Analytical performance specifications based on biological variation data - considerations, strengths and limitations.

Analytical performance specifications (APS) are typically established through one of three models: (i) outcome studies, (ii) biological variation (BV), or (iii) state-of-the-art. Presently, The APS can, for most measurands that have a stable concentration, be based on BV. BV based APS, defined for imprecision, bias, total allowable error and allowable measurement uncertainty, are applied to many different processes in the laboratory. When calculating APS, it is important to consider the different APS formulae, for what setting they are to be applied and if they are suitable for the intended purpose. In this opinion paper, we elucidate the background, limitations, strengths, and potential intended applications of the different BV based APS formulas. When using BV data to set APS, it is important to consider that all formulae are contingent on accurate and relevant BV estimates. During the last decade, efficient procedures have been established to obtain reliable BV estimates that are presented in the EFLM biological variation database. The database publishes detailed BV data for numerous measurands, global BV estimates derived from meta-analysis of quality-assured studies of similar study design and automatic calculation of BV based APS.

A standard to report biological variation data studies - based on an expert opinion.

There is a need for standards for generation and reporting of Biological Variation (BV) reference data. The absence of standards affects the quality and transportability of BV data, compromising important clinical applications. To address this issue, international expert groups under the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) have developed an online resource (https://tinyurl.com/bvmindmap) in the form of an interactive mind map that serves as a guideline for researchers planning, performing and reporting BV studies. The mind map addresses study design, data analysis, and reporting criteria, providing embedded links to relevant references and resources. It also incorporates a checklist approach, identifying a Minimum Data Set (MDS) to enable the transportability of BV data and incorporates the Biological Variation Data Critical Appraisal Checklist (BIVAC) to assess study quality. The mind map is open to access and is disseminated through the EFLM BV Database website, promoting accessibility and compliance to a reporting standard, thereby providing a tool to be used to ensure data quality, consistency, and comparability of BV data. Thus, comparable to the STARD initiative for diagnostic accuracy studies, the mind map introduces a Standard for Reporting Biological Variation Data Studies (STARBIV), which can enhance the reporting quality of BV studies, foster user confidence, provide better decision support, and be used as a tool for critical appraisal. Ongoing refinement is expected to adapt to emerging methodologies, ensuring a positive trajectory toward improving the validity and applicability of BV data in clinical practice.

A simple system change to reduce delays in emergency calls for assistance during anaesthesia in the operating theatre.

Promptly calling for assistance in an anaesthetic emergency is important. However, emergency call systems are not present in all locations where anaesthesia is administered, and in those that do have an emergency call system, the call button is often obscured by other equipment or in an unfamiliar location. Placing a red stripe from the ceiling, down the wall, to the emergency call button significantly reduces delays in activating an emergency call, demonstrating a simple but effective system change to the layout of operating theatres.

Psychology in the operating theatre: the importance of colour and cognition in the redesign of clinical systems for medication safety.

Medication errors in anaesthesia remain a leading cause of patient harm. Compared with conventional methods, use of the international colour-code standard on syringes and medication trays allows significantly more errors to be detected, and does so under conditions of cognitive load. Testing methods from experimental psychology provide important new insights for human factors research in anaesthesia and health care.

Teamwork matters: team situation awareness to build high-performing healthcare teams, a narrative review.

Healthcare today is the prerogative of teams rather than of individuals. In acute care domains such as anaesthesia, intensive care, and emergency medicine, the work is complex and fast-paced, and the team members are diverse and interdependent. Three decades of research into the behaviours of high-performing teams provides us with clear guidance on team training, demonstrating positive effects on patient safety and staff wellbeing. Here we consider team performance through the lens of situation awareness. Maintaining situation awareness is an absolute requirement for safe and effective patient management. Situation awareness is a dynamic process of perceiving cues in the environment, understanding what they mean, and predicting how the situation may evolve. In the context of acute clinical care, situation awareness can be improved if the whole team actively contributes to monitoring the environment, processing information, and planning next steps. In this narrative review, we explore the concept of situation awareness at the level of the team, the conditions required to maintain team situation awareness, and the relationship between team situation awareness, shared mental models, and team performance. Our ultimate goal is to help clinicians create the conditions required for high-functioning teams, and ultimately improve the safety of clinical care.

Systems, safety, and anaesthesia outside the operating room.

An increasing number of patients are receiving sedation or anaesthesia in locations outside of the operating room. Compared with the operating room, anaesthesia providers working in a non-operating room anaesthesia (NORA) location report significantly lower perceived levels of safety, and higher levels of anxiety, stress, and workload. These results are likely to affect the well-being of staff in NORA locations and are clinically relevant in terms of patient safety.

