ACB...ACB Scotland National Autumn Meeting Celebrating the Career of Dr Bill Bartlett Friday 9th...

In this issue

199 andCounting

Mike’s EpicCycle Ride

Updated Verification/Validation Programs

National CongenitalAnomaly andRare Disease RegistrationService

TransformingLaboratoryMedicine inScotland

Biotin Interference inImmunoassays

Brexit

The Association for Clinical Biochemistry & Laboratory Medicine | Issue 655 | October 2018

ACBNews

About ACB NewsThe Editor is responsible for the finalcontent; advertisers are responsible for thecontent of adverts. Views expressed are not necessarily those of the ACB.

Lead EditorMr Ian HanningRetiredFormerly Department of Clinical ChemistryHull Royal InfirmaryEmail: [email protected]

Associate Editors Mrs Sophie BarnesDepartment of Clinical BiochemistryCharing Cross HospitalEmail: [email protected]

Dr Gina Frederick Pathology LaboratoryRoyal Derby HospitalEmail: [email protected]

Mrs Nicola Merrett Department of Laboratory MedicineUniversity Hospital Southampton NHSFoundation TrustEmail: [email protected]

Dr Christopher PittDepartment of BiochemistryNHS Ayrshire & ArranEmail: [email protected]

Dr Derren Ready National Infection ServicePublic Health England Email: [email protected]

Situations Vacant AdvertisingPlease contact the ACB Office:Tel: 0207-403-8001 Fax: 0207-403-8006Email: [email protected]

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ACB PresidentProfessor Ian YoungTel: 028-9063-2743Email: [email protected]: @ACBPresident

ACB Home Pagehttp://www.acb.org.uk

Printed by Swan Print Ltd, BedfordISSN 1461 0337© Association for Clinical Biochemistry &Laboratory Medicine 2018

ACBNews

General News page 4

Council Nomination Form page 12

Microbiology News page 13

Practice FRCPath Style Calculations page 14

Current Topics page 16

Focus News page 23

BIVDA News page 26

Meeting Report page 28

Obituary page 29

ACB News Crossword page 30

Issue 655 • October 2018

The bi-monthly magazine for clinical science

Issue 655 | October 2018 | ACB News

Front cover: Mike Bosomworth,Director of Finance, taking a well-earned rest on his sponsoredcycle ride across Canada

Hyperkalaemia AlertIn August the ACB receivedcorrespondence about NHSI safety alertNHS/PSA/RE/2018/006 relating to themanagement of hyperkalaemia:https://www.cas.mhra.gov.uk/ViewAndAcknowledgment/viewAlert.aspx?AlertID=102787While the content of this is clearly

relevant to NHS laboratories, the ACB wasnot consulted about the alert and had noprior warning that it was to be released.The ACB believes that good practice in

UK laboratories should already address theissues highlighted, and in addition theimportance of considering pre-analyticalfactors when interpreting results, but it isclearly important for all laboratories toreview their procedures in light of thealert and supporting documents to ensurethat they are appropriate. �

4 | General News


SudokuThis month’s puzzle

Solution for August

CondolencesIt is with regret that we must inform youof the sad news that ACB Retired andFounder Member, Miss Jean WalkerSummerscales, died on 17th May 2018 atthe age of 93.Miss Summerscales joined the

Association in 1953 as a Founder Member,was based in Leeds, and retired from full-time employment in 1992. �

FiLM 2019Please note that FiLM 2019will be held on 29th & 30thJanuary 2019 at the usualvenue, Austin Court,

Birmingham. For furtherdetails, please see the advert on page 31. �

Director of ClinicalPracticeIn accordance with the provision ofArticles 14 and Bye-law 6, nominations arecalled for the position of Director ofClinical Practice. Nominations for thisposition, duly countersigned, should bemade on the nomination form on page 12 in this issue of ACB News and sentbefore 31st October 2018 to: ACB Administrative Office, 130-132 TooleyStreet, London SE1 2TU. �

This ride has proved to be a much biggerchallenge than my ride across the USA,primarily I think because the roads aremuch more difficult, if not at timesdownright dangerous. On the whole,there is no alternative to the maintransCanadian route (Highway 1 or 17depending on the province). Consequentlyone just has to ride on a very narrowhardshoulder, or in the traffic itself. The Canadians, who are extremely friendlyat all times and patient when at a roadjunction, just seem to think that they havethe right to drive at, or above the speedlimit once on the highway, irrespective ofwhat else may be present. The motorisedvehicle is king! I have been run off theroad more than once and even beenreported to the police for riding on thehighway! In Quebec Province the attitudeto cycling is completely different, withhardshoulders or cycleways to ride onmuch of the time. Cyclists are far bettertolerated if not welcome (vivre La Quebec).Unfortunately, I developed saddle sores

early in the ride and they were certainly avery real problem. Fortunately they dideventually begin to heal, but as they did, I developed what I think is metatarsalgia,especially in my right foot. The joys of longdistance cycling!I have been disappointed at the amount

of wildlife that I have seen. No moose andone black bear that was laid at the side ofthe road. In Quebec I have followed theroute of the whales, but sadly none seen.Perversely, just as I hit unseasonably late

snow in the Rockies in the US, here inCanada I hit a heatwave with temperaturesup to 43°C in the Rockies and on the prairies.Enough of the negatives. I have seen

some fantastic sights e.g. the Rockies, the Hoodoos at Drumheller, the dinosaurprovincial park in Saskatchewan. Lake

Superior region was superb and there,Agawa Bay was well worth the visit. Thescenery in Quebec has been spectacular. I have been treated to beer and shared aBBQ with a guy at a motel in Manitoba. I have met some wonderful people andseen some amazing countryside. I am now (10th September) on my way

back to Quebec City having cycled as farup the Gulf of St Lawrence as Moisie, a small village about 20 miles north east ofSept-Iles. I think that I can now fairly claimto have cycled across Canada. Althoughcycling alone, I could not have done itwithout the support of family and friendsback home and those that I have metalong the way. This will almost certainly bemy last solo long distance bike ride. It hasbeen a real challenge (around 4,000 milesthus far) and at the time of writing I stillhave about 500 miles to ride back toQuebec city. That said it has been a realexperience. As is true within the ACB,there are more genuine and friendlypeople in this world than the other kind. It is also true that challenges like this givetime for reflection and make oneappreciate just how important family andfriends really are. If you would like to sponsor me please

visit: www.virginmoneygiving.com/mikebosomworthMany thanks to those who have already

done so. �

6 | General News


Sponsored Cycle Ride . . . An Update (Week 8)Mike Bosomworth, Director of Finance

ACB Scotland National Autumn MeetingCelebrating the Career of Dr Bill Bartlett

Friday 9th November 2018The Station Hotel, Perth PH1 8HE

ACB Scotland would like to announce our forthcoming meeting.Due to generous sponsorship, this meeting is free to attend for ACB Members.

