Serosurveillance of SARS-CoV-2 in Welsh Blood Donors: Establishment of the surveillance system and results up to November 2022.

BackgroundIn 2020, Wales experienced some of the highest rates of confirmed COVID-19 cases in Europe. We set up a serosurveillance scheme using residual samples from blood donations to inform the pandemic response in Wales.AimTo identify changes in SARS-CoV-2 antibody seroprevalence in Wales by time, demography and location.MethodsResidual samples from blood donations made in Wales between 29 June 2020 and 20 November 2022 were tested for antibodies to the nucleocapsid antigen (anti-N) of SARS-CoV-2, resulting from natural infection. Donations made between 12 April 2021 and 20 November 2022 were also tested for antibodies to the spike antigen (anti-S) occurring as a result of natural infection and vaccination.ResultsAge-standardised seroprevalence of anti-N antibodies in donors remained stable (4.4-5.5%) until November 2020 before increasing to 16.7% by February 2021. Trends remained steady until November 2021 before increasing, peaking in November 2022 (80.2%). For anti-S, seroprevalence increased from 67.1% to 98.6% between May and September 2021, then remained above 99%. Anti-N seroprevalence was highest in younger donors and in donors living in urban South Wales. In contrast, seroprevalence of anti-S was highest in older donors and was similar across regions. No significant difference was observed by sex. Seroprevalence of anti-N antibodies was higher in Black, Asian and other minority ethnicities (self-reported) compared with White donors, with the converse observed for anti-S antibodies.ConclusionWe successfully set up long-term serological surveillance of SARS-CoV-2 using residual samples from blood donations, demonstrating variation based on age, ethnicity and location.

SARS-CoV-2 sero-prevalence in the workforces of three large workplaces in South Wales: a sero-epidemiological study.

BACKGROUND: Sero-prevalence studies quantify the proportion of a population that has antibodies against SARS-CoV-2, and can be used to identify the extent of the COVID-19 pandemic at a population level. The aim of the study was to assess the sero-prevalence of SARS-CoV-2 antibodies in the workforce at three workplaces: a food factory, non-food factory and call-centre. METHODS: Nine hundred ninety-three participants were recruited from three workplaces in South Wales. Participants completed a questionnaire and had a lateral flow point-of-care SARS-CoV-2 antibody test administered by a healthcare professional. The data were analysed using multivariable logistic regression, both using complete records only and following multiple imputation. RESULTS: The sero-prevalence of SARS-CoV-2 antibodies ranged from 4% (n = 17/402) in the non-food factory to 10% (n = 28/281) in the food factory (OR 2.93; 95% CI 1.26 to 6.81). After taking account of confounding factors evidence of a difference remained (cOR comparing food factory to call centre (2.93; 95% CI 1.26 to 6.81) and non-food factory (3.99; 95% CI 1.97 to 8.08) respectively). The SARS-CoV-2 antibody prevalence also varied between roles within workplaces. People working in office based roles had a 2.23 times greater conditional odds (95% CI 1.02 to 4.87) of being positive for SARS-CoV-2 antibodies than those working on the factory floor. CONCLUSION: The sero-prevalence of SARS-CoV-2 antibodies varied by workplace and work role. Whilst it is not possible to state whether these differences are due to COVID-19 transmission within the workplaces, it highlights the importance of considering COVID-19 transmission in a range of workplaces and work roles.

Acute kidney injury demographics and outcomes: changes following introduction of electronic acute kidney injury alerts-an analysis of a national dataset.

