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Objective: This study evaluates the predictive value of copeptin for syndrome of inappropriate antidiuresis (SIAD) postpituitary transsphenoidal surgery (TSS). Design: Data from 133 consecutive patients undergoing TSS (November 2017–October 2022) at Oxford University Hospitals NHS trust are presented in this retrospective study. Methods: Logistic regression (LR) and receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic utility of copeptin. The Mann–Whitney U test was used to compare copeptin levels between the SIAD and no SIAD groups. Results: Fourteen patients (10.8%) developed SIAD. Copeptin was available in 121, 53 and 87 patients for Days 1, 241 and 8 post‐TSS, respectively. LR for Day 1 copeptin to predict SIAD gave an odds ratio (OR) of 1.0 (95%CI 42 0.84–1.20, p =.99), area under‐ROC curve (AUC) was 0.49; Day 2 copeptin OR was 0.65 (95%CI 0.39–1.19, 43 p =.77), AUC was 0.57 LR for Day 1 sodium to predict SIAD gave an odds ratio (OR) of 1.0 (95%CI 0.85–1.21, p =.99), AUC was 0.50. Conclusions: In conclusion, our data provide no evidence for copeptin as a predictive marker for post‐TSS SIAD. [ABSTRACT FROM AUTHOR]

Aim: To characterise parathyroid hormone (PTH) concentrations in infants at high risk for metabolic bone disease, in order to assist clinical decisions around the use of PTH for screening. Methods: Infants born under 28 weeks' postmenstrual age or with birthweight under 1.5 kg in a tertiary neonatal unit in the UK were included. Clinical guidance was to assess PTH concentration in the first 3 weeks after birth. Clinical information was extracted from prospective records. Results: Sixty‐four infants had mean birth gestation of 26 weeks and birthweight of 882 g. Median PTH (sent on median day 18 of life) was 9.2 pmol/L (interquartile range 5.3–17 pmol/L). Sixty‐seven per cent of infants had a PTH greater than 7 pmol/L. For 22% of the infants, raised PTH was not accompanied by abnormal phosphate or alkaline phosphatase. Eighty‐nine per cent of infants tested were insufficient or deficient for 25‐hydroxyvitamin D. Conclusions: Universal screening highlights the high frequency of high PTH in this high‐risk population, implying a need for calcium supplementation. A considerable number of infants would not be identified as showing potential signs of metabolic bone disease if the assessment excludes the use of PTH. The high level of 25‐hydroxyvitamin D deficiency may be a confounder. [ABSTRACT FROM AUTHOR]

Objective: To investigate maternal lactate concentrations in labour and the puerperium. Design: Reference study. Setting: Tertiary obstetric unit. Population: 1279 pregnant women with good perinatal outcomes at term. Methods: Electronic patient records were searched for women who had lactate measured on the day of delivery or in the following 24 hours, but who were subsequently found to have a very low likelihood of sepsis, based on their outcomes. Main outcome measures: The normative distribution of lactate and C‐reactive protein (CRP), differences according to the mode of birth, and the proportion of results above the commonly used cut‐offs (≥2 and ≥4 mmol/l). Results: Lactate varied between 0.4–5.4 mmol/l (median 1.8 mmol/l, interquartile range [IQR] 1.3–2.5). It was higher in women who had vaginal deliveries than caesarean sections (median 1.9 vs. 1.6 mmol/l, pdiff < 0.001), demonstrating the association with labour (particularly active pushing in the second stage). In contrast, CRP was more elevated in women who had caesarean sections (median 71.8 mg/l) than those who had vaginal deliveries (33.4 mg/l, pdiff < 0.001). In total, 40.8% had a lactate ≥2 mmol/l, but 95.3% were <4 mmol/l. Conclusions: Lactate in labour and the puerperium is commonly elevated above the levels expected in healthy pregnant or non‐pregnant women. There is a paucity of evidence to support using lactate or CRP to make decisions about antibiotics around the time of delivery but, as lactate is rarely higher than 4 mmol/l, this upper limit may still represent a useful severity marker for the investigation and management of sepsis in labour. [ABSTRACT FROM AUTHOR]