However, prior registration is compulsory and registration forms must be received.

To view the meeting programme and register visit:http://www.acb.org.uk/whatwedo/events/regional_meetings.aspx

We would like to acknowledge the kind support for this meeting fromBIOHIT Healthcare, Alexion and Siemens. �

8 | General News


Updated versions of the ACB AssayVerification/Validation Programs, authoredby Professor Anders Kallner, have recentlybeen uploaded to the ACB website:http://www.acb.org.uk/whatwedo/science/best_practice/measurement_verification.aspxPreviously referred to as spreadsheets

A-D, these have now been renamed to thefollowing:

� Precision (imprecision) and trueness(bias) – previously “Spreadsheet A”

� Trueness (bias)a. From EQA materials - previously “Spreadsheet D”

b. From reference materials –previously “Spreadsheet C”

� ROC analyses (NEW)� Method comparison – previously“Spreadsheet B”

Instruction DocumentsEach program is now associated with aninstruction document (in PDF format) which

provides a brief background to the statisticsused in each case. Each document and itsassociated program are listed under“Program & instructions”.

Example DataDummy/example data are provided foreach spreadsheet under the “Exampledata” heading. Instructions for analysingthese data are given in the associatedinstruction document.

VerificationThese programs have been independentlyverified. Copies of the data used for theirtesting and the associated verificationdocuments are listed under the“Verification document & data” heading ineach case. The code contained within these documents can be copied and pastedinto any instance of the R statisticalcomputing environment (https://www.r-project.org/) and, given the provided testdata in each case, reproduce theverification analysis. �

Updated ACB AssayVerification/Validation ProgramsDr Ed Wilkes, Dr Zahra Khatami and Professor Anders Kallner on behalf ofthe ACB Informatics Special Interest Group

10 | General News


British Mass Spectrometry Society3rd Clinical and Forensic Specialist Group Meeting

Mass Spectrometry in the Clinical LaboratoryThursday 15th November 2018The Foresight Centre – University of Liverpool1 Brownlow Street, Liverpool L69 3GL09:30-10:00 Registration 10:00-10:15 Introduction and Purpose of the Meeting

Andrew Davison and John Dutton, SIG leaders, BMSS10:15-10:45 Historical Development of the Triple Quad Mass Spectrometer

Simon Szwandt, Thermo Scientific10:45-11:15 Coffee Break11:15-11:45 Theory and Principles of Mass Spectrometry

Chris Hopley, LGC, Teddington11:45-12:15 Method Validation in the Clinical Laboratory

Laura Owen, Salford Royal NHS Foundation Trust12:15-12:45 Quantitation in Mass Spectrometry

Lewis Couchman, ASI London12:45-13:30 Lunch13:30-14:00 Automated Mass Spectrometry: Myth or Reality?

Sally Benton, Frimley Park Hospital14:00-14:30 High Resolution Mass Spectrometry and Toxicology

Chris Reeves, Manchester Royal Infirmary14:30-15:15 Coffee Break15:15-15:45 From Mummies to Metabolites

Anna Milan and Andrew Davison, Royal Liverpool and Broadgreen University Hospital NHS Trust

15:45-16:30 Mass Spectrometry-Based Discovery, Development and Delivery of Multiplexed Protein Tests for an Era of Precision MedicineProf Steve Pennington, University College Dublin

16:30-16:40 Closing Comments and Discussion

Approved for CPD from Royal College of Pathologists and Institute of Biomedical Scientists

For further information and booking please visit:http://www.bmss.org.uk/mscl2018/registration.shtml

General News | 11


S A V E T H E D A T E

The All Wales Inherited Metabolic Disease Study Day

Wednesday 6th March 2019Venue : Cardiff

Target audience: Doctors, Nurses, Medical Trainees, Dieticians and Biochemists with an interest in metabolic disease as well as Acute Care Physicians,

Endocrinologists and Paediatricians who wish to update their knowledge on acute general metabolic and storage disorders.

Topics to include metabolic encephalopathy, acute management of metabolic disease,storage disease, mitochondrial disorders, acute porphyria, etc.

Registration: £25.00 to include all refreshments and lunch.

CPD accreditation to be applied for.

For further information and a registration form please contact: Jacqui McAleer, JM Associates, email: [email protected]

12 | Council Nomination Form


Association for Clinical Biochemistry & Laboratory Medicine

Council Nomination Form

Election of Officers/Council Members 2018

We, the undersigned, being Members of the Association nominate

Name ...............……………………………...........................................…..………………………....

Address………………………………………...........................................……………………………

………………………………………...........................................……………………………………...

………………………………………...........................................……………………………………...

for election as Director of Clinical Practice.

Name 1. …………………………… ………………………………………….Capitals Signature



I am willing to undertake the duties and responsibilities of this office if elected.

…………………………… ………………………………………….Signature Date

Please note only Ordinary and Honorary Members of the ACB may be nominated for theposition of Director of Clinical Practice.

If there is more than one nominee for this position, a ballot will be held with all votingmembers. (see Bye-Laws of the ACB items 2 & 3 and 8).

This form, duly countersigned, to be returned to:The Administrative Office

Association for Clinical Biochemistry & Laboratory Medicine130-132 Tooley StreetLondon SE1 2TU

before 31st October 2018

Microbiology News | 13


The Diggle Microbiology ChallengeThese multiple-choice questions, set by Dr Mathew Diggle, are designed with Trainees inmind and will help with preparation for the Microbiology Part 1 FRCPath exam.

Question 9 from August’s ACB NewsWhich drug potentiates the action of sulphonamides?

