The Diagnosis of Normocalcaemic Hyperparathyroidism is Strikingly Dissimilar Using Different Commercial Laboratory Assays.

We assessed the impact of intact parathyroid hormone (iPTH) and adjusted calcium analyses on Abbott, Roche and Siemens analytical platforms in the diagnosis of normocalcaemic primary hyperparathyroidism (NCPHPT). These assays are used by over 85% of clinical laboratories in the UK. Over five months, consecutive serum samples from outpatients with NCPHPT in the laboratory with Abbott assays were identified, aliquoted and stored at -80°C. Frozen aliquots were transported monthly to the other two laboratories. After thawing, samples were mixed and analysed immediately for calcium, albumin and iPTH in the laboratories with Abbott, Roche and Siemens analytical platforms. Adjusted calcium was calculated using the equation used in the respective laboratory. Diagnostic concordance of iPTH and adjusted calcium were assessed using manufacturer-provided assay-specific reference intervals and the pathology harmony reference interval respectively. Fifty-five patients with NCPHPT were identified using Abbott assays. Of these, 16 (29.1%) and 11 (20.0%) had NCPHPT, 9 (16.4%) and 13 (23.6%) had hypercalcaemic primary hyperparathyroidism, and 30 (54.6%) and 31 (56.4%) patients had normal results when analysed in laboratories with Roche and Siemens assays, respectively. The diagnosis of NCPHPT was strikingly different depending on the commercial assay used. There is a pressing need for iPTH assay harmonisation and robust reference intervals. Reference intervals may become invalid if an assay drifts, as exemplified by adjusted calcium in this study.

The diagnosis and management of subclinical hypothyroidism is assay-dependent- Implications for clinical practice.

OBJECTIVE: We assessed the commutativity of Roche and Abbott thyroid assays in the diagnosis and management of subclinical hypothyroidism (SCH). The Roche and Abbott thyroid assays are used by approximately 75% of clinical laboratories in the UK. METHOD: Consecutive samples received from primary care on patients with SCH who had a raised thyroid-stimulating hormone (TSH) <10 mIU/L and a normal free thyroxine (fT4) from two laboratories using either Roche or Abbott thyroid assays were identified over 10 working days. Following identification, samples were analysed at the other site within 24 hours. Diagnostic and management discordance were studied using the relevant manufacturer-provided reference ranges. RESULTS: We identified 93 patients with SCH (53 using the Roche assay). Roche TSH and fT4 results were respectively 40% ± 15% and 16% ± 7% higher (P < .001) compared to Abbott results. Of the 93 patients, 41 (44%) were concordant for SCH on both methods. Of the 53 patients with SCH on the Roche assays, 40 (75.5%) had normal thyroid function and 13 (24.5%) had SCH when analysed using the Abbott assays. Of the 40 patients with SCH on the Abbott assays, 28 (70%) had SCH and 12 (30%) had results indicative for levothyroxine replacement when analysed on the Roche assays. Of these 12 patients, four had TSH > 10 mIU/L, five had low fT4 and three had both. CONCLUSION: The diagnosis and management of SCH is strikingly different when using TSH and fT4 assays provided by Abbott Laboratories and Roche Diagnostics. Clinicians and laboratorians should be aware that between-assay differences and variations in reference ranges will directly impact the diagnosis and management of subclinical hypothyroidism.

The Relationship Between Intact Parathyroid Hormone and 25-Hydroxyvitamin D in United Kingdom Resident South Asians and Whites: A Comparative, Cross-Sectional Observational Study.

