The final part of the CRESS trilogy - how to evaluate the quality of stability studies.

High quality laboratory results are critical for patient management. However, poor sample quality can impact these results and patient safety. To ensure reliable and accurate results laboratories must be aware of each analyte's stability under various storage conditions and matrices to guarantee correct and dependable outcomes. This knowledge allows laboratories to define the allowable delay between sample collection and centrifugation/analysis for all analytes to guarantee appropriate results quality and interpretation. The EFLM WG-PRE therefore established a 4-step plan to tackle this issue, aiming to standardize and harmonize stability studies for improved comparison and meta-analysis. The plan included the development of checklists and how-to guides for performing and reporting stability studies as well as a central resource of stability data. This manuscript deals with the issue of evaluating publications and incorporating them into a central resource. To evaluate stability studies, the CRESS checklist was used to structure 20 sections used to judge the quality of studies. Each section has 4 levels of quality, with scores converted to numerical values and weighted based on expert opinion. Based on this, a final score ranging from A to D was determined. The procedure was then tested on six manuscripts and checked for agreement between expert judgements. The results demonstrated that the proposed evaluation process is a useful tool to distinguish between best in class manuscripts and those of lower quality. The EFLM WG-PRE strongly believes that the provided recommendations and checklists will help improving stability studies both in quality and standardisation.

Recommendations for blood sampling in emergency departments from the European Society for Emergency Medicine (EUSEM), European Society for Emergency Nursing (EuSEN), and European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase. Executive summary.

AIM: Blood Sampling Guidelines have been developed to target European emergency medicine-related professionals involved in the blood sampling process (e.g. physicians, nurses, phlebotomists working in the ED), as well as laboratory physicians and other related professionals. The guidelines population focus on adult patients. The development of these blood sampling guidelines for the ED setting is based on the collaboration of three European scientific societies that have a role to play in the preanalytical phase process: EuSEN, EFLM, and EUSEM. The elaboration of the questions was done using the PICO procedure, literature search and appraisal was based on the GRADE methodology. The final recommendations were reviewed by an international multidisciplinary external review group. RESULTS: The document includes the elaborated recommendations for the selected sixteen questions. Three in pre-sampling, eight regarding sampling, three post-sampling, and two focus on quality assurance. In general, the quality of the evidence is very low, and the strength of the recommendation in all the questions has been rated as weak. The working group in four questions elaborate the recommendations, based mainly on group experience, rating as good practice. CONCLUSIONS: The multidisciplinary working group was considered one of the major contributors to this guideline. The lack of quality information highlights the need for research in this area of the patient care process. The peculiarities of the emergency medical areas need specific considerations to minimise the possibility of errors in the preanalytical phase.

Recommendation for the design of stability studies on clinical specimens.

OBJECTIVES: Knowledge of the stability of analytes in clinical specimens is a prerequisite for proper transport and preservation of samples to avoid laboratory errors. The new version of ISO 15189:2022 and the European directive 2017/746 increase the requirements on this topic for manufacturers and laboratories. Within the project to generate a stability database of European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Preanalytical Phase (WG-PRE), the need to standardise and improve the quality of published stability studies has been detected, being a manifest deficit the absence of international guidelines for the performance of stability studies on clinical specimens. METHODS: These recommendations have been developed and summarised by consensus of the WG-PRE and are intended primarily to improve the quality of sample stability claims included in information for users provided by assay supplier companies, according to the requirements of the new European regulations and standards for accreditation. RESULTS: This document provides general recommendations for the performance of stability studies, oriented to the estimation of instability equations in the usual working conditions, allowing flexible adaptation of the maximum permissible error specifications to obtain stability limits adapted to the intended use. CONCLUSIONS: We present this recommendation based on the opinions of the EFLM WG-PRE group for the standardisation and improvement of stability studies, with the intention to improve the quality of the studies and the transferability of their results to laboratories.

Prenatal maternal cortisol, stress and anxiety, and childhood obesity at 5 years: a nested case-control study.

