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Bovine respiratory disease (BRD) causes major losses in feedlot cattle worldwide. A genetic component for BRD resistance in feedlot cattle and calves has been reported in a number of studies, with heritabilities ranging from 0.04 to 0.2. These results suggest selection could be used to reduce the incidence of BRD. Genomic selection could be an attractive approach for breeding for BRD resistance, given the phenotype is not likely to be recorded on breeding animals. In this study, we derived GEBVs for BRD resistance and assessed their accuracy in a reasonably large data set recorded for feedlot treatment of BRD (1213 Angus steers, in two feedlots). In fivefold cross validation, genomic predictions were moderately accurate (0.23 ± 0.01) when a BayesR approach was used. Expansion of this approach to include more animals and a diversity of breeds is recommended to successfully develop a GEBV for BRD resistance in feedlots for the beef industry., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Women are on average diagnosed with diabetes mellitus at later age than men but have higher mortality. As the diagnosis of diabetes mellitus is primarily based on HbA1c, the use of a non-specific reference range and cut point for diabetes mellitus that does not account for gender differences in diabetes could potentially lead to underdiagnosis of diabetes mellitus in women and missed opportunities for intervention. We investigated whether a contributing factor to the later diagnosis in women may be a difference in distribution of HbA1c in premenopausal women versus men of the same age by comparing HbA1c values in men and women across multiple sites in the UK., Methods: We analysed the HbA1c levels of 146,907 individuals who underwent single testing only and had HbA1c ≤ 50 mmol/mol between 2012 and 2019 in one laboratory (cohort 1). This was replicated in six laboratories with 938,678 individuals tested between 2019 and 2021 (cohort 2)., Results: In cohort 1, women < 50 years old had an HbA1c distribution markedly lower than that in men by a mean of 1.6 mmol/mol (p < 0.0001), while the difference in the distribution of HbA1c for individuals aged ≥ 50 years was less pronounced (mean difference 0.9 mmol/mol, p < 0.0001). For individuals under the age of 50, HbA1c in women lagged by up to 10 years compared to men. Similar findings were found in cohort 2. We estimated an additional 17% (n = 34,953) of undiagnosed women aged < 50 years in England and Wales could be reclassified to have diabetes mellitus, which may contribute to up to 64% of the difference in mortality rates between men/women with diabetes mellitus aged 16-50 years., Conclusion: The HbA1c cut point for diagnosis of diabetes mellitus may need to be re-evaluated in women under the age of 50 years. Early identification of diabetes mellitus in women has the potential to improve women's health outcomes in the longer term., (© 2023. The Author(s).)

Background: Laboratories should be aware of the stability of the analytes they are testing in order to avoid incorrect reporting and patient management. Stability studies are difficult to interpret and reproduce, with little guidance on how to determine appropriate clinical cut off values. Here we describe a standardised approach to determining stability for routine haematinics tests using published EFLM guidelines., Methods: The haematinics panel at UHNM contains vitamin B12, folate, ferritin, iron and transferrin. Blood tubes included were serum separator tubes, gel-free serum and lithium-heparin plasma. Conditions tested were room temperature, 2-8°C and -20°C. For each condition and tube, three samples were analysed in duplicate at 0, 24, 48, 72, 96 and 120 h using the Siemens Atellica platform., Results: The percentage difference was calculated for each respective blood tube and storage condition, in addition to individual analyte maximum permissible instability scores. The majority of analytes for all blood tubes were stable for 5 days or more when stored at 4-8°C and -20°C. Ferritin (excluding gel-free), iron and transferrin further showed stability >5 days when stored at room temperature. However, vitamin B12 and folate demonstrated poor stability data for all tube types tested., Conclusions: Here we describe a stability study for the haematinics panel on the Siemens Atellica platform using the standardised EFLM Checklist for Reporting Stability Studies (CRESS). The checklist was used in order to promote a standardised and transferable scientific approach to what has previously been lacking in the literature when performing stability experiments., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Blood test monitoring is essential for the management of lithium treatment and National Institute for Health and Care Excellence guidance recommends 6-monthly serum testing of thyroid function. We examined conformity to these guidelines and the impact of monitoring outside these intervals., Methods: We extracted serum lithium and thyroid hormone results at one centre between January 2009 and December 2020. We identified 266 patients who started lithium during this period with no history of thyroid abnormality within the previous 2 years and were at risk of developing thyroid abnormalities. We examined the interval between tests, time between onset of lithium testing and first thyroid-stimulating hormone (TSH) outside the laboratory reference range and assessed impact of testing outside recommended 6-monthly intervals., Results: The most common testing frequency was 3 months (±1 month), accounting for 17.3% of test intervals. Kaplan-Meier analysis showed that most thyroid dysfunction manifests within 3 years (proportion with abnormal TSH at 3 years = 91.4%, 19.9% of total patients). In the first 3 months after commencing lithium therapy, eight patients developed subclinical hypothyroidism and had clinical follow-up data available. Of these, half spontaneously normalized without clinical intervention. In the remaining patients, thyroxine replacement was only initiated after multiple occasions of subclinical hypothyroidism (median = 2 years after initiating lithium, range: 6 months to 3 years)., Conclusion: The peak interval at 3 months suggests that thyroid function is frequently checked at the same time as serum lithium, indicating too frequent testing. Our data support the recommended 6-monthly testing interval and highlight poor adherence to it., (© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Introduction: Studies show that the COVID-19 pandemic disproportionately affected people with diabetes and those from disadvantaged backgrounds. During the first 6 months of the UK lockdown, > 6.6 M glycated haemoglobin (HbA1c) tests were missed. We now report variability in the recovery of HbA1c testing, and its association with diabetes control and demographic characteristics., Methods: In a service evaluation, we examined HbA1c testing across ten UK sites (representing 9.9% of England's population) from January 2019 to December 2021. We compared monthly requests from April 2020 to those in the equivalent 2019 months. We examined effects of (i) HbA1c level, (ii) between-practice variability, and (iii) practice demographics., Results: In April 2020, monthly requests dropped to 7.9-18.1% of 2019 volumes. By July 2020, testing had recovered to 61.7-86.9% of 2019 levels. During April-June 2020, we observed a 5.1-fold variation in the reduction of HbA1c testing between general practices (12.4-63.8% of 2019 levels). There was evidence of limited prioritization of testing for patients with HbA1c > 86 mmol/mol during April-June 2020 (4.6% of total tests vs. 2.6% during 2019). Testing in areas with the highest social disadvantage was lower during the first lockdown (April-June 2020; trend test p < 0.001) and two subsequent periods (July-September and October-December 2020; both p < 0.001). By February 2021, testing in the highest deprivation group had a cumulative fall in testing of 34.9% of 2019 levels versus 24.6% in those in the lowest group., Conclusion: Our findings highlight that the pandemic response had a major impact on diabetes monitoring and screening. Despite limited test prioritization in the > 86 mmol/mol group, this failed to acknowledge that those in the 59-86 mmol/mol group require consistent monitoring to achieve the best outcomes. Our findings provide additional evidence that those from poorer backgrounds were disproportionately disadvantaged. Healthcare services should redress this health inequality., (© 2023. The Author(s).)

