2 M A NAG E M E N T & I T Healthcare data shake-up is imminent Healthcare organisations across Europe are being warned to be ready for new laws that mark the biggest shake-up in data protection legis- lation in decades. The General Data Protection Regulation (GDPR) will come into effect across Europe on 25 May and, despite the vote to leave the European Union, the British Government has con- firmed that it will be enshrined in UK law on that date. In the United Kingdom, key areas that the National Health Service (NHS) and other healthcare provid- ers are urged to be aware of include issues such as what needs to be done to instil a privacy culture and how to avoid penalties – which include heavy fines. Understanding responsibilities Whilst the new legislation affects a wide range of organisations and businesses, Freelance Data Privacy Consultant Darren Rose emphasises the importance of healthcare provid- ers being ready for the change. He explains that they need to focus on understanding the new GDPR priva- cy law and its possible implications; understanding the organisation’s responsibilities as a Data Controller; dealing with Data Processors; under- standing Data Subject Rights, and identifying sensitive personal data. Additionally, they must be aware of and understand locations and stor- age methods; Personal Information Management (PIMS); Information Security Management Systems (ISMS); risk and risk miti- gation; register breaches and the process of reporting a breach to the supervisory authority. Systems When the GDPR becomes law, Rose warned, organisations and firms need to be aware of the pos- sible heavy fines, subjects’ right to compensation, a new specific consent with evidence and rights to withdraw consent, and mandatory privacy impact assessments, manda- tory documentation of compliance and mandatory breach notifications within 72 hours of discovery. ‘I also draw organisations’ atten- tion to the potential impact of loss UK’s NHS tests management systems of reputation or judicial remedy for the data subject, which can be far reaching, even if the local super- visory authority chooses not to impose a fine on the organisation,’ Rose added. Focus on the human factor While there are stricter rules for gathering and storing sensitive data as well as increased powers for regulators, he believes this should not have a major impact on the health and social care sector as the ‘fundamental principles upon which data is gathered, transported and processed’ should already be at the heart of the organisation. ‘Individuals already responsible for deliver- ing data protection readi- ness will be very aware of the current,’ he said. ‘But, within the context of health and social care, organisations should take particular note of the inclusion of biometric (retina image- ry) and genetic data into the special categories as well as changes to sharing of data for medical research purposes and the correct use of anonymisation.’ Organisations, regardless of their sector, must understand the impor- tance of training and awareness as the cornerstone of a privacy Digitally controlled beds and patient pathways In some NHS hospitals this can be up to six hours but the Countess of Chester Hospital in north-west England says the Real-time Locating System (RTLS) it is testing has cut that from four to two-and-a- half hours, while the Luton and Dunstable Hospital – often the best performing in the UK for A&E wait time targets – says it would be impossible to hit those targets with- out the digital flow system. The Royal Wolverhampton Hospital – the first to trial the more expensive RTLS – reduced A&E breaches and also did not need to open additional wards this winter. Readjusting the focus on patient care RTLS sees tags on patients, equip- ment, such as pumps and pres- sure mattresses, as well as in staff badges. ‘It helps match patients to the skill set of staff, but also means RTL systems provide tags for patients, staff and equipment, to help match patients to staff’s skills, as well as reduce time spent looking for appliances The control centre allows staff to oversee and intervene if a patient is off track manufacturers for what the NHS needs. Some are for bed manage- ment, focusing on flow from emer- gency departments to wards, while others also take in theatres, radiol- ogy and pharmacy. Mapping the patient pathway Because there is a goal of closer cohesion between health and social care in the UK, the NHS is eying systems that bridge the gap between hospital, community and nursing home environment, a step that may positively impact down on the issue of delayed discharges with patients blocking beds before being moved to the next step of their care. Digital bed flow systems map a patient pathway throughout the hospital with various key stages highlighted. This cuts out numer- ous phone calls and means key personnel can access it via real-time wall-boards in A&E, on wards and in physiotherapy, pharmacy and thea- tres to track a patient’s whereabouts and what is needed to deliver their stage of care on the pathway. ‘If you couple it to a centralised admission/discharge function with a control room you can coordinate placement of patients with the avail- able beds across a whole hospital ad as well as a group of hospitals,’ Quinn added. ‘With the cascade of intelligence that comes out of that, you have a better chance of getting the right person into the right bed first time and can reduce delays in the care process that can occur when manu- ally co-ordinating care from multi- ple departments.’ Benefits cited by manufacturers include reduced A&E times and length of stay, better matching of staff skills to patients, and reduction of ‘dead bed’ time when one patient has left the bed before another occupies it. Digital bed management systems to improve patient flow are being test- ed in National Health Service (NHS) UK hospitals and are showing early signs of success. Innovations such as patient tracking and real-time location of equipment and staff to improve hospital efficiency are being tested at 10 sites. Leading the project, Bernard Quinn, Director of Improvement Programmes for NHS Improvement, is particularly optimistic about tech- nology that monitors bed availabil- ity and patient flow. ‘Every winter, to meet added pressures in the NHS, an additional 3,000-5,000 beds go into the system but we don’t often look at the 100,000 beds that are already there, in terms of how effectively we are using them.’ he explained. The UK has half the hospital beds it had in 1987, but sub-optimal flow still sees 95% occupancy rates. The global trend is for fewer hospital beds with the latest data showing that of the 32 OECD countries, 90% are reducing bed numbers. The USA, Denmark and Sweden appear to be making better use of their beds via flow systems and this has inspired the NHS – which treats 351,000 patients a day – to focus on making improvements. ‘Since the 1970s,’ Quinn notes. ‘industries such as car manufac- turing have shifted from labour- intensive to computerised systems but over that same period our way of managing flow has not changed.’ Convinced that digital flow tools will improve the efficiency of patient movement in hospitals, he said the NHS is now seriously assessing at a range of systems from various staff not chasing after pressure mat- tress and pumps because they have a system that can tell in real time exactly where something is because they are asset tracked.’ While the centralised admissions and discharge element – with a main control room – may remove some of the autonomy wards might have to decide who comes into their ward or not, it does see nurses released from logistics and cleaning to focus on core nursing and patient care. Quinn, who is keen to hear from other European hospitals that have used digital flow systems, said: ‘Along with Department of Health, NHS England and NHS Digital, we are jointly looking at what approach we might take from these systems, what the options are that make it affordable for the NHS, and whether a national specification might be a route to go down. At the moment there are different systems in differ- ent hospitals and we have not yet settled on the best specification.’ While academic research in the field is limited, the NHS is working EUROPEAN HOSPITAL Vol 27 Issue 2/18

