Chronic kidney disease: a large-scale population-based study of the effects of introducing the CKD-EPI formula for eGFR reporting

Objective To evaluate the effects of introducing the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula for estimated glomerular filtration rate (eGFR) reporting in the adult population in routine clinical practice with clinician-directed testing. Design Retrospective study of all creatinine measurements and calculation of eGFRs using Modification of Diet in Renal Disease (MDRD) and CKD-EPI formulae. Setting General population, Oxfordshire, UK. Participants An unselected population of around 660 000. Interventions Reporting of eGFRs using MDRD or CKD-EPI formulae. Primary and secondary outcome measures Evaluation of the effects of the CKD-EPI formula on the prevalence of different stages of chronic kidney disease (CKD). Results The CKD-EPI formula reduced the prevalence of CKD (stages 2-5) by 16.4% in patients tested in primary care. At the important stage 2-stage 3 cut-off, there was a relative reduction of 7.5% in the prevalence of CKD stages 3-5 from 15.7% to 14.5%. The CKD-EPI formula reduced the prevalence of CKD stages 3-5 in those aged <70 but increased it at ages >70. Above 70 years, the prevalence of stages 3-5 was similar with both equations for women (around 41.2%) but rose in men from 33.3% to 35.5%. CKD stages 4-5 rose by 15% due exclusively to increases in the over 70s, which could increase specialist referral rates. The CKD classification of 18.3% of all individuals who had a creatinine measurement was altered by a change from the MDRD to the CKD-EPI formula. In the UK population, the classification of up to 3 million patients could be altered, the prevalence of CKD could be reduced by up to 1.9 million and the prevalence of CKD stages 3-5 could fall by around 200 000. Conclusions Introduction of the CKD-EPI formula for eGFR reporting will reduce the prevalence of CKD in a primary care setting with current testing practice but will raise the prevalence in the over 70s age group. This has implications for clinical practice, healthcare policy and current prevalence-based funding arrangements

Routine genetic screening with a multi-gene panel in patients with pheochromocytomas

PURPOSE: Several new gene mutations have been reported in recent years to be associated with a risk of familial pheochromocytoma. However, it is unclear as to whether extensive genetic testing is required in all patients. METHODS: The clinical data of consecutive patients operated for pheochromocytoma over a decade in a tertiary referral center were reviewed. Genetic screening was performed using a 10-gene panel: RET, VHL, SDHB, SDHD, SDHA, SDHC, SDHAF2, MAX, TMEM127 and FH. RESULTS: A total of 166 patients were analyzed: 87 of them had genetic screening performed (39 M: 44.8%, 48 F: 55.2%, age range 6-81 years, mean 45±16.8 years). In total, 22/87 (25.3%) patients had germline mutations, while 65/87 (74.7%) patients presented with apparently sporadic tumors. Germline VHL mutations were identified in 11.7% of patients, RET in 6.8% (five MEN2A/MEN2 and one MEN2B/MEN3), SDHD in 2.3%, MAX in 2.3%, SDHB in 1.1%, and TMEM127 in 1.1% of patients. At diagnosis, 15.1% of patients with unilateral non-syndromic pheochromocytoma showed germline mutations. We identified 19.7% of mutations in patients with unilateral-non-recurrent pheochromocytomas within 5 years vs. 50% in the recurrent-bilateral-metastatic group (p = 0.01). Germline mutations were more frequently seen with bilateral pheochromocytomas (p = 0.001): 80% of patients with bilateral disease had germline mutations (4 VHL, 3 RET, 1 MAX). CONCLUSIONS: The advent of rapid genetic screening using a gene-panel makes it feasible to screen large cohorts of patients and provides a valuable tool to contribute to the prediction of bilateral and malignant disease and to screen family members

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

Metrics for Aggregating the Climate Effect of Different Emissions: A Unifying Framework. ESRI WP257, September 2008

Multi-gas approaches to climate change policies require a metric establishing “equivalences” among emissions of various species. Climate scientists and economists have proposed four classes of such metrics and debated their relative merits. We present a unifying framework that clarifies the relationships among them. We show that the Global Warming Potential, used in international law to compare greenhouse gases, is a special case of the Global Damage Potential, assuming (1) a finite time horizon, (2) a zero discount rate, (3) constant atmospheric concentrations, and (4) impacts that are proportional to radiactive forcing. We show that the Global Temperature change Potential is a special case of the Global Cost Potential, assuming (1) no induced technological change, and (2) a short-lived capital stock. We also show that the Global Cost Potential is a special case of the Global Damage Potential, assuming (1) zero damages below a threshold and (2) infinite damage after a threshold. The UN Framework Convention on Climate Change uses the Global Warming Potential, a simplified cost-benefit concept, even though the UNFCCC frames climate policy as a cost-effectiveness problem and should therefore use the Global Cost Potential or its simplification, the Global Temperature Potential

C-reactive protein and neutrophil count laboratory test requests from primary care:what is the demand and would substitution by point of care technology be viable?