Anaesthesia and patient safety in the socio-technical operating theatre: a narrative review spanning a century.

We review the development of technology in anaesthesia over the course of the past century, from the invention of the Boyle apparatus to the modern anaesthetic workstation with artificial intelligence assistance. We define the operating theatre as a socio-technical system, being necessarily comprised of human and technological parts, the ongoing development of which has led to a reduction in mortality during anaesthesia by an order of four magnitudes over a century. The remarkable technological advances in anaesthesia have been accompanied by important paradigm shifts in the approach to patient safety, and we describe the inter-relationship between technology and the human work environment in the development of such paradigm shifts, including the systems approach and organisational resilience. A better understanding of emerging technological advances and their effects on patient safety will allow anaesthesia to continue to be a leader in both patient safety and in the design of equipment and workspaces.

Take action now to prevent medication errors: lessons from a fatal error involving an automated dispensing cabinet.

An error in the administration of an anaesthetic medication related to an automated dispensing cabinet resulted in a patient fatality and a highly publicised criminal prosecution of a healthcare worker, which concluded in 2022. Urgent action is required to re-engineer systems and workflows to prevent such errors. Exhortation, blame, and criminal prosecution are unlikely to advance the cause of patient safety.

Interlaboratory comparison study of immunosuppressant analysis using a fully automated LC-MS/MS system.

OBJECTIVES: All guidelines recommend LC-MS/MS as the analytical method of choice for the quantification of immunosuppressants in whole blood. Until now, the lack of harmonization of methods and the complexity of the analytical technique have prevented its widespread use in clinical laboratories. This can be seen in international proficiency schemes, where more than half of the participants used immunoassays. With the Cascadion SM Clinical analyzer (Thermo Fisher Scientific, Oy, Vantaa, FI) a fully automated LC-MS/MS system has been introduced, which enables the use of LC-MS/MS without being an expert in mass spectrometry. METHODS: To verify the interlaboratory comparison of the immunosuppressant assay on this type of instrument, three centers across Europe compared 1097 routine whole blood samples, each site sharing its own samples with the other two. In other experiments, the effects of freezing and thawing of whole blood samples was studied, and the use of secondary cups instead of primary tubes was assessed. RESULTS: In the Bland-Altman plot, the comparison of the results of tacrolimus in fresh and frozen samples had an average bias of only 0.36%. The respective data for the comparison between the primary and secondary tubes had an average bias of 1.14%. The correlation coefficients for patient samples with cyclosporine A (n=411), everolimus (n=139), sirolimus (n=114) and tacrolimus (n=433) were 0.993, 0.993, 0.993 and 0.990, respectively. CONCLUSIONS: The outcome of this study demonstrates a new level of result harmonization for LC-MS/MS based immunosuppressant analysis with a commercially available fully automated platform for routine clinical application.

Patient monitoring, wearable devices, and the healthcare information ecosystem.

Conventional patient vital signs monitoring fails to detect many signs of patient deterioration, including those in the critical postoperative period. Wearable monitors can allow continuous vital signs monitoring, send data wirelessly to the electronic healthcare record, and reduce the number of unplanned admissions to intensive care.

Quality improvement in New Zealand pediatric anesthesia: National quality direction, patient experience, equity, and collaboration.

The current priorities of the quality and safety of patient care in New Zealand at a central government level are described, with a focus on equity and patient experience. Priorities between stakeholders differ. We report the current quality activities of New Zealand pediatric anesthetists in relation to these governance aims, seeking gaps and suggesting future directions to align governance priorities and local activities. International relevance is also outlined. New Zealand Maori experience health inequity. Complex systemic factors including those of systemic racism and prejudice contribute to the inequity. The specific contributions to health inequity from pediatric anesthetists are unknown but could include aspects of cultural safety, delays in treatment and treatment deficits. Patient experience is correlated positively with other quality domains. Peri-operative patient experience tools require outcomes of interest that matter to patients, including relevant cultural safety domains. Risk identification and critical event review contribute to local learnings in departments and institutions, and more widely to national and binational (with Australia) learnings. Several collaborative projects in Australia and New Zealand, whilst not primarily quality improvement projects, may improve pediatric anesthesia. These collaborations include a pediatric anesthesia professional network, a curriculum for a pediatric anesthetic fellowship, contributions to a document on standards for pediatric anesthesia, and a national quality group researching key performance indicators across New Zealand.

The evolution of methods to estimate the rate of medication error in anaesthesia.

The rate of medication errors in anaesthesia is a critical safety indicator but the methods to estimate this metric are imperfect. A number of factors that are difficult to control impact their incidence. Newer methods involving computerised records are improving retrospective and real-time monitoring of medication errors.

Need for a new paradigm in the design of alarms for patient monitors and medical devices.