4 M A NAG E M E N T & I T Increasing knowledge of rare diseases Big data advances RD diagnosis and cancer th Two major projects feeding on big data and based in Spain have recently come under the spotlight: Mendelian, a tool to expedite rare diseases diagnosis, and Harmony, an EU plat- form that aims to improve targeted therapy in haematological cancer, Mélisande Rouger reports Rare diseases affect as many as 6% of the Spanish population. Although this percentage is high, these condi- tions are individually rare, which complicates and often delays treatment, according to Ignacio Hernandez Medrano, a neurologist at Ramón y Cajal Hospital in Madrid. ‘There are more than 10,000 report- ed individually rare diseases. As a physician, maybe you will meet one such pathology in your career, and when you do, you won’t know what it looks like. No human could possibly read through all the data A few years ago, Medrano founded Mendelian, a search engine that collects and sorts out knowledge of rare genetic diseases to acceler- ate their diagnosis. Diagnosing rare diseases currently takes 7-10 years, mainly because finding informa- tion on the disease itself can prove extremely long. Thousands of public databases are available on the Internet, with infor- mation uploaded by experts in the field, but no human being is capable of reading through all this data. However, a tool that uses big data can, Medrano explained. ‘We use technology that can cope with huge amounts of data on gene variants, clinical features and other informa- tion, and filter them by items that are clinically relevant, all the while taking into account the biochemical routes,’ he said. ‘Once our platform has gathered all the results and put all the data together, it runs algo- rithms to sort out relevant informa- tion for the clinician.’ Mendelian is proving to be quite accurate. Out of a selection of 20 at risk genes selected by the platform, one turns out to be the gene causing the disease, on average, according to Medrano. Interesting results have also been found using the platform; for instance that genes may be caus- ing diseases only because they are related in nature and physiology, even though no previous research has showed so. The young company is now trying to benchmark its ser- vices comparing synthetic patients against real patients, who have pre- viously been diagnosed. Around 5,000 people have visited the platform each month over the past six months, most of them being geneticists, paediatricians, internal medicine physicians and special- ists from every discipline. Medrano expects this number to grow, as the platform will become available to patients as well, and when genetic blood tests will become more gener- ally available. The entire Harmony team Boosting targeted therapy in haematological cancer In the era of next-generation sequencing and genetic knowl- edge of the genome and cancer genome, data must be gathered to better characterise disease and improve targeted therapy, according to Jesús María Hernandez Rivas, a leading haematologist at Salamanca University Hospital. Rivas is coordinator of Harmony, a European platform for the study and discovery of the most efficient treatments for haematological malig- nancies. The platform is part of the Innovative Medicines Initiative (IMI2), and aims to assemble all the stakeholders in the field and set up A family doctor questions the psychological issues behind testing What do tests do for doctors? Monitoring white blood cells at home A thin copper wire wrapped around a channel slightly thicker than a strand of hair could be the key to manufacturing a compact electronic device capable of count- ing white blood cells from the comfort of one’s home, according to engineers at Kennesaw State University in Georgia, USA. Hoseon Lee, an assistant professor of electrical engineering in the Southern Polytechnic College of Engineering and Engineering Technology, and his team of six students, have spent the past year researching more efficient ways for chemotherapy patients to monitor their white blood cell count without frequent, and sometimes costly, visits to the hospital. As cancer treatments often lead to lower white blood cell counts and an increased risk for infection, regular testing to measure levels is necessary, according to the Mayo Clinic. To monitor white blood cell levels, many clinics use the flow cytometry, method, Lee said. The process works by dying cells a fluorescent colour which are then illuminated by a laser. As the dyed cells pass through a narrow channel, the scattered light and florescence emitted are detected, indicating an object is there. Although this technique can pro- vide many levels of insight into a patient’s health, the equipment is bulky and expensive, limiting its port- ability. ‘Flow cytometry equipment can perform lots of different func- tions: it can sort the cells, count them and do other things that aren’t entirely necessary for every patient’, Lee said. ‘If we can focus on one thing – counting cells – we can make some- thing smaller and more affordable for EUROPEAN HOSPITAL Vol 27 Issue 2/18 Dr Jessica Watson is a general practitioner (GP) and NIHR Doctoral Research Fellow at the University of Bristol in the UK with an interest in how GPs use tests in primary care. Her PhD is looking at inflammatory markers to detect inflammation in the blood. Watson’s research sets out to des cribe the probability of various diseases given the test results in primary care. She is a member of Bristol Population Health Science Institute, NIHR CLAHRC West, Bristol Medical School (PHS) and Bristol Doctoral College. in the relentless pursuit of unachiev- able certainty. Equally, normal test results can at times do little to reas- sure a patient. ‘While the unit cost of a blood test is relatively small, the downstream cascade of testing can be significant.’ Guidelines have also posed GPs problems because many patents do not necessarily fit guide- lines, Watson continued. The impor- tance of shared decision-making over tests, she pointed out, may lead to reduced testing, or even patients opting not to have a specific test. However, she noted that required time and resources in explaining the benefits to a patient, evidence, edu- cation and an acknowledgement that uncertainty is inherent in testing. While defining unnecessary blood testing is not as simple as develop- ing medical criteria and guidelines for testing, Watson concluded: ‘Over- testing harms patients, leading to a rising workload in general practice and rising costs for the NHS.’ MN Fear of neglect This ranged from fulfilling non- medical roles such as a ‘gift’ to the concerned patient in return for perhaps not taking antibiotics, for example, or used as a bridge to build a ‘therapeutic alliance’ with a patient in an attempt to lead towards better patient management. But conducting tests also managed uncertainty for the GP with fear of missing something being a common driver, as well as fear of litigation. ‘The role of the blood test can be to manage uncertainty,’ Watson said, ‘but, paradoxically, inconclusive test results can create anxiety and uncer- tainty.’ From there, it can lead to more tests and stress and create the ‘investigation momentum’ where fur- ther tests are constantly being sought m o c . k c o t s r e t t u h S / c i p o M : e c r u o S deciding whether to test or as they try to uncover underlying disease. She pointed to variability in test- ing rates across the UK with areas of over-testing and areas of under- testing and suggested that both can cause patient harm. Additionally, there is the issue of how to avoid over-diagnosis, which may divert resource from more effective inter- ventions, generate waste and ine- qualities and increase the workload of primary care. As part of her research outlined to delegates, she discussed interviews she had conducted with a selection of GPs about blood tests performed, and explored their motives for carry- ing out the blood tests. Figures show that the rates of pathol- ogy testing are continuing to rise despite a backdrop of financial con- straint within the NHS. General practitioner (GP) Dr Jessica Watson has expressed concern that some tests are being carried out for the wrong reasons – often for a non- medical purpose – and that unneces- sary tests are causing increased anxi- ety and uncertainty rather than offer- ing reassurance for some patients. Having researched this area exten- sively, at the FiLM 2018 – Frontiers in Laboratory Medicine conference in the UK this January her presenta- tion focused on ‘What do tests do for doctors? Over-diagnosis and the psychology of testing’. Over-zealous use of blood tests The conundrum faced by family doctors is ‘to test, or not to test’. Watson, who is also a NIHR Doctoral Research Fellow at the University of Bristol, said: ‘It’s a fascinating question as a researcher, but more importantly as a clinician. While medical reasons are important, what fascinated me are the psychological reasons for testing.’ Concerned that such psychologi- cal reasons for tests may be fuel- ling over-testing and over-diagnosis, she expressed increasing concern that over-zealous use of blood test investigations could actually lead to patient harm. However, she also acknowledged that doctors often face the difficult balance between

6 L A B O R AT O RY Meeting the challenge of modern laboratory demands Utilisation Management Tools bring benefits conference in Birmingham, United Kingdom, Dr Curt Hanson, Chief Medical Officer of Mayo Medical Laboratories at Mayo Clinic, Rochester, outlined the organisation’s approach, including procedures implemented to guide appropriate test ordering and education pack- ages. A key element lay in harnessing big data to help better inform the testing profile of Mayo Clinic, while continuing to cost-effectively meet the needs of clinicians and patients. It was ever more important to achieve value based care, he said, particularly in an organisation such as the Mayo Clinic, which conducts 25 million tests annually; but he stressed there were multiple com- ponents to consider. ‘To add value, you must move beyond thinking about cost effectiveness and think about clinical effectiveness. You have to think about the impact it has in terms of confidence in patient care.’ Big data can help to evalu- ate test effectiveness In his presentation – Demand utilisa- tion – the Mayo Clinic approach – he said big data was critical in under- standing populations. However, he warned: ‘We have to remember that databases are not necessarily designed for our pur- poses but getting access to them can really help us to move towards understanding value in the lab.’ With tests such as ESR v CRP, for example, big data can highlight information that can help work out the rela- tive value of such tests. ‘It gives an opportunity to look at routine tests and an opportunity to flush out waste from the system,’ Hanson said, adding that it can also look at test usage and effectiveness to work out internal guidelines on testing, and see what savings can be made. He pointed to Clinical Decision Support Tools and Utilisation Management Tools, used by the Mayo Clinic, and effective in other settings, as having clear benefits but stressed the importance of labora- torians knowing how to use these tools. CDS tools can support frequen- cy of tests, cost information, value- based testing, where there should be restriction on tests, and population health data, Hanson explained. Utilisation Management Tools can provide clinician education, help decisions, make certain tests obso- lete, restrict frequency of certain tests, review admission and treat- ment templates, look at physician profiling and report cards and estab- lish a utilisation review process for the send-outs. Laboratory strategies need clinical input Hanson also pointed out that using genetic counsellors to review high Dr Curt Hanson, Chief Medical Officer of Mayo Medical Laboratories at Mayo Clinic, Rochester, USA, is a haematopathologist with a research focus on chronic lymphocytic leukaemia (CLL) and the myeloproliferative neoplasms (MPN). He has played a key role in the development of novel flow cytometry assays to detect minimal residual disease in CLL and the application of laboratory-based prognostic risk factors. Hanson is also a Consultant and Vice Chair (Extramural Laboratory Affairs) in the Division of Haematopathology, Department of Laboratory Medicine and Pathology at Mayo Clinic. cost hereditary testing was a good move and that ‘genetic counsellors more than prove themselves in terms of value’. From a philosophical chal- lenge perspective with clinical labo- ratory utilisation, he warned that laboratorians must be ‘comfortable with degrees of uncertainty’. ‘I believe that, as laboratorians, we need to lead the way with utilisa- tion management. We have tonnes of data, let us use that to reduce that waste,’ he said. ‘In addition, as laboratorians, we must get out of the office and think clinically. We have to think differently on how value based laboratory strategies can contribute to patient care and use big data and analytics to help drive laboratory- based initiatives.’ MN m o c . k c o t s r e t t u h S / d o G h t i w : e c r u o S Faced with the constant challenge of increasing demand and a backdrop of falling reimbursement, the Mayo Clinic in the USA has adopted an innovative and proactive approach to managing its laboratory services. This has seen the US-based medical giant embrace a variety of tools and reference materials to aid clinician For an organisation such as the Mayo Clinic, which conducts 25 million tests annually, it is important to achieve value based care, Curt Hanson believes decision making, improve care and lower costs. During the FiLM 2018 – Frontiers in Laboratory Medicine January Tackling acute kidney injury The earlier the better for a significantly improved outcome settings – yet many are treated by non-nephrologists. ‘The economic significance is that it amounts to 5% of total hospital costs, a figure that is conservative by today’s standards,’ he pointed out. ‘Also, it’s increasing- ly recognised that AKI and Chronic Kidney Disease (CKD) are not sepa- rate conditions but more a spectrum of disorders.’ Mortality, length of stay, and costs worsen as AKI progresses from stage one to stage three, with an increased likelihood of CKD and renal replacement therapy costs, he said. Estimates put the total expend- iture attributable to AKI in the USA at $10 billion a year. Adressing delegates to the con- gress, organised by the Association for Clinical Biochemistry and Laboratory Medicine and the Dark Report, Kothari highlighted a case study at the 250-bed Forest Hills Hospital in Queens, New York, where they found three to four cases a day of AKI leading to an excess stay in hospital of two days per case. ‘That was a one million-a- year problem for just one hospital site,’ he observed. ‘So the idea is that, if you are able to prevent or diagnose this condition at an earlier stage, then savings throughout the entire hospital system would be enormous.’ A key issue is that AKI is often under-diagnosed and under-recog- nised, primarily through a lack of awareness among non-nephrolo- gists and lack of effective Clinical Decision Support (CDS) tools lead- ing to variable standards of care. Greater awareness through lab alert and training The solution devised by Kothari’s team saw the implementation of a real-time laboratory generated elec- tronic AKI alert using a delta check- ing algorithm. This sparked alerts involving 20 patients a day at Forest Hills Hospital. But having validated the Steps taken by a New York health system to identify and tackle acute kidney injury (AKI) at an early stage are having a significant impact on improving intervention and patient outcomes. Key to the turnaround lies in pathologists accessing big data from the laboratory, and working more closely with administrative person- nel to identify early AKI and then responding to it more quickly. Speaking at the FiLM 2018 - Frontiers in Laboratory Medicine January congress in Birmingham, UK, Tarush Kothari outlined how this had not only allowed patients to be treated more promptly at the network of New York hospi- tals where he works, but had also showed considerable cost savings and helped reduce excess hospital days related to AKI. His presentation focused on aug- menting administrative data with laboratory data to improve quality of care and enable registry-based clinical studies for AKI. In his presentation Kothari, who is a Pathology Informaticist with Northwell Health Laboratories in the USA, discussed the clinical and economic significance of a quicker response to AKI. Progressing AKI increases hospital costs Some 15-20% of all hospital patients have AKI – up to 30% in critical care alert system as being correct, they began a physician education and awareness campaign and a daily reporting on AKIs for each 24-hour period during the first six months of the pilot in 2014. That was extended to include partnering with the health informa- tion management team to improve clinical documentation and further education of physicians, nurses and medical coders. It emerged that hospital admin- istrative staff were not capturing the incidence and severity of AKI, but with further awareness the cod- ing for AKI improved dramatically and seven additional hospital sites, where they were able to replicate the algorithm fairly easily, were added in January 2015. The outcome was greater aware- ness of AKI among physicians and administrative personnel, and identifying the condition before it became serious and severe, and then implementing an effective treatment regime. ‘Only laboratory creatinine data, at least in the case of AKI, can provide more granular information on disease severity, onset, chronic- ity, duration, recovery and long- term follow up of patients,’ Kothari explained. ‘It is not just how we process specimens and generate results, but also about laboratorians getting out there and talking to clinical colleagues.’ EUROPEAN HOSPITAL Vol 27 Issue 2/18

8 I N F E C T I O N C O N T R O L No all clear for nosocomial infections The 70th Annual Meeting of the German Society for Hygiene and Microbiology Report: Brigitte Dinkloh Experts at the 70th Annual Meeting of the German Society for Hygiene and Microbiology, held in Bochum, Germany, exchanged information on newly discovered resistances. ‘Specifically, resistance against a class of antibiotics that has, so far, always been viewed as a reserve appears to be developing more intensively than previously assumed,’ explained Professor Sören Gatermann, con- gress president and head of the Department for Microbiology at Ruhr University Bochum. The cause of resistance are different enzymes which make the antibiotic ineffec- tive; its identification needs the most up-to-date molecular procedures, to determine which medication will be effective for a certain patient. There is another class of resistanc- es causing concern among scientists. Mutations in the bacterium itself lead to certain antibiotics becom- ing ineffective. These resistance mechanisms, which were neither acquired nor depend on inactivat- ing enzymes, are occurring increas- ingly. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) determines the limits up to which a bacterium is still consid- ered treatable with antibiotics. New resistances are often hard to detect, Gatermann explained, ‘so we must work on a genetic level to determine which treatments are likely to be effective for a patient.’ Cause of resistances and regional variations Therapy with antibiotics is the only The congress presidents agreed that comprehensive MRSA screening of hospital admissions wastes resources treatment to affect not only the patient treated but also all other patients. If an antibiotic is used in the intensive care unit (ICU) this not only affects the bacteria of the treat- ed patient but also the entire hospi- tal and its environment. This leads to different resistance profiles that can vary significantly from country to country. However, in-patient facili- ties account for a relatively low pro- portion (10-20%) of the overall daily doses of antibiotics administered. Antibiotics are far more commonly prescribed in out-patient care. There are also big regional differences: In the East of Germany the prescrip- tion rate is low, with the highest daily doses being prescribed in the Saarland, although this represents only half of the prescriptions in France. ‘Each patient enters hospital with between two to three kg of bacteria. Up to 10% of the population already carry multi-resistant pathogens on admission,’ explained Professor Frauke Mattner, congress president and Head of the Institute for Hygiene at the Cologne Municipal Hospitals Group. The origin of the pathogens is still unclear. It is likely that they do not originate in drinking water but are spread through food, foreign travel or intensive animal farming. A certain proportion may also be spread from patient to patient in medical facilities. Which of these causes represents which proportion of the colonisation should be the subject of research to help tackle the problem in the future. Comprehensive screening is not helpful The congress presidents agreed that comprehensive screening of patients for MRSA and multi-resistant gram- negative bacteria on admission is a waste of financial and staffing resources as well as counter-pro- ductive. Although patients in more frequent contact with hospitals and care facilities are at higher risk of colonisation with MRSA, pure MRSA screening would take no account of other pathogens. Each individual hospital should determine which risk groups typically prevail in their facility and should then decide which type of screening and proce- dures are likely to be effective. This approach corresponds with the evi- dence-based recommendations from the Robert-Koch Institute (KRINKO). Gatermann explained that higher staff levels and adherence to hygiene regulations are more effective than screening all patients, particularly for multi-resistant gram-negative bacteria. Also, the diagnostic sensi- tivity for gram-negative pathogens is not particularly high, with patients sometimes having to be examined over and over again. General screening could lead to say 400 patients declared as being colonised when, in reality, only one is, Gatermann explained. A screen- ing requirement would therefore lead to inadequate care for 399 patients. It would be better to carry out specific screening based on the epidemiology and risk group for whom the most benefit can be expected. ‘Wrong determination of resistance can also have severe con- sequences in the case of MRSA, as the patient is not given the correct antibiotic. The probability is 1:1. This means that every other patient may receive incorrect treatment.’ More university education and academisation of care Hospital hygiene has experienced staff shortages in Germany for years. Around 1,000 specialists for hospital hygiene are required. However, uni- versities are not being encouraged, and Chair of Hygiene positions are only filled with delays or not at all. Only 7 out of 35 medical faculties have a department chair of hygiene and epidemiology. However, there has been considerable improvement over the last few years in the recruit- ment of hospital hygiene profes- After receiving his doctorate, Professor Sören Gatermann began his career as a research associate at the Institutes for Microbiology at universities of Hamburg and Lübeck in Germany. His habilitation in Medical Microbiology was completed in 1991 and he received the Venia Legendi and specialist accreditation in 1992. Two years later he was awarded a C3 professorship at Mainz University. The professor has been Chair of Medical Microbiology at the Ruhr University Bochum since October 1997. From 2009 he has also headed the National Reference Laboratory for Multidrug-resistant Gram- negative Bacteria, and became head of the National Antimicrobial Susceptibility Testing Committees (NAK), the German branch of EUCAST, in 2014. Support from the other end of the world Developing new substances beyond commercial interests Partners who could hardly be further apart – yet have a lot in common – have united to fight resistant pathogens. The International Consortium for Anti-Infective Research (iCAIR) was founded last January. Hanover Medical School (MHH) and the Fraunhofer-Institute for Toxicology and Experimental Medicine (ITEM) are participants in Germany. The third partner, the Institute for Glycomics (IfG) at Griffith University, Gold Coast, Australia, is nearly 16,000 km away as the crow flies. That enormous distance has not stopped the German-Australian research cooperation from achieving its objectives: the development of new agents against infections. Professor Armin Braun, Head of Preclinical Pharmacology and In Vitro Toxicology at Fraunhofer ITEM, explains the specific potential of this long-distance alliance. Report: Wolfgang Behrends The idea behind iCAIR is simple. The partners combine their respective strengths to create a project that’s more than the sum of its parts. IfG Director Professor Mark von Itzstein contributes considerable expertise in the development, design and optimi- sation of substances; he was a major driver behind the development of Relenza, a highly effective flu medi- cation. ‘However, what was missing from his side was the translational aspect relating to toxicology, quality assurance and preclinical proof-of- concept,’ Braun explains. ITEM and MHH will contribute this know-how. Where pharmaceutical firms pull out, others step in The partners are funding the project. Fraunhofer finances the iCAIR pro- gramme; MHH and IfG fund their own projects. This financial autonomy is central to the consortium, Braun explains. ‘The pharmaceutical industry has now largely scaled down develop- ment of anti-infectives. However, iCAIR facilitates the development of ) 2 ( r h o M f l a R : h p a r g o t o h P . M E T I r e f o h n u a r F © new substances beyond commercial interests. Research is to be refinanced via own patents. ‘Making do without the develop- ment of new anti-infectives, only because the pharmaceutical industry cannot find the right business model, is no alternative.’ Alternative sources of finance, such as the Gates Foundation, public fund- ing from the BMBF (Federal Ministry of Education and Research) or the iCAIR alliance, are the way forward in this situation The activity of bronchial muscles (see monitor in background, with open bronchus) can be well observed. The bronchi dilate or expand according to the type of medication or substance administered ‘Anyone, anywhere in the world, can become infected with influenza, and the changes in social structures are increasing the problem. People are living longer and are thus more prone to infections.’ The growing number of immunosuppressed patients and those who have received organ trans- plants also offer pathogens new scope for attack. ‘There are hardly any effec- tive drugs against fungal infections in particular, which is why survival rates for outbreaks on the ICU are frequently very low.’ Helped by 3-D confocal microscopy, scientists observe individual cells of the human lung structure. This also enables them to observe the reaction of different cells, e.g. immune cells, to a selected medication Different pathogens – similar methods The need for new anti-infectives is sub- stantial: Bacteria such as Pseudomonas aeruginosa and Neisseria meningitid- is, the mould Aspergillus fumigatu, as well as influenza and para-influenza viruses are an international problem. A dizzying pace of drug development iCAIR’s biggest progress is in new agents to fight influenza. The preclini- cal proof-of-concept stage has been reached and the first drugs could be ready for clinical use in 2-3 years. By pharmaceutical standards, where development cycles can be 15 years or longer, this constitutes an almost dizzying pace. ‘Although this does not apply to all substances,’ the professor points out, ‘we can usually shave off around 1-3 years.’ This optimisation is achieved through clever division of labour: MHH and IfG concentrate on the identification of possible drug targets. The Australian partner selects and generates the substances from which new pharmaceuticals are to be developed. The subsequent preclini- cal phase is in the realm of Fraunhofer ITEM, which will also support the fur- ther clinical development and produc- tion of the substance. Although the partners are at oppo- site ends of the world, the cooperation works well, Braun says. ‘The fact that all those involved are professionals – some with decades of experience in their area of expertise – makes the cooperation really enjoyable.’ The new iCAIR consortium is already receiving good feedback from experts; several research institutions worldwide have expressed interest in participation. In the long term, this additional expertise and resources should help to develop a global net- work for the joint development of anti-infectives. The current leading topic at iCAIR is new substances against influenza: ‘Germany as well as Australia recently had huge problems with ’flu epidem- ics because vaccines are not effec- tive,’ Braun says. Meanwhile, although there has been a paradigm shift that EUROPEAN HOSPITAL Vol 27 Issue 2/18

