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 metagenomic investigation of phytoplasma diversity in Australian vegetable growing regions.

In this study, metagenomic sequence data was used to investigate the phytoplasma taxonomic diversity in vegetable-growing regions across Australia. Metagenomic sequencing was performed on 195 phytoplasma-positive samples, originating either from historic collections (n=46) or during collection efforts between January 2015 and June 2022 (n=149). The sampled hosts were classified as crop (n=155), weed (n=24), ornamental (n=7), native plant (n=6), and insect (n=3) species. Most samples came from Queensland (n=78), followed by Western Australia (n=46), the Northern Territory (n=32), New South Wales (n=17), and Victoria (n=10). Of the 195 draft phytoplasma genomes, 178 met our genome criteria for comparison using an average nucleotide identity approach. Ten distinct phytoplasma species were identified and could be classified within the 16SrII, 16SrXII (PCR only), 16SrXXV, and 16SrXXXVIII phytoplasma groups, which have all previously been recorded in Australia. The most commonly detected phytoplasma taxa in this study were species and subspecies classified within the 16SrII group (n=153), followed by strains within the 16SrXXXVIII group ('Ca. Phytoplasma stylosanthis'; n=6). Several geographic- and host-range expansions were reported, as well as mixed phytoplasma infections of 16SrII taxa and 'Ca. Phytoplasma stylosanthis'. Additionally, six previously unrecorded 16SrII taxa were identified, including five putative subspecies of 'Ca. Phytoplasma australasiaticum' and a new putative 16SrII species. PCR and sequencing of the 16S rRNA gene was a suitable triage tool for preliminary phytoplasma detection. Metagenomic sequencing, however, allowed for higher-resolution identification of the phytoplasmas, including mixed infections, than was afforded by only direct Sanger sequencing of the 16S rRNA gene. Since the metagenomic approach theoretically obtains sequences of all organisms in a sample, this approach was useful to confirm the host family, genus, and/or species. In addition to improving our understanding of the phytoplasma species that affect crop production in Australia, the study also significantly expands the genomic sequence data available in public sequence repositories to contribute to phytoplasma molecular epidemiology studies, revision of taxonomy, and improved diagnostics.

Medical Students' Self-Perceptions of Harassment During Clinical Placement.

Objectives: Exploring workplace dynamics during clinical placement is crucial to determine whether medical students are encountering safe and meaningful learning experiences. The aim of this original article is to describe medical students' reported harassment experiences whilst on clinical placement. Design: Medical students in years 4 to 6 were invited to participate in the survey. In this mixed-methods study, data collection included demographic information, responses to the Generalized Workplace Harassment Questionnaire, and qualitative commentaries. Results: Two hundred and five students completed the questionnaire. Medical students experienced harassment in areas of verbal aggression, disrespect, isolation/exclusion, threats/bribes, and physical aggression. Concerning levels of occurrence were noted for disrespect, isolation/exclusion, and verbal aggression. Conclusions: Many medical students in this study reported experiencing harassment during their clinical placements indicating that harassment during clinical placement continues to be of concern in medical education. The findings indicate that further initiatives need to be designed to identify and respond to these cases of workplace harassment and that power imbalance and safe reporting appear to be further issues of concern. It was evident that students need to feel safe enough to be able to report harassment experiences to allow managers and educators to address the full extent of the problem.

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.

Age-specific Reference Intervals of Abbott Intact PTH-Potential Impacts on Clinical Care.

Background: PTH assays are not standardized; therefore, method-specific PTH reference intervals are required for interpretation of results. PTH increases with age in adults but age-related reference intervals for the Abbott intact PTH (iPTH) assay are not available. Methods: Deidentified serum PTH results from September 2015 to November 2022 were retrieved from the laboratory information system of a laboratory serving a cosmopolitan population in central-west England for individuals aged 18 years and older if the estimated glomerular filtration rate was ≥60 mL/min, serum 25-hydroxyvitamin D was >50 nmol/L, and serum albumin-adjusted calcium and serum phosphate were within reference intervals. Age-specific reference intervals for Abbott iPTH were derived by an indirect method using the refineR algorithm. Results: PTH increased with age and correlated with age when controlled for 25-hydroxyvitamin D, estimated glomerular filtration rate, and adjusted calcium (r = 0.093, P < .001). The iPTH age-specific reference intervals for 4 age partitions of 18 to 45 years, 46 to 60 years, 61 to 80 years, and 81 to 95 years were 1.6 to 8.6 pmol/L, 1.8 to 9.5 pmol/L, 2.0 to 11.3 pmol/L, and 2.3 to 12.3 pmol/L, respectively. PTH was higher in women compared with men (P < .001). Sex-specific age-related reference intervals could not be derived because of the limited sample size. Conclusion: Age-specific Abbott iPTH reference intervals were derived. Application of age-specific reference intervals will impact the diagnosis and management of normocalcemic hyperparathyroidism, based on current definitions, and secondary hyperparathyroidism. Additional studies are required to clarify the effect of sex and ethnicity on PTH.

