofractionated stereotactic radiotherapy (hfSRT). Five sequential nodular leptomeningeal metastases up to 5.3 cm in diameter were diagnosed on MRI within 10 months and were treated with SRT. Currently the patient has no evidence of intracranial disease 24 months after last irradiation without chemotherapy or whole brain radiotherapy. This is the first report of sustained complete remission of multiple large leptomeningeal metastases achieved with hfSRT, highlighting this brain-sparing approach in selected patients with LCNEC lung cancer., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

A large evidence base demonstrates that the outcomes of COVID-19 and national and local interventions are not distributed equally across different communities. The need to inform policies and mitigation measures aimed at reducing the spread of COVID-19 highlights the need to understand the complex links between our daily activities and COVID-19 transmission that reflect the characteristics of British society. As a result of a partnership between academic and private sector researchers, we introduce a novel data driven modelling framework together with a computationally efficient approach to running complex simulation models of this type. We demonstrate the power and spatial flexibility of the framework to assess the effects of different interventions in a case study where the effects of the first UK national lockdown are estimated for the county of Devon. Here we find that an earlier lockdown is estimated to result in a lower peak in COVID-19 cases and 47% fewer infections overall during the initial COVID-19 outbreak. The framework we outline here will be crucial in gaining a greater understanding of the effects of policy interventions in different areas and within different populations., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The increasing ubiquity of smartphone data, with greater spatial and temporal coverage than achieved by traditional study designs, have the potential to provide insight into habitual physical activity patterns. This study implements and evaluates the utility of both K-means clustering and agglomerative hierarchical clustering methods in identifying weekly and yearlong physical activity behaviour trends. Characterising the demographics and choice of activity type within the identified clusters of behaviour. Across all seven clusters of seasonal activity behaviour identified, daylight saving was shown to play a key role in influencing behaviour, with increased activity in summer months. Investigation into weekly behaviours identified six clusters with varied roles, of weekday versus weekend, on the likelihood of meeting physical activity guidelines. Preferred type of physical activity likewise varied between clusters, with gender and age strongly associated with cluster membership. Key relationships are identified between weekly clusters and seasonal activity behaviour clusters, demonstrating how short-term behaviours contribute to longer-term activity patterns. Utilising unsupervised machine learning, this study demonstrates how the volume and richness of secondary app data can allow us to move away from aggregate measures of physical activity to better understand temporal variations in habitual physical activity behaviour.

Purpose: The outcomes of five fraction stereotactic radiotherapy (hfSRT) following brain metastasectomy were evaluated and compared with published series., Methods: 30 Gy in 5 fractions HfSRT prescribed to the surgical cavity was reduced to 25 Gy if the volume of 'brain-GTV' receiving 20 Gy exceeded 20 cm 3 . Endpoints were local recurrence, nodular leptomeningeal recurrence, new brain metastases and radionecrosis. The literature was searched for reports of clinical and dosimetric outcomes following postoperative hfSRT in 3-5 fractions., Results: 39 patients with 40 surgical cavities were analyzed. Cavity local control rate at 1 year was 33/40 (82.5%). 3 local failures followed 30 Gy/5 fractions and 4 with 25 Gy/5 fractions. The incidence of leptomeningeal disease (LMD) was 7/40 (17.5%). No grade 3-4 toxicities, particularly no radionecrosis, were reported. The incidence of distant brain metastases was 15/40 (37.5%). The median overall survival was 15 months. Across 13 published series, the weighted mean local control was 83.1% (adjusted for sample size), the mean incidence of LMD was 14.9% (7-34%) and the mean rate of radionecrosis was 10.3% (0-20.6%)., Conclusion: Postoperative hfSRT can be delivered with 25-30 Gy in 5 fractions with efficacy in excess of 82% and no significant toxicity when the dose to 'brain-GTV' does not exceed 20 cm 3 ., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

COVID-19 is a disease that has been shown to have outcomes that vary by certain socio-demographic and socio-economic groups. It is increasingly important that an understanding of these outcomes should be derived not from the consideration of one aspect, but by a more multi-faceted understanding of the individual. In this study use is made of a recent obesity driven classification of participants in the United Kingdom Biobank (UKB) to identify trends in COVID-19 outcomes. This classification is informed by a recently created obesity systems map, and the COVID-19 outcomes are: undertaking a test, a positive test, hospitalisation and mortality. It is demonstrated that the classification is able to identify meaningful differentials in these outcomes. This more holistic approach is recommended for identification and prioritisation of COVID-19 risk and possible long-COVID determination., (© 2021. The Author(s).)

