Lp(a): For the Accurate Detection of CVD Risk
Lp(a): For the Accurate Detection of CVD Risk
Lp(a) is an independent risk factor for cardiovascular disease (CVD), even when classical risk factors such as hypertension, elevated cholesterol, and diabetes have been taken into consideration. High levels of Lp(a) is a heredity condition, associated with complex mechanisms involving the proatherogenic and prothrombotic pathways (1).
Traditional CVD testing panel
According to the World Health Organisation (WHO), CVD is the leading cause of death globally, accounting for 31 percent of deaths, totalling 17.7 million deaths per year. 80 percent of all CVD deaths are attributed to heart attacks and strokes, equivalent to 1 in 4. Identifying those who are at a high risk of developing CVD and ensuring that they are receiving the appropriate treatment can prevent premature deaths (2).
The lipid profile is frequently used to assess an individual’s risk of CVD developing later in life. Routine tests to assess CVD risk include: triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). LDL-C has been found to strongly correlate with CVD risk (3). NICE recommend measuring total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides as the full lipid profile and then review other risk factors, including: age, diet, smoking, QRISK, co-morbidities to view risk and the management of risk (4). However, the current lipid panel needs to be adjusted to ensure that its utilisation is effective in meeting clinician and patient needs.
Lipoprotein(a)
Lipoprotein (a) or Lp(a) consists of two protein molecules, apolipoprotein (a) or apo(a) is covalently linked by a disulphide bond to the apolipoprotein B-100 or apoB-100 of a cholesterol-rich low-density lipoprotein or LDL like particle. Lp(a) is synthesised in the liver and is detectable in the bloodstream (5).
The structure of Lp(a) resembles that of the proteins involved in the breakdown of blood clots, plasminogen and tissue plasminogen activator (TPA). As a result, the biggest concern with Lp(a) is that it prohibits the ability of these proteins to break down blood clots by competing for the ‘binding to fibrin’, boosting the blood’s clotting ability within arteries, thus heightening the risk of heart attacks and strokes. Consequently, high levels of Lp(a) is characterised by atherosclerosis including coronary heart disease, peripheral vascular disease, aortic stenosis, thrombosis and stroke (6).
The Journal of the American Medical Association reviewed 36 studies in 2009 which assessed ‘the role of Lp(a) and vascular disease’ in 126,634 individuals. The study found that a 3.5-fold increase in Lp(a) levels was accompanied with a 13 percent higher risk of coronary heart events and a 10 percent higher risk of stroke (7).
Later, an Italian population study carried out on 826 individuals in 2014 found that elevated levels of Lp(a) is due to two different variations of the apo(a) gene which is determined by the kringle sequence differences at the apo(a) locus. The study found that individuals with one variation had a 50 percent greater risk of CVD, while individuals with both variations had 2.5 times greater risk (7).
According to the Lipoprotein Foundation (2015), based on genetic factors, from birth, one in five or 20% of individuals have high Lp(a) levels greater than 50mg/dL, with most blissfully unaware they have it. Overtime, high levels of Lp(a) gradually narrow the arteries, limiting blood supply to the brain, heart, kidneys and legs, increasing the risk of heart attacks and strokes (5).
Testing for high Lp(a) levels
The Lipoprotein (a) Foundation (2015) recommends that Lp(a) levels should be tested if:
- There is a family history of cardiovascular disease including stroke, heart attack, circulation problems in the legs and/or narrowing of the aorta, at a young age
- Stroke or heart attack if classical risk factors including high LDL-cholesterol, obesity, diabetes and smoking have been eliminated
- High levels of LDL-cholesterol following treatment with statins or other LDL lowering medications(5)
When selecting a Lp(a) assay, the Internal Federation of Clinical Chemistry (IFCC) (2004) Working Group on Lp(a) recommends that laboratories use assays that do not suffer from apo(a) size-related bias to minimise the potential risk of misclassification of patients for coronary heart disease (8).
The Lp(a) Foundation reference Marcovina and Albers (2016) in their recommendations for the best Lp(a) test. The study came to the following conclusions:
- Robust assays based on the Denka method, reportable in nanomoles per litre (nmol/L) are traceable to WHO/IFCC reference material
- Five-point calibrators with accuracy-based assigned target values will minimise the sensitivity of to the size of apo(a)
- Upon request, manufacturers should provide the certificate of evaluation of the calibrator and reagent lots with the relative expiration dates (9)
Benefits of the Randox Lp(a) assay
The Randox Lp(a) assay is one of the only methodologies on the market that detects the non-variable part of the Lp(a) molecule and so suffers minimal size related bias providing more accurate and consistent results. This methodology allows for the detection of Lp(a) in serum and plasma. The Randox Lp(a) kit is standardized to the WHO/IFCC reference material, SRM 2B, and is the closest in terms of agreement to the ELISA reference method.
A five-point calibrator is provided with accuracy-based assigned target values which accurately reflects the heterogeneity of isoforms present in the general population.
Liquid ready-to-use reagents are more convenient as the reagent does not need to be reconstituted, reducing the risk of errors.
Applications are available for a wide range of biochemistry analysers which details instrument-specific settings for the convenient use of the Randox Lp(a) assay on a variety of systems. Measuring units in nmol/L are available upon request.