Background: Many people with undiagnosed diabetes have hyperglycaemia when admitted to hospital. Inpatient hyperglycaemia can be an indication of diabetes mellitus but can also indicate a stress response. This study reports the extent to which an in‐hospital maximum observed random glucose measurement is an indicator of the need for in‐hospital (or subsequent) HbA1c measurement to look for undiagnosed diabetes. Methods: Blood glucose, HbA1c, age and sex were collected for all adults following admission to a UK NHS trust hospital from 1 January 2019 to 31 December 2020. We restricted the analysis to those participants who were registered with a GP practice that uses the trust laboratory and who had at least some tests requested by those practices since 2008. We stratified individuals according to their maximum in‐hospital glucose measurement and report the number of these with HbA1c measurement ≥48 mmol/mol (6.5%) prior to the index admission, and during and after admission. We calculated an estimated proportion of individuals in each blood glucose stratum without a follow‐up HbA1c who could have undiagnosed diabetes. Results: In toal, 764,241 glucose measurements were recorded for 81,763 individuals who were admitted to the Oxford University Hospitals Trust. The median (Q1, Q3) age was 70 (56, 81) years, and 53% were males. Of the population, 70.7% of individuals declared themselves to be of White ethnicity, 3.1% of Asian background, and 1.1% of Black background, with 23.1% unstated. Of those individuals, 22,375 (27.4%) had no previous HbA1c measurement recorded. A total of 1689 individuals had a diabetes‐range HbA1c during or after their hospital admission (2.5%) while we estimate an additional 1496 (2.2%) may have undiagnosed diabetes, with the greatest proportion of these having an in‐hospital glucose of ≥15 mmol/L. We estimate that the number needed to detect a possible new case of diabetes falls from 16 (in‐hospital glucose 8 mmol/L to <9 mmol/L) to 4 (14 mmol/L to <15 mmol/L). Conclusion: The number of people who need to be tested to identify an individual who may have diabetes decreases as a testing threshold based on maximum in‐hospital glucose concentration increases. Among those with hyperglycaemia and no previous HbA1c measurement in the diabetes range, there appears to be a lack of subsequent HbA1c measurement. This work identifies the potential for integrating the testing and follow‐up of people, with apparently unrecognised hospital hyperglycaemia across primary and secondary care. [ABSTRACT FROM AUTHOR]

Background: Around one million individuals in the UK have heart failure (HF), a chronic disease that causes significant morbidity and mortality. N-terminal pro-B-type natriuretic peptide (NT-proBNP) monitoring could help improve the care of patients with HF in the community. Aim: The aim of this study is to provide evidence to support the routine use of point-of-care (POC) NT-proBNP monitoring in primary care. Design & setting: In this observational cohort study, the Roche Cobas h 232 POC device was used to measure NT-proBNP in 27 patients with HF at 0, 6, and 12 months, with a subset reanalysed in the laboratory for comparison. Method: Data were analysed for within-person and between-person variability and concordance with laboratory readings using Passing-Bablok regression. GPs reported whether POC results impacted clinical decisionmaking, and patients indicated their willingness to participate in long-term cohort studies using the Likert acceptability scale. Results: Within-person variability in POC NT-proBNP over 12 months was 881 pg/mL (95% confidence interval [CI] = 380 to 1382 pg/mL). Between-person variability was 1972 pg/mL (95% CI = 1,525 to 2791 pg/mL). Passing-Bablok regression showed no significant systematic difference between POC and laboratory measurements. Patients indicated a high level of acceptability, and GP decisionmaking was affected for at least one visit in a third of patients. Conclusion: Within-person variability in POC NT-proBNP is around half of between-person variability, so detecting changes could be of use in HF management. High patient acceptability and impact on clinical decisionmaking warrant further investigation in a larger long-term cohort study. [ABSTRACT FROM AUTHOR]