The increasing ubiquity of smartphones provides a potential new data source to capture physical activity behaviours. Though not designed as a research tool, these secondary data have the potential to capture a large population over a more extensive spatial area and with longer temporality than current methods afford. This paper uses one such secondary data source from a commercial app designed to incentivise activity. We explore the new insights these data provide, alongside the sociodemographic profile of those using physical activity apps, to gain insight into both physical activity behaviour and determinants of app usage in order to evaluate the suitability of the app in providing insights into the physical activity of the population. We find app usage to be higher in females, those aged 25-50, and users more likely to live in areas where a higher proportion of the population are of a lower socioeconomic status. We ascertain longer-term patterns of app usage with increasing age and more male users reaching physical activity guideline recommendations despite longer daily activity duration recorded by female users. Additionally, we identify key weekly and seasonal trends in physical activity. This is one of the first studies to utilise a large volume of secondary physical activity app data to co-investigate usage alongside activity behaviour captured., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

The future of the meat industry will require the management of important trade-offs between economic, environmental and health aspects of both humans and animals. Understanding the patterns and trends of meat expenditure and consumption is crucial for assessing the current resilience of the system and for economic, planning, health and environmental applications. Here, we show how the technique of geodemographic classification, combined with fine scale expenditure estimates can be used to explore temporal and spatial patterns of meat expenditure in Great Britain between 2008 and 2017. Whilst the expenditure patterns of some food categories such as sausages remained relatively consistent, others such as lamb show a trend towards a reduced proportion of expenditure and increased inequality of purchases. Short term changes in expenditure patterns also occurred, potentially due to product specific price variability, price elasticities or zoonotic disease scare. Environmental attitudes, financial constraints and the prominence of communities who do not eat meat for religious or cultural reasons are likely to be driving the differences between geodemographic groups. The methodology and results could be a valuable tool for policy makers in the meat industry and beyond., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Objective: Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT)., Methods:: Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed., Results:: Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture., Conclusion: Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial., Advances in Knowledge:: This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.

The conditions in which we are born, grow, live, work and age are key drivers of health and inequalities in life chances. To maximise health and wellbeing across the whole population, we need well-coordinated action across government sectors, in areas including economic, education, welfare, labour market and housing policy. Current research struggles to offer effective decision support on the cross-sector strategic alignment of policies, and to generate evidence that gives budget holders the confidence to change the way major investment decisions are made. This open letter introduces a new research initiative in this space. The SIPHER ( Systems Science in Public Health and Health Economics Research) Consortium brings together a multi-disciplinary group of scientists from across six universities, three government partners at local, regional and national level, and ten practice partner organisations. The Consortium's vision is a shift from health policy to healthy public policy, where the wellbeing impacts of policies are a core consideration across government sectors. Researchers and policy makers will jointly tackle fundamental questions about: a) the complex causal relationships between upstream policies and wellbeing, economic and equality outcomes; b) the multi-sectoral appraisal of costs and benefits of alternative investment options; c) public values and preferences for different outcomes, and how necessary trade-offs can be negotiated; and d) creating the conditions for intelligence-led adaptive policy design that maximises progress against economic, social and health goals. Whilst our methods will be adaptable across policy topics and jurisdictions, we will initially focus on four policy areas: Inclusive Economic Growth, Adverse Childhood Experiences, Mental Wellbeing and Housing., Competing Interests: No competing interests were disclosed., (Copyright: © 2019 Meier P et al.)

We present expenditure estimates for 106 product categories across Great Britain for the years 2008-2016. Estimates are at the Local Authority District level (n = 380) and the categories cover all food, drink and tobacco commodities. Reliable, local level expenditure estimates are crucial for understanding broader market trends, assessing economic stability and for projections. This is especially important for commodities such as alcohol, tobacco and unhealthy foods due to their role in the prevalence of non-communicable diseases. There has been relatively little research into local area spatial patterns of expenditure, with existing estimates often of insufficient resolution for informing planning decisions. We use spatial microsimulation to create an archive of expenditure datasets. This was achieved by linking socio-demographic foundations with detailed datasets on individual expenditure. Whilst initially developed to aid investigations into sociodemographic trends in the meat industry, the data have reuse potential in a number of disciplines, including public health, economics, retail geography and environmental management. The framework could be applied to other regions with appropriate data.

Background: There has been considerable interest in the role of access to unhealthy food options as a determinant of weight status. There is conflict across the literature as to the existence of such an association, partly due to the dominance of cross-sectional study designs and inconsistent definitions of the food environment. The aim of our study is to use longitudinal data to examine if features of the food environment are associated to measures of adolescent weight status., Methods: Data were collected from secondary schools in Leeds (UK) and included measurements at school years 7 (ages 11/12), 9 (13/14), and 11 (15/16). Outcome variables, for weight status, were standardised body mass index and standardised waist circumference. Explanatory variables included the number of fast food outlets, supermarkets and 'other retail outlets' located within a 1 km radius of an individual's home or school, and estimated travel route between these locations (with a 500 m buffer). Multi-level models were fit to analyse the association (adjusted for confounders) between the explanatory and outcome variables. We also examined changes in our outcome variables between each time period., Results: We found few associations between the food environment and measures of adolescent weight status. Where significant associations were detected, they mainly demonstrated a positive association between the number of amenities and weight status (although effect sizes were small). Examining changes in weight status between time periods produced mainly non-significant or inconsistent associations., Conclusions: Our study found little consistent evidence of an association between features of the food environment and adolescent weight status. It suggests that policy efforts focusing on the food environment may have a limited effect at tackling the high prevalence of obesity if not supported by additional strategies.

