Archive for category: Featured Articles

Featured Articles

Severe anemia in pregnancy doubles the risk of maternal death

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Anemia in pregnancy is one of the most common medical problems pregnant women encounter in both low and high income countries. It affects some 32 million pregnant women worldwide each year and is characterized by a lack of red blood cells. Women with severe anemia will have a blood count of less than 70 grams of hemoglobin per litre of blood. It is a dangerous condition and if not prevented or treated correctly can lead to maternal death.
Highlighting the danger, an international study published in May this year, shows that women with severe anemia during pregnancy or up to seven days after delivery have double the risk of dying compared to those who don’t suffer from the condition.
Previous studies had suggested that anemia was strongly associated with maternal death, but they were not clear due to the influence of other clinical factors. This study – the largest of its kind – is the first to control factors that can influence the development of anemia in pregnancy (such as blood loss or malaria infection) and which may have skewed the results of previous studies.

The researchers emphasize that clinicians, policy makers and healthcare professionals should now focus their attention on preventing anemia, using a multifaceted approach, and not just hope that iron tablets will solve the problem.
Although anemia is a readily treatable condition, the existing approaches have so far not been able to tackle the problem, say the researchers who published their study in the MAY/ JUNE 2018  issue of The Lancet Global Health.
For the study they looked at World Health Organization data on 312,281 pregnancies in 29 countries around the world. The study results show that, when all known contributing factors are controlled for, the odds of maternal death are doubled in mothers with severe anemia.
Importantly, the relationship between severe anemia and the increased risk of maternal death is seen in different geographical areas and, by using different statistical approaches, the researchers are able to show an independent relationship between severe anemia and maternal death does exist.
Prior to this research, the absence of robust data showing evidence of the relationship between severe anemia and maternal mortality has led to a relatively low prioritization of anemia as an important condition in its own right. This new research will hopefully motivate health policy makers to sharpen their focus on the prevention of anemia during pregnancy when they shape new policy on the condition.

Strong presence of Nordic skills and innovations in life science at Arab Health 2018

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Danish, Finnish and Swedish organizations join forces to facilitate business partnering and networking at Arab Health 2018. At the event, 75 Nordic companies bring innovative life science solutions aiming to add sustainable value to the Middle East healthcare sectors and to build lasting relations between the Nordic participants and local stakeholders.

Business Finland, Business Sweden, Danish Health Tech Group and Global Pharma Consulting are coordinating four national pavilions at Arab Health 2018. To kick off the trade fair, the organizations announce an exclusive Nordic Business Partnering and Networking Reception for invited guests on Monday 29 January 2018 at 7-10 pm at the Sofitel Dubai Downtown.
“This is the only opportunity for stakeholders in the MENA region to talk to so many decision makers, officials and experts from the Nordics in one place in a relaxed setting,” explains Senior Consultant Paula Hassoon at Global Pharma Consulting, organizer of The Innovation Pavilion by Sweden.
“Joining forces with our Danish and Finnish colleagues to host a Nordic partnering and networking event brings added value to all of the participating companies,” she says.

Digital health from Finland
At the four national pavilions, the Nordic companies will showcase cutting-edge med-tech solutions and technologies to the MENA region. According to Meria Heikelä, Director at Business Finland and co-organiser of the Finnish pavilion, Finland ranks among the three strongest health technology economies in the world, with digital health being its largest high-tech export.
“Finland’s world-class research and technology competencies are the pinnacle of its health sector and one reason why Finland has one of the most efficient healthcare systems in the world. Preventive healthcare and rehabilitation solutions are among the key focus areas of Finland at Arab Health 2018,” explains Meria Heikelä.

Danish innovations in med-tech
With the annual Pavilion of Denmark at Arab Health and a recent business delegation visit to UAE and Saudi Arabia healthcare sectors, Danish Health Tech Group is committed to share the Danish med-tech strengths with stakeholders in the MENA region.
“In Denmark, we prioritize design and quality, and innovate through an inherent focus on public-private sector cooperation and by proactively involving patients and staff in the healthcare sector,” says Thomas Andersen, Head of Danish Health Tech Group.

Swedish world-class healthcare
While all the Danish companies are exhibiting with Danish Health Tech Group, Sweden offers two different pavilions.
The Innovation Pavilion by Sweden and the official Swedish pavilion each has representatives from 20 Swedish healthcare and life science companies.
“Sweden is known for its world-class’ innovations within the healthcare sector. Much of this success derives from the tradition of entrepreneurship through the close collaboration between the government, academia and industry,” says Fredrik Bodin, Trade Commissioner of Sweden to the UAE, co-organizer of the official Swedish pavilion.