BACKGROUND: Paediatric obesity is a global public health issue. Prenatal maternal mental health is potentially implicated in the development of childhood obesity. This study examined associations between prenatal maternal cortisol, self-reported stress, anxiety and depression in the second trimester, and childhood overweight and obesity at 5 years of age. METHODS: A nested case-control study was conducted using data from the Irish prospective longitudinal birth cohort SCOPE BASELINE. Cases were children with overweight or obesity, operationalised as having a BMI z-score above +2 standard deviations. Controls were children with a BMI z-score between -0.5 and 0.5 standard deviations at 5 years of age. Two to one matching by sex was conducted. Thirty-eight cases and 83 sex-matched controls were included. Maternal serum cortisol concentration and self-reported stress, anxiety and depression were measured at 15 ± 1 and 20 ± 1 weeks gestation. Conditional logistic regression analyses were conducted to examine associations between prenatal maternal cortisol and self-reported stress, anxiety and depression, and childhood overweight and obesity. RESULTS: Despite some evidence for associations between anxiety and depression, and child BMI z-scores in univariate analyses, adjusted models indicated no associations between prenatal maternal stress (OR: 1.02, 95% CI: 0.94-1.12), anxiety (OR: 1.03, 95% CI: 0.97-1.09), depression (OR: 1.04, 95% CI: 0.91-1.19), or cortisol concentration (OR: 0.99, 95% CI: 0.99-1.00) and child BMI z-score. CONCLUSION: Our findings do not provide support for associations between foetal exposure during the second trimester of pregnancy and maternal cortisol, stress and anxiety, and childhood overweight or obesity at 5 years of age.

Factors associated with SARS-CoV-2 infection in patients attending an acute hospital ambulatory assessment unit.

To describe the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mild-to-moderate patients attending for assessment. This observational study was conducted in a Model 4 tertiary referral center in Ireland. All patients referred for SARS-CoV-2 assessment over a 4-week period were included. Patient demographics, presenting symptoms, comorbidities, medications, and outcomes (including length of stay, discharge, and mortality) were collected. Two hundred and seventy-nine patients were assessed. These patients were predominantly female (62%) with a median age of 50 years (SD 16.9). Nineteen (6.8%) patients had SARS-CoV-2 detected. Dysgeusia was associated with a 16-fold increased prediction of SARS-CoV-2 positivity (p = .001; OR, 16.8; 95% CI, 3.82-73.84). Thirteen patients with SARS-COV-2 detected (68.4%) were admitted, in contrast with 38.1% (99/260) of patients with SARS-CoV-2 non-detectable or not tested (p = .001). Female patients were more likely to be hospitalized (p = .01) as were current and ex-smokers (p = .05). We describe olfactory disturbance and fever as the main presenting features in SARS-CoV-2 infection. These patients are more likely to be hospitalized with increased length of stay; however, they make up a minority of the patients assessed. "Non-detectable" patients remain likely to require prolonged hospitalization. Knowledge of predictors of hospitalization in a "non-detectable" cohort will aid future planning and discussion of patient assessment in a SARS-CoV-2 era.

How to meet ISO15189:2012 pre-analytical requirements in clinical laboratories? A consensus document by the EFLM WG-PRE.

The International Organization for Standardization (ISO) 15189:2012 standard aims to improve quality in medical laboratories through standardization of all key elements in the total testing process, including the pre-analytical phase. It is hence essential that accreditation bodies, assessing laboratories against ISO15189:2012, pay sufficient attention to auditing pre-analytical activities. However, there are significant differences in how technical auditors interpret the pre-analytical requirements described in ISO15189:2012. In this consensus document, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Pre-analytical Phase (WG-PRE) sets out to review pre-analytical requirements contained in ISO15189:2012 and provide guidance for laboratories on how to meet these requirements. The target audience for this consensus document is laboratory professionals who wish to improve the quality of the pre-analytical phase in their laboratory. For each of the ISO requirements described in ISO15189:2012, members of EFLM WG-PRE agreed by consensus on minimal recommendations and best-in-class solutions. The minimal consensus recommendation was defined as the minimal specification which laboratories should implement in their quality management system to adequately address the pre-analytical requirement described in ISO15189:2012. The best-in-class solution describes the current state-of-the-art in fulfilling a particular pre-analytical requirement in ISO15189:2012. We fully acknowledge that not every laboratory has the means to implement these best-in-class solutions, but we hope to challenge laboratories in critically evaluating and improving their current procedures by providing this expanded guidance.