A) Isoniazid B) Vancomycin C) Nitrofurantoin D) Trimethoprim E) Nalidixic Acid

AnswerD: Trimethoprim: the sulphonamides and trimethoprim are two DNA synthesis inhibitors thatdemonstrate synergy as both compounds inhibit folate synthesis, but act on differentreactions in the synthesis pathway. The sulphonamides act on early folate synthesis whereastrimethoprim acts on late folate synthesis, thus mopping up any pre-cursor molecules thatwere not inhibited by sulphonamide activity. Isoniazid is active against mycobacteria andinhibits mycolic acid synthesis. Vancomycin is a cell wall active agent that acts onpeptidoglycan cross-linking. Nitrofurantoin is a DNA synthesis inhibitor that causes damageto macromolecules such as DNA and ribosomal proteins via the activity of reduced reactiveintermediates. Nalidixic acid is also a DNA synthesis inhibitor, but which acts on DNA gyraseand topoisomerase.

Question 10What would you expect to see in a patient with Streptococcal impetigo?

A) Elevated ASO B) Elevated ASS C) Elevated anti DNase B D) Elevated anti NAD E) Elevated anti hyaluronidase

The answer to Question 10 will appear in the next issue of ACB News – enjoy! �

14 | Practice FRCPath Style Calculations


A 25 year old anorexic female was admitted via A&E with marked emaciation and thefollowing plasma results:

Urea = 1.5 mmol/L Sodium = 120 mmol/LCreatinine = 30 µmol/L Potassium = 2.5 mmol/L

On the ward a repeat blood revealed her plasma osmolality to be 248 mmol/L. A 6 h urinecollection yielded the following results:

Volume = 0.185 LOsmolality = 55 mmol/L

Calculate the free water clearance (in mL/min) and comment on your result.

The first step is to calculate the osmolar clearance (Cosm) which is the volume of plasmafrom which all filterable solutes are removed in any given time period (usually expressedin mL/min). In principle the calculation is identical to any other clearance:

Cosm = Uosm x V

Posm

Where Uosm = urine osmolality = 55 mmol/L

Posm = plasma osmolality = 248 mmol/L

V = urine flow rate in mL/min.

Multiply the volume of urine collected by 1,000 to convert from L to mL, divide by 6 toconvert from 6 h to 1 h, then finally divide by 60 to convert from 1 h to 1 min:

V = 0.185 x 1,000 = 0.514 mL/min (to 3 sig figs)6 x 60

and Cosm = 55 x 0.514 = 0.114 mL/min (to 3 sig figs) 248

The calculated difference between the urine flow rate and the osmolar clearance isknown as the free water clearance (Cwater):

Cwater = V – Cosm = 0.514 - 0.114 = 0.40 mL/min (to 2 sig figs)

The free water clearance is that excreted in addition to that required for excretion of thesolute load. Since the value is positive it represents the volume of water extracted fromthe plasma per minute. In spite of this the patient is still hyponatraemic and is most likelythe result of reduced solute available for excretion (particularly urea) due to poor intake(particularly of protein). The diluting capacity of the renal tubules is limited and thelowest attainable urine osmolality is about 50 mmol/L. With a medium protein diet

Deacon’s Challenge No 198 - Answer

Practice FRCPath Style Calculations | 15


Question 199You are setting up an assay for serum adenosine deaminase in which 20 µL of serumis first equilibrated at 37°C with 1.5 mL of buffer in a cuvette with 0.5 cm light path.The reaction is initiated by adding 25 µL of substrate then monitored by measuringthe rate of decrease in absorbance at 265 nm. Both substrate and product absorb atthis wavelength with the absorbance of inosine being 43% of that due to adenosine.

Derive a factor to convert the rate of absorbance change (per minute) to units ofadenosine deaminase activity (expressed as µmol inosine/min/L serum). The molarabsorptivity of adenosine is 13,400 L.cm-1.mol-1.

producing approx. 1200 mmol of solute (mainly urea) the maximum urine volume wouldbe 1200/50 = 24 L per day. In starvation reduced intake (even with increased tissuebreakdown) reduces the amount of solute available for excretion. If available solute wereto fall as low as 100 mmol/day then the maximum urine output would be 100/50 = 2 L perday. If fluid intake were to exceed this value then the ability to excrete water would beseriously impaired resulting in hyponatraemia.

16 | Current Topics


This report was submittedby invitation from the ACB News Lead Editor following Mailbase posting

For most of us, September always has a‘back to school’ feel, no matter how oldwe are or where we work. It is no differentfor the teams here at the NationalCongenital Anomaly and Rare DiseaseRegistration Service (NCARDRS) as weprepare to implement planned projectsand explore new ideas. NCARDRS, forthose who haven’t come across ourorganisation, is part of the NationalDisease Registration Service, which is inturn part of Public Health England. Ourremit is to collect data on people withcongenital anomalies and rare diseaseacross England and to work closely withclinicians, patient groups, public healthcolleagues, researchers and charities toimprove patient care and outcomes.We now collect data routinely from 244

healthcare providers and have 100%coverage of births in England forcongenital anomaly reporting. That isthanks to the great work of our NHSorganisers, the staff at our eight regionalcentres, the UK’s commitment to providinga world class strategy for tackling rarediseases, and the support of ourstakeholders.As we all returned from our various

summer holidays last month we began to

focus on four projects that involve ClinicalBiochemistry laboratories, each at variouslevels of progress.