The national pavilions at Arab Health 2018

  • The Innovation Pavilion by Sweden, organized by Global Pharma Consulting, located at Za’abeel Hall 6 Z6.E30
  • The Finnish Pavilion, co-organized by Business Finland and Business Oulu, located at Hall H3 A10
  • The Pavilion of Denmark, organized by Danish Health Tech Group, two pavilions located at Trade Center Arena SA.F50-59 and Za’abeel Hall 6 Z6.E30
  • The official Swedish pavilion, organized by Business Sweden and the Embassy of Sweden in Abu Dhabi, located at Za’abeel Hall 1, Z1.G50

More information to be obtained from:
Business Finland (Finpro) at www.finpro.fiBusiness Sweden’s at www.business-sweden.seDanish Health Tech Group at www.dk-healthtech.comGlobal Pharma Consulting at www.globalpharma.se

Greening hospitals: Yes we can!

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Earlier this year the American Medical Association (AMA) published an article entitled ‘Lower costs by going green!’ aimed at the healthcare sector.  They note that, in the USA, 9 – 10 percent of the nation’s total carbon dioxide emissions are generated by the health care industry – and the USA is not alone in this high carbon footprint.  In Europe the average emissions is estimated to be about 5 percent.  Cleary there is a margin for improvement.  The AMA article makes practical, money and energy saving proposals aimed at the small medical practices.  The question arises as to how this could be achieved in the larger hospital environment.  There is a trove of excellent suggestions for building new energy efficient and environmentally friendly hospitals – but what of existing hospitals?
A very useful source of information is the Global Green and Healthy Hospitals (GGHH) community.  The community of almost 1000 members have the aim to transform the health sector and foster a healthy future for people and the planet.  To achieve this aim GGHH brings together hospitals, health systems, and health organizations from around the world under the shared goal of reducing the environmental footprint of the health sector.
To achieve their aims, they suggest a 10 goal strategy: Leadership -making environmental health, safety and sustainability key organizational priorities;  substituting harmful chemicals with safer alternatives; to reduce, treat and safely dispose of healthcare waste; to reduce water consumption, as well as to source, purchase and serve sustainably locally grown, healthy food. Other goals include implementing energy saving strategies; safely manage and dispose of pharmaceuticals; transportation planning, building efficiency design; and purchasing safe and sustainable products.   
GGHH points out that there is not one model of green and healthy hospital but indicate that many health systems around the world are already taking steps to reduce their environmental footprint contributing to public health while at the same time saving money.    Initiatives such as the ‘Health Promoting Hospital Network’ originating in Europe and with the support of the World Health Organisation, is developing a set of sustainability criteria.  Such initiatives and conferences of greening the health sector are emerging in countries as diverse as Argentina, China, India, South Africa and Sweden – to name a few.
The Global Green and Healthy Hospitals agenda sets out to support these existing efforts around the world to promote greater sustainability and environmental health.  European hospitals would do well to align themselves with this community, reducing the European healthcare contribution to the carbon footprint, as well as, in many cases, saving money –immediately and in the future.

CMEF Spring is part of the world’s largest healthcare event: the Health Industry Summit (tHIS)

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The Health Industry Summit (tHIS) 2017 hosted by China and organized by Reed Sinopharm, was held in Shanghai at the National Exhibition and Convention Center from May 15th to 18th with well over 200,000 healthcare industry professionals from more than 150 countries and regions in attendance.

Now in its third edition, tHIS has been firmly established as the world’s largest health industry event with over 350,000 square meters of exhibition space and 160 individual events and conferences.  It comes at a crucial time as China drives forward its “Healthy China 2030 Plan” initiative to realize among other goals an industry growth target of RMB 16 trillion (USD 2.3 trillion, Euro 1.9 trillion) by 2030 and an increase of average citizen lifespan by 3 years to 79 years.

Key events at tHIS 2017 included China’s three top medical equipment and pharmaceutical exhibitions (CMEF, PHARMCHINA and API China) and the leading healthcare investment forum – Healthcare China 2017. This year’s investment forum was co-organized by Reed Sinopharm, JP Morgan Asset management, CICC and Sinopharm Capital and was attended by more than 1000 CEOs, investors and institutions.

The exhibition featured the entire industry value chain and showcased tens of thousands of the latest technologies and products. Emerging technologies such as VR, AR, wearables and AI featured strongly on the show floor as well as in the key forums. During tHIS 2017, the World Medical Robots Innovation and Development Summit was held to reflect the growing trend for robotics and AI applications.

