2 N E W S & M A NAG E M E N T House of Lords wants a new Office for Health and Care Sustainability Over Short-sighted politicians place NHS in jeopardy Family doc the alarm Report: Mark Nicholls The future of the National Health Service is under threat unless action is taken to address critical issues, according to members of the UK’s House of Lords. In a hard-hitting report, the House of Lords Select Committee on the Long-Term Sustainability of the NHS criticised the ‘short-sightedness’ of succes- sive governments for failing to plan effectively for the long-term future of the health service and adult social care. With longer waiting lists for patients and funding shortfalls, a recent survey suggested that 55% of people in the UK also fear the NHS will deteriorate further at a time when there remains uncertain- ty over the impact the UK’s decision to leave the EU on attracting people from other European countries to work in the NHS. Tax-funded free at the point of care still the most effec- tive way to deliver care In its report, the Committee stressed that the UK system of a tax-fund- ed, free-at-the-point-of-use National Health Service remains the most efficient way of delivering health- care, now and in the future. However, for that principle to remain, members stressed that many aspects of the way the NHS deliv- ers healthcare will have to change. Suggesting that a ‘culture of short- termism’ exists within health and social care provision in the UK, the Lords recommend that a new, inde- pendent, Office for Health and Care Sustainability should be established to look at health and care needs for the next 15-20 years. The office should report to Parliament on the impact of chang- ing demographic needs, the work- force and skills mix in the National Health Service and on health and social care funding. With a merging of health and social care in the UK, the Lords Committee expressed concern that funding between the two has been poorly co-ordinated. The report says that the failure to implement a long-term strategy to secure a skilled, well-trained and committed workforce that the health and care system will need is, the ‘biggest internal threat to the sustainability of the NHS.’ It also advocates a re- shaping of primary and secondary care, and specialised services, and pointed out that service transforma- tion is ‘at the heart of securing the long-term future of the health and care systems.’ Among the 34 recommenda- tions the committee makes are for budgetary responsibility for adult social care at a national level to be transferred to a new Department of Health and Care; NHS England to engage with general practition- ers (GPs) to examine alternative models; NHS England and NHS improvement to be merged to create a new body with simplified regula- tory functions; the Government to commission an independent review to examine the impact of pay on morale and retention of health and care staff; national and local public health budgets to be ring-fenced for at least the next ten years; a nationwide campaign to high- light the dangers of obesity; the NHS Constitution to be redrafted to emphasise that access to the NHS involves patient responsibilities as well as patient rights. A shocking lack of long- term strategic planning, says Peer of the Realm ‘The Department of Health at both the political and official level is fail- ing to think beyond the next few years,’ confirmed Lord Patel, com- mittee chairman and eminent obste- trician. ‘There is a shocking lack of long-term strategic planning in the Lord Patel KT – Narendra Babubhai Patel – is a renowned British obstetrician, cross bench peer, and Chancellor of the University of Dundee. He has served as Vice-President of the All-Party Parliamentary Group on Maternity Services since 2002 and in the group on Infertility Services since 2003. He is also Chairman of the Stem Cell Steering Committee since 2003 and a member of the Science and Technology committee. make savings to balance budgets, often meaning that the criteria for offering routine operations, such a hip replacements or cataract sur- gery, is being changed with patients having to wait longer, or until their condition has deteriorated further, before surgery is offered. Health and social care services in the UK are faced with an ageing population; people living longer with chronic conditions; an obesity crisis and rising drug costs. That is combined with difficul- ties in filling nursing or GP posts, despite the creation of more training positions, and an emphasis towards greater community care but with an infrastructure still centred on a network of district general hospitals. will be able to remain, as well as encouraging them to do so.’ Across the UK, the NHS is current- ly struggling to cope with patient demand. Funding is rising – an extra £8 billion has been made available by the present conservative govern- ment – but this still does not appear enough to cope in a health system that sees a million patients every day and employs 1.7 million per- sonnel (making this the world’s fifth biggest employer). However, despite the issues, the NHS continues to be innovative, leads ground-breaking research and conducts millions of successful – often life-saving – treatments. Last year saw £140 billion spent on health across the United Kingdom, yet patients at present are waiting longer to see their GP, or for a hospital appointment, for sur- gery, or to be seen in the Accident & Emergency (A&E) department. A key target stating that 95% of patients arriving at the emergency department should be seen within four hours has not been achieved for two years. However, the number of people- visiting A&E have risen by a third in 12 years. Hospitals and health services across the UK are also facing aus- terity measures and being asked to Danny Mortimer became Chief Executive of NHS Employers in November 2014. His first work in healthcare was as a porter and care assistant before he became a management trainee. He later held a series of director and executive roles before joining NHS Employers, the voice of employers across the English NHS. He also chairs the Cavendish Coalition of social care and health organisations. Plan to draw hospitals and local community teams clos- er together NHS England chief executive Simon Stevens has set out a five-year plan to create more integrated care, which involves hospital services working more closely with their local community teams. However, there remains an imbal- ance in health and social care fund- ing with significantly more money still spent on front-line healthcare than social care. No chance: Still vulnerable to cyber attack Continued from page 1 methodically and routinely apply patches and upgrades; use antivi- rus software and keep it updated; back up data files regularly and fre- quently; and teach staff to check the veracity of attachments and links in emails they receive, because this is often the route through which ran- somware first infects an organisa- tion’s computers. AXREM - the trade association representing suppliers of diagnos- tic medical imaging, radiotherapy, healthcare IT and care equipment in the UK – warned that, while patches were available for medical imaging systems, robust network defences are critical in preventing future attacks. While suppliers have been focus- ing on restoring operation of systems compromised by the Ransomware attack, and protecting systems from further risk, AXREM pointed out that, as medical imaging systems are classified as medical devices and subject to strict regulation, suppliers are obliged to rigorously test soft- ware updates and patches to ensure that functionality and safety is not compromised. The organisation warned that ‘for this reason, the reliance upon pro- vision of clinical product software patches for defending against mal- ware attacks does not provide a sustainable option’, and stressed: ‘therefore, robust network defences are strongly recommended to pre- vent against future attacks’. Professor Jane Dacre was elected President of the Royal College of Physicians (RCP) in April 2014 and is an honorary consultant physician and rheumatologist at the Whittington Hospital in north London, professor of medical education, and director of UCL Medical School in London. NHS. To solve this we need a new body that is independent of govern- ment and is able to identify clearly the healthcare needs of a chang- ing and ageing population and the staffing and funding the NHS will require to meet those needs.’ 15-20-year plans, but NHS will also need bigger funds especially for low paid He emphasised the need to look ahead and plan for 15-20 years into the future. ‘We also need to recognise the NHS will need more money. NHS spending will need to rise at least as fast as GDP for 10 years after 2020,’ he added. ‘One area where more spending will be required is on pay for lower paid staff.’ Commenting on the House of Lords Select Committee report, the Royal College of Physicians (RCP) President Jane Dacre welcomed the report’s focus on transformation and the call for a long-term strategy on caring for a changing popula- tion. ‘If we are to improve the care for patients we treat, as clinicians, in collaboration with patients, we need to reshape the secondary and specialist care we provide.’ Danny Mortimer, chief executive of NHS Employers, said: ‘It’s impera- tive the health and social care sector is able to attract and recruit the right staff in order to protect its future, whether that be from the UK or abroad. ‘We also agree that there is a need to give assurances to EU nationals, who make up 6% of the health and care workforce, that they Report: Madeleine van de Wouw Three quarters of Dutch general prac- titioners (GPs: family doctors) expe- rience an increasing work pressure, according to a recent survey of the National Association of General Practitioners (LHV). Especially even- ing, night and weekend services at GP Emergency Posts (Dutch: HAP) are found to be heavy duty, in addi- tion to their daily practice. Too big a success Established some 15 years ago to relieve individual service pressure on GPs and to improve healthcare, the HAPs (which are not Hospital Emergency Posts) soon became too big a success. Initially intended for patients needing urgent care, they HAPs are increasingly used by patients who either don’t have a per- sonal family doctor, or by those who actually don’t have urgent medical issues. This puts at risk patients who do need immediate care, because they might have to wait longer. It also increases healthcare costs and, to make enlarge the problem, work pressure has increased rather than decreased. The HAP, in itself, has become an emergency. Different questions Besides the extra HAP work, pop- ulation aging, increasing psycho- logical complaints, refugees influx, decentralisation of youth care and on-going care for chronic patients are factors in increasing work pres- sure. ‘People are becoming increasingly concerned with health and want to resolve issues and complaints imme- diately,’ observes Andy Kwee (50), an independent GP in Almelo, with a medium-size practice (approxi- mately 2,200 patients). ‘The most important task of a GP was to make a diagnosis. Nowadays patients check their medical complaints on the Internet and find the most ter- rible diseases. As family doctors it’s our job to reassure the patient, make him or her feel comfortable again and after that try to diagnose. Given all of that, the ten minutes we have for a consultation are not nearly long enough.’ Administrative hassle In addition to all this the GP received additional duties. For instance taking over certain forms of hospital care, such as monitoring diabetes patients. ‘And,’ Kwee points out, ‘there are so many forms and papers you have to fill in for health- care providers, the government and health insurers. Then, I don’t even count the individual requests by patients who need a letter from me for some reason or other. Compared to 2015, the costs of staff in 2016 increased by 40 percent because I employed more assistants to take over some of my work. Our public health minister may emphasise that the pressure and the administrative hassle are not too bad, but unfortu- nately she’s wrong about that.’ This is confirmed by the LHV: ‘When choosing the policy to organ- ise more care in the first line, the EUROPEAN HOSPITAL Vol 26 Issue 3/17