Background: Monitoring is the mainstay of chronic kidney disease management in primary care; however, there is little evidence about the best way to do this.Aim: To compare the effectiveness of estimated glomerular filtration rate (eGFR) derived from serum creatinine and serum cystatin C to predict renal function decline among those with a recent eGFR of 30-89 ml/min/1.73 m2.Design and Setting: Observational cohort study in UK primary care.Method: Serum creatinine and serum cystatin C were both measured at seven study visits over 2 years in 750 patients aged ≥18 years with an eGFR of 30-89 ml/min/1.73 m2 within the previous year. The primary outcome was change in eGFR derived from serum creatinine or serum cystatin C between 6 and 24 months.Results: Average change in eGFR was 0.51 ml/min/1.73 m2/year when estimated by serum creatinine and -2.35 ml/min/1.73 m2/year when estimated by serum cystatin C. The c-statistic for predicting renal decline using serum creatininederived eGFR was 0.495 (95% confidence interval [CI] = 0.471 to 0.519). The equivalent c-statistic using serum cystatin C-derived eGFR was 0.497 (95% CI = 0.468 to 0.525). Similar results were obtained when restricting analyses to those aged ≥75 or <75 years, or with eGFR ≥60 ml/min/1.73 m2. In those with eGFR <60 ml/min/1.73 m2, serum cystatin C-derived eGFR was more predictive than serum creatinine-derived eGFR for future decline in kidney function.Conclusion: In the primary analysis neither eGFR estimated from serum creatinine nor from serum cystatin C predicted future change in kidney function, partly due to small changes during 2 years. In some secondary analyses there was a suggestion that serum cystatin C was a more useful biomarker to estimate eGFR, especially in those with a baseline eGFR <60 ml/min/1.73 m2. [ABSTRACT FROM AUTHOR]

Context Cardiac disease is the leading cause of maternal mortality in the UK, so accurate cardiovascular diagnoses in pregnancy are essential. BNP (B-type natriuretic peptide) and NT-pro BNP (N-terminal-pro BNP) are useful clinical tools for investigating suspected peripartum cardiomyopathy but, as the pregnancy-specific reference intervals are undefined, it is uncertain how they should be interpreted in pregnant women. Objectives To define trimester-specific 95% reference intervals for BNP and NT-pro BNP in pregnancy. Methods Longitudinal study of 260 healthy pregnant women, with sampling in each trimester. Results The upper reference limit for NT-pro BNP was 200 pg/mL in the first and second trimesters, and 150 pg/mL in the third. Levels were significantly reduced in overweight women in the third trimester (P  = .0001), which supports the partitioning of reference intervals by body mass index (BMI). The upper limit for BNP was 50 pg/mL, with no detectable trimester-related differences. Although other biomarkers (hemoglobin and platelets) fell throughout pregnancy, both natriuretic peptides were initially elevated before falling by the third trimester, suggesting that the observed changes in natriuretic peptides are driven by dynamic interplay between cardiac strain and progressive hemodilution. NT-pro BNP in the first trimester was inversely associated with neonatal birthweight at term (P  = .011). Conclusion Cardiac biomarkers have an important role for investigating suspected disease in high-risk pregnant women, but a robust assessment of the levels expected in healthy pregnant women is an essential prerequisite to their application in clinical practice. This study has defined trimester- and BMI-specific reference intervals for NT-pro BNP and BNP, which may improve how women with suspected cardiovascular disease are investigated in pregnancy. [ABSTRACT FROM AUTHOR]

Abstract Background The National Health Service Prostate Cancer Risk Management Programme (PCRMP) has recommended that screening for prostate cancer is available for asymptomatic men, on the understanding that they have been provided with full and balanced information about the advantages and limitations of the prostate-specific antigen (PSA) test. Guidance has been distributed to all GPs in England and Wales to assist in the provision of information to men. This study aimed to elicit GPs' accounts of their discussions with asymptomatic men who consult with concerns about prostate cancer in order to identify the degree to which the PCRMP guidance was reflected in these consultations. Methods Qualitative interview study. Semi-structured telephone interviews with 21 GPs from 18 GP practices in Oxfordshire. Results All GPs reported undertaking some discussion with asymptomatic men about the PSA test. They described focussing most of the discussion on the false-positive and false-negative rates of the test, and the risks associated with a prostate biopsy. They reported less discussion of the potential for diagnosing indolent cancers, the dilemmas regarding treatment options for localised prostate cancer and the potential benefits of testing. Considerable variation existed between GPs in their accounts of the degree of detail given, and GP's presentation of information appeared to be affected by their personal views of the PSA test. Conclusion The GPs in this study appear to recognise the importance of discussions regarding PSA testing; however, a full and balanced picture of the associated advantages and limitations does not seem to be consistently conveyed. Factors specific to PSA testing which appeared to have an impact on the GPs' discussions were the GP's personal opinions of the PSA test, and the need to counter men's primarily positive views of the benefits of PSA testing. Awareness of the impact of their views on the consultations may help GPs give men a more balanced presentation of the benefits and limitations of the PSA test.