Over 7000 exhibiting companies from 30 countries were at the show including medical device giants like GE, United Imaging, Siemens, Philips and Mindray as well as major pharmaceutical groups in China including Sinopharm, Shanghai Pharma and CR Pharmaceuticals.  The majority of the most innovative companies in the medical field choose CMEF as their global or Asia Pacific new product launch platform and more than 600 new product launches took place during the 4 days of the show. Among the new products released, United imaging launched its uVR 4D vision explorer platform, enabling more detailed dissect structure and spatial information, while GE launched its first cloud-based digital application for medical equipment management APM (asset performance management), which was developed by their China team. BGI also attended with their gene sequencer BGISEQ-500, a benchtop high-throughput open sequencing platform that provides end-to-end solutions.
Natural Health and Nutrition Expo were among the fastest growing segments in the portfolio, helped by the expected population boom in light of the reversal of the single child policy last year as well as a growing health-conscious middle class in China. Popular international brands like Blackmores, Nature Made and Garden of Life made their debut at the show along with 700 suppliers of health food and supplements, bringing with them popular product lines tailored to the Chinese market.

The Health Industry Summit is organized by Reed Sinopharm, a joint venture between the world’s leading event organizer Reed Exhibitions and China’s leading state-owned medical & pharmaceutical group Sinopharm, ranked number 199 on the latest Fortune 500 list released in July. Its next edition will be held in April 2018 in Shanghai while the 78th China International Medical Equipment Fair (CMEF Autumn 2017) is to take place in Yunnan at the Kunming Dianchi Convention & Exhibition Centre from October 29 to November 1.

Visitor profile
The vast majority of visitors naturally came from China, covering all regions and healthcare sectors. However, there was also a growing segment of international visitors. Topping the list of foreign countries was India with a 20% share of international attendees followed by Korea (15%), Pakistan, Japan, USA, Russia and Germany.

Overall, CMEF visitors spanned the entire medical area – both healthcare and medical device industry. Distributors of medical devices constituted the largest single visitor group with 45% of the total followed by hospital build and design (26%) and rehabilitation centre professionals (see detailed visitor composition chart on previous page).

National pavilions
The international participation is increasing, reflecting the growing importance of China’s healthcare industry. Further adding to the show’s attraction, a large number of national pavilions were featured in a dedicated hall where a constant stream of visitors could view the latest products and technology of companies from countries as diverse as Switzerland, Canada, Taiwan or Germany. For the first time the US and Pakistan had country group exhibits while the Spanish Medical Technology Association (FENIN) led some Spanish companies to make their appearance at the CMEF Spanish pavilion and the German Land of Thuringia organized a regional exhibit for the first time.

Prehospital – Hospital – Homecare

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Automation and integration of LC-MS/MS services into the clinical laboratory workflow

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Despite significant inherent advantages of liquid chromatography-tandem mass spectrometry (LC-MS/MS) over immunoassay techniques in clinical laboratory applications, its adoption into routine practice has been slower than might have been expected. The barriers to more widespread uptake are a function of issues in the laboratory workflow. This article analyses those issues and discusses how they can be overcome by improved automation and integration with the laboratory information management system, drawing on examples from the North West London Pathology (NWLP) clinical laboratories at Imperial College Healthcare NHS Trust.

by Dr Emma L. Williams

Introduction
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has seen over two decades of use in specialist clinical laboratories in the UK, offering a number of significant advantages over immunoassay techniques. These advantages include increased specificity, sensitivity and accuracy, as well as the detection of multiple analytes within a single assay. There is no need for an antibody for analyte detection and the method is not susceptible to the antibody-based interferences that plague immunoassays [1]. LC-MS/MS is suitable for multiple sample matrices and avoids the need for radioactive tracers. LC-MS/MS assays also have a wider dynamic measurement range and have improved between-method bias when compared to immunoassays.

LC-MS/MS initially played a role in specialist clinical laboratories in areas such as newborn screening, inborn errors of metabolism, toxicology and in immunosuppressant and therapeutic drug monitoring. More recently LC-MS/MS has established a role in diagnostic endocrinology, with the first appearance of LC/MS-MS for the measurement of vitamin D in the international vitamin D external quality assurance scheme (DEQAS) in 2005. There are now over 150 labs registered in this scheme using LC/MS-MS for the measurement of vitamin D. However, automated immunoassay still dominates and represents 69% of participants registered in the DEQAS scheme. Why has there not been more widespread adoption?

A number of issues have inhibited wider adoption and routine use of LC/MS-MS in the clinical laboratory. First among these is the use of labour-intensive manual workflows, which result in lower throughput, decreased productivity and longer turnaround time. Furthermore, a high level of technical expertise is needed, not only for method development, but also for troubleshooting assay and equipment failures. In addition to the high initial capital costs of purchasing the equipment, ongoing personnel costs are higher because of the need for more technically competent staff. With a clear understanding of where the bottlenecks in the process arise, these barriers can be overcome.

