Fostering teaching-learning through workplace based assessment in postgraduate chemical pathology residency program using virtual learning environment.

BACKGROUND: The principle of workplace based assessment (WBA) is to assess trainees at work with feedback integrated into the program simultaneously. A student driven WBA model was introduced and perception evaluation of this teaching method was done subsequently by taking feedback from the faculty as well as the postgraduate trainees (PGs) of a residency program. METHODS: Descriptive multimethod study was conducted. A WBA program was designed for PGs in Chemical Pathology on Moodle and forms utilized were case-based discussion (CBD), direct observation of practical skills (DOPS) and evaluation of clinical events (ECE). Consented assessors and PGs were trained on WBA through a workshop. Pretest and posttest to assess PGs knowledge before and after WBA were conducted. Every time a WBA form was filled, perception of PGs and assessors towards WBA, time taken to conduct single WBA and feedback were recorded. Faculty and PGs qualitative feedback on perception of WBA was taken via interviews. WBA tools data and qualitative feedback were used to evaluate the acceptability and feasibility of the new tools. RESULTS: Six eligible PGs and seventeen assessors participated in this study. A total of 79 CBDs (assessors n = 7 and PGs n = 6), 12 ECEs (assessors n = 6 and PGs n = 5), and 20 DOPS (assessors n = 6 and PGs n = 6) were documented. PGs average pretest score was 55.6%, which was improved to 96.4% in posttest; p value< 0.05. Scores of annual assessment before and after implementation of WBA also showed significant improvement, p value 0.039, Overall mean time taken to evaluate PG's was 12.6 ± 9.9 min and feedback time 9.2 ± 7.4 min. Mean WBA process satisfaction of assessors and PGs on Likert scale of 1 to 10 was 8 ± 1 and 8.3 ± 0.8 respectively. CONCLUSION: Both assessors and fellows were satisfied with introduction and implementation of WBA. It gave the fellows opportunity to interact with assessors more often and learn from their rich experience. Gain in knowledge of PGs was identified from the statistically significant improvement in PGs' assessment scores after WBA implementation.

Influence of cytokine gene polymorphisms on proinflammatory/anti-inflammatory cytokine imbalance in premature coronary artery disease.

BACKGROUND: Genetic information has the potential to create a more personalised, prompt, early and accurate risk evaluation. The effect of these genetic variants on the serum biomarker levels (phenotype) needs to be studied to assess their potential causal role in the pathogenesis of premature coronary artery disease (PCAD). Objectives were to determine the genotypic distribution of interleukin (IL) 18, tumour necrosis factor-α (TNFA), IL6 and IL10 single nucleotide polymorphisms (SNPs) in Pakistani PCAD cases and disease free controls and to study the effect of these gene polymorphisms on the serum cytokine levels (IL18, TNFA, IL6 and IL10) and cytokine imbalance (IL18:IL10 and TNFA:IL10). MATERIAL AND METHODS: The case-control study was carried out in National University of Sciences and Technology, Islamabad in collaboration with the Cardiovascular Genetics Institute, University College London, UK. Subjects (n=340) with >70% stenosis in at least a single major coronary artery on angiography were taken as PCAD cases along with 310 angiographically verified controls. ELISA was performed for measuring the concentrations of serum IL18, TNFA, IL6 and IL10. Genotyping was done using TAQMAN assay. RESULTS: The risk allele frequencies (RAFs) of rs1800795 (IL6) and rs187238 (IL18) cytokine gene promoter SNPs were significantly higher in the PCAD cases as compared with the controls. Serum IL18 and IL10 levels were significantly greater in the IL18 rs187238 GG genotype patients while serum IL18 and IL6 levels were significantly higher in patients having the IL6 rs1800795 CC genotype. IL18 SNP rs1946519 significantly altered the IL18, TNFA, IL6, IL18/IL10 and TNFA/IL10 ratio levels followed by TNFA SNP rs1800629 which significantly altered the serum levels of IL18, IL18:IL-0 and TNFA:IL10 ratios. CONCLUSIONS: The association of the selected SNPs with differential serum cytokine levels especially the cytokine imbalance points towards their potential causal role in the immune inflammatory pathogenic pathway of PCAD.