Aims: We previously showed that the glycated haemoglobin (HbA1c) testing frequency links to diabetes control. Here, we examine the effect of variability in test interval, adjusted for the frequency, on change in HbA1c ( Δ HbA1c). Materials & Methods . HbA1c results were collected on 83,872 people with HbA1c results at baseline and 5 years (±3 months) later and ≥6 tests during this period. We calculated the standard deviation (SD) of test interval for each individual and examined the link between deciles of SD of the test interval and Δ HbA1c level, stratified by baseline HbA1c., Results: In general, less variability in testing frequency (more consistent monitoring) was associated with better diabetes control. This was most evident with moderately raised baseline HbA1c levels (7.0-9.0% (54-75 mmol/mol)). For example, in those with a starting HbA1c of 7.0-7.5% (54-58 mmol/mol), the lowest SD decile was associated with little change in HbA1c over 5 years, while for those with the highest decile, HbA1c rose by 0.4-0.6% (4-6 mmol/mol; p < 0.0001). Multivariate analysis showed that the association was independent of the age/sex/hospital site. Subanalysis suggested that the effect was most pronounced in those aged <65 years with baseline HbA1c of 7.0-7.5% (54-58 mmol/mol). We observed a 6.7-fold variation in the proportion of people in the top-three SD deciles across general practices., Conclusions: These findings indicate that the consistency of testing interval, not the just number of tests/year, is important in maintaining diabetes control, especially in those with moderately raised HbA1c levels. Systems to improve regularity of HbA1c testing are therefore needed, especially given the impact of COVID-19 on diabetes monitoring., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Anthony A. Fryer et al.)

Background: Finger prick blood glucose (BG) monitoring remains a mainstay of management in people with type 2 diabetes (T2DM) who take sulphonylurea (SU) drugs or insulin. We recently examined patient experience of BG monitoring in people with type 1 diabetes (T1DM). There has not been any recent comprehensive assessment of the performance of BG monitoring strips or the patient experience of BG strips in people with T2DM in the UK., Methods: An online self-reported questionnaire containing 44 questions, prepared following consultation with clinicians and patients, was circulated to people with T2DM. 186 responders provided completed responses (25.5% return rate). Fixed responses were coded numerically (eg not confident = 0 fairly confident = 1)., Results: Of responders, 84% were treated with insulin in addition to other agents. 75% reported having had an HbA1c check in the previous 6 months. For those with reported HbA1c ≥ 65 mmol/mol, a majority of people (70%) were concerned or really concerned about the shorter term consequences of running a high HbA1c This contrasted with those who did not know their recent HbA1c, of whom only 33% were concerned/really concerned and those with HbA1c <65 mmol/mol of whom 35% were concerned. Regarding BG monitoring/insulin adjustment, only 25% of responders reported having sufficient information with 13% believing that the accuracy and precision of their BG metre was being independently checked. Only 9% recalled discussing BG metre accuracy when their latest metre was provided and only 7% were aware of the International Standardisation Organisation (ISO) standards for BG metres. 77% did not recall discussing BG metre performance with a healthcare professional., Conclusion: The group surveyed comprised engaged people with T2DM but even within this group there was significant variation in (a) awareness of shorter term risks, (b) confidence in their ability to implement appropriate insulin dosage (c) awareness of the limitations of BG monitoring technology. There is clearly an area where changes in education/support would benefit many., (© 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder., Aims: This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases., Method: We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40-0.79 mmol/L; 0.80-0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history., Results: For tests within the recommended range (0.40-0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40-0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80-0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4-0.79 mmol/L group (2%), irrespective of testing frequency., Conclusion: We propose that for those who achieve 12 months of lithium tests within the 0.40-0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80-0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.

Context: Adrenal incidentalomas (AIs) are increasingly being identified during unrelated imaging. Unlike AI clinical management, data on referral patterns in routine practice are lacking., Objective: This work aimed to identify factors associated with AI referral., Methods: We linked data from imaging reports and outpatient bookings from a large UK teaching hospital. We examined (i) AI prevalence and (ii) pattern of referral to endocrinology, stratified by age, imaging modality, scan anatomical site, requesting clinical specialty, and temporal trends. Using key radiology phrases to identify scans reporting potential AI, we identified 4097 individuals from 479 945 scan reports (2015-2019). Main outcome measures included prevalence of AI and referral rates., Results: Overall, AI lesions were identified in 1.2% of scans. They were more prevalent in abdomen computed tomography and magnetic resonance imaging scans (3.0% and 0.6%, respectively). Scans performed increased 7.7% year-on-year from 2015 to 2019, with a more pronounced increase in the number with AI lesions (14.7% per year).Only 394 of 4097 patients (9.6%) had a documented endocrinology referral code within 90 days, with medical (11.8%) more likely to refer than surgical (7.2%) specialties ( P  < .001). Despite prevalence increasing with age, older patients were less likely to be referred ( P  < .001)., Conclusion: While overall AI prevalence appeared low, scan numbers are large and rising; the number with identified AI are increasing still further. The poor AI referral rates, even in centers such as ours where dedicated AI multidisciplinary team meetings and digital management systems are used, highlights the need for new streamlined, clinically effective systems and processes to appropriately manage the AI workload., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Advancing physical therapy interventions for children and young people is a high research priority. This includes research to describe and specify the control condition, typically 'current care', for effectiveness trials. This paper aims to identify physical therapy outcomes commonly targeted, and intervention techniques and approaches commonly used, by physiotherapists working with children (aged 2-19 years) with mobility limitations in the United Kingdom., Methods: A cross-sectional survey. Participants were recruited through the interactive Chartered Society of Physiotherapy members-only online discussion forum, the Association of Paediatric Chartered Physiotherapists, direct emails and snowball sampling within the authors' professional networks and Twitter. Data were collected using a structured online questionnaire and analysed using descriptive statistics., Results: We received 146 responses, 95/146 (65.1%) of which were fully complete. Therapists reported targeting 367 unique outcome constructs, of which 193 (52.6%) mapped onto activities and participation (e.g. moving around using equipment, maintaining body position and walking), 158 (43.1%) on body functions (e.g. muscle strength, joint mobility and gait functions), 11 (3.0%) on body structure (e.g. muscle length) and 3 (0.8%) on environmental factors (e.g. access home environment, access school environment and family confidence). The most commonly used interventions related to postural management (115/133 of respondents, 86.4%) and exercise therapy (116/137, 84.67%) and included techniques such as 'use equipment' (118/137, 86.1%), 'instruct how to do something' (117/137, 85.4%), 'practice' (105/137, 76.6%) and 'stretch' (99/137, 72.3%)., Conclusions: In designing trials, current care can be described as a combination of biomechanical and physiological techniques and approaches targeted at body functions and through that to activity and participation. Although some environmental behaviour change techniques and strategies were reported, the explicit use of these in current care appears limited., (© 2021 John Wiley & Sons Ltd.)