4 N E W S & M A NAG E M E N T Software offers specifically designed deep learning algorithms AI develops beyond the breast Access, accuracy and efficiency are at the core of Samsung’s healthcare strategy, explained Insuk Song, Vice President of Product Planning, Healthcare and Medical Equipment at Samsung Electronics, during our exclusive European Hospital interview. Samsung, the Korean giant, is now proceding with its artificial intelligence (AI) deployment, notably with the S-Detect software to help ultrasound professionals detect and characterise lesions in breast cancer. Interview: Mélisande Rouger and Daniela Zimmerman EH: Samsung is present in many industries. How does that experi- ence translate into healthcare? Insuk Song: ‘We bring technologi- cal excellence from the electronics segment, which has strong syner- gies with healthcare. One is defi- nitely imaging excellence. We are the leading provider of TV, with latest display technology such as the QLED TV. Many of our engi- neers come from the visual display background. Image processing and how to generate the best image is in our DNA. ‘We are also very experienced in thinking of customer needs in terms of design and user experi- ence. We are regularly awarded for our work in electronics design, and, earlier this year, three of our ultrasound products and one digital X-ray received the iF design award. ‘Patients still need to adopt very difficult postures for medical imag- ing examinations, so we see that as an opportunity to innovate and accelerate innovations in an indus- try long dominated by a few key players. We are working on effi- ciency of workflow and ergonom- ic measures. Expediting workflow while easing ergonomic pain is a consideration for patients. If they’re comfortable, you can scan them much easier, so it’s win-win for them and the hospital.’ What distinguishes Samsung in the healthcare market? ‘Mobility is our strong suit. Access is an issue: population is ageing and access to the hospital is some- times a challenge, so making things small and accessible for patients anywhere is essential. In hospital a lot of patients are also immobile. Our mobile digital X-ray GM85 is one of the smallest and lightest in the world, and can go anywhere in the hospital. We will present our updated mobile fleet, at the upcom- ing RSNA. ‘Diagnostic accuracy is fundamen- tal to this industry. Good image quality is a base, but we are add- ing additional software capability to enhance the diagnostic capability of the radiologist or clinician, by enabling them to see beyond their own eyesight.’ How are your research projects in AI and deep learning tools advancing? ‘We started working in that field a long time ago! We launched AI tools for breast cancer (BC) diag- nosis – but nobody listened then. There was a lot of mental resistance and regulatory bodies are always very careful when a new diagnostic product arises. ‘Our S-Detect software, which uses specifically designed deep learning algorithms, is a great tool to help radiologists diagnose BC. They don’t need extra help for cases that are black and white; but they may do for tricky cases. Even experienced professionals are some- times faced with challenging cases. What we claim is that we’re their second opinion, we’re here to help them double check. This software is not just run on our own brain, it is based on the experience of many radiologists. So you run S-Detect to see what other people might think of the tricky case at hand. ‘AI is now a trend and it’s easier to work in that area. We’re trying to expand the capability of computer- aided diagnostic software in ultra- sound and digital X-ray. We will also see chances of expanding it to other modalities and to other organs. S-Detect started in the breast, but it has already expanded to the thyroid and we’re looking at other potential targets, the liver, for example. ‘Whilst we receive a lot of support from this trend, it has raised the bar for regulatory bodies, which will now probably make a new regula- tion to ensure patient safety.’ You have international branches. Where do you encounter the most difficulties? ‘Every market has its own chal- lenges. For example, Europe is dif- ficult because it has different lan- guages and cultures. Although we treat Europe as Europe, there are many countries with different gov- ernments and regulations, so you need multiple strategies to obtain the same result. ‘In the case of the United States, things are also very dif- ferent from one state to another. Every customer is different in his or Tens of thousands of refugees arrived in Munich ‘We saw unimaginable medical conditions’ In a vulnerable system the most vul- nerable users suffer most – and in the German hospital surgical care system the most vulnerable are chil- dren – and, above all, immigrant children. Quite a bit of whingeing was heard at the 134th German Surgery Congress in Munich regarding the inadequate framework conditions to provide safe and reliable surgi- cal services in hospitals and pri- vate practices: not enough staff, too much bureaucracy, the commodifi- cation of healthcare. But, there were also encouraging news, surprisingly in the context of demographic change. Demographic change is not only about an age- ing population, it is also about the growing number of children due to increasing birth rates in Germany and the influx of immigrant children and adolescents. Their care is a par- ticular challenge to the healthcare system, not only in financial terms but also right upon hospital admis- sion. Munich medics beat a huge challenge In summer 2015, Munich showed true grit when tens of thousands of refugees, many of them children and teens, arrived in the city after a gruelling journey in the sweltering heat and had to be provided with medical care right in the reception camp. ‘Among the refugees we saw unimaginable medical conditions,’ reports Professor Stuart Hosie, Medical Director of the Department of Paediatric Surgery at Klinikum Schwabing, still visibly shocked. ‘We saw a kidney tumour that covered the entire abdomen. We saw families who carried their children, paraple- gic after a war injury, all the way to Germany. Not to mention the TBC cases in numbers that were to be expected.’ It was a state of emer- gency in all hospitals throughout Munich but, looking back, the pae- diatric surgeon is proud to say ‘the hospitals took on and mastered the enormous challenge of caring for the refugee children’. It was a steep learning curve for everybody involved. One major take-home lesson: without volun- teers the feat would not have been possible. In the reception camp Bayernkaserne in Munich three vol- unteer paediatricians had a first look at the children so they could be sent on to the hospital in the Munich centre in an orderly fashion. There, samples were taken to test for multi-resistant bacteria. According to Hosie unaccompanied adolescents were a difficult group as many of them refused to stay in the hospitals, while others were grate- ful for the help they received and enjoyed the ‘luxurious’ hospital care. Hospital staff as interpreters Immigrant children who need med- ical care and their families are under extreme stress and the diffi- cult overall situation is exacerbated by language and communication problems. Hosie: ‘We were lucky to be able to draw upon our pool of foreign staff.’ More than 100 employees with basic clinical or nursing training and mostly native speakers of 35 foreign languages offer interpreting help in all sites of the Munich Municipal Hospital Group. 75 percent of the internal inter- preters have a nursing background. The internal interpreting service not only supports the hospital staff with diagnoses and medical reports and information sessions, but is also available free of charge for patients and their families. Foreign patients, however, who are scheduled for treatment, have to pay the interpreting service and most patients from Arab countries bring along their own interpreters. Intercultural care is a major and important task for the hospital: Of the German cities with more than 200,000 inhabitants, Munich has the second largest percentage of foreigners (23.0 percent) with Frankfurt holding the top spot (25.9 percent). Serving approximately 1,000 non- German patients per month, the Munich Municipal Hospital Group is assumed to be the largest provider of in-patient services for immigrants. The group‘s department for inter- cultural care wants to dismantle linguistic and cultural access bar- riers, increase intercultural compe- tency in the care of non-German patients and develop a service offer- ing geared towards immigrants. The experienced nurse often observes more A brochure, published by the Federal Government’s Commissioner for Migrants, Refugees and Integration, on the particular needs of immi- grant patients supports the efforts. Paediatric surgeon Hosie points out that today all major paediatric clin- ics in the larger cities are well pre- pared to meet these needs. However, children require ade- quate care across all clinical disci- plines and there is a marked lack Insuk Song PhD took on the role of Vice President and Product Planning Team Leader at Samsung Electronics in 2016. Prior to this she was the firm’s VP of HME Marketing and, from 2009- 2014, Senior Director of APAC Sales & Marketing for GE Healthcare, following her employment as Senior Consultant for the MacKinsey&Company (2001- 2009). her own way. Although they buy the same machine, customers have their own requirements in terms of image quality. One setting will be fine for some but not for others.’ Can you learn from TV or mobile technology customers? ‘Samsung Electronics operates in most countries, so we leverage with every culture and understand basic market culture. But healthcare is different. Although you know the TV market very well, that does not mean you know hospital markets. For healthcare you need to acquire additional capabilities that are very specific to this industry. ‘We see the synergy with mobile technology at some point. With the challenges in healthcare systems today there are increasing needs to integrate patient care in the hospital as well as home, and we know it could be a great asset for us to offer that within the same product.’ Following studies at the University Nueva Granada, Professor Stuart Hosie received his medical training at the Military Academy and Central Military Hospital in Santa Fé de Bogotá in Columbia (1981 to 1987). He his interest in paediatric surgery began in 1988, at University Hospital Eppendorf, Hamburg, Germany. In 1991, based in Düsseldorf, he became licenced to practice in Germany. Via Mannheim, Hosie went to Heidelberg, completing his habilitation there in 2003. In 2006 he was appointed Professor for Paediatric Surgery at Technical University Munich. He is also Medical Director of the Clinic of Paediatric Surgery at Schwabing Hospital, a facility of the Munich Municipal Hospital Group. The professor is also a member of the board of the German Society for Paediatric Surgery (DGKCH). of comprehensive paediatric centres providing child-oriented environ- ments that are suited for teaching. The crucial issue, however, is the shortage of paediatric nurses since the number of nurses correlates with mortality, no matter the coun- try of origin of the young patients. As Hosie underlines, ‘an experi- enced nurse sees more that an inex- perienced physician’ EUROPEAN HOSPITAL Vol 26 Issue 3/17