Figure 1 depicts the six main steps of a typical LC/MS-MS workflow, from sample receipt and extraction, separation in the LC, MS/MS analysis, data review and reporting of the results [2]. Of these steps it is the pre- and post-analytical stages that are the most time consuming and therefore if there is a focus on streamlining these, maximum benefit can be achieved. A number of steps can be taken to streamline the workflow, and these come under three broad headings of reduced manual processes, increased throughput and improved integration. Dependence on manual processes can be reduced by the automation of liquid handling and extraction, use of barcode reading for worklist generation and implementation of automated data analysis. Throughput can be increased with strategic column and sample management and by analyte multiplexing. Integration can be improved by bi-directional interfacing of the LC/MS-MS system to the laboratory information management system (LIMS) allowing automatic worklist upload and results download. These three strategic areas will be discussed in more detail below.

Reduced manual processes
Unlike the case with immunoassay, samples for LC-MS/MS usually require extraction prior to analysis. Historically this extraction step utilized liquid–liquid extraction or protein precipitation, these being carried out after the addition of internal standard to the calibrators, quality controls and patient samples. All of these steps involved manual pipetting and were very slow and time consuming. Use of an automated liquid-handling platform for the pipetting of samples and addition of internal standard allows some of the steps of liquid–liquid extraction and protein-precipitation methods to be automated. These liquid-handling platforms are available from a number of suppliers including Hamilton and Tecan.

With the advent of 96-well plate technology it became possible to carry out fully automated off-line solid phase extraction (SPE) using platforms such as the Freedom Evo (Tecan) and the Biomek NX (Beckman Coulter). More recently, supported liquid extraction (SLE), which allows solvent extraction to occur on a diatomaceous earth inert support, has also become available in a 96-well plate format. The Extrahera system (Biotage) enables automation of SLE by carrying out all of the pipetting and extraction steps required. In the NWLP laboratory, this system is used for the extraction of patient samples for vitamin D measurement by LC-MS/MS. A sample throughput of up to 50,000 samples per annum is achieved with capacity remaining for additional extractions for use in other LC-MS/MS applications. The system is robust and reliable with good pipetting precision and uses disposable pipette tips, thus avoiding sample carry over. Figure 2 depicts the Tecan Freedom Evo 200 and Biotage Extrahera liquid handlers in use in the NWLP laboratory.

In some manufacturers’ LC-MS/MS systems, on-line sample preparation and extraction is enabled by use of turbo flow or 2D chromatography. On-line protein precipitation and SPE is also now available using the Clinical Laboratory Automated sample preparation Module (CLAM)-2000 (Shimadzu Corporation) [3] and the Rapidfire 365 MS system (Agilent) [4] respectively. These latter examples most closely resemble the immunoassay workflow, whereby samples are introduced into the analytical system without any sample preparation or pre-treatment.

Increased throughput
Increased throughput can be achieved through the use of column and sample managers, allowing multiple assay batches to be queued up for overnight analysis of different LC-MS/MS assays. LC multiplexing enables multiple columns to be coupled to one tandem mass spectrometry system, maximizing the MS detection capability. In this approach, the use of quaternary solvent pumps in the LC enables column switching between different columns using different mobile phases. Finally there is analyte multiplexing, which can use manufacturers’ kits or in-house laboratory developed tests (LDTs). This approach enables multiple analytes to be detected in a single chromatographic separation by the use of multiple reaction monitoring for MS/MS detection. Perkin Elmer and Chromsystems both provide kits enabling the simultaneous measurement of multiple steroid hormones within a single assay panel. In the NWLP laboratory an in-house LDT steroid panel for the simultaneous measurement of androstenedione, 17-hydroxyprogesterone and testosterone has been implemented. This multiplexed assay has replaced the previous stand-alone assays for these analytes, thus increasing throughput and offering faster turnaround time. The assay utilizes off-line SPE using Waters Oasis PRiME HLB 96-well plates and the Tecan Freedom Evo 200 automated liquid handler [5].

Improved integration
Improved integration can be achieved by the use of bi-directional interfacing between the LIMS and the LC-MS/MS instrument software. Nowadays, manufacturers of LC-MS/MS systems offer customer support to allow their systems to be interfaced to the LIMS. One example is the MassLynx LIMS interface (Waters), which enables both worklist download and results upload. The MassLynx LIMS interface is accessed via the LC-MS/MS system software allowing sample worklists, created by barcode scanning of the patient samples, to be imported directly. Following peak integration and analyte quantitation the results are directly transmitted from the LC-MS/MS to the LIMS via an HL7 interface. This avoids the need for manual transcription thus saving a great deal of staff time and eliminating transcription errors.

