Effect of COVID-19 lockdown on glycated haemoglobin testing and utilisation in KwaZulu-Natal, South Africa.

Background: Diabetic monitoring and treatment guidelines are easily accessible, but compliance is poor in KwaZulu-Natal. The coronavirus disease 2019 (COVID-19) pandemic had a devastating impact on diabetic healthcare, both directly and through public health interventions. Objective: This study aimed to close the gaps in knowledge concerning glycated haemoglobin (HbA1c) test utilisation and how this was affected by the COVID-19 lockdown in KwaZulu-Natal. Methods: We reviewed HbA1c test volumes and results from public health facilities in the 11 health districts in KwaZulu-Natal, South Africa. We compared testing trends and glycaemic control between two 10-month study periods before (March 2019 - December 2019) and during (March 2020 - December 2020) the COVID-19 pandemic. Results: The number of HbA1c tests performed decreased 6.1% during the pandemic period, with 173 760 HbA1c tests performed in 2019 and 163 236 HbA1c tests performed in 2020. There was a statistically significant increase in the average HbA1c level during the pandemic (mean HbA1c level in the pre-pandemic period: 70.5 mmol/mol [8.6%] versus mean HbA1c level in the pandemic period: 72.7 mmol/mol [8.8%]; p-value < 0.001). Of patients with suboptimal HbA1c results (83 421 in 2019, 83 259 in 2020), 11 656 (14.0%) in 2019 and 10 086 (12.1%) in 2020 had more than one HbA1c test performed during the study period. Conclusion: The COVID-19 pandemic impacted glycaemic monitoring in KwaZulu-Natal with lower HbA1c test volumes and worse glycaemic control seen during the pandemic. HbA1c testing practices are not in keeping with recommended guidelines. What this study adds: The study demonstrates that the COVID-19 pandemic impacted HbA1c utilisation in KwaZulu-Natal. Importantly, HbA1c testing practices in KwaZulu-Natal are not in keeping with Society for Endocrinology, Metabolism and Diabetes of South Africa guidelines regarding the monitoring of diabetic patients, and this requires more attention for future diabetic healthcare interventions.

Evaluation of tumour marker utilisation and impact of electronic gatekeeping in the province of KwaZulu-Natal, South Africa.

Background: Inappropriate testing remains a high healthcare cost driver. Tumour marker tests are more expensive than routine chemistry testing. Implementing test demand management systems like electronic gatekeeping (EGK) has reportedly decreased test requests. Objective: This study aimed to describe the appropriateness of tumour marker tests, carcinoembryonic antigen, alpha foetal protein, prostate-specific antigen, carbohydrate antigen 19-9, cancer antigen 15-3, cancer antigen 125, and human chorionic gonadotropin, and determine the effectiveness of the EGK used in the public health sector in KwaZulu-Natal, South Africa. Methods: Tumour marker test data for the KwaZulu-Natal province were extracted from the National Health Laboratory Service Central Data Warehouse for 01 January 2017 - 30 June 2017 (pre-EGK) and 01 January 2018 - 30 June 2018 (post-EGK implementation). Questionnaires were sent to the clinicians in the regional hospitals ordering the most tumour marker tests to assess ordering practices. In addition, we assessed monthly rejection reports to determine the effect of the EGK. Results: The EGK minimally reduced tumour marker requests or associated costs (1.4% average EGK rejection rate). An overall 18% increase in the tumour marker tests occurred in 2018. The data suggest inappropriate tumour marker test utilisation, particularly for screening. Conclusion: The introduction of EGK as a test demand management had little impact on tumour marker test requests and costs. Continuous education and reiteration of indications for tumour marker test use are required. What this study adds: This study demonstrates the ineffectiveness of EGK in tumour marker orders, and provides some insight as to why these markers are being ordered, which is important in trying to decrease inappropriate ordering of these tests.

Assessment of Sigma Metrics for Routine Chemistry Testing in 4 Laboratories in Kwa-Zulu Natal, South Africa.