Background: Improving feedlot performance, carcase weight and quality is a primary goal of the beef industry worldwide. Here, we used data from 3408 Australian Angus steers from seven years of birth (YOB) cohorts (2011-2017) with a minimal level of sire linkage and that were genotyped for 45,152 SNPs. Phenotypic records included two feedlot and five carcase traits, namely average daily gain (ADG), average daily dry matter intake (DMI), carcase weight (CWT), carcase eye muscle area (EMA), carcase Meat Standard Australia marbling score (MBL), carcase ossification score (OSS) and carcase subcutaneous rib fat depth (RIB). Using a 7-way cross-validation based on YOB cohorts, we tested the quality of genomic predictions using the linear regression (LR) method compared to the traditional method (Pearson's correlation between the genomic estimated breeding value (GEBV) and its associated adjusted phenotype divided by the square root of heritability); explored the factors, such as heritability, validation cohort, and phenotype that affect estimates of accuracy, bias, and dispersion calculated with the LR method; and suggested a novel interpretation for translating differences in accuracy into phenotypic differences, based on GEBV quartiles (Q1Q4)., Results: Heritability (h 2 ) estimates were generally moderate to high (from 0.29 for ADG to 0.53 for CWT). We found a strong correlation (0.73, P-value < 0.001) between accuracies using the traditional method and those using the LR method, although the LR method was less affected by random variation within and across years and showed a better ability to discriminate between extreme GEBV quartiles. We confirmed that bias of GEBV was not significantly affected by h 2 , validation cohort or trait. Similarly, validation cohort was not a significant source of variation for any of the GEBV quality metrics. Finally, we observed that the phenotypic differences were larger for higher accuracies., Conclusions: Our estimates of h 2 and GEBV quality metrics suggest a potential for accurate genomic selection of Australian Angus for feedlot performance and carcase traits. In addition, the Q1Q4 measure presented here easily translates into possible gains of genomic selection in terms of phenotypic differences and thus provides a more tangible output for commercial beef cattle producers., (© 2021. The Author(s).)

Introduction: Women with gestational diabetes (GDM) are at greatly increased risk of type 2 diabetes (T2DM). The UK guidance recommends screening for T2DM at around 6-week postpartum and annually thereafter. We evaluated conformity to this guidance in two separate time periods., Methods: The proportion of tests performed within guidance was assessed using longitudinal plasma glucose and glycated haemoglobin data in two cohorts (1999-2007, n = 251; 2015-2016, n = 260) from hospital records on women previously diagnosed with GDM., Results: In the 1999-2007 and 2015-2016 cohorts, 59.8% and 35.0% of women had the recommended postpartum testing, respectively (P < .001); just 13.5% and 14.2%, respectively, underwent the first annual test on time. During long-term follow-up of the 1999-2007 cohort (median follow-up: 12.3 years), the proportion of women tested in any given year averaged 34.2% over a 17-year period; there was a progressive decline in the proportion of women receiving a yearly test with time since delivery (P = .002). Over the follow-up period, 85 women from the 1999-2007 cohort developed blood test results in the diabetic range with a median time to presumed DM diagnosis of 5.2 years (range 0.11-15.95 years). Kaplan-Meier analysis showed that 18.8% of women had blood test results in the diabetes range by 5-year postpartum and 37.8% by 10-year postpartum., Conclusions: Despite high profile guidelines and a clear clinical rationale to screen women with a past diagnosis of GDM, many women did not receive adequate screening for T2DM both in the short term and long term. This suggests that alternative approaches are needed to ensure effective follow-up of this high-risk group. To have an impact, interventions need to be tailored to a young, generally healthy group in which traditional approaches to follow-up may not be best suited., (© 2021 John Wiley & Sons Ltd.)