A proposed Common Training Framework for Specialists in Laboratory Medicine under EU Directive 2013/55/EC (The Recognition of Professional Qualifications).

European Union (EU) Directive 2013/55/EC (The Recognition of Professional Qualifications) allows Member States to decide on a common set of minimum knowledge, skills and competences that are needed to pursue a given profession through a Common Training Framework. To be adopted the framework must combine the knowledge, skills and competences of at least one third of the Member States. Professionals who have gained their qualifications under a Common Training Framework will be able to have these recognised automatically within the Union. The backbone of the European Federation of Clinical Chemistry and Laboratory Medicine's (EFLM) proposed Common Training Framework for non-medical Specialists in Laboratory Medicine is outlined here. It is based on an Equivalence of Standards in education, training, qualifications, knowledge, skills, competences and the professional conduct associated with specialist practice. In proposing the recognition of specialist practice EFLM has identified 15 EU Member States able to meet Equivalence and in whom the profession and/or its training is regulated (an additional EU Commission requirement). The framework supports and contributes to the Directive's enabling goals for increasing professional mobility, safeguarding consumers and ensuring a more equitable distribution of skills and expertise across the Member States. It represents EFLM's position statement and provides a template for professional societies and/or competent authorities to engage with the EU Commission.

Managing hemolyzed samples in clinical laboratories.

Hemolysis is conventionally defined as membrane disruption of red blood cells and other blood cells that is accompanied by subsequent release of intracellular components into the serum or plasma. It accounts for over 60% of blood sample rejections in the laboratory and is the most common preanalytical error in laboratory medicine. Hemolysis can occur both in vivo and in vitro. Intravascular hemolysis (in vivo) is always associated with an underlying pathological condition or disease, and thus careful steps should always be taken by the laboratory to exclude in vivo hemolysis with confidence. In vitro hemolysis, on the other hand, is highly preventable. It may occur at all stages of the preanalytical phase (i.e. sample collection, transport, handling and storage), and may lead to clinically relevant, yet spurious, changes in patient results by interfering with laboratory measurements. Hemolysis interference is exerted through several mechanisms: (1) spectrophotometric interference, (2) release of intracellular components, (3) sample dilution and (4) chemical interference. The degree of interference observed depends on the level of hemolysis and also on the assay methodology. Recent evidence shows that preanalytical practices related to detection and management of hemolyzed samples are highly heterogeneous and need to be standardized. The Working Group for Preanalytical Phase (WG-PRE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has published many recommendations for facilitating standardization and improvement of this important preanalytical issue. Some key EFLM WG-PRE publications related to hemolysis involve: (i) a call for more transparency and some practical recommendations for improving the harmonization of the automatic assessment of serum indices and their clinical usefulness, specifically the hemolysis index (H-index), (ii) recommendations on how to manage local quality assurance of serum or plasma hemolysis/icterus/lipemia-indices (HIL-indices) and (iii) recommendations on how to detect and manage hemolyzed samples in clinical chemistry testing. In this review we provide a comprehensive overview of hemolysis, including its causes and effects on clinical laboratory assays. Furthermore, we list and discuss the most recent recommendations aimed at managing hemolyzed samples in everyday practice. Given the high prevalence of hemolyzed blood samples, the associated costs, the great heterogeneity in how hemolysis is handled across healthcare settings, countries and continents, and increasing patient cross-border mobility, standardization and quality improvement processes aimed at combatting this important preanalytical problem are clearly warranted.

The CRESS checklist for reporting stability studies: on behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase (WG-PRE).

