Improved management of acute kidney injury in primary care using e-alerts and an educational outreach programme.

Purpose: Acute kidney injury (AKI) detected in primary care is associated with increased morbidity and mortality. AKI electronic alerts (e-alerts) and educational programmes have recently been implemented but their contribution to improve AKI care is unknown. This project aimed to improve response to AKI detected in primary care and used a factorial design to evaluate the impact of the UK National Health Service (NHS) AKI e-alert and AKI educational outreach sessions on time to response to primary care AKI stages 2 and 3 between April and August 2016. Methods: A total of 46 primary care practices were randomized into four groups. A 2 × 2 factorial design exposed each group to different combinations of two interventions. The primary outcome was 'time to repeat test' or hospitalization following AKI e-alert for stages 2 and 3. Yates algorithm was used to evaluate the impact of each intervention. Time to response and mortality pre- and post-intervention were analysed using Mann-Whitney U test and chi-square test respectively. The factorial design included two interventions: an AKI educational outreach programme and the NHS AKI e-alerts. Results: 1807 (0.8%) primary care blood tests demonstrated AKI 1-3 (78.3% stage 1, 14.8% stage 2, 6.9% stage 3). There were 391 stage 2 and 3 events from 251 patients. E-alerts demonstrated a reduction in mean response time (-29 hours). Educational outreach had a smaller effect (-3 hours). Median response time to AKI 2 and 3 pre- and post-interventions was 27 hours versus 16 hours respectively (P = 0.037). Stage 2 and 3 event-related 30-day all-cause mortality decreased following the interventions (15.6% versus 3.9% P = 0.036). Conclusion: AKI e-alerts in primary care hasten response to AKI 2 and 3 and reduce all-cause mortality. Educational outreach sessions further improve response time.

A Quality Improvement Project to Minimize COVID-19 Infections in Patients Receiving Haemodialysis and the Role of Routine Surveillance Using Nose and Throat Swabs for SARS-CoV-2 rRT-PCR and Serum Antibody Testing.

BACKGROUND: Patients receiving in-centre haemodialysis (ICHD) are highly vulnerable to COVID-19. OBJECTIVE: We created a quality improvement (QI) project aimed to eliminate outbreaks of COVID-19 in haemodialysis units and evaluated the utility of surveillance rRT-PCR test and SARS-CoV-2 serum antibodies for prompt identification of patients infected with COVID-19. METHODS: A multifaceted QI programme including a bundle of infection prevention control (IPC) measures was implemented across 5 ICHD units following the first wave of the pandemic in June 2020. Primary outcomes evaluated before and after QI implementation were incidence of outbreaks and severe COVID-19 illness defined as COVID-19-related death or hospitalization. Secondary outcomes included the proportion of patients identified in the pre-symptomatic/asymptomatic phase on surveillance rRT-PCR screening and the incidence and longevity of SARS-CoV-2 antibody response. RESULTS: Following the implementation of the QI project, there were no further outbreaks. Pre- and post-implementation comparison showed a significant reduction in COVID-19-related mortality and hospitalization (26 vs. 13 events, respectively, p < 0.001). Surveillance rRT-PCR screening identified 39 asymptomatic or pre-symptomatic cases out of a total of 59 rRT-PCR-positive patients (39/59, 66%). SARS-CoV-2 antibody levels were detected in 72/74 (97%) rRT-PCR-positive patients. Amongst rRT-PCR-positive patients diagnosed before August 2020, 96% had detectable antibodies until January 2021 (days from the rRT-PCR test to last antibody testing, 245-280). CONCLUSIONS: Systematic implementation of a bundle of IPC measures using QI methodology and surveillance rRT-PCR eliminated outbreaks in HD facilities. Most HD patients mount and sustain antibody response to COVID-19 for over 8 months.

Paired sensitivity analysis of four SARS-CoV-2 serological immunoassays in a longitudinal cohort of convalescent hospital staff.