BACKGROUND: Sigma metrics is a quantitative management tool. This study assessed the Six Sigma score for 26 chemistry analytes, compared scores with different total allowable errors (TEa) and use of scores for internal quality control (IQC) rules in 4 Laboratories in Kwa-Zulu Natal, South Africa. METHODS: Utilizing 6 months of IQC SD, CV, and bias data on albumin, alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase, bicarbonate, calcium, total cholesterol, creatine kinase, chloride, creatinine, gamma glutamyl transferase, glucose, HDL-cholesterol, potassium, lactate dehydrogenase, magnesium, sodium, inorganic phosphate, direct bilirubin, total bilirubin, triglycerides, total protein, urea nitrogen, uric acid, and C-reactive protein (CRP) Six Sigma scores were calculated using Microsoft Excel 2016 and ideal IQC rules were determined. Six Sigma scores using Ricos et al. 2014, Royal College of Pathologists Australasia, and Clinical Laboratory Improvement Amendments TEas were compared. RESULTS: For levels 1, 2, and 3 respectively, analytes scoring >3 sigma was 9 (35%), 12 (46%), and 14 (54%) in Laboratory A; Laboratory B had 15 (58%), 19 (73%), and 17 (65%); Laboratory C had 12 (46%), 13 (50%), and 15 (58%); and Laboratory D had 13 (50%), 18 (69%), and 18 (69%). Albumin, calcium, sodium, magnesium, bicarbonate, and chloride scored <3; CRP scored >6 for all. In Laboratories A, B, C, and D, 7 (27%), 7 (27%), 6 (23%), and 8 (31%) analytes, respectively, required only 1 IQC rule. One of 21 analytes for Laboratories C and D, 3 for Laboratory A, and 0 for Laboratory B had the same sigma score with all 3 databases. CONCLUSION: Despite South Africa being a developing nation, many analytes are able to achieve >3 sigma.

Comparison of 24-hour versus random urine samples for determination and quantification of Bence Jones protein in a South African population.

BACKGROUND: The International Myeloma Working Group and College of American Pathologists recommend a 24-h urine collection to determine the Bence Jones protein (BJP) excretion level for monitoring treatment response in patients with multiple myeloma (MM). There are several issues related to sample collection and the method is prone to inaccuracy. OBJECTIVE: This study compared measured 24-h to random urine collections for the quantitation of BJP in a South African population. METHODS: Sixty-six patients with MM submitted random urine samples with their routine 24-h urine collection from April 2016 - March 2018. Measured 24-h urine BJP was compared to two estimated 24-h BJP excretions calculated as follows: Estimation 1 (E1): Estimated 24-h BJP (mg/24 h) = Urine BJP/Creatinine ratio (mg/mmol) × 10. Estimation 2 (E2): Estimated 24-h BJP (mg/24 h) = Urine BJP/Creatinine ratio (mg/mmol) × 15 mg/kg for women or × 20 mg/kg for men. RESULTS: Correlation of estimation equations E1 and E2 to the measured 24-h urine BJP was 0.893. Patients showed no difference in classification of treatment response using either the E1 or E2 estimation equations when compared to the measured 24-h urine BJP results. CONCLUSION: This study demonstrates that the estimated 24-h BJP shows a high degree of correlation with the measured 24-h BJP and can likely be used to monitor treatment response in South African patients with MM.

A pilot study: Relationship between Bisphenol A, Bisphenol A glucuronide and sex steroid hormone levels in cord blood in A South African population.

Exposure to Bisphenol A (BPA) during early development particularly in- utero has been linked to a wide range of pathology. The aim of this study was to examine the relationship of BPA and its naturally occurring metabolite BPA-glucuronide (BPA-g) with sex steroid hormone levels in South African mother-child pairs. Third-trimester serum maternal samples and matching cord blood samples were analyzed for BPA, BPA-g and nine sex steroid hormones using liquid chromatography tandem mass spectrometry (LC-MS/MS). Sixty maternal and child pairs were analyzed. Rank correlation demonstrated a significant positive relationship between cord blood estradiol and cord blood BPA (p = 0.002) and maternal BPA levels (p = 0.02) respectively. Cord blood testosterone from male infants showed a negative Spearman's correlation (r=-0.5, p = 0.02) with maternal BPA-g. There was no statistical difference in total testosterone levels in cord blood from male and female infants. The findings of the current study indicate a significant relationship between some key sex steroid hormones namely testosterone, dihydrotestosterone and estradiol and fetal exposure BPA.