Ethnic differences in intact parathyroid hormone (iPTH) at similar total 25 hydroxyvitamin D [25(OH)D] concentrations have been reported between US resident Whites, Blacks, and Hispanics, but this has not been studied between South Asians and Whites. We, therefore, compared the iPTH relationship to 25(OH)D in UK resident South Asians and Whites. A comparative, cross-sectional observational study in which demographic and laboratory data on South Asian and White residents of Wolverhampton, UK were analyzed. Log-log models measured the association between 25(OH)D and the interaction term of ethnicity and iPTH. Seven hundred and seventy-two patients consisting of 315 white subjects (208 women) and 457 South Asian subjects (331 women) were studied. Compared to South Asians, White subjects were older, had higher serum concentrations of 25(OH)D, creatinine (lower eGFR), adjusted calcium and magnesium, but similar concentrations of iPTH and phosphate. In an adjusted model, variables significantly associated with 25(OH)D included age, creatinine, adjusted calcium and ethnicity; but not iPTH and the interaction term of ethnicity and iPTH (beta coefficient -0.071, 95% CI -0.209, 0.067, p=0.32). In our study cohort, iPTH was not, per se, influenced by 25 (OH)D. We found no ethnic differences in the association between iPTH and 25(OH)D between South Asians and White UK residents.

Early availability of laboratory results increases same day ward discharge rates.

BACKGROUND: Delayed discharge reduces hospital efficiency and inconveniences patients. Most hospitals discharge in the afternoon, whereas the most common admission time is mid-morning. Consequently, new patients wait for the beds of patients who are fit to be discharged. Earlier discharge may, therefore, improve patient flow. We investigated the impact of early phlebotomy with early availability of laboratory results on patient discharge rates and discharge time. METHODS: Discharge rates, discharge time and sample turnaround time were assessed before (1 October 2014 to 31 December 2014) and after (1 October 2015 to 31 December 2015) introduction of earlier phlebotomy with availability of laboratory results prior to the ward rounds on two surgical wards. RESULTS: Following the intervention, over 95% of results were available before 8:30 am in 2015 as compared to less than 1% in 2014. Specimen turnaround times were similar in both study periods. Even after adjustment for age, gender, admission type and length of admission, the same day discharge rate was higher in 2015 compared to 2014 (60% vs. 52%; p<0.002), but time of discharge was unchanged. CONCLUSIONS: Early availability of blood results prior to ward rounds increased ward discharges but did not affect discharge time.

The frequency of testing for glycated haemoglobin, HbA1c, is linked to the probability of achieving target levels in patients with suboptimally controlled diabetes mellitus.

Background We previously showed, in patients with diabetes, that >50% of monitoring tests for glycated haemoglobin (HbA1c) are outside recommended intervals and that this is linked to diabetes control. Here, we examined the effect of tests/year on achievement of commonly utilised HbA1c targets and on HbA1c changes over time. Methods Data on 20,690 adults with diabetes with a baseline HbA1c of >53 mmol/mol (7%) were extracted from Clinical Biochemistry Laboratory records at three UK hospitals. We examined the effect of HbA1c tests/year on (i) the probability of achieving targets of ≤53 mmol/mol (7%) and ≤48 mmol/mol (6.5%) in a year using multi-state modelling and (ii) the changes in mean HbA1c using a linear mixed-effects model. Results The probabilities of achieving ≤53 mmol/mol (7%) and ≤48 mmol/mol (6.5%) targets within 1 year were 0.20 (95% confidence interval: 0.19-0.21) and 0.10 (0.09-0.10), respectively. Compared with four tests/year, having one test or more than four tests/year were associated with lower likelihoods of achieving either target; two to three tests/year gave similar likelihoods to four tests/year. Mean HbA1c levels were higher in patients who had one test/year compared to those with four tests/year (mean difference: 2.64 mmol/mol [0.24%], p<0.001). Conclusions We showed that ≥80% of patients with suboptimal control are not achieving commonly recommended HbA1c targets within 1 year, highlighting the major challenge facing healthcare services. We also demonstrated that, although appropriate monitoring frequency is important, testing every 6 months is as effective as quarterly testing, supporting international recommendations. We suggest that the importance HbA1c monitoring frequency is being insufficiently recognised in diabetes management.

Salivary testosterone changes during oral glucose tolerance tests in overweight and obese men - Postprandial or circadian variation?

