The influence of socioeconomic status on presentation and outcome of acute kidney injury.

AIM: Although socioeconomic background is known to impact on the incidence and progression of chronic kidney disease, its influence of on the presentation and outcome for acute kidney injury is not known and is the subject of this study. DESIGN: The Welsh National electronic AKI reporting system was used to identify all cases of AKI in patients >18 years of age between March 2015 and November 2017. METHODS: Socioeconomic classification of patients was derived from the Welsh Index Multiple Deprivation score (WIMD). Patients were grouped according to the WIMD score by their postcode, and the ranked data were categorized into percentiles and correlated with incidence and measures of AKI severity and outcome. RESULTS: Date was collected on a total of 57 654 patients. Increased deprivation was associated with higher AKI incidence rates, more episodes of AKI per patient and more severe AKI at presentation. In contrast 90-day mortality was highest in the most affluent areas. Mortality in affluent areas was driven by increased patient age. Corrected for age 90-day mortality was higher in areas of increased deprivation. CONCLUSION: This study highlights that AKI incidence presentation and outcomes are adversely affected by social deprivation. Further studies are required to understand the extent to which these differences reflect patient related factors or regional differences in provision and access to care.

Adding a new dimension to the weekend effect: an analysis of a national data set of electronic AKI alerts.

BACKGROUND: Increased mortality related to differences in delivery of weekend clinical care is the subject of much debate. AIM: We compared mortality following detection of acute kidney injury (AKI) on week and weekend days across community and hospital settings. DESIGN: A prospective national cohort study, with AKI identified using the Welsh National electronic AKI reporting system. METHODS: Data were collected on outcome for all cases of adult AKI in Wales between 1 November 2013 and 31 January 2017. RESULTS: There were a total of 107 298 episodes. Weekday detection of AKI was associated with 28.8% (26 439); 90-day mortality compared to 90-day mortality of 31.9% (4551) for AKI detected on weekdays (RR: 1.11, 95% CI: 1.08-1.14, P < 0.001, HR: 1.16 95% CI: 1.12-1.20, P < 0.001). There was no 'weekend effect' for mortality associated with hospital-acquired AKI. Weekday detection of community-acquired AKI (CA-AKI) was associated with a 22.6% (10 356) mortality compared with weekend detection of CA-AKI, which was associated with a 28.6% (1619) mortality (RR: 1.26, 95% CI: 1.21-1.32, P < 0.001, HR: 1.34, 95%CI: 1.28-1.42, P < 0.001). The excess mortality in weekend CA-AKI was driven by CA-AKI detected at the weekend that was not admitted to hospital compared with CA-AKI detected on weekdays which was admitted to hospital (34.5% vs. 19.1%, RR: 1.8, 95% CI: 1.69-1.91, P < 0.001, HR: 2.03, 95% CI: 1.88-2.19, P < 0.001). CONCLUSION: 'Weekend effect' in AKI relates to access to in-patient care for patients presenting predominantly to hospital emergency departments with AKI at the weekend.

Community acquired acute kidney injury: findings from a large population cohort.

BACKGROUND: The extent of patient contact with medical services prior to development of community acquired-acute kidney injury (CA-AKI)is unknown. AIM: We examined the relationship between incident CA-AKI alerts, previous contact with hospital or primary care and clinical outcomes. DESIGN: A prospective national cohort study of all electronic AKIalerts representing adult CA-AKI. METHODS: Data were collected for all cases of adult (≥18 years of age) CA-AKI in Wales between 1 November 2013 and 31 January 2017. RESULTS: There were a total of 50 560 incident CA-AKI alerts. In 46.8% there was a measurement of renal function in the 30 days prior to the AKI alert. In this group, in 63.8% this was in a hospital setting, of which 37.6% were as an inpatient and 37.5% in Accident and Emergency. Progression of AKI to a higher AKI stage (13.1 vs. 9.8%, P < 0.001) (or for AKI 3 an increase of > 50% from the creatinine value generating the alert), the proportion of patients admitted to Intensive Care (5.5 vs. 4.9%, P = 0.001) and 90-day mortality (27.2 vs. 18.5%, P < 0.001) was significantly higher for patients with a recent test. 90-day mortality was highest for patients with a recent test taken in an inpatient setting prior to CA-AKI (30.9%). CONCLUSION: Almost half of all patients presenting with CA-AKI are already known to medical services, the majority of which have had recent measurement of renal function in a hospital setting, suggesting that AKI for at least some of these may potentially be predictable and/or avoidable.

