Calculated globulin (CG) as a screening test for antibody deficiency.

Calculated globulin (total protein - albumin) is usually tested as part of a liver function test profile in both primary and secondary care and determines the serum globulin concentration, of which immunoglobulins are a major component. The main use hitherto of calculated globulin is to detect paraproteins when the level is high. This study investigated the potential to use low levels of calculated globulin to detect antibody deficiency. Serum samples with calculated globulin cut-off < 18 g/l based on results of a pilot study were collected from nine hospitals in Wales over a 12-month period. Anonymized request information was obtained and the samples tested for immunoglobulin levels, serum electrophoresis and, if appropriate, immunofixation. A method comparison for albumin measurement using bromocresol green and bromocresol purple was undertaken. Eighty-nine per cent (737 of 826) samples had an immunoglobulin (Ig)G level of < 6 g/l using the bromocresol green methodology with a cut-off of < 18 g/l, and 56% (459) had an IgG of < 4 g/l. Patients with both secondary and primary antibody deficiency were discovered and serum electrophoresis and immunofixation showed that 1·2% (10) had previously undetected small paraproteins associated with immune-paresis. Using bromocresol purple, 74% of samples had an IgG of < 6 g/l using a cut-off of < 23 g/l. Screening using calculated globulin with defined cut-off values detects both primary and secondary antibody deficiency and new paraproteins associated with immune-paresis. It is cheap, widely available and under-utilized. Antibody-deficient patients have been discovered using information from calculated globulin values, shortening diagnostic delay and time to treatment with immunoglobulin replacement therapy.

The effect of different analytical platforms and methods on the performance of population-specific adjusted calcium equation.

BACKGROUND: A recent attempt to improve the diagnostic value of adjusted calcium addressed a primary care-specific adjusted calcium equation, but validated the new equation for Roche Cobas, BCG and NM-BAPTA methods only. In this study, we aim to validate a population-specific equation for other methods and platforms. METHOD: We collected retrospective patient data-sets from 15 hospital laboratories using a range of commercially available analytical platforms and methods for calcium and albumin measurements. Raw data-sets were collected and filtered according to Payne's criteria, and separate adjusted calcium equations were derived for hospitalized and primary care patients. RESULTS: Mean albumin and calcium results were significantly higher in primary care populations (P < 0.0001). The prevalence of hypocalcaemia using adjusted calcium ranged between 6% and 44% for inpatient data-sets and was higher in users of BCG methods. The application of community-specific adjustment equation to primary care data-sets reduced the prevalence of hypocalcaemia (mean 1.7%, range 0.8-3.7%). CONCLUSION: We demonstrated that the use of a community-specific calcium adjustment equation to a primary care population reduces both the percentage and the variation of hypocalcaemia between different laboratories.

Albumin and calcium reference interval using healthy individuals and a data-mining approach.

BACKGROUND: Harmonization of reference intervals for analytes that have a sound calibration and metrological traceability is a widely recommended practice. The UK Pathology Harmony has recently harmonized reference intervals for calcium and albumin. In this study, we have determined the reference intervals for calcium and albumin on the UK's most commonly used analytical platforms. METHOD: A prospective reference population of healthy individuals was recruited according to the IFCC CRIDL criteria. A second indirect population was collected from 14 primary care setting and measured in laboratories using various analytical platforms and methods (Roche, Abbott, Beckman and Siemens analytical platforms). RESULTS: In total, 299 subjects were recruited; the central 95th centile values for calcium for three out of four analytical platforms were in a close agreement with UK Pathology Harmony reference intervals of 2.2-2.6 mmol/L. Reference intervals of BCG methods from both cohorts and irrespective of analytical platforms were higher for both lower and upper reference limits than those for BCP. In comparison, the indirect study showed an age-related variation. The younger population reference intervals varied by up to 5.7% at the lower reference limit and up to 12% at the upper reference limit compared with Pathology Harmony reference intervals, and the older population showed a variation of up to 14% at both limits. CONCLUSION: While calcium reference intervals can be a subject for harmonization, albumin reference intervals studied showed large variation which is unsupportive of embracing a common reference interval for albumin.

The long-term impact of eGFR reporting on referral patterns.

BACKGROUND: The prognostic significance of CKD has driven the widespread introduction of automated estimated glomerular filtration rate (eGFR) reporting, and the incorporation of CKD in the revised Quality Outcomes Framework (QOF) of the General Medical Services (GMS) contract in the U.K. AIMS: To assess the long-term impact of the introduction of these two initiatives, on patient referral numbers to a nephrology service. METHODS: Data was collected on the numbers and basic characteristics of all new patients referred from April 2005 to March 2011, to one NHS Health Board. RESULTS: Introduction of eGFR reporting and CKD QOF domains was associated with a significant increase in the number of referrals, which was sustained. The initiatives also led to a sustained increase in the mean age of the patients at referral, predominantly due to an increase in the age of female patients referred. There was also an increase in the proportion of female patients referred. In the immediate aftermath of the introduction of change there was a transient decrease in the average eGFR at referral, a decrease in age of patients referred with an eGFR <15ml/min and an increase in the eGFR of patients >70yrs of age. CONCLUSIONS: The data demonstrates significant and sustained increase in numbers of referrals. In the short term this was associated with a reduction in referral of elderly patients with stage 5 CKD and an increase in elderly patients with mild renal impairment. In the longer term we saw an increase in referral of an older female population.