BACKGROUND: Electronic alerts for acute kidney injury (AKI) have been widely advocated. Our aim was to describe the changes in AKI demographics and outcomes following implementation of a national electronic AKI alert programme. METHODS: A prospective national cohort study was undertaken to collect data on all cases of AKI in adult patients (≥18 years of age) between 1 April 2015 and 31 March 2019. RESULTS: Over the period of data collection, there were 193 838 AKI episodes in a total of 132 599 patients. The lowest incidence of AKI was seen in the first year after implementation of electronic alerts. A 30-day mortality was highest in Year 1 and significantly lower in all subsequent years. A direct comparison of mortality in Years 1 and 4 demonstrated a significantly increased relative risk (RR) of death in Year 1: RR = 1.08 [95% confidence interval (CI) 1.054-1.114 P < 0.001]. This translates into a number needed to treat in Year 4 for one additional patient to survive of 69.5 (95% CI 51.7-106.2) when directly comparing the outcomes across the 2 years. The increase in the number of cases and improved outcomes was more pronounced in community-acquired AKI, and was associated with a significant increase in patient hospitalization. CONCLUSIONS: This study represents the first large-scale dataset to clearly demonstrate that a national AKI alerting system which highlights AKI is associated with a change in both AKI demographics and patient outcomes.

Acute Kidney Injury in Children Based on Electronic Alerts.

OBJECTIVE: To define the incidence and outcome of acute kidney injury (AKI) in pediatrics using data collected from a national electronic alert system. STUDY DESIGN: A prospective national cohort study was undertaken to collect data on all cases of pediatric AKI, excluding neonates, identified by an e-alert, from April 2015 to March 2019. RESULTS: There were 2472 alerts in a total of 1719 patients, giving an incidence of 77.3 per 100 000 person-years. Of the patients, 84.2% of all AKI were stage 1 and 58.3% occurred with a triggering creatinine within the reference range. The incidence of AKI was associated with measures of social deprivation. Thirty-day mortality was 1.7% but was significantly higher in hospital-acquired AKI (2.1%), compared with community-acquired AKI (0.8%, P < .001) and was associated with the severity of AKI at presentation. A significant proportion of patients had no repeat measure of creatinine (39.8%). This was higher in community-acquired AKI (69.7%) compared with hospital-acquired AKI (43.0%, P < .001), and higher in patients alerting with patients triggering with a creatinine within the reference range (48.4% vs 24.5%, P < .001). The majority of patients (84.7%) experienced only 1 AKI episode. Repeated episodes of AKI were associated with increased 30-mortaltiy (11.6% vs 4.6%, P < .001) and higher residual renal impairment (13.3% vs 5.4%, P < .001). CONCLUSIONS: The results suggest that the significance of the alert is missed in many cases reflecting that a large proportion of cases represent modest elevations in serum creatinine (SCr), triggered by a SCr level that may be interpreted as being normal despite a significant increase from the baseline for the patient.

Recurrent acute kidney injury: predictors and impact in a large population-based cohort.

BACKGROUND: This study examined the impact of recurrent episodes of acute kidney injury (AKI) on patient outcomes. METHODS: The Welsh National electronic AKI reporting system was used to identify all cases of AKI in patients ≥18 years of age between April 2015 and September 2018. Patients were grouped according to the number of AKI episodes they experienced with each patient's first episode described as their index episode. We compared the demography and patient outcomes of those patients with a single AKI episode with those patients with multiple AKI episodes. Analysis included 153 776 AKI episodes in 111 528 patients. RESULTS: Of those who experienced AKI and survived their index episode, 29.3% experienced a second episode, 9.9% a third episode and 4.0% experienced fourth or more episodes. Thirty-day mortality for those patients with multiple episodes of AKI was significantly higher than for those patients with a single episode (31.3% versus 24.9%, P < 0.001). Following a single episode, recovery to baseline renal function at 30 days was achieved in 83.6% of patients and was significantly higher than for patients who had repeated episodes (77.8%, P < 0.001). For surviving patients, non-recovery of renal function following any AKI episode was significantly associated with a higher probability of a further AKI episode (33.4% versus 41.0%, P < 0.001). Furthermore, with each episode of AKI the likelihood of a subsequent episode also increased (31.0% versus 43.2% versus 51.2% versus 51.7% following a first, second, third and fourth episode, P < 0.001 for all comparisons). CONCLUSIONS: The results of this study provide an important contribution to the debate regarding the need for risk stratification for recurrent AKI. The data suggest that such a tool would be useful given the poor patient and renal outcomes associated with recurrent AKI episodes as highlighted by this study.