References
- Li, Yonghong, et al. Genetic Variants in the Apolipoprotein(a) Gene and Coronary Heart Disease. Circulation: Genomic and Precision Medicine. [Online] October 2011. [Cited: April 24, 2018.] http://circgenetics.ahajournals.org/content/4/5/565.
- World Health Organisation. Cardiovascular Disease. [Online] 2017. [Cited: April 30, 2018.] http://www.who.int/cardiovascular_diseases/en/.
- Doc’s Opinion. Lipoprotein (a). [Online] 2013. [Cited: April 30, 2018.] https://www.docsopinion.com/health-and-nutrition/lipids/lipoprotein-a/.
- National Institutional for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification. [Online] July 2014. [Cited: April 30, 2018.] https://www.nice.org.uk/guidance/cg181/chapter/1-recommendations#lipid-modification-therapy-for-the-primary-and-secondary-prevention-of-cvd-2.
- Lipoprotein(a) Foundation. Understand Inherited Lipoprotein(a). [Online] 2015. [Cited: April 24, 2018.] http://www.lipoproteinafoundation.org/?page=UnderstandLpa.
- Heart UK. Lipoprotein (a). [Online] June 23, 2014. [Cited: April 24, 2018.] https://heartuk.org.uk/files/uploads/huk_fs_mfss_lipoprotein_02.pdf.
- Ashley, Robert. High lipoprotein(a) levels may indicate heart disease in some. The Brunswick News. [Online] March 05, 2018. [Cited: April 24, 2018.] https://thebrunswicknews.com/opinion/advice_columns/high-lipoprotein-a-levels-may-indicate-heart-disease-in-some/article_16ab1049-7a6f-5da0-8966-59e94ae31b6d.html.
- Dati, F; Tate, J R; Marcovina, S M; Steinmetz, A; International Federation of Clinical Chemistry and Laboratory Medicine; IFCC Working Group for Lipoprotein(a) Assay Standardization. First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay–Lp(a) SRM 2B. NCBI. [Online] 2004. [Cited: April 30, 2018.] https://www.ncbi.nlm.nih.gov/pubmed/15259385.
- Tsimikas, Sotirios. A Test in Context: Lipoprotein(a) – Diagnosis, Prognosis, Controversies, and Emergining Therapies. 6, s.l. : Elsevier, 2017, Vol. 69. 0735-1097.
If you are a cardiologist or a laboratory who are interested in running cardiology and lipid assays, Randox offer a wide range of high-quality, routine and niche assays including: adiponectin, H-FABP, sLDL, TxBCardio, HDL2/3-C, Homocysteine, Apo C-II, Apo C-III and Apo E. These can be run on most automated biochemistry analysers.
Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers.
For more information, visit: https://www.randox.com/lipoprotein-a or email: reagents@randox.com
Is Biomarker Multiplexing the future of kidney disease screening?
Chronic Kidney Disease (CKD) is both a cause and a consequence of cardiovascular diseases, and is an increasing burden on global health. As diabetes, obesity and hypertension incidences continue to rise and the world’s population steadily ages, CKD’s prevalence is already estimated to be between 11% and 13% globally for all five KDOQI stages, with a majority in Stage 3 (about 90% of all stages).
With early stages of CKD being asymptomatic and current diagnostic tools (proteinuria determined by albumin to creatinine ratio and decreased renal function estimated from GFR using the CKD-EPI equation) are insufficiently sensitive to detect most cases up to stage 3, it is likely that the true prevalence of CKD is still underestimated. Therefore the need to improve both early diagnostics and overall CKD outcome is all the more critical.
Accordingly, biomarker research has been intense in the field of renal disease for at least 10 years with a number of promising candidates emerging, some now well-known by specialists: Cystatin C, NGAL or KIM-1 for example.
However, further novel biomarkers, assessed in combination using a properly developed multiplex assays can allow superior insight into CKD than what their individual performance could achieve. This also largely stems from selecting the markers that are indicative of complementary mechanisms that contribute to the development of CKD.
When assayed together from a single serum sample and after combinatorial analysis has been applied, these biomarkers can open new avenues in the management of CKD, such as proper diagnosis of the condition from Stage 1, clear differentiation between stages and monitoring of the progression pace of the disease. Early screening of patients at risk of CKD is now within reach and it is expected that its systematic use will have a profound impact on health system economics.
Another area of interest in renal research is Acute Kidney Injury (AKI) which may arise as a result of cardiac surgery and can subsequently lead to CKD. AKI detection is also of significant interest in the field of drug development, where early stage toxicity is still a large cause of new drug marketing withdrawal. Hence selecting and qualifying kidney tissue damage biomarkers, and assembling them into a multiplex panel is a key priority to those involved in early stage clinical trials.
An AKI panel has been worked out using the same principles as those used in the development of the CKD panel: high individual diagnostic value and multiple, independent cellular targets. This panel is now ready for final clinical qualification and will be one of the first of several organ-targeted safety panels aiming to become standard for drug induced toxicity screening.
It is key to the adoption of multiplex testing that proper validation guidelines be published and that careful, matrix-based validation data is made available to potential users. It is essential that multiplexed testing comes to the front line of testing in the field, so it can deliver to its full potential and start translating into public health improvement and cost savings. Technology is ready, let’s make a start!
