The investigation of interferences in immunoassay

Immunoassay procedures have a wide application in clinical medicine and as such are used throughout clinical biochemistry laboratories both for urgent and routine testing. Clinicians and laboratory personnel are often presented with immunoassay results which are inconsistent with clinical findings. Without a high index of suspicion interferences will often not be suspected. Artifactual results can be due to a range of interferences in immunoassays which can include cross reacting substances, heterophile antibodies, autoantibodies and the high dose hook effect. Further, pre-analytical aspects and certain disease states can influence the potential for interference in immunoassays. Practical solutions for investigation of artifactual results in the setting of the routine clinical laboratory are provided

The importance of low level QC for high sensitivity troponin assays

BACKGROUND With the advent of the new high-sensitivity troponin assays, it is becoming critical to measure troponin accurately to low concentrations. To ensure assay performance is acceptable, appropriate QC must be run. METHODS In addition to the routine use of commercial QC material, we prepared pools of human QC material with low troponin concentrations close to the limit of quantitation, and ran these regularly on our laboratory analysers. RESULTS Over 3 years we found no drift or shift in our hs-cTnI assay. We found that only the very low concentration human QC material gave warning of precision problems with the hs-cTnI assay. At the time of the documented poor assay precision, the higher concentration QC material indicated satisfactory performance. CONCLUSIONS Choice of QC material with an appropriate concentration is important for any assay. For hs-cTn assays, it is of particular importance to use control material with a concentration near to the limit of quantitation

Complement Inhibition as a Proposed Neuroprotective Strategy following Cardiac Arrest

Out-of-hospital cardiac arrest (OHCA) is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following return of spontaneous circulation. A dearth of effective treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R) injury following successful resuscitation from OHCA. Emerging preclinical as well as recent human clinical evidence suggests that activation of the complement cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA. In addition, it is well established that complement inhibition improves outcome in both global and focal models of brain ischemia. Due to the profound impact of GCI/R injury following OHCA, and the relative lack of effective neuroprotective strategies for this pathologic process, complement inhibition provides an exciting opportunity to augment existing treatments to improve patient outcomes. To this end, this paper will explore the pathophysiology of complement-mediated GCI/R injury following OHCA

Monitoring the hepatitis C epidemic in England and evaluating intervention scale-up using routinely collected data.

In England, 160 000 individuals were estimated to be chronically infected with hepatitis C virus (HCV) in 2005 and the burden of severe HCV-related liver disease has increased steadily for the past 15 years. Direct-acting antiviral treatments can clear infection in most patients, motivating HCV elimination targets. However, the current burden of HCV is unknown and new methods are required to monitor progress. We employed a Bayesian back-calculation approach, combining data on severe HCV-related liver disease and disease progression, to reconstruct historical HCV incidence and estimate current prevalence in England. We explicitly modelled infections occurring in people who inject drugs, the key risk group, allowing information on the size of this population and surveillance data on HCV prevalence to inform recent incidence. We estimated that there were 143 000 chronic infections in 2015 (95% credible interval 123 000-161 000), with 34% and 54% in those with recent and past injecting drug use, respectively. Following the planned scale-up of new treatments, chronic infections were predicted to fall to 113 400 (94 900-132 400) by the end of 2018 and to 89 500 (71 300-108 600) by the end of 2020. Numbers developing severe HCV-related liver disease were predicted to fall by at least 24% from 2015 to 2020. Thus, we describe a coherent framework to monitor progress using routinely collected data, which can be extended to incorporate additional data sources. Planned treatment scale-up is likely to achieve 2020 WHO targets for HCV morbidity, but substantial efforts will be required to ensure that HCV testing and patient engagement are sufficiently high

Effects of Changes in Adiposity and Physical Activity on Preadolescent Insulin Resistance: The Australian LOOK Longitudinal Study

