Randox Health features in Sunday Times article
Randox Health features in Sunday Times article
One writerās first health MoT showed her cholesterol in the red. It forced a dramatic lifestyle rejig, but the hard part was making the changes stick
In February my colleague Matt Rudd sent a pleading email: āHelp! I need volunteers for a blood health panel screening. Hooked on the fact that a million people in the UK have undiagnosed T2 diabetes.ā
My Italian grandmother had diabetes. I had never had a proper health check in my life. It probably wasnāt a bad idea to have an MoT.
By my reckoning, I was in reasonable nick for a 37-year-old mother of a two and a five-year-old: I cooked from scratch, didnāt eat red meat and cycled (occasionally and slowly) to work. I banked on getting the health equivalent of a B+.
But I very much did not get a B+. The results from my Ā£65 āvitalā Randox Health check were graded byĀ a traffic light system. Ten per cent of me was, firmly, in the alarming red zone and 13 per cent was amber. The (main) issue was not pre-diabetes, butĀ high cholesterol. My total was 6.22 mmol (millimoles per litre) when it should have been less than 5.
āIām really freaking out,ā I messaged my partner, Tom. āIām going to get heart disease. Or have a stroke.ā
Closer inspection showed that my LDL, which Google informed me was the bad kind of cholesterol, the kind that clogs up the arteries and kills you, was 3.56. It should have been below 3. My iron levels were also low, again throwing up more red. And I wasnāt fit. My body mass index was in the green but I had the metabolic age of a 40-year-old. āThis is really sub-optimal,ā I added to Tom.
But it was the high cholesterol, which is usually without symptoms, that bothered me. Nearly 50 per cent of the population is estimated to have high cholesterol and it often runs in families, explains Julie Ward, a cardiac nurse at the British Health Foundation. āItās really prevalent in society, but often people, especially younger people, have no idea at all until they get checked. The key is to talk to your relatives, to your parents. Ask them if thereās a family history.ā
I peppered my trim mum with anxious messages. Why didnāt I know about this? āI told you that I had high cholesterol,ā she replied. When? āYou were 14.ā Somewhere between the Smirnoff Ice and Marlboro Lights, that particular health concern apparently hadnāt lodged in my mind.
I told my twin brother about our genetic predisposition, which he seemed relaxed about. I was anything but relaxed. I think it was the recognition that I could no longer āwing itā that struck me. Call it my coming of age. And my worries spiralled from there: I wanted to be around and healthy for my children as they grew up. Which meant that as Sir Keir Starmer said about the NHS, I had two options: reform or die.
The question was: what to do about it? Changing habits, some of which developed in childhood, is extremely challenging. I took a hard-nosed look at my lifestyle. Exercise didnāt really feature, other than the 25-minute cycle to the office and a bit of tennis. None of which, Tom pointed out, made me break into a sweat.
I ate lots of vegetables, fish and pulses, but I also ate cheese straws, crisps and pasta. At restaurants, I was all about fried and/or beige: croquetas, any kind of tempura, burrata, tuna tostadas. The bread basket. Nor did I ever contemplate the long rigmarole of putting our kids to bed without eating a hefty wedge of toasted sourdough, butter and mature cheddar.
So what could I do? The answers were predictable: exercise, cut out saturated fats (found in cakes, biscuits, pastries, processed food), eat more pulses and vegetables, and eat plenty more seeds, nuts, oily fish and avocado, all sources of good cholesterol, the kind that takes the bad away from the arteries.
Letās retest in six months, suggested Matt Rudd. Here was a competition, something I could get on board with.
āIām making radical changes,ā I told Tom as I filled our online Sainsburyās cart with butter beans, chickpeas and beetroot (none of which I much liked). āNo more bread, white pasta, potatoes, white rice. No cheese, no deep-fried food. No moreTonyās Chocolonely. And Iām going to work out two mornings a week.ā
The first major test came two days later when we went on a rare childfree trip to Venice, home of cichetti and Aperol Spritz. At 6pm, drinking white wine beside the lagoon, I was presented with a (free) plate of tiny smoked salmon white bread sandwiches and bruschette piled with salted cod.Oh tentazione!
But I had decided to go cold turkey. Any other approach and I knew my willpower would evaporate before Tom could say āstrokeā. Dinner was torture: obviously I wanted the spaghetti alle vongole but instead I made myself order cuttlefish stew (no carbs!).
Back in London, I carried on. Toast with butter and marmite was replaced with chia and flaxseed-heavy oat bircher. My mid-afternoon snack of pop chips became walnuts and almonds. A salad for the old me was 60 per cent crouton.
Dinner became something like veggie chilli, no rice, or spicy butter beans with spinach and tofu. Biscuits, cakes and puddings were taken off my menu. As was my after-supper chocolate.
Classpass, a monthly subscription that gets you access to various gym classes, also worked for me. Mainly because its policy is to fine you for missing a class. Brutal but effective.
It takes 60 days to form a habit, Tom kept telling me when I wavered: donāt give up. A dogma confirmed by Jenna Hope, a nutritionist who advises her clients on how to break and reform habits. āItās hard, but there are tricks,ā she says. One is to focus on what is making you sit down on the sofa with a tub of ice cream after work. āIf that is what you do for relaxation, you need to replace the ice cream with something else, something healthy. Donāt just say, āIām not having ice cream any moreā, thatās much harder.ā
Each person is different, she says, some need to make changes slowly. Others, like me, need to go nuclear. Either way, the key is consistency.
Competitiveness also drove me. I wanted to beat Matt Rudd. Though when he opened his desk drawer to reveal a supermarket-sized stack of Jammy Dodgers, Mini Cheddars and Haribo, I realised heād given up.
By two months in, I was feeling a hell of a lot of better. I no longer had stomach aches and I was fitter and had lost weight. Iād also developed a taste for crouton-free salad.
Take the Randox test, my editor kept asking me. But I was worried: what if, after all this effort and self-denial, my cholesterol hadnāt changed? Can you even do anything about it when it runs in your family?
Last week, I caved andtook the test. The great news was that I had reduced my metabolic age from 40 to 23. And my cholesterol? Still red but definitely leaning more pink: from a total of 6.22 it had dropped to 5.6. And the bad kind was now at the healthy level, below 3, at 2.79 mmol.
āThatās a really good level,ā said Joanna Lilburn, a scientific consultant at Randox. āAnd I wouldnāt worry about the total level because a lot of that is good cholesterol.ā
Which is what I wanted to hear. Lifestyle changes were working. Albeit slowly. What I didnāt want to hear is that cholesterol levels increase as you age. Which means that now, warned Lilburn, comes the hard part. āItās about keeping it going.ā
Read full article here: I had high cholesterol at 37. The cure was tougher than I imagined (thetimes.com)
Understanding Xanthochromia
Understanding Xanthochromia
When faced with a potential subarachnoid haemorrhage (SAH), the tools we use to diagnose can quite literally be life-saving. Cerebrospinal fluid (CSF) analysis plays a pivotal role, especially when common diagnostic tools like Computed Tomography (CT) scans might not catch early signs.
Traditionally, xanthochromia detection relied on visual assessment – a method that suffers from inconsistency due to subjective interpretation and lacks uniformity across the industry. Today, spectrophotometry has emerged as the preferred method for its precision and reliability in detecting xanthochromia. To ensure the highest accuracy, this technique requires stringent quality control measures. Here, we discuss xanthochromia and SAH, before introducing our dedicated Xanthochromia true third-party control.
What is Xanthochromia?
Xanthochromia, derived from the Greek word, ‘xanthos,’ meaning yellow, refers to the yellow, or sometimes pink, discolouration of CSF, primarily due to bilirubin, a by-product of haemoglobin breakdown. Why does this matter? Because it’s a tell-tale sign of bleeding within the brain, often indicating SAH when CT scans don’t. Understanding this can help us catch and treat critical conditions before they worsen. Xanthochromia may also be an indicator of intracerebral haemorrhage, brain tumours, infection, or severe systemic jaundice1.
