The advances in cancer research achieved in the last 50 years have been remarkable and have provided a deeper knowledge of this disease in many of its conceptual and biochemical aspects. From viewing a tumor as a ‘simple’ aggregate of mutant cells and focusing on detecting key cell changes leading to the tumorigenesis, the understanding of cancer has broadened to consider it as a complex organ interacting with its close and far surroundings through tumor and non-tumor cells, metabolic mechanisms, and immune processes. Metabolism and the immune system have been linked to tumorigenesis and malignancy progression along with cancer-specific genetic mutations. However, most technologies developed to overcome the barriers to earlier detection are focused solely on genetic information. The concept of cancer as a complex organ has led to research on other analytical techniques, with the quest of finding a more sensitive and cost-effective comprehensive approach. Furthermore, artificial intelligence has gained broader consensus in the oncology community as a powerful tool with the potential to revolutionize cancer diagnosis for physicians. We herein explore the relevance of the concept of cancer as a complex organ interacting with the bodily surroundings, and focus on promising emerging technologies seeking to diagnose cancer earlier, such as liquid biopsies. We highlight the importance of a comprehensive approach to encompass all the tumor and non-tumor derived information salient to earlier cancer detection.

Femoral shaft fractures are common injuries in children 2 to 7 years of age, with treatments ranging from casting to flexible intramedullary nails (FIN). Each treatment has unique attributes and outcomes are overall similar. Given equivalent outcomes, we hypothesized that a shared decision-making process, using adaptive conjoint analysis (ACA), can be used to assess individual family situations to determine ultimate treatment choice. An interactive survey incorporating an ACA exercise to elicit the preferences of individuals was created. Amazon Mechanical Turk was used to recruit survey respondents simulating the at-risk population. Basic demographic information and family characteristics were collected. Sawtooth Software was utilized to generate relative importance values of five treatment attributes and determine subjects' ultimate treatment choice. Student's t-test or Wilcoxon rank sum test was used to compare relative importance between groups. The final analysis included 186 subjects with 147 (79%) choosing casting as their ultimate treatment choice, while 39 (21%) chose FIN. Need for second surgery had the highest overall average relative importance (42.0), followed by a chance of serious complications (24.6), time away from school (12.9), effort required by caregivers (11.0), and return to activities (9.6). Most respondents (85%) indicated the generated relative importance of attributes aligned "very well or well" with their preferences. For those who chose casting instead of FIN, the need for secondary surgery (43.9 vs. 34.8, P <0.001) and the chance of serious complications (25.9 vs. 19.6, P <0.001) were the most important factors. In addition, returning to activities, the burden to caregivers, and time away from school were all significantly more important to those choosing surgery versus casting (12.6 vs. 8.7 P <0.001, 12.6 vs. 9.8 P =0.014, 16.6 vs. 11.7 P <0.001, respectively). Our decision-making tool accurately identified subjects' treatment preferences and appropriately aligned them with a treatment decision. Given the increased emphasis on shared decision-making in health care, this tool may have the potential to improve shared decision-making and family understanding, leading to improved satisfaction rates and overall outcomes. Level-III.

To assess the clinical outcomes and cost-effectiveness of using two different reduced pressure compression systems in treating newly diagnosed venous leg ulcers (VLUs) in clinical practice, from the perspective of the UK's National Health Service (NHS). This was a modelling study based on a retrospective cohort analysis of the case records of patients with a newly diagnosed VLU, randomly extracted from The Health Improvement Network (THIN) database, who were initially treated with a two-layer cohesive compression bandage (TLCCB Lite; Coban 2 Lite, 3M, US) or a two-layer compression system (TLCS Reduced; Ktwo Reduced, Urgo, France). No significant differences were detected between the groups. Nevertheless, analysis of covariance (ANCOVA) was performed to enable differences in patients' outcomes between the groups to be adjusted for any heterogeneity in baseline covariates. Clinical outcomes and cost-effectiveness of the alternative compression systems were estimated over 12 months after starting treatment. Time from wound onset to starting compression was a mean of two months. The probability of healing at 12 months was 0.59 in the TLCCB Lite group and 0.53 in the TLCS Reduced group. Patients in the TLCCB Lite group experienced a marginally better health-related quality of life (HRQoL) of 0.02 quality-adjusted life years (QALYs) per patient compared to those in the TLCS Reduced group. The 12-month NHS wound management cost was £3883 per patient treated with TLCCB Lite and £4235 per patient treated with TLCS Reduced. When the analysis was repeated without ANCOVA, the findings from the base case analysis remained unchanged (i.e., use of TLCCB Lite improved outcomes at lower cost). Within the study's limitations, treating newly diagnosed VLUs with TLCCB Lite instead of TLCS Reduced potentially affords a cost-effective use of NHS-funded resources in clinical practice, since it is expected to result in an increased healing rate, better HRQoL and a lower NHS wound management cost.