PITUITARY IMAGING BY MRI AND ITS CORRELATION WITH BIOCHEMICAL PARAMETERS IN THE EVALUATION OF MEN WITH HYPOGONADOTROPIC HYPOGONADISM.

Objective: A significant ambiguity still remains about which patient deserves a magnetic resonance imaging (MRI) scan of the pituitary during evaluation of hypogonadotropic hypogonadism (HH) in men. Methods: Retrospective case series of 175 men with HH referred over 6 years. Results: A total of 49.7% of men had total testosterone (TT) levels lower than the Endocrine Society threshold of 5.2 nmol/L. One-hundred forty-two patients (81.2%) had normal appearance of pituitary MRI, whereas others had different spectrum of abnormalities (empty sella [n = 16], macroadenoma [n = 8], microadenoma [n = 8], and pituitary cyst [n = 1]). In men with TT in the lowest quartile, MRI pituitary findings were not significantly different from men in the remaining quartiles (P = .50). Patients with raised prolactin had higher number of abnormal MRI findings (38.9% vs. 13.7%; P = .0014) and adenomatous lesions (macro and micro) (27.8% vs. 4.3%; P = .01) in comparison to men with normal prolactin. The prolactin levels (median [interquartile range]) were highest in men with macroadenomas in both groups (9,950 [915]; P = .007 and 300 [68.0] mU/L; P = .02, respectively), with concomitant lower levels of other pituitary hormones. Multivariate logistic regression showed an association of abnormal pituitary MRI with insulin-like growth factor 1 (IGF-1) standard deviation score (SDS) (odds ratio [OR], 1.78 [95% confidence interval (CI), 1.15 to 2.77]; P = .009) and prolactin (OR, 1.00 [95% CI, 1.00 to 1.03]; P = .01). Conclusion: MRI of the pituitary is not warranted in all patients with HH, as the yield of identifiable abnormalities is quite low. Anatomic lesions are likely to be present only when low levels of TT (<5.2 nmol/L) are found concomitantly with high levels of prolactin and/or low IGF-1 SDS. Abbreviations: CI = confidence interval; FT4 = free thyroxine; GH = growth hormone; HH = hypogonadotropic hypogonadism; IGF-1 = insulin-like growth factor; LH = luteinizing hormone; MRI = magnetic resonance imaging; OR = odds ratio; SDS = standard deviation score; TSH = thyroid-stimulating hormone; TT = total testosterone.

SEASONAL VARIATION OF VITAMIN D AND SERUM THYROTROPIN LEVELS AND ITS RELATIONSHIP IN A EUTHYROID CAUCASIAN POPULATION.

OBJECTIVE: It is unclear whether seasonal variations in vitamin D concentrations affect the hypothalamo-pituitary-thyroid axis. We investigated the seasonal variability of vitamin D and serum thyrotropin (TSH) levels and their interrelationship. METHODS: Analysis of 401 patients referred with nonspecific symptoms of tiredness who had simultaneous measurements of 25-hydroxyvitamin D3 (25[OH]D3) and thyroid function. Patients were categorized according to the season of blood sampling and their vitamin D status. RESULTS: 25(OH)D3 levels were higher in spring-summer season compared to autumn-winter (47.9 ± 22.2 nmol/L vs. 42.8 ± 21.8 nmol/L; P = .02). Higher median (interquartile range) TSH levels were found in autumn-winter (1.9 [1.2] mU/L vs. 1.8 [1.1] mU/L; P = .10). Across different seasons, 25(OH)D3 levels were observed to be higher in lower quartiles of TSH, and the inverse relationship was maintained uniformly in the higher quartiles of TSH. An independent inverse relationship could be established between 25(OH)D3 levels and TSH by regression analysis across both season groups (autumn-winter: r = -0.0248; P<.00001 and spring-summer: r = -0.0209; P<.00001). We also observed that TSH varied according to 25(OH)D3 status, with higher TSH found in patients with vitamin D insufficiency or deficiency in comparison to patients who had sufficient or optimal levels across different seasons. CONCLUSION: Our study shows seasonal variability in 25(OH)D3 production and TSH secretion in euthyroid subjects and that an inverse relationship exists between them. Further studies are needed to see if vitamin D replacement would be beneficial in patients with borderline thyroid function abnormalities. ABBREVIATIONS: 25(OH)D2 = 25-hydroxyvitamin D2; 25(OH)D3 = 25-hydroxyvitamin D3; AITD = autoimmune thyroid disease; FT4 = free thyroxine; TFT = thyroid function test; TSH = thyrotropin; UVB = ultraviolet B.