Interprofessional Learning in Multidisciplinary Healthcare Teams Is Associated With Reduced Patient Mortality: A Quantitative Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study is to identify quantitative evidence for the efficacy of interprofessional learning (IPL) to improve patient outcomes. METHODS: We conducted a systematic review and meta-analysis of quantitative patient outcomes after IPL in multidisciplinary healthcare teams reported in the Medline, Scopus, PsycInfo, Embase, and CINAHL databases. RESULTS: In 2022, we screened 15,248 reports to include 20 and extracted rates of mortality and primary outcomes in conventional care groups and intervention groups (involving initiatives to promote IPL in multidisciplinary teams). The meta-analysis of the 13 studies reporting mortality outcomes demonstrated that the 7166 patients in the intervention group had a significant 28% (95% confidence interval [CI], 40%-14%; P < 0.0003) reduced risk of dying compared with the 6809 patients in the conventional care group. The meta-analysis of the 14 studies reporting other treatment-related adverse outcomes demonstrated that the 4789 patients in the intervention group had a significant 23% (95% CI, 33%-12%; P < 0.0001) reduced risk of experiencing an adverse outcome during care compared with the 4129 patients in the conventional care group. Sensitivity analysis, involving the exclusion of the 20% of individual studies with the widest 95% CIs, confirmed the precision and reliability of our findings. CONCLUSIONS: We believe that our results are the first to demonstrate significant quantitative evidence for the efficacy of IPL to translate into changes in clinical practice and improved patient outcomes. Our results reinforce earlier qualitative work of the value of IPL, but further prospective quantitative and mixed-methods research is needed to better define such benefits.

Validation of the Generalized Workplace Harassment Questionnaire for Use with Medical Students.

The Generalized Workplace Harassment Questionnaire (GWHQ) has not been validated among medical students whilst they are on clinical placements. Therefore, this study aims to validate its use when applied to this cohort. A sample of 205 medical students in their clinical training phase completed the GWHQ. To examine the validity of the proposed factor structure of the validated 25-item GWHQ, which was reduced to from the original 29-item set, a confirmatory factor analysis was conducted. Model fit was appraised by evaluating the comparative fit index (CFI), the root mean square error of approximation (RMSEA), and the standardized root mean squared residual (SRMR). Spearman's rho correlation coefficients were applied to correlations between factors. With the exclusion of Item 19, the resulting fit was improved. In the revised model for a 24-item GWHQ, CFI = 0.995, RMSEA = 0.047, and SRMR = 0.115. Overall, the fit met the criteria for two fit indices and was thus deemed to be acceptable. Factor loadings ranged from 0.49 to 0.96. The Spearman's rho correlation coefficient between Verbal and Covert Hostility was high, although all correlations with Physical Hostility were weak. In conclusion, the amended 24-item version of the GWHQ is a valid instrument for appraising instances of harassment or hostility within clinical placements attended by medical students in New Zealand.

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.

UK Reference Intervals for Parathyroid Hormone Using Abbott Methods.

Background: Diagnosis of hyperparathyroidism requires measurement of parathyroid hormone (PTH) in the context of the plasma calcium and other factors, such as vitamin D status and renal function. Accurate classification depends upon an appropriate population reference interval. We examined local population plasma PTH reference intervals at four different UK sites using a common platform. Methods: Plasma PTH results were extracted from laboratory information systems at four different UK sites, all using the Abbott Architect i2000 method. We included only people with normal adjusted serum calcium, magnesium, vitamin D, and renal function. Following outlier rejection lower and upper reference limits were derived. Results: An overall reference interval for plasma PTH of 3.0-13.7 pmol/L was observed using a non-parametric approach compared to 2.9-14.1 pmol/L using a parametric approach, notably higher than the manufacturer's representative range of 1.6-7.2 pmol/L. We also noted statistically significant differences (p < 0.00001) between some sites with upper limits ranging from 11.5 to 15.8 pmol/L which may be due to different population characteristics of each group. Conclusion: Locally derived reference intervals may be beneficial for UK populations and revised upper thresholds are necessary when using the Abbott PTH method to avoid inappropriate classification of patients as having hyperparathyroidism.

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.

11ß-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial.