To assess the clinical outcomes and cost-effectiveness of using a two-layer cohesive compression bandage (TLCCB; Coban 2, 3M, US) compared with a two-layer compression system (TLCS; KTwo, Urgo, France) and a cohesive inelastic bandage system (CIBR; Actico, L&R, Germany) in treating newly diagnosed venous leg ulcers (VLUs) in clinical practice, from the perspective of the UK's National Health Service (NHS). This was a modelling study based on a retrospective cohort analysis of the case records of patients with a newly diagnosed VLU randomly extracted from the The Health Improvement Network (THIN) database who were treated with TLCCB, TLCS or CIBR. No significant differences were detected between the groups. Nevertheless, analysis of covariance was performed to enable differences in patients' outcomes between the groups to be adjusted for any heterogeneity in baseline covariates. Clinical outcomes and cost-effectiveness of the alternative compression systems were estimated over 12 months after starting treatment. There were 250 patients in each group. Time from wound onset to starting compression was a mean of two months. The healing distribution of the TLCCB-treated patients was significantly different from that of the other two cohorts (p=0.003); the probability of healing at 12 months was 0.62, 0.51 and 0.49 in the TLCCB, TLCS and CIBR groups, respectively. Patients treated with TLCCB experienced better health-related quality of life (HRQoL) over 12 months (0.86 quality-adjusted life years (QALYs) per patient), compared with those treated with TLCS and CIBR (0.83 and 0.82 QALYs per patient, respectively). The 12-month NHS wound management cost was £3693, £4451 and £4399 per patient in the TLCCB, TLCS and CIBR groups, respectively. Within the model's limitations, treating newly diagnosed VLUs with TLCCB instead of the other two compression systems appears to afford a more cost-effective use of NHS-funded resources in clinical practice, since it is expected to result in increased healing, better HRQoL and a lower wound management cost for the NHS.

ObjectiveTo assess the impact of the COVID-19 pandemic on venous leg ulcer (VLU) management by the UK’s health services and associated outcomes.DesignRetrospective cohort analysis of the electronic records of patients from The Health Improvement Network database.SettingClinical practice in primary and secondary care.ParticipantsA cohort of 1946 patients of whom 1263, 1153 and 733 had a VLU in 2019, 2020 and 2021, respectively.Primary and secondary outcome measuresClinical outcomes and wound-related healthcare resource use.ResultsVLU healing rate in 2020 and 2021 decreased by 16% and 42%, respectively, compared with 2019 and time to heal increased by >85%. An estimated 3% of patients in 2020 and 2021 had a COVID-19 infection. Also, 1% of patients in both years had VLU-related sepsis, 0.1%–0.2% developed gangrene and 0.3% and 0.6% underwent an amputation on part of the foot or lower limb in 2020 and 2021 (of whom 57% had diabetes), respectively. The number of community-based face-to-face clinician visits decreased by >50% in both years and >35% fewer patients were referred to a hospital specialist. In 2020 and 2021, up to 20% of patients were prescribed dressings without compression compared with 5% in 2019. The total number of wound care products prescribed in 2020 and 2021 was >50% less than that prescribed in 2019, possibly due to the decreased frequency of dressing change from a mean of once every 11 days in 2019 to once every 21 days in 2020 and 2021.ConclusionsThere was a significant trend towards decreasing care during 2020 and 2021, which was outside the boundaries considered to be good care. This led to poorer outcomes including lower VLU healing rates and increased risk of amputation. Hence, the COVID-19 pandemic appears to have had a deleterious impact on the health of patients with a VLU.

In 2020, school closures in England due to the Coronavirus (‘Covid-19’) pandemic resulted in the cancellation of high-stakes examinations and their replacement with teacher-based assessments. These changes represented a significant change for students who had been preparing to undertake examinations for the ‘end-of-school’ General Certificate of Secondary Education (GCSE). This research reports part of a survey that explored the experiences of these students, with a particular focus on students’ psychological responses. Two hundred and twelve students responded to a questionnaire survey that asked them to reflect on their feelings about the changes to the GCSE assessment. Responses were analysed using both thematic and content analysis and revealed five themes: Issues of control; Issues of fairness; Issues of communication and decision making; A shifted path; and The impact of the changes. We re-emphasise the attested value of forms of ongoing dialogue with students about their assessment experiences and consultation with them about decision making in assessment in order to inform planning to optimise student assessment experience.