The incidence of pediatric acute kidney injury is increased when identified by a change in a creatinine-based electronic alert.

A prospective national cohort study was undertaken to collect data on all cases of pediatric (under 18 yrs of age) acute kidney injury (AKI) identified by a biochemistry-based electronic alert using the Welsh National electronic AKI reporting system. Herein we describe the utility and limitation of using this modification of the KDIGO creatinine-based system data set to characterize pediatric AKI. Of 1,343 incident episodes over a 30-month period, 34.5% occurred in neonates of which 83.8% were AKI stage 1. Neonatal 30-day mortality was 4.1%, with 73.3% of this being accounted for by patients treated in an Intensive Care Unit. In the non-neonatal group, 76.1% were AKI stage 1. Hospital-acquired AKI accounted for 40.1% of episodes while community-acquired AKI represented 29.4% of cases within which 33.9% were admitted to hospital and 30.5% of cases were unclassified. Non-neonatal 30-day mortality was 1.2%, with half of this accounted for by patients treated in the Intensive Care Unit. Nonrecovery of renal function at 30 days occurred in 28% and was significantly higher in patients not admitted to hospital (45% vs. 20%). The reported incidence of AKI in children was far greater than previously reported in studies reliant on clinical identification of adult AKI or hospital coding data. Mortality was highest in neonates and driven by those in the Intensive Care Unit. Nonrecovery of renal function and persistent renal impairment was more common in non-neonates and was especially high in patients with community-acquired AKI who were not hospitalized.

Seasonal pattern of incidence and outcome of Acute Kidney Injury: A national study of Welsh AKI electronic alerts.

OBJECTIVES: To identify any seasonal variation in the occurrence of, and outcome following Acute Kidney Injury. METHODS: The study utilised the biochemistry based AKI electronic (e)-alert system established across the Welsh National Health Service to collect data on all AKI episodes to identify changes in incidence and outcome over one calendar year (1st October 2015 and the 30th September 2016). RESULTS: There were total of 48 457 incident AKI alerts. The highest proportion of AKI episodes was seen in the quarter of January to March (26.2%), and the lowest in the quarter of October to December (23.3%, P < .001). The same trend was seen for both community-acquired and hospital-acquired AKI sub-sets. Overall 90 day mortality for all AKI was 27.3%. In contrast with the seasonal trend in AKI occurrence, 90 day mortality after the incident AKI alert was significantly higher in the quarters of January to March and October to December compared with the quarters of April to June and July to September (P < .001) consistent with excess winter mortality reported for likely underlying diseases which precipitate AKI. CONCLUSIONS: In summary we report for the first time in a large national cohort, a seasonal variation in the incidence and outcomes of AKI. The results demonstrate distinct trends in the incidence and outcome of AKI.

Utilising routine clinical laboratory data to support quality improvement in health care: Application of a national acute kidney injury alert system as a proof of concept.

BACKGROUND: Acute kidney injury (AKI) is a global health issue known to cause avoidable harm and death. Improvement in its prevention and management is therefore considered an important goal for the health-care sector. The work here aimed to develop a tool which could be used to robustly and reliably measure, monitor, and compare the effectiveness of health-care interventions related to AKI across the Welsh NHS, a mechanism which did not exist previously. METHODS: Using serum creatinine (SCr) as a biomarker for AKI and a validated national data-set collected from the all Wales Laboratory Information Management System, work involved applying Donabedian's framework to develop indicators with which to measure outcomes related to AKI, and exploring the potential of statistical process control (SPC) techniques for analysing data on these indicators. RESULTS: Rate of AKI incidence and 30-day AKI-associated mortality are proposed as valid, feasible indicators with which to measure the effectiveness of health-care interventions related to AKI. The control chart, funnel plot, and Pareto chart are proposed as appropriate, robust SPC techniques to analyse and visualise variation in AKI-related outcomes. CONCLUSIONS: This work demonstrates that routinely collected large SCr data offer a significant opportunity to monitor and therefore inform improvement in patient outcomes related to AKI. Moreover, while this work concerns utilisation of SCr data for improvement in AKI strategies, it is a proof of concept which could be replicated for other routinely collected clinical laboratory data, to improve the prevention and/or management of the conditions to which they relate.

