Reduction in Chest CT Severity and Improved Hospital Outcomes in SARS-CoV-2 Omicron Compared with Delta Variant Infection.

Background The SARS-Cov-2 Omicron variant demonstrates rapid spread but reduced disease severity. Studies evaluating lung imaging findings of Omicron infection versus non-Omicron infection remain lacking. Purpose To compare the Omicron variant with the SARS-CoV-2 Delta variant according to their chest CT radiologic pattern, biochemical parameters, clinical severity, and hospital outcomes after adjusting for vaccination status. Materials and Methods This retrospective study included hospitalized adult patients with reverse transcriptase-polymerase chain reaction test results positive for SARS-CoV-2, with CT pulmonary angiography performed within 7 days of admission between December 1, 2021, and January 14, 2022. Multiple readers performed blinded radiologic analyses that included RSNA CT classification, chest CT severity score (CTSS) (range, 0 [least severe] to 25 [most severe]), and CT imaging features, including bronchial wall thickening. Results A total of 106 patients (Delta group, n = 66; Omicron group, n = 40) were evaluated (overall mean age, 58 years ± 18 [SD]; 58 men). In the Omicron group, 37% of CT pulmonary angiograms (15 of 40 patients) were categorized as normal compared with 15% (10 of 66 patients) of angiograms in the Delta group (P = .016). A generalized linear model was used to control for confounding variables, including vaccination status, and Omicron infection was associated with a CTSS that was 7.2 points lower than that associated with Delta infection (ß = -7.2; 95% CI: -9.9, -4.5; P < .001). Bronchial wall thickening was more common with Omicron infection than with Delta infection (odds ratio [OR], 2.4; 95% CI: 1.01, 5.92; P = .04). A booster shot was associated with a protective effect for chest infection (median CTSS, 5; IQR, 0-11) when compared with unvaccinated individuals (median CTSS, 11; IQR, 7.5-14.0) (P = .03). The Delta variant was associated with a higher OR of severe disease (OR, 4.6; 95% CI: 1.2, 26; P = .01) and admission to a critical care unit (OR, 7.0; 95% CI: 1.5, 66; P = .004) when compared with the Omicron variant. Conclusion The SARS-CoV-2 Omicron variant was associated with fewer and less severe changes on chest CT images compared with the Delta variant. Patients with Omicron infection had greater frequency of bronchial wall thickening but less severe disease and improved hospital outcomes when compared with patients with Delta infection. © RSNA, 2022 Online supplemental material is available for this article.

Characterisation of parathyroid hormone concentration in extremely preterm or very low birthweight infants in routine clinical screening for metabolic bone disease: A service evaluation cohort study.

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.

Combining faecal immunochemical testing with blood test results for colorectal cancer risk stratification: a consecutive cohort of 16,604 patients presenting to primary care.

BACKGROUND: Faecal immunochemical tests (FITs) are used to triage primary care patients with symptoms that could be caused by colorectal cancer for referral to colonoscopy. The aim of this study was to determine whether combining FIT with routine blood test results could improve the performance of FIT in the primary care setting. METHODS: Results of all consecutive FITs requested by primary care providers between March 2017 and December 2020 were retrieved from the Oxford University Hospitals NHS Foundation Trust. Demographic factors (age, sex), reason for referral, and results of blood tests within 90 days were also retrieved. Patients were followed up for incident colorectal cancer in linked hospital records. The sensitivity, specificity, positive and negative predictive values of FIT alone, FIT paired with blood test results, and several multivariable FIT models, were compared. RESULTS: One hundred thirty-nine colorectal cancers were diagnosed (0.8%). Sensitivity and specificity of FIT alone at a threshold of 10 µg Hb/g were 92.1 and 91.5% respectively. Compared to FIT alone, blood test results did not improve the performance of FIT. Pairing blood test results with FIT increased specificity but decreased sensitivity. Multivariable models including blood tests performed similarly to FIT alone. CONCLUSIONS: FIT is a highly sensitive tool for identifying higher risk individuals presenting to primary care with lower risk symptoms. Combining blood test results with FIT does not appear to lead to better discrimination for colorectal cancer than using FIT alone.

The potential for utilising in-hospital glucose measurements to detect individuals at high risk of previously undiagnosed diabetes: Retrospective cohort study.

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.

How should we interpret lactate in labour? A reference study.

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.

Trends in Cancer Antigen 125 testing 2003-2014: A primary care population-based cohort study using laboratory data.