Acute kidney injury electronic alerts in primary care - findings from a large population cohort.

BACKGROUND: Electronic reporting of AKI has been used to aid early AKI recognition although its relevance to CA-AKI and primary care has not been described. AIMS: We described the characteristics and clinical outcomes of patients with CA-AKI, and AKI identified in primary care (PC-AKI) through AKI e-Alerts. DESIGN: A prospective national cohort study was undertaken to collect data on all e-alerts representing adult CA-AKI. METHOD: The study utilized the biochemistry based AKI electronic (e)-alert system that is established across the Welsh National Health Service. RESULTS: 28.8% of the 22 723 CA-AKI e-alerts were classified as PC-AKI. Ninety-day mortality was 24.0% and lower for PC-AKI vs. non-primary care (non-PC) CA-AKI. Hospitalization was 22.3% for PC-AKI and associated with greater disease severity, higher mortality, but better renal outcomes (non-recovery: 18.1% vs. 21.6%; progression of pre-existing CKD: 40.5% vs. 58.3%). 49.1% of PC-AKI had a repeat test within 7 days, 42.5% between 7 and 90 days, and 8.4% was not repeated within 90 days. There was significantly more non-recovery (24.0% vs. 17.9%) and progression of pre-existing CKD (63.3% vs. 47.0%) in patients with late repeated measurement of renal function compared to those with early repeated measurement of renal function. CONCLUSION: The data demonstrate the clinical utility of AKI e-alerts in primary care. We recommend that a clinical review, or referral together with a repeat measurement of renal function within 7 days should be considered an appropriate response to AKI e-alerts in primary care.

Serum thyrotrophin at baseline predicts the natural course of subclinical hyperthyroidism.

OBJECTIVE: Optimal therapeutic strategies for subclinical hyperthyroidism are undecided. Overt disease develops in a minority of cases, but the risk factors for progression remain unclear. We examined whether a baseline thyrotrophin (TSH) predicted progression to overt hyperthyroidism in asymptomatic individuals with subclinical hyperthyroidism. DESIGN, PATIENTS AND MEASUREMENTS: This was a retrospective study of 323 patients with subclinical hyperthyroidism seen in our institution from 2003 to 2010 (mean age 71 years, males 26·9%, females 73·1%, mean follow-up duration 32 months, range 6-93 months). Serum TSH and free thyroxine (FT4) were documented at baseline and during follow-up. After excluding individuals with nonthyroid causes of low TSH, patients were grouped according to initial TSH as: TSH 0·10-0·39 mU/l (grade I) and TSH < 0·10 mU/l (grade II). RESULTS: Only 38 patients (11·8%) developed overt hyperthyroidism with annual progression rates of 0·6-3·7%. Most patients reverted to normal thyroid status (31·6%) or remained subclinically hyperthyroid (56·7%). Progression to frank hyperthyroidism was higher in grade II than in grade I patients (20·3% vs 6·8%, P < 0·001, Chi square test). Kaplan-Meier curves showed faster progression rates in grade II than grade I (P < 0·001, log rank test). In stepwise multivariate Cox regression analysis, TSH < 0·1 mU/l was associated with overt hyperthyroidism (hazard ratio 3·4, confidence interval 1·6-7·0), whereas age, gender, FT4 and aetiological diagnosis were not associated with hyperthyroidism. CONCLUSIONS: Thyrotrophin predicts overt hyperthyroidism in asymptomatic individuals with subclinical hyperthyroidism. Patients with TSH < 0·10 mU/l have a higher risk of progressing to hyperthyroidism than those with TSH 0·10-0·39 mU/l.

Predicting dysglycaemia in patients under investigation for acute coronary syndrome.