Wilson’s Disease

This project involves the introduction ofprospective reporting of new confirmedand suspected cases of Wilson’s Disease bythe Supra-Regional Assay Service (SAS). It is based on the existing reporting systemfor lead poisoning in children. The newsystem entails the submission of a shortform to NCARDRS via email when a testindicates Wilson’s Disease. Laboratorieswill shortly receive a letter describing thereporting system, a copy of the form andinstructions for safe completed formtransfer.This is part of a bigger national project

on determining the prevalence of Wilson’sDisease. We’ve been delighted by thesupport that we’ve received from theClinical Biochemistry community on thisproject, including Dr Paul Cook(Southampton) and Godfrey Gillet(Sheffield), who are members of theWilson’s Disease Special Interest Group.Godfrey introduced us to the ACBMailbase Discussion List, which has led tosome rewarding interactions with ourcolleagues in Clinical Biochemistry. We will continue to use the Mailbase toupdate you on the progress of our work.Jeanette Aston, our Rare Disease DataLiaison, is the NCARDRS contact on theMailbase and can be contacted by email:[email protected]

The National CongenitalAnomaly and Rare DiseaseRegistration ServiceMary Bythell and Jeanette Aston, both from the RegistrationService

Current Topics | 17


Non-Invasive Prenatal Screening At the same time, we’ve been preparingfor the NHS Fetal Anomaly ScreeningProgramme Non-Invasive Prenatal Testing(NIPT) Programme. We will be collectingdata to support the evaluative roll outfrom the Clinical Biochemistry laboratories.Preparatory work is well underway and wethank those of you who have beeninvolved with helping us to set up therequired data feeds. This has been amassive undertaking and we will updateyou on the progress in a future ACB Newsedition.

Inherited Metabolic Diseases

Before the end of the financial year, weaim to have systems in place forprospective reporting on confirmed andsuspected cases of the newborn blood spotinherited metabolic diseases. This workwill not only support our phenylketonuria(PHE) screening colleagues, but will allowus to collect identifiable data to supportunderstanding, treatment and improvedpatient outcomes for these conditions. We will be in touch with heads oflaboratories to discuss this soon.

ANCA-Associated Vasculitis

Finally, Dr Fiona Peace (Nottingham) hasbeen leading on a project with us todetermine the national prevalence ratesfor some rare rheumatological conditions.We will be contacting Immunologylaboratory colleagues in the comingmonths to scope how we might worktogether to get a better understanding of these conditions, particularly ANCA-associated vasculitis.Nothing stands still for long and it can

be hard to keep up in this fast changingenvironment. We rely on our clinicalcolleagues to help us to navigate thecomplexity and nuance of congenitalanomalies and rare disease. WhatNCARDRS offers is the potential to look atthese issues from a national (England)perspective. We look forward tocollaborating with you on these and otherprojects. If you would like to discuss any of the

projects mentioned in the article or haveideas for new ones, please contact Mary Bythell, Head of Rare DiseaseRegistration for NCARDRS by email:[email protected] �

Jeanette Aston Mary Bythell

18 | Current Topics


NHSScotland provides healthcare to apopulation of approximately 5.3 millionpeople across an area that constitutes athird of the UK land mass. It is a complexorganisation that faces challenges aroundrising demand and many other drivers forchange common to the rest of the UK.These drivers in combination with afundamental requirement to deliver bettercare, better experience of care and bettercost of care (Triple Aim) are driving theneed for transformation of services. It follows that underpinning services, such as those provided by laboratories,must also undergo transformation to

deliver future requirements of theevolving healthcare system. Given thedependence of patient pathways andoutcomes upon laboratory outputs, failureto deliver transformed services that areoptimally configured to address both localand national priorities will compromise thevalue of investment in diagnostics anddelivery of Triple Aim. New serviceconfigurations need to deliver equitabilityof access, efficiency in delivery,effectiveness in impact, resiliency andsustainability of service and be not leastaffordable. Taking all these issues intoaccount, a process involving service

Transforming NHSScotland’sLaboratory Medicine Services:A Blueprint for a FutureDr Bill Bartlett, Clinical Lead National Laboratories Programme NHSNational Services Scotland; and Mr Paul Hawkins, Chief ExecutiveNHSFife and Chair of the Laboratories Oversight Board

Operational structures being developed to enable regional delivery of adistributed service model for laboratories that is nationally consistent

providers and stakeholders has resulted inthe agreement to move forward with thedevelopment of a Distributed ServiceModel (DSM) for laboratory services withinNHSScotland. A blueprint and set ofguiding principles have been developed toenable the DSM delivery under a newgovernance structure. This sees theestablishment of a Laboratory OversightBoard to facilitate the development of theDSM through new Regional structures.NHS National Services Scotland (NSS) hasbeen tasked by the Scottish ChiefExecutives group with delivery of aNational Laboratories Programme whichhas been allocated £6.7m to progressinitial key work to enable the DSMdevelopment. The current National Laboratories

Programme has arisen from workundertaken through the NHSScotlandShared Services Programme (SSP). Thatprogramme was extended to deliver aHealth Portfolio that included laboratoriesin 2015. In 2016 a small team wasestablished within the SSP Health portfoliotasked specifically to development of thelaboratories element. That team workedwith the laboratory service providers andother stakeholders through a number ofworkshops to develop a position paper onlaboratory shared services that waspresented to NHSScotland Chief Executivesin October 2016. That paper included adetailed PESTEL and SWOT analysis of thecurrent service model and also took intoaccount work undertaken byNHSScotland’s Managed DiagnosticsNetworks presented to the DiagnosticSteering Group in 2015. It resulted in amandate to move forward to delivery of astrategic paper based on a proposal todevelop a DSM for laboratory services inScotland and to establish a small numberof working groups around informationtechnology, data and innovativetechnology (e.g. digital pathology). The position paper also identified a set of

guiding principles to be followed in thedevelopment of services to realise theconcept of the DSM. The DSM strategy paper was delivered in

July 2017 and described the case forchange with a high-level description of theproposed model emerging throughextensive stakeholder engagement. The contention put forward was thatstakeholders agreed that there is anopportunity to use the significantresources – workforce, facilities,equipment and finance – available toHealth Boards to deliver laboratoryservices in a way that is more efficient,effective, equitable, resilient andaffordable. The DSM concept is one ofdelivery of an optimal serviceconfiguration in the various localitiesacross Scotland. The delivery units are toprovide the correct volume, range andrepertoire of tests reported within anappropriate timescale to meet the needsof the locality and configured as a wholeto enable delivery of national priorities inthe context of Triple Aim. A strategic aimof the DSM is therefore delivery of anoptimal distribution of laboratory servicesacross Scotland with concentration ofworkloads and sharing of expertise acrosswider geographical areas. The concept isone that addresses drivers for change andrequires delivery of a functionaldistribution of service across the system todeliver whole healthcare system value andresilience rather than de factocentralisation in order to reduce the costof the laboratory service. Delivery of the DSM will depend upon

coordination across and betweenlaboratories and standardisation ofoperating procedures across services. In planning terms this will equate to asingle virtual service functioning toconsistent standards across the widerorganisations while different aspects ofservice are delivered by the relevantoperational unit at the most appropriate