sion. ‘We did a clinical trial and tested an anti PD-L1 for liver metas- tasis. A few months after treatment onset, we saw very good response in the liver of this peritoneal lymph node,’ she said. ‘We suggested the possibility of flare phenomenon and performed cytology by lymph node aspiration. This showed mature lymphocyte, so we continued the treatment and the liver response was very good. The lymph node disappeared.’ Updating guidelines for new responses New criteria have been developed to help manage the new respons- es. To overcome the limitation of RECIST criteria to assess these spe- cific changes in tumour burden, so- called irRC criteria were established, on the basis of WHO criteria (bi- dimensional measurements, end tar- get lesion + five cutaneous targets). ‘This was designed for melanoma. The main difference from classi- cal WHO criteria is the inclusion of measurements of new target lesions into disease assessments and the need of a four-week CT re- assessment to confirm progression,’ Dromain explained. Dow-Mu Koh MD is consultant radiologist in functional imaging and Professor for functional cancer imaging at the UK’s Royal Marsden Hospital and its academic partner The Institute of Cancer Research (ICR). His research focuses on functional imaging techniques for tumour assessment. Things did not turn out so well in clinical practice. ‘It was a real night- mare to have 15 target lesions, with two-dimensional measurements. So, the RECIST working group estab- lished i-RECIST (a new consensus guideline that recommends assess- ing lesions – target, non-target and new – separately) based on one-dimensional measurements and including the same choice of lesions,’ she said. Pseudo-progression should be considered until PD is confirmed, but scientific rationale is lacking Male with metastatic melanoma commencing on immunotherapy drugs nivolumab and ipilimumab. Pre-treatment (top) contrast-enhanced T1-weighted image shows enhancing metastasis in left temporal lobe (arrow), associated with low ADC value (791 x 10-6 mm2/s). Treated for eight weeks, the lesion shows minimal change on the T1-weighted image (arrow) but demonstrates 20% increase in the ADC value (948 x 10-6 mm2/s). 16 weeks after treatment (bottom row), the lesion has regressed, showing no appreciable enhancement on the T1-weighted image, although residual post-treatment high ADC value cystic area is visible 1 0 R A D I O LO G Y ‘A true shift in oncology’ Immunotherapy advances Report: Mélisande Rouger Bigger lesions, better outcomes - With immunotherapy, CT may show big- ger lesions, which doesn’t necessar- ily mean the disease is progressing. As treatment works, it can cause ‘pseudo disease progression’ – just one of the many revolutions immu- notherapy triggers in cancer imaging, expert Professor Clarisse Dromain explained during ECR 2018. A range of new immunotherapy approaches in recent years include non-specific immune-stimulant, adoptive T-cell therapy and immune checkpoint inhibitors (anti CTLA-4, anti PD1 and anti PDL1). The immune check- point inhibitors (ICIs) – commonly used and intensively studied – pro- foundly impact on cancer treatment, she explained. ‘Their mechanism of action signifies a true shift in oncol- ogy. Instead of targeting tumour cells, ICIs target the immune system to break cancer tolerance and stimu- late anti-tumour immune response.’ These new (2011) drugs for mela- noma, lung, bladder, renal, and head and neck cancer, have shown a remarkable and long-lasting treat- ment response. ICIs trigger immune and T-cell activation, producing unusual response patterns. ‘First we observe delayed response – a lot of sta- ble disease with very slow, steady decline in total tumour volume; this is really a long duration response.’ If immunotherapy stops, the response duration without progression is very long. ‘This is really specific to immu- notherapy.’ Dealing with pseudo-progression Imaging has revealed new respons- es, e.g. flare phenomenon and response after initial increase in tumour border and initial appear- ance of new lesions. ‘These new responses are called pseudo-pro- gression, and could be due either to tumour site infiltration by immune cells or continued tumour growth until a sufficient response develops due to the time required to mount an adaptive immune response,’ Dromain explained. Recent research suggests that pseudo progression with anti PD-L1 may appear in about 5% of patients. An increase of tumour burden dur- ing immune checkpoint blockade (ICB) treatment is more likely to reflect true progression than pseu- do-progression, Dromain said. ‘We talk a lot about pseudo- progression, but true progression is more common.’ The immune system may be more reactive in a younger population and pseudo-progression could be associated with a clinical worsening, especially in lung cancer. Pseudo- progression may occur any time, but mostly appears around 12 weeks after therapy onset, especially in melanoma. Additionally, pseudo- progression may concern all organs, but most commonly lymph nodes, lung and liver. After three types of chemothera- py, a patient with colic cancer MSI positive – a very nice indication for immunotherapy – showed progres- Radiologists must also recog- nise and visualise immune related events: one MRI strength is to seek the presence of hypophysitis, Koh noted. ‘We know that this has higher incidence with CTLA-4 blockade; it has a reported incidence of 17%, and may be associated with pitui- tary failure associated with low ACTH and TSH levels.’ A patient often experiences fatigue and head- aches. e n n a s u a L V U H C n i a m o r D . C : e c r u o S Radiation garment lowers exposur Zero-Gravity suspended radiation protec In today’s operating rooms, increasing fluoroscopic procedures keep inter- ventionists at work longer, wearing the hugely heavy lead aprons neces- sary for protection against radiation. Chronic back pain is often accepted as something that simply comes with the job. Relief has arrived at last in the form of Zero-Gravity, a suspended radiation protection sys- tem designed to increase radiation protection whilst also eliminating the weight burden for the operator. With his team, Dr Andreas H Mahnken, Director of the Diagnostic and Interventional Radiology Clinic at Marburg University Hospital, Germany, found significant differ- ences when comparing the suspend- ed Zero-Gravity system to several conventional ones. Asked about the link between wearing lead aprons and chronic back pain, Dr Andreas Mahnken pointed out that several survey- based studies in English-speaking countries, such as the USA and UK, have focused on cardiology depart- ments. ‘Around half of all respond- ents working in interventional car- diology said they’ve had back pain from wearing lead aprons. Thirty- five percent of these complaints are lumbar spine-related, 25 percent concern the cervical spine, and we see knee and hip complaints in 20 percent of cases. ‘Orthopaedic problems happen much more often than cataracts or haematological diseases, but they haven’t been studied much, so far.’ At last year’s ECR Mahnken pre- sented results of his own study, which compared the orthopaedic burden of various radiation protec- tion systems. What did he discover? ‘We found clear differences between the radiation protection systems when it comes to physical strain on the user. The Zero-Gravity system reduced shoulder strain by about 80 percent.’ EUROPEAN HOSPITAL Vol 27 Issue 2/18 Clarisse Dromain MD PhD, head of the cancer imaging department at Gustave Roussy Cancer Campus University Hospital, Paris, researches interventional and diagnostic breast imaging. She is a member of the European Society of Radiology and several other international and national scientific organisations. regarding a time window to do so, Dromain explained. ‘Studies give different results. For example, Nishino et al observed 103 patients with melanoma, with 4% of pseudo-progression. Median time to peak tumour burden was 5.5 months, median time to the first scan showing tumour burden decrease, compared to the prior scan, was 6.8 months. ‘All patients had two or more consecutive scans demonstrating PD over four-week time frame before response. Recently the RANO work- ing group on neuro-oncology rec- ommended a three-month period for PD confirmation.’ Immunotherapy follow-up with MRI Today, immunotherapy is notable in imaging, but follow-up with CT is not assured in the peripheral limbs, brain and bone marrow, whereas MRI offers specific benefits and, combined with PET, may bring even more results. Research is needed on quantitative techniques and trac- ers developed to fully exploit that potential, Professor Dow-Mu Koh (Sutton/UK) believes. Imaging assesses treatment response, predicts response and patient benefit, identifies complica- tions, offers disease prognosis and evaluates relapse, Koh said, adding: ‘We are quite far from achieving these objectives.’ MRI techniques provide morpho- logical and functional imaging – and the potential for hybrid imaging. Research continues on using soft tissue contrast of MRI to enhance disease assessment, especially in disease sites that are poorly visual- ised with CT. Koh: ‘MRI is useful in areas not naturally included by CT studies, for instance peripheral limb. Small brain metastases can challenge CT, as can disease confined to bone marrow.’ Current iRecist criteria enables iden- tification and documentation of responses not typically observed in traditional systemic treatment. The new (2017) guideline enables classification of assessments after i-unconfirmed progressive disease (iUPD) has occurred – with follow- ing disease progression confirma- tion in 4-8 weeks. Spotlight on flare reaction Radiologists must beware of chal- lenges inherent in follow-up imag- ing within that time. ‘What we’re observing at eight weeks is pseudo- progression or the so-called flare reaction,’ Koh explained. The situ- ation that needs MRI imaging is usually more complex than for CT. ‘Lesions can grow,’ he added. ‘In our research we noted a decrease after 16 weeks, and after 24 weeks the lesion was totally gone.’

