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World Diabetes Day: The Biggest Burden on the NHS

14 November 2018

World Diabetes Day

Diabetes

Approximately 400,000 people in the UK are living with type 1 diabetes, with over 29,000 being children and young people [1]. Type 1 diabetes affects 96% of all children with diabetes in England and Wales, with incidences increasing by approximately 4% each year.

Globally, the UK has the fifth highest rate of type 1 diabetes diagnosis in children (aged up to 14) with 85% of these children having no family history of the condition. Whilst the condition isn’t fatal and can be managed, it cannot be cured. Type 1 diabetes increases the risk of developing other health problems such as heart disease, stroke, foot and circulation problems, sight problems including blindness, nerve damage and kidney problems. However, many of these related conditions are preventable and it is recommended to stabilise blood sugar levels, attend diabetes appointments regularly and complete a diabetes course to educate patients and family members and prevent the risk of further help complications[2].

Diabetes in children

Children under five are at the highest risk of developing diabetic ketoacidosis due to a late diagnosis and it is also thought to be due to of lack of public knowledge of the signs and symptoms attributed to type 1 diabetes. Such symptoms include:

  • Frequent urination as the kidneys are trying to expel excess sugar in the blood, resulting in dehydration which leads to extreme thirst.
  • Increased hunger or unexpected weight loss because the body is unable to attain enough energy from food
  • Slow healing cuts as high blood sugar levels can affect blood flow which can cause nerve damage.
  • Fatigue as the body is unable to convert sugar into energy
  • Irritable behaviour combined with other symptoms can be a means of concern

Diabetes and the NHS

Diabetes costs the NHS approximately £9.8 billion per year, an estimate of 10% of total expenditures. Hospital admissions of children and young people with diabetes presents a considerable burden on themselves, their families and the NHS. It is estimated that approximately 80% of these cases are potentially avoidable.

A report produced by the National Paediatric Diabetes Audit found that although the numbers of admissions didn’t significantly differ year to year, it highlighted differences in terms of socio-economic risk factors:

  • Living in a deprived area increases the risk of hospital admissions which can be attributed to lack of education in the community about diabetic symptoms and the management of diabetes.
  • Children below 5 years of age have a 35% increased risk of hospitalisation compared to those aged 5-9
  • Females have a 33% increased risk of developing type 1 diabetes compared to males.
  • Children with poor diabetes control have a twelve-fold increased risk of hospital admission
  • Insulin pump users have a 27% increased risk of hospital admission compared to those who use insulin injections.
Figure A. Number of preventable paediatric diabetes admissions  [3] 

Prevention

There are campaigns in place to aid in the early diagnosis of type 1 diabetes which mainly focus on raising awareness of the signs and symptoms of diabetes. On this World Diabetes Day, it is important to know that it is not just simply the responsibility of the diabetic patient to prevent admission but the main responsibility lies with the diabetic teams that inform the families with children who are diagnosed with type 1 diabetes.

Paediatric diabetes teams should ensure that the families and the children receive structured education for self-management when diagnosed and throughout the illness. In doing so, the diabetic teams should implement blood ketone testing from diagnosis and utilise the nationally agreed hypoglycaemia management guidelines. It is also important that diabetic teams are fully aware of the patient characteristics associated with a greater risk of admission and that they use this knowledge to develop anti-admission strategies specifically tailored to the needs of each individual group.

Primary care practitioners should seek access to a specialist diabetic team who they can refer to when deciding if a patient requires admission to hospital. Furthermore, they should access blood glucose and ketone testing to identify patients at risk of diabetic ketoacidosis that require hospital admission.

How Randox can Help

Randox offer a range of assays to diagnosis and monitor diabetes and to monitor associated complications.  Some of these tests are unique to Randox, including:

Fructosamine

The Randox fructosamine assay employs the enzymatic method which offers improved specificity and reliability compared to conventional NBT-based methods. The Randox enzymatic method does not suffer from non-specific interferences unlike other commercially available fructosamine assays.