Clinical and diagnostic findings in patients with elevated cerebrospinal bilirubin.

INTRODUCTION: Cerebrospinal fluid (CSF) spectroscopy can identify subarachnoid haemorrhage (SAH) when CT is negative in patients presenting with acute severe headache. The primary objective of this study was to evaluate the clinical use and usefulness of CSF spectrophotometry. Secondary objectives were to identify other causes of elevated CSF bilirubin, to analyse headache descriptions and to compare clinical features in patients with an elevated CSF bilirubin among those with and without an intracranial vascular cause of SAH (avSAH). METHODS: Consecutive patients admitted to two hospitals in Enniskillen and Londonderry between 1 January 2004 and 30 September 2014 with CSF spectroscopy bilirubin results were identified from a clinical chemistry laboratory dataset. Patients with elevated CSF bilirubin were studied. Clinical demographics, delays to investigation and final diagnoses were recorded. Patients with avSAH were compared with patients without avSAH. RESULTS: Among 1813 patients with CSF spectrophotometry results, requests increased more than threefold during the study (p<0.001). Fifty-six patients had elevated CSF bilirubin. Ten (17.9%) had avSAH, of which 8 (14.3%) had aneurysmal SAH. Non-vascular causes of elevated CSF bilirubin included meningitis, spontaneous intracranial hypotension and carcinomatous meningitis. Headache descriptions varied. Time from headache onset to admission, CT scan and lumbar puncture did not differ significantly for patients with avSAH and non-avSAH. CSF red cell counts were higher among patients with avSAH than patients with non-avSAH (p=0.005). CONCLUSIONS: CSF bilirubin measurement has an important role in identifying avSAH in CT-negative patients presenting with a thunderclap headache. Better clinical selection of patients is required as CSF spectrophotometry, although sensitive, is not specific for SAH.

Identification of Pre-examination Errors in the Chemical Pathology Laboratory at the University Hospital of the West Indies.

This study evaluated the types and frequencies of pre-examination errors recorded in the chemical pathology laboratory at the University Hospital of the West Indies, Jamaica. This was a retrospective analysis of errors recorded over a three year period. Data analysis was done on an average of 519,084 samples collected and tested per year. Samples included blood, urine, stool and other fluids. Pre-examination errors were identified and recorded following visual inspection of the samples and corresponding request forms by laboratory staff, then subsequently by the Senior Medical Technologist. Errors were generally classified as inappropriate sample (58 %), inappropriate form (23.4 %), inappropriate sample volume (9.3 %) and inappropriate sample tube (9.3 %). Over 90 % of recorded pre-examination errors were related to blood samples while urine samples accounted for 6.8 % error. Pre-examination errors were lower at this study location than elsewhere. Measures aimed at reducing instances of these errors are recommended for improved laboratory quality output.

Understanding the role of mitochondria in the pathogenesis of chronic pain.

Chronic pain is a major public health problem. Mitochondria play important roles in a myriad of cellular processes and mitochondrial dysfunction has been implicated in multiple neurological disorders. This review aims to provide an insight into advances in understanding of the role of mitochondrial dysfunction in the pathogenesis of chronic pain. The results show that the five major mitochondrial functions (the mitochondrial energy generating system, reactive oxygen species generation, mitochondrial permeability transition pore, apoptotic pathways and intracellular calcium mobilisation) may play critical roles in neuropathic and inflammatory pain. Therefore, protecting mitochondrial function would be a promising strategy to alleviate or prevent chronic pain states. Related chronic inflammatory and neuropathic pain models, as well as the spectral characteristics of current fluorescent probes to detect mitochondria in pain studies, are also discussed.