Modern computerised medical devices emit large numbers of tone-based alerts and alarms. Notifications that comprise auditory icons or natural human speech substantially increase the psychological salience of alerts and alarms and may allow a larger set of notifications to be used, as they do not require memorisation of arbitrary sounds.

The efficacy of mindful practice in improving diagnosis in healthcare: a systematic review and evidence synthesis.

Despite a variety of definitions of mindfulness, over the past 20 years there have been increasing claims that mindful practice is helpful in improving the accuracy of clinical diagnosis. We performed a systematic review and evidence synthesis in order to: determine the nature and definitions of mindful practice and associated terms; evaluate the quality of evidence for the benefits of mindful practice; and conclude whether mindful practice may reduce diagnostic error. We screened 14397 refereed reports from the five common literature databases, to include 33 reports related to the use of mindful practice in clinical diagnosis. Our evidence synthesis contained no randomised controlled trials (level I evidence) of mindful practice, the majority of supporting evidence (26 reports or 79%) comprised conceptual commentary or opinion (level IV evidence). However, 2 supporting reports constituted controlled studies without randomisation (level IIa), 1 report was quasi-experimental (level IIb), and 4 reports were comparative studies (level III). Thus, we may tentatively conclude that mindful practice appears promising as a method of improving diagnostic accuracy, but that further definitive studies of efficacy are required. We identified a taxonomy of 71 terms related to mindful practice, 7 of which were deemed core terms due to being each cited 5 times or more. The 7 core terms appear to be sufficient to describe the findings at higher levels of evidence in our evidence synthesis, suggesting that future definitive studies of mindful practice should focus on these common core terms in order to promote more generalisable findings.

How might access to postgraduate medical education in regional and rural locations be best improved? A scoping review.

Rural medical education is known as one of the most effective strategies in improving rural recruitment and retention. The aim was to identify modes of delivery to improve access to rural postgraduate medical education. Arksey and O'Malley's methodological framework was used for conducting scoping reviews. CINAHL, Google Scholar, ERIC, PsycINFO, Medline and PubMed were searched to identify peer-reviewed English-language literature published between 2000 and 2019 focusing on postgraduate rural and regional medical education. A total of 102 articles were identified, with 51 included in the final analysis after applying inclusion and exclusion criteria. Outcome measures included: article type; research methodology; date of publication; country of origin; and study population. Through iterative reading, common themes were identified. A typology of 6 content themes emerged as follows: rural curriculum; procedural skills; rurally based learning; service delivery; workforce; and distance learning. The majority of articles focused on rural curriculum, and rurally based learning, with half originating from Australia or New Zealand. Although results strongly emphasised context and curriculum in rural environments, lack of specific and pragmatic approaches was noted. Surprisingly, few articles focused on rural distance learning utilising information and communication technology. Pathways to improve rural education access include recognition of the unique rural context in curriculums; development of rural educational faculty; and creation of opportunities for rural specialist training. Emphasis should be given for education provided through rural centres rather than urban facilities. Use of information technology could be increased, for example in remote trainee supervision programs.

Cuticular Structure Proteomics in the Pea Aphid Acyrthosiphon pisum Reveals New Plant Virus Receptor Candidates at the Tip of Maxillary Stylets.

Aphids are phloem-feeding insects known as major pests in agriculture that are able to transmit hundreds of plant viruses. The majority of these viruses, classified as noncirculative, are retained and transported on the inner surface of the cuticle of the needle-like mouthparts while the aphids move from plant to plant. Identification of receptors of viruses within insect vectors is a key challenge because they are promising targets for alternative control strategies. The acrostyle, an organ discovered earlier within the common food/salivary canal at the tip of aphid maxillary stylets, displays proteins at the cuticle-fluid interface, some of which are receptors of noncirculative viruses. To assess the presence of stylet- and acrostyle-specific proteins and identify putative receptors, we have developed a comprehensive comparative analysis of the proteomes of four cuticular anatomical structures of the pea aphid, stylets, antennae, legs, and wings. In addition, we performed systematic immunolabeling detection of the cuticular proteins identified by mass spectrometry in dissected stylets. We thereby establish the first proteome of stylets of an insect and determine the minimal repertoire of the cuticular proteins composing the acrostyle. Most importantly, we propose a short list of plant virus receptor candidates, among which RR-1 proteins are remarkably predominant. The data are available via ProteomeXchange (PXD016517).

Effective virtual patient simulators for medical communication training: A systematic review.