Dr Claire Huguet
Randox Biosciences – Head of Biomarkers
For further information about kidney disease screening from Randox Biosciences, please contact randoxpr@randox.com
Measurement Uncertainty Vs Total Error
In a recent article, Error Methods Are More Practical, But Uncertainty Methods May Still Be Preferred, James Westgard comments on the latest developments in the debate on the use of analytical total error (TE) and measurement uncertainty (MU), a debate which has been regularly revisited for the last twenty years. This blog aims to briefly explore the benefits of MU and TE and attempt to draw a conclusion on which is most beneficial in the clinical laboratory.
Many things can undermine a measurement. Measurements are never made under perfect conditions and in a laboratory, errors and uncertainties can come from (Good Practice Guide No. 11, 2012):
- The measuring instrument – instruments can suffer from errors including bias, changes due to ageing, wear, poor readability, and noise.
- The item being measured – the sample may be unstable.
- The measurement process – the analyte may be difficult to measure
- ‘Imported’ uncertainties – calibration of the instrument.
- User error – skill and judgement of the operator can affect the accuracy of a measurement.
- Sampling issues – the measurements you make must be properly representative of the process you are trying to assess. I.e. not using fully commutable controls will mean your quality control process is not reflective of a true patient sample.
Random and systematic errors
The effects that give rise to uncertainty in a measurement can be either random or systematic, below are some examples of these in a laboratory.
- Random – bubbles in reagent, temperature fluctuation, poor operator technique.
- Systematic – sample handling, reagent change, instrument calibration (bias), inappropriate method.
Total Error (TE) or Total Analytical Error (TAE) represents the overall error in a test result that is attributed to imprecision (%CV) and inaccuracy (%Bias), it is the combination of both random and systematic errors. The concept of error assumes that the difference between the measured result and the ‘true value’, or reference quantity value, can be calculated (Oosterhuis et al., 2017).
TE is calculated using the below formula:
TE = %BIAS + (1.96 * %CV)
Measurement Uncertainty is the margin of uncertainty, or doubt, that exists about the result of any measurement.
There is always margin of doubt associated with any measurement as well as the confidence in that doubt, which states how sure we are that the ‘true value’ is within that margin. Both the significance, or interval, and the confidence level are needed to quantify an uncertainty.
For example, a piece of string may measure 20 cm plus or minus 1 cm with a 95% confidence level, so we are 95% sure that the piece of string is between 19 cm and 21 cm in length (Good Practice Guide No. 11, 2012).
Standards such as ISO 15189 require that laboratories must determine uncertainty for each test. Measurement Uncertainty is specifically mentioned in section 5.5.8.3:
“The laboratory shall determine measurement uncertainty for each measurement procedure in the examination phases used to report measured quantity values on patients’ samples. The laboratory shall define the performance requirements for the measurement uncertainty of each measurement procedure and regularly review estimates of measurement uncertainty.”
Uncertainty is calculated using the below formula:
u = √A2+B2
U = 2 x u
Where:
A = SD of the Intra-assay precision
B = SD of the Inter-assay precision
u = Standard Uncertainty
U = Uncertainty of Measurement
Error methods, compared with uncertainty methods, offer simpler, more intuitive and practical procedures for calculating measurement uncertainty and conducting quality assurance in laboratory medicine (Oosterhuis et al., 2018).
It is important not to confuse the terms ‘error’ and ‘uncertainty’.
- Error is the difference between the measured value and the ‘true value’.
- Uncertainty is a quantification of the doubt about the measurement result.
Whenever possible we try to correct for any known errors: for example, by applying corrections from calibration certificates. But any error whose value we do not know is a source of uncertainty (Good Practice Guide No. 11, 2012).
While Total Error methods are firmly rooted in laboratory medicine, a transition to the Measurement Uncertainty methods has taken place in other fields of metrology. TE methods are commonly intertwined with quality assurance, analytical performance specifications and Six Sigma methods. However, Total Error and Measurement Uncertainty are different but very closely related and can be complementary when evaluating measurement data.
Whether you prefer Measurement Uncertainty, Total Error, or believe that they should be used together, Randox can help. Our interlaboratory QC data management software, Acusera 24•7, automatically calculates both Total Error and Measurement Uncertainty. This makes it easier for you to meet the requirements of ISO:15189 and other regulatory bodies.
This is an example of the type of report generated by the 247 software. MU is displayed for each test and each lot of control in use therefore eliminating the need for manual calculation and multiple spreadsheets.
Fig. A
Fig. B
Fig. A and Fig. B above are examples of report generated by the 24•7 software. Fig.A shows how MU is displayed for each test and each lot of control in use therefore eliminating the need for manual calculation and multiple spreadsheets. Fig. B shows TE displayed for each test.
Acusera Third Party Controls
The Importance of ISO 15189
Good Practice Guide No. 11. (2012). Retrieved from http://publications.npl.co.uk/npl_web/pdf/mgpg11.pdf
Hill, E. (2017). Improving Laboratory Performance Through Quality Control.