To ensure that clinical laboratories produce results that are both accurate and of clinical utility it is essential that only samples of adequate quality are analysed. Although various studies and databases assessing the stability of analytes in different settings do exist, guidance on how to perform and report stability studies is lacking. This results in studies that often do not report essential information, thus compromising transferability of the data. The aim of this manuscript is to describe the Checklist for Reporting Stability Studies (CRESS) against which future studies should be reported to ensure standardisation of reporting and easy assessment of transferability of studies to other healthcare settings. The EFLM WG-PRE (European Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Preanalytical Phase) produced the CRESS checklist following a detailed literature review and extensive discussions resulting in consensus agreement. The checklist consists of 20 items covering all the aspects that should be considered when producing a report on a stability study including details of what should be included for each item and a rationale as to why. Adherence to the CRESS checklist will ensure that studies are reported in a transparent and replicable way. This will allow other laboratories to assess whether published data meet the stability criteria required in their own particular healthcare scenario. The EFLM WG-PRE encourage researchers and authors to use the CRESS checklist as a guide to planning stability studies and to produce standardised reporting of future stability studies.

Use of a standard urine assay for measuring the phosphate content of beverages.

Hyperphosphatemia is strongly associated with cardiovascular morbidity and mortality in patients with chronic kidney disease. Phosphate in beverages is readily absorbed and could have a significant impact on serum phosphate levels. Patients are routinely warned about the phosphoric acid in colas, but information on the phosphate content of other beverages is difficult to find. We have shown that the phosphomolybdate method, which is used in the vast majority of hospital laboratories for measuring phosphate in urine, can give an accurate measurement of the phosphate content of beer, cider, wine, and soft drinks. No change to the standard assay protocol is required. There was considerable variation between different types of wine and beer, probably due to the methods of production. The information the assay provides could enable staff providing dietary advice to compare locally available beverages and help patients to avoid or limit their intake of those with high phosphate content.

Current practice and recommendations for managing transgender patient data in clinical laboratories in the United Kingdom and Republic of Ireland.

BACKGROUND: Transgender people may avoid seeking medical care due to previous negative experiences and fear of discrimination. Clinical laboratories can contribute to a poor patient experience and clinical outcome when the design and functionality of laboratory information management systems (LIMS) do not consider the needs of transgender patients. This survey aimed to capture current practices in United Kingdom and Republic of Ireland clinical laboratories concerning how transgender patient data and test requests are managed throughout the total testing process. METHODS: An anonymous survey was distributed to clinical laboratory professionals in November 2021. Thirty-three questions covered how gender variables are recorded for transgender patients and used to inform gender-specific calculations, test access, and reference intervals (RIs). RESULTS: Of the 66 respondents, 70% were based in laboratories in England, with a majority of laboratories having ISO 15189 accreditation and processing 1000-10,000 blood samples daily. Eighty-five percent stated that their LIMS had a single field recording sex or gender information. Forty-three percent did not limit test access based on gender, but 68% did not append RIs for patients with unknown or indeterminate gender. CONCLUSIONS: This survey was the first to quantify how clinical laboratories manage sex and gender information and report results for transgender and non-binary patients, and details several key recommendations based on the survey responses.

Challenges of providing biochemistry results in a patient with Evans syndrome.

A case report of in vivo hemolysis in a female patient with Evans syndrome is described. The patient was admitted with anemia and jaundice and, during her 26-day hospital admission, had 83 samples taken for biochemistry analyses. The laboratory hemolytic index (HI) was frequently elevated due to persistent complement-mediated in vivo hemolysis despite multiple lines of therapy. Initially, the release of many biochemical parameters was blocked per the manufacturer´s recommendations and reported as "sample hemolyzed". The patient developed severe acute kidney injury, ultimately requiring dialysis. Automated and timely reporting of indicative creatinine and other biochemical results in the context of ongoing hemolysis, therefore, became essential to patient care. Following a review of literature from various sources, a laboratory algorithm was designed to ensure the timely release of numerical biochemical values, where possible, with appropriate interpretative comments appended. Biochemistry, hematology, and nephrology teams were in regular communication to ensure patient samples were rapidly identified, analyzed and validated according to the algorithm, informing timely, safe and appropriate patient care. Ultimately, the patient died due to multiple disease- and treatment-related complications. In conjunction with clinical users, laboratories should plan for situations, such as in vivo hemolysis, where significant unavoidable interferences in biochemistry methodologies may occur in an ongoing manner for certain patients. Reporting categorical or best-estimate biochemistry results in such cases can be safer for patients than failing to report any results. Interpretation of these results by clinical teams requires input from appropriately trained and qualified laboratory personnel.