Background: The CARdiac MARker Guideline Uptake in Europe (CAMARGUE) program is a multi-country audit of the use of cardiac biomarkers in routine clinical practice., Methods: An email link to a web-based questionnaire of 30 multiple-choice questions was distributed via the professional societies in Europe., Results: 374 questionnaires were returned from 39 countries, the majority of which were in northern Europe with a response rate of 8.2%-42.0%. The majority of the respondents were from hospitals with proportionately more responses from central hospitals than district hospitals. Cardiac troponin was the preferred cardiac biomarker, evenly split between cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Aspartate transaminase and lactate dehydrogenase are no longer offered as cardiac biomarkers. Creatine kinase, creatine kinase MB isoenzyme, and myoglobin continue to be offered as part of the cardiac biomarker profile in approximately on 50% of respondents. There is widespread utilization of high sensitivity (hs) troponin assays. The majority of cTnT users measure hs-cTnT. 29.5% of laboratories measure cTnI by a non-hs method but there has been substantial conversion to hs-cTnI. The majority of respondents used ng/L and use the 99th percentile as the upper reference limit (71.9% of respondents). A range of diagnostic protocols are in use., Conclusions: There is widespread utilization of hs troponin methods. A significant minority do not use the 99th percentile as recommended and there is, as yet, little uptake of very rapid diagnostic strategies. Education of laboratory professionals and clinicians remains a priority., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The short synacthen test (SST) is the most commonly performed investigation to assess adrenal function. Appropriate criteria for when an SST is performed are subject to debate. We investigated how random serum cortisol levels relate to SST response., Methods: We examined random cortisol measurements taken between 04.40-23.55 p.m. results of SST baseline and 30-/60-min cortisol performed over 12 months (225 SSTs) at Salford Royal Hospital. Serum cortisol was measured on the Siemens Centaur Analyser.A 30-60-min cortisol concentration of ≥450 nmol/L defined a pass; 350-449 nmol/L defined borderline., Results: Patients only proceeded to SST if random cortisol was <400 nmol/L. For those not on corticosteroids for at least 2 weeks, 42/43 (97.7%) cases with random cortisol concentration of ≥200 nmol/L had an SST 'pass'. The relation was less clear with corticosteroid treatment (19/35 cases; 54%).For those not taking glucocorticoid treatment (including inhaled/topical corticosteroids) in the previous 2 weeks, 91.8% of SSTs were pass/2.7% borderline/5.5% fail. For those on steroids, 51.9% of SSTs were a pass/11.4% were borderline.In relation to the postsynacthen cortisol pass cut-off of ≥450 nmol/L, in 15/207 (7.2%) of cases, the 60-min cortisol was ≥450 nmol/L (adequate adrenocortical function), but 30-min cortisol was below this. In all cases where the 30-min cortisol did indicate a pass (i.e. was ≥450 nmol/L) the 60-min cortisol was also ≥450 nmol/L., Conclusion: Our findings suggest that if the random cortisol level is ≥200 nmol/L, regardless of the time of day and the person was not taking corticosteroid treatment in the previous 2 weeks, SST may not be needed. Our data also suggests that 60-min cortisol retains utility., Competing Interests: There are no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

In animal breeding and genetics, the ability to cope with disease, here defined as immune competence (IC), with minimal detriment to growth and fertility is a desired objective which addresses both animal production and welfare considerations. However, defining and objectively measuring IC phenotypes using testing methods which are practical to apply on-farm has been challenging. Based on previously described protocols, we measured both cell-mediated immune response (Cell-IR) and antibody-mediated immune response (Ab-IR) and combined these measures to determine an animal's IC. Using a population of 2,853 Australian Angus steers and heifers, we compared 2 alternative methods to combine both metrics into a single phenotype to be used as a tool for the genetic improvement of IC. The first method, named ZMEAN, is obtained by taking the average of the individual metrics after subjecting each to a Z-score standardization. The second, ImmuneDEX (IDEX), is a weighted average that considers the correlation between Cell-IR and Ab-IR, as well as the difference in ranking of individuals by each metric, and uses these as weights in the averaging. Both simulation and real data were used to understand the behavior of ZMEAN and IDEX. To further ascertain the relationship between IDEX and other traits of economic importance, we evaluated a range of traits related to growth, feedlot performance, and carcass characteristics. We report estimates of heritability of 0.31 ± 0.06 for Cell-IR, 0.42 ± 0.06 for Ab-IR, 0.42 ± 0.06 for ZMEAN and 0.370 ± 0.06 for IDEX, as well as a unity genetic correlation (rg) between ZMEAN and IDEX. While a moderately positive rg was estimated between Cell-IR and Ab-IR (rg = 0.33 ± 0.12), strongly positive estimates were obtained between IDEX and Cell-IR (rg = 0.80 ± 0.05) and between IDEX and Ab-IR (rg = 0.85 ± 0.04). We obtained a moderately negative rg between IC traits and growth including an rg = -0.38 ± 0.14 between IDEX and weaning weight, and negligible with carcass fat measurements, including an rg = -0.03 ± 0.12 between IDEX and marbling. Given that breeding with a sole focus on production might inadvertently increase susceptibility to disease and associated antibiotic use, our analyses suggest that ImmuneDEX will provide a basis to breed animals that are both highly productive and with an enhanced ability to resist disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Accurate diagnosis of polycystic ovarian syndrome (PCOS) enables clinical interventions/cardiometabolic risk factor management. Diagnosis can take over 2 years and multiple clinician contacts. We examined patterns of PCOS-associated biochemical investigations following initial consultation prior to pelvic ultrasound scan (USS)., Methods: We determined in 206 women (i) the range of different biochemical test panels used in the diagnosis of PCOS in primary/secondary care prior to USS relative to national guidance in the UK and (ii) the relation between testing patterns and time to USS to highlight potential delays introduced by inappropriate testing., Results: In these 206 women, 47 different test combinations were requested at initial venepuncture; only 7 (3%) had the test panel suggested in UK guidance (follicle-stimulating hormone/luteinizing hormone/testosterone/sex hormone-binding globulin/prolactin). The number of tests performed prior to USS varied from one test to all seven tests. There was an inverse relation between the number of biochemistry tests requested at initial venepuncture episode and 'time to scan'. Those who had <3 tests had a significantly longer time from first request to USS (median 70 days) than those with 3-7 tests (median 40 days; P  = 0.002). One venepuncture episode prior to USS was associated with shorter 'time to scan' (median 29 days) than those with 2-4 episodes (median 255 days; P  < 0.001)., Conclusion: There was no identifiable pattern to biochemical investigations requested as part of the initial diagnostic evaluation in women with suspected PCOS. We recommend standardization of the initial biochemical panel of analytes for PCOS workup, with incorporation into hospital/general practice ordering software systems., Competing Interests: There are no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: I have read and understood The BMJ policy on declaration of interests and declare the following interests: none. Provenance and peer review: commissioned, based on an idea from the author; externally peer reviewed.