Oosterhuis, W., Bayat, H., Armbruster, D., Coskun, A., Freeman, K., & Kallner, A. et al. (2017). The use of error and uncertainty methods in the medical laboratory. Clinical Chemistry and Laboratory Medicine (CCLM), 56(2). http://dx.doi.org/10.1515/cclm-2017-0341
Westgard, J. (2018). Error Methods Are More Practical, But Uncertainty Methods May Still Be Preferred. Clinical Chemistry, 64(4), 636-638. http://dx.doi.org/10.1373/clinchem.2017.284406
The RX series celebrate Medical Laboratory Professionals Week
Medical Laboratory Professionals Week is taking place this year from 22nd– 28th April 2018. This is an annual celebration of professionals working in the laboratory, highlighting and recognising their contributions to medicine and healthcare.
To celebrate Medical Laboratory Professionals Week the RX series interviewed Aidan Murphy, one of our laboratory analysts at Randox to find out more about what his job in the lab entails day-to-day. Aidan works with the RX series of clinical chemistry analysers and Randox QC on a daily basis.
We asked Aidan a few questions about his life as a scientist. See what he gets up to in Randox on a daily basis …
1. What attracted you to a career in laboratory science?
Science has always interested me in both my academic and personal life, I always aspired to get a science based degree and after achieving this I now hope to improve my laboratory skills to increase my employability.
2. What were your stronger subjects at school?
My strongest subjects in school were biology, chemistry, music and politics. Some of which are more applicable to my current role than others.
3. What does your job in Randox entail?
My job entails a variety of roles ranging from testing Randox diagnostic kits before they’re released to customers as well as maintenance and precision checks of the machines in our lab.
4. What aspects of your job do you enjoy the most?
The independence in my job is great. Knowing what I have to do at the start of each week and the deadlines to do these jobs requires me to organise and prioritise my work accordingly.
5. What are some common preconceived ideas the public have about what laboratory staff do?
From my friends’ ideas of what I do in the lab I have found that a stereotypical image of a lab is one of a dark quiet lab full of strange equipment and even stranger people. However fortunately my lab is a lively one and thankfully with normal people.
6. In your opinion, what are the most important aspects of laboratory work?
Following correct protocols and procedures are imperative in an efficient laboratory. As well as this, good lab practice and good hygiene can have a massive effect on the accuracy of our results.
7. What’s in your lab coat pocket?
My lab coat pockets are quite boring. I have a pair of safety goggles, some post-its and some pens and markers.
8. In what ways does your work make a difference to people’s lives?
Randox is dedicated to improving the quality of diagnostics globally, so knowing that the kits that I have tested are then sent to customers to be used in patient diagnosis gives me a level of job satisfaction that I haven’t got from previous jobs.
Aidan is a fundamental member of the Randox team and plays an essential role in the diagnosis and prevention of disease through his work. Without our valuable laboratory team working extremely hard behind the scenes the lifesaving work we do here at Randox would not be possible.
To find out more about Randox products contact us at theRXseries@randox.com.
Check out our social media sites for more on Medical Laboratory Professionals Week.
Could there be 5 types of diabetes?
A peer-reviewed study, published in The Lancet Medical Journal suggests there are five types of diabetes. Could diabetes be more complex than we once thought? Could diabetes be segmented into five separate diseases?
What is diabetes?
Diabetes is an incurable disease which prohibits the body’s ability to produce and respond to insulin. Currently, diabetes is classified into two main forms, type 1 and type 2.
Type 1 diabetes is an autoimmune disease which manifests in childhood. In type 1 diabetes, the body’s white blood cells attack the insulin-producing cells in the pancreas. As a result, individuals with Type 1 diabetes rely on the injection of insulin for the remainder of their lives.
Type 1 diabetes affects 10 percent of individuals with diabetes. 96 percent of children diagnosed with diabetes have type 1. Type 1 diabetes in children is commonly diagnosed between the ages of 10 and 14. The prevalence of type 1 diabetes in children and young people (under the age of 19) is 1 in every 430-530 and the incidence of type 1 in children under 14 years of age is 24.5/100,000 (Diabetes UK, 2014).
Type 2 diabetes is the result of insulin resistance, meaning that the pancreas does not produce enough insulin or the body’s cells do not respond to the insulin produced. As type 2 diabetes is a mixed condition, with varying degrees of severity, there are a few methods to manage the disease, including dietary control, medication and insulin injections.
Type 2 diabetes is the most common form of diabetes, affecting 90 percent of individuals with diabetes, and has now become a global burden. The global prevalence of diabetes has almost doubled from 4.7 percent in 1980 to 8.5 percent in 2014, with a total of 422 million adults living with diabetes in 2014. It is expected to rise to 592 million by 2035. In 2012, diabetes accounted for 1.5 million deaths globally with hypertension causing a further 2.2 million deaths. 43 percent of these deaths occurred before 70 years of age. Previously type 2 diabetes was commonly seen in young adults but is now commonly seen in children as well. In 2017, 14% more children and teenagers in the UK were treated for diabetes compared to the year before (World Health Organization, 2016).
In both forms of diabetes, hyperglycemia can occur which can lead to number of associated complications including renal disease, cardiovascular disease, nerve damage and retinopathy.
The novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables – peer-review study
This new research studied 13,270 individuals from different demographic cohorts with newly diagnosed diabetes, taking into consideration body weight, blood sugar control and the presence of antibodies, in Sweden and Finland.