Introduction: Mass appraisals in the rental housing market are far less common than those in the sales market. However, there is evidence for substantial growth in the rental market and this lack of insight hampers commercial organisations and local and national governments in understanding this market., Case Description: This case study uses data that are supplied from a property listings web site and are unique in their scale, with over 1.2 million rental property listings available over a 2 year period. The data is analysed in a large data institute using generalised linear regression, machine learning and a pseudo practitioner based approach., Discussion and Evaluation: The study should be seen as a practical guide for property professionals and academics wishing to undertake such appraisals and looking for guidance on the best methods to use. It also provides insight into the property characteristics which most influence rental listing price., Conclusions: From the regression analysis, attributes that increase the rental listing price are: the number of rooms in the property, proximity to central London and to railway stations, being located in more affluent neighbourhoods and being close to local amenities and better performing schools. Of the machine learning algorithms used, the two tree based approaches were seen to outperform the regression based approaches. In terms of a simple measure of the median appraisal error, a practitioner based approach is seen to outperform the modelling approaches. A practical finding is that the application of sophisticated machine learning algorithms to big data is still a challenge for modern desktop PCs.

Many STIs are known to disproportionately affect men who have sex with men (MSM) in the UK; therefore, regular asymptomatic screening that is easy to access is vital among this group. Asymptomatic screening pathways can reduce long clinic waits, which may encourage more people to attend for screening. We therefore developed and trialled an asymptomatic pathway for MSM within our service. This extended our previous pathway, which allowed asymptomatic service users to fill in a questionnaire and see a healthcare support worker, to include MSM, as it previously had not. The service has been implemented and rolled out successfully. We believe that this model for asymptomatic screening among MSM can reduce clinic visit duration. This should increase accessibility and also allow trained staff to manage more complex patients, while allowing for risk identification and health promotion among those MSM who may be at higher risk., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

A 36-year-old Caucasian homosexual man was found to have HIV infection on routine screening. He had an eight-year history of chronic diarrhoea, which pre-dated the HIV diagnosis and did not improve after the introduction of combination antiretroviral therapy. After referral to the Gastroenterology department, he underwent fibreoptic colonoscopy. Colonic biopsies revealed the presence of intestinal spirochaetosis. He received a two-week course of metronidazole, which led to complete resolution of his diarrhoea. Intestinal spirochaetosis should be considered in the differential diagnosis of patients with HIV infection and chronic diarrhoea without other apparent cause.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.

Questions Under Study: The aim of this retrospective analysis was to evaluate the safety and efficacy of local hyperthermia (HT) and reirradiation (ReRT) in the management of preirradiated locoregional recurrent breast cancers at Kantonsspital Aarau, Switzerland., Methods: Twenty-four previously irradiated patients who had developed locoregional recurrences in the chest wall or breast, with or without regional lymph node involvement, were reirradiated to a mean dose of 36.8 Gy (range 20-50 Gy) delivered at a mean dose per fraction of 2.33 Gy (range 1.8-4.0 Gy). All patients received local HT at 41 to 43 °C, once or twice a week prior to radiotherapy. Online thermometry was carried out during the hyperthermia sessions., Results: An overall objective response rate of 91.7% (22/24) with a complete response in 66.7% (16/24) of patients and partial response in 25% (6/24) of patients was observed. Post-thermoradiotherapy follow-up ranged from 1 to 38 months (median 10 months). The 3-year actuarial local control rate was 59.7%. More patients who attained complete response had sustained locoregional control until their death or last follow-up when compared with those who were partial or non-responders (median local disease-free survival for complete responders not reached; for partial and non-responders 4 months; p <0.001). Post-retreatment median overall survival for all 24 patients was 10 months. Grade III/IV acute toxicity was seen in only one patient and no patient had any significant late morbidity., Conclusions: ReRT and HT is an effective and a safe modality to treat locoregional recurrences in previously irradiated breast cancers. The approach can lead to sustainable long-term palliation with minimal morbidity.

This case describes a young white British man with a one-year history of recurrent genital ulceration managed by the GP. Initially this was thought to be a drug reaction; however, presentation at our genitourinary medicine clinic and onward review with dermatology allowed the diagnosis of Behçet's disease to be made. The clinical diagnosis was made based on painful oral and genital ulcers, eye irritation, erythema nodosum and positive pathergy test. Treatment with oral prednisolone was initiated by dermatology, which resulted in rapid improvement in the genital ulceration. This case highlights that clinicians should consider Behçet's disease in patients with recurrent genital ulceration to ensure prompt diagnosis and prevention of systemic involvement., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)