Subarachnoid Haemorrhage
SAH is a spontaneous intracranial bleed characterised by significant mortality and morbidity rates. Approximately 12% of patients die before receiving medical attention, 33% within 48 hours, and 50% within 30 days of an SAH. Among the survivors, half suffer from permanent disabilities, with an estimated lifetime cost more than double that of an ischemic stroke2. Patients which have displayed symptoms often complain of severe headache, nausea, vomiting, photophobia and/or phonophobia3.
CT scans, particularly non-contrasted CTs of the brain or CT angiograms (CTAs), are often the first line of diagnostic tools for suspected SAH. However, up to 5% of SAH cases may not show any signs of haemorrhage on these scans within the first 24 hours, with this figure rising to 50% by the end of the first week and remaining around 30% by the second week4.
In contrast, xanthochromia in the CSF can be detected as early as two hours after a bleed and is observed in over 90% of patients within 12 hours of an SAH event. This detection can persist for up to three to four weeks, offering a critical diagnostic window that imaging alone might miss. The conversion from haem to bilirubin in CSF takes roughly 6 to 12 hours, suggesting that xanthochromia is most reliably identified between 6- and 12-hours post-bleed. More than 75% of patients may still present with xanthochromia at 21 days following an SAH1.
Pathophysiology explained
A ruptured cerebral aneurysm will begin to leak blood into the CSF. This blood is gradually degraded by macrophages to yield various by-products including oxyhaemoglobin, which is subsequently converted to bilirubin in a process lasting between 6 and 12 hours1. Crucially, this conversion to bilirubin can only occur in vivo, providing a unique marker for diagnosing subarachnoid haemorrhage when observed in the CSF1.
The Importance of Accurate Detection
In many parts of the world, including the US, visual detection remains a common initial test for xanthochromia in CSF.
- Procedure: Spinning a CSF sample in a centrifuge and comparing the supernatant against a vial of water, held against a white backdrop to detect a yellow or pink tint.
- Indication: A change in colour indicates that blood has been present in the spinal fluid for at least two hours, with all patients showing signs by 12 hours post-bleed1.
However, this method is prone to false positives due to:
- Dietary influences: High intake of carotenoids (like carrots and spinach).
- Medication: Use of Rifampin.
- Medical conditions: Clinical jaundice or high protein levels in CSF, which can be seen in conditions like carcinomatosis and meningitis1.
Spectrophotometry
Spectrophotometry offers a more precise alternative by measuring light absorption in materials at specific wavelengths:
- It can detect the presence of bilirubin, which absorbs light at 440 to 460 nm, a definitive indicator of xanthochromia.
- Advantages over visual detection: This method eliminates the interference from other pigments or proteins and can distinguish bilirubin from oxyhaemoglobin, crucial for accurate diagnosis.
Quality control is crucial in spectrophotometry to ensure the accuracy and reliability of xanthochromia tests:
- Regular Maintenance: Routine checks and maintenance of the spectrophotometer are fundamental to its operation. This helps in maintaining the instrument’s precision in measuring light absorption at specific wavelengths crucial for detecting bilirubin in CSF.
- Calibration: Calibrating the spectrophotometer with known standards is essential. This process adjusts the instrument to measure the absorption accurately, particularly vital given bilirubin’s narrow detection window between 440 and 460 nm.
Implementing these stringent QC measures enhances the diagnostic precision of spectrophotometry, boosting confidence in the results. Such practices ensure that patients are diagnosed accurately and receive timely, appropriate treatment, solidifying the value of advanced diagnostic techniques in medical settings.
Introducing Randox Xanthochromia Controls
Diagnosing SAH swiftly and precisely is critical due to its significant immediate and long-term impacts. To aid precise detection, our Liquid Frozen Xanthochromia Positive & Negative Controls are essential tools for laboratories conducting CSF analysis. Here’s what makes them stand out:
- Dedicated Xanthochromia true third-party control with only 2 analytes for limited cross-reactivity – Bilirubin & Oxyhaemoglobin
- 2-day open vial stability at 2° to 8°C and a 11-week shelf life from date of manufacture when stored at -18ºC to -24ºC.
- Liquid frozen control provides suitable matrix in an easy-to-use format.
- Consistent, clinically significant values.
- Suitable for use with UV spectrophotometers, these controls help monitor bilirubin and oxyhaemoglobin levels effectively.
The Randox Xanthochromia Controls are ideally suited for laboratories, both public and private, as well as researchers who perform CSF analysis. Their use is crucial in ensuring the precision of SAH testing, which contributes to more accurate diagnostics and ultimately leads to better patient outcomes.
Considering the crucial role of accurate xanthochromia detection in diagnosing SAH, isn’t it time to review your lab’s capabilities? Explore how Randox Xanthochromia Controls can enhance your diagnostic processes. For more details on how to get these tools in your lab, contact us at marketing@randox.com.
In the fight against conditions like SAH, every second and every test counts. Equip your lab with Randox Xanthochromia Controls to ensure that your diagnostics are as precise and reliable as possible, helping save lives and improve healthcare outcomes.
References
-
- Dugas C, Jamal Z, Bollu PC. Xanthochromia. StatPearls Publishing; 2024. Accessed August 5, 2024. https://www.ncbi.nlm.nih.gov/books/NBK526048/
- Sehba FA, Hou J, Pluta RM, Zhang JH. The importance of early brain injury after subarachnoid hemorrhage. Prog Neurobiol. 2012;97(1):14-37. doi:10.1016/j.pneurobio.2012.02.003
- NHS. Subarachnoid haemorrhage. https://www.nhs.uk/conditions/subarachnoid-haemorrhage/.
- Chakraborty T, Daneshmand A, Lanzino G, Hocker S. CT-Negative Subarachnoid Hemorrhage in the First Six Hours. Journal of Stroke and Cerebrovascular Diseases. 2020;29(12):105300. doi:10.1016/j.jstrokecerebrovasdis.2020.105300
Routine healthcare could save billions and boost survival rates for cancer and serious diseases.
Reports show that “improvement in life expectancy have ground to a halt” and more than one in five deaths are considered “avoidable”. It warns that since the 1960 the UK has “declined from being ranked first for life expectancy among G7 countries to being ranked second last”.Ā
Dr. FitzGerald said: “This is a shameful drop of quality care, and it should be a national disgrace that our healthcare provider has failed us so badly.”
Pushing for the UK to follow the example of Japan, where the average person can expect to live more than 84 years, he said: “Japan is leading the way in healthcare testing. It has the highest life expectancy of all G7 nations, and it routinely tests for far more than we do in the UK.
“Major benefits for them have included a massive 25 per cent fall in diabetes rates among those at risk of developing the disease.”
The Office for National Statistics sounded the alarm bell about declining life expectancy in the UK earlier this year. Life expectancy at birth for men in the 2020-22 period fell by 38 weeks to 78.6 compared with 2017-2019;Ā for women, it went down by 23 weeks to 82.6 years.
There is strong concern that in Britain people are much more likely to enjoy long lives if they are better off. In 2021, there was alarm when it was reported that a man living in Kensington and Chelsea, one of the country’s richest areas, could be expected to live 27 years longer than a counterpart in Blackpool.
Dr. FitzGerald is pushing for a far more ambitious programme of testing than the health MOTs offered to people aged 40-plus on the NHS.
Claiming that the “NHS is creaking at the seams”, he said: “By investing in preventative measures, the NHS will be far more effective and therefore far better value for money for the taxpayer.”
The biochemist, who in 1982 founded his company in a converted chicken house in Crumlin in Northern Ireland, argues Britain “must do better”. He said, “Improving the health and prosperity of the nation is an important goal – and this initiative can more than pay for itself. More importantly, it will be greater than a simple money saving exercise.
It can and will save lives. It is time for government to step up and deliver for the British people. A Department for Health and Social Care spokeswoman said: “We will transform the NHS from a late diagnosis, late treatment health service, to one that catches illness earlier and prevents it in the first place. We will start by doubling the number of diagnostic scanners to help speed up diagnosis and treatment.”