Challenges of managing snakebite envenomation in a deployed setting.

Snake bite envenomation causes a significant health burden globally, especially in austere or resource poor settings. This case series describes envenomation in two adults and two children presenting to the Role 3 Medical Treatment Facility in Camp Bastion, Afghanistan. Each case has similarities with respect to the coagulopathy of envenomation but differs in terms of time delay to presentation and response to treatment, including reactions to antivenom. We discuss the challenges and ethical dilemmas in delayed-presentation snakebite, the diagnosis and treatment of coagulopathy and the role of antivenom and surgical debridement.

Admission plasma potassium and length of hospital stay: a meta-analysis.

OBJECTIVE: Hypokalaemia and hyperkalaemia ('dyskalaemia') are commonly seen in patients requiring emergency hospital admission. The adverse effect of dyskalaemia on mortality is well described but there are few data for the effect on hospital length of stay. We sought to determine the association of serum potassium concentration with in-hospital length of stay. DESIGN: Systematic review and meta-analysis. DATA SOURCES: A structured search of MEDLINE, PubMed and SCOPUS databases to 19 March 2021. ELIGIBILITY CRITERIA: Observational cohort studies defining exposure of interest as serum potassium levels (at admission or within the first 72 hours) and with outcome of interest as length of hospital stay. Studies had to provide estimates of length of stay as a comparison between normokalaemia and defined ranges of hyperkalaemia or hypokalaemia. DATA EXTRACTION AND SYNTHESIS: We identified 39 articles published to March 2021 that met the inclusion and exclusion criteria. Study selection, data extraction and quality assessment were carried out by two reviewers working independently and in duplicate, to assessed eligibility and risk of bias, and extract data from eligible studies. Random effects models were used to pool estimates across the included studies. Meta-analyses were performed using Cochrane-RevMan. RESULTS: Five studies were included in the meta-analysis. Compared with the reference group (3.5-5.0 mmol/L), the pooled raw differences of medians were 4.45 (95% CI 2.71 to 6.91), 1.99 (95% CI 0.03 to 3.94), 0.98 (95% CI 0.91 to 1.05), 1.51 (95% CI 1.03 to 2.0), 1 (95% CI 0.75 to 1.25) and 2.76 (95% CI 1.24 to 4.29) for patients with potassium levels of <2.5, 2.5 to <3.0, 3.0 to <3.5, <5 to 5.5, <5.5 to 6 and >6.0 mmol/L, respectively. CONCLUSION: Hospital length of stay follows a U-shaped distribution, with duration of admission being twofold greater at the extremes of the potassium range.

Urinary Metabolic Distinction of Niemann-Pick Class 1 Disease through the Use of Subgroup Discovery.

In this investigation, we outline the applications of a data mining technique known as Subgroup Discovery (SD) to the analysis of a sample size-limited metabolomics-based dataset. The SD technique utilized a supervised learning strategy, which lies midway between classificational and descriptive criteria, in which given the descriptive property of a dataset (i.e., the response target variable of interest), the primary objective was to discover subgroups with behaviours that are distinguishable from those of the complete set (albeit with a differential statistical distribution). These approaches have, for the first time, been successfully employed for the analysis of aromatic metabolite patterns within an NMR-based urinary dataset collected from a small cohort of patients with the lysosomal storage disorder Niemann-Pick class 1 (NPC1) disease (n = 12) and utilized to distinguish these from a larger number of heterozygous (parental) control participants. These subgroup discovery strategies discovered two different NPC1 disease-specific metabolically sequential rules which permitted the reliable identification of NPC1 patients; the first of these involved 'normal' (intermediate) urinary concentrations of xanthurenate, 4-aminobenzoate, hippurate and quinaldate, and disease-downregulated levels of nicotinate and trigonelline, whereas the second comprised 'normal' 4-aminobenzoate, indoxyl sulphate, hippurate, 3-methylhistidine and quinaldate concentrations, and again downregulated nicotinate and trigonelline levels. Correspondingly, a series of five subgroup rules were generated for the heterozygous carrier control group, and 'biomarkers' featured in these included low histidine, 1-methylnicotinamide and 4-aminobenzoate concentrations, together with 'normal' levels of hippurate, hypoxanthine, quinolinate and hypoxanthine. These significant disease group-specific rules were consistent with imbalances in the combined tryptophan-nicotinamide, tryptophan, kynurenine and tyrosine metabolic pathways, along with dysregulations in those featuring histidine, 3-methylhistidine and 4-hydroxybenzoate. In principle, the novel subgroup discovery approach employed here should also be readily applicable to solving metabolomics-type problems of this nature which feature rare disease classification groupings with only limited patient participant and sample sizes available.

Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part III: Implementations for the Diagnosis of Non-Cancerous Disorders, Both Oral and Systemic.

This communication represents Part III of our series of reports based on the applications of human saliva as a useful and conveniently collectable medium for the discovery, identification and monitoring of biomarkers, which are of some merit for the diagnosis of human diseases. Such biomarkers, or others reflecting the dysfunction of specific disease-associated metabolic pathways, may also be employed for the prognostic pathological tracking of these diseases. Part I of this series set the experimental and logistical groundwork for this report, and the preceding paper, Part II, featured the applications of newly developed metabolomics technologies to the diagnosis and severity grading of human cancer conditions, both oral and systemic. Clearly, there are many benefits, both scientific and economic, associated with the donation of human saliva samples (usually as whole mouth saliva) from humans consenting to and participating in investigations focused on the discovery of biomolecular markers of diseases. These include usually non-invasive collection protocols, relatively low cost when compared against blood sample collection, and no requirement for clinical supervision during collection episodes. This paper is centred on the employment and value of 'state-of-the-art' metabolomics technologies to the diagnosis and prognosis of a wide range of non-cancerous human diseases. Firstly, these include common oral diseases such as periodontal diseases (from type 1 (gingivitis) to type 4 (advanced periodontitis)), and dental caries. Secondly, a wide range of extra-oral (systemic) conditions are covered, most notably diabetes types 1 and 2, cardiovascular and neurological diseases, and Sjögren's syndrome, along with a series of viral infections, e.g., pharyngitis, influenza, HIV and COVID-19. Since the authors' major research interests lie in the area of the principles and applications of NMR-linked metabolomics techniques, many, but not all, of the studies reviewed were conducted using these technologies, with special attention being given to recommended protocols for their operation and management, for example, satisfactory experimental model designs; sample collection and laboratory processing techniques; the selection of sample-specific NMR pulse sequences for saliva analysis; and strategies available for the confirmation of resonance assignments for both endogenous and exogenous molecules in this biofluid. This article also features an original case study, which is focussed on the use of NMR-based salivary metabolomics techniques to provide some key biomarkers for the diagnosis of pharyngitis, and an example of how to 'police' such studies and to recognise participants who perceive that they actually have this disorder but do not from their metabolic profiles and multivariate analysis pattern-based clusterings. The biochemical and clinical significance of these multidimensional metabolomics investigations are discussed in detail.

Retrospective analysis to describe trends in first-ever prostate-specific antigen (PSA) testing for primary healthcare facilities in the Gauteng Province, South Africa, between 2006 and 2016.

