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Staphylococcus argenteus and Staphylococcus schweitzeri, previously known as divergent Staphylococcus aureus clonal lineages, have been recently established as novel, difficult-to-delimit, coagulase-positive species within the S. aureus complex. Methicillin-resistant strains of S. argenteus are known from Australia and the UK. Knowledge of their epidemiology, medical significance and transmission risk is limited and partly contradictory, hampering definitive recommendations. There is mounting evidence that the pathogenicity of S. argenteus is similar to that of 'classical' S. aureus , while as yet no S. schweitzeri infections have been reported. To provide decision support on whether and how to distinguish and report both species. PubMed, searched for S. argenteus and S. schweitzeri. This position paper reviews the main characteristics of both species and draws conclusions for microbiological diagnostics and surveillance as well as infection prevention and control measures. We propose not distinguishing within the S. aureus complex for routine reporting purposes until there is evidence that pathogenicity or clinical outcome differ markedly between the different species. Primarily for research purposes, suitably equipped laboratories are encouraged to differentiate between S. argenteus and S. schweitzeri. Caution is urged if these novel species are explicitly reported. In such cases, a specific comment should be added (i.e. 'member of the S.aureus complex') to prevent confusion with less- or non-pathogenic staphylococci. Prioritizing aspects of patient safety, methicillin-resistant isolates should be handled as recommended for methicillin-resistant Staphylococcus aureus (MRSA). In these cases, the clinician responsible should be directly contacted and informed by the diagnosing microbiological laboratory, as they would be for MRSA. Research is warranted to clarify the epidemiology, clinical impact and implications for infection control of such isolates. [ABSTRACT FROM AUTHOR]

Introduction: To contribute to addressing diagnostic health inequalities in the United Kingdom, this review aimed to investigate determinants of diagnostic service use amongst people experiencing high deprivation in the United Kingdom. Methods: A systematic review was conducted using three databases (EBSCO, Web of Science and SCOPUS) to search studies pertaining to diagnostic service use amongst people experiencing high deprivation. Search terms related to diagnostics, barriers and facilitators to access and deprivation. Articles were included if they discussed facilitators and/or barriers to diagnostic service access, contained participants' direct perspectives and focussed on individuals experiencing high deprivation in the United Kingdom. Articles were excluded if the full text was unretrievable, only abstracts were available, the research did not focus on adults experiencing high deprivation in the United Kingdom, those not including participants' direct perspectives (e.g., quantitative studies) and papers unavailable in English. Results: Of 14,717 initial papers, 18 were included in the final review. Determinants were grouped into three themes (Beliefs and Behaviours, Emotional and Psychological Factors and Practical Factors), made up of 15 sub‐themes. These were mapped to a conceptual model, which illustrates that Beliefs and Behaviours interact with Emotional and Psychological Factors to influence Motivation to access diagnostic services. Motivation then influences and is influenced by Practical Factors, resulting in a Decision to Access or Not. This decision influences Beliefs and Behaviours and/or Emotional and Psychological Factors such that the cycle begins again. Conclusion: Decision‐making regarding diagnostic service use for people experiencing high deprivation in the United Kingdom is complex. The conceptual model illustrates this complexity, as well as the mediative, interactive and iterative nature of the process. The model should be applied in policy and practice to enable understanding of the factors influencing access to diagnostic services and to design interventions that address identified determinants. Patient or Public Contribution: Consulting lived experience experts was imperative in understanding whether and how the existing literature captures the lived experience of those experiencing high deprivation in South England. The model was presented to lived experience experts, who corroborated findings, highlighted significant factors for them and introduced issues that were not identified in the review. [ABSTRACT FROM AUTHOR]