Dr. FitzGerald is pushing for a far more ambitious programme of testing than the health MOTs offered to people aged 40–plus on the NHS. Claiming that the ‘NHS’ is creaking at the seems, he said: “By investing in preventative measures, the NHS will be far more effective and therefore far better value for money for the taxpayer.
“More importantly, it will be greater than simple money saving exercise.Ā It can and will save lives. It is time for the government to step up and deliver for the British people. A Department for Health and Social Care spokeswoman said: “We will transform the NHS from a late diagnosis, late treatment health service, to one that catches illness earlier and prevents it in the first place. We will start by doubling the number of diagnostic scanners to help speed up diagnosis and treatment.”
Health Secretary Wes Streeting has ordered a ‘full and independent investigation into the state of the NHS to uncover the biggest challenges facing the health service.
Words by David Williamson, The Sunday Express
Randox Health ā Optimising Performance as Official Diagnostic Health partner of Team GB for Paris 2024
Randox Healthās unique diagnostic technologies have been supporting Team GB throughout their journey to the Paris 2024 Olympic Games ā from preparation to their hard-earned success of over 40 Olympic medals and will continue to help optimise the teamās performance during the remainder of the competition.Ā
Randoxās Vivalytic diagnostics machine has been in action during Paris 2024. These fully automated, all-in-one molecular diagnostic machines are powered by Randoxās unique Biochip Technology and are capable of checking for a wide range of respiratory infections, enabling multiple test results from just one sample.
āAs a Sport and Exercise Medicine Consultant working with elite athletes, itās important we know the pathogen driving the disease process to be able to target management appropriately. With Randox supplying this useful technology in our performance environments, we can optimally manage both the athletes and wider team safely and efficiently.ā
āOur aim, along with the teams of experts assisting our athletes is simple ā to ensure that Team GB is in peak physical and mental condition as they get to the starting line.ā Dr. Lisa Hyland, who is working as a Team GB HQ Doctor
Find out how Randox Technologies help Team GB reach Olympic success with our Vivalytic Point of Care testing
Team GBās Chief Medical Officer, Niall Elliott, said that Randox was helping in three critical areas of health testing for athletes ā iron metabolism, vitamin D levels ā critical to the immune system and muscle power ā and glucose or energy levels. āIt is a fascinating journey, the testing we can do.ā
Over the last year, Randox have been working closely with Team GB brand ambassadors, to ensure they are perfectly placed to perform their utmost at the Olympic Games. Each of them have undertaken a Randox Health Everyman and Everywoman diagnostic health test package at one of the Randox Health clinics, to measure their conditions as they get to that starting line in Paris.
As one star, Duncan Scott, Team GBās most decorated Olympic swimmer, put it: āIf it makes one per cent difference itās 100% worth it.ā
āEverything you do as a swimmer is being channelled through the window of your technique but thereās external factors such as nutrition, recovery, sleep that contribute those one percents towards how youāre going to be inside the pool when it matters the most. With that in mind, I think the Randox Health Everyman check was spot on and Iām glad that Iāve done it.ā
Team GB sprinter and double Olympic medallist Daryll Neita the Everywoman test, calling it, āthe most in-depth testing Iāve ever had.ā
āItās amazing that the Everywoman test discovers things that could help my performance whether itās how I recover to deficiencies but also our sport is about marginal gains, centimetres, millimetres, the finest of margins and through tests like this, it lets you stay on-top of your health helping you achieve optimal performance or even a mental boost that youāre healthy.ā
Adds Dr. Peter FitzGerald, Founder and Managing Director of Randox Health, āAnd these technologies are not just for athletes ā our diagnostic packages and analysers are designed to make a difference to everyoneās life ā to help us make the most of all the opportunities life has to offer.ā
Lipoprotein (a): Molar or Mass?
Lipoprotein (a): Molar or Mass?
Lipoprotein (a) was first identified in 1963. However, it’s been in the last decade we’ve seen significant advances in our understanding of this ambiguous molecule and its relationship with cardiovascular disease (CVD) risk.
Lp(a) is a macromolecular lipoprotein complex1 which is thought to display proatherogenic, proinflammatory2 and prothrombotic3 potential and is considered an independent causal risk factor for various types of CVD4. These properties provide several mechanisms in which elevated Lp(a) levels may contribute to CVD however the true nature of Lp(a)’s relationship to CVD remains largely enigmatic.
Although some of the first studies failed to find a causal relationship, advances in quantification methods soon led to data which showed this relationship did in fact exist. It has been shown that those with the highest levels of Lp(a) are at a 1.5x increased risk of cardiovascular-related death, 1.6x risk of stroke, and up to 4x risk of heart attack when compared with those with the lowest levels5.
Accurate measurement of Lp(a) is crucial in determining CVD risk. Quantification methods which account for the size-related variability of Lp(a) molecules are known to produce less bias when compared with those which do not. The Randox Lp(a) reagent is based on the Denka Seiken method which has been shown to produce minimal size-related bias. This assay has FDA 510(K) clearance, illustrating its reliability and safety. Furthermore, the Randox Lp(a) assay is reported in nmol/L, is traceable to the WHO/IFCC reference material, and provides acceptable bias compared with the Northwest Lipid Metabolism Diabetes Research Laboratory (NLMDRKL) gold standard method.
Physiology and Genetics
Synthesised mainly in the liver, Lp(a), like Low-density lipoprotein (LDL) cholesterol, is composed of a lipid centre made of cholesteryl esters and triacylglycerols, surrounded by a shell of phospholipids, free cholesterol, and an apoB-100 molecule. The major difference between other LDL cholesterol molecules and Lp(a) is the presence of a polymorphic glycoprotein, apo(a), bound to apoB-100 by a single disulphide bond5. It is this apo(a) molecule which contributes to Lp(a)’s pathophysiology.
Apo(a) is thought to have evolved from the plasminogen gene (PLG) around 40 million years ago and shares 78-100% sequence homology within the untranslated and coding regions of the fibrinolytic enzyme1. Like plasminogen, apo(a) contains unique domains named kringles4. While plasminogen contains 5 different kringle structures (KI to KV), apo(a) has lost KI through KIII and instead contains several forms of KIV, namely, 1 copy of KIV1 and KIV3-10, 1-40 copies of KIV2, 1 copy of KV and an inactive protein domain at the carboxyl terminus of the molecule7. These hydrophilic subunits are highly polymorphic due to the variation in KIV2 repeats.
Individuals may possess two different isoforms of apo(a), one of which will have been passed down from each parent, that are expressed codominantly1. These isoforms are dependent on the number of KIV2 repeats they contain2. Isoforms with less KIV2 repeats produce smaller apo(a) isoforms which are found at a higher concentration compared with larger isoforms6 due to the increased rate at which the smaller molecules can be synthesised4. The polymorphisms in KIV2 repeats account for up to 70% of the variation seen in concentration between individuals, with the remainder being attributed to differences in protein folding, transport, and single nucleotide polymorphisms (SNPs)4. SNPs are central in the heterogeneity of apo(a), effecting RNA splicing, nonsense mutations and 5’ untranslated region of the LPA gene resulting in shorter gene translation4,6.
Mass versus Molar?
The quantification of Lp(a) levels is essential in evaluating CVD risk, yet the units of measurement—mass (mg/dL) versus molar (nmol/L) – play a critical role in the accuracy and reliability of these assessments. Historically, Lp(a) levels have been expressed in mass units (mg/dL), but recent advances advocate for the use of molar units (nmol/L) due to their ability to account for molecular variability7.