Aims: C-reactive protein (CRP) and neutrophil count (NC) are important diagnostic indicators of inflammation. Point-of-care (POC) technologies for these markers are available but rarely used in community settings in the UK. To inform the potential for POC tests, it is necessary to understand the demand for testing. We aimed to describe the frequency of CRP and NC test requests from primary care to central laboratory services, describe variability between practices and assess the relationship between the tests.Methods: We described the number of patients with either or both laboratory tests, and the volume of testing per individual and per practice, in a retrospective cohort of all adults in general practices in Oxfordshire, 2014–2016.Results: 372 017 CRP and 776 581 NC tests in 160 883 and 275 093 patients, respectively, were requested from 69 practices. CRP was tested mainly in combination with NC, while the latter was more often tested alone. The median (IQR) of CRP and NC tests/person tested was 1 (1–2) and 2 (1–3), respectively. The median (IQR) tests/ practice/week was 36 (22–52) and 72 (50–108), and per 1000 persons registered/practice/week was 4 (3–5) and 8 (7–9), respectively. The median (IQR) CRP and NC concentrations were 2.7 (0.9–7.9)mg/dL and 4.1 (3.1–5.5)×109/L, respectively.Conclusions: The high demand for CRP and NC testing in the community, and the range of results falling within the reportable range for current POC technologies highlight the opportunity for laboratory testing to be supplemented by POC testing in general practice

Requirement for cystatin C testing in chronic kidney disease:a retrospective population-based study

Creatinine-based estimated glomerular filtration rate (eGFR) determines chronic kidney disease (CKD) stage, but underestimates renal function. The 2014 updated guidance from the National Institute for Health and Care Excellence (NICE) recommends that GPs reduce overdiagnosis of CKD stage 3a (eGFR 45-60 ml/min/1.73 m2) by using the renal biomarker cystatin C.To determine the population requirement for cystatin C testing, compared with current national availability of the assay.Retrospective study of primary care laboratory requests in Oxfordshire, England.The first creatinine results from tests ordered in primary care over a 6-year period (2008-2014) in a population of 600 000 in Oxfordshire were analysed and the number of patients with CKD stage 3a without proteinuria (who, in accordance with NICE guidance, required cystatin C) was determined. A conservative estimate of the national need was provided by scaling the population of Oxfordshire to the national population (CKD prevalence in the county is below the national average). Cystatin C assay availability was determined using national databases of laboratory assay provision.From a population of 600 000, there were 22 240 individuals with stable stage 3a CKD and no proteinuria. As the population of Oxfordshire equates to 1% of the UK population, there is an initial requirement for at least 2 million people to have their CKD status determined with cystatin C testing. Eight laboratories (2.1% of UK laboratories) reported cystatin C assay provision.There is a substantial gap between cystatin C assay requirements in primary care and national assay provision. This is a major barrier to implementing NICE guidance

Broad external validation of a multivariable risk prediction model for gastrointestinal malignancy in iron deficiency anaemia.

BACKGROUND: Using two large datasets from Dorset, we previously reported an internally validated multivariable risk model for predicting the risk of GI malignancy in IDA-the IDIOM score. The aim of this retrospective observational study was to validate the IDIOM model using two independent external datasets. METHODS: The external validation datasets were collected, in a secondary care setting, by different investigators from cohorts in Oxford and Sheffield derived under different circumstances, comprising 1117 and 474 patients with confirmed IDA respectively. The data were anonymised prior to analysis. The predictive performance of the original model was evaluated by estimating measures of calibration, discrimination and clinical utility using the validation datasets. RESULTS: The discrimination of the original model using the external validation data was 70% (95% CI 65, 75) for the Oxford dataset and 70% (95% CI 61, 79) for the Sheffield dataset. The analysis of mean, weak, flexible and across the risk groups' calibration showed no tendency for under or over-estimated risks in the combined validation data. Decision curve analysis demonstrated the clinical value of the IDIOM model with a net benefit that is higher than 'investigate all' and 'investigate no-one' strategies up to a threshold of 18% in the combined validation data, using a risk cut-off of around 1.2% to categorise patients into the very low risk group showed that none of the patients stratified in this risk group proved to have GI cancer on investigation in the validation datasets. CONCLUSION: This external validation exercise has shown promising results for the IDIOM model in predicting the risk of underlying GI malignancy in independent IDA datasets collected in different clinical settings

Broad external validation of a multivariable risk prediction model for gastrointestinal malignancy in iron deficiency anaemia.

BACKGROUND: Using two large datasets from Dorset, we previously reported an internally validated multivariable risk model for predicting the risk of GI malignancy in IDA-the IDIOM score. The aim of this retrospective observational study was to validate the IDIOM model using two independent external datasets. METHODS: The external validation datasets were collected, in a secondary care setting, by different investigators from cohorts in Oxford and Sheffield derived under different circumstances, comprising 1117 and 474 patients with confirmed IDA respectively. The data were anonymised prior to analysis. The predictive performance of the original model was evaluated by estimating measures of calibration, discrimination and clinical utility using the validation datasets. RESULTS: The discrimination of the original model using the external validation data was 70% (95% CI 65, 75) for the Oxford dataset and 70% (95% CI 61, 79) for the Sheffield dataset. The analysis of mean, weak, flexible and across the risk groups' calibration showed no tendency for under or over-estimated risks in the combined validation data. Decision curve analysis demonstrated the clinical value of the IDIOM model with a net benefit that is higher than 'investigate all' and 'investigate no-one' strategies up to a threshold of 18% in the combined validation data, using a risk cut-off of around 1.2% to categorise patients into the very low risk group showed that none of the patients stratified in this risk group proved to have GI cancer on investigation in the validation datasets. CONCLUSION: This external validation exercise has shown promising results for the IDIOM model in predicting the risk of underlying GI malignancy in independent IDA datasets collected in different clinical settings

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). W e 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 chr omatography-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 statis tical 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 replacem ent therapy. When adherence was inserted into the regression model, it was the on ly factor affecting dMC. Conclusions: sFC and uFC levels are not helpful in guiding dMC titration. T reatment adherence impacts on clinical variables used to assess MC replacement and should be included as part of routine care in patients with PAI