Assessment of twelve echovirus virus-neutralisation assays in Europe: recommendations for harmonisation of non-polio enterovirus sero-surveillance studies.

Non-polio enteroviruses (NPEV) cause significant disease worldwide. Population-based sero-surveillance, by measuring antibodies against specific NPEV types, provides additional information on past circulation and the prediction for future upsurges. Virus neutralisation assays (VNA), the current method of choice for measuring NPEV type specific antibodies, are not entirely standardised. Via the European Non-Polio Enterovirus Network, we organised a VNA quality assessment in which twelve laboratories participated. We provided five echovirus (E) types (E1, E18, E30 G2, E30 G6 and E6) and intravenous immunoglobulins (IVIG) as a sample for the NPEV VNA quality assessment. Differences in VNA protocols and neutralising Ab (nAb) titres were found between the participating laboratories with geometric coefficients of variation ranging from 10.3-62.9 %. Mixed-effects regression analysis indicated a small but significant effect of type of cell line used. Harmonisation of cell line passage number, however, did not improve variation between laboratories. Calibration by making use of a reference sample, reduced variation between laboratories but differences in nAb titres remained higher than two log2 dilution steps. In conclusion, sero-surveillance data from different laboratories should be compared with caution and standardised protocols are needed.

Myths and Methodologies: Standardisation in human physiology research-should we control the controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

The Getting It right First Time (GIRFT) programme in urology; rationale and methodology.

The Getting It Right First Time (GIRFT) programme is a quality improvement initiative covering the National Health Service in England. The programme aims to standardise clinical practices and improve patient and system level outcomes by utilising data-driven insights and clinically-led recommendations. There are GIRFT workstreams for every medical and surgical specialty, including urology. Defining features of the GIRFT methodology are that it is clinically led by experienced clinicians, data-driven, and specialty specific. Each specialty workstream conducts deep-dive visits to every hospital, analysing performance data and engaging with clinicians and management to identify and share improvement priorities. For urology, GIRFT has completed deep-dive visits and published reports outlining priority areas for development. Reports include recommendations pertaining to streamlining care pathways, reducing the acuity of care environments, enhancing emergency services, optimising utilisation of outpatient services, and workforce training and utilisation. The GIRFT academy provides guides for implementing best practices specific to priority areas of care. These include important disease pathways, and GIRFT-advocated innovations such as urology investigation units and urology area networks. GIRFT offers clinical transformation, cost reduction, equity in access to care, and leaner models of care that are often more environmentally sustainable. Evaluation efforts of the programme have focussed on assessing the adoption of GIRFT recommendations, understanding barriers to change, and modelling the climate impact of advocated practices.

Standardisation and harmonisation of thyroid-stimulating hormone measurements: historical, current, and future perspectives.

Thyroid-stimulating hormone (TSH) is an important clinical marker in the diagnosis and management of thyroid disease. TSH measurements are reported in milli-International Units per Litre (mIU/L), traceable to a World Health Organisation (WHO) reference material. There is a wide variety of commercial immunoassays for TSH measurements available, which have historically been poorly harmonised due to a lack of commutability of the WHO reference materials with patient samples. This led to the recent development of a serum-based reference panel for TSH, traceable to the WHO reference material, available via the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC), aimed at harmonisation of TSH immunoassays. This report describes recent developments in the TSH reference system, including establishment of the 4th WHO International Standard for TSH, and aims to clarify the relationship between the available reference materials and their intended uses. This 4th WHO IS is widely available and defines the unit of TSH activity, therefore its continued existence is of paramount importance, however it continues to show a lack of commutability with patient in many TSH immunoassays. This makes the C-STFT TSH panel, albeit available in restricted numbers, a critical resource to ensure better TSH assay harmonisation.

Artificial intelligence for ultrasound scanning in regional anaesthesia: a scoping review of the evidence from multiple disciplines.