Mass measurement of Lp(a) quantifies the total mass of Lp(a) particles in a given volume of blood, expressed in milligrams per decilitre (mg/dL). This method has been widely used and aligns with other lipid measurements such as cholesterol and triglycerides8. However, it does not account for the significant variability in the size and composition of Lp(a) particles. This can result in an overestimation of Lp(a) concentration in those with large apo(a) isoforms, and conversely underestimation of concentrations in patients with small apo(a) isoforms9. Consequently, two individuals with the same mass concentration of Lp(a) may have vastly different particle numbers and sizes, leading to potential discrepancies in risk assessment10.
In contrast, molar measurement expresses the concentration of Lp(a) particles in terms of their molar quantity, measured in nanomoles per litre (nmol/L). This approach provides a more accurate reflection of the number of Lp(a) particles present, irrespective of their size11. By focusing on particle count rather than mass, molar measurement offers a standardised and minimally biased method that better accounts for the heterogeneity of Lp(a) particles12.
The conversion between mass and molar units is not straightforward due to the variability in the molecular weight of Lp(a) particles. A commonly used conversion factor is approximately 2.5, meaning 1 mg/dL of Lp(a) is roughly equivalent to 2.5 nmol/L13. However, this factor can vary depending on the specific characteristics of the Lp(a) particles in a given sample. For this reason, converting between units is discouraged by various relevant organisations including the European Atherosclerosis (EAS)6.
Clinical guidelines and risk assessments have traditionally been based on mass concentrations, but the shift towards molar units is gaining traction. The Randox Lp(a) assay, which reports in nmol/L and is traceable to the WHO/IFCC reference material, exemplifies this trend. This assay not only provides a more accurate measurement but also aligns with the NLMDRKL gold standard method, ensuring minimal size-related bias14.
The choice between mass and molar measurements has significant clinical implications. Accurate assessment of Lp(a) levels is crucial for identifying individuals at risk of CVD and implementing appropriate interventions. As the understanding of Lp(a) continues to evolve, the adoption of molar measurement is expected to enhance the precision and reliability of Lp(a) testing, ultimately improving patient outcomes.
Randox Lp(a) Reagent
For the reasons above, the European Atherosclerosis Society (EAS) recommends that Lp(a) measurement is of the particles (molar) rather than the total mass, to provide a result with minimal size-related bias.
The Randox Lp(a) assay has FDA 510(K) clearance and is one of the only methodologies on the market that detects the non-variable part of the Lp(a) molecule and therefore suffers minimal size related bias providing more accurate and consistent results. The Randox Lp(a) kit is standardised to the WHO/IFCC reference material, SRM 2B, and is the closest in terms of agreement to the ELISA reference method. We also provide a five-point calibrator with accuracy-based assigned target values which accurately reflects the heterogeneity of isoforms present in the general population. 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.
Features
- Excellent Correlation and Precision: The Randox Lp(a) assay demonstrates excellent performance, evidenced by a correlation coefficient of r=0.995 when compared with other commercially available methods and a within-run precision of less than 2.54%.
- 510(K) Cleared: Randox’s Lp(a) assay has received FDA 510(k) clearance, signifying its safety and effectiveness and ensuring healthcare professionals can trust its accurate and reliable cardiovascular risk assessments.
- Dedicated Five-Point Calibrator Available: Five-point calibrator with accuracy-based assigned target values (in nmol/l) is available, accurately reflecting the heterogeneity of the apo(a) isoforms. Dedicated Lp(a) control is available offering a complete testing package.
- WHO/IFCC Reference Material: The Randox Lp(a) assay is reported in nmol/l and traceable to the WHO/IFCC reference material (IFCC SRM 2B) and provides an acceptable bias compared with the Northwest Lipid Metabolism Diabetes Research Laboratory (NLMDRKL) gold standard method.
- Applications Available: Applications are available detailing instrument-specific settings for the convenient use of the Randox Lp(a) assay on a wide range of clinical chemistry analysers.
- Liquid Ready-To-Use: The Randox Lp(a) assay is available in a liquid ready-to-use format for convenience and ease-of-use.
One study15 compared 5 commercially available Lp(a) assays on an automated clinical chemistry analyser. The assays tested were manufactured by Diazyme, Kamiya, MedTest, Roche, and Randox. The authors show that all the assays tested met the manufacturers claims for sensitivity, linearity, and precision. However, significant bias was observed in 4 out of 5 assays. The only assay which did not display significant bias was the Randox Lp(a) Assay which is traceable to WHO/IFCC reference material. This report highlights the importance of measuring and reporting Lp(a) in molar concentration rather than in mass units to facilitate standardisation and harmonisation in Lp(a) testing15.
Conclusions
In conclusion, understanding and accurately measuring Lp(a) is crucial for assessing CVD risk. Despite its enigmatic nature, recent advancements have clarified Lp(a)’s role as a significant independent risk factor for CVD. The shift from mass to molar measurement units is enhancing the precision and reliability of Lp(a) assessments, with the Randox Lp(a) assay leading the way in providing minimal size-related bias and accurate results.
To ensure the most accurate and reliable assessment of your patients’ cardiovascular risk, consider integrating the Randox Lp(a) assay into your diagnostic toolkit. With its FDA 510(k) clearance, traceability to WHO/IFCC reference material, and high precision, the Randox Lp(a) assay is an essential component for any modern clinical laboratory.
Integrate the Randox Lp(a) assay into your practice today to enhance the precision of your cardiovascular risk evaluations.
References
- Schmidt K, Noureen A, Kronenberg F, Utermann G. Structure, function, and genetics of lipoprotein (a). J Lipid Res. 2016;57(8):1339-1359. doi:10.1194/jlr.R067314
- Zafrir B, Aker A, Saliba W. Extreme lipoprotein(a) in clinical practice: A cross sectional study. International Journal of Cardiology Cardiovascular Risk and Prevention. 2023;16:200173. doi:10.1016/j.ijcrp.2023.200173
- Dal Pino B, Gorini F, Gaggini M, Landi P, Pingitore A, Vassalle C. Lipoprotein(a), Cardiovascular Events and Sex Differences: A Single Cardiological Unit Experience. J Clin Med. 2023;12(3):764. doi:10.3390/jcm12030764
- Stürzebecher PE, Schorr JJ, Klebs SHG, Laufs U. Trends and consequences of lipoprotein(a) testing: Cross-sectional and longitudinal health insurance claims database analyses. Atherosclerosis. 2023;367:24-33. doi:10.1016/j.atherosclerosis.2023.01.014
- Scheel P, Meyer J, Blumenthal R, Martin S. Lipoprotein(a) in Clinical Practice. Latest in Cardiology. Published online July 2, 2019. Accessed March 22, 2024. https://www.acc.org/Latest-in-Cardiology/Articles/2019/07/02/08/05/Lipoproteina-in-Clinical-Practice
- Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925-3946. doi:10.1093/eurheartj/ehac361
- Kronenberg F. Lipoprotein(a) measurement issues: Are we making a mountain out of a molehill? Atherosclerosis. 2022;349:123-135. doi:10.1016/j.atherosclerosis.2022.04.008
- Scharnagl H, Stojakovic T, Dieplinger B, et al. Comparison of lipoprotein (a) serum concentrations measured by six commercially available immunoassays. Atherosclerosis. 2019;289:206-213. doi:10.1016/j.atherosclerosis.2019.08.015
- Tsimikas S. A Test in Context: Lipoprotein(a). J Am Coll Cardiol. 2017;69(6):692-711. doi:10.1016/j.jacc.2016.11.042
- Kamstrup PR. Lipoprotein(a) and Cardiovascular Disease. Clin Chem. 2021;67(1):154-166. doi:10.1093/clinchem/hvaa247
- Langsted A, Kamstrup PR, Nordestgaard BG. High lipoprotein(a) and high risk of mortality. Eur Heart J. 2019;40(33):2760-2770. doi:10.1093/eurheartj/ehy902
- Afshar M, Rong J, Zhan Y, et al. Risks of Incident Cardiovascular Disease Associated With Concomitant Elevations in Lipoprotein(a) and Low‐Density Lipoprotein Cholesterol—The Framingham Heart Study. J Am Heart Assoc. 2020;9(18). doi:10.1161/JAHA.119.014711
- Zheng W, Chilazi M, Park J, et al. Assessing the Accuracy of Estimated Lipoprotein(a) Cholesterol and Lipoprotein(a)‐Free Low‐Density Lipoprotein Cholesterol. J Am Heart Assoc. 2022;11(2). doi:10.1161/JAHA.121.023136
- Madsen CM, Kamstrup PR, Langsted A, Varbo A, Nordestgaard BG. Lipoprotein(a)-Lowering by 50 mg/dL (105 nmol/L) May Be Needed to Reduce Cardiovascular Disease 20% in Secondary Prevention. Arterioscler Thromb Vasc Biol. 2020;40(1):255-266. doi:10.1161/ATVBAHA.119.312951
- Wyness SP, Genzen JR. Performance evaluation of five lipoprotein(a) immunoassays on the Roche cobas c501 chemistry analyzer. Pract Lab Med. 2021;25:e00218. doi:10.1016/j.plabm.2021.e00218
Blood test for over-40s could save the economy Ā£12bn a year if offered on NHS – OCO report
The NHS currently offers health MOTs to patients aged 40 to 75. However, the five-yearly check is normally limited to blood pressure and cholesterol, along with height, weight and waist measurements.