This peer-reviewed study identified 5 disease clusters of diabetes, which have significantly different patient characteristics and risk of diabetic complications. The researchers also noted that the genetic associations in the clusters differed from those seen in traditional type 2 diabetes.
Cluster One – Severe autoimmune diabetes (SAID)
SAID is similar to type 1 diabetes. SAID manifests in childhood, in patients with a low BMI, have poor blood sugar and metabolic control due to insulin deficiency and GADA. 6% of individuals studied in the ANDIS study were identified with having SAID.
Cluster Two – Severe insulin-deficient diabetes (SIDD)
SIDD is similar to SAID, however, GADA is negative. This means that the characteristics of SIDD are the same as SAID, young, of a healthy weight and struggled to make insulin, however, SIDD is not the result of an autoimmune disorder as no autoantibodies are present. Patients have a higher risk of diabetic retinopathy. 18% of subjects in the ANDIS study were identified with having SIDD.
Cluster Three – Severe insulin-resistant diabetes (SIRD)
SIRD is similar to that of type 2 diabetes and is characterised by insulin-resistance and a high BMI. Patients with SIRD are the most insulin resistant and have a significantly higher risk of kidney disease, and microalbuminuria, and non-alcoholic fatty liver disease. 15% of subjects in the ANDIS study were identified as having SIRD.
Cluster Four – Mild obesity-related diabetes (MOD)
MOD is a mild form of diabetes which generally affects a younger age group. This is not characterised by insulin resistance but by obesity as their metabolic rates are close to normal. 22% of subjects in the ANDIS study were identified as having MOD.
Cluster Five – Mild age-related diabetes (MARD)
MARD is the most common form of diabetes manifesting later in life compared to the previous four clusters. Patients with MARD have mild problems with glucose regulation, similar to MOD. 39% of subjects in the ANDIS study were identified with having MARD.
This new sub-classification of diabetes could potentially enable doctors to effectively diagnose diabetes earlier, through the characterisation of each cluster, including: BMI measurements, age, presence of autoantibodies, measuring HbA1c levels, ketoacidosis, and measuring fasting blood glucose levels. This will enable a reduction in the incidence of diabetes complications and the early identification of associated complications, and so patient care can be tailored, thus improving healthcare (NHS, 2018) (The Week, 2018) (Ahlqvist, et al., 2018) (Collier, 2018) (Gallagher, 2018).
The Randox diabetes reagents cover the full spectrum of laboratory testing requirements from risk assessment, using our Adiponectin assay, to disease diagnosis and monitoring, using our HbA1c, glucose and fructosamine assays, to the monitoring of associated complications, using our albumin, beta-2 microglobulin, creatinine, cystatin c, d-3-hydroxybutyrate, microalbumin and NEFA assays.
Whilst this study is valuable, alone it is not sufficient for changes in the diabetes treatment guidelines to be implemented, as the study only represents a small proportion of those with diabetes. For this study to lead the way, the clusters and associated complications will need to be verified in ethnicities and geographical locations to determine whether this new sub-stratification is scientifically relevant.
References
Ahlqvist, E. et al., 2018. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. [Online]
Available at: http://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30051-2/fulltext?elsca1=tlpr
[Accessed 16 April 2018].
Collier, J., 2018. Diabetes: Study proposes five types, not two. [Online]
Available at: https://www.medicalnewstoday.com/articles/321097.php
[Accessed 16 April 2018].
Diabetes UK, 2014. Diabetes: Facts and Stats. [Online]
Available at: https://www.diabetes.org.uk/resources-s3/2017-11/diabetes-key-stats-guidelines-april2014.pdf
[Accessed 16 April 2018].
Gallagher, J., 2018. Diabetes is actually five seperate diseases, research suggests. [Online]
Available at: http://www.bbc.co.uk/news/health-43246261
[Accessed 16 April 2018].
NHS, 2018. Are there actually 5 types of diabetes?. [Online]
Available at: https://www.nhs.uk/news/diabetes/are-there-actually-5-types-diabetes/
[Accessed 16 April 2018].
The Week, 2018. What are the five types of diabetes?. [Online]
Available at: http://www.theweek.co.uk/health/92048/what-are-the-five-types-of-diabetes
[Accessed 16 April 2018].
World Health Organization, 2016. Global Report on Diabetes, Geneva: World Health Organization.
If you are a clinician, dietitian or laboratory who are interested in running diabetes assays, Randox offer a wide range of high-quality routine and niche assays including: fructosamine, glucose, HbA1c for diagnosing and monitoring diabetes, albumin, beta-2 microglobulin, creatinine, cystatin c, NEFA, microalbumin, and d-3-hydroxybutyrate to monitor associated complications, and adiponectin as a biomarker for diabetes risk assessment. These assays can be run on most automated biochemistry analysers.
Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.
For more information, visit: https://www.randox.com/diabetes-reagents or email: reagents@randox.com
The Importance of Meeting ISO 15189 Requirements
Laboratory accreditation provides formal recognition to competent laboratories, providing a means for customers to identify and select reliable services (CALA, n.d.). Use of accreditation standards by clinical laboratories enables them to drive gains in quality, customer satisfaction, and financial performance. This is essential at a time when laboratory budgets are shrinking.