To reduce the risk and the required bureaucracy for accessing public funding, the EC has developed a mechanism to grant money to consortia to be used to fund to startups, SMEs and Midcaps to start, evolve or transition their offer to increase their competitivity in the market, in turn providing benefit for the entire European economy.This paper presents the experience in managing what is actually 3rd party (or cascading) funding in two different European Innovation Action Projects in the manufacturing domain. The paper discusses the design and implementation phases and provides the detail on how to manage the processes to ensure fairness, efficiency, and effectiveness that is lacking from the EC's formal documentation.

BackgroundAlthough tuberculosis (TB) is a curable disease, treatment is complex and prolonged, requiring considerable commitment from patients. This study aimed to understand the common perspectives of TB patients across Brazil, Russia, India, China, and South Africa throughout their disease journey, including the emotional, psychological, and practical challenges that patients and their families face.MethodsThis qualitative market research study was conducted between July 2020 and February 2021. Eight TB patients from each country (n = 40) completed health questionnaires, video/telephone interviews, and diaries regarding their experiences of TB. Additionally, 52 household members were interviewed. Patients at different stages of their TB treatment journey, from a range of socioeconomic groups, with or without TB risk factors were sought. Anonymized data underwent triangulation and thematic analysis by iterative coding of statements.ResultsThe sample included 23 men and 17 women aged 13–60 years old, with risk factors for TB reported by 23/40 patients. Although patients were from different countries and cultural backgrounds, experiencing diverse health system contexts, five themes emerged as common across the sample. 1) Economic hardship from loss of income and medical/travel expenses. 2) Widespread stigma, delaying presentation and deeply affecting patients’ emotional wellbeing. 3) TB and HIV co-infection was particularly challenging, but increased TB awareness and accelerated diagnosis. 4) Disruption to family life strained relationships and increased patients’ feelings of isolation and loneliness. 5) The COVID-19 pandemic made it easier for TB patients to keep their condition private, but disrupted access to services.ConclusionsDespite disparate cultural, socio-economic, and systemic contexts across countries, TB patients experience common challenges. A robust examination of the needs of individual patients and their families is required to improve the patient experience, encourage adherence, and promote cure, given the limitations of current treatment.

To estimate whether the topical debriding agent, Debrichem, could potentially afford the UK's National Health Service (NHS) a cost-effective intervention for the management of hard-to-heal venous leg ulcers (VLUs). A Markov model was constructed depicting the management of hard-to-heal VLUs with Debrichem plus standard care (SC) or SC alone over a period of 12 months. The model was populated with inputs from an indirect comparison of two propensity score-matched cohorts. The model estimated the cost-effectiveness of the two interventions in terms of the incremental cost per quality-adjusted life year (QALY) gained at 2019/20 prices. Addition of Debrichem to a SC protocol to treat hard-to-heal VLUs was found to increase the probability of healing by 75% (from 0.35 to 0.61) by 12 months, and to increase health-related quality of life over 12 months from 0.74 to 0.84 QALYs per patient. The 12-month cost of treatment with Debrichem plus SC (£3128 per patient) instead of SC alone (£7195 per patient) has the potential to reduce the total NHS cost of wound management by up to 57%. Hence, Debrichem was estimated to improve health outcomes for less cost. Sensitivity analysis showed that Debrichem plus SC remained a cost-effective (dominant) treatment with plausible variations in costs and effectiveness. Within the limitations of the study, the addition of Debrichem to a SC protocol potentially affords a cost-effective treatment to the NHS for managing hard-to-heal VLUs.

Abstract This paper presents the architecture and features of RiskScape software. RiskScape is an open-source software with a flexible modelling engine for multi-hazard risk analysis. The RiskScape engine implements modeller-defined risk quantification workflows as ‘model pipelines’. Model pipeline steps and functions analyse hazard, exposure, and vulnerability data across different spatio-temporal domains using geoprocessing and spatial sampling operations. The RiskScape engine supports deterministic and probabilistic risk quantification, with several probabilistic-based modes described in this paper. RiskScape advances modelling software for multi-hazard risk analysis through several implementation features. The RiskScape engine operates model pipelines independent of system prescribed model input data classifications or standards. Multiple hazard types, metric intensities, and temporal occurrence information is geometry processed and sampled to create coverage data of simultaneous or sequenced multi-hazard events at object-exposure locations. Escalating multi-hazard event impacts are then determined for object-exposures using scripted conditional or nested statements that apply vulnerability functions in a logical sequence of temporal hazard and impact occurrence. These model features, supported by open geospatial consortium standard geospatial data files and operations, expedite RiskScape for modelling multi-hazard risk at any geographical location or scale.