In conversation with Daniela Zimmermann, Executive Director of European Hospital, Tracy Accardi, Hologic’s Vice President (Global R&D), spoke of the importance of innovation, tomosynthesis, artificial intelligence/deep learning and open dialogue with the radiology community. cancer presents itself. We want our algorithms to tell the difference between a mass that the radiologist should worry about and one that can be dismissed.’ Hologic addresses a broad spectrum of gynaecological, perinatal, aes- thetic, skeletal and breast wom- en’s health issues. To enhance this approach, Tracy Accardi, of Hologic, explained the importance of work- ing closely with radiologists. ‘We are seeing the benefits of the significant level of investment we have been making over the last sev- eral years in bringing new products to the market. Within that, every- thing we do is around improving workflow for the radiologist and the technologist – and improving the experience for the patient. ‘When you think about tomosyn- thesis, for example, everybody rais- es concern about the time it takes to read an image. We constantly work on image quality and continue to develop a detection process that takes in more information from a pixel perspective, but does not increase the time it takes to do the scan or read the image. This turns out to be a win for both the patient and the radiologist. ‘When we talk about a focus on workflow improvements, we need to get smarter with how to help radi- ologists so they are comfortable that they have looked at everything they need to look at with tomosynthesis and are not overwhelmed by the amount of data. We have more than three years invested into looking at how to use deep learning to read the tomosynthesis data and direct radiologists to the things that they should be most concerned about.’ How could deep learning, arti- ficial intelligence and big data work? ‘We make continuous investments to ensure we have broad mammog- raphy data sets representing full variations of density and diagnostic outcome. To make deep learning really work, the more data you have, the smarter your algorithms are, so we’re very focused on case collection. We know we will need thousands of known cancers with pathologically confirmed outcomes so that we can teach the algorithm how to find those occurrences in the data. ‘We have developed the ability to grade how well our algorithms are working. I think our competitive edge is that we have developed a lot of knowledge over time about how to interpret mammography images, and have invested in learning how radiologists think and what they need to do deliver the best stand- ard of care. We know that we need to look at all the ways that breast Other than wait and see, how do you safely distinguish slow grow- ing masses? ‘There are indications of a fast grow- ing or aggressive cancer, for exam- ple the presence of spiculations or unusual vascularization in the image. If a mass is perfectly round and smooth walled it is most likely non-malignant and you can train your algorithms to know the differ- ence. The more three-dimensional your data is – and tomosynthesis is a perfect example – the better your algorithm can be. The radiologist needs to be able to focus on the observations where the algorithm cannot be positive.’ Might deep learning replace the radiologist? ‘From a deep learning perspective, the space was held back for a long time given available tools and limited processing capability. Developments over the last several years have delivered significant improvement at reasonable cost in both areas. I believe we’ll see significant industry investment in delivering the promise of deep learning to the radiologist, and I’m very excited about that. ‘What I’m fascinated about is that, with deep learning, you have to make very sure you are asking the Envisioning a simple and solid decision tree Promising radiomics for breast MRI To develop a precise way to treat breast cancer needs standardisation and quantification of data – the only way to extract prognostic infor- mation on a large scale. Zero-GravityTM Weightless Radiation Protection biotronik.com Report: Michael Krassnitzer ‘Breast cancer rates are continuously increasing, and we don’t yet have a means of prevention,’ said Dr Clemens Kaiser, from the Medical Faculty Mannheim, at Heidelberg University, who believes the only way to save more patients from death, after pro- viding the best possible diagnostics procedures, is via precision medicine: the right treatment at the earliest possible time. The radiologist spoke of the implementation of precision medicine for breast cancer during a Siemens Healthineers satellite sym- posium held at the 2018 European Radiology Congress in Vienna. Dynamic multiparametric breast MRI showing cancer in the left breast 1 2 R A D I O LO G Y Finding the right algorithms to tackle big data AI and machine learning algorithm the right questions, other- wise you don’t get the right answers. It sounds very simple, but you can otherwise fool yourself about what you think the algorithm is telling you. We have invested a lot of time speaking with radiologists around the world about how they want to see deep learning help them with questions that they want to try to answer. ‘Deep is not about replacing the radiologist, it’s about making radiologists as efficient and positive as they can be about their diagnoses, and perhaps not having to look at 40-50% of the images that are not going to be a problem. Giving the radiologists the ability to confidently focus on just the cases that are flagged with issues is the primary goal.’ learning Do you see more adopters, or will process be slow? ‘While capabilities of deep learn- ing are being felt all around us in our daily lives – I anticipate that adoption in the interpretation of mammography will be relatively slow because the radiologist, quite rightly, needs to be extremely confi- dent. At Hologic, we are completely committed to delivering solutions that gain that level of confidence.’ What is the next step? ‘Our focus is on continuously amass- ing fully validated tomosynthesis images, consulting with radiologists and training our algorithms to estab- Strong prognostic tool In Kaiser’s view, the key to precision medicine in breast cancer treatment is MRI: ‘Breast MRI images deliver a lot of prognostic information,’ he confirmed. Studies have shown that breast MRI data allows conclusions as to the risk of metastases. Other stud- ies have shown a link between breast MRI data and chances of survival. ‘Breast MRI is a strong, non-invasive prognostic tool,’ Kaiser confirmed. The inner structure, or margin of the tumour, oedema, the hook sign (a tumour branch) or necrosis – all of these can contain important informa- tion that can be decisive for treatment. The problem is that automatic quantification of all these factors and ability to derive prognoses from them is not yet possible. ‘However, the pre- requisites are there,’ Kaiser empha- sised. The amount of medical data available is escalating – keyword: big data. Whilst in 1980 it still took seven years for the entire volume of available medical data to double, this now takes only a year. It is esti- In 2014 Tracy C Accardi MSc (MEng) joined Hologic as Vice President of Global Research and Development at the Breast and Skeletal Health Division, where she leads a globally diverse team of 220 engineers and scientists, to develop systems for 2-D and 3-D mammography, breast diagnosis/biopsy, and bone densitometry. Prior to this appointment, she was Chief Technology Officer at OmniGuide Surgical for two years, leading development and marketing of advanced surgical energy solutions for minimally invasive surgery. Earlier roles include those at MedNest Consulting, Coviedien, Codman & Shurtleff (a division of Johnson & Johnson), Philips Healthcare and General Electric (GE). Among other commitments, Tracy Accardi is on the board of ‘A Better Chance’, a non-profit organisation in New York City committed to the education of academically talented, promising young women from under-served communities. lish clinical support and compre- hensive claims. ‘We will build toward our future with deep learning. I firmly believe that deep learning is critical to glob- ally transform breast patient care through insight-driven, innovative solutions.’ Radiologist Clemens Kaiser MD BA is a Senior Consultant and Head of the Division for Multimodal Breast Diagnostics at the Institute for Clinical Radiology and Nuclear Medicine, University Hospital Mannheim, Germany. He held his International Business Administration (EMA) diploma and Bachelor of Arts in Marketing Management, before gaining a PhD in medicine at the Friedrich-Schiller Univer- sity Jena. His dissertation was entitled ‘Duct-obstruction-sign – duct ectasia for differential diagnosis of DCIS vs papilloma in breast MRI’. mated that by 2020 it will only take 73 days. The capability of computers has also increased in line with the level required for these tasks – a modern mobile telephone is 32,000 times faster than the best computers avail- able at the time of the moon landings. Data quantification ‘Radiomics’ might be the solution. The word describes a combination of medical image processing and radio- logical research into the analysis of quantitative image characteristics in large, medical image databases. This is based on the idea of being able to make statistical statements about tis- sue characteristics, diagnoses and the course of diseases using radiological Continued on page 15 EUROPEAN HOSPITAL Vol 27 Issue 2/18

1 4 R A D I O LO G Y Gadolinium deposit in the brain A real threat or a phantom debate? The European Medicines Agency (EMA) decided to suspend authori- sation for certain linear gado- linium agents. The review by the Committee for Medicinal Products for Human Use (CHMP) states: ‘There is currently no evidence that gadolinium deposition in the brain has caused any harm to patients; however EMA has recommended restrictions and suspensions for some intravenous linear agents in order to prevent any risks that could potentially be associated with gadolinium brain deposition.’ Our EH correspond- ent spoke with Dr Alexander Radbruch, radiologist at the German Cancer Research Center in Heidelberg and at University Hospital Essen, who published several articles on gadolinium deposition in the brain. Report: Sascha Keutel Dr Radbruch, would you explain the decision of EMA, to suspend the authorisation of four intravenous linear gadolinium based contrast agents for most of the indications in the EU? ‘Generally, a comprehensive risk ben- efit analysis has to be performed prior to the administration of every medica- tion. For gadolinium based contrast agents GBCAs) this risk-benefit analy- sis includes – among other factors such as diagnostic efficacy and the risk of further side effects – also the potential gadolinium deposition risk. y c n e g A s e n i c i d e M n a e p o r u E © Contrast agent retention in the nucleus dentatus after 13 doses of a linear gadolinium- containing contrast agent since 2006 (Image courtesy of Professor Ernst Rummeny, Klinikum rechts der Isar, Munich Technical University). Even though we do not know if any clinical correlates exist for the gado- linium deposition, the EMA decided that it is favorable to minimize the amount gadolinium in the body. Since numerous studies provided evidence that the total amount of gadolinium in the brain can be reduced when mac- rocyclic GBCAs are used the EMA pur- sued a “precautionary approach” and concluded that the risk benefit ratio is no longer favourable for the linear GBCAs. Exceptions of this regulation are exclusively the use of gaobenate www.cars-iny.org CARS 2018 COMPUTER ASSISTED RADIOLOGY AND SURGERY 32nd Inyernayional Congress and Exhibiyion Main Themes Main Th  Medica  Medical Imaging  Compuyed Maxillofacial Imaging  Compu Compu  Image Processing and Visualizayion  Mulyidisciplinary Compuyayional Anayomy  E-Healyh and IHE  Compuyer Aided Diagnosis  Compuyer Assisyed Radiayion Therapy  Image and Model Guided Therapy  Personalized Medicine  Surgical Navigayion  Surgical Roboyics and Insyrumenyayion  Surgical Simulayion and Educayion  Compuyer Assisyed Oryhopaedic and Spinal Surgery  Compuyer Assisyed Head and Neck, and ENT Surgery  Image Guided Neurosurgery  Minimally Invasive Cardiovascular and  Informayion Processing in Compuyer-Assisyed  Digiyal Operaying Room  Human-Machine Inyerface  Payhology Informayics  Machine Inyelligence  Inyegrayed Payieny Care rayed Payieny Care  Tumor Boards or Boards  Innovayive Clinical Invesyigayions vayive Clinical Invesyigayions Thoracoabdominal Surgery Inyervenyion June 20–23, 2018 Berlin, Germany or gadoxetic acid for liver imaging and gadopentetic acid for intraarticular joint imaging. Unlike the EU, the USA’s regu- latory body, Food and Drug Administration (FDA) currently does not see a need for action. Why are their opinions so different? ‘The FDA acknowledges that linear gadolinium based contrast agents deposit more gadolinium than mac- rocyclics. However, they come to a different conclusion within their risk benefit analysis and it seems that they will not remove any product from the market as long as no clinical cor- relates of gadolinium deposition are proven.’ What is the current research status? ‘Animal experiments indicate that 24 hours post injection similar amounts of GBCAs – linear as well as mac- rocyclic – can be found, first in the cerebrospinal fluid and 24 hours later in the brain. However, four weeks after injection the total concentration of gadolinium in the brain is much higher with linear GBCAs than with macrocyclics – the latter being just slightly above the level of detection. Further animal experiments provided evidence to explain this finding: While the intact chelate is washed out over time for both – linear and macrocyclic GBCAs – the linear GBCAs partly dechelate and subsequently bind to different partners (eg macromole- cules) which finally cause the hyper- intensities seen on T1 weighted imag- es. ‘In macrocyclic GBCAs, however, no gadolinium release was detected. Consequently, the statement that all contrast agents deposit gadolinium is partly misleading. Gadolinium depo- sition is a process which has to be monitored over time: the intact che- late can temporarily be detected in the brain after both linear and macrocy- clic GBCAs administration. However, dechelated gadolinium, which poten- tially stays in the brain, is found only after use of linear GBCAs.’ CARS 2018 President Volkmar Falk, MD, PhD (D) Congress 2018 Organizing Committee Chriutou Angelopoulou, DDS (USA) Elizabeth Beckmann, BSc (UK) Leonard Berliner, MD (USA) Ulrich Bick, MD (D) Davide Caramella, MD (I) Kevin Cleary, PhD (USA) Mario A. Cypko, PhD (NL) Takeyouhi Dohi, PhD (J) Kunio Doi, PhD (USA) Volkmar Falk, MD (D) Allan G. Farman, PhD, DSc (USA) Hubertuu Feuuuner, MD (D) Guy Frija, MD (F) Miguel A. González Balleuter, PhD (E) Makoto Hauhizume, MD, PhD, FACS (J) Youhihiko Hayakawa, PhD (J) Javier Herrero Jover, MD, PhD (E) David Hilderbrand (USA) Kiyonari Inamura, PhD (J) Pierre Jannin, PhD (F) Leo Joukowicz, PhD (IL) Tina Kapur, PhD (USA) Heinz U. Lemke, PhD (D) (Chair) Kenuaku Mori, PhD (J) Hironobu Nakamura, MD, PhD (J) Nauuir Navab, PhD (D) Terry M. Peteru, PhD (CDN) Ouman M. Ratib, MD, PhD (CH) Hanu G. Ringertz, MD, PhD (S) Ramin Shahidi, PhD (USA) Hiroyuki Youhida, PhD (USA) PD Dr Alexander Radbruch is a radiologist at the German Cancer Research Centre in Heidelberg and at the University Hospital Essen. He has published numerous papers on gadolinium retention and in 2015 showed, for the first time, that differences in gadolinium retention in the brain exist between macrocyclic and linear gadolinium-containing contrast agents. In 2017, the radiologist was chosen by colleagues in the category ‘Radiological Research’ as one of the world’s 15 most influential people. Does the decision to restrict author- isation without proof of damage lead to unnecessary confusion among physicians? Do you under- stand this growing insecurity, even patient’s fears? ‘In my opinion, the increasing uncer- tainty among