Diagnostic firms sell private blood tests which can check for 200 types of disease, including most common cancers.
A report by OCO Global, an independent consultancy firm, says that if the NHS provided these more comprehensive health checks, problems would be detected far earlier, ultimately saving lives and money.
The research, which has been sent to Wes Streeting, the Health Secretary says that although each check would cost around Ā£230 – a bill for the NHS of around Ā£650 million a year – they would reap major rewards.
Modelling suggests that, after 16 years, the annual boost to the economy would amount to Ā£11.7 billion – Ā£1.83 billion in treatment costs, around Ā£5.8 billion wider savings from health improvements and an indirect benefit of Ā£4 billion – based on the assumption that around half of people take up the tests.
The report was commissioned by Randox, the UK’s biggest diagnostics firm, which carried out millions of PCR tests during the Covid-19 pandemic.
It claims that the blood testās 200 data points would enable far earlier diagnosis, similar to an approach in countries such as Japan and South Korea, where the checks are mandatory and linked to health insurance.
In Japan, which has the highest life expectancy of all G7 nations, such checks have seen a 25 per cent fall in diabetes rates, among those suffering from pre-diabetes rates, among those suffering from pre-diabetes.
The report highlights the intense pressures on the NHS, with waiting list of more than seven million, and 185 million working days lost to sickness every year.
“For too long the UK has been behind the curve on health testing, with less testing carried out than any other developed country. This means that serious diseases are detected too late, with the consequence of more cost for the NHS, more suffering for the patient, and often premature death.ā David Davis, former chairman of the Commons Public Accounts Committee
āImproving the health and prosperity of the nation is a lofty goal – and the report shows this initiative can more than pay for itself.āDr Peter FitzGerald, Randoxās managing director
Words by Laura Donnelly, The Telegraph
Read full article here: https://www.telegraph.co.uk/news/2024/08/04/nhs-cancer-blood-test-save-12bn-research/
Alzheimer’s Disease, ApoE & Risk Detection
Alzheimer’s Disease, ApoE4 & Risk Detection
Alzheimer’s disease touches all of us, whether directly through an affected loved one or through its frequent presence in the news. Alzheimer’s disease is a progressive neurodegenerative disorder characterised by cognitive decline, memory loss, and functional impairments. It is the most common cause of dementia, affecting millions of individuals worldwide 1 and posing significant challenges to healthcare systems. As the global population ages, the prevalence of Alzheimer’s disease is expected to rise, highlighting the urgent need for effective diagnostic and therapeutic strategies.
The current methods used to diagnose Alzheimer’s disease consist of clinical assessment and supporting neuroimaging techniques which can be expensive and, in some cases, fail to provide a definitive diagnosis at the early stages required to facilitate timely intervention and slow disease progression.
With novel therapeutics which aim to slow the progression of Alzheimer’s Disease achieving approval in the United States and being considered for approval in other countries, diagnostics which can identify those at risk of developing this disease are more important than ever. Biomarkers have emerged as vital tools in the early detection and risk assessment of Alzheimer’s disease. Among these, the apolipoprotein E gene (ApoE) has garnered significant attention. The apolipoprotein E protein (ApoE) exists in three common isoforms: ApoE2, ApoE3, and ApoE4. These isoforms combine to form six common genotypes in the general population. Notably, the presence of the ApoE4 allele is associated with a significantly increased risk of developing Alzheimer’s disease.
The Randox ApoE4 Array marks a significant advancement in Alzheimer’s disease biomarkers. This quick and sensitive blood test allows direct ApoE4 genotyping, eliminating the need for traditional molecular techniques. With its fast and accurate results, healthcare providers can efficiently assess an individual’s genetic risk for Alzheimer’s disease.
In this article, we present a summary of our latest whitepaper: Alzheimer’s Disease, ApoE4 & Risk Detection in which we explore the critical role of ApoE genotyping in Alzheimer’s Disease, the innovative technology behind the Randox ApoE4 Array, and its implications for clinical practice. You can download this whitepaper through the link below.
Apolipoprotein E and Alzheimer’s Risk
The ApoE gene transcribes a 229 amino acid protein which primarily functions to mediate lipid transport in the brain and periphery. ApoE is also involved in immune modulation, synapse regeneration, and the clearance/degradation of amyloid-β, a peptide crucial to the development of Alzheimer’s disease2.
There are 3 common isoforms of the human ApoE, differentiated through single nucleotide polymorphisms (SNPs) at amino acid positions 112 and 1582:
These three isoforms combine to produce six common genotypes: E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, and E4/E4. Each genotype is associated with a different level of risk for developing Alzheimer’s disease, with the ApoE4 and ApoE2 isoforms presenting the highest3 and lowest risk 4 respectively.
The structural differences among ApoE isoforms affect their ability to bind lipids, receptors, and amyloid-β, influencing cognitive decline. ApoE2 and ApoE3 bind effectively to HDL (High density lipoprotein), while ApoE4 binds to VLDL (Very low-density lipoprotein), resulting in poor lipidation and toxic aggregates1,2. Cholesterol is crucial for brain function, supporting membrane integrity, signal transduction, and amyloid-β regulation. The interaction of ApoE with amyloid-β regulates amyloid plaque formation, influencing Alzheimer’s disease onset. Cholesterol must be converted to 24S-hydroxycholesterol to cross the blood-brain barrier. Poor cholesterol and phospholipid transport by ApoE4 increases the risk of late-onset Alzheimer’s disease in E4 carriers2.
Randox ApoE Array
The Randox ApoE4 Array is a rapid and highly sensitive blood test that facilitates direct ApoE4 genotyping without the need for traditional molecular techniques. It measures both total ApoE and ApoE4 protein levels directly from a plasma sample, using the ApoE4/total ApoE ratio to classify the ApoE4 status as negative or positive. Additionally, the array can distinguish between heterozygous and homozygous individuals among ApoE4 positive samples, aiding in the assessment of Alzheimer’s disease risk.
Using Randox proprietary chemiluminescent biochip-sandwich immunoassays, the array provides accurate results within three hours from a minimally invasive plasma sample. This method has shown 100% concordance with genotypes achieved through restriction fragment length polymorphism (RFLP) in two separate centres5. Compared to other methods like isoelectric focusing, mass spectrometry, bead-based immunoassay, Sandwich ELISA, and PCR, the Randox ApoE Array offers advantages in speed, simplicity, and automation.
Clinical Implications
The Randox ApoE Array offers significant benefits for managing Alzheimer’s disease through early detection and personalised treatment plans. This minimally invasive blood test identifies individuals at higher genetic risk for Alzheimer’s Disease enabling:
- Timely Interventions: Early identification allows for preventive measures and lifestyle modifications, such as cognitive training and increased physical activity, to delay symptom onset.