BACKGROUND: Serum total testosterone (T) decreases postprandially. Postprandial salivary testosterone (SalT) responses, however, have not been studied. We report on the effect of glucose ingestion on fasting SalT concentrations. OBJECTIVE: To investigate the effect of oral glucose ingestion on fasting SalT. METHODS: Salivary and blood samples were collected between 09.00 and 09.30 and 2 hours after a 75g oral glucose load in 32 men with mean (standard deviation) age of 52 (5.7) years and body mass index of 32.6 (5.56) kg/m2. Free T and bioavailable testosterone (BAT) were calculated using the Vermeulen equation. RESULTS: Two hours following oral glucose, there was a decrease in fasting mean (standard deviation) SalT [178.2 (56.6) versus 146.0 (42.2) pmol/L; P = .0003], serum cortisol [332 (105.0) versus 239 (75.3) nmol/L; P = <0.0001], prolactin [193 (75.0) versus 127 (55.9) mIU/L; P = <0.0001] and TSH [1.60 (0.801) versus 1.16 (0.584) mIU/L; P = <0.0001]. Plasma glucose increased [6.2 (0.72) versus 8.1 (3.71) mmol/L; P = .0029]. Serum total T, SHBG, albumin, Free T, BAT, gonadotrophins and FT4 remained unchanged. CONCLUSIONS: SalT decreased postprandially. A concomitant decrease in serum cortisol, prolactin and TSH reflecting diurnal variation offers an alternative explanation for the decrease in SalT independent of food consumption. Further studies are required to determine whether morning temporal changes in SalT are related to food consumption or circadian rhythm or both.

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.

The effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on serum uric acid in patients without gout: a prospective study.

OBJECTIVE: Acute gout is associated with a decrease in serum uric acid (SUA) that is considered to be in response to acute inflammation but it may be a feature of gout itself. We, therefore, aimed to investigate the effect of the acute systemic inflammatory response (SIR) on SUA concentrations in subjects without gout. METHODS: SUA and urinary excretion of uric acid (UA) (expressed as fractional excretion of UA; FEua%) were measured in 30 patients before and 48 h after elective knee or hip surgery. The SIR was assessed by measuring serum CRP and urine microalbumin excretion [expressed as the albumin-creatinine ratio (ACR)] before and after surgery in the same patients. RESULTS: The mean (s.d.) serum CRP increased following surgery [5.0 (5.5) vs 116.0 (81.2) mg/l; P < 0.0001) as did urine ACR [0.85 (1.03) vs 2.10 (2.60) mg/mmol; P = 0.004]. SUA decreased following surgery [312 (64) vs 282 (82) µmol/l; P = 0.0033] but FEua% was unchanged [6.4 (2.3) vs 7.3 (3.3)%; P = 0.1726]. CONCLUSION: The SIR is associated with a decrease in SUA concentrations in normouricaemic patients without gout. The decrease in SUA concentrations is not due to increased urinary excretion of UA. This study supports the notion that the decrease in SUA during acute gout is due to the associated SIR rather than gout per se.

Managing ethylenediaminetetraacetic acid (EDTA) interference in EDTA contaminated samples - selectivity in reporting analytes.

BACKGROUND: The widely accepted practice of not reporting any results from ethylenediaminetetraacetic acid (EDTA) contaminated samples necessitates repeat phlebotomy and could delay clinical management decisions. EDTA, however, interferes variably or not at all in assays. EDTA concentration in contaminated samples, like serum indices, therefore, could be used to selectively report the result of analytes not affected at measured EDTA concentration. METHODS: A serum pool, level 1 and level 3 internal quality control materials were spiked with tripotassium-EDTA to create samples with EDTA concentration up to 6.0 mmol/L. EDTA and 45 common and critically important analytes were measured on Abbott Architect to identify EDTA concentrations for analytes where the change in concentration exceeded their respective reference change value (RCV) for unidirectional change at 95% probability. RESULTS: Serum potassium increased and calcium decreased exceeding RCV at 0.17 mmol/L EDTA. Alkaline phosphatase (ALP) decreased exceeding RCV at EDTA >1.86 mmol/L. The decrease in iron did not exceed a wide RCV of 61.9% until maximum spiked EDTA but exceeded the desirable specification for allowable total error (30.7%) at EDTA >1.86 mmol/L. The small decrease in magnesium did not exceed RCV. EDTA up to the concentration in blood collection tubes did not affect the results of any other measured analyte. CONCLUSIONS: Only serum potassium, calcium, ALP and iron studies, of the 45 analytes studied, should not be reported in EDTA contaminated samples. EDTA concentration cut-offs for selective reporting would further facilitate reporting of these analytes in EDTA contaminated samples.