To understand Cancer Antigen 125 (CA125) testing in primary care in relation to a national guideline, we conducted a retrospective observational study including CA125 data from a well-defined region in the UK, from 2003 to 2014. 51,033 CA125 tests from 30,737 women were stratified by month and year of testing, location of test request and patient age. Absolute numbers and rates of testing, rates and proportions of positive and negative tests, and frequencies of single and repeat tests were calculated. Negative binomial and logistic regression were used to test the effect of the guideline's introduction. Primary care testing spiked in the three months following the release of the guideline. However, there was no difference in the increase in testing observed across age groups. The proportion of positive tests decreased over time despite both the rates of positive and negative tests increasing. Retesting and repeat testing were associated with the initial CA125 value with no significant difference between women whose first test was 30-35 and >35 IU/L. Large studies using linked data are required to investigate the impact of increasing CA125 testing on onward intervention and patient outcomes. CA125 guidelines should be refined to avoid over-investigation in low risk age-groups.

Baseline morning cortisol level as a predictor of pituitary-adrenal reserve: a comparison across three assays.

CONTEXT: The short ACTH stimulation test (250 µg) is the dynamic test most frequently used to assess adrenal function. It is possible that a single basal cortisol could be used to predict the dynamic response, but research has been hampered by the use of different assays and thresholds. OBJECTIVE: To propose a morning baseline cortisol criterion of three of the most commonly used modern cortisol immunoassays - Advia Centaur (Siemens), Architect (Abbott) and the Roche Modular System (Roche) - that could predict adrenal sufficiency. DESIGN: Observational, retrospective cross-sectional study at two centres. PATIENTS AND MEASUREMENTS: Retrospective analysis of the results of 1019 Short Synacthen tests (SSTs) with the Advia Centaur, 449 SSTs with the Architect and 2050 SSTs with the Roche Modular System assay. Serum cortisol levels were measured prior to injection of 250 µg Synacthen and after 30 min. Overall, we were able to collate data from a total of 3518 SSTs in 3571 patients. RESULTS: Using receiver-operator curve analysis, baseline cortisol levels for predicting passing the SST with 100% specificity were 358 nmol/l for Siemens, 336 nmol/l for Abbott and 506 nmol/l for Roche. Utilizing these criteria, 589, 158 and 578 SSTs, respectively, for Siemens, Abbott and Roche immunoassays could have been avoided. CONCLUSIONS: We have defined assay-specific morning cortisol levels that are able to predict the integrity of the hypothalamo-pituitary-adrenal axis. We propose that this represents a valid tool for the initial assessment of adrenal function and has the potential to obviate the need for dynamic testing in a significant number of patients.

Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data.

BACKGROUND: Lithium is a widely used and highly effective treatment for mood disorders, but causes poorly characterised adverse effects in kidney and endocrine systems. We aimed to analyse laboratory information system data to determine the incidence of renal, thyroid, and parathyroid dysfunction associated with lithium use. METHODS: In a retrospective analysis of laboratory data from Oxford University Hospitals National Health Service Trust (Oxfordshire, UK), we investigated the incidence of renal, thyroid, and parathyroid dysfunction in patients (aged ≥18 years) who had at least two creatinine, thyrotropin, calcium, glycated haemoglobin, or lithium measurements between Oct 1, 1982, and March 31, 2014, compared with controls who had not had lithium measurements taken. We used survival analysis and Cox regression to estimate the hazard ratio (HR) for each event with lithium use, age, sex, and diabetes as covariates. FINDINGS: Adjusting for age, sex, and diabetes, presence of lithium in serum was associated with an increased risk of stage three chronic kidney disease (HR 1·93, 95% CI 1·76-2·12; p<0·0001), hypothyroidism (2·31, 2·05-2·60; p<0·0001), and raised total serum calcium concentration (1·43, 1·21-1·69; p<0·0001), but not with hyperthyroidism (1·22, 0·96-1·55; p=0·1010) or raised adjusted calcium concentration (1·08, 0·88-1·34; p=0·4602). Women were at greater risk of development of renal and thyroid disorders than were men, with younger women at higher risk than older women. The adverse effects occurred early in treatment (HR <1 for length of treatment with lithium). Higher than median lithium concentrations were associated with increased risk of all adverse outcomes. INTERPRETATION: Lithium treatment is associated with a decline in renal function, hypothyroidism, and hypercalcaemia. Women younger than 60 years and people with lithium concentrations higher than median are at greatest risk. Because lithium remains a treatment of choice for bipolar disorder, patients need baseline measures of renal, thyroid, and parathyroid function and regular long-term monitoring. FUNDING: None.

Increasing burden of community-acquired pneumonia leading to hospitalisation, 1998-2014.

BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of mortality and morbidity in many countries but few recent large-scale studies have examined trends in its incidence. METHODS: Incidence of CAP leading to hospitalisation in one UK region (Oxfordshire) was calculated over calendar time using routinely collected diagnostic codes, and modelled using piecewise-linear Poisson regression. Further models considered other related diagnoses, typical administrative outcomes, and blood and microbiology test results at admission to determine whether CAP trends could be explained by changes in case-mix, coding practices or admission procedures. RESULTS: CAP increased by 4.2%/year (95% CI 3.6 to 4.8) from 1998 to 2008, and subsequently much faster at 8.8%/year (95% CI 7.8 to 9.7) from 2009 to 2014. Pneumonia-related conditions also increased significantly over this period. Length of stay and 30-day mortality decreased slightly in later years, but the proportions with abnormal neutrophils, urea and C reactive protein (CRP) did not change (p>0.2). The proportion with severely abnormal CRP (>100 mg/L) decreased slightly in later years. Trends were similar in all age groups. Streptococcus pneumoniae was the most common causative organism found; however other organisms, particularly Enterobacteriaceae, increased in incidence over the study period (p<0.001). CONCLUSIONS: Hospitalisations for CAP have been increasing rapidly in Oxfordshire, particularly since 2008. There is little evidence that this is due only to changes in pneumonia coding, an ageing population or patients with substantially less severe disease being admitted more frequently. Healthcare planning to address potential further increases in admissions and consequent antibiotic prescribing should be a priority.

Point-of-care testing of electrolytes and calcium using blood gas analysers: it is time we trusted the results.

BACKGROUND: Point-of-care testing allows rapid analysis of samples to facilitate prompt clinical decisions. Electrolyte and calcium abnormalities are common in acutely ill patients and can be associated with life-threatening consequences. There is uncertainty whether clinical decisions can be based on the results obtained from blood gas analysers or if laboratory results should be awaited. OBJECTIVES: To assess the agreement between sodium, potassium and calcium results from blood gas and laboratory mainstream analysers in a tertiary centre, with a network consisting of one referral and two peripheral hospitals, consisting of three networked clinical biochemistry laboratories. METHOD: Using the laboratory information management system database and over 11 000 paired samples in three hospital sites, the results of sodium, potassium and ionised calcium on blood gas analysers were studied over a 5-year period and compared with the corresponding laboratory results from the same patients booked in the laboratory within 1 h. RESULTS: The Pearson's linear correlation coefficient between laboratory and blood gas results for sodium, potassium and calcium were 0.92, 0.84 and 0.78, respectively. Deming regression analysis showed a slope of 1.04 and an intercept of -5.7 for sodium, slope of 0.93 and an intercept of 0.22 for potassium and a slope of 1.23 with an intercept of -0.55 for calcium. With some strict statistical assumptions, percentages of results lying outside the least significant difference were 9%, 26.7% and 20.8% for sodium, potassium and calcium, respectively. CONCLUSIONS: Most clinicians wait for the laboratory confirmation of results generated by blood gas analysers. In a large retrospective study we have shown that there is sufficient agreement between the results obtained from the blood gas and laboratory analysers to enable prompt clinical decisions to be made.

Effect of bilateral internal mammary artery grafts on long-term survival: a meta-analysis approach.

BACKGROUND: Although the potential survival benefit of bilateral internal mammary artery (BIMA) grafting in comparison with single internal mammary artery (SIMA) grafting has been emphasized by many investigators, the use of BIMA is still low in clinical practice in the absence of randomized trials and long-term results. In the current study, we aimed to assess if there is a long-term survival benefit of BIMA up to 10 years after coronary bypass surgery. METHODS AND RESULTS: We selected published articles comparing survival between SIMA and BIMA patients with follow-up duration of more than a mean of 9 years. We evaluated the log hazard ratio with 95% confidence interval for included studies by using a random-effects meta-analysis. Nine eligible observational studies provided 15 583 patients (8270 SIMA and 7313 BIMA) for meta-analysis. Five studies used propensity score methods for statistical adjustment, 2 with a propensity score-based patient-matching method and 3 with quintile-based stratification. A significant reduction in mortality by using BIMA was observed (hazard ratio, 0.79; 95% confidence interval, 0.75-0.84); no study showed any significantly harmful effect of BIMA on survival. Subgroups of studies using different statistical approaches-unmatched, quintile-based propensity score analysis, and propensity score-based exact patient matching-all showed the survival benefit of BIMA grafting. CONCLUSIONS: BIMA grafting appears to have better survival with up to 10 years follow-up in comparison with SIMA grafting. Long-term survival benefit of BIMA seems to continue in the second decade after surgery. An ongoing randomized trial comparing SIMA and BIMA groups will add evidence on this issue.