- Regular Monitoring: High-risk individuals can be monitored for cognitive changes, enabling early intervention for mild cognitive impairment.
Personalised Treatment Plans
Accurate ApoE genotyping supports personalised treatment:
- Targeted Therapies: ApoE phenotype informs the selection of therapies, especially for ApoE4 carriers.
- Risk Stratification: Patients can be stratified by genetic risk for targeted preventive measures.
- Optimised Medication: Genotype information guides medication choices, enhancing efficacy.
- Family Counselling: Genotyping aids family counselling, advising on preventive measures and monitoring.
Conclusions
The Randox ApoE Array represents a groundbreaking advancement in the early detection and management of Alzheimer’s disease. By providing a rapid, highly sensitive, and minimally invasive method for ApoE genotyping, it empowers healthcare providers to implement timely interventions and personalised treatment plans. This innovative approach not only enhances the accuracy of Alzheimer’s risk assessment but also supports the development of targeted therapies and optimised medication regimens, ultimately improving patient outcomes.
Early detection of Alzheimer’s disease allows for proactive measures that can delay the onset of symptoms, while personalised treatment strategies tailored to an individual’s genetic profile offer a more effective management approach. Furthermore, the array’s capability to provide real-time insights into a patient’s disease stage makes it an invaluable tool in the fight against Alzheimer’s disease.
For a deeper understanding of the critical role of ApoE genotyping in Alzheimer’s disease and the innovative technology behind the Randox ApoE Array, we invite you to download our comprehensive whitepaper be clicking on the image below. You can also visit our website to access this and other valuable resources and to learn more about the Randox ApoE4 Array.
References
- Raulin AC, Doss S V., Trottier ZA, Ikezu TC, Bu G, Liu CC. ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies. Mol Neurodegener. 2022;17(1):72. doi:10.1186/s13024-022-00574-4
- Husain MA, Laurent B, Plourde M. APOE and Alzheimer’s Disease: From Lipid Transport to Physiopathology and Therapeutics. Front Neurosci. 2021;15. doi:10.3389/fnins.2021.630502
- Qian J, Wolters FJ, Beiser A, et al. APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts. PLoS Med. 2017;14(3):e1002254. doi:10.1371/journal.pmed.1002254
- Reiman EM, Arboleda-Velasquez JF, Quiroz YT, et al. Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat Commun. 2020;11(1):667. doi:10.1038/s41467-019-14279-8
- Badrnya S, Doherty T, Richardson C, et al. Development of a new biochip array for APOE4 classification from plasma samples using immunoassay-based methods. Clinical Chemistry and Laboratory Medicine (CCLM). 2018;56(5):796-802. doi:10.1515/cclm-2017-0618
The medical techniques keeping Team GB healthy during the Olympic Games
There was a time when you could count the number of British gold medallists on the fingers of one hand. Back in the 1960s and 1970s, winning an Olympics event made you a household name overnight.
Anne Packer, Lynn Davies, Mary Peters, David Hemery, Anita Lonsbrough, ā to name a few of the few ā were feted across the land to pulling off the seemingly impossible ā beating the world, usually in track and field or the swimming pool.
But all that has changed.
London 2012 (29 gold medals); Rio de Janeiro 2016 (27 gold); Tokyo 2020 but actually in 2021 (22 gold).
Time was when most Olympics hopefuls were fanatical amateurs, prepared to turn out on some bleak and chilly track, strip down to their shorts and practise their sport in front of an equally dedicated but minority audience.
Not any more. The British medals haul, however you measure it, is also top of the tree on an international basis. A country of fewer than 70 million people typically comes in the top three or four on the planet behind only the likes of such giants such as the USA and China. We even beat the Australians ā on a regular basis.
This has not happened by accident.
Obviously, a huge amount of credit must go to the athletes themselves and their coaches. Their talent and dedication will be fully on display in Paris this week when the Games return to France for the first time in exactly 100 years.
But there is much more to it than that.Ā Team GBĀ has revolutionised British Olympics in recent years. The team numbers more than 300 and for only the second time in our history, there will be more women (172) than male (155) competitors.
Professional coaches, physios, nutritionists, and mind game experts will abound.
The Greatest Show on Earth will dominate our TV screens, social media, press and national conversation for a fortnight (and more).
These are some of the reasons why Randox, Europeās biggest diagnostic company, is sponsoring Team GB. We love supporting the athletes behind mega sporting events (The Grand National, for instance) and it does not come any more mega than Paris 2024.
We were there the last time ā Tokyo 2020 ā but in challenging circumstances. Tokyo 2020 actually took place in 2021, postponed for a year because of theĀ CovidĀ pandemic.The glittering contests were performed in front of empty stadiums and sports halls after the Olympic authorities, understandably anxious to avert a super-spreader car crash, prohibited spectators.
Founded in 1982, Randox conducted more than 27 millionĀ CovidĀ tests in the UK and offered support to Team GB three years ago for a very specific and vital purpose ā to help stop the spread ofĀ CovidĀ among the athletes and their support teams. It worked. Despite the fears of the Olympic authorities, the plethora of measures taken to safeguard contestants, meant that only one athlete fell sick and was unable to compete.
Not so this time. 15 million people, two million from abroad, are expected to swamp the French capital over late July and early August.
Our Vivalytic diagnostic machine, used in Tokyo to test all our athletes forĀ Covid, will be in action again. But this time, we will be casting the net far wider, checking for a range of respiratory infections that can lay contestants low.
Our aim, along with the teams of experts assisting our athletes is simple ā to ensure that Team GB is in peak physical and mental condition as they get to the starting line.
We have also been working closely with our brand ambassadors to ensure that they are perfectly placed to perform to their utmost in Paris. All of them have undertaken our Everyman and Everywoman diagnostic health testing packages at one of our health clinics, to measure their condition as they prepare for Paris.
As one star, Duncan Scott, our most decorated Olympic swimmer, put it: āIf it makes one per cent difference, itās 100 per cent worth it.
āIt excited me that it was essentially a head-to-toe MOT and thereās areas Iāve never really had much data, on but also last year I had an IgE (antibody) deficiency impacting my immune system which made training so inconsistent as some days I felt sluggish.
āThis year has been much more consistent after picking up on it which makes me wish I had something like this, as if I did this last year or 24 months ago, itād have been ideal going in unknown and then picking up on it as a risk rather than me getting frustrated and being ill.ā
Top sprinter Daryll Neita, a multiple medal winner, took the Everywoman test, āthe most in-depth testing Iāve ever had.ā
Her verdict points to the confidence boost of knowing you are in peak condition physically: āAlthough Iāve not had any recent health concerns, itās amazing that the Everywoman test discovers things that could help my performance.
āWhether itās how I recover or deficiencies, but also our sport is about marginal gains, centimetres, millimetres, the finest of margins and through tests like this, it lets you stay on-top of your health, helping you achieve optimal performance or even a mental boost that youāre healthy.ā
Team GBās Chief Medical Officer Niall Elliott, said that Randox was helping in three critical areas of health testing for athletes ā iron metabolism, vitamin D levels – critical to the immune system and muscle power – and glucose or energy levels. āIt is a fascinating journey, the testing we can do.ā
This must be the best prepared ā and the most safeguarded ā Team GB ever to leave our shores.
As devotees of the wonderful film, Chariots of Fire, will know, they have much to live up to. Back in the 1924 Paris Olympics, Harold Abrahams in the 100 metres and Eric Liddell in the 400 metres both emerged triumphant. On top of their legendary feats, Britain secured seven more gold medals.
We can only hope and pray that our champions, bolstered by the latest in sports science, can achieve even greater heights.