6 R A D I O LO G Y Future professionals across Europe The growing role and value of sonog Report: Fabrizio D’Abate and Angelo La Leggia Ultrasound is often the first line of imaging used in the diagnostic pathway of a patient’s journey into hospital. Additionally, the increased prevalence of chronic conditions and changes in the demographics of the general population has led to an increased demand for ultrasound. Fast-growing advances in technol- ogy also shift ultrasound into a more prominent role in patient diagnosis and clinical management. Ultrasound finds application in the prevention and diagnosis of a vari- ety of conditions. However, the safety and accu- racy of ultrasound assessments need appropriate training and extensive experience of the operator. These are the reasons behind the develop- ment of the role of sonographers. A sonographer is a healthcare profes- sional (non-medical doctor) who specialise in the use of ultrasound technology to produce diagnostic scans that will be integrated in the diagnostic process to help the medi- cal doctor to formulate the final diagnosis. This profession is well established in the USA, Canada, Australia, New Zealand and most of all in the United Kingdom, where the health- care system heavily relies on these professionals. The UK appears to represent a unique reality in Europe, and in the world, where such pro- fessionals are entitled to not only perform an ultrasound examina- tion but are also responsible for interpretation and reporting of the ultrasound findings. Professional certification The requirements for clinical prac- tice vary greatly from country to country. Because of the high levels of decisional latitude and diagnostic input, sonography requires special- ised education, often at postgradu- ate level through a master’s degree. Many countries require medical sonographers to have professional certification. Sonographers must understand physics, cross sectional anatomy, physiology and pathology as well as understand the symptoms and treat- ments involved in the condition. The areas of specialisation vary, some of which include: cardiology, vascular medicine, musculoskeletal, abdomen, soft tissues and small parts, obstetrics and gynaecology, paediatric, and neurology. The real- ity of sonographers across Europe is heterogeneous and is restricted to a few countries; sonographers now practice in Sweden, Denmark, Italy, Portugal, Norway and The Netherlands – some as part of pilot studies. Furthermore, physicians in Germany are beginning to view UK ultrasound services with interest and some countries are exploring the possibility for sonographers to be responsible for the interpreta- tion and reporting of the findings as well. The majority of sonographers employed in the Mediterranean countries fall mainly within the field of cardiology and vascular surgery. The lack of a uniform, pan- European, standardised structure for ultrasound training has been com- pounded by inconsistent regulatory norms across countries. This has negatively impacted the quality of technical training and the level of professional competency. With rising demand for faster, economical ultrasound exams, the lack of skilled, trained and qualified sonographers is intensifying pres- sure on clinicians. The specific lack of these competent healthcare pro- fessionals across Europe is related to the fact that, although in most European countries ultrasound is taught during residency to doctors only, there are no uniform stand- Angelo La Leggia MSc PhDc is a clinical scientist, specialised in Echocardiography. He gained a BSc in cardiac physiology at the University of Milan, and then focused on cardiovascular imaging, obtaining an MSc in cardiovascular sonography. He then gained another MSc in healthcare science and is completing his PhD in Clinical Research in Cardiology ‘as a result of my great passion for research’. La Leggia spent eight years in the cardiovascular department in Legnano, Italy and moved to London in May 2016. He is now a specialist echocardiographer at the Royal Brompton Hospital. His interest lies in 3-D echocardiography and Speckle Tracking imaging in valvular pathology, specifically in patients undergoing interventional and surgical repair. Machines are learning fast Recognising pattern, predicting survival Language recognition on the smartphone, spam filters in the e-mail programme, personalised product recommendations by Amazon or Netflix – all share one feature: they are based on an algorithm that recognises patterns in a set of data. This artificial generation of knowledge is called machine learning. , p u o r g s i s y l a n A e g a m I l a c i d e m o B i , r e k c o G l n e B r D f o y s e t r u o C n o d n o L , e g e l l o C l a i r e p m I , g n i t u p m o C f o t n e m t r a p e D Report: Michael Krassnitzer Radiology, in which huge data vol- umes are produced, is an increas- ingly important playground for machine learning. The analysis of quantitative image features in large medical databases is meant to allow statistic descriptions of tissue char- acteristics, diagnoses and course of diseases. At Imperial College, London, for example, a system called MALIBO (MAchine Learning In whole Body Oncology) is being developed that aims to detect tumours in whole- body MR images – without human intervention. So far, the system has looked at whole-body MRI scans of healthy volunteers to learn to iden- tify organs and their components. The ‘teachers’ are radiologists who marked and named the structures to be recognised in the MRI scans. This enabled the systems to identify organs and their components fully automatically in new whole-body MRI scans. Two different methods of machine learning were tested in this project: the principle of artificial neuronal networks that simulates the interac- High-resolution whole-body MR image of segmented structures tion of neurons in the brain, and so-called classification forests, i.e. large volumes of parallel decision- making paths. The former method was found to be superior to the latter. In the meantime MALIBO has entered phase 2, the recognition of primary tumours. ‘We have seen some good results in the detection of colorectal cancers,’ Dr Amandeep Sandhu Meng MBBS, a radiologist on the project team, reported. Training an algorIthm using 200 images This ambitious research project is but one among many presented in the session on machine learning at the European Congress of Radiology (ECR 2017) in Vienna from 1- 5 March 2017. A team at the University of Valencia (Spain) developed an algo- rithm that can identify and charac- terise individual vertebral bodies on CT scans of spinal columns. The algorithm, which was ‘trained’ on 200 images of healthy and diseased spinal columns, assesses 90 percent of scans it has not previously pro- cessed correctly. At Bari University (Italy) a research team evaluated a computer-assist- ed decision-making system (CAD), EUROPEAN HOSPITAL Vol 26 Issue 3/17

8 R A D I O LO G Y Seeking an efficient therapy for the progressive stage of MS PET offers new multiple sclerosis insights Positron Emission Tomography (PET) is helping to provide MS experts some insight into what drives pro- gression of the disease. PET also has the potential to quantify the effects of new, targeted therapies on MS patients, according to consultant neurologist Professor Bruno Stankoff. Professor Bruno Stankoff is a consultant neurologist at the MS Centre, in Saint- Antoine Hospital, Paris, and co-head of the team researching myelination and remyelination in the CNS: mechanisms, imaging and therapy, at the Brain and Spinal Cord Institute (ICM), in La Pitié- Salpêtrière Hospital. He leads several projects aimed at imaging remyelination, neurodegeneration, and microglial inflammation in MS. their lesions while others are not so strong in terms of remyelination, but this may help in prognosis when the disease is diagnosed by better iden- tifying the patients who will need treatment to promote lesion repair. Another key finding is in quantify- ing neuro-inflammation in patients with different forms of MS, which he believes may offer a marker of progression – that those with more inflammation may be more prone to having a progressive form of MS. The team is working on a study that combines PET and MRI to develop and assess a new imaging biomarker that has the potential to be used as an index of neurodegen- eration in multiple sclerosis. PET and the isotypically radiofluorinated form of Flumazenil (FMZ) will be used to assess neuronal damage at the early phase of either relapsing or primary progressive MS. * Research across long-term effects and prognosis, imaging techniques, B-cell depletion therapies, personalised care, immune response and progressive MS was presented at ECTRIMS 2016 (London, UK. 14-17 September). The congress themes included understanding the mechanisms of disease progression; new research findings including immune and mitochondrial abnormalities; approaches to early treatment; evolving approaches thanks to better understanding and personalised treatment; long-term treatment effects and prognosis; new insights from registry and cohort studies; new directions in progressive MS research; imaging neuroprotection and repair, and advances in imaging techniques. Report: Mark Nicholls The role of PET was among the key topics at the recent European for Treatment and Committee Research in Multiple Sclerosis (ECTRIMS) annual congress, held in London. Speaking after his pres- entation ‘PET imaging of cellular and molecular abnormalities in MS’ at the congress - which is a ded- icated platform to promote and enhance research in MS – neu- rologist Professor Bruno Stankoff expanded on the potential of PET in advancing knowledge and treat- ments of the condition. PET, he said, might offer an insight into an ‘improved compre- hension of what drives MS progres- sion’, whilst also shaping the devel- opment of new treatments. ‘These are not therapies targeting relapses but targeting root mechanisms and,’ he added, ‘with PET used to evalu- ate the effect of some therapies that promote endogenous myelin repair, decrease neuro-inflammation or decrease neurodegeneration.’ MRI remains a proven modality in the diagnosis of MS, but PET has the advantage of enabling very spe- cific imaging directed to cellular or molecular components. ‘PET is very specific, very sensitive to changes and we can quantify the image,’ explained Stankoff, who is a con- sultant neurologist at the MS Centre, Saint-Antoine Hospital, Paris. ‘We have taken advantage of technique to approach some biological mecha- nisms that could identify MS patho- physiology and MS progression.’ In his on-going research with PET for MS, Stankoff and team have sought to quantify the dynamics of TRUECOIN* Study Demonstrates Again: myelin loss and repair; image neu- ro-inflammation related to innate immune cells, and the use PET to quantify the normal compartments of neurodegeneration in core differ- ent stages of the disease. ‘By focus- ing on these we might quantify two of the main mechanisms that can drive progression of the disease, the success or failure of endogenous lesions repair and the level and localisation of neuro-inflammation,’ he explained. While stressing that the work is still at the research stage rather than in daily clinical practice, he sug- gested that the benefits to patients would become clearer in the mid- or long-term, rather than the short- term. ‘The benefit is shortening of the timeframe to develop some efficient therapy for the progres- sive stage of the disease,’ Stankoff explained, adding that, so far, results are promising and PET has already provided some important answers in the field of MS. With individual patients, it can show how some people can repair BIOTRONIK Home Monitoring Reduces Mortality Meta-analysis of Home Monitoring trials TRUST, ECOST and IN-TIME shows the reduction of all-cause mortality in ICD patients * Hindricks G et al., Daily remote monitoring of implantable cardioverter-defibrillators: Pooled individual patient data from IN-TIME, ECOST, and TRUST trials suggest a mechanism of clinical benefit, ESC Congress 2016, Rome. www.biotronik.com Latest adv might not enter clinic soon Current advances such as phase- contrast CT are taking medical imaging further but their use in clinical practice may have to wait up to a decade, prominent physi- cist predicts. By Mélisande Rouger Cooperation between medical spe- cialists and biomedical engineers is having a fresh start as healthcare pro- fessionals were invited to the annual meeting of the Spanish Biomedical Engineers Society (CASEIB 2016) in November in Valencia. Researchers and key representa- tives from all across the country shared expertise during dedicated roundtables and sessions to try and tailor technological advances to cur- rent healthcare needs, notably in medical imaging. During the meet- ing, José María Benlloch, a profes- sor of investigation at the Spanish Superior Council for Scientific Investigation at Valencia Polytechnic University, presented the newest advances in medical imaging tech- niques. The long held perception that CT is better for hard tissues imaging and MRI better for soft tissues is about to become history, according to Benlloch, who obtained the Spanish National Investigation Award in 2014 for applying parti- cle physics techniques to molecular imaging in biomedicine. However, years will pass before some of these improvements can benefit popula- tion healthcare, he believes. ‘Phase-contrast will change the paradigm and bring CT into soft tissue imaging. However the tech- nique will not enter clinical practice before 10 to 15 years, because we first need a coherent source of X-rays. I believe X-ray techniques using laser will become such a source and will be much more affordable in the future.’ Unlike CT spectroscopy, a mature technique that will enter clinical practice in three to five years accord- ing to Benlloch, phase-contrast CT is still facing a number of technologi- cal challenges. For X-ray detectors to be sensitive to phase-contrast, resolutions in the one micrometer range are needed. Researchers are working on these developments, but they still have a long road ahead.’ ‘We can achieve this resolution by placing a rack on detectors with poorer resolution, but in doing so we lose a lot of X-ray power. Clearly significant technological advances are still lacking for the technique to become financially available and be used in most hospitals,’ he said. trademark difficulty in imaging hard tissues could soon be solved as well, as Benlloch and his team are currently working on MRI solutions for dental applications, in which dentists could not only see teeth but also the surrounding soft tissues. MRI’s ‘This is very interesting for den- tists because it will not use radia- tion. They will be able to image gums and things that are now almost invisible on X-ray,’ he said. This new MRI development uses a permanent magnet applied to only a small part of the body. It also uses a EUROPEAN HOSPITAL Vol 26 Issue 3/17

1 0 R A D I O LO G Y The GBCA satellite symposium Clinicians define an optimal approach for MRI contrast to maximize benefit Gadolinium-based contrast agents are an essential component of MRI exams, but are challenged by findings of residual depositions of gadolinium in the body, even though the clinical relevance remains unknown. Three clinicians described how changes to MRI protocols and dose levels for contrast media can optimise the balance between benefit and risk for patients and radiologists. For magnetic resonance imaging (MRI) examinations the use of gadolinium- based contrast agents (GBCAs) is essential to detect and characterise cancerous tumours and delineate and assess vascular disease. The safety profile of GBCAs has always been considered highly favourable with few relevant contraindications and a lower rate of acute adverse reactions than are seen for iodinated contrast agents used for X-ray based imaging. When an association between GBCAs and nephrogenic systemic fibrosis (NSF) was described in 2006, confidence was shaken, provoking a debate regarding the risk versus the benefit of these compounds. Thanks to well-documented studies and changes to MRI protocols, the debate subsided and, since 2009, no further cases of NSF have been reported. However, debate was re- ignited in 2014 with the first reports of increased signal intensity in the brain after the administration of these agents. To provide an update for radi- ologists at the European Congress of Radiology (ECR 2017, in Vienna) on the use of GBCAs and how they can best optimise the balance between risk and benefits, three prominent experts presented insights into the current state of the debate during a satellite symposium hosted by Bracco Imaging. Dr Francesco Sardanelli, Professor of Radiology at the University of Milan, Director of the Department of Radiology at the Research Hospital Policlinico San Donato in Milan, Italy, said: ‘In a context where our knowledge is still limited and confusion and false sim- Dr Francesco Sardanelli Dr Luis Martí-Bonmatí Dr Josef Vymazal plifications make our practice more difficult, we need to continuously re- evaluate the available evidence and to make careful clinical judgment of the profile of each individual patient. The future will be a less standard- ised approach for gadolinium-based contrast agent usage, an application of personalised medicine to the field of MRI.’ The emergence of findings for NSF came in the context of what Sardanelli compared to a ‘perfect storm’ yet had a positive impact on clinical practice, because it forced radiologists to rethink the value of unenhanced MRI, to better apply technical tools for accurate diag- nosis, to screen for renal failure patients as candidates for GBCA injection, and to accurately describe the type and dose of contrast agent for each patient. The current discussion, he said, focuses mainly on gadolinium accu- mulation in the brain, yet the clinical relevance of the findings remains unknown. At this point, no clinical consequences, and no neurological symptoms have been associated with brain signal increases in patients who were injected with GBCAs. ‘The high impact that this message has is that brain is brain,’ he noted, outlining key points for balancing diagnostic performance with safety. First is to rethink the indications for GBCAs. Where one in three MRI examinations today includes con- trast-enhanced scans, a reassessment of the necessity of a GBCA injection, ‘could reduce this rate, but probably it will be difficult to go below one in four’. A second issue is to take into consideration the age and clinical profile of the patient, he said, while radiologists might also rethink the GBCA dose to determine if less is better. On this point, Dr Luis Martí- Bonmatí, director of medical imaging at La Fe University and Polytechnic University Hospital in Valencia, Spain, discussed the potential for determining an optimal approach in the use of gadolinium contrast agents in order to achieve the maxi- mum benefit. Acknowledging the concerns, he said, ‘It is relevant to recognise the extremely impor- tant role that contrast-enhanced MRI studies have in defining the pres- ence and characteristics of so many different diseases and pathologies. The issue then becomes how to strengthen contrast enhancement across most indications that require contrast injection to achieve the highest diagnostic confidence.’ this point no clinical manifestations have been described in connection with the phenomenon. Martí-Bonmatí focused on the contrast agent property known as relaxivity, a measure of the degree to which a given amount of con- trast agent shortens the T1- and T2-weighted relaxation times of tis- sue and how these values can be exploited depending on the clinical need, to increase enhancement or to lower the dose of the agent used. Not all contrast agents based on gadolinium are equal, he noted. Three chelated compounds are cat- egorised as high-risk for NSF, while five others, are classified as medium- or low-risk in Europe. Regarding gadolinium depositions in the brain the current evidence is inconsistent. In all cases high-risk chelates and double or triple dose administra- tions are to be avoided, particularly for patients with renal insufficiency. Using lower-risk gadolinium che- lates the lowest dose should be administered to obtain the clinical information required. On this point he demonstrated how the selection of an appropriate contrast agent and use of higher field strength can maximise clinical information while minimising the risk for patients. Contrast media with high relaxivity allow the maximum visual enhance- ment, depiction and characterisation, enable the use of low doses and thereby assure the greatest possible benefit for both the patient and cli- nician. Dr Josef Vymazal from Na Homolce Hospital in Prague, Czech Republic, said he is ‘deeply con- vinced that this is still a work in pro- gress and we should be very careful about conclusions drawn about the topic of gadolinium deposition’. He emphasised that the mechanism by which GBCAs penetrate into the brain is still not