This paper presents a methodology that is designed for rapid exploratory analysis of the outputs from ensembles of climate models, especially when these outputs consist of maps. The approach formalizes and extends the technique of "intermodel empirical orthogonal function" analysis, combining multivariate analysis of variance techniques with singular value decompositions (SVDs) of structured components of the ensemble data matrix. The SVDs yield spatial patterns associated with these components, which we call ensemble principal patterns (EPPs). A unique hierarchical partitioning of variation is obtained for balanced ensembles in which all combinations of factors, such as GCM and RCM pairs in a regional ensemble, appear with equal frequency: suggestions are also proposed to handle unbalanced ensembles without imputing missing values or discarding runs. Applications include the selection of ensemble members to propagate uncertainty into subsequent analyses, and the diagnosis of modes of variation associated with specific model variants or parameter perturbations. The approach is illustrated using outputs from the EuroCORDEX regional ensemble over the United Kingdom. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is the most common cancer among men. Diagnosis and risk stratification of prostate cancer can be challenging due to gaps in our understanding of the disease as well as the limitations of tests used in clinical practice. Extracellular vesicles are microscopic particles containing genetic material, proteins and other molecules that are released by cells. Urine contains extracellular vesicles which can originate from the prostate gland. This review addresses how extracellular vesicles are involved in the development of prostate cancer, as well as how urinary extracellular vesicles can be analysed to diagnose and monitor prostate cancer. Prostate cancer is the most common non-cutaneous cancer among men in the UK, causing significant health and economic burdens. Diagnosis and risk prognostication can be challenging due to the genetic and clinical heterogeneity of prostate cancer as well as uncertainties in our knowledge of the underlying biology and natural history of disease development. Urinary extracellular vesicles (EVs) are microscopic, lipid bilayer defined particles released by cells that carry a variety of molecular cargoes including nucleic acids, proteins and other molecules. Urine is a plentiful source of prostate-derived EVs. In this narrative review, we summarise the evidence on the function of urinary EVs and their applications in the evolving field of prostate cancer diagnostics and active surveillance. EVs are implicated in the development of all hallmarks of prostate cancer, and this knowledge has been applied to the development of multiple diagnostic tests, which are largely based on RNA and miRNA. Common gene probes included in multi-probe tests include PCA3 and ERG, and the miRNAs miR-21 and miR-141. The next decade will likely bring further improvements in the diagnostic accuracy of biomarkers as well as insights into molecular biological mechanisms of action that can be translated into opportunities in precision uro-oncology. [ABSTRACT FROM AUTHOR]

Background: On admission to hospital, patients with community-acquired pneumonia (CAP), undergo extensive diagnostic testing. Two high-throughput laboratory-based PCR panels which return a result in 5.5 hours (h) have been developed to test for pathogens commonly associated with upper (Respiratory 1 Panel) and lower (Respiratory 3 Panel) respiratory tract infections (GeneFirst, Oxford). These could replace multiple diagnostic tests currently used. Methods: An online survey, completed by senior clinicians in the UK, France and Spain, was used to collect data on the diagnostic testing of immunocompetent and immunocompromised adults admitted to hospital with CAP, including the cost of diagnostics. Data were used to inform a cost-comparison model. For each country, the average cost of diagnostic testing per patient was calculated separately for immunocompetent and immunocompromised patients. The model compared three testing strategies with standard of care (SoC). In the Panel 1 strategy, the Respiratory 1 Panel was used for patients that would otherwise have tests which could be replaced by Respiratory 1 Panel, equivalent strategies for Respiratory 3 Panel and for both panels combined were assessed. Results: In total, 48 surveys were completed (UK = 17; France = 15; Spain = 16). Compared with SoC, the Panel 1 + 3 strategy was most favourable, resulting in cost savings for immunocompetent and immunocompromised patients respectively, of €22.09 (£18.50) and €26.12 (£21.88) in the UK, €99.60 and €108.77 in France and €27.07 and €51.87 in Spain. Conclusion: In all three countries, the use of these respiratory panels could reduce the average cost of diagnostics used for patients admitted to hospital with CAP. [ABSTRACT FROM AUTHOR]