Genetic strategies aimed at improving general immune competence (IC) have the potential to reduce the incidence and severity of disease in beef production systems, with resulting benefits of improved animal health and welfare and reduced reliance on antibiotics to prevent and treat disease. Implementation of such strategies first requires that methodologies be developed to phenotype animals for IC and demonstration that these phenotypes are associated with health outcomes. We have developed a methodology to identify IC phenotypes in beef steers during the yard weaning period, which is both practical to apply on-farm and does not restrict the future sale of tested animals. In the current study, a total of 838 Angus steers, previously IC phenotyped at weaning, were categorized as low (n = 98), average (n = 653), or high (n = 88) for the IC phenotype. Detailed health and productivity data were collected on all steers during feedlot finishing, and associations between IC phenotype, health outcomes, and productivity were investigated. A favorable association between IC phenotype and number of mortalities during feedlot finishing was observed with higher mortalities recorded in low IC steers (6.1%) as compared with average (1.2%, P < 0.001) or high (0%, P = 0.018) IC steers. Disease incidence was numerically highest in low IC steers (15.3 cases/100 animals) and similar in average IC steers (10.1 cases/100 animals) and high IC steers (10.2 cases/100 animals); however, differences between groups were not significant. No significant influence of IC phenotype on average daily gain was observed, suggesting that selection for improved IC is unlikely to incur a significant penalty to production. The potential economic benefits of selecting for IC in the feedlot production environment were calculated. Health-associated costs were calculated as the sum of lost production costs, lost capital investment costs, and disease treatment costs. Based on these calculations, health-associated costs were estimated at AUS$103/head in low IC steers, AUS$25/head in average IC steers, and AUS$4/head in high IC steers, respectively. These findings suggest that selection for IC has the potential to reduce mortalities during feedlot finishing and, as a consequence, improve the health and welfare of cattle in the feedlot production environment and reduce health-associated costs incurred by feedlot operators., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The improvement of carcass traits is an important breeding objective in beef cattle breeding programs. The most common way of selecting for improvement in carcass traits is via indirect selection using ultrasound scanning of selection candidates which are submitted to genetic evaluation programs. Two systems used to analyze ultrasound images to predict carcass traits are the Pie Medical Esaote Aquila ( PIE ) and Central Ultrasound Processing ( CUP ). This study compared the ability of the two systems to predict carcass traits for genetic evaluation in Australian Angus cattle. Genetic and phenotypic parameters were estimated using data from 1,648 Angus steers which were ultrasound scanned twice with both systems, first at feedlot entry and then following 100 d in the feedlot. The traits interpreted from ultrasound scanning included eye muscle area ( EMA ), rib fat ( RIB ) rump fat ( RUMP ), and intramuscular fat ( IMF ). Abattoir carcass data were collected on all steers following the full feedlot feeding period of 285 d. For all ultrasound scan traits, CUP resulted in higher phenotypic and genetic variances compared to the PIE. For IMF, CUP had higher heritability at feedlot intake (0.51 for CUP compared to 0.37 for PIE) and after 100 d feeding (0.54 for CUP compared to 0.45 PIE). CUP predicted IMF also tended to have stronger correlations with the breeding objective traits of carcass IMF and marbling traits, both genetically (ranging from 0.59 to 0.75 for CUP compared to 0.45-0.63 for PIE) and phenotypically (ranging from 0.27 to 0.43 for CUP compared to 0.19-0.28 for PIE). Ultrasound scan EMA was the only group of traits in which the heritabilities were higher for PIE (0.52 for PIE compared to 0.40 for CUP at feedlot intake and 0.46 for PIE compared to 0.43 for CUP at 100 d of feeding), however with similar relationships to the breeding objective carcass EMA observed. For subcutaneous fat traits of ultrasound RIB and RUMP, the heritabilites and genetic correlations to the related carcass traits were similar, with the exception being the higher heritability observed for CUP predicted RUMP at feedlot intake at 0.52 compared to 0.38 for PIE. The results from this study indicates that the CUP system, compared to PIE, provides an advantage for genetic evaluation of carcass traits in Angus cattle, particularly for the IMF and associated marbling traits., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Background: Bipolar disorder is the fourth most common mental health condition, affecting ~ 1% of UK adults. Lithium is an effective treatment for prevention of relapse and hospital admission, and is widely recommended as a first-line treatment. We previously showed in other areas that laboratory testing patterns are variable with sub-optimal conformity to guidance. We therefore examined lithium results and requesting patterns relative to monitoring recommendations., Methods: Data on serum lithium levels and intervals between requests were extracted from Clinical Biochemistry laboratory information systems at the University Hospitals of North Midlands, Salford Royal Foundation Trust and Pennine Acute Hospitals from 2012 to 2018 (46,555 requests; 3371 individuals). Data were examined with respect to region/source of request, age and sex., Results: Across all sites, lithium levels on many requests were outside the recommended UK therapeutic range (0.4-0.99 mmol/L); 19.2% below the range and 6.1% above the range (median [Li]: 0.60 mmol/L). A small percentage were found at the extremes (3.2% at < 0.1 mmol/L, 1.0% at ≥1.4 mmol/L). Most requests were from general practice (56.3%) or mental health units (34.4%), though those in the toxic range (≥1.4 mmol/L) were more likely to be from secondary care (63.9%). For requesting intervals, there was a distinct peak at 12 weeks, consistent with guidance for those stabilised on lithium therapy. There was no peak at 6 months, as recommended for those aged < 65 years on unchanging therapy, though re-test intervals in this age group were more likely to be longer. There was a peak at 0-7 days, reflecting those requiring closer monitoring (e.g. treatment initiation, toxicity). However, for those with initial lithium concentrations within the BNF range (0.4-0.99 mmol/L), 69.4% of tests were requested outside expected testing frequencies., Conclusions: Our data showed: (a) lithium levels are often maintained at the lower end of the recommended therapeutic range, (b) patterns of lithium results and testing frequency were comparable across three UK sites with differing models of care and, (c) re-test intervals demonstrate a noticeable peak at the recommended 3-monthly, but not at 6-monthly intervals. Many tests were repeated outside expected frequencies, indicating the need for measures to minimise inappropriate testing.

Background: The National Health Service spends £170 million on blood glucose monitoring (BGM) strips each year and there are pressures to use cheaper less accurate strips. Technology is also being used to increase test frequency with less focus on accuracy.Previous modeling/real-world data analysis highlighted that actual blood glucose variability can be more than twice blood glucose meter reported variability (BGMV). We applied those results to the Parkes error grid to highlight potential clinical impact., Method: BGMV is defined as the percent of deviation from reference that contains 95% of results. Four categories were modeled: laboratory (<5%), high accuracy strips (<10%), ISO 2013 (<15%), and ISO 2003 (<20%) (includes some strips still used).The Parkes error grid model with its associated category of risk including "alter clinical decision" and "affect clinical outcomes" was used, with the profile of frequency of expected results fitted into each BGM accuracy category., Results: Applying to single readings, almost all strip accuracy ranges derived in a controlled setting fell within the category: clinically accurate/no effect on outcomes areas.However modeling the possible blood glucose distribution in more detail, 30.6% of longer term results of the strips with current ISO accuracy would fall into the "alter clinical action" category. For previous ISO strips, this rose to 44.1%, and for the latest higher accuracy strips, this fell to 12.8%., Conclusion: There is a minimum standard of accuracy needed to ensure that clinical outcomes are not put at risk. This study highlights the potential for amplification of imprecision with less accurate BGM strips.