Neonatal plasma TSH--estimated upper reference intervals for diagnosis and follow up of congenital hypothyroidism.

Age- and method-dependent plasma TSH reference intervals are essential for the diagnosis and management of congenital hypothyroidism. However, accurate reference intervals for plasma TSH have not been adequately defined due to the difficulties in obtaining samples from a healthy paediatric population. To overcome the difficulties in generating such intervals we estimated method-dependent plasma TSH upper-reference intervals by determining the blood spot TSH upper-reference interval from newborn blood spot TSH screening data (N = 10,697) and then derived method-dependent conversion factors for blood spot TSH to plasma TSH concentration from paired-blood spot and plasma TSH measurements. The upper reference interval for blood spot TSH of 3.04 mU/L was obtained from the 97.5th centile of the selected data. Using experimentally-derived conversion factors, estimates of plasma TSH upper reference intervals of 7.6, 6.3, 7.3, 8.3 and 6.5 mU/L were obtained for the Siemens Centaur, Abbott Architect, Roche Elecsys E170, Siemens Immulite 2000 and Beckman access HYPERsensitive TSH assays respectively. These estimated method-dependent plasma TSH upper reference intervals will be of great practical use to clinicians to diagnose and to follow up infants found to have increased blood spot TSH concentrations identified by Newborn Screening programmes.

Using electronic AKI alerts to define the epidemiology of acute kidney injury in renal transplants.

BACKGROUND: Little is known regarding the impact of acute kidney injury (AKI) on renal transplant outcome. Our aim was to define the incidence and outcome of AKI in renal transplant patients using data collected from a national AKI electronic alert system METHODS: The study represents a prospective national cohort study collecting data on 1224 renal transplants recipients with a functioning renal transplant, between April 2015 and March 2019. RESULTS: Four hundred forty patients experienced at least one episode of AKI giving an incidence rate of 35.4%. Sixty-four point seven% of episodes were AKI stage 1, 7.3% AKI stage 2 and 28% AKI stage 3. Only 6.2% of episodes occurred in the context of rejection. Forty-three point five% of AKI episodes were associated with sepsis. AKI was associated with pre-existing renal dysfunction, and a primary renal diagnosis of diabetic nephropathy. AKI was more prevalent in recipients from a donor after cardiac death (26.4% vs. 21.4%, p < 0.05) compared to the non-AKI cohort. Following AKI, 30-day mortality was 19.8% and overall mortality was 34.8%, compared to 8.4% in the non AKI cohort (RR 4.06, 95% CI 3.1-5.3, p < 0.001). Graft survival (GS), and death censored graft survival (DCGS) censored at 4 years, in the AKI cohort were significantly lower than in the non AKI group (p < 0.0001 for GS and DCGS). CONCLUSION: The study provides a detailed characterisation of AKI in renal transplant recipients highlighting its significant negative impact on patient and graft survival.

Acute Kidney Injury, Age, and Socioeconomic Deprivation: Evaluation of a National Data Set.