Current Topics | 19


20 | Current Topics


level whether national, regional, HealthBoard level, individual hospital orcommunity. The detailed strategy paper was

approved and work subsequentlyundertaken to develop a full business casepresented to CEs in April of 2018. This builton previous work with further input froman IT Group, a Data Group and DSMDesign Group. The case reflected therequirement identified in the earlierposition paper to take an incrementalapproach to the delivery of the DSM, the emerging regionalisation agendaarising from the publication of the ScottishGovernment’s Health and Social CareDelivery Plan in 2016 and the need to havea new governance structure to support thisagenda and further ensure and assurenational consistency of service. Thebusiness case was accepted and fundingwas allocated to a National LaboratoriesProgramme with the following Keydeliverables from the business case:

� A new governance structure thatsupports the delivery of a DSM with

national consistency.� A National Laboratories Blueprint forthe DSM. Delivering a vision for thelaboratory services focusing on process,organisation, technology andinformation.

� IT Connectivity, with all Scottishlaboratories implementing NPEx for lab to lab electronic ordering.

� Data sharing, through development ofa national data platform to supportbusiness and clinical intelligencerequirements.

� A high level specification for LIMS toenable national consistency in a keyprocurement area.

It is important to note that theincremental approach is being taken withthe view of achieving short to mediumterm benefits, adding value to laboratoryservices while maintaining a clear focus onthe longer-term transformational changerequired to deliver the optimal DSM. The final form of the DSM will ultimatelyreflect function, meeting the needs ofstakeholders, which in turn will be defined

Desirable attributes of NHSScotland’s future distributed service model for laboratory services

Current Topics | 21


by the requirements of NHSScotland’shealthcare delivery model evolving in thecontext of the National Clinical Strategy. Longer term benefits are anticipated

that are both financial and non-financial,in part these will be achieved through theappropriate consolidation of services,facilities and equipment and whole systemlaboratory service redesign. The businesscase illustrated the potential benefits oflaboratory service transformation withexamples from current initiatives inScotland. It also recognised the fact thatdelivery of optimised services withappropriate allocation of resources has thepotential to deliver significantdownstream benefits to overall healthcaredelivery and the potential to addresscurrent risks (e.g. service resilience,requirement for investment in newtechnologies). Clearly there is a drive forchange to address the issues of variationand waste within the current system, butthis should be seen as an opportunity toidentify resource to invest intodevelopments that increase theeffectiveness and thus value of theallocated resource envelope.Developments in technology, informationand knowledge management, artificialintelligence, the medical evidence baseand the emergence of new modes ofpractice (precision medicine) will challengethe delivery model and potentiallyenhance the value of redesigned services. The scale and complexity of the task to

be undertaken to deliver the DSM shouldnot be underestimated. NHSScotland’sclinical laboratory services are currentlyprovided by 14 territorial and 2 specialHealth Boards (Scottish National BloodTransfusion Service, Golden JubileeNational Hospital) and have a projectedspend of £1.5 billion over the next fiveyears. Focusing on the territorial Boards itis estimated that over 3,800 full timeequivalent staff are directly involved inservice delivery across 27 sites out of 87

laboratories. In addition, total NHS serviceprovision also includes a number ofnational services commissioned by NSS;there is therefore a considerable resourcemanaged and applied through a complexmodel with multiple stakeholders involvedin service provision and usage. Followingthe publication of the Health and SocialCare Delivery Plan, the territorial Boardshave been allocated to 3 regions for thepurposes of planning:

The governance structure for thedelivery of the DSM will be delivered viathe formation of operational boards forlaboratories in each of the three Regionalstructures feeding into a LaboratoriesOversight Board (LOB). Those regionalboards are seeking delegated authorityfrom their constituent Health Boards toenable change. The LOB has a membershipthat enables input from regional, nationaland partnership perspectives and is chairedby Paul Hawkins the NHS CE for NHSFife.Included within the LOB’s remit andpurpose is the responsibility for aligningnational and regional plans forlaboratories transformational change and

North RegionNHSGrampianNHSHighlandNHSOrkneyNHSShetlandNHSTaysideNHSWestern Isles

East RegionNHSBordersNHSFifeNHSLothian

West RegionNHSAyrshire & ArranNHSDumfries and GallowayNHSForth ValleyHHSGreater Glasgow & ClydeNHSLanarkshire

22 | Current Topics


ensuring that the Laboratories Programmealigns to the strategic direction of NHSScotland. The latter will be enabled by theavailability of the national laboratoriesblueprint. At the first meeting of the LOBit was agreed that the blueprint andguiding principles for the DSM should beembedded within the terms of referenceof the Regional Operational Boards toenable delivery of a vision for servicesacross NHSScotland shared and thusconsistent.The National Laboratories Blueprint

(NLB) attempts to capture the here andnow of the current laboratory servicesmodel, identifies the steps that need to betaken to deliver the desired future modelfor laboratory services and identifies thedesired endpoints to be delivered by theDSM. It supports an incremental approachto transformation that if adopted byplanners will enable delivery of thenational strategy for laboratories andprogression towards a DSM that will meet the needs of NHSScotland today andin the future. The current focus on laboratories in

Scotland presents both challenges andopportunity for those providing services.The approach has delivered a clear visionfor the future of services that necessitatesservice transformation. This clearly

delivers challenge to the old order ofthings. The drivers for change impactingon the current service model are increasingin number and severity and drive the needfor the transformation. Not all are adverse.The availability of new technologies andnew approaches to service delivery thatsupport new ways of working provide new opportunities for all working inlaboratories. In addition the approachbeing taken to transformation in Scotland recognises the value ofdiagnostics in healthcare and has at itscore a focus on value and not cost with akey focus being the Triple Aim. This isbeing increasingly recognised and is apositive for those proposing servicedevelopments. The combination of theDSM blueprint, the guiding principles, the new governance structures, increasedunderstanding of the value of diagnosticsin healthcare and the adoption of anincremental approach to change towards an optimal delivery modelprovides massive opportunities for thefuture of laboratory diagnostics inScotland.