Background: The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) initiated the CArdiac MARker Guidelines Uptake in Europe (CAMARGUE) Study to survey if current biomarker testing for heart failure (HF) in Europe is in accordance with up-dated guidelines., Methods: A web-based questionnaire was distributed to clinical laboratories via European biochemical societies in 2019. Questions covered the type of natriuretic peptide (NP) assays performed, decision limits for HF, and opinion concerning requirement of different thresholds in patients with renal failure or obesity., Results: There were 347 participating laboratories mostly from European countries with 266 offering NP testing. NP testing was increased from 67% to 77% between 2013 and 2019. NT-proBNP remained the preferred biomarker. Recommended decision limits were implemented for BNP (85%) and better focused for NT-proBNP (40%) than in the previous survey. The survey revealed that laboratorians are willing to support the translation of adjusted cut-off values for age, gender and for patients with conditions like renal insufficiency., Conclusion: Guidelines stimulate clinical laboratories to offer NP testing with high value for the diagnosis and management of HF, and to present adjusted medical decision limits. Future guidelines should encourage the use of personalized cut-offs for some confounding factors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The self-management of type 1 diabetes (T1DM) has moved forward in many areas over the last 40 years. Our study asked people with T1DM what is their experience of blood glucose (BG) monitoring day to day and how this influences decisions about insulin dosing., Methods: An on-line self-reported questionnaire containing 44 questions prepared after consultation with clinicians and patients was circulated to people with T1DM 116 responders provided completed responses. Fixed responses were allocated specific values (e.g. not confident = 0 fairly confident = 1). Multivariate regression analysis was carried out. Only those 5 factors with p-value <0.05 were retained., Results: 59% of respondents were >50 years old and 66% had diabetes for >20 years, with 63% of patients reporting HbA1c results ≤8% or 64 mmol/mol. Findings included; 75% used only 1 m; 56% had used the same meter for ≥3 years; 10% had tried flash monitors; 47% were concerned about current BG level; 85% were concerned about long-term impact of higher BG. 72% of respondents keep BG level high to avoid hypoglycaemia; 25% used ≥7 mmol/L as pre-meal BG target to calculate dose; 65% were concerned they might be over/under-dosing; 83% did not discuss accuracy when choosing meter. However 85% were confident in their meter's performance. The factors that linked to LOWER HbA1c included LESS units of basal insulin (p < 0.001), HIGHER number of daily BG tests (p = 0.008), LOWER bedtime blood glucose (p = 0.009), HIGHER patient's concern over long-term impact of high BG (BG) (p < 0.009 but LOWER patient's concern over current BG values (p = 0.009). The final statistical model could explain 41% of the observed variation in HbA1c., Conclusion: Many people still run their BG high to avoid hypoglycaemia. Concern about the longer-term consequences of suboptimal glycaemic control was associated with a lower HbA1c and is an area to explore in the future when considering how to help people with T1DM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The CArdiac MARker Guidelines Uptake in Europe Study (CAMARGUE) initiated by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) aims to survey the current use of evidence-based guidelines for dyslipidemia testing in Europe., Methods: In 2019 a web-based questionnaire was distributed via EFLM National Societies to clinical laboratories in Europe. Questions covered pre-analytics, analytical methods, measurement units, flagging of decision thresholds, and use of decision-enhancing comments., Results: Returns were obtained from 452 laboratories from 28 countries. Most laboratories always use nonfasting blood samples for lipid assays (66%). Lipid profiles are reported in mmol/L by 59% of the laboratories, mainly from 14 countries promoting the use of SI units. Important differences in flagging of decision thresholds were observed, with less than half of the laboratories applying the guideline-recommended LDL cholesterol threshold. Only 17% of the laboratories add an alert comment when familial hypercholesterolemia is suspected and 23% when risk of pancreatitis from hypertriglyceridemia is high., Conclusions: There are marked differences among laboratories in Europe in terms of pre-analytical, analytical, and post-analytical lipid management that could have an important clinical impact. This relates to different availability of assays or different laboratory practices on reporting and flagging of lipid profiles., Competing Interests: Declaration of Competing Interest The authors have no other competing interests or conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: United Kingdom national guidelines do not recommend routine testing for thyroid disease in people with type 2 diabetes mellitus (T2DM). However, some studies suggest an increased risk of thyroid dysfunction in T2DM. The aim of this study was to evaluate the current practice of screening for thyroid disease in patients with T2DM., Methods: Patients with pre-existing T2DM ( n  = 339) were selected from records for routine glycated haemoglobin testing performed in December 2008. Using routinely collected primary/secondary care data from 2009 to 2017, we examined longitudinal thyroid-stimulating hormone and free thyroxine requests to determine the overall proportion of patients screened for thyroid dysfunction and the time interval between thyroid tests requested., Results: Thirty-three patients (9.7%) had pre-existing thyroid disease. Of the remaining 306 patients, 96.4% had at least one thyroid test during the follow-up period. When the time interval between tests was evaluated in these patients, there was a discrete peak in thyroid function test requests at 12 months, consistent with routine annual testing. Most requests (77%) originated from a general practice setting., Conclusions: Contrary to current guidelines, we have provided evidence suggestive of regular screening for thyroid dysfunction in patients with T2DM, particularly in general practice. The appropriateness of this practice remains unclear, but may warrant further examination to assess the clinical benefits of screening, balanced against cost.

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total - HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) [Lp(a)]-cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds.