AIMS: To examine methods for the identification of previously undetected dysglycaemia [diabetes and impaired glucose tolerance (IGT)] in patients investigated for possible acute coronary syndrome. Specifically, we wished to examine whether the recently advocated use of glycosylated haemoglobin (HbA1c) would enhance detection rates for diabetes in these patients. METHODS: Patients (n = 200) investigated for possible acute coronary syndrome and not previously known to have diabetes were recruited and anthropometric data collected. Random plasma glucose concentrations followed by oral glucose tolerance tests, HbA1c, fasting lipids, high sensitivity C-reactive protein and homeostatic modular assessment-insulin resistance were obtained during admission. Following discharge, the fasting plasma glucose (FPG) was repeated to determine the importance of sequential fasting levels. The accuracy of individual tests, combinations and sequential testing was assessed using receiver operating characteristic curves. A predictive index (PI) was generated using stepwise logistic regression models. RESULTS: The prevalence of diabetes and IGT were 21 and 32%, respectively. FPG >6.0 mmol/l and HbA1c ≥ 6.0% had specificities of 94.9% and 93.6% but sensitivities of only 31.7 and 39.0%, respectively. Combination and sequential testing provided little additional benefit. Use of a PI comprising FPG, HbA1c and age provided the best overall performance (75.6% sensitivity, 77.1% specificity, negative predictive value 92.4%). CONCLUSION: Our data confirm the high prevalence of dysglycaemia in this cohort. The commonly advocated screening tools have significant limitations if used in isolation, combination or sequentially. Our approach using a PI offers improved performance partly as it uses continuous data rather than arbitrary cut-off values.

Can a random serum cortisol reduce the need for short synacthen tests in acute medical admissions?

BACKGROUND: Short synacthen tests (SSTs) are frequently performed in medical inpatients with suspected adrenocortical insufficiency. The utility of a random or baseline serum cortisol in this setting is unclear. We determined random cortisol thresholds that safely preclude SSTs in acute medical admissions. METHODS: We analysed SSTs in acute non-critically ill general medical patients (n = 166, median age 66, range 15-94 y; men 48%, women 52%). The SST was defined according to the 30-min cortisol as 'pass' (>550 nmol/L) or 'fail' (< or =550 nmol/L). Receiver operating characteristics (ROC) curves were generated to determine the predictive value of the basal cortisol for a failed SST. RESULTS: Of 166 SSTs, a pass was seen in 127 (76.5%) tests, while 39 (23.5%) tests failed the SST. ROC curves showed that no single cut-off point of the baseline cortisol was adequately both sensitive and specific for failing the SST despite a good overall predictive value (area under curve 0.94; 95% confidence interval 0.89-0.98). A basal cortisol <420 nmol/L had 100% sensitivity and 54% specificity for failing the SST, while a basal cortisol <142 nmol/L had 100% specificity and 35% sensitivity. Restricting the SST to patients with a basal cortisol <420 nmol/L would have prevented 44% of SSTs while correctly identifying all patients who failed the SST. CONCLUSION: A baseline serum cortisol may prevent unnecessary SSTs in medical inpatients with suspected adrenocortical insufficiency. However, SSTs are still indicated in patients with random cortisol <420 nmol/L, or where the suspicion of adrenal insufficiency is compelling.

Rosiglitazone produces a greater reduction in circulating platelet activity compared with gliclazide in patients with type 2 diabetes mellitus--an effect probably mediated by direct platelet PPARgamma activation.

AIMS: Type 2 diabetes mellitus (T2DM) is associated with enhanced platelet activation. We conducted a randomised double-blind study to compare the effects of combination metformin and rosiglitazone or metformin and gliclazide therapy on platelet function in persons with T2DM. METHODS: Fifty subjects on metformin monotherapy received either rosiglitazone 4 mg or gliclazide 80 mg. HbA1c, HOMA-R, markers of platelet activation, inflammation, endothelial activation and oxidative stress were measured at baseline and after 24 weeks of treatment. Separate in vitro platelet function studies were conducted on platelets pre-incubated with rosiglitazone and gliclazide. RESULTS: A significantly greater reduction in platelet aggregation was observed in the rosiglitazone treated group compared to gliclazide. HbA1c and markers of endothelial activation were reduced to a similar extent in both groups. A significant reduction in HOMA-R, markers of inflammation and oxidative stress was only observed with rosiglitazone. Reduction in platelet aggregation with rosiglitazone correlated with reduction in oxidative stress. In the in vitro study, rosiglitazone produced significantly greater reduction in platelet aggregation compared with gliclazide. CONCLUSION: Greater reduction in platelet activity observed with rosiglitazone may be related to reduced oxidative stress and a possible direct PPARgamma mediated effect on platelet function.

The effects of dietary advice and vouchers on the intake of fruit and fruit juice by pregnant women in a deprived area: a controlled trial.