OBJECTIVES: The objective of our study was to use laboratory data to describe prostate-specific antigen (PSA) testing trends for primary healthcare (PHC) services from a single province. PHC is a basic package of services offered to local communities, serving as the first point of contact within the health system. These services are offered at clinics and community health centres (CHC), the latter providing additional maternity, accident and emergency services. DESIGN: The retrospective descriptive study design was used. METHODS: We analysed national laboratory data between 2006 and 2016 for men ≥30 years in the Gauteng Province. We used the probabilistic matching algorithm to create first-ever PSA cohort. We used the hot-deck imputation to assign missing race group values and the district health information system facility descriptors to identify PHC testing. We reported patient numbers by calendar year, age category and race group as well as descriptive statistics. We used multivariable logistic regression to assess any association for race group and age with a PSA ≥4 µg/L. RESULTS: Between 2006 and 2016, numbers of men tested increased from 1782 to 67 025, respectively, with 186 984/239 506 (78.1%) tests were from clinics. The majority of testing was for men in the 50-59 age category (31.5%) and Black Africans (86.4%). We reported a median of 0.9 µg/L that increased with age. A PSA ≥4 µg/L was reported for 11.7% of men, increasing to 35.5% for the ≥70 age category. The logistic regression reported that the adjusted odds of having a PSA ≥4 µg/L was significantly lower for Indian/Asians, multiracials and whites than for Black Africans (p value<0.0001). CONCLUSIONS: Our study has shown a marked increase in PSA testing from clinics and CHC suggestive of screening for prostate cancer. The approaches reported in this study can be extended for national data.

Protocol for an observational study investigating hormones triggering the onset of sustained lactation: the INSIGHT study.

INTRODUCTION: Lactation is a hormonally controlled process that promotes infant growth and neurodevelopment and reduces the long-term maternal risk of diabetes, cardiovascular disease and breast cancer. Hormones, such as prolactin and progesterone, mediate mammary development during pregnancy and are critical for initiating copious milk secretion within 24-72 hours post partum. However, the hormone concentrations mediating lactation onset are ill defined. METHODS AND ANALYSIS: The primary objective of the investigating hormones triggering the onset of sustained lactation study is to establish reference intervals for the circulating hormone concentrations initiating postpartum milk secretion. The study will also assess how maternal factors such as parity, pregnancy comorbidities and complications during labour and delivery, which are known to delay lactation, may affect hormone concentrations. This single-centre observational study will recruit up to 1068 pregnant women over a 3-year period. A baseline blood sample will be obtained at 36 weeks' gestation. Participants will be monitored during postpartum days 1-4. Lactation onset will be reported using a validated breast fullness scale. Blood samples will be collected before and after a breastfeed on up to two occasions per day during postpartum days 1-4. Colostrum, milk and spot urine samples will be obtained on a single occasion. Serum hormone reference intervals will be calculated as mean±1.96 SD, with 90% CIs determined for the upper and lower reference limits. Differences in hormone values between healthy breastfeeding women and those at risk of delayed onset of lactation will be assessed by repeated measures two-way analysis of variance or a mixed linear model. Correlations between serum hormone concentrations and milk composition and volume will provide insights into the endocrine regulation of milk synthesis. ETHICS AND DISSEMINATION: Approval for this study had been granted by the East of England-Cambridgeshire and Hertfordshire Research Ethics Committee (REC No. 20/EE/0172), by the Health Research Authority (HRA), and by the Oxford University Hospitals National Health Service Foundation Trust. The findings will be published in high-ranking journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN12667795.

Heat illness experience at BMH Shaibah, Basra, during Operation TELIC: May-July 2003.

This is an observational study of heat-related illness in UK Service Personnel deployed into summer conditions in Northern Kuwait and Southern Iraq. Among 622 hospitalisations reported during a 9-week period at the historical British Military Hospital, Shaibah, 303 consecutive admissions are reviewed in detail. Several clinical syndromes attributable to thermal stress were observed. These ranged from self-limiting debility to life-threatening failures of homeostasis, with 5.0% developing a critical care requirement. Hyponatraemia was a commonly occurring electrolyte disturbance by which, relative to the local reference range, a majority of heat-attributed admissions were affected. Reductions in measured serum sodium could be profound (<125 mmol/L in 20.1% of all heat-related casualties). Hypokalaemia was observed in half of cases, though only a minority were affected by severely low potassium (<2.5 mmol/L in 4.0%). Despite preventive measures prescribed on hospital discharge, illness and significant biochemical derangements could recur upon return to duties in the heat. We reiterate the need for primary prevention of heat illness wherever possible and importance of early, effective interventions to treat and protect Service Personnel from secondary injury. We also highlight the requirement for comprehensive assessment to inform prognostication and occupational decision-making in relation to extreme climatic heat, including aeromedical evacuation. We draw additional attention to the contribution of psychological factors in select cases and identify research questions to improve understanding of environment-induced incapacitation in general.