Reducing sample rejection in Durban, South Africa.

OBJECTIVES: Rejections of clinical chemistry specimens delays the availability of results, which may impact patient management. The study aims to measure sample rejection rate, identify reasons for sample rejection, evaluate the effect of a campaign to reduce rejection rates and discover which clinical units produced the most insufficient specimen. METHODS: The study measured specimen rejection rates and the contributions of different rejection reasons in calendar 2016 and April 2018-March 2019. The study undertook a 7-intervention campaign to reduce specimen rejection during the 2018-2019 intervention period. It compared rejections rates, number of months with rejection rates ≤1.2%, and distribution of rejection reasons between the two year-long intervals. The study also determined the origin for specimens rejected for the most common rejection reason during one month in the second period. RESULTS: The overall rejection rate fell significantly from 1.4% in pre-intervention period to 1.2% in the intervention period. The number of months with rejection rates within the target range increased significantly from 2 in the post-intervention period to 6 in the intervention period. Insufficient, hemolysed, and 'too-old' specimen decreased significantly, however, insufficient specimen remained the most frequent rejection reason. In February 2019, one-third of all insufficient specimen came from neonatal units and 24% from the pediatric units. CONCLUSIONS: Interventions decreased significantly both overall and monthly rejection rates above target levels. Insufficient, hemolysed, 'too-old' specimen, became significantly less frequent, however, insufficient specimen remained the most frequent rejection reason. Over a month, most insufficient specimen came from neonatal and pediatric sites.

A pilot study: Bisphenol-A and Bisphenol-A glucuronide levels in mother and child pairs in a South African population.

Exposure to Bisphenol A (BPA) during early development particularly in- utero has been linked to a wide range of pathology. The aim of this study was to determine serum levels of BPA and its naturally occurring metabolite BPA-glucuronide (BPA-g) in South African mother-child pairs. METHOD: Third-trimester serum maternal samples and matching cord blood samples were analysed for BPA and BPA-g using LC-MS/MS. RESULTS: Ninety maternal and child pairs were analysed. BPA was detectable in more than 25% of maternal and cord blood samples. Spearman correlation demonstrated significant positive correlation between maternal and child BPA and BPA-g levels with correlation coefficients of 0.892 and 0.744, respectively. A significant positive association between cord BPA levels and child birth-weight (p = 0.02) as well as with maternal BMI (p = 0.04) was noted. CONCLUSION: This is the first study to describe the presence of detectable BPA levels using LC-MS/MS methodology in a South African population.