understood, and to The unique properties of gado- linium are what have made this metal in a chelated form an essen- tial part of almost all MRI contrast agents, he explained. In an analysis of published and presented works, Vymazal showed that, as yet, there is no data available on the chemical form in which gadolinium is depos- ited and that work is needed to elab- orate this. In addition, the potential contributions of other metals known to reduce T1 and T2 relaxation times and to deposit in deep nuclei of the brain, such as iron, copper and man- ganese, have not yet been assessed, he said. Building on these findings, in a study completed just days ahead of the ECR congress, Vymazal opened a path for further clinical investigation on what he called a new concept focused on ‘gadoferritin’ or gado- linium-ferretin complexes, a com- pound developed at the Institute of Organic Chemistry and Biochemistry in Prague. Signal intensity report- ed in deep-brain nuclei may be explained by the presence of such gadolinium-ferretin complexes, the study suggests. In the end, he stated, it is possible that the chemical form in which gadolinium complexes are retained in the various brain areas may vary over time, and more than one form may coexist at the same time. In summary, Vymazal noted that while gadolinium deposition in vari- ous organs, including brain, bone, skin and liver, has been demon- strated by pathological evidence for all GBCAs, including both linear and macrocyclic agents, at this time there is insufficient evidence to allow con- clusions to be drawn concerning the clinical impact of this phenomenon. The latest cardiac devices feature MRI AutoDetect Cardiac device patients can be scanned field strength MRI scans without any scanning area restrictions. This can be especially important for patients with comorbidities such as cancers or single- or multi-vessel disease in patients with coronary artery disease, which can require in-depth examination of tissue in anatomical regions that might previously have been restricted. Recent technological advances have generated a wave of MR-conditional devices that increase patient access to often crucial MRI scans. However, the processes involved in system selection and configuration before and after MRI scans can prove to be time-consuming and complex. Biotronik provides various possi- bilities to maximise patient access to MRI while streamlining workflows for clinicians. Automatic recognition of MRI zone To simplify processes for clinicians, devices in the latest range of pace- makers, ICDs and cardiac resynchro- nisation therapy devices feature MRI AutoDetect – a technology that ena- bles the device to automatically rec- ognise when it is in an MRI environ- ment within a programmable time window of up to 14 days. When an MRI environment is sensed, the device automatically converts into MRI mode and then returns back to full functionality after the scan is complete. This reduces the number of patient visits required to config- ure the device and also minimises the duration of reduced therapy. Increased MRI accessibility Dr Geraint Morton, at Portsmouth Hospitals NHS Trust, United Kingdom, emphasises the impor- tance of MRI access. ‘Cardiac patients with comorbidities such as neurological diseases, or orthopae- dic conditions, often require MRI, so it’s essential to maximise accessi- bility. The care and management of comorbidities can be compromised in many cases if patients can’t have an MRI scan.’ In addition to the existing approv- al of 1.5-T MRI scans with full-body scanning options, Biotronik recently received CE approval for 3.0-T full- body scanning with devices in its latest range of MR-conditional pace- makers. As a result, clinicians have more flexibility to perform high Biotronik develops ProMRI portfolio online tool ‘To further ease the complexi- ties surrounding MRI for cardiac patients, Biotronik recently intro- duced the online tool ProMRIcheck. com, which enables physicians to verify the MR conditionality of Biotronik device systems prospec- tively or retrospectively to implanta- tion,’ the company reports. ‘With the world’s largest range of implantable cardiac systems approved for MRI scans in its ProMRI portfolio and a variety of accompanying technolo- gies, Biotronik improves MRI acces- sibility for cardiac patients while simplifying the processes involved for clinicians.’ EUROPEAN HOSPITAL Vol 26 Issue 3/17

1 2 L A B O R AT O RY Seeking greater harmonisation in laboratory medicine Unifying recognition of professional qualifications Improved harmonisation of laboratory medicine practice across Europe will help lead to better patient outcomes and produce comparable laboratory information irrespective of where and how the data have been generated, Mark Nicholls reports With harmonisation regarded as a fundamental aspect of quality in laboratory medicine, it is high on the agenda of delegates to the EuroMedLab 2017 congress to be held between 11-15 June at the Megaron Athens International Conference Centre, Greece. Harmonisation involves all the steps of the service (pre-analytical, analytical, and post analyical phase) as well as embracing aspects of the profession in a symposium host- ed by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM). This will pro- vide four lectures dealing with the harmonisation of the pre-analytical phase, medical laboratory accredi- tation, the mutual recognition of professional qualifications across Europe, as well as continuous pro- fessional development. Gilbert Wieringa chairs the European Federation of Clinical Chemistry and Laboratory Medicine’s (EFLM) Professional Committee and is clinical lead for Laboratory Medicine in Bolton, England. Formerly the healthcare scientists programme lead in the Department of Health, and Greater Manchester Primary Care Trusts’ pathology lead, his main interests are in the provision of antenatal screening services, quality assurance for ‘high street’ diagnostics and the harmonisation of growth hormone measurements. of Chair Speaking to European Hospital ahead of the conference, Gilbert Wieringa, EFLM’s Professional Committee, explained the importance of harmonising the recognition of professional quali- fications. ‘It’s to ensure that lab- oratory medicine is practised to common standards, so that patient safety is protected irrespective of which country the specialist ema- nates from. ‘Under EU Commission Directive 2013/55/EU – the Recognition of Professional Qualifications – har- monisation would extend opportu- nities for specialists to practice in other EU countries without having “compensation measures” imposed on them such as the re-taking of local professional exams; in turn it could also catalyse a more equitable distribution of skills and resources across the EU.’ Dr Wieringa will highlight how EU Commission Directive 2013/55/ EU provides a passport to profes- sional migration across EU borders for professions that can work to a Common Training Framework. He will also point to EFLM hold- ing a Register of ‘Specialists in Laboratory Medicine’; how the organisation is pursuing recognition as a unique cohort amongst labo- ratory medicine practitioners, and how achieving recognition raises the profile of the contribution of laboratory medicine to better health and best care. Formed in 2007 through the merg- er of the Forum of European Societies of Clinical Chemistry (FESCC) and the European Communities Confederation of Clinical Chemistry (EC4), the EFLM connects National Societies of Clinical Chemistry and Laboratory Medicine to create a platform for all European specialists in laboratory medicine. A strong advocate of the Register of specialists, in adding weight to the argument for their recognition, in his talk Wieringa also intends to describe the backbone work that already carried out by EFLM and its predecessor organisation EC4 in set- ting standards for specialist practice, establishing the Register, an expect- ed code of conduct, and adoption of the unifying term ‘Specialist in Laboratory Medicine’. He will offer guidance on how people can join the Register, as well as share an update on progress with implementation of the Recognition Directive at the EU Commission. While medical staff already enjoys professional migration as members of the sectoral professions, the Directive offers equal opportunity to science and pharmacy trained specialists, once a Common Training Framework has been adopted by one third of the EU member states (i.e. 10). It remains unclear how long the harmonisation process will take, though EFLM is maintaining close contact with its leads at the EU Commission throughout. the Laboratory The session will also hear from Wim Huisman, previously Head of for Clinical Chemistry and Haematology at the Medical Centre Haaglanden in Leidschendam; Ana-Maria Simundic, Professor in the Department of Medical Biochemistry at Zagreb University, and Elizabeta Topic, Professor of Medical Biochemistry at the Faculty of Pharmacy and Biochemistry University of Zagreb. * The EuroMedLab 2017 ELFM symposium ‘Harmonisation in laboratory medicine’: 10.30am-12.30pm, 12 June. Venue: Skalkotas Hall, Megaron Athens International Conference Centre, Greece. MiniCollect weds carrier tube Since autumn 2016 a small tube has been making daily life easier for users and patients. A simple but effective addition now offers many new advantages in analysis, the manufacturer reports. Following the successful launch of MiniCollect, a new capillary blood collection system, Greiner Bio-One has launched the tube MiniCollect Complete to simplify the analysis process. For centrifugation, MiniCollect tubes can be threaded into a Premium carrier tube using a simple rotational movement, the Austrian manufacturer Grenier Bio-One reports. ‘In the Complete version, the MiniCollect tube is already irre- versibly assembled in the carrier tube. This brings many advantages for sample analysis in instruments.’ When combined, the dimensions correspond to a standard 13 x 75 mm tube format, the firm adds. ‘This allows the tube to be placed directly into a standard centrifuge adapt- er. Previously, it was necessary to adjust the settings on the analysis device, because the tube format was different for venous and capil- lary blood samples. The combined tube means that both capillary and venous blood samples can now be analysed in the same way, without complex modification of the device. ‘Another advantage is that the carrier tubes can be identified using standard label formats. MiniCollect Complete are primary tubes. Both blood collection and subsequent analyses can be carried out using the same tube. It is not necessary to transfer the sample material to a secondary tube for analysis.’ The tube also has a new cap. ‘The membrane can be pierced by a cap-piercing analysis needle while the cap is closed, before automati- cally resealing after the needle is removed,’ Greiner adds. ‘The caps are completely sealed, meet the highest standards and can be sent via pneumatic post with confidence, and without losing any sample material.’ filling volumes Combined filling volume and integrated blood collection scoop Combined for the EDTA and serum tubes make the preparation of samples more straightforward, the firm points out. ‘Two easily visible filling marks on the tube provide greater flexibil- ity for use. It’s no longer necessary to decide on a certain volume in advance, which reduces logistical efforts.’ The blood collection scoop inte- grated into the wide tube opening enables the drop of blood to be transferred to the MiniCollect pri- mary tube quickly and easily, mini- mising adhesion. ‘The sample imme- diately comes into contact with the additive inside the tube.’ No to unnecessary agitation The sight of a puncture needle often causes anxiety in children. ‘One of the main advantages for our young patients is that the safety mechanism of the MiniCollect safety lancets means that no needle is visible at any point before or after the puncture. This makes the situa- tion more relaxing for all involved,’ explains Petra Langmayr, former paediatric nurse and product spe- cialist at Greiner Bio-One. After the puncture, the needle retracts automatically and is safely enclosed within the plastic casing. The risk of needlestick injuries is prevented. * Product availability depends on country-specific registrations. EUROPEAN HOSPITAL Vol 26 Issue 3/17