� Given the importance of this article, it is also published in the CollegeBulletin and in the IBMS Gazette. �

www.sharedservices.scot.nhs.uk/health-portfolio/programmes/laboratories/

Focus News | 23


Report of an IndustrySponsored Workshop at Focus 2018

Focus 2018 featured an industry workshopon biotin interference in immunoassays,sponsored by Abbott. The workshop wasvery well attended, reflecting the currentinterest in the topic, and was chaired byMike Hallworth (Shrewsbury), who beganwith a short introductory presentation. Mike opened by referring to a clinical

case poster presented at Focus in 2017.1

A premature male infant with multiplecomorbidities began having seizures onday 13 of life. Thyroid function tests weredone as part of the metabolic work-up onday 34 and showed free T4 (fT4) >100pmol/L and TSH <0.02 mU/L, suggestinggross hyperthyroidism. The baby wasclinically euthyroid, and the mother’sthyroid function was normal. The child wasstarted on carbimazole, and thyroidfunction tests on day 38 were normal. On further investigation, it was discoveredthat biotin had been prescribed, but wasstopped on day 35. A diagnosis of pseudo-thyrotoxicosis secondary to biotininterference in the assays was made.Biotin is a small, water soluble B vitamin

– sometimes called vitamin B7 (or vitaminH in older terminology). The UK NutrientReference Value (NRV; formerly known asthe recommended daily allowance, RDA) is50 micrograms per day. Biotin is widelydistributed in food, and biotin deficiencyon a normal diet is rare.

Biotin is used in treating multiplesclerosis as part of a Phase 3 trial in largedoses – 100-300 milligrams per day, and itis also used in smaller doses (5-30 mg/day)as treatment for some inborn errors ofmetabolism and some forms of alopecia.Those are fairly well-defined patientgroups, and biotin interference inimmunoassays has been relatively easy tospot in the past. However, high-dose biotinis now being promoted as a foodsupplement that improves hair growth,strengthens nails and improves skin,among other claimed effects. Such claimshave been made by Khloe Kardashian,2

among others, although there is littlescientific evidence to support such a rolefor biotin. The preparations marketed forthese purposes contain 5-10 milligrams ofbiotin, over 100 times the UK NRV. Incontrast, standard multivitamin tabletssuch as those used in vitaminsupplementation in pregnancy onlycontain two to three times the NRV,around 100-150 micrograms of biotin.Biotin in high doses can cause a problem

in immunoassays that use the biotin-streptavidin link as part of the assayarchitecture. The FDA in the United Statesissued a warning in November 2017 statingthat biotin can significantly interfere withcertain laboratory tests and cause incorrecttest results which may go undetected.3

This warning has served to increase theawareness of the problem, yet heightening the confusion surrounding it. Manufacturers who use thebiotin-streptavidin link in some or all theirimmunoassays include Roche Diagnostics,

Biotin Interference inImmunoassays: The Kardashian Effect?Mike Hallworth, Focus 2018 Chair

Siemens Healthcare Diagnostics, BeckmanCoulter and Ortho-Clinical Diagnostics.4

Manufacturers whose assays are notaffected include Abbott Diagnostics4 andTosoh Bioscience.In non-competitive sandwich assays such

as those used for large molecules – e.g.peptide hormones like TSH – the analyte issandwiched between the signal antibodyand the biotinylated capture antibody,which links the sandwich to a streptavidin-coated solid phase. Excessbiotin in the sample saturates thestreptavidin binding sites preventingadherence of the antibody-antigencomplex, falsely decreasing the detectedsignal and creating a falsely low result.4

However, in competitive immunoassayssuch as used for small molecules likethyroid and steroid hormones,endogenous analyte competes withlabelled analyte for the binding site on abiotinylated antibody. In this case, whenexcess sample biotin prevents binding ofbiotinylated antibody to the solid phase,the effect of reduced label binding is tomimic high analyte concentrations.4

The scene is thus set in the thyroid area fora ‘perfect storm’ – biotin interferenceproduces apparently suppressed TSHconcentrations and apparently highthyroid hormone levels, and mimicsthyrotoxicosis. In other clinical settings,falsely high steroid hormoneconcentrations (e.g. cortisol andtestosterone) may lead to misdiagnosis of an adrenal tumour.5

The problem is that the patient may notknow they are taking biotin, or how muchthey are taking (some of these productsare labelled with their constituents in verysmall print), the laboratory will not knowif the specimen contains biotin and thephysician could make a diagnostic decisionbased on inaccurate laboratory results.Mike concluded the presentation with

several questions for discussion:

� How common is the problem?� How big a dose is required to causeinterference?

� How do we assess the clinical risk?� Who is responsible if harm is causedbecause of interference?

� How can the interference be detectedand prevented?

� How do we communicate the problemin a balanced way to clinicians andpatients, given that not allmanufacturers’ assays are affected andnot all analytes are affected?

He introduced the panel – Dr ChrisChaloner, Consultant Paediatric Biochemistat the Manchester University NHSFoundation Trust, Mr Finlay MacKenzie,Director of Birmingham Quality, and Dr Gordon Avery, Scientific AffairsManager for Abbott Diagnostics. Severalmembers of the audience had had directexperience of the problem, and LanceSandle (Trafford General Hospital)described a very recent case in his hospital.In terms of communicating the problem,one audience member stated that they puta comment about the potential for biotininterference on every immunoassay reportissued, and others have called attention tothe problem in laboratory handbooks andmemos or newsletters to users. But howwidely are these read? Do cliniciansremember to ask about whether patientsare taking biotin? Do the patients alwaysknow? If patients present as anemergency, it may not be possible to askthem.There was also discussion about the

pharmacokinetics of biotin interference,and how long patients need to be offbiotin before valid results can be obtained.The half-life is stated as 8-18 hours, andRoche in their Biotin Toolkit6 and packageinserts publish advice that patients takingbiotin doses >5000 micrograms shouldwait at least 8 hours after the last biotinadministration before being tested. There