Learn more about the Randox Fructosamine test

D-3-Hydroxybutyrate (Ranbut)

The Randox D-3-Hydroxybutyrate (Ranbut) assay detects the most abundant and sensitive ketone in the body, D-3-Hydroxybutyrate. The Randox Ranbut assay is used for the diagnosis of ketosis, more specifically diabetic ketoacidosis. Other commercially available tests, such as the nitroprusside method, are less sensitive as they only detect acetone and acetoacetate, not D-3-Hydroxybutyrate.

Learn more about the Randox D-3-Hydroxybutyrate test

Adiponectin

The Randox adiponectin assay is a biomarker in diabetes testing as adiponectin is a protein hormone responsible for regulating the metabolism of lipids and glucose and influences the body’s response to insulin. Adiponectin levels inversely correlates with abdominal visceral fat levels.

Want to know more?

Contact us or visit our Diabetes panel page to learn more.




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  • References

    [1] National Paediatric Diabetes Audit and Royal College of Paediatrics and Child Health, National Paediatric Diabetes Audit Report 2012-15: Part 2, 2017

    [2] NHS, “Avoiding Complications” – Type 1 Diabetes, Available at: https://www.nhs.uk/conditions/type-1-diabetes/avoiding-complications/ [Accessed on 24th October 2018].

    [3] “Potentially Preventable Pediatric Hospital Inpatient Stays for Asthma and Diabetes, 2003-2012”, www.hcup-us.ahrq.gov, 2015. [Online] Available: https://www.hcup-us.ahrq.gov/reports/statbriefs/sb192-Pediatric-Preventable-Hospitalizations-Asthma-Diabetes.jsp [Accessed 08-Nov-18]


Flu Season – Molecular Infectious Disease Testing

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Spotlight Home        IQC        EQA        Infectious Diseases

28 September 2018

Flu Season

Influenza (Flu)

Flu is a contagious respiratory illness cause by influenza viruses that infect the throat, nose, and sometimes lungs. It can cause illness and sometimes death. Getting vaccinated is the best way to prevent catching flu [1].

There are four types of seasonal flu, A, B, C, and D. Types A and B cause seasonal epidemics of disease. Illnesses range from severe to mild and can even result in death in high risk groups. High risk groups include, pregnant women, children under 5 years of age, the elderly, and people with chronic or immunosuppressive medical conditions [2].

Symptoms of Flu [3]

• Sudden fever (temperature above 38C)
• Feeling tired
• Headache
• Sore throat
• Loss of appetite
• Aching
• Chesty cough

Diagnosing Flu

A test to detect Influenza viruses can be used to determine whether a patient has the flu. A swab is taken from either the nose or back of the throat and sent for testing. Molecular assays can be used to detect genetic material of the virus [4]. Molecular methods play an important role in the diagnosis and surveillance of influenza viruses. Molecular diagnostics allow timely and accurate detection of influenza and are already implemented in many laboratories. The combination of automated purification of nucleic acids with real-time PCR should enable even more rapid identification of viral pathogens such as influenza viruses in clinical material [5].

The spread of Flu

Flu season begins as early as October, reaches its peak in February, and ends in March. In the southern hemisphere, flu season falls between June and September. Wherever it’s cold, it’s flu season. This can be seen in Figure A below, which shows google searches for the term ‘flu’ for the last five years for USA (northern hemisphere) and Australia (southern hemisphere). It is obvious that flu is prevalent at different times in the northern and southern hemisphere.

However, it’s a common misconception that flu is caused by the cold. There are many theories as to why the flu season comes in winter [7]:

1. People spend more time indoors, with windows closed, not getting fresh air.
2. A lack of Vitamin D and melatonin from reduced sunlight, weakening the immune system.
3. Influenza virus thrives in the cold, dry air of winter

Of course, there have been attempts to test these theories, but animals do not contract the virus like humans, so testing is difficult. A researcher named Peter Palese decided to test theory 3 after finding an old medical journal article that reported guinea pigs are infected and spread the flu like humans.