Dealing with digital paralysis: Surviving a cyberattack in a National Cancer center.

INTRODUCTION: Cyberattacks represent a growing threat for healthcare delivery globally. We assess the impact and implications of a cyberattack on a cancer center in Ireland. METHODS: On May 14th 2021 (day 0) Cork University Hospital (CUH) Cancer Center was involved in the first national healthcare ransomware attack in Ireland. Contingency plans were only present in laboratory services who had previously experienced information technology (IT) failures. No hospital cyberattack emergency plan was in place. Departmental logs of activity for 120 days after the attack were reviewed and compared with historical activity records. Daily sample deficits (routine daily number of samples analyzed - number of samples analyzed during cyberattack) were calculated. Categorical variables are reported as median and range. Qualitative data were collected via reflective essays and interviews with key stakeholders from affected departments in CUH. RESULTS: On day 0, all IT systems were shut down. Radiotherapy (RT) treatment and cancer surgeries stopped, outpatient activity fell by 50%. hematology, biochemistry and radiology capacity fell by 90% (daily sample deficit (DSD) 2700 samples), 75% (DSD 2250 samples), and 90% (100% mammography/PET scan) respectively. Histopathology reporting times doubled (7 to 15 days). Radiotherapy (RT) was interrupted for 113 patients in CUH. The median treatment gap duration was six days for category 1 patients and 10 for the remaining patients. Partner organizations paused all IT links with CUH. Outsourcing of radiology and radiotherapy commenced, alternative communication networks and national conference calls in RT and Clinical Trials were established. By day 28 Email communication was restored. By day 210 reporting and data storage backlogs were cleared and over 2000 computers were checked/replaced. CONCLUSION: Cyberattacks have rapid, profound and protracted impacts. While laboratory and diagnostic deficits were readily quantified, the impact of disrupted/delayed care on patient outcomes is less readily quantifiable. Cyberawareness and cyberattack plans need to be embedded in healthcare. POLICY SUMMARY: Cyberattacks pose significant challenges for healthcare systems, impacting patient care, clinical outcomes, and staff wellbeing. This study provides a comprehensive review of the impact of the Conti ransomware attack on cancer services in Cork University Hospital (CUH), the first cyberattack on a national health service. Our study highlights the widespread disruption caused by a cyberattack including shutdown of information technology (IT) services, marked reduction in outpatient activity, temporary cessation of essential services such as radiation therapy. We provide a framework for other institutions for mitigating the impact of a cyberattack, underscoring the need for a cyberpreparedness plan similar to those made for natural disasters and the profound legacy of a cyberattack on patient care.

Hepatitis C community prevalence is over-estimated: a prospective, birth cohort study.

BACKGROUND: Hepatitis C virus infection is often asymptomatic, and many patients may be unaware they are infected. Community-based, birth cohort screening has been advocated to identify these patients. It has been estimated that 0.7-1% of individuals born between 1965 and 1985 in Ireland are infected. The cost-effectiveness of screening is critically dependent on the population prevalence. AIMS: The aim is to determine the community prevalence of hepatitis C virus infection in the birth cohort 1965-1985. METHODS: Residual serum samples from blood tests ordered by community general practitioners were anonymised and analysed for the presence of hepatitis C antibody ± antigen. Twelve large general hospitals throughout the country participated. RESULTS: A total of 14,320 samples were tested, 9347 of which were from the birth cohort 1965-1985. Seventy-two samples were positive for hepatitis C antibody of which 12 were positive for hepatitis C antigen (17%). The overall prevalence of hepatitis C antigen in the birth cohort was 0.09%. A higher prevalence (0.39%) was identified in males in two urban areas of Dublin. CONCLUSIONS: Hepatitis C virus seroprevalence was much lower than previously estimated. The proportion of antibody positive patients with hepatitis C antigen was also lower than expected suggesting the effects of treatment and/or high spontaneous viral clearance. Universal birth cohort screening is unlikely to be cost-effective. Targeted birth cohort screening in high prevalence areas could be considered.

Instructions on appropriate fasting prior to phlebotomy; effects on patient awareness, preparation, and biochemical parameters.