The application of sigma metrics in the laboratory to assess quality control processes in South Africa.

Background: Laboratories use quality control processes to monitor and evaluate analytical performance in terms of precision and bias. Sigma metrics provide an objective assessment of laboratory quality using the total allowable error as an additional parameter. Objective: This study aimed to determine the sigma metrics of analytes when using different total allowable error guidelines. Methods: A retrospective analysis was performed on 19 general chemistry analytes at Charlotte Maxeke Johannesburg Academic Hospital in South Africa between January 2017 and December 2017. Sigma metrics were calculated on two identical analysers, using internal quality control data and total allowable error guidelines from the Ricos biological variation database and three alternative sources (the Royal College of Pathologists of Australasia, the Clinical Laboratory Improvements Amendment, and the European Federation of Clinical Chemistry and Laboratory Medicine). Results: The sigma performance was similar on both analysers but varied based on the guideline used, with the Clinical Laboratory Improvements Amendment guidelines resulting in the best sigma metrics (53% of analytes on one analyser and 46% on the other had acceptable sigma metrics) and the Royal College of Pathologists of Australia guidelines being the most stringent (21% and 23%). Sodium and chloride performed poorly across all guidelines (sigma < 3). There were also month-to-month variations that may result in acceptable sigma despite poor performance during certain months. Conclusion: The sigma varies greatly depending on the total allowable error, but could be a valuable tool to save time and decrease costs in high-volume laboratories. Sigma metrics calculations need to be standardised.

Biomarkers and outcomes in hospitalised patients with COVID-19: a prospective registry.

OBJECTIVES: To determine association of biomarkers-high-sensitivity C reactive protein (hsCRP), D-dimer, interleukin-6 (IL-6), lactic dehydrogenase (LDH), ferritin and neutrophil-lymphocyte ratio (NLR)-at hospitalisation with outcomes in COVID-19. DESIGN AND SETTING: Tertiary-care hospital based prospective registry. PARTICIPANTS: Successive virologically confirmed patients with COVID-19 hospitalised from April 2020 to July 2021 were prospectively recruited. Details of clinical presentation, investigations, management and outcomes were obtained. PRIMARY AND SECONDARY OUTCOME MEASURES: All biomarkers were divided into tertiles to determine associations with clinical features and outcomes. Primary outcome was all-cause deaths and secondary outcome was oxygen requirement, non-invasive and invasive ventilation, dialysis, duration of stay in ICU and hospital. Numerical data are presented in median and interquartile range (IQR 25-75). Univariate and multivariate (age, sex, risk factors, comorbidities, treatments) ORs and 95% CIs were calculated. RESULTS: 3036 virologically confirmed patients with COVID-19 were detected and 1251 hospitalised. Men were 70.0%, aged >60 years 44.8%, hypertension 44.1%, diabetes 39.6% and cardiovascular disease 18.9%. Median symptom duration was 5 days (IQR 4-7) and oxygen saturation 95% (90%-97%). Total white cell count was 6.9×109/L (5.0-9.8), neutrophils 79.2% (68.1%-88.2%), lymphocytes 15.8% (8.7%-25.5%) and creatinine 0.93 mg/dL (0.78-1.22). Median (IQR) for biomarkers were hsCRP 6.9 mg/dL (2.2-18.9), D-dimer 464 ng/dL (201-982), IL-6 20.1 ng/dL (6.5-60.4), LDH 284 mg/dL (220-396) and ferritin 351 mg/dL (159-676). Oxygen support at admission was in 38.6%, subsequent non-invasive or invasive ventilatory support in 11.0% and 11.6%, and haemodialysis in 38 (3.1%). 173 (13.9%) patients died and 15 (1.2%) transferred to hospice care. For each biomarker, compared with the first, those in the second and third tertiles had more clinical and laboratory abnormalities, and oxygen, ventilatory and dialysis support. Multivariate-adjusted ORs (95% CI) for deaths in second and third versus first tertiles, respectively, were hsCRP 2.24 (1.11 to 4.50) and 12.56 (6.76 to 23.35); D-dimer 3.44 (1.59 to 7.44) and 14.42 (7.09 to 29.30); IL-6 2.56 (1.13 to 5.10) and 10.85 (5.82 to 20.22); ferritin 2.88 (1.49 to 5.58) and 8.19 (4.41 to 15.20); LDH 1.75 (0.81 to 3.75) and 9.29 (4.75 to 18.14); and NLR 3.47 (1.68 to 7.14) and 17.71 (9.12 to 34.39) (p<0.001). CONCLUSION: High levels of biomarkers-hsCRP, D-dimer, IL-6, LDH, ferritin and NLR-in COVID-19 are associated with more severe illness and higher in-hospital mortality. NLR, a widely available investigation, provides information similar to more expensive biomarkers.