The ultimate aim of LC-MS/MS integration is to achieve complete integration of LC-MS/MS instruments into the automated workflow of high-throughput routine clinical laboratories. With the recent launch of the Cascadion LC-MS/MS analyser (Thermo Fisher Scientific) this ultimate aim has now been achieved [6]. This analyser offers a complete LC-MS/MS solution including primary blood tube sampling, on-board sample extraction, LIMS connectivity and a random access workflow enabling the provision of a 24/7 service. Traceable manufacturer’s kits are offered for the measurement of a panel of immunosuppressant drugs, testosterone and vitamin D with further assay kits in the development pipeline. The Cascadion analyser is shown in Figure 3.

Summary
LC/MS-MS automation and integration is now a reality, allowing faster sample processing and improved turnaround time, as well as offering increased staff productivity, improved quality and reduced error rate. Staff time is liberated for further service development, allowing the more rapid introduction of validated in-house LDTs into the assay repertoire. Finally there is the possibility of complete analyser integration allowing routine, high-throughput analysis, as is already the standard approach for the common immunoassay platforms. This exciting development will support the more widespread adoption of LC-MS/MS in the routine clinical laboratory by offering complete automation and integration, overcoming the barriers discussed in this article and enabling the inherent advantages of LC/MS-MS in clinical laboratory practice to be more fully realized.

References
1. Jones AM, Honour JW. Unusual results from immunoassays and the role of the clinical endocrinologist. Clin Endocrinol Oxf 2006; 64: 234–244.
2. Zhang YV, Rockwood A. Impact of automation on mass spectrometry. Clin Chim Acta 2015; 450: 298–303.
3. Shimadzu. CLAM-2000. Fully automated sample preparation module for LCMS. (https://www.shimadzu.com/an/lcms/clam/index.html).
4. Jannetto PJ, Langman LJ. High-throughput online solid-phase extraction tandem mass spectrometry: Is it right for your clinical laboratory? Clin Biochem 2016; 49: 1032–1034.
5. Williams EL. LC-MS/MS measurement of serum steroids in the clinical laboratory. Clinical Laboratory International 2017; Sept: 18–20.
6. ThermoFisher Scientific. Cascadion SM Clinical Analyzer (www.thermofisher.com/cascadion).

The author
Emma L. Williams PhD, FRCPath
North West London Pathology, Imperial College Healthcare NHS Trust, London, UK

E-mail: emma.walker15@nhs.net

THE COVID-19 THREAT

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As the threat of a COVID-19 pandemic stares us in the face, it may be opportune to consider some scenarios ahead, especially in light of lessons from other, similar outbreaks in recent decades.
The first problem is sporadic bursts of public concern, alternating with periods of denial. Managing both requires measured doses of reliable information from authoritative sources. Such measurement is a delicate art at the best of times. During a crisis, media hype can mutate it easily into mass misinformation.
Similarly, the threat of terrorism has close parallels with each of the above aspects.

Wallonia at Medica 2020

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Intensive care in the emergency department: emergence of new models

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The ICU (intensive care unit) is easily one of a hospital’s highest value resources. A scarcity of intensive care beds means patients require prioritization when demand exceeds supply.  As a result, there are frequent delays in admission to an ICU. Though it is accepted that such delays adversely impact patient outcomes, there has been little data on the relationship between bed availability in an ICU and processes of care for patients who develop sudden clinical deterioration – especially in the context of an emergency department (ED). Recently, studies seeking to address this gap have provided renewed momentum to such discussions. They have also dovetailed with other efforts, such as specialist training in critical care for emergency medicine students and residents. However, the area generating maximum interest is a dedicated ICU within an emergency department.
Balancing needs, finding beds
Critically ill patients are commonplace in emergency medicine. They require aggressive and timely care, but emergency medicine clinicians have to balance their needs with those of other patients in their facility. In addition, due to constraints in beds in the ICU, increasing numbers of critically ill patients require to be boarded for prolonged periods of time in the ED. Adding to this problem is a shortage of beds in EDs too.
One of the most vexed questions is whether ED physicians consider bed availability in an ICU as part of their triage decisions, thereby impacting, in a potentially profound manner, on patient outcomes and resource utilization in both the ED and ICU. In effect, does a high availability of ICU beds lead to a bias in admission of patients who are either too well or too ill to benefit ? On the other side, does a low availability then lead to denying admission to ED patients, who would otherwise have been accepted to the ICU?

ED-ICU interface demands attention
In 2013, a study by the George Washington University School of Public Health and Health Sciences in Washington, DC, found that the volume of ICU admissions from EDs in the US had increased sharply, by almost 50 percent, in the period 2001-2009.1 During this period, another study found that the number of ICU beds across the country had increased only 15%, from 67,579 to 77,809.2
In other words, it is clear that ICU admissions from EDs have been increasing at a faster rate than ED visits. The George Washington University study found that though lengths of mean ED and hospital stays had not changed significantly, the mean ICU admission spends over 5 hours in the ED prior to transfer to an ICU bed. As a result, its authors concluded, there was a need for more emphasis on the ED-ICU interface and for critical care delivered in the ED.