Some key benefits include:
- Recognition of testing competence – as mentioned above, customers can recognise the competence of a lab with an internationally recognised standard.
- Marketing advantage – accreditation can be an effective marketing tool as labs can demonstrate their quality and overall competence.
- Benchmark for performance – laboratories can determine whether they are performing to the appropriate standards and provides them with a benchmark to maintain that standard.
To maintain the global recognition gained from accreditation, labs are evaluated regularly by an accreditation body to ensure their continued compliance with requirements, and to check that standards are being maintained. (CALA, n.d.).
In a comprehensive study conducted by Rohr et al. (2016) it was found that, while accounting for as little as 2% of total healthcare expenditure, in vitro diagnostics (IVD) account for 66% (two thirds) of clinical decisions. Despite such a small percentage of budget dedicated to it, IVD plays a huge role in patient care so it is vital that there is guidance in place to ensure quality standards are met. Poor performance of tests at any stage of care and treatment can reduce the effectiveness of treatment and deny appropriate care to patients in need (Peter et al., 2010).
ISO 15189 is an international accreditation standard that specifies the quality management system requirements particular to medical laboratories and exists to encourage interlaboratory standardisation, it is recognised globally.
Meeting ISO Requirements
Scroll through below to learn how ISO 15189 regulates aspects of a clinical laboratory and how Randox can help you meet these suggestions.
Review of QC data
“The laboratory shall have a procedure to prevent the release of patient results in the event of quality control failure. When the QC rules are violated and indicate that examination results are likely to contain clinically significant errors, the results shall be rejected…QC data shall be reviewed at regular intervals to detect trends in examination performance”
– ISO 15189:2012
Acusera 24∙7 will automatically apply QC multi-rules, alert you to or reject any results that violate the QC multi-rules or performance limits, generate a variety of charts allowing visual identification of trends and provide access to real-time peer group data to assist with the troubleshooting process.
Calculation of MU
“The laboratory shall determine measurement uncertainty for each measurement procedure in the examination phases used to report measured quantity values on patients’ samples. The laboratory shall define the performance requirements for the measurement uncertainty of each measurement procedure and regularly review estimates of measurement uncertainty.”
– ISO 15189:2012
Acusera 24∙7 is the only QC data management platform that incorporates the automatic calculation of Measurement Uncertainty (MU) as well as other performance metrics, including Total Error.
More about Measurement Uncertainty and how Acusera 24∙7 can help
Commutability
“The laboratory shall use quality control materials that react to the examining system in a manner as close as possible to patient samples”
– ISO 15189:2012
Acusera True Third Party Controls are fully commutable, behaving like a real patient sample, reducing the need to re-assign QC target values when the reagent batch is changed, reducing labour and costs.
Medical decision levels
“The laboratory should choose concentrations of control materials, wherever possible, especially at or near clinical decision values, which ensure the validity of decisions made”
– ISO 15189:2012
Acusera True Third Party Controls are designed to challenge instruments across the entire clinical reporting range.
Comparison of results across instruments
“Laboratories with two or more analysers for examinations, should have a defined mechanism for comparison of results across analysers”
– ISO 15189:2012
Acusera 24∙7 is capable of combining multiple data sets on a single Levey-Jennings, Histogram of Performance Summary chart, enabling at-a-glance performance review and comparative performance assessment. A unique multi-instrument report is also available via our RIQAS EQA programme allowing performance of each instrument to be compared.
Third Party Control
“Use of independent third party control materials should be considered, either instead of, or in addition to, any control materials supplied by the reagent or instrument manufacturer”
– ISO 15189:2012
Acusera True Third Party Controls are manufactured completely independently of and calibrators and assigned values through a pool of instruments across the world, making them true third party controls.
At a conference in Belgium in 2016, data, which highlighted the most common areas of non-conformance in laboratories, showed that nonconformities were most prevalent in sections 5.5 and 5.6 of ISO 15189. This data is visualised in fig. A below. Furthermore, a study by Munene et al. (2017) has had similar findings, as visualised in fig. B. The greatest number of nonconformities occur in the sections that are concerned with insufficient assay validation and quality of examination procedures. These studies specifically identified the lack of independent controls, QC not at clinically relevant levels, commutability issues, and a lack of interlaboratory comparison as major issues.
Randox Quality Control products are designed to target these areas, making it easier to conform to ISO 15189 standards.
Fig. A
Fig. B
Acusera Third Party Controls
Interlaboratory Data Management
CALA. The Advantages of Being an Accredited Laboratory. Canadian Association for Laboratory Accreditation. Retrieved from http://www.cala.ca/ilac_the_advantages_of_being.pdf
Munene, S., Songok, J., Munene, D., & Carter, J. (2017). Implementing a regional integrated laboratory proficiency testing scheme for peripheral health facilities in East Africa. Biochemia Medica, 110-113. http://dx.doi.org/10.11613/bm.2017.014
Peter, T., Rotz, P., Blair, D., Khine, A., Freeman, R., & Murtagh, M. (2010). Impact of Laboratory Accreditation on Patient Care and the Health System. American Journal Of Clinical Pathology, 134(4), 550-555. http://dx.doi.org/10.1309/ajcph1skq1hnwghf
Rohr, U., Binder, C., Dieterle, T., Giusti, F., Messina, C., & Toerien, E. et al. (2016). The Value of In Vitro Diagnostic Testing in Medical Practice: A Status Report. PLOS ONE, 11(3), e0149856. http://dx.doi.org/10.1371/journal.pone.0149856
Randox Testing Services: The difference between CBD Oil, Cannabis Oil and Hemp Oil
CBD Oil, Cannabis Oil and Hemp Oil are naturally produced from the plant Cannabis Sativa. This article will aim to distinguish between the different variations, and highlights differences in their use, abuse and legal standing.