Effect of automated feedback laboratory comments promoting good phlebotomy practice on the frequency of ethylenediaminetetraacetic acid (EDTA) contamination of serum samples.

BACKGROUND: Ethylenediaminetetraacetic acid (EDTA) contamination of serum samples is common but under-recognized unless EDTA is measured. Incorrect order of draw with closed phlebotomy (vacutainer) does not cause EDTA contamination. EDTA contamination occurs largely or solely during open phlebotomy due to syringe tip or needle-tip contamination when delivering blood into EDTA sample tubes before other sample tubes or direct transfer of blood from EDTA containing tubes to other tubes. Therefore, preference for closed phlebotomy or following the order of tube fill when open phlebotomy is used may reduce EDTA contamination. METHODS: The laboratory's comments for EDTA-contaminated serum samples were amended to encourage closed phlebotomy and with open phlebotomy filling of serum tubes before EDTA and fluoride-EDTA tubes. The weekly frequency of EDTA sample contamination, normalized for weekly urea and electrolyte (U&E) requests, was studied 52 weeks before and 43 weeks after amending the comments. RESULTS: Median (IQR) frequency of EDTA-contaminated samples per week per 10,000 U&Es decreased by 58% [5.6 (3.1-9.2) versus 2.3 (1.1-4.4); P < 0.001] after the introduction of the new comment. CONCLUSION: Explicit automated laboratory feedback comments promoting closed phlebotomy and order of tube fill with open phlebotomy were associated with a 58% reduction in EDTA-contaminated samples and thus may play a role in improving phlebotomy practise.

Acid freezes uricolysis in addition to glycolysis: Utility of fluoride-EDTA-citrate tube in the measurement of uric acid for patients administered rasburicase.

BACKGROUND: In samples from patients administered rasburicase, ex vivo uricolysis leads to spuriously low uric acid results. The manufacturer's recommendation of storing the sample in ice-water until analysis, however, does not fully arrest uricolysis. Since uricase activity is affected by pH and metal chelators, we assessed uricolysis inhibition in sodium fluoride-ethylenediaminetetraacetic acid (EDTA)-citrate sample tube (FC Mix tube, Greiner) used primarily for plasma glucose. METHOD: A serum pool was spiked with rasburicase and uric acid measured at 15, 45, 90, 150, 240 and 1080 min in a lithium heparin tube in ice-water, plain tube at room temperature (RT), EDTA tube at RT, FC Mix tube in ice-water, FC Mix tube at RT and FC Mix tube at RT prepared by dissolving FC Mix in serum. RESULTS: The rate of urate decay was lowest in the FC Mix tube independent of temperature, then lithium heparin tube in ice-water, then EDTA tube at RT and highest in the plain tube at RT. Uric acid concentrations in the prepared FC Mix tube at RT and heparin tube in ice-water were, respectively, 98.2% and 93.8% of control values at 90 min, 97.1% and 89.3% of control values at 4 h, and remained higher in the prepared FC Mix tube at all time points. CONCLUSION: NaF-EDTA-citrate mixture largely arrested rasburicase mediated ex vivo uricolysis without the need for sample cooling. We propose that sample tubes containing NaF-EDTA-citrate be used for the measurement of uric acid in patients administered rasburicase.

Clinical concordance assessment should be an integral component of laboratory method comparison studies: A regression transference of routine clinical data approach.