Background: The risk of myocardial infarction (MI) increases during pregnancy, particularly in women with pre-eclampsia. MI is diagnosed by measuring high blood levels of cardiac-specific troponin (cTn), although this may be elevated in women with pre-eclampsia without MI, which increases diagnostic uncertainty. It is unclear how much cTn is elevated in uncomplicated and complicated pregnancy, which may affect whether the existing reference intervals can be used in pregnant women. Previous reviews have not investigated high-sensitivity troponin in pregnancy, compared to older, less sensitive methods. Methods: Electronic searches using the terms "troponin I" or "troponin T", and "pregnancy", "pregnancy complications" or "obstetrics". cTn levels were extracted from studies of women with uncomplicated pregnancies or pre-eclampsia. Results: The search identified ten studies with 1581 women. Eight studies used contemporary methods that may be too insensitive to use reliably in this clinical setting. Two studies used high-sensitivity assays, with one reporting an elevation in troponin I (TnI) in pre-eclampsia compared to uncomplicated pregnancy, and the other only examining women with pre-eclampsia. Seven studies compared cTn between women with pre-eclampsia or uncomplicated pregnancy using any assay. Seven studies showed elevated TnI in pre-eclampsia compared to uncomplicated pregnancy or non-pregnant women. One study measured troponin T (TnT) in pregnancy but did not examine pre-eclampsia. Conclusion: TnI appears to be elevated in pre-eclampsia, irrespective of methodology, which may reflect the role of cardiac stress in this condition. TnI may be similar in healthy pregnant and non-pregnant women, but we found no literature reporting pregnancy-specific reference intervals using high-sensitivity tests. This limits broader application of cTn in pregnancy. There is a need to define reference intervals for cTn in pregnant women, which should involve serial sampling throughout pregnancy, with careful consideration for gestational age and body mass index, which cause dynamic changes in normal maternal physiology. [ABSTRACT FROM AUTHOR]