Glucocorticoids prescribed to limit inflammation, have significant adverse effects. As 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) regenerates active glucocorticoid, we investigated whether 11ß-HSD1 inhibition with AZD4017 could mitigate adverse glucocorticoid effects without compromising their anti-inflammatory actions. We conducted a proof-of-concept, randomized, double-blind, placebo-controlled study at Research Unit, Churchill Hospital, Oxford, UK (NCT03111810). 32 healthy male volunteers were randomized to AZD4017 or placebo, alongside prednisolone treatment. Although the primary endpoint of the study (change in glucose disposal during a two-step hyperinsulinemic, normoglycemic clamp) wasn't met, hepatic insulin sensitivity worsened in the placebo-treated but not in the AZD4017-treated group. Protective effects of AZD4017 on markers of lipid metabolism and bone turnover were observed. Night-time blood pressure was higher in the placebo-treated but not in the AZD4017-treated group. Urinary (5aTHF+THF)/THE ratio was lower in the AZD4017-treated but remained the same in the placebo-treated group. Most anti-inflammatory actions of prednisolone persisted with AZD4017 co-treatment. Four adverse events were reported with AZD4017 and no serious adverse events. Here we show that co-administration of AZD4017 with prednisolone in men is a potential strategy to limit adverse glucocorticoid effects.

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.

Perceived barriers to the implementation of social distancing in the COVID-19 pandemic in Iran during 2020-2021: A cross-sectional study.

Background and Aims: This research has been on the effective role of social distancing in preventing the spread of COVID-19 and the obstacles to its implementation. The results of this research can highlight the major barriers to distancing and suggest appropriate solutions to remove them. Methods: We conducted this cross-sectional study during 2020-2021 among 277 faculty members, students of medical universities and ordinary people of Khuzestan province in southwestern Iran. We included them in this study by sampling at convenience. The data collection tool was a researcher-constructed questionnaire that we distributed among the statistical sample through social networks (WhatsApp and Telegram). Results: Mean ± SD = economic barriers 4.49 (0.65), cultural barriers 4.48 (0.70), social barriers 4.40 (0.61), political barriers 4.28 (0.64), educational barriers in universities and schools 4.27 (0.53) and Educational barriers at societal level 3.82 (1.08) were the self-reported obstacles (perceived) to social distancing during the Covid-19 pandemic. Comparison of occupational groups with faculty members showed that only scores of academic barriers have a significant difference between occupational groups (p < 0.001). Conclusion: The role of economic barriers, cultural barriers and social barriers in social distancing was very prominent. One of our remarkable results was that there is adequate training for people on the proper implementation of the principles of social distance in the prevention of the Covid-19 pandemic. The responsibility of all members of society to observe social distancing as a moral and even legal duty can be the first step to protect the health of citizens against COVID-19. We can, therefore, use some planned interventions. This must be within the framework of economic, cultural, social and political structures of society.

Vitamin D status: a U-shaped relationship for SARS-CoV-2 seropositivity in UK healthcare workers.

BACKGROUND: There is increasing evidence that vitamin D (VD) deficiency may increase individuals' risk of COVID-19 infection and susceptibility. We aimed to determine the relationship between VD deficiency and sufficiency and COVID-19 seropositivity within healthcare workers. METHODS: The study included an observational cohort of healthcare workers who isolated due to COVID-19 symptoms from 12 May to 22 May 2020, from the University Hospitals Birmingham National Health Service Foundation Trust. Data collected included SARS-CoV-2 seroconversion status, serum 25(OH)D3 levels, age, body mass index (BMI), sex, ethnicity, job role and comorbidities. Participants were grouped into four VD categories: (1) Severe VD deficiency (VD<30 nmol/L); (2) VD deficiency (30 nmol/L ≤VD<50 nmol/L); (3) VD insufficiency (50 nmol/L ≤VD<75 nmol/L); (4) VD sufficiency (VD≥75 nmol/L). RESULTS: When VD levels were compared against COVID-19 seropositivity rate, a U-shaped curve was identified. This trend repeated when participants were split into subgroups of age, sex, ethnicity, BMI and comorbidity status. Significant difference was identified in the COVID-19 seropositivity rate between VD groups in the total population and between groups of men and women; black, Asian and minority ethnic (BAME) group; BMI<30 (kg/m2); 0 and +1 comorbidities; the majority of which were differences when the severely VD deficient category were compared with the other groups. A larger proportion of those within the BAME group (vs white ethnicity) were severely VD deficient (p<0.00001). A larger proportion of the 0 comorbidity subgroup were VD deficient in comparison to the 1+ comorbidity subgroup (p=0.046). CONCLUSIONS: Our study has shown a U-shaped relationship for COVID-19 seropositivity in UK healthcare workers. Further investigation is required to determine whether high VD levels can have a detrimental effect on susceptibility to COVID-19 infection. Future randomised clinical trials of VD supplementation could potentially identify 'optimal' VD levels, allowing for targeted therapeutic treatment for those at risk.

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.