Manufacturer-provided assay-specific reference intervals may not compensate for between assay differences leading to method related clinical discordance. Not all laboratories, however, assess clinical concordance as part of method comparison studies. We assessed the utility of method comparison data combined with routine clinical data to assess method related clinical concordance in the diagnosis and management of subclinical hypothyroidism (SCH). Passing-Bablok method comparison regression analysis was performed for both thyroid stimulating hormone (TSH) and free thyroxine (fT4) from 100 samples analysed by Abbott and Roche methods. Primary care samples indicative of SCH were identified from the laboratory information system (LIMS) of two laboratories (one with Roche methods and one with Abbott) over four months. For Roche and Abbott TSH and fT4 results, the Passing-Bablok regression equations were used to predict Abbott and Roche results respectively. The predicted results were interpreted using manufacturer-provided assay-specific reference intervals and compared to those of the previous SCH sample exchange study. On laboratory method comparison, Roche TSH and fT4 results were 30 ± 13% and 16 ± 7% higher compared to Abbott assays respectively. Of those with results indicative of SCH by Roche assays, 76.8% would have had normal thyroid function using predicted Abbott assay results and 46.9% of those with results indicative of SCH by Abbott assays would have had a biochemical indication for levothyroxine replacement using predicted Roche assay results. The results from the regression-based approach were comparable to the previous SCH sample exchange study. A regression-based approach using routine method comparison data and real-world clinical data identifies potential clinical discordance. We suggest that clinical concordance assessment be an integral component of laboratory method comparison studies.

Conflicting effects of haemolysis on plasma sodium and chloride are due to different haemolysis study protocols: A case for standardisation.

BACKGROUND: Haemolysis has been reported as having a positive, negative or no effect on plasma sodium (PNa) and chloride (PCl). We investigated the haemoltytic effect of different haemolysis protocols on PNa and PCl using modelling and laboratory experiments. METHODS: In a modelling experiment, percentage change and recovery due to dilution in routinely (in vitro) haemolysed samples were compared against shear stress haemolysis and samples spiked with haemolysate from whole blood freeze-thaw, packed cells freeze-thaw and osmotic shock protocols. The results were compared against a control base pool. Additionally, for the osmotic shock method, results were compared against saline- and deionised water (DIW)-spiked controls. In a laboratory experiment, percentage change and recovery were similarly compared using haemolysate from whole blood freeze-thaw and osmotic shock protocols. PNa, PCl and H-index were measured on the Abbott Architect and haemoglobin on the Sysmex XN-9000. RESULTS: In the modelling experiment, the percentage decrease in PNa and PCl was similar in in vitro haemolysis, shear stress haemolysis, whole blood freeze-thaw haemolysis and packed cells freeze-thaw haemolysis and this was lower compared to the osmotic shock method. In the laboratory experiment, the change in PNa compared to the base pool was less (p < 0.001) per unit increase in H-index in the freeze-thaw method (-0.33 mmol, 95% CI -0.35 to -0.31) compared to the osmotic shock method (-0.65 mmol, 95% CI -0.66 to -0.64). PCl did not change with haemolysis in the freeze-thaw method and changed by -0.21 ± 0.01 mmol per unit increase in the H-index in the osmotic shock method. Recovery of PNa and PCl increased with increasing H-index in both methods. CONCLUSION: The osmotic shock protocol is inappropriate for haemolysis studies because of dilution with DIW used for cell lysis. Recovery calculations may incorrectly compensate for genuine dilution caused by haemolysis.

Comparative Evaluation of Two NGAL Automated Immunoassays in Urine and Plasma.

BACKGROUND: Acute kidney injury (AKI), a frequent and serious complication of hospitalized patients, is associated with increased mortality and morbidity. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for the early identification of AKI. We report a comparative laboratory verification of the Abbott Diagnostics (ARCHITECT® urine NGAL) and BioPorto Diagnostics (NGAL TestTM) assays including an assessment of the Abbott assay's performance in EDTA plasma. METHODS: Intra-/interbatch imprecision, linearity, recovery, and limit of quantitation (LoQ) were assessed and an interassay comparison performed (n = 51). Between-laboratory agreement was assessed against other laboratories using the Abbott (n = 48) and BioPorto (n = 94) assays. Plasma NGAL (pNGAL) levels were measured in non-AKI patients with a range of estimated glomerular filtration rates (n = 80). RESULTS: Coefficients of variation (CVs) for intra- and interbatch imprecision were 0.7%-12.4% and 1.9%-27.5% for the BioPorto assay, respectively, and 1.4%-6.3%/3.4%-6.8%, respectively, for the Abbott assay. The BioPorto assay exhibited a higher LoQ (27.5 ng/mL vs 1.2 ng/mL). Both assays were linear over the range 5-6000 ng/mL. Recovery of recombinant NGAL was 113.1 ± 7.1% and 96.5 ± 7.8% for the Abbott and BioPorto assays, respectively. On average, the Abbott assay gave results 9.2% lower than the BioPorto assay. Mean differences of 0.2% (Abbott) and 20.2% (BioPorto) were observed in the between-laboratory comparison. In patients without AKI, pNGAL levels were inversely proportional to eGFR. CONCLUSIONS: Performance of the Abbott and BioPorto assays was similar although the latter performed less well at lower NGAL concentrations. The Abbott assay tended to yield lower results, exhibited a lower LoQ and over-recovered NGAL. Although only Conformité Européenne-marked and marketed for use in urine, the Abbott assay demonstrated equivalent performance to the BioPorto assay with EDTA plasma.