Colistin is a last resort drug for the treatment of multiple drug-resistant (MDR) Gram-negative bacterial infections. Rapid methods to detect resistance are highly desirable. Here, we evaluated the performance of a commercially available MALDI-TOF MS-based assay for colistin resistance testing in Escherichia coli at two different sites. Ninety clinical E. coli isolates were provided by France and tested in Germany and UK using a MALDI-TOF MS-based colistin resistance assay. Lipid A molecules of the bacterial cell membrane were extracted using the MBT Lipid Xtract Kit™ (RUO; Bruker Daltonics, Germany). Spectra acquisition and evaluation were performed by the MBT HT LipidART Module of MBT Compass HT (RUO; Bruker Daltonics) on a MALDI Biotyper® sirius system (Bruker Daltonics) in negative ion mode. Phenotypic colistin resistance was determined by broth microdilution (MICRONAUT MIC-Strip Colistin, Bruker Daltonics) and used as a reference. Comparing the results of the MALDI-TOF MS-based colistin resistance assay with the data of the phenotypic reference method for the UK, sensitivity and specificity for the detection of colistin resistance were 97.1% (33/34) and 96.4% (53/55), respectively. Germany showed 97.1% (33/34) sensitivity and 100% (55/55) specificity for the detection of colistin resistance by MALDI-TOF MS. Applying the MBT Lipid Xtract™ Kit in combination with MALDI-TOF MS and dedicated software showed excellent performances for E. coli. Analytical and clinical validation studies must be performed to demonstrate the performance of the method as a diagnostic tool. [ABSTRACT FROM AUTHOR]

This paper analyses the politics of regulatory expansion within the diagnostics sector. Since 1990, an informal, clinician-led process of diagnostic innovation within the UK NHS has been challenged by new mechanisms for the evaluation of diagnostics. We describe these diagnostic reforms as a process of fragmented regulatory expansion. New governance mechanisms function as regulatory niches : discrete spaces within an overarching sociotechnical regime. The boundaries of regulatory niches are organisational and epistemological. Organisational boundaries map onto established communities of practice that constitute the regulatory target; epistemological boundaries are defined by distinctive evaluation frameworks. Niches are also distinguished by their outcomes (rate of positive decisions) and their origins. Niche formation was triggered by five drivers: public scandal; technological change; marketisation; institutional isomorphism; and transnational policy transfer. Each niche was triggered by a unique confluence of these drivers, but common to all were historic shifts in healthcare politics, as the rise of evidence-based medicine intersected with the centralising impulse of the regulatory state, which encroached on clinical autonomy in a contest for power that is increasingly mediated by influential non-governmental organisations. • Regulation of diagnostics in the UK has undergone a process of fragmented expansion. • Three "regulatory niches" have emerged since the 1990s. • Regulatory niches are discrete spaces within the overarching sociotechnical regime. • Each niche has specific organisational and epistemological boundaries. • They differ in outcomes (rates of regulatory approval) and origins. [ABSTRACT FROM AUTHOR]

Summary: Diagnostic testing is routinely performed by the equine clinician when dealing with suspected infectious disease cases and outbreaks. Optimal sample timing, choice and handling are fundamental to attain an accurate diagnosis, and a good understanding of laboratory‐based sample analysis techniques, and their validation is necessary for effective diagnostic test result interpretation. This two‐part series highlights the importance of interpreting results bearing testing limitations and specific clinical findings in mind, and on these foundations, the treating clinician should always be well placed to deal with equine infectious diseases. Part 1 in this series will provide a treating clinician with an overview of the importance of testing horses in infectious disease outbreaks and how this is achieved. The different laboratory testing options available for agent detection and their methods will also be discussed. Part 2 will summarise serological (antibody) testing techniques, sample processing (including how tests are performed and validated) and result interpretation. [ABSTRACT FROM AUTHOR]

Aims: Application of advanced molecular pathology in rare tumours is hindered by low sample numbers, access to specialised expertise/technologies and tissue/assay QC and rapid reporting requirements. We assessed the feasibility of co‐ordinated real‐time centralised pathology review (CPR), encompassing molecular diagnostics and contemporary genomics (RNA‐seq/DNA methylation‐array). Methods: This nationwide trial in medulloblastoma (<80 UK diagnoses/year) introduced a national reference centre (NRC) and assessed its performance and reporting to World Health Organisation standards. Paired frozen/formalin‐fixed, paraffin‐embedded tumour material were co‐submitted from 135 patients (16 referral centres). Results: Complete CPR diagnostics were successful for 88% (120/135). Inadequate sampling was the most common cause of failure; biomaterials were typically suitable for methylation‐array (129/135, 94%), but frozen tissues commonly fell below RNA‐seq QC requirements (53/135, 39%). Late reporting was most often due to delayed submission. CPR assigned or altered histological variant (vs local diagnosis) for 40/135 tumours (30%). Benchmarking/QC of specific biomarker assays impacted test results; fluorescent in‐situ hybridisation most accurately identified high‐risk MYC/MYCN amplification (20/135, 15%), while combined methods (CTNNB1/chr6 status, methylation‐array subgrouping) best defined favourable‐risk WNT tumours (14/135; 10%). Engagement of a specialist pathologist panel was essential for consensus assessment of histological variants and immunohistochemistry. Overall, CPR altered clinical risk‐status for 29% of patients. Conclusion: National real‐time CPR is feasible, delivering robust diagnostics to WHO criteria and assignment of clinical risk‐status, significantly altering clinical management. Recommendations and experience from our study are applicable to advanced molecular diagnostics systems, both local and centralised, across rare tumour types, enabling their application in biomarker‐driven routine diagnostics and clinical/research studies. [ABSTRACT FROM AUTHOR]