physicians and patients as well as an unreasonable decline of GBCAs in clinically indicated situ- ations is indeed the biggest threat in the current debate. Personally, I hope that the uncertainty will subside as time goes by. It’s important to point out that the entire debate might be a phantom debate - an issue without substance. ‘Generally, we need to explain our patients that GBCAs are an impor- tant component of clinical routine and often allow life-saving diagnoses. To date, GBCAs have been applied approximately 450 million times worldwide – 50 percent of these might have been linear and despite of this enormous number, no clini- cal correlates of the depositions are known, yet. However, we should not forget that it also took us almost 10 years to disentangle the correlation between gadolinium and NSF. This experience with NSF might be one of the reasons why the EMA followed its precaution- ary approach. Are there potential alternatives to gadolinium-containing agents? ‘Currently, a lot of research on con- trast-free MRI techniques is being conducted. At the German Cancer Research Centre we recently showed that sugar might potentially be used as contrast agent for brain tumour patients. Moreover, I’m sure, going toward diffusion-weighted imag- ing, which does not require contrast agents at all, will play a crucial role. However, I don’t see any technique that, in the short run, might replace GBCAs. Could the debate lead to an overall ban? ‘I’m sure there won’t be an overall ban. A ban would be absurd in view of the immense clinical benefit of GBCAs. I do hope that, in Europe, suspending the authorisation for linear GBCAs will calm the waves. Nobody can tell where the regulatory debate in the USA is heading. At the end of the day, I guess, markets will create facts. Look at paediatrics: Over the past two years, this field has witnessed a major shift in the USA and today 95 percent of GBCAs used are macrocyclic. Such developments might make regulatory decision superfluous.’ EUROPEAN HOSPITAL Vol 27 Issue 2/18

1 6 R A D I O LO G Y Unilateral higher education is the way forward Swiss radiographers face many challenges money. The trend for a bachelor’s level is spreading through Europe and hopefully we’ll follow this trend as soon as possible,’ he said. The radiographer in Switzerland faces many issues, from having the right education to positioning themselves both professionally and legally in the healthcare continuum. Before a large audience at ECR 2018, Yves Jaermann, head of the radiographers service Riviera- Chablais Hospital in Vaud Valay, reviewed the situation in his country Report: Mélisande Rouger The profession of radiographer was born in 1896, when the first X-ray machines were installed in hospi- tals. In Switzerland, radiographers began to organise themselves soon after. A professional association was founded in 1946. ‘This shows our forefathers realised how impor- tant it would be to promote and defend their activity as a profession,’ Jaermann pointed out. Yet, according to him, the old idea of radiographers being the radi- ologists’ helpers still haunts com- mon memory. ‘It’s still present in the mind of some radiologists and radiographers, who are ashamed. Fortunately younger generations have a vision of complementary professional roles,’ he said. A bachelor degree adds value Among reasons for this sticky belief is that the education of Swiss radiog- raphers remains unequal throughout the country. The bachelor’s level was introduced in the French- speaking zone of Switzerland in 2002. However, in the rest of the country, radiographers can only take a diploma of high- er education, which undoubtedly has less value, Jaermann explained. ‘The professional skills of both diplomas are considered equivalent, but here I have to insist on the added value of the bachelor level. Students are made aware of research; their bachelor thesis is a first approach to this field. These young professionals have a slightly different professional behaviour, and position themselves more clearly in a partnership with other professionals, such as radi- ologists. They have learned to learn and become much quicker in daily routine with every kind of modality,’ he said. There are great advantages to hav- ing a bachelor’s degree. Conversely, pathways to clinical practice with a university level cost quite a few additional years of studies and more But trilingual and multicultural Switzerland is a complex setting to homogenise education. The Swiss Association of Radiographers recently fought to establish a bach- elor’s level on the national level, a battle lost in 2015. Defending their role as experts Swiss radiographers have yet anoth- er challenge to face because, not only them but also chiropractors, medical assistants, doctors in private practices, theatre support workers, cardio technicians and nurses are entitled to perform X-ray examina- tions. Trilingual and multicultural Switzerland is a complex setting to homogenise education Meanwhile, radiographers are responsible for radio-protection, according to the Federal Office of Public Health; but they do not always have the necessary author- ity and time to apply the rules and safety guidelines, Jaermann argued. ‘As a result, some surgeons do not respect some basic radio- protection rules, except for them- selves,’ he said. ‘So radiographers must defend their roles as experts and must assume this role in thea- tres for supervising non-specialised professionals, in accordance with the law.’ Radiographers also have to develop new fields of activities The education of radiographers remains unequal throughout Switzerland: While the bachelor’s level was introduced in the French-speaking zone in 2002, radiographers still take a diploma of higher education in the rest of the country Yves Jaermann has headed the radiographers’ service at Riviera-Chablais Hospital in Vaud Valay, Switzerland, since 1993. Before joining the Riviera-Chablais Hospital, he spent two years in Algiers, at the Issad Hassani University Hospital as radiographer and radiology teacher. under the radiologist’s supervision. For starters, Jaermann suggested letting radiographers perform ultra- sound examinations, with radiolo- gists’ final approval. ‘US is time consuming and radiographers cost much less than radiologists and would deliver reproducible images,’ he said. X-ray To increase their autonomy with CT or MRI, radiographers could delegate part of the standard to medical assistants. ‘Radiographers would be responsible for quality and continuous professional development for these assis- tants. This is a new way of thinking, which might lead to discussion.’ Stepping out of the shadow Legislation is the ultimate bat- tlefield for radiographers, who must be included in any legisla- tion that regulates healthcare pro- fessions. Jaermann is convinced that the only way to do so will be to expand the bachelor’s level nation- ally and acquire more skills. Further education will be par- amount, and evolution of radio- graphers’ training has to be in a step with the evolution of nuclear medicine, radiotherapy and radio diagnostics. ‘Studying three domains is essential. With the new hybrid machines we have a foot in two or even three domains – think about radiotherapy using CT, ultrasound or even MR next,’ he explained. Finally, tighter cooperation will be mandatory to help secure changes. ‘Our head radiographers must work together to support projects. And our radiographers need to be more ambitious. They have to be prouder and not live in the shadow of other professions any more,’ Jaermann concluded. ‘Our professional asso- ciation has to intensify its political influence.’ m o c . k c o t s r e t t u h S / s o t o h P n o i l l i B : e c r u o S EUROPEAN HOSPITAL Vol 27 Issue 2/18 ESC Congress Mundch 201825-29 AugustWhere the world of cardiology comestogetherwww.escarddo.org/ESC2018#ESCcongressSAVE ON REGISTRATIONEarly registration deadline - 31 MayBecome an ESC Professional Member & save moreDISCOVER THE SCIENTIFICPROGRAMME Late-Breaking Sciencesubmission deadline: 21 May