24 | Focus News


was discussion about whether the effectsof biotin could persist for longer at veryhigh doses such as those used in multiplesclerosis. Also, some commercial assaysseem to be more robust than others, andthe thresholds for interference arevariously quoted in the literature in termsof dose or in terms of specimen biotinconcentration, which adds to theconfusion. The risk is currently not wellquantified.Discussion around detecting and

avoiding the interference included theimportance of good clinical liaison andawareness of the clinical picture – but ifthe effect of interference is to produce afalse undetectable troponin result in apatient in the ED (as in the FDA safetyreport [3]), then this will be very hard tospot clinically. Obviously, rechecking resultson a different platform that does not usethe biotin-streptavidin link will helpidentify interferences – but again, youmust suspect that they are present to golooking for them. It would be helpful tobe able to measure biotin, possibly by massspectrometry, both to assess the incidenceof high concentrations in routine samplesand to identify potential interference.There are papers in the literature whichsuggest pre-treating samples with astreptavidin solid phase to strip out anyexcess biotin before analysis.7

Other speakers from the audienceemphasised the importance of two-waycommunication with users and withpatients about the nature and limitationsof laboratory testing, stressing that this isnot the only form of interference we dealwith, and a sense of perspective isrequired. The importance of a thoroughunderstanding of the assays used in yourlaboratory was stressed. One interestingsuggestion was that the Kardashians couldbe involved to help communicate theproblems with biotin!

Mike closed by thanking the panellistsand the audience for their time and theirparticipation in what had been aninteresting and productive workshop. He also thanked Abbott for organisingsuch a topical and popular session.

1. Leveret H, Wei C, Garrison L. An unusualcase of thyrotoxicosis: when numbersdon’t add up. P062 at Focus 2017, Leeds.www.acb.org.uk/whatwedo/events/national_meetings/focus-2017/abstracts/poster-abstracts#abstractid1061Accessed 16 July 2018.

2. In Style. Khloe Kardashian uses theseunexpected vitamins to metabolise fats.https://www.instyle.com/beauty/health-fitness/khloe-kardashian-biotin-vitamin2Accessed 16 July 2018.

3. US Food and Drug Administration. The FDA warns that biotin may interferewith lab tests: FDA safety communication.https://www.fda.gov/medicaldevices/safety/alertsandnotices/ucm586505.htmAccessed 16 July 2018.

4. Colon PJ, Greene DN. Biotin interferencein clinical immunoassays. J Appl Lab MedMay 2018 doi: 10.1373/jalm.2017.024257

5. Stieglitz HM, Korpi-Steiner N, KatzmanB, Mersereau JE, Styner M. Suspectedtestosterone-producing tumour in apatient taking biotin supplements. J Endocr Soc 2018; 2: 563-9. doi:10.1210/js/2018.00069

6. Roche Diagnostics. Biotin facts.https://biotinfacts.roche.com/toolkit/Accessed 16 July 2018.

7. Trambas CM, Lu ZX, Yen T, Sikaris K.Depletion of biotin using streptavidin-coated magnetic beads: a validatedsolution to the problem of biotininterference in streptavidin-basedmethods. Ann Clin Biochem 2018; 55:216-226. �

* Disclosure: Mike received a fee from AbbottDiagnostics for chairing the workshop, but notfor this article.

Focus News | 25


26 | BIVDA News


I almost feel that I need to apologise as I write this, as I think we are all weary ofBrexit, which has been discussed almost asmuch as the weather over the past twoyears. However, once I got back from agreat AACC meeting – have to loveChicago – it became very clear that Brexithad really come home to roost withinMinisterial Offices in Whitehall, despitebeing in Parliamentary recess for thesummer.The main focus in August was getting

everything aligned for the possibility of a‘no deal’ Brexit. Until now, this had beenoff the table as have any discussions wehave had with officials. The official line isstill very much that they anticipate a dealbeing made and this is not a signal thatindustry (and UK citizens) should bealarmed. However, it is hard to avoid beingcynical and this is exactly how I have seenthis!On 23rd August a number of technical

notices relating to Life Sciences Regulationpost-Brexit were published and these canbe seen on the Department for Exiting theEU (DExEU) website. On the same daythere was a letter sent to IVD suppliers

from the Secretary of State for Health andSocial Care (DHSC), Matt Hancock, onensuring supply of diagnostics (and othermedical devices) in the case of a ‘no deal’scenario. I have also been havingdiscussions with officials in DHSC who areviewing Pathology services as critical. At least the message about 70% ofinformation for patients is reliant onlaboratory medicine has hit home.The Government is looking at increasing

stockholding at a national level andsuppliers are now being asked to considertheir own contingency plans and if theyneed to increase production. For manyshort shelf-life products this may not bepossible, of course. It is hard to providemuch detail as we are having a meeting onprocurement issues in two days from whenI write this, with DHSC officials there totalk to companies face to face; we havebeen keen to ensure they understand thatmost of Pathology reagents and suppliesdo not come through the NHS SupplyChain (now in category towers) but underthe auspices of Managed EquipmentServices.The IVD industry position has to be that

while we will do everything to keepsupport for patients as paramount, theindustry cannot be expected to bail theGovernment out by absorbing all the cost,whether this is stockpiling in warehouses,picking up any extra customs costs,increasing production with no guaranteeof additional stock being sold etc. Within the industry our concerns remain

focused on how the regulation will beimpacted, whether staff will be impactedand how the supply chain will be impacted(raw materials and part finished product

Industry Insights: The ‘B’ WordDoris-Ann Williams, Chief Executive, BIVDA

are shipped constantly around the EU,regardless of where the final product maybe manufactured).BIVDA will continue to keep dialogues

going and the Pathology Alliance and itsconstituent member seems a great channelto do this. Please do also talk to your ownsuppliers, but remember that we are all inthis mess together and they may very wellnot be able to give you any answers!Meanwhile, changing the subject

completely, the Secretary of State has

come out to state his three priorities forHealth and Social Care:

� The NHS workforce

� Prevention

� Technology (not just digital orinnovative products but enabling theNHS to be in a position to maximisetheir use).

