Advancing Biomarker Development Through Convergent Engagement: Summary Report of the 2nd International Danube Symposium on Biomarker Development, Molecular Imaging and Applied Diagnostics; March 14-16, 2018; Vienna, Austria.

Here, we report on the outcome of the 2nd International Danube Symposium on advanced biomarker development that was held in Vienna, Austria, in early 2018. During the meeting, cross-speciality participants assessed critical aspects of non-invasive, quantitative biomarker development in view of the need to expand our understanding of disease mechanisms and the definition of appropriate strategies both for molecular diagnostics and personalised therapies. More specifically, panelists addressed the main topics, including the current status of disease characterisation by means of non-invasive imaging, histopathology and liquid biopsies as well as strategies of gaining new understanding of disease formation, modulation and plasticity to large-scale molecular imaging as well as integrative multi-platform approaches. Highlights of the 2018 meeting included dedicated sessions on non-invasive disease characterisation, development of disease and therapeutic tailored biomarkers, standardisation and quality measures in biospecimens, new therapeutic approaches and socio-economic challenges of biomarker developments. The scientific programme was accompanied by a roundtable discussion on identification and implementation of sustainable strategies to address the educational needs in the rapidly evolving field of molecular diagnostics. The central theme that emanated from the 2nd Donau Symposium was the importance of the conceptualisation and implementation of a convergent approach towards a disease characterisation beyond lesion-counting "lumpology" for a cost-effective and patient-centric diagnosis, therapy planning, guidance and monitoring. This involves a judicious choice of diagnostic means, the adoption of clinical decision support systems and, above all, a new way of communication involving all stakeholders across modalities and specialities. Moreover, complex diseases require a comprehensive diagnosis by converging parameters from different disciplines, which will finally yield to a precise therapeutic guidance and outcome prediction. While it is attractive to focus on technical advances alone, it is important to develop a patient-centric approach, thus asking "What can we do with our expertise to help patients?"

Patients with surgical wounds healing by secondary intention: A prospective, cohort study.

BACKGROUND: Surgical wounds healing by secondary intention can be difficult and costly to manage and are profoundly under researched. This prospective inception, cohort study aimed to derive a better understanding of surgical wounds healing by secondary intention and to facilitate the design of future research investigating effective treatments. OBJECTIVES: To investigate the clinical characteristics of patients with surgical wounds healing by secondary intention and the surgeries that preceded their wounds; to clearly delineate the clinical outcomes of these patients, specifically focusing on time to wound healing and its determinants; to explore the types of treatments for surgical wounds healing by secondary intention; and to assess the impact surgical wounds healing by secondary intention have on patients' quality of life. DESIGN: Prospective, inception cohort study. SETTING: Acute and community settings in eight sites across two large centres in the United Kingdom (Hull and Leeds, UK). METHODS: Patients with a surgical wounds healing by secondary intention (an open wound, <3 weeks' duration, resulting from surgery), were recruited and followed up for at least 12 months. Key outcome events included: time to healing; treatment type; infection; hospital re-admission and further procedures; health-related quality of life and pain. RESULTS: In total, 393 patients were recruited. Common co-morbidities were cardiovascular disease (38%), diabetes (26%) and peripheral vascular disease (14.5%). Baseline median SWHSI area was 6 cm2 (range 0.01-1200). Abdominal (n = 132), foot (n = 59), leg (n = 58) and peri-anal (n = 34) wounds were common. The majority of wounds (236, 60.1%) were intentionally left open following surgery; the remainder were mostly dehisced wounds. Healing was observed in 320 (81.4%) wounds with a median time to healing of 86 days (95% CI: 75-130). Factors associated with delayed healing included wound infection at any point and baseline wound area above the median. Health-related quality of life scores were low at baseline but improved with time and healing. CONCLUSIONS: This is the first inception cohort study in patients with surgical wounds healing by secondary intention. Patient characteristics have been clearly defined, with prolonged healing times and adverse events being common impacting on patient's health-related quality of life. Areas for, and factors crucial to the design of, future research have been identified.

Association between self-reported hearing impairment and diabetes: a Brazilian population-based study: Association between self-reported hearing impairment and diabetes in adults.