Cannabis is the name given to the common drug of abuse, made from various parts of the Cannabis Sativa plant that contain a high level of a chemical called THC (tetrahydrocannabinol). THC is the chemical responsible for most of cannabis’s psychological effects. It stimulates cells in the brain to release dopamine and interferes with how information is processed in the hippocampus, the part of the brain responsible for forming new memories. Strains of Cannabis Sativa are specifically bred for their high THC content in resinous glands on their flowers and some leaves.
Cannabis Oil contains a high level of THC and if administered can result in psychoactive effects. There is a growing movement to legalise THC in the form of oils or capsules for medicinal use (pain relief), however, like cannabis itself, it is currently illegal to possess, or supply cannabis oil in the UK.
CBD (or cannabidiol), like THC, is another chemical component extracted from the Cannabis Sativa plant. Unlike THC, CBD is not psychoactive and does not produce a ‘high’. CBD is derived from a specific hemp strain that is high in CBD and low in THC and is extracted from the whole plant (and not just the seed like hemp seed oil). The use of CBD oil is becoming widespread for its reported health-giving benefits. It is perfectly legal to use (because it contains negligible amounts of THC) and can be purchased from health food shops and on-line.
However, it is also sometimes (mistakenly) referred to as ‘cannabis oil’ which causes confusion.
Hemp is a fast-growing strain of Cannabis Sativa specifically bred for its fibre (for textile use), oils (including CBD oil) and nutritional benefits among its ever-expanding range of uses. However, hemp is bred to be low in THC. Hemp seed oil is acquired by pressing the hemp seeds only and contains neither THC nor CBD. Hemp oil is perfectly legal and you may find it in some health food products or even beauty products.
Effects of Cannabis
Cannabis is the most commonly abused drug in the UK and can produce a range of side-effects including an increased risk of developing a psychotic illness. For an extensive list of the side-effects of regular cannabis use download our free educational resource: http://www.randoxtestingservices.com/download/Effects-of-Cannabis-Poster.pdf
About Randox Testing Services
Randox Testing Services is a market leader in the drug and alcohol testing industry. Our expertise is relied upon by a range of leading safety-critical companies across the world.
We pride ourselves on helping our customers improve the health and safety of their working environment through helping them implement a comprehensive substance misuse policy. As experts in our field we ensure that we are aware of current drug trends and issues that are affecting society.
Contact us today at testingservices@randox.com or call 028 9445 1011 to speak with one of our experts.
The Importance of Equine Health
With the Grand National around the corner, Randox Reagents have investigated the importance of equine health, focusing on racehorses.
Maintaining good health in racehorses is vital as proper management can reduce the incidence of many disease conditions. Racehorses are bred, raised, and trained to perform as athletes. Therefore, it is vital that the performance health of racehorses is continually assessed to ensure that they are physically fit, happy and healthy.
Racehorse’s have a busy life. They are broken in from 18 months of age, usually using traditional methods such as long reining, followed by accepting a rider and training alongside other horses. At 2 years of age, the real training begins which focuses on fitness and speed rather than ‘schooling’ the horse in the conventional way. This training is undertaken alongside another horse to teach the trainee horse how to race but at the same time, it is taught to settle and listen to the jockey.
In peak season, the horse’s weekly exercise regime consists of: two days of fast gallop work with steady trotting or cantering the rest of the week, with a rest day on Sunday’s (depending on races scheduled for the horse).
The most important bodily systems for top athletic performance in racehorses include:
Skeletal system (including bone, tendons and ligaments) problems such as torn or stretched ligaments or tendons or a broken bone will be very painful, inducing lameness and prohibiting performance
Muscles enable the horse to perform. Fatigued or damaged muscles will result in poor performance as the horse cannot generate enough energy and strength to maintain its high performance
Respiratory system (nasal passages, throat and lungs) problems prohibits the normal flow of oxygen through the body, which prohibits the energy required for exercise
Cardiovascular system (heart, blood vessels, volume of blood and red blood cells) problems prohibits the movement of oxygen from the lungs to the muscles, again prohibiting the generation of energy required for exercise.
Central nervous system (CNS) problems can result in the loss of coordination and the fine control that accompanies minor problems to the CNS can significantly prohibit exercise performance
Due to the intense training that racehorses undergo, it is vitally important that their health is continually assessed to diagnose and treat injuries and the jockey allows the horse time to recover from the injury. The most common sites of injury include: forelegs, back and pelvis such as bowed tendon (tendonitis), strained suspensory ligaments, splints, osselets, sesamoid fractures, condylar fractures, knee fractures, bone chips, bucked skins and pin firing. It is vitally important that racehorses are allowed time to rest and heal after an injury. Training or racing a horse whilst injured can be detrimental.