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol (=total - HDL cholesterol) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDL cholesterol is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDL cholesterol shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a)-cholesterol is part of measured or calculated LDL cholesterol and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDL cholesterol decline poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDL cholesterol or apolipoprotein B, especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDL cholesterol includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apolipoprotein B measurement can detect elevated LDL particle numbers often unidentified on the basis of LDL cholesterol alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Selection for production traits with little or no emphasis on health-related traits has the potential to increase susceptibility to disease in food-producing animals. A possible genetic strategy to mitigate such effects is to include both production and health traits in the breeding objective when selecting animals. For this to occur, reliable methodologies are required to assess beneficial health traits, such as the immune capacity of animals. We describe here a methodology to assess the immune competence of beef cattle which is both practical to apply on farm and does not restrict the future sale of tested animals. The methodology also accommodates variation in prior vaccination history of cohorts of animals being tested. In the present study, the immune competence phenotype of 1,100 Angus calves was assessed during yard weaning. Genetic parameters associated with immune competence traits were estimated and associations between immune competence, temperament, and stress-coping ability traits were investigated. Results suggested that immune competence traits, related to an animal's ability to mount both antibody and cell-mediated immune responses, are moderately heritable (h2 = 0.32 ± 0.09 and 0.27 ± 0.08, respectively) and favorably genetically correlated with the temperament trait, flight time (r = 0.63 ± 0.31 and 0.60 ± 0.29 with antibody and cell-mediated immune responses, respectively). Development of methodologies to assess the immune competence phenotype of beef cattle is a critical first step in the establishment of genetic selection strategies aimed at improving the general disease resistance of beef herds. Strategies aimed at reducing the incidence of disease in beef cattle are expected to significantly improve animal health and welfare, reduce reliance on the use of antibiotics to treat disease, and reduce disease-associated costs incurred by producers., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The development of cardiovascular disease is intimately linked to elevated levels of low-density lipoprotein (LDL) cholesterol in the blood. Hepatic LDL receptor (LDLR) levels regulate the amount of plasma LDL. We identified the secreted zinc metalloproteinase, bone morphogenetic protein 1 (BMP1), as responsible for the cleavage of human LDLR within its extracellular ligand-binding repeats at Gly 171 ↓Asp 172 . The resulting 120 kDa membrane-bound C-terminal fragment (CTF) of LDLR had reduced capacity to bind LDL and when expressed in LDLR null cells had compromised LDL uptake as compared to the full length receptor. Pharmacological inhibition of BMP1 or siRNA-mediated knockdown prevented the generation of the 120 kDa CTF and resulted in an increase in LDL uptake into cells. The 120 kDa CTF was detected in the livers from humans and mice expressing human LDLR. Collectively, these results identify that BMP1 regulates cellular LDL uptake and may provide a target to modulate plasma LDL cholesterol.

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.

Background: Testosterone, the most important androgen produced by the testes, plays an integral role in male health. Testosterone levels are increasingly being checked in primary healthcare as awareness of the risks of male hypogonadism grows., Aim: To investigate what tests are performed to screen for hypogonadism and to exclude secondary hypogonadism., Design and Setting: All participants attended general practices in the UK., Methods: Data search was performed using the EMIS®: clinical database (provider of the majority of GP operating systems in Cheshire). The anonymised records of male patients aged 18-98 years who had undergone a check of serum testosterone during a 10-year period were analysed., Results: Overall screening rate was 4.3%. Of 8 788 men with a testosterone result, 1 924 men (21.9%) had a total testosterone level <10 nmol/L. Just 689 of 8 788 men (7.8%) had a sex hormone-binding globulin (SHBG) result, corresponding to 30.5% of those potentially hypogonadal. Estimated free testosterone was negatively associated with BMI (Spearman's rho -0.2, p<0.001) as was total testosterone in the over 50 s. Of 1 924 potentially hypogonadal men with a serum testosterone <10 nmol/L, 588 of 1 924 (30.6%) had a check of serum prolactin. 46.3% and 41.7% had LH and FSH measured, respectively. Only 19.1% of 1 924 men with a hypogonadal total testosterone level were subsequently put on testosterone replacement. The percentage of men in the relatively socially disadvantaged category was similar for both eugonadal and hypogonadal men with a much higher rate of screening for hypogonadism in more socially advantaged men., Conclusions: Screening in primary healthcare identified a significant minority of men who had potential hypogonadism. Interpretation of a low serum testosterone requires measurement of serum prolactin, LH and FSH in order to rule out secondary hypogonadism. We suggest that this becomes part of routine screening with a balanced screening approach across the socioeconomic spectrum., Competing Interests: None of the authors had any conflict of financial or personal interest in regard of this study., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Polycystic ovarian syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age. We examined the specific tests that are done in primary care to lead to the diagnosis of PCOS, and to support the diagnosis once made., Methods: One thousand seven hundred and ninety-seven women were identified from a pooled GP practice database. The search included all patients defined with PCOS or related terms. Records included demographic information, medical history (diagnoses), blood test results and whether a pelvic ultrasound scan had been performed., Results: The most common age of PCOS diagnosis was 20-29 years; 67.7% of the women had at least one concomitant Read-coded diagnosis. Most pelvic ultrasound scans were performed in the month immediately prior to diagnosis. In the 12 months prior to the diagnosis of PCOS being made, 30.5% of women underwent a measurement of their serum total testosterone level while 29.6% had their serum SHBG measured. For serum oestradiol, the corresponding statistics were 28.4%, LH 45.3% and for FSH 45.5% checked before diagnosis. Fasting blood glucose, random glucose and HbA1c were checked in 10.2%, 18.8% and 4.2%, of women before diagnosis, respectively, but in only 7.9%, 6.0% and 3.4% of women in the 24 months after diagnosis. There was a tendency for endocrine testing (oestradiol, LH, FSH, testosterone, SHBG) to peak in the weeks before diagnosis. For plasma glucose, testing was performed more evenly over time as for serum cholesterol. Of all women diagnosed with PCOS, 32.8% were prescribed metformin, 3.7% antihypertensives, 2.2% statins and 63.5% an oestrogen-containing contraceptive pill or HRT., Conclusion: The underlying pathophysiology of PCOS is still not fully understood. As a result, treatment is often focused on individual symptoms, not the syndrome itself. Robust laboratory led protocols would provide the necessary information to enable an appropriate diagnostic evaluation/cardometabolic monitoring., (© 2017 John Wiley & Sons Ltd.)