BACKGROUND In a previous longitudinal analysis of our cohort as 8 to 10 year-olds, insulin resistance (IR) increased with age, but was not modified by changes in percent body fat (%BF), and was only responsive to changes in physical activity (PA) in boys. We aimed to determine whether these responses persisted as the children approached adolescence. METHODS In this prospective cohort study, 256 boys and 278 girls were assessed at ages 8, 10 and 12 years for fasting blood glucose and insulin, %BF (dual energy X-ray absorptiometry); PA (7-day pedometers), fitness (multistage run); and pubertal development (Tanner stage). RESULTS From age 8 to 12 years, the median homeostatic model of IR (HOMA-IR) doubled in boys and increased 250% in girls. By age 12, 23% of boys and 31% of girls had elevated IR, as indicated by HOMA-IR greater than 3. Longitudinal relationships, with important adjustments for covariates body weight, PA, %BF, Tanner score and socioeconomic status showed that, on average, for every 1 unit reduction of %BF, HOMA-IR was lowered by 2.2% (95% CI 0.04-4) in girls and 1.6% (95% CI 0-3.2) in boys. Furthermore, in boys but not girls, HOMA-IR was decreased by 3.5% (95%CI 0.5-6.5) if PA was increased by 2100 steps/day. CONCLUSION Evidence that a quarter of our apparently healthy 12 year-old Australians possessed elevated IR suggests that community-based education and prevention strategies may be warranted. Responsiveness of IR to changes in %BF in both sexes during late preadolescence and to changes in PA in the boys provides a specific basis for targeting elevated IR. That body weight was a strong covariate of IR, independent of %BF, points to the importance of adjusting for weight in correctly assessing these relationships in growing children.Financial support was provided by the Commonwealth Education Trust (London, UK), the Board of Trustees and The Canberra Hospital Salaried Staff Specialists Private Practice Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Contrasting longitudinal and cross-sectional relationships between insulin resistance and percentage of body fat, fitness, and physical activity in children - the LOOK study

Telford RD, Cunningham RB, Shaw JE, Dunstan DW, Lafferty ARA, Reynolds GJ, Hickman PE, Southcott E, Potter JM, Waring P, Telford RM. Contrasting longitudinal and cross-sectional relationships between insulin resistance and percentage of body fat, fitnes

Association between opioid agonist therapy use and HIV testing uptake among people who have recently injected drugs:a systematic review and meta-analysis

BACKGROUND AND AIM: Globally, nearly one in five people who inject drugs (PWID) are living with HIV, and the rate of new HIV infections in PWID is increasing in some settings. Early diagnosis is crucial for effective HIV control. We reviewed the evidence on the association between opioid agonist therapy (OAT) and HIV testing uptake among PWID. METHODS: We conducted a systematic review searching MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and PsycINFO for studies published from January 2000 to March 2019. Reference lists and conference proceedings were hand-searched. Observational and intervention studies were eligible for inclusion. Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. Meta-analyses were conducted using random-effects models. RESULTS: Of 13 373 records identified, 11 studies from Australia, Europe, Malaysia and the United States were included. All studies had at least a serious risk of bias, largely due to confounding and selection bias, making it difficult to draw causal conclusions from the evidence. Ten studies provided data on the association between current OAT use and recent HIV testing. Six showed a positive association, while four provided little evidence of an association: pooled odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.28-2.27. Looking at having ever been on OAT and having ever been HIV tested, seven studies showed a positive association and three showed either weak or no evidence of an association: pooled OR = 3.82, 95% CI = 2.96-4.95. CONCLUSIONS: Opioid agonist therapy may increase uptake of HIV testing among people who inject drugs, providing further evidence that opioid agonist therapy improves the HIV treatment care cascade

Reduction in the population prevalence of hepatitis C virus viraemia among people who inject drugs associated with scale-up of direct-acting anti-viral therapy in community drug services:REAL WORLD DATA

BACKGROUND AND AIMS: There has been little empirical evidence to show the 'real-world' impact of scaling-up direct-acting anti-viral (DAA) treatment among people who inject drugs (PWID) on hepatitis C virus (HCV) viraemia at a population level. We aimed to assess the population impact of rapid DAA scale-up to PWID delivered through community services-including drug treatment, pharmacies, needle exchanges and prisons-in the Tayside region of Scotland, compared with Greater Glasgow and Clyde (GGC) and the Rest of Scotland (RoS). FINDINGS: Uptake of HCV therapy (last year) among PWID between 2013-14 and 2017-18 increased from 15 to 43% in Tayside, 6 to 16% in GGC and 11 to 23% in RoS. Between 2010 and 2017-18, the prevalence of HCV viraemia (among antibody-positives) declined from 73 to 44% in Tayside, 67 to 58% in GGC and 64 to 55% in RoS. The decline in viraemia was greater in Tayside [2017-18 adjusted odds ratio (aOR) = 0.47, 95% confidence interval (CI) = 0.30-0.75, P = 0.001] than elsewhere in Scotland (2017-18 aOR = 0.89, 95% CI = 0.74-1.07, P = 0.220) relative to the baseline of 2013-14 in RoS (including GGC). Per-protocol SVR rates among PWID treated in community sites did not differ from those treated in hospital sites in Tayside (97.4 versus 100.0%, P = 0.099). CONCLUSIONS: Scale-up of direct-acting anti-viral treatment among people who inject drugs can be achieved through hepatitis C virus (HCV) testing and treatment in community drug services while maintaining high sustained viral response rates and, in the Tayside region of Scotland, has led to a substantial reduction in chronic HCV in the population