Google Searches for 'Flu' in USA and Australia for the last 5 years
Figure A. Google Searches for ‘Flu’ in USA and Australia for the last 5 years [6]

Having set up cages with varying temperatures and relative humidity, he observed how they affected the spread of the flu virus. He found Influenza spread more effectively in cold, dry air [8].

A theory about why this is the case is associated with how the virus moves through the air. When someone breaths out, they release little virus-containing droplets in to the air. The droplet then begins to evaporate. A lower relative humidity means there is less water in the air, meaning there is more room in the air for additional moisture, allowing the droplets to evaporate. A higher humidity means the droplet can’t evaporate because there isn’t as much room for more moisture, and the virus is not suspended into the air [9].

Whatever the case, the fact remains: when winter comes around, the flu will follow.

Prevention

You can avoid catching the flu by getting the flu shot, investing in a humidifier, keeping your hands clean, and limiting contact with those who are already ill. Immunity gained from vaccination decreases over time, so annual vaccination is recommended. Vaccines are most effective when they closely match viruses in circulation. The constantly evolving nature of Influenza viruses requires the WHO Global Surveillance and Response System to monitor influenza viruses around the world and update vaccinations accordingly.

Personal protective measures can be taken in addition to vaccination [2]:

• Properly washing and drying the hands
• Covering the mouth and nose when coughing and sneezing
• Self-isolation when showing symptoms of influenza
• Avoiding contact with sick people
• Avoiding touching the eyes, nose, and mouth

How Randox can Help

Randox offers molecular controls, calibrators, and EQA programmes for respiratory infection testing, which includes Influenza A and B, Adenovirus, Rhinovirus, and others.

Want to know more?

Contact us or visit our Qnostics page to learn more.

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  • References

    [1] “Key Facts About Influenza (Flu) | Seasonal Influenza (Flu) | CDC”, Cdc.gov, 2018. [Online]. Available: https://www.cdc.gov/flu/keyfacts.htm. [Accessed: 25- Sep- 2018].

    [2] “Influenza (Seasonal)”, World Health Organization, 2018. [Online]. Available: http://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal). [Accessed: 27- Sep- 2018].

    [3] “Flu”, nhs.uk, 2018. [Online]. Available: https://www.nhs.uk/conditions/flu/. [Accessed: 25- Sep- 2018].

    [4] “Diagnosing Flu | Seasonal Influenza (Flu) | CDC”, Cdc.gov, 2018. [Online]. Available: https://www.cdc.gov/flu/about/qa/testing.htm. [Accessed: 25- Sep- 2018].

    [5] J. Ellis and M. Zambon, “Molecular diagnosis of influenza”, Reviews in Medical Virology, vol. 12, no. 6, pp. 375-389, 2002.

    [6] “Google Trends”, Google.com, 2018. [Online]. Available: https://trends.google.com/trends/. [Accessed: 26- Sep- 2018].

    [7] “The Reason for the Season: why flu strikes in winter – Science in the News”, Science in the News, 2014. [Online]. Available: http://sitn.hms.harvard.edu/flash/2014/the-reason-for-the-season-why-flu-strikes-in-winter/. [Accessed: 26- Sep- 2018].

    [8] A. Lowen, S. Mubareka, J. Steel and P. Palese, “Influenza Virus Transmission Is Dependent on Relative Humidity and Temperature”, PLoS Pathogens, vol. 3, no. 10, p. e151, 2007.

    [9] “Why Is There a Winter Flu Season?”, Popsci.com, 2013. [Online]. Available: https://www.popsci.com/science/article/2013-01/fyi-why-winter-flu-season#page-5. [Accessed: 26- Sep- 2018].