Serum albumin and mortality in patients with HIV and end-stage renal failure on peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is an easily implementable dialysis modality in end-stage renal disease (ESRD). PD may improve access to renal replacement therapy in low- and middle-income countries; however, these countries have a higher prevalence of protein-energy wasting in patients and poorer socioeconomic conditions. We evaluated the effects of HIV infection on serum albumin levels in ESRD patients starting continuous ambulatory PD (CAPD) and mortality outcomes. METHODS: We conducted a single-center prospective cohort study of consecutive incident CAPD patients recruited from two hospitals in Durban, South Africa, from September 2012 to February 2015. Seventy HIV-negative and 70 HIV-positive ESRD patients were followed monthly for serum albumin levels and mortality events during the first 18 months of CAPD therapy. RESULTS: The HIV-positive cohort recorded 28 deaths (40%) among patients with a functional CAPD catheter at 18 months and 13 deaths (18.6%) in the HIV-negative cohort (p = 0.005). The mean serum albumin levels were lower in the HIV-positive cohort than in the HIV-negative cohort during the 18-month follow-up. The mean difference in serum albumin levels between the two cohorts was 4.24 g/L (95% confidence interval [CI] 2.02-6.46, p<0.001) at baseline and 3.99 g/L (95% CI 1.19-6.79, p = 0.006) at 18 months. HIV-positive status (adjusted regression coefficient -2.84, CI -5.00--0.67, p = 0.011), diabetes (adjusted coefficient -2.85; CI, -5.58--0.12; p = 0.041), and serum C-reactive protein and blood hemoglobin levels were independent predictors of serum albumin levels on multivariable linear regression. Baseline serum albumin <25 g/L (subdistribution-hazard ratio [SHR] 13.06, 95% CI 3.09-55.14, p<0.001) and CD4+ cell count <200 cells/µL (SHR 3.2, CI 1.38-7.45, p = 0.007) were independent predictors of mortality in our competing risk model. CONCLUSIONS: HIV infection can adversely affect serum albumin levels in ESRD patients managed with CAPD, while low baseline serum albumin levels and impaired immunity reliably predict mortality.

Novel glomerular filtration markers.

Chronic kidney disease is currently assessed by estimated glomerular filtration rate, a mathematical construct based on creatinine or creatinine and cystatin concentration. Creatinine-based equations have improved with standardization efforts and the Modification of Diet in Renal Disease Study (MDRD) and CKD-Epidemiology Collaboration Study (CKD-EPI). Because the measurement of creatinine is subject to interference from non-GFR determinants, alternative markers have long been sought. These have included cystatin C and low molecular weight proteins like ß2-microglobulin and beta trace protein. Tubular disease often occurs before glomerular filtration is impaired and investigators have investigated the excretion of other low molecular weight proteins such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule-1 and N-acetyl-ß-d-glucosaminidase. While preliminary, there is some evidence linking these analytes with GFR, disease stage and mortality. Although asymmetrical dimethyl arginine, an inhibitor of nitric oxide, has been shown to be associated with progression of renal disease, symmetric dimethyl arginine may be a better marker. Recent work has also explored the potential of microRNA (miRNA) analysis and metabolomics studies to further elucidate this complex pathophysiologic disease process. Investigators hope to improve our ability to detect CKD by the use of test panels, i.e., various marker combinations thereof. Unfortunately, most of these markers lack standardization unlike traditional measures that rely on creatinine and cystatin C measurement.

Secretory tumors of the pituitary gland: a clinical biochemistry perspective.

The pituitary gland is responsible for the production and/or secretion of various hormones that play a vital role in regulating endocrine function within the body. Secretory tumors of the anterior pituitary predominantly, pituitary adenomas, collectively account for 10%-25% of central nervous system tumors requiring surgical treatment. The most common secretory tumors are prolactinomas, which can be diagnosed by basal prolactin levels. Acromegaly can be diagnosed by basal insulin growth-like factor 1 levels and the failure of growth hormone (GH) to suppress during an oral glucose tolerance test. Cushing disease can be diagnosed by demonstrating hypercortisolemia evidenced by increased salivary cortisol levels in the evening, increased urine free cortisol excretion and failure of plasma cortisol to suppress following oral dexamethasone given overnight (1.0 mg). We also discuss the diagnosis of the rarer thyroid-stimulating hormone and gonadotrophin secretory tumors. Morbidity is associated with tumor occurrence, clinical sequelae as well as the related medical, surgical and radiological management. This review focuses on the pathogenesis of secretory tumors of the anterior pituitary with emphasis on molecular mechanisms associated with tumorigenesis and the major role of the clinical chemistry laboratory in diagnosis and management of these tumors.

Prevalence of Primary Hypertension and Risk Factors in Grade XII Learners in KwaZulu-Natal, South Africa.