INTRODUCTION: This study examined the relationship among age, measures of social deprivation, and incidence and outcome of acute kidney injury (AKI). METHODS: The Welsh National electronic AKI reporting system was used to identify all cases of AKI in patients 18 years or older between March 2015 and January 2017. Socioeconomic classification of patients was derived from the Welsh Index of Multiple Deprivation (WIMD). Patients were grouped according to their WIMD score, and Multivariate Cox proportional hazard modeling was used to adjust the data for age. The ranked data were categorized into percentiles and correlated with incidence, and measures of AKI severity and outcome. RESULTS: Analysis included 57,654 patients. For the whole cohort, the highest 90-day survival was associated with the most socially deprived cohorts. There was a significant negative relationship between age-adjusted incidence of AKI and the WIMD score. In patients 60 years or older, there was an inverse correlation between WIMD score and survival that was not evident in those younger than 60. AKI severity at presentation was worse in patients from areas of social deprivation. Social deprivation was associated with a significantly higher proportion of preexisting chronic kidney disease (CKD) in patients with AKI older than 60, but not in those younger than 60. CONCLUSION: Overall mortality following AKI was higher in least-deprived areas, reflecting an older patient cohort. In contrast, social deprivation was associated with higher age-adjusted AKI incidence and age-adjusted mortality following AKI. The excess mortality observed in more deprived areas was associated with more severe AKI and a higher proportion of preexisting CKD.

Relationship between serum thyrotropin and urine albumin excretion in euthyroid subjects with diabetes.

BACKGROUND: Microalbuminuria represents vascular and endothelial dysfunction. Thyroid hormones can influence urine albumin excretion as it exerts crucial effects on the kidney and on the vascular system. This study explores the relationship between serum thyrotropin and urine albumin excretion in euthyroid patients with diabetes. METHODS: A total of 433 patients with type 1 or 2 diabetes were included in this retrospective cross-sectional study. Data included anthropometric measurements and biochemical parameters from diabetes clinic. Males with urine albumin creatinine ratio >2.5 and female's >3.5 mg/mmoL were considered to have microalbuminuria. RESULTS: 34.9% of the patients had microalbuminuria. Prevalence of microalbuminuria increased according to TSH quartiles (26.9, 34.6, 38.5 and 44.9%, P for trend = 0.02). In a fully adjusted logistic regression model, higher TSH concentrations were associated with high prevalence of microalbuminuria (adjusted odds ratio 2.06 [95% CI: 1.14-3.72]; P = 0.02), while comparing the highest with the lowest quartile of TSH. Multiple linear regression analysis showed an independent association between serum TSH and urine albumin creatinine ratio (ß = 0.007, t = 2.03 and P = 0.04). The risk of having microalbuminuria was higher with rise in TSH concentration in patients with younger age (<65 years), raised body mass index (≥25 kg/m2), hypertension, type 2 diabetes and hyperlipidaemia and age was the most important determinant ( P for interaction = 0.02). CONCLUSION: Serum TSH even in the euthyroid range was positively associated with microalbuminuria in euthyroid patients with diabetes independent of traditional risk factors. This relationship was strongest in patients with components of the metabolic syndrome.

Primary therapy of Graves' disease and cardiovascular morbidity and mortality: a linked-record cohort study.