Biochip vs ELISA: Which testing platform is right for me?

Biochip Vs ELISA

Randox Toxicology’s latest video series, ‘Biochip Vs ELISA’, highlights our routine and novel ELISA products and how they differ from Biochip Array Technology.

Showcasing the journey and ongoing brand evolution of Randox Toxicology, these videos will help you to discover which method is right for you!

Episode 1: Meet ELISA

Episode 1 “Meet ELISA” uses speed reading to showcase Randox Toxicology’s extensive and ever-expanding ELISA test menu, including our range of New Psychoactive Substances, drugs of abuse, stimulants, analgesics and sedatives. Manufactured in the United Kingdom, our continuous reinvestment in research and development has enabled us to develop a range of exclusive ELISA kits such as, Mitragynine, MT-45, and U-47700 which was involved in the death of the famous singer Prince.

 

Our cost effective ELISA kits are the highest quality on the market and results provide excellent correlation with confirmatory methods, typically <10% CV.

Episode 2: Meet Biochip

Based on ELISA principles, Episode 2 “Meet Biochip” illustrates Biochip Array Technology as a solid-state device with discrete test sites onto which antibodies specific to different drug compounds are immobilised and stabilised. Moving away from traditional single analyte assays, Biochip Array Technology boasts cutting-edge multiplex testing capabilities for rapid and accurate drug detection from a single sample.

As the primary manufacturers of Biochip Array Technology, Randox Toxicology offer the most advanced screening technology on the market. With the world’s largest test menu capable of detecting over 500 drugs, Randox Toxicology are changing the landscape of drugs of abuse testing.

Episode 3: Biochip Vs ELISA

Episode 3 “Biochip Vs ELISA” gives you the opportunity to hear from a professional! Laura Keery our Senior Research and Development Team Leader gives you a behind the scenes look at our Biochip Array Technology and ELISA products in action at our new Science Park, answering some of those must know questions.

Episode 4: Biochip Vs ELISA 360-Degrees

If you missed it at SOFT-TIAFT 2017, our Biochip Vs ELISA 360-degree video allows you to experience Biochip and ELISA in action.

Discover which method is right for you! #biochipvselisa

For more information about our revolutionary Biochip Array Technology and ELISA kits, email info@randoxtoxicology.com or visit www.randoxtoxicology.com

 

 

 

 

 


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

  1. 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.
  2. World Health Organisation. Cardiovascular Disease. [Online] 2017. [Cited: April 30, 2018.] http://www.who.int/cardiovascular_diseases/en/.
  3. Doc’s Opinion. Lipoprotein (a). [Online] 2013. [Cited: April 30, 2018.] https://www.docsopinion.com/health-and-nutrition/lipids/lipoprotein-a/.
  4. 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.
  5. Lipoprotein(a) Foundation. Understand Inherited Lipoprotein(a). [Online] 2015. [Cited: April 24, 2018.] http://www.lipoproteinafoundation.org/?page=UnderstandLpa.
  6. Heart UK. Lipoprotein (a). [Online] June 23, 2014. [Cited: April 24, 2018.] https://heartuk.org.uk/files/uploads/huk_fs_mfss_lipoprotein_02.pdf.
  7. 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.
  8. 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.
  9. 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.

Where do errors and uncertainty come from?

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)

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 (MU)

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).

Conclusion

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.

How Randox can help

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

Measurement Uncertainty

Fig. B

Total Error vs Measurement Uncertainty

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.

Measurement Uncertainty vs Total Error
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The Importance of ISO 15189

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References

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 Chemistry64(4), 636-638. http://dx.doi.org/10.1373/clinchem.2017.284406


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.).

Impact on healthcare

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

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.

The Importance of Meeting ISO 15189 Requirements

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

ISO 15189 requirements - non-conformances

Fig. B

ISO 15189 requirements - non-conformances
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References

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 Pathology134(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 ONE11(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.

 

 

 


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