BACKGROUND: Artificial intelligence (AI) for ultrasound scanning in regional anaesthesia is a rapidly developing interdisciplinary field. There is a risk that work could be undertaken in parallel by different elements of the community but with a lack of knowledge transfer between disciplines, leading to repetition and diverging methodologies. This scoping review aimed to identify and map the available literature on the accuracy and utility of AI systems for ultrasound scanning in regional anaesthesia. METHODS: A literature search was conducted using Medline, Embase, CINAHL, IEEE Xplore, and ACM Digital Library. Clinical trial registries, a registry of doctoral theses, regulatory authority databases, and websites of learned societies in the field were searched. Online commercial sources were also reviewed. RESULTS: In total, 13,014 sources were identified; 116 were included for full-text review. A marked change in AI techniques was noted in 2016-17, from which point on the predominant technique used was deep learning. Methods of evaluating accuracy are variable, meaning it is impossible to compare the performance of one model with another. Evaluations of utility are more comparable, but predominantly gained from the simulation setting with limited clinical data on efficacy or safety. Study methodology and reporting lack standardisation. CONCLUSIONS: There is a lack of structure to the evaluation of accuracy and utility of AI for ultrasound scanning in regional anaesthesia, which hinders rigorous appraisal and clinical uptake. A framework for consistent evaluation is needed to inform model evaluation, allow comparison between approaches/models, and facilitate appropriate clinical adoption.

Leading in the development, standardised evaluation, and adoption of artificial intelligence in clinical practice: regional anaesthesia as an example.

A recent study by Suissa and colleagues explored the clinical relevance of a medical image segmentation metric (Dice metric) commonly used in the field of artificial intelligence (AI). They showed that pixel-wise agreement for physician identification of structures on ultrasound images is variable, and a relatively low Dice metric (0.34) correlated to a substantial agreement on subjective clinical assessment. We highlight the need to bring structure and clinical perspective to the evaluation of medical AI, which clinicians are best placed to direct.

Demonstrating the reliability of in vivo metabolomics based chemical grouping: towards best practice.

While grouping/read-across is widely used to fill data gaps, chemical registration dossiers are often rejected due to weak category justifications based on structural similarity only. Metabolomics provides a route to robust chemical categories via evidence of shared molecular effects across source and target substances. To gain international acceptance, this approach must demonstrate high reliability, and best-practice guidance is required. The MetAbolomics ring Trial for CHemical groupING (MATCHING), comprising six industrial, government and academic ring-trial partners, evaluated inter-laboratory reproducibility and worked towards best-practice. An independent team selected eight substances (WY-14643, 4-chloro-3-nitroaniline, 17α-methyl-testosterone, trenbolone, aniline, dichlorprop-p, 2-chloroaniline, fenofibrate); ring-trial partners were blinded to their identities and modes-of-action. Plasma samples were derived from 28-day rat tests (two doses per substance), aliquoted, and distributed to partners. Each partner applied their preferred liquid chromatography-mass spectrometry (LC-MS) metabolomics workflows to acquire, process, quality assess, statistically analyze and report their grouping results to the European Chemicals Agency, to ensure the blinding conditions of the ring trial. Five of six partners, whose metabolomics datasets passed quality control, correctly identified the grouping of eight test substances into three categories, for both male and female rats. Strikingly, this was achieved even though a range of metabolomics approaches were used. Through assessing intrastudy quality-control samples, the sixth partner observed high technical variation and was unable to group the substances. By comparing workflows, we conclude that some heterogeneity in metabolomics methods is not detrimental to consistent grouping, and that assessing data quality prior to grouping is essential. We recommend development of international guidance for quality-control acceptance criteria. This study demonstrates the reliability of metabolomics for chemical grouping and works towards best-practice.

An international perspective on young stroke incidence and risk factors: a scoping review.