BACKGROUND: Graves' disease is routinely treated with antithyroid drugs, radioiodine, or surgery, but whether the choice of initial therapy influences long-term outcomes is uncertain. We evaluated cardiovascular morbidity and mortality according to the method and effectiveness of primary therapy in Graves' disease. METHODS: In this retrospective cohort study, we identified patients with hyperthyroidism, diagnosed between Jan 1, 1998, and Dec 31, 2013, from a thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) test register in south Wales, UK, and imported their clinical data into the All-Wales Secure Anonymised Information Linkage (SAIL) Databank (Swansea University, Swansea, UK). Patients with Graves' disease, defined by positive TRAb tests, were selected for the study, and their clinical data were linked with outcomes in SAIL. We had no exclusion criteria. Patients were matched by age and sex to a control population (1:4) in the SAIL database. Patients were grouped by treatment within 1 year of diagnosis into the antithyroid drug group, radioiodine with resolved hyperthyroidism group (radioiodine group A), or radioiodine with unresolved hyperthyroidism group (radioiodine group B). We used landmark Kaplan-Meier and Cox regression models to analyse the association of treatment with the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiovascular events (myocardial infarction, heart failure, ischaemic stroke, or death) with the landmark set at 1 year after diagnosis. We analysed the association between outcomes and concentration of TSH using Cox regression and outcomes and free thyroxine (FT4) concentration using restricted cubic-spline regression models. FINDINGS: We extracted patient-level data on 4189 patients (3414 [81·5%] females and 775 [18·5%] males) with Graves' disease and 16 756 controls (13 656 [81·5%] females and 3100 [18·5%] males). In landmark analyses, 3587 patients were in the antithyroid drug group, 250 were in radioiodine group A, 182 were in radioiodine group B. Patients had increased all-cause mortality compared with controls (hazard ratio [HR] 1·22, 95% CI 1·05-1·42). Compared with patients in the antithyroid drug group, mortality was lower among those in radioiodine group A (HR 0·50, 95% CI 0·29-0·85), but not for those in radioiodine group B (HR 1·51, 95% CI 0·96-2·37). Persistently low TSH concentrations at 1 year after diagnosis were associated with increased mortality independent of treatment method (HR 1·55, 95% CI 1·08-2·24). Spline regressions showed a positive non-linear relationship between FT4 concentrations at 1 year and all-cause mortality. INTERPRETATION: Regardless of the method of treatment, early and effective control of hyperthyroidism among patients with Graves' disease is associated with improved survival compared with less effective control. Rapid and sustained control of hyperthyroidism should be prioritised in the management of Graves' disease and early definitive treatment with radioiodine should be offered to patients who are unlikely to achieve remission with antithyroid drugs alone. FUNDING: National Institute for Social Care and Health Research, Wales.

Utility of electronic AKI alerts in intensive care: A national multicentre cohort study.

BACKGROUND: Electronic AKI alerts highlight changes in serum creatinine compared to the patient's own baseline. Our aim was to identify all AKI alerts and describe the relationship between electronic AKI alerts and outcome for AKI treated in the Intensive Care Unit (ICU) in a national multicentre cohort. METHODS: A prospective cohort study was undertaken between November 2013 and April 2016, collecting data on electronic AKI alerts issued. RESULTS: 10% of 47,090 incident AKI alerts were associated with ICU admission. 90-day mortality was 38.2%. Within the ICU cohort 48.8% alerted in ICU. 51.2% were transferred to ICU within 7days of the alert, of which 37.8% alerted in a hospital setting (HA-AKI) and 62.2% in a community setting (CA-AKI). Mortality was higher in patients transferred to ICU following the alert compared to those who had an incident alert on the ICU (p<0.001), and was higher in HA-AKI (45.3%) compared to CA-AKI (39.5%) (35.0%, p=0.01). In the surviving patients, the proportion of patient recovering renal function following, was significantly higher in HA-AKI alerting (84.2%, p=0.004) and CA-AKI alerting patients (87.6%, p<0.001) compared to patients alerting on the ICU (78.3%). CONCLUSION: The study provides a nationwide characterisation of AKI in ICU highlighting the high incidence and its impact on patient outcome. The data also suggests that within the cohort of AKI patients treated in the ICU there are significant differences in the presentation and outcome between those patients that require transfer to the ICU after AKI is identified and those who develop AKI following ICU admission. Moreover, the study demonstrates that using AKI e-alerts provides a centralised resource which does not rely on clinical diagnosis of AKI or coding, resulting in a robust data set which can be used to define the incidence and outcome of AKI in the ICU setting.

Acute Kidney Injury in the Era of the AKI E-Alert.