Diagnostic performance of serum calprotectin in discriminating active from inactive ulcerative colitis in an outpatient setting.

There are limited and conflicting data on the value of serum calprotectin (sCp) in discriminating active from inactive disease activity in ulcerative colitis (UC). Faecal calprotectin (fCp), sCp, serum C-reactive protein (sCRP) and platelets were compared in patients with UC who had clinically active (n = 29) and clinically inactive (n = 42) disease. Serum calprotectin was measured with Bühlmann® (BMN sCp) and ImmunodiagnostikTM (IDK sCp) assays. Median (interquartile range) fCp was higher in active than inactive disease [1004 (466-1922) versus 151 (55-280) µg/g; p < 0.0001). BMN sCp [4534 (3387-6416) versus 4031 (2401-5414) ng/mL; p = 0.1825], IDK sCp [4531 (2920-6433) versus 3307 (2104-4789) ng/mL; p = 0.1065], sCRP [ 4 (2-8) versus 2 (1-4) mg/L; p = 0.0638) and platelets [269 (233-331) versus 280 (227-325) ×10-9/L; p = 0.8055] were similar in active and inactive disease respectively. The area under the receiver operator characteristics curves with 95% confidence limits were 0.85 (0.76-0.94) for fCp, 0.61 (0.47-0.74) for BMN sCp, 0.61 (0.48-0.75) for IDK sCp, 0.69 (0.56-0.81) for sCRP and 0.52 (0.38-0.66) for blood platelets. Faecal calprotectin is the optimum biomarker for discriminating between active and inactive UC. The diagnostic performance of sCp, irrespective of assay, and systemic biomarkers was poor; of these sCRP performed best.

Utility of plasma NGAL for the diagnosis of AKI following cardiac surgery requiring cardiopulmonary bypass: a systematic review and meta-analysis.

The objective of this study was to assess the diagnostic value of plasma neutrophil gelatinase-associated lipocalin (pNGAL) for the early diagnosis of acute kidney injury (AKI) in adult patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Electronic databases and other resources were systematically searched for relevant studies. Risk of bias was assessed using the Quality Assessment for Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Studies were assigned to a sub-group based on the timing of the pNGAL sample in relation to the cessation of CPB. These were < 4 h, 4-8 h, 12 h or 24 h post-cessation of CPB. Summary values for sensitivity and specificity were estimated using the hierarchical summary receiver operator characteristic (ROC) curve model. A random-effects meta-analysis of each pair of sensitivity and specificity estimates from each included study was performed. In total, 3131 patients from 16 studies were included. When taken at 4-8 h following CPB, pNGAL had superior performance for the diagnosis of AKI in the defined population when compared to earlier and later time points. Prediction regions and confidence intervals, however, demonstrated significant variability in pooled estimates of sensitivity and specificity. This is likely due to population and study design heterogeneity, lack of standardisation of assays and thresholds, and inability to distinguish the different molecular forms of NGAL. In conclusion, the diagnostic utility of pNGAL in this clinical setting is inconclusive and large individual studies of representative populations of cardiac surgery patients using assays that specifically detect NGAL in its monomeric form are required.

Biochemical assessment of adequate levothyroxine replacement in primary hypothyroidism differs with different TSH assays: potential clinical implications.