Summary: Background: Faecal immunochemical testing (FIT) is recommended by the National Institute for Health and Care Excellence (NICE) to triage symptomatic primary care patients for further investigation of colorectal cancer. Aim: To ascertain the diagnostic performance of FIT in symptomatic adult primary care patients. Methods: Faecal samples from routine primary care practice in Oxfordshire, UK were analysed using the HM‐JACKarc FIT method between March 2017 and March 2020. Clinical details were recorded. Patients were followed for up to 36 months in linked hospital records for evidence of benign and serious (colorectal cancer, high‐risk adenomas and bowel inflammation) colorectal disease. The diagnostic accuracy of FIT is reported by gender, age group and FIT threshold. Results: In 9896 adult patients with at least 6‐month follow‐up, a FIT result ≥10 µg Hb/g faeces had a sensitivity for colorectal cancer of 90.5% (95% CI 84.9%‐96.1%), specificity 91.3% (90.8%‐91.9%), positive predictive value (PPV) 10.1% (8.15%‐12.0%) and negative predictive value (NPV) 99.9% (99.8%‐100.0%). The PPV and specificity for serious colorectal disease were higher and the sensitivity and NPV lower than for colorectal cancer alone. The area under the curve for all adults did not change substantially by gender or by increasing the minimum age of testing. Using ≥10 µg Hb/g faeces, 10% of adults would be investigated to detect 91% of cancers, a number needed to scope of ten to detect one cancer. Using ≥7, ≥50 and ≥150 µg Hb/g faeces, 11%, 4% and 3% of adults would be investigated, and 91%, 74% and 54% cancers detected, respectively. Conclusion: A FIT threshold of ≥10 µg Hb/g faeces would be appropriate to triage adult patients presenting to primary care with symptoms of serious colorectal disease. FIT may be used to reprioritise patients referred with colorectal cancer symptoms whose investigations have been delayed by the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Background: In patients with phaeochromocytomas or paragangliomas (PPGLs), 24-h urine collections for metanephrines (uMNs) are cumbersome. Objective: To evaluate the diagnostic utility of ratios to creatinine of 'spot' uMNs. Methods: Concentrations of uMNs and plasma metanephrines (pMNs) were me asured by HPLC-mass-spectrometry. We retrospectively compared correlations of 24-h-urine output and ratio to creatinine in historical specimens and prospectively assessed 24-h and contemporaneous spot urines and , where possible, pMNs. Using trimmed log-transformed values, we derived reference intervals based on age and sex for spot urines. We used multiples of upper limit of normal (ULNs) to compare areas under curves (AUCs) for receiver-operator characteristic curves of individual, and sum and product of, components. Results: In 3143 24-h-urine specimens on 2416 patients, the correlation coefficients between the ratios and outputs of metanephrine, normetanephrine and 3-methoxytyramine in 24-h urines were 0.983, 0.905 and 0.875, respectively. In 96 patients, the correlations between plasma concentrations, urine output and ratios in spot specimens were similar to those for raw output or ratios in 24-h specimens. Of the 160 patients with PPGLs, the CIs for AUCs for individual metabolites overlapped for all four types of measurement, as did those for the sum of the multiple ULNs although these were slightly higher (AUC for spot urine: 0.838 (0.529-1) , plasma: 0.929 (0.874-0.984) and output: 0.858 (0.764-0.952)). Conclusions: Ratios of fractionated metanephrines to creatinine in spot urine samples appear to have a similar diagnostic power to other measurements. The ease of spot urine collection may facilitate diagnosis and follow-up of PPGLs through improved patient compliance. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a largely asymptomatic condition of diminished renal function, which may not be detected until advanced stages without screening.Aim: To establish undiagnosed and overall CKD prevalence using a cross-sectional analysis.Design and Setting: Longitudinal cohort study in UK primary care.Method: Participants aged ≥60 years were invited to attend CKD screening visits to determine whether they had reduced renal function (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 or albumin:creatinine ratio ≥3 mg/mmol). Those with existing CKD, low eGFR, evidence of albuminuria, or two positive screening tests attended a baseline assessment (CKD cohort).Results: A total of 3207 participants were recruited and 861 attended the baseline assessment. The CKD cohort consisted of 327 people with existing CKD, 257 people with CKD diagnosed through screening (CKD prevalence of 18.2%, 95% confidence interval [CI] = 16.9 to 19.6), and 277 with borderline/transient decreased renal function. In the CKD cohort, 54.4% were female, mean standard deviation (SD) age was 74.0 (SD 6.9) years, and mean eGFR was 58.0 (SD 18.4) ml/min/1.73 m2. Of the 584 with confirmed CKD, 44.0% were diagnosed through screening. Over half of the CKD cohort (51.9%, 447/861) fell into CKD stages 3-5 at their baseline assessment, giving an overall prevalence of CKD stages 3-5 of 13.9% (95% CI = 12.8 to 15.1). More people had reduced eGFR using the Modification of Diet in Renal Disease (MDRD) equation than with CKD Epidemiology Collaboration (CKD-EPI) equation in the 60-75-year age group and more had reduced eGFR using CKD-EPI in the ≥80-year age group.Conclusion: This study found that around 44.0% of people living with CKD are undiagnosed without screening, and prevalence of CKD stages 1-5 was 18.2% in participants aged >60 years. Follow-up will provide data on annual incidence, rate of CKD progression, determinants of rapid progression, and predictors of cardiovascular events. [ABSTRACT FROM AUTHOR]

Introduction. Adrenocortical carcinomas (ACCs) are infrequently reported to present with severe hypoglycemia syndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by tumor cells. Adrenocorticotropic hormone- (ACTH) independent hypercortisolism is the norm of hormonally active ACCs, but aberrant ACTH production by tumor cells can theoretically cause ACTH-dependent hypercortisolism. The purpose of this report was to present a case of an ACC manifested with the co-occurrence of two extremely rare presentations. Case Description. We present a rare case of a 43-year-old male patient admitted with recurrent episodes of severe non-ketotic and non-insulin-mediated hypoglycemia due to IGF-II mediated disease and ACTH-dependent Cushing's syndrome. He was diagnosed with a diffusely disseminated adrenocortical carcinoma with immunohistochemistry of tumor cells showing focal ACTH immunostain positivity. Conclusion. Non-islet cell tumor hypoglycemia and ACTH-dependent Cushing's syndrome are extremely rare presentations of an ACC, and co-occurrence of these entities in a single patient is never reported in the literature. [ABSTRACT FROM AUTHOR]

We read with interest the article by Groenendijk et al., in which normative pregnancy-specific levels are reported for 41 routine haematological and biochemical tests.[1] We appreciated this well-executed reference study for its rigorous approach to investigating partitioning by gestational age. Pregnancy-specific reference intervals for BNP and NT-pro BNP - Changes in natriuretic peptides related to pregnancy. [Extracted from the article]