Words by Dr. Peter FitzGerald, Sunday Express https://www.express.co.uk/news/politics/1925873/medical-techniques-keeping-team-gb
Active vs Total Vitamin B12
Total vs Active B12
Vitamin B12, or cobalamin, is a vital water-soluble vitamin that plays an essential role in myelination initiation and development, cellular energy and fatty acid metabolism. It is a cofactor for enzymes methionine synthase and L-methyl-malonyl-coenzyme A mutase and, in addition to folate, is essential for DNA and protein synthesis. In the UK, up to 6% of adults under 60 have been diagnosed with Vitamin B12 deficiency and figures are much higher in elderly populations1. Additionally, these data do not consider the high rates of missed diagnosis associated with B12 deficiency, which some reports claim to be as high as 26%2. New guidance from the National Institute of Health and Care Excellence (NICE) advise that Active vitamin B12 testing is recommended for some groups of patients. In this article, we’ll look at this essential vitamin, B12 deficiency and the associated complications, compare the biomarkers used to diagnose B12 deficiency, and finally, present the new Acusera Active B12 Control.
Aetiology
Vitamin B12 deficiency can arise due to dietary insufficiency, malabsorption resulting from damage to the small intestine, often caused by conditions like Coeliac disease or Crohn’s disease, or via pernicious anaemia – an autoimmune condition which results in an inability to absorb vitamin B12.
It is a common problem in the elderly population – bodily stores of vitamin B12 can take up to 20 years to become depleted, meaning complications have often already begun before diagnosis occurs. The most common source of vitamin B12 comes from dietary intake of animal products therefore vegetarian dietary requirements are considered a considerable risk factor for vitamin B12 deficiency.
Pathophysiology and Complications
Vitamin B12 deficiency significantly impacts health, affecting various bodily functions, potentially leading to a range of complications. Megaloblastic anaemia is a common complication associated with vitamin B12 deficiency and is characterised by the presence of large red blood cell precursors (megaloblasts) in the bone marrow3. The lack of vitamin B12 results in impaired DNA synthesis and an inhibition of nuclear division. However, cytoplasmic maturation is less effected. This results in asynchronous maturation of the nucleus and cytoplasm in erythrocytes and causes the synthesis of abnormally large megaloblasts. This causes the cessation of DNA synthesis and DNA replication errors, culminating in apoptotic cell death. Common symptoms of megaloblastic anaemia include weakness, shortness of breath, palpitations, tachycardia, Hunter glossitis or splenomegaly3.
Pernicious anaemia is a condition commonly associated by vitamin B12 deficiency. Pernicious anaemia is an autoimmune disorder which affects the gastric mucosa resulting in impaired absorption of vitamin B12. Common symptoms of pernicious anaemia include glossitis, hair loss, dry skin, memory loss, poor concentration, poor sleep, confusion and dizziness, shortness of breath, Diarrhoea, indigestion, loss of appetite, mood swings and suicidal thoughts.
Neurological issues may also arise, including numbness, mobility loss, and memory issues, and in some cases, depression4. Additionally, B12 deficiency is linked to increased risks of cardiovascular events5, infertility6, and autoimmune diseases like multiple sclerosis7 and lupus8. In children, vitamin B12 deficiency can manifest as failure of brain and overall growth and development, developmental regression, hypotonia, lethargy, hyperirritability, or coma9.
Active B12 as a marker of Deficiency
There are several markers of vitamin B12 deficiency. The most used in clinical practice are total vitamin B12, homocysteine, methylmalonic acid (MMA), and Holotranscobalamin (HoloTC) – also known as Active B12. HoloTC accounts for between 10-30% of total B12 and is the metabolically active form of vitamin B12.
When compared with total B12 quantification, HoloTC measurement has been shown to be a more sensitive and specific biomarker of B12 deficiency, particularly at borderline clinical levels10, in various cohorts11,12 including those on vegan diets13 – a known risk factor for B12 deficiency. Furthermore, HoloTC was shown to provide the higher diagnostic accuracy in clinical and subclinical B12 deficiency versus Total B12, MMA and homocysteine with significantly higher accuracy in women over 5011 – a population at high risk of B12 deficiency.
In response to the mounting evidence of the superior utility of HoloTC quantification, the National Institute for Health and Care Excellence (NICE) have produced new guidelines recommending either total B12 or HoloTC for the initial testing of suspected vitamin B12 deficiency. These guidelines specify the use of active B12 during pregnancy and suggest that active B12 might provide a more specific assessment in certain clinical contexts.
Acusera Active B12 Control
For the reasons stated above, Randox are proud to present the Acusera Active Vitamin B12 Control. This control is designed for use with in vitro diagnostic assays for the quantitative determination of HoloTC in human serum and plasma and is suitable for use on a variety of analysers. This true third-party control is provided in a liquid ready-to-use format reducing preparation time and has an impressive 30-day open vial stability, helping to minimise waste. Like all Acusera controls, the Active B12 Control is supplied at consistent, clinically relevant levels to ensure the test system is challenged at the critical decision limits used to aid diagnosis. Furthermore, this control is provided with assayed target values for a range of analysers which are available through our new SmartDocs portal.
Summary of Benefits:
- Dedicated, HoloTC control.
- 30-day Open Stability.
- 2-year shelf life.
- Liquid Ready-to-use.
- Human Serum Based.
- Consistent, clinically significant values.
- True third-party controls.
- Assayed target values.
Ensure the accuracy of your vitamin B12 testing with Randox’s Acusera Active Vitamin B12 Control. Join the other laboratories around the world who trust Acusera to help deliver reliable, clinically relevant test results. Contact us today at marketing@randox.com to learn more and order your supply of the Acusera Active B12 Control.
References
- Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014;349(sep04 1):g5226-g5226. doi:10.1136/bmj.g5226
- Oh RC, Brown DL. Vitamin B 12 Deficiency Clinical Manifestations of Vitamin B 12 Deficiency. Vol 67.; 2003. www.aafp.org/afp
- Hariz A, Bhattacharya PT. Megaloblastic Anemia. StatPerals Publishing; 2024.
- Patel S V., Makwana AB, Gandhi AU, Tarani G, Patel J, Bhavsar V. Factors associated with vitamin B12 deficiency in adults attending tertiary care Hospital in Vadodara: a case control study. Egypt J Intern Med. 2022;34(1):11. doi:10.1186/s43162-022-00104-0
- Pawlak R, Parrott SJ, Raj S, Cullum-Dugan D, Lucus D. How prevalent is vitamin B12 deficiency among vegetarians? Nutr Rev. 2013;71(2):110-117. doi:10.1111/nure.12001
- Green R, Graff JP. Megaloblastic Anemia. In: Atlas of Diagnostic Hematology. Elsevier; 2021:47-51. doi:10.1016/B978-0-323-56738-1.00004-X
- Najafi MR, Shaygannajad V, Mirpourian M, Gholamrezaei A. Vitamin B(12) Deficiency and Multiple Sclerosis; Is there Any Association? Int J Prev Med. 2012;3(4):286-289.
- Segal R, Baumoehl Y, Elkayam O, et al. Anemia, serum vitamin B12, and folic acid in patients with rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus. Rheumatol Int. 2004;24(1):14-19. doi:10.1007/s00296-003-0323-2
- Stabler SP. Vitamin B12 Deficiency. New England Journal of Medicine. 2013;368(2):149-160. doi:10.1056/NEJMcp1113996
- Bondu JD, Nellickal AJ, Jeyaseelan L, Geethanjali FS. Assessing Diagnostic Accuracy of Serum Holotranscobalamin (Active-B12) in Comparison with Other Markers of Vitamin B12 Deficiency. Indian Journal of Clinical Biochemistry. 2020;35(3):367-372. doi:10.1007/s12291-019-00835-y
- Jarquin Campos A, Risch L, Nydegger U, et al. Diagnostic Accuracy of Holotranscobalamin, Vitamin B12, Methylmalonic Acid, and Homocysteine in Detecting B12 Deficiency in a Large, Mixed Patient Population. Dis Markers. 2020;2020:1-11. doi:10.1155/2020/7468506
- Verma A, Aggarwal S, Garg S, Kaushik S, Chowdhury D. Comparison of Serum Holotranscobalamin with Serum Vitamin B12 in Population Prone to Megaloblastic Anemia and their Correlation with Nerve Conduction Study. Indian Journal of Clinical Biochemistry. 2023;38(1):42-50. doi:10.1007/s12291-022-01027-x
- Lederer AK, Hannibal L, Hettich M, et al. Vitamin B12 Status Upon Short-Term Intervention with a Vegan Diet—A Randomized Controlled Trial in Healthy Participants. Nutrients. 2019;11(11):2815. doi:10.3390/nu11112815
Bordetella Detection & Species Identification Educational Guide
Bordetella Detection and Species Identification with the Vivalytic
Cases of Bordetella infections are rising across Europe. Bordetella species are responsible for whooping cough, or pertussis, which literally means violet cough. Vaccine deployment in the 1940s saw a reduction in the morbidity and mortality associated with these infections and now, healthy adults can be expected to make a full recovery. However, vulnerable populations, such as children, the elderly and the immunocompromised, have been shown to be at increased risk of more severe and long-lasting side effects, including increased risk of mortality.