OBJECTIVE: To examine the effectiveness of two methods of increasing fruit and fruit juice intake in pregnancy: midwives' advice and vouchers exchangeable for juice. DESIGN: Pregnant women were randomly allocated to three groups: a control group, who received usual care; an advice group, given advice and leaflets promoting fruit and fruit juice consumption; and a voucher group, given vouchers exchangeable for fruit juice from a milk delivery firm. Dietary questionnaires were administered at ~16, 20 and 32 weeks of pregnancy. Serum beta-carotene was measured at 16 and 32 weeks. SETTING: An antenatal clinic in a deprived area. SUBJECTS: Pregnant women aged 17 years and over. RESULTS: The study comprised 190 women. Frequency of fruit consumption declined during pregnancy in all groups, but that of fruit juice increased substantially in the voucher group. Serum beta-carotene concentration increased in the voucher group, from 106.2 to 141.8 micromol l(-1) in women with measurements on both occasions (P = 0.003), decreased from 120.0 to 99.8 micromol l(-1) in the control group (P = 0.005), and was unchanged in the advice group. CONCLUSIONS: Pregnant women drink more fruit juice if they receive vouchers exchangeable for juice supplied by the milk delivery service. Midwives' advice to eat more fruit has no great effect. Providing vouchers for fruit juice is a simple method of increasing its intake in a deprived population and may be useful for other sections of the community.

The prevalence of anti-acetylcholinesterase antibodies in autoimmune disease.

A robust and precise enzyme linked immunosorbent assay (ELISA) with proven sensitivity and specificity has been employed to detect human antibodies (allogenic/autogenic) to human acetylcholinesterase (AChE). The sensitivity of the method has been established using mouse monoclonal antibodies (0.8 ng/ml) and uniquely, human sera positive for anti-Yt(a) allogenic antibodies, to one phenotypic form (most common) of human AChE. The latter was also used as the positive human control to ensure functionality of the assay. The ELISA method was used to establish a normal distribution curve for absorbance values employing sera from healthy blood donors Subsequently, the ELISA was employed to investigate the prevalence of anti-AChE antibodies in patients with confirmed autoimmune disease and patients with non-autoimmune thyroid disease (diseased control). The results indicate that there is not a high prevalence of anti-AChE antibodies in patients with confirmed autoimmune disease. The lack of anti-AChE autoantibodies in patients' with clinically apparent Graves' ophthalmopathy, mitigates against there being a causal role of such antibodies in Graves' associated eye disease.

Autoantibodies to acetylcholinesterase revisited.

A sensitive and specific enzyme linked immunosorbent assay (ELISA) utilizing human recombinant acetylcholinesterase has been employed for the detection of human antibodies to human acetylcholinesterase. The method can detect allogenic antibodies to the Yt(a) form of human erythrocyte AChE. Adaptation of this ELISA method allowed the IgG subclass typing of IgG anti-AChE antibodies, which could help to determine the possible role of these antibodies in the aetiology of any neurological conditions. Routine serological investigations established the AChE phenotype of each of the patients recruited, to determine whether anti-AChE antibodies were allogenic or autogenic in origin. These techniques were used to determine the incidence of autoantibodies to AChE in patients with neurological conditions, including the subtypes of motor neuron disease. The data presented are not consistent with earlier reports of a high incidence of autoantibodies to AChE in amyotrophic lateral sclerosis and progressive muscular atrophy.

Detection of anti-Yta antibodies using a sensitive and specific enzyme-linked immunosorbent assay.

A specific, sensitive and semi-quantitative enzyme-linked immunosorbent assay (ELISA) is described to detect anti-Yta antibodies in human serum. Recombinant acetylcholinesterase (AChE E.C.3.1.1.7) was employed as the coating antigen in the microtitre plate and horseradish peroxidase (HRP)-conjugated specific antibody (IgG) was used as the secondary antibody. The method developed showed excellent sensitivity, detecting a titre > 1 in 600,000 (3.5 ng/mL mouse IgG protein) for mouse monoclonal (mMAb) anti-AChE antibody. No cross-reaction was seen with other common blood group antibodies, confirming the specificity of the method. The recombinant antigen's AChE phenotype was confirmed as Yta, as no reaction was detected with anti-Ytb-positive sera. The ELISA method correlated closely with the established serological grading system used routinely in blood transfusion laboratories.