Severe hyperkalaemia: demographics and outcome.

BACKGROUND: Few studies have evaluated the prevalence of severe hyperkalaemia in unselected patient populations. We identified all episodes of severe hyperkalaemia occurring in 1 year, and described patient demographics, clinical response and outcome. We also assessed junior doctor knowledge of its causes and significance. MATERIALS AND METHODS: A retrospective interrogation of the database of the regional biochemical laboratory identified all episodes of severe hyperkalaemia (K≥ 6.5 mmol/L) occurring in 2011. The understanding of trainee doctors of the importance, causes and treatment of severe hyperkalaemia was assessed by structured questionnaire. RESULTS: Severe hyperkalaemia was recorded in 433 samples (365 patients) giving a prevalence of 0.11%. Thirty-six per cent of episodes occurred in patients under the care of a nephrologist, who were significantly younger than those not under the care of a nephrologist. In the nephrology cohort, 86% occurred in patients with chronic kidney disease (CKD), the majority of which had CKD Stage 5. In the non-nephrology cohort, only 65% occurred in the context of CKD, which was equally distributed between Stages 3 and 5 CKD. In both patient groups, roughly 50% of episodes occurred in association with acute kidney injury (AKI). Acute mortality (death within 48 h of documented severe hyperkalaemia) was higher in the non-nephrology compared with the nephrology cohort. Time to repeat serum potassium was influenced by the clinical setting with shorter time to repeat for acute care compared with ward settings. Assessment of trainee doctor's knowledge suggested significant deficiencies in relation to severe hyperkalaemia. CONCLUSIONS: The prevalence of severe hyperkalaemia was low and occurred predominantly in the context of CKD and/or AKI. The majority of episodes occurred in patients not under the care of a nephrologist. Variability in time to repeat serum potassium levels suggested deficiencies in care, and assessment of trainee doctor's knowledge suggests the need for further educational initiatives to highlight its importance.

Recurrent urolithiasis following parathyroidectomy for primary hyperparathyroidism.

INTRODUCTION: The effect of parathyroidectomy on the incidence of recurrent stone formation is uncertain. We aimed to compare the biochemistry and recurrence rate of urolithiasis in patients with primary hyperparathyroidism (pHPT) and stone formation (SF) and non-stone formation (NSF) with idiopathic stone formers (ISF). METHODS: Patients with pHPT and SF (Group 1) were identified from a prospective database. pHPT patients and NSF (Group 2) and ISFs (Group 3) were randomly selected from respective databases to form three equal groups. Preoperative and postoperative biochemical data were analysed and recurrent urolithiasis diagnosed if present on follow-up radiology. Out-of-area patients were asked about recurrence via telephone. RESULTS: From July 2002 to October 2011, 640 patients had parathyroidectomy for pHPT. Of these, 66 (10.3%) had a history of renal colic; one was lost to follow-up. Patient demographics were similar across all three groups. Three months post-parathyroidectomy, Groups 1 and 2 had significantly reduced serum calcium concentrations (p<0.01). Group 1 had lower urinary calcium excretion after parathyroidectomy (p<0.01), but estimated glomerular filtration rate did not change following surgery. During median follow-up of 4.33 years (0.25-9 years) in Groups 1 and 2 and 5.08 years (0.810-8 years) in Group 3, one patient (1.5%) in Group 1 and 16 patients (25%) in Group 3 had recurrent urolithiasis (p<0.01). No Group 2 patients developed stones. CONCLUSION: Curative parathyroidectomy confers a low recurrence rate for urolithiasis, but does not prevent recurrence in all patients. Further research should aim to identify the risk factors for continued SF in these patients.

The influence of liberal alcohol consumption on glucose metabolism in patients with type 1 diabetes: a pilot study.

BACKGROUND: Little is known about the consequences of excessive alcohol ingestion in patients with type 1 diabetes. AIM: To examine the metabolic effects of acute ingestion of liberal amounts of alcohol in patients with type 1 diabetes. DESIGN: A pilot study using a randomized, placebo controlled, double blind design in Hospital Clinical Research Unit. METHODS: The study included 10 patients with type 1 diabetes (seven male, age 43.9 +/- 9.0 years, duration of diabetes 17.3 +/- 13.8 years, HbA(1c) 8.0 +/- 1.5%) who had a standard 600-calorie lunch on two separate occasions, together with either white wine (men eight units, women six units), or an equivalent volume of alcohol-free wine. Bloods were collected before lunch and hourly for 4 h for glucose, intermediary metabolites, counter-regulatory hormones and inflammatory markers. RESULTS: There were no significant differences between alcohol and alcohol-free days in levels of glucose, triglycerides, free fatty acids, glycerol, cortisol and growth hormone. In contrast, lactate levels rose in response to the meal but with alcohol the overall response was augmented (P = 0.014). Beta-hydroxybutyrate levels were suppressed post-prandially on the alcohol-free day but were significantly elevated with alcohol (P < 0.001). CONCLUSION: A rise in ketones following alcohol ingestion occurred despite subjects being in a strictly controlled environment with no interruption in insulin administration. Such individuals might be at risk of significant ketosis in less-controlled circumstances where insulin administration might be more erratic. Patient education material should contain information to highlight these potential problems.