Copeptin and the syndrome of inappropriate antidiuresis (SIAD) after pituitary transsphenoidal surgery.

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.

FIT negative clinic as a safety net for low-risk patients with colorectal cancer: impact on endoscopy and radiology utilisation-a retrospective cohort study.

Background: Faecal immunochemical testing (FIT) is recommended by the National Institute for Health and Care Excellence to triage symptomatic primary care patients who have unexplained symptoms but do not meet the criteria for a suspected lower gastrointestinal cancer pathway. During the COVID-19 pandemic, FIT was used to triage patients referred with urgent 2-week wait (2ww) cancer referrals instead of a direct-to-test strategy. FIT-negative patients were assessed and safety netted in a FIT negative clinic. Methods: We reviewed case notes for 622 patients referred on a 2ww pathway and seen in a FIT negative clinic between June 2020 and April 2021 in a tertiary care hospital. We collected information on demographics, indication for referral, dates for referral, clinic visit, investigations and long-term outcomes. Results: The average age of the patients was 71.5 years with 54% female, and a median follow-up of 2.5 years. Indications for referrals included: anaemia (11%), iron deficiency (24%), weight loss (9%), bleeding per rectum (5%) and change in bowel habits (61%). Of the cases, 28% (95% CI 24% to 31%) had endoscopic (15%, 95% CI 12% to 18%) and/or radiological (20%, 95% CI 17% to 23%) investigations requested after clinic review, and among those investigated, malignancy rate was 1.7%, with rectosigmoid neuroendocrine tumour, oesophageal cancer and lung adenocarcinoma. Conclusion: A FIT negative clinic provides a safety net for patients with unexplained symptoms but low risk of colorectal cancer. These real-world data demonstrate significantly reduced demand on endoscopy and radiology services for FIT-negative patients referred via the 2ww pathway.

Severe acute myositis and myocarditis on initiation of 6-weekly pembrolizumab post-COVID-19 mRNA vaccination.

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within 1 month of receiving the initial cycle of the anti-PD-1 drug pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination.

Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection.

BACKGROUND: Despite substantial interest in biomarkers, their impact on clinical outcomes and variation with bacterial strain has rarely been explored using integrated databases. METHODS: From September 2006 to May 2011, strains isolated from Clostridium difficile toxin enzyme immunoassay (EIA)-positive fecal samples from Oxfordshire, United Kingdom (approximately 600,000 people) underwent multilocus sequence typing. Fourteen-day mortality and levels of 15 baseline biomarkers were compared between consecutive C. difficile infections (CDIs) from different clades/sequence types (STs) and EIA-negative controls using Cox and normal regression adjusted for demographic/clinical factors. RESULTS: Fourteen-day mortality was 13% in 2222 adults with 2745 EIA-positive samples (median, 78 years) vs 5% in 20,722 adults with 27,550 EIA-negative samples (median, 74 years) (absolute attributable mortality, 7.7%; 95% CI, 6.4%-9.0%). Mortality was highest in clade 5 CDIs (25% [16 of 63]; polymerase chain reaction (PCR) ribotype 078/ST 11), then clade 2 (20% [111 of 560]; 99% PCR ribotype 027/ST 1) versus clade 1 (12% [137 of 1168]; adjusted P < .0001). Within clade 1, 14-day mortality was only 4% (3 of 84) in ST 44 (PCR ribotype 015) (adjusted P = .05 vs other clade 1). Mean baseline neutrophil counts also varied significantly by genotype: 12.4, 11.6, and 9.5 × 10(9) neutrophils/L for clades 5, 2 and 1, respectively, vs 7.0 × 10(9) neutrophils/L in EIA-negative controls (P < .0001) and 7.9 × 10(9) neutrophils/L in ST 44 (P = .08). There were strong associations between C. difficile-type-specific effects on mortality and neutrophil/white cell counts (rho = 0.48), C-reactive-protein (rho = 0.43), eosinophil counts (rho = -0.45), and serum albumin (rho = -0.47). Biomarkers predicted 30%-40% of clade-specific mortality differences. CONCLUSIONS: C. difficile genotype predicts mortality, and excess mortality correlates with genotype-specific changes in biomarkers, strongly implicating inflammatory pathways as a major influence on poor outcome after CDI. PCR ribotype 078/ST 11 (clade 5) leads to severe CDI; thus ongoing surveillance remains essential.

Diagnostic accuracy of urine dipstick testing in screening for microalbuminuria in type 2 diabetes: a cohort study in primary care.