BACKGROUND: SARS-CoV-2 serological testing has seen extensive academic and clinical use from investigating correlates of immunity to seroprevalence, convalescent plasma and vaccine trials. Interpretation of these studies will depend on robust validation of the longitudinal sensitivities of these assays, especially in the context of mild disease which makes up the majority of the Coronavirus Disease 2019 (COVID-19) caseload. METHODS: Hospital staff (n = 94) returning to work following polymerase chain reaction confirmed COVID-19 were offered antibody testing to assist with laboratory verification. Initial specimens were collected at median 29 days post-symptom onset and run on the Roche, Abbott, Siemens and DiaSorin platforms. Re-sampling occurred at median 142 days from a subset of the initial cohort (n = 62) that had volunteered to provide further serum samples to assist in longitudinal sensitivity analysis. Samples that were not run across all four platforms were excluded from analysis. RESULTS: Comparative sensitivity analysis was conducted on 89/94 of the initial specimens and 55/62 of the repeat specimens. Sensitivity at initial sampling ranged from 78 to 87% across platforms. At re-sampling, sensitivities were: 100% (Roche), 45% (Abbott), 100% (Siemens), and 80% (DiaSorin). Paired analysis using the longitudinal cohort (n = 55) demonstrated stable or increasing median assay values on three platforms, with a clear reduction seen only on the Abbott platform (4.78 to 1.34) with corresponding sensitivity drop-off (81.8% to 45.4%). CONCLUSION: The Abbott assay demonstrated sensitivity drop-off and decrease in median assay signal below detection threshold at four to five months. This has implications on the interpretation and design of future studies.

The importance of acute kidney injury in suspected community acquired infection.

BACKGROUND: Most sepsis and acute kidney injury (AKI) cases are community acquired (CA). The aim of this study was to evaluate the characteristics of suspected community acquired infection (sCA-I) and CA-AKI and their impact upon patient outcomes. METHODS: All adult creatinine blood tests from non-elective, non-dialysis attendances to a single centre over a 29-month period were analysed retrospectively. We defined sCA-I and CA-AKI cases as antibiotic prescription and AKI alert within 48 hours of attendance respectively. Binary logistic regression models were created to determine associations with 30-day mortality, intensive care unit (ICU) admission and length of stay (LOS) dichotomised at median. RESULTS: Of 61,471 attendances 28.1% and 5.7% suffered sCA-I or CA-AKI in isolation respectively, 3.4% suffered both. sCA-I was present in 58.8% of CA-AKI cases and CA-AKI was present in 11.9% of CA-I cases. The combination of sCA-I and CA-AKI was associated with a higher risk for all outcomes compared to sCA-I or CA-AKI in isolation. The 30-day mortality was 8.1%, 11.8% and 26.2% in patients with sCA-I, CA-AKI and when sCA-I and CA-AKI occurred in combination respectively. The adjusted odds ratios (OR) and 95% confidence intervals (CI) for 30-day mortality, ICU admission and LOS for sCA-I combined with CA-AKI stage 1 were OR 6.09:CI: 5.21-7.12, OR 12.52 CI: 10.54-14.88 and OR 8.97 CI: 7.62-10.56, respectively, and for combined sCA-I and CA-AKI stage 3 were OR 9.23 CI: 6.91-12.33, OR 29.26 CI: 22.46-38.18 and OR 9.48 CI: 6.82-13.18 respectively. CONCLUSION: The combination of sCA-I and CA-AKI is associated with worse outcomes.

Interference with serum indices measurement, but not chemical analysis, on the Roche Modular by Patent Blue V.

BACKGROUND: Patent Blue V is an inert dye increasingly being used during cancer surgery to identify the sentinel lymph node. We recently discovered three cases with falsely elevated lipaemic indices on the Roche Modular, following intramammary injection of Patent Blue. This, and other potential interferences by Patent Blue, is examined in this study. METHODS: Serum samples which visually appeared normal, haemolysed or icteric were spiked with Patent Blue to a concentration of 7.3 mg/L and the effect on the lipaemic, haemolysis and icteric indices and routine chemical analyses (sodium, potassium, urea, creatinine, bilirubin, alanine aminotransferase, gamma-glutamyltransferase, aspartate aminotransferase, magnesium, creatine kinase, lactate dehydrogenase, amylase, albumin, calcium and phosphate) undertaken. Dose-response curves in the range of 4.9 mg/L to 22.7 mg/L of Patent Blue were established for normal, icteric and haemolysed pooled serum samples. RESULTS: Significant positive interference by 7.3 mg/L of Patent Blue was observed in the lipaemic index, with an increase of 149 +/- 6.3 (mean +/- standard deviation [SD]; P < 0.001). Significant negative interference was observed in both the haemolysis and icteric indices, with decreases of 71 +/- 9.7 (P < 0.001) and 46 +/- 8.9 (P < 0.001), respectively. Patent Blue had a linear dose-response effect on the serum indices. No significant differences were observed in the chemical analyses assessed. CONCLUSIONS: The effects observed on the Roche Modular serum index measurements with Patent Blue raises the novel concept of interference in methods routinely used to detect interference. Despite Patent Blue having no direct effect on chemical analysis, failure to reliably detect potential interference, particularly haemolysis, may lead to misleading results being issued.