Does lactate enhance the prognostic accuracy of the quick Sequential Organ Failure Assessment for adult patients with sepsis? A systematic review.

OBJECTIVES: To investigate whether adding lactate to the quick Sequential (sepsis-related) Organ Failure Assessment (qSOFA) improves the prediction of mortality in adult hospital patients, compared with qSOFA alone. DESIGN: Systematic review in accordance with Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies guidelines. DATA SOURCES: Embase, Medline, PubMed, SCOPUS, Web of Science, CINAHL and Open Grey databases were searched in November 2020. ELIGIBILITY CRITERIA: Original research studies published after 2016 comparing qSOFA in combination with lactate (LqSOFA) with qSOFA alone in adult patients with sepsis in hospital. The language was restricted to English. DATA EXTRACTION AND SYNTHESIS: Title and abstract screening, full-text screening, data extraction and quality assessment (using Quality Assessment of Diagnostic Accuracy Studies-2) were conducted independently by two reviewers. Extracted data were collected into tables and diagnostic test accuracy was compared between the two tests. RESULTS: We identified 1621 studies, of which 11 met our inclusion criteria. Overall, there was a low risk of bias across all studies. The area under the receiver operating characteristic (AUROC) curve for qSOFA was improved by the addition of lactate in 9 of the 10 studies reporting it. Sensitivity was increased in three of seven studies that reported it. Specificity was increased in four of seven studies that reported it. Of the six studies set exclusively within the emergency department, five published AUROCs, all of which reported an increase following the addition of lactate. Sensitivity and specificity results varied throughout the included studies. Due to insufficient data and heterogeneity of studies, a meta-analysis was not performed. CONCLUSIONS: LqSOFA is an effective tool for identifying mortality risk both in adult inpatients with sepsis and those in the emergency department. LqSOFA increases AUROC over qSOFA alone, particularly within the emergency department. However, further original research is required to provide a stronger base of evidence in lactate measurement timing, as well as prospective trials to strengthen evidence and reduce bias. PROSPERO REGISTRATION NUMBER: CRD42020207648.

Core curriculum in pathology for future Irish medical students.