Hypertension in childhood leads to hypertension in adult life, the strongest risk factor being obesity. This study determined the prevalence of primary hypertension and its risk factors in Grade XII learners in KwaZulu-Natal, South Africa, from March 2016 to June 2017. Weight, height, body mass index (BMI), random finger prick cholesterol and glucose, and spot urine for an albumin : creatinine ratio were measured. An average of three separate blood pressure readings taken was at least 5 minutes apart. Five hundred and sixty-four learners had weight, height, and BMI; 536 had random blood glucose; and 545 had cholesterol and random spot urine albumin : creatinine ratios measured. Prehypertension was detected in 168 (29.7%) and hypertension in 77 (13.7%) of learners. Ninety (15.9%) were overweight and 75 (13,3%) were obese. Hypercholesterolaemia was present in 58 (10.8%) and a high spot random urine albumin : creatinine ratio in 5 (1.0%). None had a high blood glucose level. Both prehypertension and hypertension in all learners showed a significant increase with increasing BMI. Six (1.0%) learners had metabolic syndrome. Female learners in other racial groups (defined as Indian, mixed race, and White learners), overweight, and obese learners showed significantly higher rates of hypercholesterolaemia. We showed overweight and obesity as risk factors for prehypertension and hypertension. This presages the need for an appropriate diet and adequate exercise in a child's school career.

Long-term use of continuous subcutaneous hydrocortisone infusion therapy in patients with congenital adrenal hyperplasia.

BACKGROUND: In a phase 2 short-term (6 months) study of patients with congenital adrenal hyperplasia (CAH), continuous subcutaneous hydrocortisone infusion (CSHI) was found to be a safe, effective and well-tolerated method of replacing cortisol with improved disease and patient-related outcomes. OBJECTIVE: To evaluate the safety and efficacy of long-term CSHI. DESIGN: Single-centre, open-label, phase 2 extension study. PATIENTS: Five adults with classic CAH. MEASUREMENTS: Biomarkers of disease control, metabolic indices and health-related quality-of-life (HRQoL) estimates. RESULTS: Six of eight patients chose to continue on long-term CSHI therapy. Compared to baseline, eighteen months of CSHI resulted in decreased (P = 0.043) 0700-hour ACTH, 17-hydroxyprogesterone, androstenedione and progesterone; increased whole-body lean mass (P = 0.024); and improved HRQoL, especially symptoms of adrenal insufficiency (P = 0.003). Findings at six and eighteen months did not differ, and improvements achieved in androgen control, lean body mass and HRQoL after 6 months of CSHI were maintained at eighteen months. The hydrocortisone dose appeared to decrease with time [6 vs 18 months: 38.3 ± 8.8 vs 33.6 ± 12.2 mg/day (P = 0.062)], especially in women receiving oral contraceptives. Reduction of testicular adrenal rest and adrenal size observed at 6 months remained stable. In one patient, an adrenal adenoma continually decreased over time. Subjective improvement in hirsutism was reported. CONCLUSIONS: Long-term use of CSHI is a safe and well-tolerated treatment option in a select set of adults with classic CAH. Improvements observed short term in disease control and subjective health status continued long term.

Evaluation of the CKD-EPI creatinine based glomerular filtration rate estimating equation in Black African and Indian adults in KwaZulu-Natal, South Africa.