Training emergency physicians in the ICU
The roots of this complex combination of challenges go back several decades. One good example is a time-based study, published in 1993 in the peer-reviewed journal ‘Critical Care Medicine’.3  The authors, from Houston, Texas-based Methodist Hospital’s Department of Emergency Services, noted that not only did critically ill patients “constitute an important proportion of emergency department practice”, but also needed treatment in the ED “for significant periods of time.”  One of the solutions they proposed was for emergency medicine practitioners to “receive training in the continuing management of critically ill patients.”
The above approach was also witnessed in Europe. In Belgium, for example, an official paper from 1995, titled ‘How to become an intensivist’, proposes that a candidate with an “agreement in Emergency medicine has to make another year of ICU formation.”4

Pathways remained unclear
In subsequent years, there was significant growth in emergency medicine residents pursuing critical care fellowship training, and a reconsideration of the role played by the ED in caring for the critically ill. Nevertheless, there still was a lack of clarity in ways to acquire advanced training in critical care for emergency medicine residents.
In December 2002, an article in ‘Current Opinion in Critical Care’ complained that although ED care for critically ill patients was shown to significantly impact mortality, “formal critical care training for emergency physicians” was still “limited.”5
Less than three years later, another peer-reviewed journal, ‘Annals of Emergency Medicine’, noted that in spite of growing demand for critical care services, most critical care medicine fellowships did not accept emergency medicine residents, “and those who do successfully complete a fellowship do not have access to a US certification examination in critical care medicine.”6  The authors proposed “expansion of the J-1 visa waiver program for foreign medical graduates,” but said the only sensible long-term approach was to strengthen the relationship between emergency medicine and critical care medicine.

Critical care medicine as emergency medicine sub-specialty
In the US, the Accreditation Council for Graduate Medical Education (ACGME) approved critical care medicine as a sub-specialty for emergency medicine physicians in 2011. The following year, the surgical critical care fellowship pathway was approved for emergency physicians interested in becoming board-eligible intensivists.
Currently, the most common training pathways are via combinations of critical care medicine with internal medicine and anaesthesiology, and alongside surgical critical care and neurocritical care. Career pathways for physicians trained in emergency and critical care medicine are also evolving, with options in both community and academic settings.

The role of professional societies
Leading professional societies in emergency medicine and critical care have set up focused sections on the interface between the two areas to stimulate interest as well as provide support to medical students and residents.
Examples from the US include the Emergency Medicine Residents’ Association (EMRA), whose Critical Care Division maintains a comprehensive database of training opportunities across the country,7  and regularly publishes alerts on key developments in critical care. Another interesting initiative is the Coalition for Critical Care Medicine in the Emergency Department (C3MED), which was set up in 2003 and hosts an active email discussion forum.8
Similar efforts have been undertaken by the American College of Emergency Physicians (ACEP),9  the Society of Critical Care Medicine (SCCM),10  the American Association of Emergency Medicine11  and the Society for Academic Emergency Medicine (SAEM).12
In Europe, one of the best-known initiatives to harmonize convergence of the ED and the ICU is ISICEM, the International Symposium on Intensive Care and Emergency Medicine. This non-profit organization, headquartered in Brussels, was set up in 1980. It currently runs a series of eight annual events, covering different aspects of intensive care and emergency medicine. Over the years, participation has grown from about 200 to over 6,000 from more than 100 countries.
 
Impact of ED on ICU: US and European studies
There have also been concerted efforts to assess the impact of emergency department volume and boarding times on ICU admission and patient outcomes. Two recent studies have catalysed considerable new attention in the topic.
The first is a retrospective cohort study on critically-ill ED patients for whom a consult for medical ICU admission had been requested over a 21-month period. It was published in ‘Critical Care Medicine’ last year by a US-based team from the Icahn School of Medicine at Mount Sinai, New York, and titled ‘Effect of Emergency Department and ICU Occupancy on Admission Decisions and Outcomes for Critically Ill Patients’.
The authors conclude that ICU admission decisions for critically ill ED patients were affected by ICU bed availability. However, higher ED volume and other ICU occupancy did not play a role. They also found that prolonged ED boarding times were associated with worse patient outcomes, suggesting a need for improved throughput and targeted care for patients awaiting ICU admission.
In August 2019, ‘Critical Care Medicine’ published findings online from another study on this topic, this one by a Dutch team from  six University Medical Centres at Amsterdam, Groningen, Leiden, Nijmegen, Rotterdam and Utrecht, along with the country’s National Intensive Care Evaluation (NICE) foundation.13  The retrospective observational cohort study conducted a registry analysis of 14,788 patients from the six hospitals, and found an association between emergency department to ICU time greater than 2.4 hours and increased hospital mortality after ICU admission