OBJECTIVES: This study investigated the effect of appropriate pre-phlebotomy instructions on patients' awareness of the need to fast, their fasting status at phlebotomy, and the measurement of specific biochemical analytes and indices. METHODS: While booking their phlebotomy appointments, two-hundred outpatients, with a wide range of pre-existing medical conditions, were recruited and randomly assigned to either control or intervention groups. The control group received no instructions while the intervention group was verbally instructed to fast for precisely 12 h prior to their appointment. Serum samples were collected from participants to quantify common biochemical analytes and serum indices, some of which were known to be influenced by fasting status, such as triglyceride and the lipaemic index. At the same appointment, participants completed a survey assessing their perception of, and adherence to, fasting requirements. RESULTS: In the intervention group, 99% responded that they had fasted before phlebotomy vs. 16% of controls. Subjects stated they fasted for 12 h in 51% of the intervention group and 7% of the controls. Median concentrations for potassium and total bilirubin were statistically, but not clinically, significantly different. In the study, a single patient in the intervention group was found to have a lipaemic sample. CONCLUSIONS: Without instruction, it appears few patients will fast appropriately prior to blood collection. This study suggests that most patients recall and adhere to verbal instructions regarding fasting. Though many in the control group stated they did not fast, triglyceride concentration and lipaemia were not significantly different from the intervention group, and biochemical analyses appear unaffected by fasting status.

A survey of practice in the management of haemolysis, icterus and lipaemia in blood specimens in the United Kingdom and Republic of Ireland.

BACKGROUND: Haemolysis, icterus and lipaemia (HIL) are common interferants in laboratory medicine, potentially impacting patient care. This survey investigates HIL management in medical laboratories across the UK and Republic of Ireland (ROI). METHODS: A survey was sent to members of key professional organisations for laboratory medicine in the UK and ROI. Questions related to the detection, monitoring, quality control, and management of HIL. RESULTS: In total, responses from 124 laboratories were analysed, predominantly from England (52%) and ROI (36%). Most responses were from public hospitals with biochemistry services (90%), serving primary care (91%), inpatients (91%), and outpatients (89%). Most laboratories monitored H (98%), I (88%), and L (96%) using automated indices (93%), alone or in combination with visual inspection.Manufacturer-stated cut-offs were used by 83% and were applied to general chemistries in 79%, and immunoassays in 50%. Where HIL cut-offs are breached, 64% withheld results, while 96% reported interference to users. HIL were defined using numeric scales (70%) and ordinal scales (26%). HIL targets exist in 35% of laboratories, and 54% have attempted to reduce HIL. Internal Quality Control for HIL was lacking in 62% of laboratories, and just 18% of respondents have participated in External Quality Assurance. Laboratories agree manufacturers should: standardise HIL reporting (94%), ensure comparability between platforms (94%), and provide information on HIL cross-reactivity (99%). Respondents (99%) showed interest in evidence-based, standardised HIL cut-offs. CONCLUSIONS: Most respondents monitor HIL, although the wide variation in practice may differentially affect clinical care. Laboratories seem receptive to education and advice on HIL management.

Thyroid dysfunction in a UK hepatitis C population treated with interferon-alpha and ribavirin combination therapy.

OBJECTIVE: To assess the incidence of thyroid dysfunction (TD) in a UK cohort of patients with hepatitis C virus (HCV) infection treated with interferon-alpha (IFNalpha) and ribavirin combination therapy (IFN/RBV). DESIGN, PATIENTS AND MEASUREMENTS: A retrospective study of 288 patients who received IFN/RBV for HCV during a 2-year period from January 2006 was performed. Thyroid function was assessed during a 24-week or 48-week course of IFN/RBV. If serum thyrotrophin (TSH) became undetectable (<0.01 mU/l) and serum free thyroxine (T4) was raised, a diagnostic thyroid isotope scan was performed. RESULTS: Full medical records were examined for 260 patients (172 men, 88 women) included in the study, of whom 22.3% (16.9% of men, 33.0% of women) developed TD during IFN/RBV. In total, 10.4% developed a suppressed serum TSH (0.8% Graves' disease, 9.6% transient thyroiditis) while 11.9% developed an elevated serum TSH with 1.5% becoming permanently hypothyroid and requiring levothyroxine therapy. Women had a relative risk (RR) for developing TD of 1.96 (CI: 1.75-3.03, P = 0.004). A serum TSH > or =1.75 mU/l and a positive thyroid peroxidase (TPO) antibody titre pretherapy were associated with RRs for progression to TD of 6.02 (CI: 2.95-12.78, P < 0.0001) and 4.35 (CI: 2.58-6.52; P < 0.0001), respectively, while combination of baseline TSH and TPO antibody data predicted progression to TD with a sensitivity of 94.7%. CONCLUSIONS: Although TD was common in this cohort, just 2.3% developed TD that required ongoing therapy. Pre-IFN/RBV serum TSH and TPO antibody titre were found to predict progression to TD in this group of patients.