BACKGROUND: The estimation of glomerular filtration rate (GFR) plays a vital role in assessment of the renal function. This study evaluated the performance of the CKD-EPIcreat and MDRD equations in the South African Kwa-Zulu Natal population. OBJECTIVES: The objectives if the study were to compare the of CKD-EPIcreat and MDRD equations in the selected population to the measured GFR using Sodium Technetium-99 m-diethylene-triamine-pentaacetate clearance derived GFR. METHOD: Records of adult patients with measured GFR performed at the Nuclear Medicine Department at Inkosi Albert Luthuli Central Hospital, Durban, South Africa from 1 April 2014 to 31 March 2016 were reviewed. eGFR for all included patients was calculated using the MDRD equation without African American correction factor and the CKD-EPIcreat equation with and without the African American correction factor for the Black African patients. Statistical comparison of the eGFR with measured GFR was performed with Bland Altman bias plots, Wilcoxon match pairs signed ranks test and accuracy within 10% and 30%.ROC curve analysis assessed the sensitivity and specificity at eGFR <90 and < 60 ml/min/1.73m2. RESULTS: After exclusion, 287 patients were included for analysis with sufficient numbers for only the Black African and Indian patients. None of the equations showed accuracy of eGFR within 30% of measured GFR for 90% of patients. In the Black African population, the CKD-EPIcreat equation without the correction factor performed best. 17% and 14.4% of the Black African participants would be reclassified with the CKD-EPIcreat equation without and with the African American correction factor respectively compared to mGFR at a cut-off of 60 mls/min/1.73m2. CONCLUSION: None of the evaluated equations attained the 2002 KDOQI benchmark of P30 >90%. 11.1-17% of individuals would have been incorrectly classified using the CKD-EPIcreat equation.

Evaluation of the revised Schwartz creatinine-based glomerular filtration rate estimating equation in Black African children in KwaZulu-Natal, South Africa.

Background The use of serum creatinine equations for estimating glomerular filtration rate is well known in adults and children. We evaluated the revised Schwartz creatinine-based estimated glomerular filtration rate prediction equation in Black African children in KwaZulu-Natal, South Africa. Methods Review of medical records of all Black African patients aged 2-18 years old who have had glomerular filtration rate determined by intravenous Technetium-99 m-diethylene-triamine-pentaacetate, for the period 1 January 2010 to 31 December 2014 at the Inkosi Albert Luthuli Central Hospital, Durban, South Africa was performed. Estimated glomerular filtration rate result obtained using the revised Schwartz equation was compared to Technetium-99 m-diethylene-triamine-pentaacetate plasma clearance measured glomerular filtration rate. Accuracy of the estimated glomerular filtration rate equations within 10% (P10) and 30% (P30) of the measured glomerular filtration rate, sensitivity and specificity for predicting glomerular filtration rate < 60 mL/min/1.73 m2 and < 30 mL/min/1.73 m2 was determined. Results Results from 148 African children between 2 and 18 years old were analysed. P10 and P30 values were 16 and 49%, respectively. Sensitivity of 92.9% (95% CI: 80.5-85), specificity of 95.3 (95% CI: 89.3-98.5) and AUC of 0.96 (95% CI 0.92-0.99) were obtained for measured estimated glomerular filtration rate < 60 mL/min/1.73 m2. Sensitivity of 88.2% (95% CI: 63.6-98.5), specificity of 90.8 (95% CI: 84.5-95.2) and area under the curve of 0.93 (95% CI 0.88-0.96) were obtained for measured estimated glomerular filtration rate < 30 mL/min/1.73 m2. Conclusions The revised Schwartz equation did not meet the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines of 90% of estimated glomerular filtration rate results within 30% of measured glomerular filtration rate.

A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia.

CONTEXT: Classic congenital adrenal hyperplasia (CAH) management remains challenging, given that supraphysiologic glucocorticoid doses are often needed to optimally suppress the ACTH-driven adrenal androgen overproduction. OBJECTIVE: This study sought to approximate physiologic cortisol secretion via continuous subcutaneous hydrocortisone infusion (CSHI) and evaluate the safety and efficacy of CSHI in patients with difficult-to-treat CAH. DESIGN: Eight adult patients with classic CAH participated in a single-center open-label phase I-II study comparing CSHI to conventional oral glucocorticoid treatment. All patients had elevated adrenal steroids and one or more comorbidities at study entry. Assessment while receiving conventional therapy at baseline and 6 months following CSHI included: 24-hour hormonal sampling, metabolic and radiologic evaluation, health-related quality-of-life (HRQoL), and fatigue questionnaires. MAIN OUTCOME MEASURES: The ability of CSHI to approximate physiologic cortisol secretion and the percent of patients with 0700-hour 17-hydroxyprogesterone (17-OHP) ≤1200 ng/dL was measured. RESULTS: CSHI approximated physiologic cortisol secretion. Compared with baseline, 6 months of CSHI resulted in decreased 0700-hour and 24-hour area under the curve 17-OHP, androstenedione, ACTH, and progesterone, increased osteocalcin, c-telopeptide and lean mass, and improved HRQoL (and SF-36 Vitality Score), and fatigue. One of three amenorrheic women resumed menses. One man had reduction of testicular adrenal rest tissue. CONCLUSIONS: CSHI is a safe and well-tolerated modality of cortisol replacement that effectively approximates physiologic cortisol secretion in patients with classic CAH poorly controlled on conventional therapy. Improved adrenal steroid control and positive effects on HRQoL suggest that CSHI should be considered a treatment option for classic CAH. The long-term effect on established comorbidities requires further study.