The challenge to balance limited resources with infinite demand has encouraged an evolution in the way health care services are managed and operated. Chronic wound management is complex and prolonged, and places a considerable financial burden on health services. A typical driver of cost includes the necessity to change dressings on a regular basis. Over the last few decades, several scientific and biological advances have furthered the development of wound care products and facilitated wound management. This article investigates some of the major advancements that have occurred within the wound-care arena during the last 5 years and how these advancements are being translated to provide better delivery of clinical care to patients. [ABSTRACT FROM AUTHOR]

This is the first record of a fish nidovirus isolated from a consignment of goldfish at the United Kingdom (UK) border. The full-length viral genome was 25,985 nt, sharing a 97.9% nucleotide identity with the Chinook salmon bafinivirus (CSBV) NIDO with two deletions of 537 and 480 nt on the ORF Ia protein. To assess the potential impact on UK fish species, Atlantic salmon, common carp and goldfish were exposed to the virus via an intraperitoneal (IP) injection and bath challenge. Moribundity was recorded in only 8% of IP-injected goldfish. A high viral load, ≈107 of the CSBV PpIa gene, was measured in the kidney of moribund goldfish. Mild histopathological changes were observed in the kidneys of challenged carps. Ultrastructural observations in renal tubule epithelial cells of goldfish showed cylindrical tubes (≈15 nm in diameter) and tubular structures budding spherical virions (≈200 nm in diameter) with external spike-like structures. Negative staining showed both circular and bacilliform virions. Seroconversion was measured in common carp and goldfish but not in Atlantic salmon. This study reinforces the potential risk of novel and emerging pathogens being introduced to recipient countries via the international ornamental fish trade and the importance of regular full health screens at the border inspection posts to reduce this risk. [ABSTRACT FROM AUTHOR]

Background: Commissioning innovative health technologies is typically complex and multi-faceted. Drawing on the negotiated order perspective, we explore the process by which commissioning organisations make their decisions to commission innovative health technologies. The empirical backdrop to this discussion is provided by a case study exploring the commissioning considerations for a new photoplethysmography-based diagnostic technology for peripheral arterial disease in primary care in the UK.Methods: The research involved an empirical case study of four Clinical Commissioning Groups (CCGs) involved in the commissioning of services in primary and secondary care. Semi-structured in-depth interviews (16 in total) and two focus groups (a total of eight people participated, four in each group) were conducted with key individuals involved in commissioning services in the NHS including (i) senior NHS clinical leaders and directors (ii) commissioners and health care managers across CCGs and (iii) local general practitioners.Results: Commissioning of a new diagnostic technology for peripheral arterial disease in primary care involves high levels of protracted negotiations over funding between providers and commissioners, alliance building, conflict resolution and compromise of objectives where the outcomes of change are highly contingent upon interventions made across different care settings. Our evidence illustrates how reconfigurations of inter-organisational relations, and of clinical and related work practices required for the successful implementation of a new technology could become the major challenge in commissioning negotiations.Conclusions: Innovative health technologies such as the diagnostic technology for peripheral arterial disease are commissioned in care pathways where the value of such technology is realised by those delivering care to patients. The detail of how care pathways are commissioned is complex and involves high degrees of uncertainty concerning such issues as prioritisation decisions, patient benefits, clinical buy-in, value for money and unintended consequences. Recent developments in the new care models and integrated care systems (ICSs) in the UK offer a unique opportunity for the successful commissioning arrangements of innovative health technologies in primary care such as the new diagnostic technology for peripheral arterial disease. [ABSTRACT FROM AUTHOR]