With demand for endocrine tests steadily increasing year-on-year, we examined thyroid function test (TFT) frequencies in patients on levothyroxine replacement therapy to assess the effect of initial TFT results and request source on TFT re-testing interval. All TFTs performed by the Clinical Biochemistry Departments at the Salford Royal Hospital (2009-2012; 288 263 requests from 139 793 patients) and University Hospital of North Midlands (2011-2014; 579 156 requests from 193 035 patients) were extracted from the laboratory computer systems. Of these, 54 894 tests were on 13 297 patients confirmed to be on levothyroxine therapy in the test cohort (Salford) and 67 298 requests on 11 971 patients in the confirmatory cohort (North Midlands). In the test cohort, median TFT re-testing interval in the total group was 19.1 weeks (IQR 9.1-37.7 weeks), with clearly defined peaks in TFT re-testing evident at 6 and 12 months and a prominent broad peak at 1-3 months. Median re-test interval was much lower than recommended (52 weeks) for those with normal TFTs at 31.3 weeks (30.6 weeks for the confirmatory cohort). Where thyroid-stimulating hormone (TSH) was elevated and free thyroxine (fT4) was below the reference range, re-test interval was much longer than is recommended (8 weeks) at 13.4-17.6 weeks (7.1-23.4 weeks in the confirmatory cohort), as was the interval when TSH was below and fT4 was above the normal range, at 16.7-25.6 weeks (27.5-31.9 weeks in the confirmatory cohort). Our findings show that the majority of TFT requests are requested outside recommended intervals and within-practice variability is high. A new approach to ensuring optimum monitoring frequency is required. Direct requesting from the clinical laboratory may provide one such solution., Competing Interests: Conflict of Interest: The authors have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Gestational diabetes mellitus (GDM; approximately 5% of pregnancies) represents the most important risk factor for development of later-onset diabetes mellitus. We examined concordance between GDM diagnosis defined using the original 1999 World Health Organization (WHO) criteria and the more recent 2013 WHO criteria and 2015 National Institute for Health and Care Excellence (NICE) criteria. We studied two groups: a case-control group of 257 GDM positive and 266 GDM negative cases, and an incident cohort 699 GDM positive and 6,231 GDM negative cases. In the incident cohort, GDM prevalence was 3.7% (WHO 1999 criteria), 11.4% (NICE 2015 criteria) and 13.7% (WHO 2013 criteria). Our results showed that a significant number of additional cases are detected using the more recent NICE and WHO criteria than the original 1999 WHO criteria, but these additional cases represent an intermediate group with 'moderate' dysglycaemia (abnormal blood glucose levels). Our results also show that use of these newer criteria misses a similar group of intermediate cases that were defined as GDM by the 1999 WHO criteria and that glycated haemoglobin in isolation is unlikely to replace the oral glucose tolerance test in GDM diagnosis., (© Royal College of Physicians 2017. All rights reserved.)

Background: The aim of this survey was to investigate how well heart failure (HF) guidelines for use of natriuretic peptides (NPs) have been implemented in laboratory practice in Europe and North America., Methods: In 2013 and 2014, a web-based questionnaire was distributed via North American and European biochemical societies. Questions covered assay performed, reason for method choice, decision limits for HF, and laboratory accreditation status., Results: There were 442 European Union and 91 North American participating laboratories with response rates of 50% and 64% from major or university hospitals, respectively. NP measurements were offered in 67% of European Union and 58% of North American respondents. N-terminal pro-B-type natriuretic peptide (NT-proBNP) was most widely used in Europe (68%) and B-type natriuretic peptide (BNP) was more commonly used (58%) in North America. The most frequent reason for use of a specific assay was the availability of instruments that measure either NT-proBNP (51%) or BNP (67%). For diagnosis of acute HF, NT-proBNP decision limits were diverse; age-dependent limits based on the 2012 European Society of Cardiology (ESC) recommendations were used in only 17% of European sites and 26% of North American sites. For BNP, the guideline-recommended acute HF decision limit of 100 ng/L was better adhered to in Europe (48%) and North America (57%). Surprisingly, similar decision limits were stated for acute and chronic HF by >50% of respondents., Conclusions: NP measurement for HF diagnosis was available in >50% of responding laboratories. However, guideline recommended cutoff values for both acute and chronic HF were still implemented in <30% of participating medical centers., (© 2016 American Association for Clinical Chemistry.)

Background: We undertook an assessment of current use of evidence-based guidelines for the use of cardiac biomarkers in Europe (EU) and North America (NA)., Methods: In 2013-2014 a web-based questionnaire was distributed via NA and EU biochemical societies. Questions covered cardiac biomarkers measured, analytical methods used, decision thresholds, and use of decision-making protocols. Results were collated using a central database and analyzed using comparative and descriptive nonparametric statistics., Results: In EU, returns were obtained from 442 hospitals, 50% central or university hospitals, and 39% from local hospitals from 35 countries with 395/442 (89%) provided an acute service. In NA there were 91 responses (63.7% central or university hospitals, 19.8% community hospitals) with 76/91 (83.5%) providing an acute service. Cardiac troponin was the preferred cardiac biomarker in 99.5% (EU) and 98.7% (NA), and the first line marker in 97.7% (EU) and 97.4% (NA). There were important differences in the choice of decision limits and their derivations. The origin of the information was also significantly different, with EU vs NA as follows: package insert, 61.9% vs 40%; publications, 17.1% vs 15.0%; local clinical or analytical validation choice, 21.0% vs 45.0%; P = 0.0003., Conclusions: There are significant differences between EU and NA use of cardiac biomarkers. This probably relates to different availability of assays between EU and NA (such as high-sensitivity troponin assays) and different laboratory practices on assay introduction (greater local evaluation of assay performance occurred in NA)., (© 2016 American Association for Clinical Chemistry.)

Introduction: Increased plasma low-density lipoprotein (LDL) cholesterol is a significant risk factor for cardiovascular disease. Plasma LDL-cholesterol is controlled through its uptake into cells upon binding the LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the LDLR and promotes its degradation, resulting in increased plasma LDL-cholesterol. Inhibiting the action of PCSK9 on the LDLR has emerged as a novel therapeutic target for hypercholesterolemia., Areas Covered: We briefly describe the identification and initial characterisation of PCSK9, before detailing the molecular mechanisms involved in its interaction with the LDLR. We highlight the potential sites for therapeutic intervention in this pathway and describe the current status of therapeutic approaches, including blocking antibodies, siRNA, antisense oligonucleotides and small-molecule inhibitors. The potential limitations of such approaches are also discussed., Expert Opinion: There is a wealth of evidence indicating that inhibition of PCSK9 is a highly desirable approach to combat hypercholesterolemia, with several agents in preclinical and clinical development. However, further research is required to fully understand the biological role of PCSK9 and whether its inhibition may have adverse effects in certain groups of patients, for example, those with liver disease.