An improved micro-method for the measurement of steroid profiles by APPI-LC-MS/MS and its use in assessing diurnal effects on steroid concentrations and optimizing the diagnosis and treatment of adrenal insufficiency and CAH.

Our goals were to (1) develop an improved micro-method usable for neonates for steroid profile measurements and a method to measure androsterone, a key steroid in the recently described androgen backdoor pathway together, with dehydroepiandrosterone and (2) to assess if dehydroepiandrosterone diurnal concentration fluctuations exist potentially necessitating strict adherence to time of blood sample draw and requirement of separate time-dependent reference intervals. Liquid chromatography-tandem mass spectrometry was performed with an atmospheric pressure photoionization source [1]. For each sample 50µL (100µL for the backdoor pathway) of serum was deproteinized by adding 75µL (150µL for the backdoor pathway) of acetonitrile containing the internal standards. After centrifugation, 75µL (150µL for the backdoor pathway) of supernatant was diluted with 250µL of water and injected onto a Poroshell 120 EC-C8 column (SB-C8 column for the backdoor pathway). Within-run coefficients of variation ranged from 2.4 to 10.4% and between-day coefficients of variation from 2.9 to 11.2%. Comparison studies yielded correlation coefficient between 0.97 and 1.00 with recoveries of 90% or greater. Our methods analyze a 9 steroid profile and an additional 2 steroid profile (backdoor pathway) with minimal sample volume (usable in neonates optimizing early diagnosis of endocrinopathies and genetic diseases). Low limits of quantitation make these methods ideal for steroid measurement in women and prepubertal children. As diurnal variations of dehydroepiandrosterone and other steroids [2] concentrations are clinically significant we recommend that separate reference intervals be developed for 8 am, 8 pm, and midnight sample draws. The use of this approach in improving the diagnosis of patients with adrenal insufficiency and congenital adrenal hyperplasia is discussed.

CUSUM-Logistic Regression analysis for the rapid detection of errors in clinical laboratory test results.

OBJECTIVE: The main drawback of the periodic analysis of quality control (QC) material is that test performance is not monitored in time periods between QC analyses, potentially leading to the reporting of faulty test results. The objective of this study was to develop a patient based QC procedure for the more timely detection of test errors. METHOD: Results from a Chem-14 panel measured on the Beckman LX20 analyzer were used to develop the model. Each test result was predicted from the other 13 members of the panel by multiple regression, which resulted in correlation coefficients between the predicted and measured result of >0.7 for 8 of the 14 tests. A logistic regression model, which utilized the measured test result, the predicted test result, the day of the week and time of day, was then developed for predicting test errors. The output of the logistic regression was tallied by a daily CUSUM approach and used to predict test errors, with a fixed specificity of 90%. RESULTS: The mean average run length (ARL) before error detection by CUSUM-Logistic Regression (CSLR) was 20 with a mean sensitivity of 97%, which was considerably shorter than the mean ARL of 53 (sensitivity 87.5%) for a simple prediction model that only used the measured result for error detection. CONCLUSION: A CUSUM-Logistic Regression analysis of patient laboratory data can be an effective approach for the rapid and sensitive detection of clinical laboratory errors.