Reflective testing--what do our service users think?

BACKGROUND: Reflective testing incorporates the clinical judgement, knowledge and experience of an individual biochemist to request additional tests appropriate to the clinical scenario. Despite being vigorously debated within the biochemistry profession, little is known about how the clinicians directly involved in patient care feel about it. We have conducted a survey to elicit our service users' opinion of reflective testing. METHODS: Ten clinical scenarios, each involving the possible addition of a specific test, were circulated to 520 hospital doctors and 152 general practitioners. The four response options were to add further tests, phone and discuss the case, add a comment to the original results or do nothing. RESULTS: A total of 216 (32%) responses were received. Overall, the majority were in favour of 'adding on' free triiodothyronine (86%), gamma-glutamyltransferase (78%), lipid profile (59%), thyroid peroxidase antibodies (63%), pituitary hormones (58%), troponin (55%) and serum electrophoresis (68%) in the given scenarios. However, only 30% would like a pregnancy test added and only 45% a prostate-specific antigen added without prior consultation. The response differed according to grade and specialty. CONCLUSIONS: Reflective testing is generally welcomed by our service users, provided the nature and implications of the specific test is considered in addition to the full clinical scenario.

Spuriously raised serum creatinine associated with an excipient present in an intravenous dexamethasone formulation.

Although the active pharmaceutical ingredient remains constant, the excipients used will vary according to the manufacturer. This case report is of spuriously raised serum creatinine due to an excipient in one particular intravenous dexamethasone formulation. A patient had three serum creatinine measurements of 102, 369 and 91 µmol/L over a four-hour period. The second result was believed to be spurious and appropriate investigations were instigated. The patient had received dexamethasone intravenously between the first and second blood samples. This was administered as a bolus via a cannula in the dorsum of the hand, and the blood sample was taken by venepuncture of the antecubital fossa of the same arm approximately five minutes later. The dexamethasone used (Hospira UK Ltd) contained creatinine at a concentration of 70,720 µmol/L, with a total of 170 µmol of creatinine given to the patient. Assuming a volume of distribution of 40 L in a 70-kg man, an increase in serum creatinine of 4-5 µmol/L would be expected once equilibrated. It is thought that the serum creatinine result observed was a consequence of the creatinine excipient in the dexamethasone not having completely distributed throughout the body and still being at relatively high concentrations within the limb into which it had been administered. Intravenous dexamethasone can lead to spurious creatinine results, not due to analytical interference but rather the analytically correct measurement of creatinine added as an excipient. This case clearly demonstrates the impact preanalytical factors can have on the accuracy of results.

Comparison of serum cortisol measurement by immunoassay and liquid chromatography-tandem mass spectrometry in patients receiving the 11ß-hydroxylase inhibitor metyrapone.

BACKGROUND: The accurate measurement of cortisol by immunoassay is compromised by the potential for cross-reactivity of reagent antibodies with structurally related steroids present in serum. This susceptibility is potentiated when normal steroid metabolism is altered pharmaceutically by antisteroidogenic drugs utilized in the management of Cushing's syndrome to moderate cortisol production. The clinical implications of falsely elevated cortisol results include over-treatment and unrecognized hypoadrenalism. To investigate the effect of the 11ß-hydroxylase inhibitor metyrapone on serum cortisol assay, a comparison of measurement by immunoassay versus liquid chromatography-tandem mass spectrometry (LC-MS/MS) was conducted. METHODS: Cortisol was measured in serum from three patient groups: (1) patients receiving metyrapone (n = 112 samples from 10 patients); (2) control group of patients diagnosed with Cushing's syndrome currently receiving no treatment (n = 31); and (3) control group of patients with no adrenal pathology and not receiving medication known to interfere in cortisol immunoassay (n = 67). RESULTS: Bland-Altman plots showed agreement between methods for the control group (bias = 1.1% [-4.3 nmol/L]) and Cushing's control group (bias = 1.3% [-3.7 nmol/L]). This was in stark contrast to the metyrapone therapy group (bias = 23% [59 nmol/L]). The difference between LC-MS/MS versus immunoassay in the metyrapone therapy group positively correlated with metyrapone dose and serum 11-deoxycortisol concentration (Pearson's correlation coefficient r = 0.47, 95% CI 0.32-0.61; P < 0.0001). CONCLUSIONS: These data show that liability of immunoassay measurement of serum cortisol to interference in patients receiving metyrapone may lead to erroneous clinical decisions concerning dose titration.