1 4 L A B O R AT O RY IFCC experts unite to establish clear values A new era for lab medicine A new drive to increase the clinical effectiveness of laboratory medicine and take the discipline into a new era is being launched, Mark Nicholls reports outcome; determine the impact that laboratory medicine should have on this outcome; gather evidence from the literature, or from a new study, to determine the actual impact of laboratory medicine data; prepare a report in a standard format leading to a recommendation on how to use laboratory medicine investigations to optimise clinical outcome; pub- lish the report in a standard format creating a freely available, growing electronic library of studies link- ing clinical outcomes to laboratory medicine results. Beastall suggests that a grow- ing e-library of clinical effectiveness reports will provide a resource for laboratory medicine specialists to use in collaboration with their local physicians, and over time that will lead to greater harmonisation in the clinical application and use of labo- ratory medicine results. To generate momentum in the project, an international cohort of laboratory medicine specialists will- ing to use the structure will need to be recruited, with IFCC co-ordi- nating studies and providing advice. Entering a new era ‘There is widespread recognition that laboratory medicine is entering a new era of impact on healthcare,’ Beastall believes. ‘To date, the focus has been on the growing availability of new tools and new technologies to improve the quality and expand the repertoire of investigation, espe- cially at the molecular level. ‘There needs to be a parallel drive to educate users of laboratory medi- cine services that the way in which by different laboratories – Beastall maintains that this focus on improv- ing analytical quality is not, by itself, sufficient to bring maximum benefit to patients. ‘Improving the clinical effectiveness of laboratory medicine relies on the optimal delivery of the right test, to the right patient at the right time, coupled with a con- sistent interpretation of the results obtained, which are then translated into an evidence-based decision that will lead to the optimal clinical out- come for individual patients.’ He also pointed out that there are currently few clear examples of the link between the result of a laboratory medicine investigation and the optimal clinical outcome for patients. This may be down to vari- ous reasons, such as the ‘weight of other clinical and diagnostic infor- mation and evidence that the physi- cian has to consider’. To address this, the approach in the new IFCC programme is to start with a single defined clinical outcome and then provide evidence of the impact that laboratory medi- cine results have in delivering that outcome. Beastall’s presentation aims to define appropriate clinical outcomes and give examples of how labora- tory medicine impacts on them. The IFCC proposed structure is constructed around a standard tem- plate for conducting clinical effec- tiveness studies with five defined stages: identify a specific clinical Hindered by proteins and the human proteome complexity Graham Beastall is a former President of the IFCC, having served as President from 2009-2014. Prior to 2009 he was Clinical Lead for a multi-site network Department of Clinical Biochemistry in Glasgow. He has published extensively on biochemical endocrinology and led IFCC projects to demonstrate the value of laboratory medicine in healthcare and to promote the need for increasing clinical effectiveness. Beastall was formerly President of the Association for Clinical Biochemistry (ACB) and Vice President of the Royal College of Pathologists (RCPath) in the United Kingdom. new results may be used will be critical to the delivery of improved clinical outcomes.’ Such a move will enable patholo- gists and laboratory medicine spe- cialists to provide a better service to users and patients. ‘The broader impact of the initiative should be a gradual recognition by physicians, other healthcare professionals and patients of the importance of labora- tory medicine,’ he added. However, he stressed that success of the new initiative will depend on others accepting the invitation to embrace the proposed structure, perform clinical effectiveness studies and report them in a standard format. * The IFCC Symposium: ‘Increasing clinical effectiveness in laboratory medicine’. 13 June. 10.30am-12.30pm Skalkotas Hall, Megaron Athens Centre, . Vathany Kulasingam is a clinical biochemist at the University Health Network in Toronto, an Assistant Professor at the Faculty of Medicine, University of Toronto and Fellow of the Canadian Academy of Clinical Biochemistry. Her current interests include novel tumour biomarker discovery and application of proteomics to clinical practice. discovery while highlighting the difficulties associated with cancer biomarker discovery and why many promising cancer biomarkers fail in the clinic. Also speaking at the session is Henry Rodriguez, Director of the Office of Cancer Clinical Proteomics Research at the National Cancer Institute at NIH, focusing on ‘Proteogenomic analysis of cancer: New opportunities in cancer biol- ogy and precision medicine’, and Professor Catherine Alix-Panabières from the Faculty of Medicine at the University of Montpellier, on ‘Gfr and drug dosage adaptation: are we still in the mist?’ * 12 June. 10.30am-12.30pm. ‘Advances in cancer biomarker discovery’ symposium. Lambrakis Hall, Megaron Athens International Conference Centre. EUROPEAN HOSPITAL Vol 26 Issue 3/17 While there are ~20,000 protein- coding genes, Kulasingam said, the human protein is estimated to have 500,000-1,000,000 proteo forms because of single nucleotide vari- ants, alternative splicing and post- translational modifications. ‘Mass spectrometry can provide both structural as well as quantita- tive information, that’s the key. Will this yield novel biomarkers? I’m not sure yet because we do not have such data, but I think this is one avenue to explore. ‘We now have a strong under- standing of the importance of good study design, appreciating pre-ana- lytical considerations, asking the correct biological questions, and we understand the importance of hav- ing good biorepositories.’ That need for good clinical infor- mation and samples is now more clearly recognised for biomarker discovery and validation, particu- larly after work carried out using more conveniently accessible sam- ples had unintentionally led to false discoveries. No major discovery since the ’80s With limited discoveries in serum biomarkers, with nothing major since the 1980s, Kulasingam believes the way is now clearer to advance cancer biomarker discovery but adds, ‘We have come a long way but I think we still have a while to go.’ This symposium in Athens will offer participants a greater under- standing of how systems biology can contribute to new biomarker Coupled with steps to harmonise laboratory medicine services across Europe, a move to make lab medi- cine more clinically effective is being spearheaded by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The latest position will be out- lined at the EuroMedLab 2017 con- gress, booked for 11-15 June at the Megaron Athens International Conference Centre. Former IFCC President Dr Graham Beastall will deliver a presentation looking at ‘a proposed structure for defining, undertaking and reporting studies to assess the clinical effec- tiveness of laboratory medicine’. Presentations from other speak- ers aim to define and demonstrate clinical effectiveness in this field. ‘Laboratory medicine results influ- ence a high percentage of all clinical decisions,’ Beastall confirmed during our European Hospital interview. However, this impact is diluted by variability in the services provided, the results obtained and the way in which those results are used. Improving clinical effectiveness is not enough ‘Consequently,’ he pointed out, ‘there is a global programme to har- monise the practice and delivery of laboratory medicine for the benefit of the patient.’ While the harmonisation pro- gramme has several dimensions - many of which are targeted at reduc- ing the variability in results provided Report: Mark Nicholls Cancer biomarker testing represents an important element of the clinical biochemistry service, yet progress in this area in the last two decades has been slow. With no major new serum cancer biomarkers introduced into clinical use within the last 10 years - despite advances in various omics tech- nologies - experts are continuing to work hard to unlock the technologi- cal potential to advance the diagnos- tic and treatment options available to patients. Strategies to discover and validate novel biomarkers A symposium on advances in bio- marker discovery, will examine strat- egies for discovering and validating novel cancer biomarkers by using a combination of omics technologies, during the EuroMedLab 2017 con- gress in Athens this June.* Among the speakers will be Dr Vathany Kulasingam, from the University Health Network in Toronto, Canada, who will focus on mass spectrometry as a tool for cancer biomarker discovery. ‘Mass spectrometry,’ she pointed out, ‘is a powerful analytical tool and the use of this technology for this applica- Strategies to advance cancer biomarkers tion is not novel. However, very few serum cancer markers have reached the patient. For what reason? What are the hurdles?’ The huge complexity of the human proteome Points she will focus on are the chal- lenges associated with biomarker discovery, including the complex- ity of the proteins and human pro- teome, the importance of having a good biorepository and a good study design to avoid bias. ‘It’s important to use this technology to help us understand the biology of the disease,’ she added. ‘We must have a fundamental initial question to ask and we have to understand the disease and its biology. We can use mass spectrometry to help us understand that and then refine our questions better.’ However, a major challenge has arisen due to the under-estimation of the human proteome complexity.