AIM: Thyroid stimulating hormone (TSH) assays provided by Abbott Laboratories and Roche Diagnostics are used by approximately 75% of laboratories in the UK. We assessed the potential impact of Abbott and Roche TSH assay differences on the biochemical assessment of levothyroxine replacement in primary hypothyroidism. METHOD: Samples from 100 consecutive primary care patients (83 women, median age 64 years, IQR 51-73 years) with primary hypothyroidism on adequate levothyroxine based on an Abbott Architect TSH in the reference range were analysed for TSH on Roche cobas within 24 hours. The Abbott and Roche TSH results were compared. Over 1 year, TSH results from patients in primary care from the laboratories with Abbott and Roche methods were compared. RESULTS: The median (IQR) Roche TSH (2.5 (1.3-3.6) mIU/L) was 30%±10% higher (p<0.001) than Abbott TSH (1.9 (1.1-2.6) mIU/L). Although all Abbott TSH results were in the Abbott specific reference range, 14 patients (14%) had Roche TSH results above the Roche specific reference range. In the 1 year gather, Roche TSH (1.9 (1.3-2.9) mIU/L, n=103 932) results were higher (p<0.001) than Abbott TSH (1.5 (1.0-2.2) mIU/L, n=1 10 544) results. The TSH results were above their assay-specific upper reference limit in 10.7% of Roche results and 4.2% of Abbott results. CONCLUSION: Biochemical assessment of levothyroxine replacement may be dependent on the type of TSH assay. Laboratorians and clinicians should be aware that the lack of harmonisation between TSH methods and their assay-specific reference ranges may potentially lead to different patient management decisions. We suggest lot verification in laboratories should include processes to identify cumulative drift in assay performance.

COVID-19 seroprevalence after the first UK wave of the pandemic and its association with the physical and mental wellbeing of secondary care healthcare workers.

Objectives: To determine the seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody status amongst healthcare workers (HCWs) working through the first wave of the Coronavirus (COVID-19) pandemic in 2020. To examine the association of seroprevalence and self-reported COVID-19 symptoms with occupation, sex, and ethnicity; and how these factors were associated with physical and mental wellbeing. Design: Single-centre cohort study. Setting: Large public hospital in the United Kingdom. Intervention: All HCWs who had been tested for anti-SARS-CoV-2 immunoglobulin (Ig) G nucleocapsid antibody in summer 2020 were asked to complete an electronic survey focusing on their physical and mental health in Winter 2020-21. This survey was comprised of the Short Form 12v2, Physical Component Summary (PCS), Mental Component Summary (MCS), and Generalised Anxiety Disorder 7-item (GAD-7) questionnaires. Results: 7604/9781 (77.7%) HCWs were antibody tested, of which 1082 completed the full survey. Antibody testing was conducted between 17/06/20-30/07/20, during which time our seroprevalence rate was 28% (299/1082). Of those self-reporting COVID-19 symptoms, 51% (201/395) were antibody positive. Antibody-positive participants had lower PCS scores (p = 0.016), indicating poorer physical health. Lower PCS scores were also found in those deemed high risk for COVID-19 by their GP (p = 0.001), and those aged >44 years (p = 0.009). Antibody-negative participants had lower MCS scores (p = 0.044), indicating poorer mental health. Those who self-reported COVID-19 symptoms had lower PCS scores (p=<0.001) than those with no symptoms. Lower MCS scores were found in women (p = 0.001), Caucasians (p = 0.018), non-clinicians (p = 0.001), and those aged <44 years (p = 0.009). Significantly higher GAD-7 anxiety scores were evident in staff aged <44 years (p = 0.023), and those with self-reported COVID symptoms (p = 0.031). Doctors had lower GAD-7 anxiety scores (p = 0.009). Conclusion: Self-reported symptoms did not correlate with seroprevalence; data surrounding this can be useful for future workforce planning. Interventions are needed to reduce the mental and physical burden of the pandemic on HCWs. Further work is needed to identify which particular HCWs may require further support, to ensure well-being and effective patient care. Trial registration: Sponsor Protocol number - 2020COV112, Clinicaltrials.gov number -NCT04527432.