BACKGROUND: Stroke among younger age groups is increasing globally. While there is a focus on research conducted on people under 65 years who have had a stroke, there is a paucity of data on the incidence and risk factors of stroke among younger people (≤ 30 years). This scoping review examines evidence on incidence and risk factors for perinatal, paediatric and young adult stroke globally. METHODS: The review was guided by the Joanna Briggs Institute's scoping review methodology. A systematic search was conducted on 23rd March 2022 across Medline Ovid, Embase, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The eligibility criteria included all study designs providing information on the incidence and risk factors of stroke among young people (≤ 30 years) in the last ten years. RESULTS: A total of 5750 articles were identified. After screening, 471 articles (224 cohort studies (47.6%), 164 case studies/case series (34.8%), 35 reviews (7.4%), 30 case-control (6.4%) and 18 combinations of designs (3.8%) were included. There was data from 50 different countries, 199 studies were from high-income countries, upper and middle income (n = 38), lower middle-income (n = 39), low-income (n = 3) countries, international study (n = 7) and a further 185 articles did not state the country of research. Most of the studies (63%) focused on risk factors while incidence constituted 37%. Incidence data were reported heterogeneously across studies, leading to an inability to synthesise data. The three most frequently reported risk factors for perinatal stroke were infections, cardiac conditions, and intrapartum factors. Vasculopathies, infection and cardiac conditions accounted for most reported risk factors for paediatric stroke, while chronic conditions such as diabetes mellitus, vasculopathies and cardiac conditions accounted for the most reported risk factors among young adults. CONCLUSION: This review has highlighted different stroke risk factors for each age cohort of people under 30 years. The low number of epidemiological studies suggests that further research of this type is needed to fully understand the incidence and risk factors in young stroke. A standardised reporting of age groupings of incidence data is imperative to enable the comparison of data from different geographical locations.

The Need for European Surveillance of CDI.

Since the turn of the millennium, the epidemiology of Clostridioides difficile infection (CDI) has continued to challenge. Changes in clinical presentation, severity of disease, descriptions of new risk factors and the occurrence of outbreaks all emphasised the importance of early diagnosis and standardised surveillance systems. However, a lack of consensus on case definitions, clinical guidelines and optimal laboratory diagnostics across Europe has led to the underestimation of CDI and impeded comparison between countries. These inconsistencies have prevented the true burden of disease from being appreciated.Acceptance that a multi-country CDI surveillance program and optimised diagnostic strategies are required has built the foundations for a more robust, unified surveillance. The concerted efforts of the European Centre for Disease Prevention and Control (ECDC) CDI networks led to the development of the European surveillance protocol and an over-arching long-term CDI surveillance strategy for 2014-2020, which has been followed by the development of surveillance systems in at least 20 European countries. However, surveillance activities in individual countries have slowed during the COVID-19 pandemic as resources were diverted to the global health crisis. A renewed and strengthened focus on CDI surveillance and prevention is therefore urgently needed post COVID-19.

Race in clinical trials in Sweden: How regulatory and medical standards in clinical research trump the post-racial discourse.

The post-racial discourse that permeates many Western European countries depicts society as having moved beyond race concepts and classifications. This article focuses on Sweden, a country that, in line with the post-racial thinking, declares race to be an offensive and unscientific concept. The article investigates what happens when this post-racial discourse meets clinical research standards that encourage, if not demand, the collection of data on patient race. Through an analysis of the reporting of patient race in 76 multinational trials with at least one study site in Sweden, and a review of the regulatory and medical standards and trial documents that direct the collection of patient race in trials, we show how race classification is kept intact in trials despite conflicting with post-racial norms and conventions. Notably, our findings diverge from the way racialisation is typically assumed to work in Sweden and related countries. We argue this is possible because the two incompatible understandings of race are 'distributed' (Mol, 2002, The body multiple: Ontology in medical practice, Duke University Press) among different social worlds. The distribution, we propose, is upheld through the paucity of major debate on why and how race classification should be carried out in clinical trials in Europe as this allows contradictions to remain unspoken.