1 6 L A B O R AT O RY Liquid chromatography tandem mass analysis Wanted: an automated clinical LC-MS/MS analyser with broad, expandable testing menu Combining the physical separation power of liquid chromatography with the mass analysis capability of mass spectrometry – i.e. liquid chro- matography tandem mass spectrom- etry (LC-MS/MS) – enables accurate, sensitive and selective separation, detection and identification of mol- ecules in complex mixtures such as blood, serum and urine. Senior biomedical scientists from the Cardiff and Vale University Health Board, United Kingdom, con- sider LC-MS/MS an important tool in running powerful diagnostic analy- ses across a range of applications, including endocrinology, toxicology and metabolic screening. However, like many other clinical diagnostic laboratories around the world, they admit they do not use the technol- ogy to its full potential. Here, Gareth Jones, Luke Griffiths and Paul Bramhall, members of the Cardiff team, describe obstacles that prevent wider adoption of the technology and share their belief that a standardised and automated clinical LC-MS/MS analyser with a broad and expandable testing menu may overcome the challenges of current methods. This could estab- lish LC-MS/MS as the technology of choice for clinical diagnostic testing. The challenges It is well recognised that current LC-MS/MS systems have a limited testing menu. This makes it time consuming for laboratory profes- sionals to develop, review and vali- date new assays that would allow them to run a wider variety of tests. Additionally, analyses performed using current LC-MS/MS methods involve several complex manual steps, including sample acquisition and preparation. Complexity is further increased hours service.’ For all these reasons, automated immunoassays have remained the preferred method within clinical diagnostic laboratories for many years. Yet, modern LC-MS/MS tech- niques offer some considerable ben- efits. The analytical power of LC-MS/MS For certain analytes, immunoassays can be subject to interferences, lim- iting their specificity and reducing the quality of results compared to LC-MS/MS. In addition, immuno- assay-based methods can be very time consuming. ‘Some tests take only two minutes using LC-MS/MS compared to the 40 minutes it takes to use an immunoassay-based test,’ Luke Griffiths points out. A further disadvantage of immu- noassay-based tests is that they are developed in kit form and require FDA approval – a procedure that may take a few years to complete. ‘There have been cases where we have waited two years for an immu- noassay kit to become available. Alternatively, after completing vali- dation and verification on an LC-MS/ MS system you could have run a test immediately,’ Paul Bramhall explains. As always, cost is an important consideration in evaluating different analytical methods. ‘LC-MS/MS does require a greater outlay upfront,’ because, in many cases, multiple separate tests must be performed to generate a single analytical result, leading to considerable time and cost inefficiencies. ‘Using our cur- rent LC-MS/MS systems,’ Gareth Jones explains, ‘we have to spend up to four days undertaking three different tests to obtain a full steroid profile. It would be much more cost- effective if these tests could be run simultaneously on one instrument.’ Another key challenge is the lack of laboratory staff sufficiently trained to use LC-MS/MS technol- ogy to its full potential. ‘Due to the overly technical nature of our cur- rent LC-MS/MS systems, only six of our team of 60 biomedical scientists have the specialist skills necessary to run them,’ Jones adds. ‘This poses a particular problem for our out-of- Significantly shorter therapy durations may be sufficient Killer bugs put on the critical list While new agents to fight virulent pathogens are in the pipeline, a new study pinpoints where a recent addition is already being applied in the clinic, John Brosky reports Bacterial resistance to antibiotic therapies is a global crisis that recently prompted the World Health Organisation (WHO) to publish its first ever list of pathogens consid- ered to be a priority for the threat they pose to human health. Among the 12 pathogens singled out, a virulent bacterium named Pseudomonas Aeruginosa was among three considered to be criti- cal in terms of need for new thera- pies to combat this killer. A new strategy to fight these often fatal infections has emerged in the form of combination therapies, where a parent drug capable of neutralising the harmful bacteria is paired with an agent that can either protect the active molecule from bacterial resistance tricks, or else can facilitate the penetration of the second agent into the bacterial cell so the neutralising molecule can go to work. Many of these promising new agents are still in pre-clinical stages, and some are moving through clini- cal trials. In other words, few are ready and approved for prime time use in intensive care units (ICUs) where patients are suffering. A clinical pharmacist specialising in infectious diseases at Sinai-Grace Hospital in Detroit, Michigan, Jason Pogue, Pharm.D, set out to learn where one of the more promising newer agents is actually being used in the clinic and the effectiveness of its use. Randomised controlled trials of the combination of the parent drug ceftolozane with an inhibitor agent tazobactam, in target populations, will ultimately answer the ques- tion of efficacy for clinicians, he said. Ahead of that key piece of evidence, Pogue said a description of real-world utilisation is helpful to describe for clinicians what has been done in clinical practice as a supplement to clinical trial data. At the 2017 European Congress of Clinical Microbiology and Infectious Diseases, held in Vienna this April, Pogue presented a poster including 293 patients receiving the ceftolo- zane-tazobactam therapy who were identified through an electronic research database of 315 hospitals in the United States maintained by the Becton Dickinson Company. The study was supported by Merck & Co., which manufactures the ceftolozane-tazobactam combina- tion therapy under the brand name Zerbaxa. Pseudomonal infections are complicated and can be life threatening. The common pathogen Pseudomonas Aeruginosa, for example, frequently causes nosocomial infections such as pneumonia, urinary tract infections and bacteremia Among the 293 patients there were 314 treatments, most often started in the ICU and most often to treat respiratory tract infections. The most common pathogen was Pseudomonas Aeruginosa, which was isolated in 241 cases or 77% of the combination courses of treat- ment. The conclusion for the study remains necessarily inconclusive as to the effectiveness of treatment, Pogue said. Instead the data is descriptive of how the therapy is being applied, particularly as these data show the agent is being used outside of the labelled indication in nearly half the cases. In a next step, the pharmacist said, the study lends itself to a comparison to patient populations who received other therapies for the same type of conditions identi- fied in the ceftolozane-tazobactam study, bringing clinicians closer to the efficacy question ahead of the results from clinical trials, and as a complement to those trial results once published. ‘As these data show, the pri- mary use of ceftolozane/tazobac- tam in the clinic is for respiratory tract infections with Pseudomonas Aeruginosa. However, the published evidence to support this is very lim- ited. Approval of this combination was granted on the basis of effi- cacy against specific disease states (urinary tract infections and intra abdominal infections), not against a pathogen. Yet, because thank- fully these resistant organisms are relatively rare, there is unfortunately a lower likelihood they will be encountered in a registry trial for drug approval. The clinical concern for drug resistant P. aeruginosa is in the respiratory tract where, as Dr Jason Pogue is an infectious diseases clinical pharmacist at Sinai-Grace Hospital in Detroit, MI. He also serves as an assistant clinical professor of medicine at the Wayne State University School of Medicine. He received a bachelor degree in Chemistry from Gannon University before obtaining his doctor of pharmacy degree from the University of Pittsburgh. He then completed a PGY-1 residency at the University of Pittsburgh Medical Centre, after which he left Pennsylvania for Michigan to obtain his PGY-2 ID training at the University of Michigan Health Systems. His research interests focus on epidemiology and treatment of multi-drug resistant Gram-negative organisms and antimicrobial stewardship, and he has co-authored over 70 peer reviewed articles, 100 abstracts at national and international meetings and multiple book chapters in these areas. Pogue was recently invited to become an advisor for USCAST, an organisation that aims to standardise antimicrobial susceptibility breakpoints in the USA. stated, data are currently lacking,’ he said. ‘What we found through our analysis is that the primary use of ceftolozane/tazobactam appears to be for Pseudomonas Aeruginosa in patients with nosocomial pneumo- nia and, while the combination drug is not approved for that indication, EUROPEAN HOSPITAL Vol 26 Issue 3/17