BACKGROUND AND OBJECTIVES: Our aim was to use a national electronic AKI alert to define the incidence and outcome of all episodes of community- and hospital-acquired adult AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective national cohort study was undertaken in a population of 3.06 million. Data were collected between March of 2015 and August of 2015. All patients with adult (≥18 years of age) AKI were identified to define the incidence and outcome of all episodes of community- and hospital-acquired AKI in adults. Mortality and renal outcomes were assessed at 90 days. RESULTS: There was a total of 31,601 alerts representing 17,689 incident episodes, giving an incidence of AKI of 577 per 100,000 population. Community-acquired AKI accounted for 49.3% of all incident episodes, and 42% occurred in the context of preexisting CKD (Chronic Kidney Disease Epidemiology Collaboration eGFR); 90-day mortality rate was 25.6%, and 23.7% of episodes progressed to a higher AKI stage than the stage associated with the alert. AKI electronic alert stage and peak AKI stage were associated with mortality, and mortality was significantly higher for hospital-acquired AKI compared with alerts generated in a community setting. Among patients who survived to 90 days after the AKI electronic alert, those who were not hospitalized had a lower rate of renal recovery and a greater likelihood of developing an eGFR<60 ml/min per 1.73 m2 for the first time, which may be indicative of development of de novo CKD. CONCLUSIONS: The reported incidence of AKI is far greater than the previously reported incidence in studies reliant on clinical identification of adult AKI or hospital coding data. Although an electronic alert system is Information Technology driven and therefore, lacks intelligence and clinical context, these data can be used to identify deficiencies in care, guide the development of appropriate intervention strategies, and provide a baseline against which the effectiveness of these interventions may be measured.

Predicting malignancy in thyroid nodules: feasibility of a predictive model integrating clinical, biochemical, and ultrasound characteristics.

BACKGROUND: Although the majority of thyroid nodules are benign the process of excluding malignancy is challenging and sometimes involves unnecessary surgical procedures. We explored the development of a predictive model for malignancy in thyroid nodules by integrating a combination of simple demographic, biochemical, and ultrasound characteristics. METHODS: Retrospective case-record review. We reviewed records of patients with thyroid nodules referred to our institution from 2004 to 2011 (n = 536; female 84 %, mean age 51 years). All malignancy was proven histologically while benign disease was either confirmed histologically, or on cytology with minimum 36-month observation period. We focused on the following predictors: age, sex, smoking status, thyroid hormones (FT4 and TSH) and nodule characteristics on ultrasound. Variables were included in a multivariate logistic regression and bootstrap analyses were used to confirm results. RESULTS: Independent predictors of malignancy in the fully adjusted model were TSH (OR 1.53, 95 % CI 1.10, 2.12, p = 0.01), male gender (OR 3.45, 95 % CI 1.33, 8.92, p = 0.01), microcalcifications (OR 6.32, 95 % CI 2.82, 14.1, p < 0.001), and irregular nodule margins (OR 5.45, 95 % CI 1.61, 18.6, p = 0.006) Bootstrap analyses strengthened these associations and a parsimonious analysis consisting of these variables and age-group demonstrated an area under the curve of 0.77. A predictive score was sensitive (86.9 %) at low scores and highly specific (94.87 %) at higher scores for distinguishing benign from malignant disease. CONCLUSIONS: A predictive model for malignancy using a combination of clinical, biochemical, and radiological characteristics may support clinicians in reducing unnecessary invasive procedures in patients with thyroid nodules.

Acute kidney injury risk assessment at the hospital front door: what is the best measure of risk?

BACKGROUND: We examined the prevalence of acute kidney injury (AKI) risk factors in the emergency medical unit, generated a modified risk assessment tool and tested its ability to predict AKI. METHODS: A total of 1196 patients admitted to medical admission units were assessed for patient-associated AKI risk factors. Subsequently, 898 patients were assessed for a limited number of fixed risk factors with the addition of hypotension and sepsis. This was correlated to AKI episodes. RESULTS: In the first cohort, the prevalence of AKI risk factors was 2.1 ± 2.0 per patient, with a positive relationship between age and the number of risk factors and a higher number of risk factors in patients ≥65 years. In the second cohort, 12.3% presented with or developed AKI. Patients with AKI were older and had a higher number of AKI risk factors. In the AKI cohort, 72% of the patients had two or more AKI risk factors compared with 43% of the cohort with no AKI. When age ≥65 years was added as an independent risk factor, 84% of those with AKI had two or more AKI risk factors compared with 55% of those with no AKI. Receiver operating characteristic analysis suggests that the use of common patient-associated known AKI risk factors performs no better than age alone as a predictor of AKI. CONCLUSIONS: Detailed assessment of well-established patient-associated AKI risk factors may not facilitate clinicians to apportion risk. This suggests that additional work is required to develop a more sensitive validated AKI-predictive tool that would be useful in this clinical setting.