Ad-hoc and hybrid models
At present, there are two approaches to the challenge of intensive care in the ED. The more common is to have an emergency physician intensivist working standard ED shifts, and lending expertise on an ad-hoc basis to critically ill patients. A recent development is a ‘hybrid’ model. This earmarks a dedicated area of the emergency department for ramping up care to critically ill patients, with a dedicated physician providing intensive care only to such patients, typically for periods longer than an hour.
Supporters of the hybrid model state that it is easier and less expensive to establish with extra costs involving only the dedicated ED-ICU physician.

The ED-ICU
One of the most watched developments in recent years in care for critically ill patients in an ED is the development of ED-ICUs (emergency department intensive care units).
Two such facilities in the US, Stony Brook Resuscitation and Acute Critical Care Unit (RACC) in New York and Emergency Critical Care Center (EC3) in Michigan are considered as being both ED-ICU pioneers and best-of-class references for the concept.
EC3 is considered to be among the world’s most advanced emergency critical care centres. It was opened in February 2015 and has five resuscitation trauma bays and nine patient rooms, located adjacent to the main adult emergency department.
Due to this reputation, the case for ED-ICUs was strengthened after a recent study by EC3 found convincing improvements in survival as well as reduced inpatient ICU admissions.14  In effect, an ED-ICU can improve care and survival rates for the entire emergency department population.15
The EC3 study covered 350,000 ED patient encounters, and found that implementation of an ED-based ICU was associated with significant reductions in risk-adjusted 30-day mortality among patients, from 2.13 to 1.83 percent. The median time to ICU-level care for critically ill patients decreased from 5.3 hours to 3.4 hours, while the hospital ICU admission rate from the ED dropped from 3.2 percent to 2.8 percent.

References
1.https://www.sciencedaily.com/releases/2013/05/130514212946.htm2.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351597/3.https://www.ncbi.nlm.nih.gov/pubmed/8319477/4.http://www.siz.be/education/training-in-critical-care/5.https://www.ncbi.nlm.nih.gov/pubmed/124545496.https://pdfs.semanticscholar.org/4f1b/5cea333174e599784e6a2d80c9b55b868b2e.pdf7.https://www.emra.org/fellowships/critical-care-fellowships/8.c3med@yahoogroups.com9.https://www.acep.org/criticalcaresection/10.http://www.sccm.org/Member-Center/Sections/Pages/Emergency-Medicine.aspx11.http://www.aaem.org/membership/critical-care-section12.https://community.saem.org/communities/community-home?CommunityKey=5dc206d8-d248-4f71-aecd-e0490cdc3ba913.https://insights.ovid.com/pubmed?pmid=3139332114.https://jamanetwork.com/journals/jamanetworkopen/fullarticle/273862515.https://medicalxpress.com/news/2019-07-department-based-intensive-patient-survival.html

Dose reduction in CT – universal set of standards is achievable, says new study

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Since its introduction in 1973, X-ray computed tomography (CT) has become a leading modality for diagnostic imaging. The advantages of CT are manifold. Above all, they include rapid scanning and small spatial resolution, which allows for relatively quick and accurate diagnosis of injuries and disease. CT has also been an imaging tool of choice for the staging and treatment follow-up of cancer.

Growth in use, but variations between countries
Overall, CT use has grown rapidly. The total number of scans in the US is estimated to be in the region of 80 million a year. In England, the National Health Service (NHS) reported 4.8 million CT scans in 2016/17, which is 40 percent more than the 3.4 million MRI scans done during that year. CT usage has also been growing rapidly – in England at about 8% annually, compared to just 1.5% for X-rays and 5% for ultrasound.
Nevertheless, there are significant variations between countries in the intensity of CT use. According to data from the Paris-based Organization for Economic Cooperation and Development (OECD), the annual rate of CT scans per 1,000 inhabitants ranges from a high of 225-230 in the US and Japan, to a low of 37 in Finland. The rate is about 80 in Italy, 90 in the Netherlands, 110 in Spain, 140 in Germany and 200 in Belgium and France.
Differences in radiation dosing practice
Though large, such divergences are considered to be less significant than differences in radiation dose to which patients are exposed, for the same condition. In December 2007, a study published in ‘European Radiology Supplement’ had found dosage could have been halved in many cases without impacting on image quality. Another study two years later revealed a 13-fold difference between the lowest and highest radiation doses used for identical CT procedures by four clinical sites in the neighbourhood of San Francisco.
Concerns about such issues have been dramatically highlighted after a major new international study, which attributes differences in dosage to the person doing the scanning rather than to patients or equipment. The study, published in ‘The British Medical Journal’ (BMJ) in January 2019, found that patient characteristics, make and model of scanner, and type of hospital where the CT scan was done had little effect on the amount of radiation used.