Case report of spuriously low sodium and calcium in a 36-year-old male in primary care.

An unseparated serum specimen for a 36-year-old male was received from primary care. The specimen arrived in the laboratory at Cork University Hospital one day after collection, as documented on the paper request card, and was promptly centrifuged. Analysis was delayed for three days due to operational constraints and serum indices were run at the same time as the biochemical analyses. Results showed a moderately haemolysed specimen with remarkably low concentrations of both sodium (119 mmol/L) and total calcium (1.15 mmol/L), with all other parameters within their appropriate reference intervals (RIs). The complete report was released electronically and both sodium and calcium results were phoned to, and acknowledged by, the requesting general practitioner (GP). Discussion between the medical scientists and clinical biochemist on duty raised the possibility that the specimen was significantly older than initially thought. Further discussion of results with the GP clarified that the documented time of collection corresponded with specimen receipt by the courier, rather than the time of phlebotomy. Thus, the specimen was 7 days old when received in the laboratory and 10 days old when analysed. This case illustrates the dangers of multiple convergent preanalytical errors. Laboratories should be mindful of the stability of analytes in unseparated blood and unusual patterns of results which might suggest a specimen is "old", and that this may coexist with erroneous request information. Any potential adverse effects on patient care were prevented in this case by laboratory vigilance.

Case report of a phantom pheochromocytoma.

Plasma free metanephrines or urinary fractionated metanephrines are the biochemical tests of choice for the diagnosis of pheochromocytoma as they have greater sensitivity and specificity than catecholamines for pheochromocytoma detection. This case highlights the preanalytical factors which can influence metanephrine measurement and cause a false positive result. It describes a patient with a high pre-test probability of pheochromocytoma due to hypertension and a past medical history of adrenalectomy for a purported pheochromocytoma in her home country. When biochemical screening revealed grossly elevated urine normetanephrine in the presence of a previously identified right adrenal lesion, there was high clinical suspicion of a pheochromocytoma. However, functional imaging did not support this view which prompted additional testing with plasma metanephrines. Results for plasma and urine metanephrines were discordant and preanalytical drug interference was suspected. Patient medications were reviewed and sulfasalazine, an anti-inflammatory drug was identified as the most likely analytical interferent. Urinary fractionated metanephrines were re-analysed using liquid chromatography tandem mass spectrometry (LC-MS/MS) and all metanephrines were within their reference intervals. This case illustrates how method-specific analytical drug interference prompted unnecessary expensive imaging, heightened patient anxiety and resulted in lengthy investigations for what turned out to be a phantom pheochromocytoma.

COVID-19 in adults: test menu for hospital blood science laboratories.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), is a respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Clinical Blood Sciences Laboratory (CBSL) plays a key role in supporting the monitoring and management of patients with COVID-19 disease. OBJECTIVE: To provide a comprehensive CBSL testing protocol to support the medical management of SARS-CoV-2 infection. METHODS: Description of the biochemical, haematological and immunological tests that have a role in the assessment and monitoring of patients with COVID-19 infection. RESULTS: We provide a test menu for clinical laboratories to ensure the effective monitoring, management and prognostication of COVID-19 patients in hospital. CONCLUSION: Given the rapidity with which patients with COVID-19 disease can deteriorate, we recommend regular testing with vigilance paid to the rate and trajectory of change in each of these parameters.