Randox Equine Panel
Randox offer 10 scientifically proven assays for equine health which are made from the same high-quality material as our human assays, providing accurate and precise results. These assays have extensive measuring ranges for the accurate detection of disease or inflammation which are suitable for use with serum, plasma and whole blood. Instrument specific applications (ISA’s) are available for an extensive range of biochemistry analysers suitable for use with manual, semi-automated and fully automated analysers.
The Randox range of assays, suitable for equine use, cover a range of biomarkers:
Adiponectin is used to assess equine metabolic syndrome (EMS) which is characterised by obesity, regional adiposity, insulin resistance, and susceptibility to laminitis. Laminitis is one of the most common causes of lameness in horses. It is a painful and potentially crippling condition, which in severe cases usually results in the horse being humanely euthanised.
Aspartate Aminotransferase (AST) levels directly correlate with the severity of muscle inflammation or damage, or liver damage. The highest levels of AST will be seen around 24hours after muscle injury and persist for 2-3 weeks.
CK-NAC is a sensitive marker for the detection of musculoskeletal diseases; and is useful to assess the extent of severe muscle trauma, crush injuries, and burns and the likelihood of developing rhabdomyolysis.
For health professionals
If you are a veterinarian or laboratory who are interested in running equine assays, Randox offer a wide range of high-quality routine and niche assays including: albumin, alkaline phosphatase, bilirubin, calcium, GLDH, glucose and urea. These can be run on most automated biochemistry analysers.
Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.
For more information, email reagents@randox.com
Benefits of High-Sensitivity Troponin I (hs-TnI)
Benefits of High-Sensitivity Troponin I (hs-TnI)
Chest pain is a common symptom; 20% to 40% of the population will experience chest pain during their lifetime. There are many causes of chest pain, some of which are benign, while others are potentially life threatening. Importantly, in patients with chest pain caused by an acute coronary syndrome (ACS) or angina, there are effective treatments to improve symptoms and prolong life, emphasising the importance of early diagnosis in patients where chest pain may be of cardiac origin (Skinner et al, 2010). Chest pain is one of the most common reasons for emergency admission to hospital and is a heavy burden on health-care resources. A strategy to identify low-risk patients suitable for immediate discharge would have major benefits (Shah et al., 2015).
RIQAS Liquid Cardiac Programme
Interlaboratory data Management
Ford, C. (2017). Benefits of High Sensitivity Cardiac Troponin I at Admission. Clinical Laboratory Management Association, (July/August 2017), 22-24.
Shah, A., Anand, A., Sandoval, Y., Lee, K., Smith, S., & Adamson, P. et al. (2015). High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. The Lancet, 386(10012), 2481-2488. http://dx.doi.org/10.1016/s0140-6736(15)00391-8
Skinner, J., Smeeth, L., Kendall, J., Adams, P., & Timmis, A. (2010). NICE guidance. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. Heart, 96(12), 974-978. http://dx.doi.org/10.1136/hrt.2009.190066
Extreme Weather Results in High Risk of Mycotoxin Contamination
Mycotoxin contamination is a real and constant threat for feed and animal compound producers globally. Recently the University of Guelph, Guelph, Ontairo stated that the different geographical locations of cattle mean between 10 and 20 mycotoxins can be present at once. This is a result of extreme weather patterns across the US with excess moisture and drought in different areas causing an increase in the frequency of mycotoxins, creating challenges in protecting livestock from ingesting contaminated feed.
The most common mycotoxins found are Aflatoxin, Fusarium, Deoxynivalenol and Zearalenone. Aflatoxin is produced by Aspergillus flavus, a tropical fungus that thrives in high humidity and affects an animal’s liver, causing cancer in more extreme cases. Fusarium can develop in most temperate climates across the U.S and Canada. Fusarium poses a higher threat than other toxins as there are hundreds of different chemical structures to analyse to enable identification of the Fusarium.
Difficulties also arise in finding an analytical method sensitive enough to detect mycotoxins at low levels of contamination as small amounts can still lead to fatal results in horses, dogs and cats.
To prevent mycotoxin infection in feed, processors can implement a routine screening procedure with the help of Randox Food Diagnostics. Randox Food offer a multiplex screening system for the simultaneous detection of up to 10 of the world’s most prevalent mycotoxins including: Paxilline, Fumonisins (part of the Fusarium group), Ochratoxin A, Aflatoxin G1/G2, Aflatoxin B1/B2, Ergot Alkaloids, Diacetoxyscirpenol, Deoxynivalenol, T2 Toxin and Zearalenone. All compounds are screened at low limits of detection using Biochip Array Technology.
Biochip Array Technology is a patented technology created by Randox to facilitate the detection of contaminants and drug residues with over 20 evaluated matrices in feed (see full list below).
| Animal Feed (Complete) | Millet | Sunflower |
| Barley | Mustard Seed | Wheat |
| Beet | Palm Kernel | Grass |
| Buckwheat | Rapeseed | Whey |
| Corn/Maize | Rice | Linseed |
| Cotton Seed | Rye | Feed Pea |
| Distillers Grain | Silage | Vetches (Vica) |
| Hay | Soya | Oat |
To learn more about Mycotoxin testing with Randox Food Diagnostics email, info@randoxfooddiagnostics.com