1 8 I N F E C T I O N C O N T R O L Call to screen refugees for MRSA and MDGRO upon hospital admission Screening, isolation, hygiene equal money well spent MRSA among refugees Comprehensive examinations of 143 refugee patients* hailing mostly from Afghanistan and Syria, which were conducted between June and December 2015, showed a high prevalence of MRSA, ESBL and MDRGN upon hospital admission. The figures exceed not only those of the general population but, alarmingly, also those found in high-risk groups, such as residents of nursing homes or home care service patients. Professor Ursel Heudorf of the Department of Infectiology and Hygiene at the Public Health Office in Frankfurt, Germany, is therefore demanding general screening of refugee patients upon hospital admission. Groningen, Holland 2014 Ingolstadt, Frankfurt, Frankfurt, Frankfurt Uni Uni 2016 2015 2016 2016 KH Israel, 2014 t n e c r e P 16 14 12 10 8 6 4 2 0 Professor Ursel Heudorf MD, Public Health Physician and Deputy Director and Director of the Hygiene Department at the Public Health Office in Frankfurt/ Main, Germany, is an expert in hygiene in medical and community facilities with a focus on multi-resistant organisms. She initiated and today heads the MDRO (Multi Drug Resistant Organism) Network Rhine-Main, which offers a wide range of services for the general public and an expert audience – such as studies on MDRO prevalence in non-acute clinical settings. The network conducted the largest multi-centre study on MDRO among refugee patients to date (all studies and further information available on www.mre-rhein-main.de). Data speak the truth - In the popula- tion at large, MRSA rates are below one percent. Among groups at risk, such as nursing home residents, it is six to nine percent. However, among the refugee patients examined in the Rhine-Main region 9.8 percent carried MRSA. -Found to be pre- sent in approximately eight percent of the general population, these organisms were detected in risk groups between 7.5 percent (dialy- sis patients), 14 percent (patients of home care services) and 18 to 27 percent (nursing home residents). During the above-mentioned study the organisms were pre- sent in 23 percent of the refugee patients, with 1.8 percent carry- ing MDRGN bacteria, resistant to four classes of antibiotics. Thus, refugee patients present a more severe health threat for themselves and others than the typical at-risk groups in Germany, even though the patients were primarily young and presumably without an extended history of hospital stays. ‘The result was surprising and warrants a re- evaluation of this patient group,’ says Professor Ursel Heudorf, Public Health Physician and Director of the Hygiene Department at the Public Health Office in Frankfurt/Main, MRSA among refugees 4MRGN among refugees t n e c r e P 16 14 12 10 8 6 4 2 0 Ingolstadt, 2016 Uni Frankfurt 2015 Groningen, Holland 2014 Netherlands The 2014 Frankfurt, Frankfurt, KH 2016 Uni 2016 t n e c r e P 6 5 4 3 2 1 0 Israel, 2014 Ingolstadt, 2016 Groningen, Holland 2014 Netherlands The 2014 Frankfurt, Frankfurt, Frankfurt KH 2016 Uni 2015 Uni 2016 Israel, 2014 4MRGN among refugees t n e c r e P KH 2016 Uni Ingolstadt, 6 5 4 3 2 1 0 Germany. While elderly people stay in hospital frequently and are treat- ed with antibiotics, they have always been considered an at-risk group and undergo suitable hygiene pro- cedures, refugee patients only now have been understood to be on a similar risk level and require corre- sponding hygiene measures. Groningen, Holland 2014 Questioning why Why such a large prevalence of MDRO? Heudorf assumes one rea- son to be ‘improper antibiotics man- agement in the countries of origin of the refugees’. The lack of product quality assurance in the countries of origin, where antibiotics are fre- quently sold over the counter and might contain a lower concentration of active ingredients, might be one factor; costs might be a second one. Frankfurt, Frankfurt, 2016 2016 Since the pharmaceuticals are freely available on the market they may be taken as long as they can be afford- ed. This may lead to antibiotics therapy being stopped prematurely since the patients subjectively feel better. ‘There are several conditions that promote resistance,’ Heudorf concludes. Uni Israel, 2014 Frankfurt 2015 Evidence-based recommendation Therefore, she considers it ‘impor- tant to screen all refugee patients upon hospital admission’. Even the Robert Koch Institute (RKI), which previously tests only if warranted by the individual patient’s medical history, now also supports screening for MRSA and 4MDGRN upon hospital admission. Medical history-based tests are recommended difficult to implement in practice, as Heudorf points out: ‘Too compli- cated, too error-prone. Due to lan- guage problems on both sides, the validity of the information provided is questionable.’ Thus, systematic screening and initiation of hygiene measures should be performed regardless of the information provided by refugee patients during anamnesis. Heudorf is well-equipped to master future challenges. ‘Our study in the Rhine- Main area was prompted by the lack of knowledge on our new and relevant patient group – refugees. The results allow us to design an evidence-based approach.’ Preventive isolation Depending on the procedure, each test will cost between three and 50 euros. The gold standard remains the culture on a petri dish. PCR is faster, but provides rather too many false positives. Heudorf recommends preven- tive isolation even before the test results are available, to be able to decide on the next steps based on results. Isolation, however, means more costs both in terms of time and human resources, for example changing times for staff. Isolation also requires more space, since only one bed can be used per room. However, financial considera- tions notwithstanding, Heudorf is convinced that ‘if an outbreak of multi-resistant pathogens is to be prevented in a hospital, in the end money spent on screening, isolation and hygiene is always money well spent.’ Significantly shorter therapy durations may be sufficient Dangerous travel companions Trips around the globe, healthcare tourism, migration; we are mobile – and so are bacteria. Particularly dreaded are multi-drug resistant bacteria that ‘hop’ on their host during a hospital stay and are car- ried across the border. At MEDICA 2017 Labmed Forum Dr Andreas Ambrosch, Head of the Central Lab at Krankenhaus Barmherzige Brüder in Regensburg, Germany, will discuss these unwelcome inter- national travel companions. in Scandinavia, the Scientists Netherlands and Germany have conducted comprehensive research on the link between increasing human mobility and the spread of bacterial resistance. Several stud- ies with healthy volunteer subjects showed that travellers who were initially pathogen-negative carried multidrug-resistant bacteria upon their return, in most cases ESBL- producing E. coli or Klebsiella spp. type CTX-M (ESBL = extended spec- trum beta-lactamase). High-risk trips involved India (80%), followed by the rest of Asia (slightly below 50%), the Middle East and Southern Europe (approx. 15%). These and other studies found traveller’s diarrhoea and antibiotics therapies during the trip to be inde- pendent risk factors. Average length of colonisation with ESBL-producing bacteria was 30 days; in 10% of the cases, how- ever, the pathogen continued to be present after one year. Even fam- ily members who had not travelled were infected (12%). Healthcare tourism According to the general, as well as the healthcare, media, in Germany infections with pan-resistant bacte- ria (with colistin the only therapy option left) are frequently traced back to patients who received emer- gency care in a foreign hospital. Thus, the first European patient to be diagnosed with carbapenemase type NDM-1 (New Delhi Metallo- beta-lactamase-1) was a Swede who had undergone treatment in New Delhi, India. Patient Zero, in a major outbreak of KPC-2 carbapenemase-producing Klebsiella at a German universi- ty hospital, had previously been treated in a Greek hospital. It took almost three years to end the out- break: more than a hundred patients had been colonised and infected, at least 15 died of the infection. A recently published study on the incidences of multi-drug resistant bacteria in foreign hospital patients in Frankfurt reported highly resistant carbapenemase-producing bacteria, particularly Acinetobacter bauman- nii, in 5% of the cases. The last two patients in our facility in Regensburg found to carry Acinetobacter bau- mannii resp. KPC-2 Klebsiella classi- fied as 4MDRGN (multi-drug resist- ant Gram-negative bacteria resistant to 4 classes of antibiotics), were previously treated in a hospital in Hungary (relating to Thailand). Immigrant population The high number of immigrants currently entering Germany raises public concern, politically as well as in terms of healthcare. Medically speaking, this concern is not entire- ly unfounded: a recent study on the prevalence of hygiene-relevant pathogens in immigrants at an admission centre in the Saarland showed 40% of the people tested to carry MDRGN resistant to two or three classes of antibiotics (for comparison: 5-10% – regional differ- ences – among patients in German hospitals). Most frequently, E. coli or Klebsiella spp. were identified. A study testing unaccompanied minors in Frankfurt, 70% of whom hailed from Afghanistan, showed very similar results: in 34% of peo- ple tested, ESBL-producing bacteria were detected, 8% of which were categorised as 3MDRGN (incl. qui- nolone resistance). No pan-resistant species (4MDRGN) were found. An updated statement by Robert Koch Institute now recommends screening of refugees upon hos- pital admission due to the high prevalence of multi-drug resistant bacteria in some countries of ori- EUROPEAN HOSPITAL Vol 26 Issue 3/17

WORLD FORUM FOR MEDICINE 13 –16 NOVEMBER 2017 DÜSSELDORF GERMANY www.medica.de Every year in November, the World Forum for Medicine, with approximately 5,000 exhibitors, is an outstanding meeting point for experts from all across the world. In addition to a compre- hensive trade exhibition, an ambitious supporting programme also awaits you in Düsseldorf. Here, innovative solutions for medical laboratories as well as a versatile range of laboratory and diagnostics technology will be presented to you. At MEDICA, you fi nd the entire spectrum of medicine for your very specifi c thematic areas. BE PART OF THE NO.1! LABMED FORUM The Intefdisciplinafy Fascination dcfeening tests: Can you diagnose cancef ffom blood? Thfombosis pfophylaxis Iithout labofatofy tests: HoI ceftain afe the neI anticoagulants? NeI tissue ffom stem cells: Is this the futufe of thefapy fof diabetes and heaft attacks? Wave of fefugees in Gefmany: Is thefe noI a thfeat of neI infections? Current issues from medicine and research will be discussed at the MEDICA LABMED FORUM in Düsseldorf from 13 to 16 Novembef 2017. Under the guiding principle “The Intefdisciplinafy Fascination”, laboratory medicine, molecular pathology, microbiology, medical technology and life sciences present themselves as innovation drivers, which will provide new impulses for all areas of medicine. Doctors and patients, health policymakers and healthcare providers, media representatives and all other visitors of the “world’s largest medical trade fair“ are invited to four exciting theme days with top-class lectures and podium discussions. The events take place each day from 11 a.m. to 4 p.m. and are free of charge for trade fair visitors. The conference language is English. Fouf theme days Monday, 13 November: Cancef diseases Tuesday, 14 November: Cafdiovasculaf diseases Wednesday, 15 November: Innovative diabetes diagnostics Thursday, 16 November: Infection and migfation Fufthef infofmation Messe Düsseldorf GmbH, Project Management MEDICA E-mail: GiesenH@messe-duesseldorf.de Trillium GmbH Medizinischer Fachverlag E-mail: georg.hoffmann@trillium.de