So, I am looking forward to some usefulinput on these issues over the next fewmonths. �

BIVDA News | 27


28 | Meeting Report


The 2018 meeting was held at St Thomas’Hospital London. Dr Wassif, National AuditLead, opened the meeting and announcedthat this year, for the first time, all 15abstracts submitted to the National AuditCommittee for this meeting will bepublished on the Annals of ClinicalBiochemistry website. This shouldencourage more of our members to submithigh quality abstracts next year.The morning session was an interesting

and thought-provoking series of talks anddiscussion around the clinical utility andimplications of low calculated globulins byDr Pecararo (University of Naples) and Professor Jolles (University Hospital,Wales). Interestingly, in Wales, a lowcalculated globulins is now the commonestreason for referral to theimmunodeficiency service. Patients onclozapine represented a significantproportion of patients detected in primarycare with low calculated globulins,highlighting this patient group is atincreased risk of immunodeficiency.A national survey of current practice,

carried out and presented by Dr Zouwail(University Hospital, Wales) highlightedthe variation in practice across the country.The discussion highlighted the need tocontinue to analyse total protein as part ofa liver profile and to encouragelaboratories to report calculated globulins(since, apart from a little IT intervention,this is in the unique position of beingessentially a free addition to abiochemistry profile). A lack of agreedstandards was highlighted, as was theneed for a consensus cut-off for calculatedglobulins and appropriate actions to betaken by laboratories for results falling

outside agreed limits.The afternoon session focussed on using

troponin to facilitate early discharge fromthe emergency department. Professor Mills(Royal Infirmary of Edinburgh) took timeout of his annual leave to give an excellentinsight into the High-STEACS trial andpathway. This was very well received andmade the audience think differently aboutusing troponin cut-offs. The nationalaudit, carried out and presented by Dr Jerina, was a re-audit of practiceoriginally carried out in 2014. There is stilla huge variation in practice across thecountry, in terms of the timing betweentroponin samples, cut-offs used for singlerule in, for second sample positivity andfor delta changes. The majority ofparticipants in 2018 are using an admissionand 3 hour troponin guided protocolcompared to the majority in 2014 using anadmission and 6 hour protocol. The audithighlighted the need for a revised ACB troponin working group consensusdocument to incorporate European Societyof Cardiology (ESC) guidelines, as well asthe results from the High-STEACS trial. A selection of local audits from the UK

were presented with a range of topicsincluding AKI alerts in primary care byJane Oakey, FSH in menopause by Dan Turnock and trace element requestingby Roger Bromley. Many delegatesmentioned throughout the networkingthat all aspects of this meeting weretranslational to local practice and wouldimprove patient care. A worthwhile trip to London with time

during lunch for a quick wander overWestminster Bridge to see Big Ben! �

National Audit MeetingDr Natalie Hunt, Lancashire Teaching Hospitals

Obituary | 29


Heather was always proud to announcethat she was born in Driffield, EastYorkshire, on 12 August 1949. Her parents,Geoff and Mary Warters, moved fromFoxholes to Humble Bee Farm, Flixton, in 1954, and they survived initially withhand-pumped water from the well and noelectricity, just paraffin or hand-pumpedTilly lamps.Her first job was at Scarborough

Hospital’s Clinical Pathology Departmentand, after a few years, she moved to NorthTees Hospital. She worked hard andeventually achieved the status ofConsultant Biochemist. During this time,she worked part-time while she raisedJoanna and Jonathan. She won all herbattles with the hospital administration,first enabling women to wear trousers atwork, then her various promotion battleswith the Personnel Manager (he admittedlater that she was his ‘only failure’!). She managed to do a BusinessManagement degree during this time, too.When she retired, Heather took up the

saxophone and she was a founder-memberof the Buckrose Concert Band, in whichshe played the baritone saxophone.Nothing was allowed to interfere with herWednesday evening band practices atWetwang, or with most of the dozen or soconcerts (‘gigs’) that the band playedaround Yorkshire every year, or on theBand’s two trips to the Continent. Themost memorable and emotional was when the band was invited to play at theLast-Post ceremony at the World War IMemorial in Ypres.Heather was an active person and a keen

gardener, always with several projects onthe go, or thinking about what would beher next project! Associated with hergardening, she was on the Committee of

the Rillington Show, and she entered andwon prizes for her jams and gardenproduce. More recently, she joined theFoxholes Art Group, and some of her workachieved Best in Class at the RillingtonShow. Her next project, which she sadlywill be unable to accomplish, was tobecome a Fellow of the Institute ofAdvance Motoring, the more advancedqualification offered by the IAM.Heather is sorely missed by her husband,

Gordon Malan, children Joanna andJonathan, grandchildren Nina and Edith,and brother David Warters, and her manyother family members and friends.

Dr Gordon Malan

Note from the Editor� Heather was also Chair of the (as it was then) ACB Northern Regionand Regional Council Representative,1996-1997. �

Heather Mary Thornes12 August 1949 to 2 July 2018

30 | Crossword


ACB News CrosswordSet by Rugosa

Solution for August’s Crossword

Across 8 Father develops an eponymous disease (6)9 Accident report retains doctor as advocate (8)10 Decline heading for takeaways for food? (4)11 Genesis of charged particles problem not left

in isolation (10)12 Eagerly expecting a character from Ezekiel (4)13 Complete chemical process, reseal unit

components (10)17 Alternate puerperal end product (4)18 Closely observing some turnkey in gaol (5)19 Denial of French internet connection (4)21 Potential energy transferred from

exceptional athlete with tan (6,4)23 Former graduate back for test (4)24 Fracture clinic not a provider of peptide

hormone (10)28 Kind of blow that can lower analytical

results (4)29 Potentially is deadly: treated like this? (8)30 Straight in with hard-line arguments (6)

Down 1 Mother, take your time, act unwell (8)2 Trained initial class: for example,

conversion of old scientific scale (10)3 Legal transfer of original antigens

manuscript (10)4 Prepare plasma for politician's doctor (4)5 Charge carriers exploding: endless noise (4)6 Metabolic problem following non-NHS

gunshot treatment (4)7 Clinic ignored problematic inconclusive

blood type (6)14 Fend off unrefined waste material (5)15 Fitting point of view, held four-square (5,5)16 Hansel rang about German histopathologist

(10)20 Distributed aid along an oblique line (8)22 A burden on one having a neurological

condition (6)25 Inhibited unresponsive infection (4)26 Investigate intestinal content (4)27 Acknowledges greetings (4)

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