Traditional methods of identifying Bordetella infections take the form of culture, which can take up to 7 days due to the fastidious and slow-growing nature of these bacteria and provide limited sensitivity1,2. To provide a faster and more sensitive method for the identification of whooping cough pathogens, Randox, in partnership with Bosch, are proud to introduce the Vivalytic Bordetella Cartridge. This real-time PCR assay allows detection of B. pertussis, B. parapertussis and B. holmesii on the Vivalytic system, a universal, fully automated, cartridge-based platform enabling high-plex and low-plex testing, providing an all-in-one solution for molecular diagnostics.
To help you understand the implications of Bordetella infections and those of the Vivalytic system, we have produced a new educational guide, covering the Bordetella species responsible for whooping cough; the pathophysiology and complications associated with these infections; the Vivalytic platform and the benefits it can bring to your laboratory; and finally, a summary of findings presented at ESCMID 2024 in which the Vivalytic Bordetella cartridge showed excellent results. Here, we present this educational guide and a summary of its contents. You can download this guide for free by clicking the download link below.
The Scale of the Bordetella Problem
The rates of positive identification of Bordetella infection are increasing throughout Europe. In England, between January and March 2024, there were 2793 laboratory confirmed cases of whooping cough causing the deaths of 5 infants, compared with a total of 858 cases in 20233. A rudimentary projection model estimates that without intervention, whooping cough cases in the England could total over 15,000 cases by the end of 2024. Rising cases are not isolated to the UK – increased rates of diagnosis have also been reported in Denmark, Spain, and Croatia4. Increased numbers of infections illustrate the need for novel and rapid diagnostics to identify those who have been infected and help reduce the transmission of these bacteria.
Bordetella genus
Bacteria of the Bordetella genus are gram-negative coccobacilli5 which are important pathogens in human medicine as they colonise the respiratory tract leading to a range of pulmonary and bronchial infections6. There are 3 main species associated with whooping cough: of B. pertussis, B. parapertussis (Classical Bordetella) and B. holmesii (pertussis-like disease pathogen).
Pertussis is caused by Classical Bordetella: B. pertussis and B. parapertussis. Despite widespread vaccination cases are rising, partially due to waning immunity. Pertussis is highly contagious and particularly dangerous for infants, who account for most pertussis-related deaths. The disease progresses through three phases: catarrhal (cold-like symptoms), paroxysmal (severe coughing fits), and convalescent (persistent cough). Classical Bordetella species share over 98% DNA sequence similarity and share many crucial virulence factors like toxins adenylate cyclase toxin (ACT), pertussis toxin (PXT), and dermonecrotic toxin5 yet there are variations in potential hosts and disease. For example, B. pertussis is an exclusively human pathogen, whereas B. parapertussis can infect both humans and sheep6.
Bordetella holmesii causes pertussis-like symptoms but is ofen less severe. Unlike classical Bordetella, B. holmesii can cause bacteraemia, especially in immunocompromised individuals. Accurate diagnosis of B. holmesii remains challenging due to its similarities with other Bordetella species.
Whooping cough can lead to complications such as pneumonia, which may develop if fever persists beyond the catarrhal phase2. CNS complications like seizures and encephalopathy occur in less than 2% of cases, often due to hypoxia, hypoglycaemia, toxins, or secondary infections2. Bordetella toxins, especially PXT, increase histamine sensitivity and insulin secretion. Infants are especially at risk of bradycardia, hypotension, and cardiac arrest.
Vivalytic Bordetella Cartridge
To enhance the detection and species identification of Bordetella, Randox introduces the Vivalytic Bordetella cartridge. This user-friendly assay is designed to detect B. pertussis, B. parapertussis, and B. holmesii from a single nasopharyngeal swab or aspirate sample. Utilising Real-time PCR, it enables rapid and accurate detection up to four weeks after symptom onset, differentiating between human pathogenic Bordetella species. With a time to result of just 47 minutes, this assay is invaluable for patient diagnosis and the containment of Bordetella, helping to reduce aerogenic transmission.
Summary of Benefits:
- Sample Volume – 300μl.
- Sample Type – Nasopharyngeal swab sample or aspirates.
- Real-time PCR detection.
- Time to result – ~47 minutes.
- Detection of B. pertussis, B. parapertussis, and B. holmesii.
Rapid and Accurate Detection of Whooping Cough in Clinical Samples
Zimmerman, 2024
At the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2024 congress, the Vivalytic Bordetella array showed excellent performance, with a 97.7% concordance and a 97.9% positive percent agreement (PPA) with the reference method.7 It accurately identified all additional positive samples and maintained over 98% PPA across spiked samples, even at low levels. The system’s invalid result rate was notably low at 0.6%, compared to 2.9% with the BioGX assay7.
The conclusions drawn from this investigation are as follows:
- The Vivalytic Bordetella cartridge provided excellent concordance with a sensitive reference method and delivered fast and accurate results.
- This assay is ideal for both hospital laboratories and outpatient settings, thanks to its user-friendly design and quick turnaround times.
- Early identification of infected patients will aid in preventing the spread of re-emerging whooping cough epidemics.
Conclusion
As Bordetella infections rise across Europe, rapid and accurate detection is crucial. The Vivalytic Bordetella Cartridge offers a fast, reliable solution, identifying B. pertussis, B. parapertussis, and B. holmesii with high accuracy in just 47 minutes. This advanced diagnostic tool can help reduce transmission and manage whooping cough effectively.
Take control of your diagnostic capabilities and ensure the best care for your patients. Download our comprehensive educational guide to learn more about Bordetella infections and the benefits of the Vivalytic system.
For more information on the Vivalytic, the panels mentioned, or any of our products, don’t hesitate to reach out to us at marketing@randox.com.
References
- Lauria AM, Zabbo CP. Pertussis. StatPearls Publishing; 2024. Accessed June 12, 2024. https://www.ncbi.nlm.nih.gov/books/NBK519008/
- Pittet LF, Posfay-Barbe KM. Bordetella holmesii: Still Emerging and Elusive 20 Years On. Microbiol Spectr. 2016;4(2). doi:10.1128/microbiolspec.EI10-0003-2015
- UK Health and Security Agency. Confirmed Cases of Pertussis in England by Month.; 2024.
- Smout E, Mellon D, Rae M. Whooping cough rises sharply in UK and Europe. BMJ. Published online April 2, 2024:q736. doi:10.1136/bmj.q736
- Rivera I, Linz B, Harvill ET. Evolution and Conservation of Bordetella Intracellular Survival in Eukaryotic Host Cells. Front Microbiol. 2020;11. doi:10.3389/fmicb.2020.557819
- Hamidou Soumana I, Linz B, Harvill ET. Environmental Origin of the Genus Bordetella. Front Microbiol. 2017;8. doi:10.3389/fmicb.2017.00028
- Zimmerman S. Rapid and Accurate Detection of Whooping Cough in Clinical Samples.; 2024.