BACKGROUND: Clinical guidelines recommend annual screening for microalbuminuria in diabetes. Detection of microalbuminuria is important because it is associated with increased morbidity and mortality. Dipstick tests for microalbuminuria may be convenient, but their accuracy is uncertain. OBJECTIVE: To assess the utility of urine dipstick testing for microalbuminuria in type 2 diabetes. METHODS: In a 6-week cohort study in four general practices in Oxfordshire, UK, first-pass urine samples were obtained at two weekly intervals from patients with type 2 diabetes and tested in the practice using Micral-Test and Microalbustix urine dipsticks. Parallel samples were sent for laboratory albumin-creatinine ratio (ACR) assay. Results of single dipstick tests and sequences of dipstick and laboratory tests were compared with a clinical testing strategy based on current guidelines to assess the accuracy and estimate costs of testing. RESULTS: The prevalence of microalbuminuria was 12.5% (n = 88). Mean (standard deviation) age was 68 (10) years, 56 (57%) were men. Median (interquartile range) diabetes duration was 6.2 (2.0-10.0) years. The sensitivity and specificity, respectively, of a single Micral-Test were 91.7% and 44.0% and of a Microalbustix test 33.3% and 92.0%. Testing strategies involving dipstick and laboratory ACR measurements or dipstick tests had similar accuracy. The costs of using dipstick tests were overall lower than laboratory ACR-based testing. CONCLUSIONS: Dipstick testing in this study did not reliably identify diabetes patients with microalbuminuria. Although dipstick testing would decrease testing costs, it could either fail to diagnose most patients with microalbuminuria or increase the numbers of patients retested depending on the dipstick used.

UK Reference Intervals for Parathyroid Hormone Using Abbott Methods.

Background: Diagnosis of hyperparathyroidism requires measurement of parathyroid hormone (PTH) in the context of the plasma calcium and other factors, such as vitamin D status and renal function. Accurate classification depends upon an appropriate population reference interval. We examined local population plasma PTH reference intervals at four different UK sites using a common platform. Methods: Plasma PTH results were extracted from laboratory information systems at four different UK sites, all using the Abbott Architect i2000 method. We included only people with normal adjusted serum calcium, magnesium, vitamin D, and renal function. Following outlier rejection lower and upper reference limits were derived. Results: An overall reference interval for plasma PTH of 3.0-13.7 pmol/L was observed using a non-parametric approach compared to 2.9-14.1 pmol/L using a parametric approach, notably higher than the manufacturer's representative range of 1.6-7.2 pmol/L. We also noted statistically significant differences (p < 0.00001) between some sites with upper limits ranging from 11.5 to 15.8 pmol/L which may be due to different population characteristics of each group. Conclusion: Locally derived reference intervals may be beneficial for UK populations and revised upper thresholds are necessary when using the Abbott PTH method to avoid inappropriate classification of patients as having hyperparathyroidism.

Assessing treatment adherence is crucial to determine adequacy of mineralocorticoid therapy.

Background: There is no consensus strategy for mineralocorticoid (MC) therapy titration in patients with primary adrenal insufficiency (PAI). We aim to measure serum fludrocortisone (sFC) and urine fludrocortisone (uFC) levels and to determine their utility, alongside clinical/biochemical variables and treatment adherence to guide MC replacement dose titration. Methods: Multi-centre, observational, cross-sectional study on 41 patients with PAI on MC replacement therapy. sFC and uFC levels (measured by liquid chromatography-tandem mass spectrometry), plasma renin concentration (PRC), electrolytes (Na+, K+), mean arterial blood pressure (MAP), total daily glucocorticoid (dGC) and MC (dMC) dose, and assessment of treatment adherence were incorporated into statistical models. Results: We observed a close relationship between sFC and uFC (r = 0.434, P = 0.005) and between sFC and the time from the last fludrocortisone dose (r = -0.355, P = 0.023). Total dMC dose was related to dGC dose (r = 0.556, P < 0.001), K+ (r = -0.388, P = 0.013) as well as sFC (r = 0.356, P = 0.022) and uFC (r = 0.531, P < 0.001). PRC was related to Na+ (r = 0.517, P < 0.001) and MAP (r = -0.427, P = 0.006), but not to MC dose, sFC or uFC. Regression analyses did not support a role for sFC, uFC or PRC measurements and confirmed K+ (B = -44.593, P = 0.005) as the most important variable to guide dMC titration. Of the patients, 32% were non-adherent with replacement therapy. When adherence was inserted into the regression model, it was the only factor affecting dMC. Conclusions: sFC and uFC levels are not helpful in guiding dMC titration. Treatment adherence impacts on clinical variables used to assess MC replacement and should be included as part of routine care in patients with PAI.