BACKGROUND: Some studies have already explored the relationship between diabetes and hearing loss; however, this relationship has still not been well established, especially due to methodological limitations related to lack of control for confounders. The aim of this study was to analyze the association between self-reported hearing impairment and diabetes among adults in Brazil, controlling for sociodemographic and occupational exposure to ototoxic agents. METHODS: This is a cross-sectional study based on data collected by the National Health Survey of 2013 in Brazil. A total of 60,202 individuals aged≥18 years were interviewed. Crude and adjusted prevalence ratios were calculated using the Poisson regression model with robust estimation of the variance. All analyzes were performed considering the appropriated weights imposed by the complex sample design. RESULTS: Hearing loss prevalence was 2.56% (95%CI: 2.34-2.79). It was higher in males, older age groups, white and individuals with lower levels of schooling. Diabetes was positively and significantly associated with hearing loss in the crude analysis (PRcrude = 2.92; 95%CI: 2.75-3.11) and also in the analysis adjusted for gender, age, skin color, schooling, smoking, alcohol consumption and occupational exposure (PRadj = 1.46; 95%CI: 1.32-1.61). CONCLUSIONS: The present results suggest that individuals with diabetes have higher prevalence of hearing impairment. There is the need of longitudinal studies to investigate if diabetes is a risk factor to hearing impairment.

Systematic review and mixed treatment comparison: dressings to heal diabetic foot ulcers.

AIMS/HYPOTHESIS: Foot ulcers in people with diabetes are a common and serious global health issue. Dressings form a key part of ulcer treatment. Existing systematic reviews are limited by the lack of head-to-head comparisons of alternative dressings in a field where there are several different dressing options. We aimed to determine the relative effects of alternative wound dressings on the healing of diabetic foot ulcers. METHODS: This study was a systematic review involving Bayesian mixed treatment comparison. We included randomised controlled trials evaluating the effects on diabetic foot ulcer healing of one or more wound dressings. There were no restrictions based on language or publication status. RESULTS: Fifteen eligible studies, evaluating nine dressing types, were included. Ten direct treatment comparisons were made. Whilst there was increased healing associated with hydrogel and foam dressings compared with basic wound contact materials, these findings were based on data from small studies at unclear or high risk of bias. The mixed treatment comparison suggested that hydrocolloid-matrix dressings were associated with higher odds of ulcer healing than all other dressing types; there was a high degree of uncertainty around these estimates, which were deemed to be of very low quality. CONCLUSIONS/INTERPRETATION: These findings summarise all available trial evidence regarding the use of dressings to heal diabetic foot ulcers. More expensive dressings may offer no advantages in terms of healing than cheaper basic dressings. In addition, evidence pointing to a difference in favour of 'advanced' dressing types over basic wound contact materials is of low or very low quality.

Economic evaluation of a randomized controlled trial of ultrasound therapy for hard-to-heal venous leg ulcers.

BACKGROUND: A pragmatic, multicentre randomized controlled trial (VenUS III) was conducted to determine whether low-dose ultrasound therapy increased the healing rate of hard-to-heal leg ulcers. This study was a cost-effectiveness analysis of the trial data. METHODS: Cost-effectiveness and cost-utility analyses were conducted alongside the VenUS III trial, in which patients were randomly allocated to either ultrasound treatment administered weekly for 12 weeks along with standard care, or standard care alone. The time horizon was 12 months and based on the UK National Health Service (NHS) perspective. RESULTS: The base-case analysis showed that ultrasound therapy added to standard care was likely to be more costly and provide no extra benefit over standard care alone. Individuals who received ultrasound treatment plus standard care took a mean of 14.7 (95 per cent confidence interval - 32.7 to 56.8) days longer to heal, had 0.009 (-0.042 to 0.024) fewer quality-adjusted life years and had higher treatment costs by £ 197.88 (-35.19 to 420.32). Based on these point estimates, ultrasound therapy plus standard care for leg ulcers was dominated by standard care alone. The analysis of uncertainty showed that this treatment strategy is unlikely to be cost-effective. CONCLUSION: Ultrasound treatment was not cost-effective for hard-to-heal leg ulcers and should not be recommended for adoption in the NHS.

Cost-effectiveness analysis of general anaesthesia versus local anaesthesia for carotid surgery (GALA Trial).

BACKGROUND: Health outcomes and costs are both important when deciding whether general (GA) or local (LA) anaesthesia should be used during carotid endarterectomy. The aim of this study was to assess the cost-effectiveness of carotid endarterectomy under LA or GA in patients with symptomatic or asymptomatic carotid stenosis for whom surgery was advised. METHODS: Using patient-level data from a large, multinational, randomized controlled trial (GALA Trial) time free from stroke, myocardial infarction or death, and costs incurred were evaluated. The cost-effectiveness outcome was incremental cost per day free from an event, within a time horizon of 30 days. RESULTS: A patient undergoing carotid endarterectomy under LA incurred fewer costs (mean difference pound178) and had a slightly longer event-free survival (difference 0.16 days, but the 95 per cent confidence limits around this estimate were wide) compared with a patient who had GA. Existing uncertainty did not have a significant impact on the decision to adopt LA, over a wide range of willingness-to-pay values. CONCLUSION: If cost-effectiveness was considered in the decision to adopt GA or LA for carotid endarterectomy, given the evidence provided by this study, LA is likely to be the favoured treatment for patients for whom either anaesthetic approach is clinically appropriate.