CONTEXT: Despite the growing use of virtual patients (VPs) in medical education, few studies have explored the features and effectiveness of VP-based medical communication skills training. We undertook a systematic review to summarise the design and evaluation of VP-based medical communication skills training systems in order to identify features of successful cases. METHODS: Following PRISMA guidelines, we searched four databases for studies published between 2006 and 2018. Using a refined classification scheme, we extracted data on instructional design (scenario and instructional intervention), technological design (modality and interaction), and evaluation (user experience, learning effectiveness and evaluator). We assessed the quality of studies using the Medical Education Research Study Quality Instrument (MERSQI) and the QualSyst standard assessment criteria. RESULTS: A total of 14 studies were included for review. Of these, 85.7% (n = 12) were quantitative and 71.4% (n = 10) involved undergraduate students. The most common VP training scenario was history taking followed by the delivery of bad news. Diverse instructional interventions, including tutorials, learning activities, and feedback, were embedded in the VPs. The first-person perspective animated within-screen size VP was a popular technological feature. Most evaluations concerned the reality of simulation (for user experience) and skill in expressing empathy (as a learning outcome). Of the eight comparative studies, half reported significant attitude or skill improvements in the VP group. The distinct features of VPs shown to be effective were well-designed instructional interventions (eg, a pre-activity with a protocol-informed tutorial), and post-activity (eg, debrief or reflection), scaffolding and human feedback, but not system feedback. CONCLUSIONS: Evidence-based VP training can enable students to gain communication skills in a safe and affordable learning environment. Elaborate technology alone cannot guarantee effective learning, but evidence-based instructional interventions can facilitate its optimal use and bring about better learning outcomes.

Preparedness of medical students and junior doctors for their role as clinical leaders: A systematic review.

Introduction: Clinical leadership skills are essential across all levels of a healthcare organization and must be employed by those most appropriate to the situation, regardless of position or profession. However, most medical students and junior doctors remain unaware of how leadership can be assimilated into their everyday clinical practice.Aim: To investigate the perceived preparedness of medical students and junior doctors for their role as clinical leaders.Methods: A systematic search was performed of the MEDLINE, ERIC and PubMed databases. Papers pertaining to medical students and junior doctors that included primary data on preparedness for clinical leadership or behaviors associated with being a clinical leader were included.Results: Sixteen papers were included and analyzed after screening 254. No studies specifically assessed the transition to clinical leader. Evidence suggests that new graduates perceive leadership as individualistic and hierarchical, and that they are only partially prepared to fill this role. Preparedness for clinical leadership was associated with increasing responsibility, experience and time-served.Conclusions: New graduates are unlikely to question senior colleagues as they lack leadership-specific communication skills. Further research is required into how to actively promote leadership in medical students and ease the transition to leadership roles within clinical teams.

Identification of Plant Virus Receptor Candidates in the Stylets of Their Aphid Vectors.

Plant viruses transmitted by insects cause tremendous losses in most important crops around the world. The identification of receptors of plant viruses within their insect vectors is a key challenge to understanding the mechanisms of transmission and offers an avenue for future alternative control strategies to limit viral spread. We here report the identification of two cuticular proteins within aphid mouthparts, and we provide experimental support for the role of one of them in the transmission of a noncirculative virus. These two proteins, named Stylin-01 and Stylin-02, belong to the RR-1 cuticular protein subfamily and are highly conserved among aphid species. Using an immunolabeling approach, they were localized in the maxillary stylets of the pea aphid Acyrthosiphon pisum and the green peach aphid Myzus persicae, in the acrostyle, an organ earlier shown to harbor receptors of a noncirculative virus. A peptide motif present at the C termini of both Stylin-01 and Stylin-02 is readily accessible all over the surface of the acrostyle. Competition for in vitro binding to the acrostyle was observed between an antibody targeting this peptide and the helper component protein P2 of Cauliflower mosaic virus Furthermore, silencing the stylin-01 but not stylin-02 gene through RNA interference decreased the efficiency of Cauliflower mosaic virus transmission by Myzus persicae These results identify the first cuticular proteins ever reported within arthropod mouthparts and distinguish Stylin-01 as the best candidate receptor for the aphid transmission of noncirculative plant viruses.IMPORTANCE Most noncirculative plant viruses transmitted by insect vectors bind to their mouthparts. They are acquired and inoculated within seconds when insects hop from plant to plant. The receptors involved remain totally elusive due to a long-standing technical bottleneck in working with insect cuticle. Here we characterize the role of the two first cuticular proteins ever identified in arthropod mouthparts. A domain of these proteins is directly accessible at the surface of the cuticle of the acrostyle, an organ at the tip of aphid stylets. The acrostyle has been shown to bind a plant virus, and we consistently demonstrated that one of the identified proteins is involved in viral transmission. Our findings provide an approach to identify proteins in insect mouthparts and point at an unprecedented gene candidate for a plant virus receptor.