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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s13300-023-01482-6.Correction to: Diabetes Therhttps://doi.org/10.1007/s13300-023-01482-6In this article, the author name Christopher J. Duff was incorrectly written as Christof J. Duff.The original article has been corrected.By David Holland; Anthony A. Fryer; Mike Stedman; Fahmy W. F. Hanna; Christopher J. Duff; Lewis Green; Jonathan Scargill; Ian Halsall; Neil Gaskell; Jonathon D. Howe; Adrian H. Heald and Pensee WuReported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

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 (ΔHbA1c). 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 ΔHbA1c 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction 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. Methods 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). Results 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). Conclusion 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

The article offers information on association between type 2 diabetes mellitus (T2DM) and thyroid disease. Topics discussed include increased prevalence of thyroid dysfunctionin T2DM is of importance with regard to thyroid disease; increased prevalence of thyroid disease in patients with T2DM; and role played by hypothyroidism in developing diabetic complications.

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 Gly171↓Asp172. 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. [ABSTRACT FROM AUTHOR]

Bipolar affective disorder is one of the leading causes of disability worldwide and carries a substantial risk of suicide. Here we determined for GP practices in one area of England, the relation of the interval between lithium level checks at GP practice level and psychiatric admission rate for inpatient treatment, for people with bipolar affective disorder monitored at each GP surgery. We found that the more frequently the tests are requested at the GP practice, the lower the number of admissions per individual. This is relevant to everyday clinical practice and supports the implementation of measures to ensure GP practice engagement with people with bipolar disorder, in order to reduce hospital admissions in this condition. This article is protected by copyright. All rights reserved. [ABSTRACT FROM AUTHOR]