Pathology is important in training to become a medical doctor but as curricula become more integrated, there is a risk that key aspects of pathology may be excluded. Following a survey of the current delivery of teaching in Ireland under the auspices of the Faculty of Pathology at the Royal College of Physicians of Ireland, suggested components of a core curriculum in pathology have been developed to be delivered at some stage during the medical course. These have been based on key principles and themes required by the Medical Council in Ireland. Professionalism is one of the core principles emphasised by the Medical Council. It includes the role of the pathologist in patient care and other professional values such as patient-centred care, clinical competencies and skills, e.g. explaining results, and knowledge under the various sub-disciplines, i.e. histopathology (including neuropathology), clinical microbiology, haematology, chemical pathology and immunology. In each of these, we suggest key aspects and activities that the medical graduate should be comfortable in carrying out. The methods of delivery of teaching and assessment across pathology disciplines have evolved and adapted to recent circumstances. Lessons have been learned and insights gained during the COVID-19 pandemic as educators have risen to the challenge of continuing to educate medical students. Integrated and multi-disciplinary teaching is recommended to reflect best the professional environment of the medical graduate who works as an integral part of a multi-disciplinary team, with the minimum dependence on the traditional lecture, where at all possible. Finally, options on assessment are discussed, e.g. multiple-choice questions, including their respective advantages and disadvantages.

Female Presidents of the "Royal College of Pathologists": Their Achievements and Contributions.

The Royal College of Pathologists (RCPath) celebrates its Diamond Jubilee in 2022 since its opening by Her Majesty Queen Elizabeth II in 1962. One of the main remits of RCPath is the overseeing of the training of pathologists and scientists working in pathology's 17 different specialties within the United Kingdom and across the globe. During its 60 years, three female Presidents have been elected: Dame Barbara Clayton (1984-1987), Dr. Suzannah (Suzy) Lishman CBE (2014-2017), and Prof. Joanne (Jo) Martin (2017-2020). Whilst Clayton specialised in Chemical Pathology and its relevance to public health, both Lishman and Martin are diagnostic cellular histopathologists with differing areas of expertise. This article reviews the contributions of these three distinguished and inspirational female pathologists to Pathology ("the science behind the cure"), to healthcare, public health and education, medical research, and to teaching. It highlights their qualities as leaders and mentors for those not only in medicine but in other career settings.

Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part II: Applications to the Diagnosis and Prognostic Monitoring of Oral and Systemic Cancers.

Human saliva offers many advantages over other biofluids regarding its use and value as a bioanalytical medium for the identification and prognostic monitoring of human diseases, mainly because its collection is largely non-invasive, is relatively cheap, and does not require any major clinical supervision, nor supervisory input. Indeed, participants donating this biofluid for such purposes, including the identification, validation and quantification of surrogate biomarkers, may easily self-collect such samples in their homes following the provision of full collection details to them by researchers. In this report, the authors have focused on the applications of metabolomics technologies to the diagnosis and progressive severity monitoring of human cancer conditions, firstly oral cancers (e.g., oral cavity squamous cell carcinoma), and secondly extra-oral (systemic) cancers such as lung, breast and prostate cancers. For each publication reviewed, the authors provide a detailed evaluation and critical appraisal of the experimental design, sample size, ease of sample collection (usually but not exclusively as whole mouth saliva (WMS)), their transport, length of storage and preparation for analysis. Moreover, recommended protocols for the optimisation of NMR pulse sequences for analysis, along with the application of methods and techniques for verifying and resonance assignments and validating the quantification of biomolecules responsible, are critically considered. In view of the authors' specialisms and research interests, the majority of these investigations were conducted using NMR-based metabolomics techniques. The extension of these studies to determinations of metabolic pathways which have been pathologically disturbed in these diseases is also assessed here and reviewed. Where available, data for the monitoring of patients' responses to chemotherapeutic treatments, and in one case, radiotherapy, are also evaluated herein. Additionally, a novel case study featured evaluates the molecular nature, levels and diagnostic potential of 1H NMR-detectable salivary 'acute-phase' glycoprotein carbohydrate side chains, and/or their monomeric saccharide derivatives, as biomarkers for cancer and inflammatory conditions.