Analysis of 2 million CT scans in 151 institutions
The BMJ study was based on a massive effort by a research team led by Dr. Rebecca Smith-Bindman, a professor in the Department of Radiology and Biomedical Imaging at the University of California San Francisco (UCSF). The researchers analysed dose data for over 2 million CT scans of the abdomen, chest and head, at 151 institutions in seven countries.
Their findings are likely to resonate strongly, given the association of radiation with cancer. Although CT scans account for a minority of diagnostic radiologic procedures, they use large amounts of radiation per image. Some estimates suggest that CT contributes nearly half the US population’s radiation dose from all medical examinations. The figure in England is higher, at 68 percent, although plain radiography is used five times more often than CT in the country (22.9 million procedures in 2016/17 versus 4.8 million).

Cancer risks of CT
The association with cancer has been controversial, especially when predictions of the impact of CT scanning have been based on a linear-no-threshold dose-response model. Some have argued that CT radiation doses are too low to produce any health effect.
There is also uncertainty about how to calculate risk accurately. This is because of a host of factors. Firstly, radiologists are not necessarily familiar with CT radiation exposure descriptors (volume CT dose index and dose length product). Secondly, there have been a series of revisions about the relative sensitivity of organs to radiation. Finally, radiation dose in units such as millisieverts (mSv) are used to estimate population risks based on generic models, not individual patient calculated dose. Indeed, the radiation dose in a typical CT scan (1–14 mSv depending on the exam) is similar to the annual dose received from natural sources, such as radon and cosmic radiation – which typically varies from 1 to 10 mSv, depending on where a person lives.

Even small risks justify search for solutions
Nevertheless, the current consensus is that, even if the risk of cancer from CT imaging is small, the economic burden of treatment of the proportionately reduced number may well be significant, given the high prices of cancer treatment.
Neither does anyone question the logic of attacking even a small cancer risk. In December 2009, a report in ‘The Archives of Internal Medicine’ made a detailed assessment of projected cancer risks due to CT scans in the US. The study was conducted by a team from the Radiation Epidemiology Branch of the National Cancer Institute (NCI), and argued that changes in practice might help to avoid the possibility of reaching an attributable risk of 29,000 cancer cases based on CT scans in the year 2007. The authors also observed that the impact would be largest in abdomen, pelvis and chest CT scans in adults aged 35 to 54 years.

Unnecessary scans
One of the most vexatious issues concerns CT scans which are not medically necessary, especially when it concerns repeat imaging of a particular patient – and the ensuing enhancement of cancer risk. According to one estimate, unnecessary scans could account for as much as 30 percent of CTs in the US. In Europe, such a figure is also likely to be high in countries such as Belgium and France where per capita CT scan levels are close to those of the US.
Though the US state of California has passed a law requiring documentation in a patient’s medical record of radiation dose used for every CT scan, compliance has been inconsistent. Perspectives in Europe are problematic too. For example, the European Union collects dose levels in Europe, but there are major differences in definitions and data collection techniques.

Progress in pediatric dosing
Until the NCI study at the end of 2009, the emphasis on reducing CT cancer risks had largely been on pediatric scans. The authors of that paper noted there was evidence of pediatric doses being reduced as a result of social marketing campaigns such as Image Gently. The latter was launched in 2008 by the Alliance for Radiation Safety in Pediatric Imaging.

Lessons from the pediatric dose control campaign
One of the key recommendations of Image Gently was to promote standardization of pediatric dose measurements and display across vendor equipment.
This is precisely what the recent BMJ study proposes to do for all patients. The authors of the study assessed mean effective doses and proportions of high dose examinations (defined as CT scans with doses above the 75th percentile defined during a baseline period) for abdomen, chest, combined chest and abdomen, and head CT. These were classified by patient characteristics (sex, age, and size), type of institution (trauma centre, 24×7 care provision, academic and private hospital), practice volumes, machine manufacturer and model, country etc. The figures were adjusted for patient characteristics, using hierarchical linear and logistic regression.
For example, after taking into account patient factors, a fourfold range in radiation doses still existed in abdominal scans. Similar variations were found for chest and combined chest-and-abdomen scans.

Huge variations in dose
The BMJ study found that variations in radiation dose across institutions and countries were huge. For abdomen CT examinations, the mean effective radiation dose differed by a factor of four, with a 17-fold range in the share of high dose examinations (4 to 69%). Variations in mean effective dose for chest scans and combined chest plus abdomen scans were also close to four times, while the share of high dose exams varied from 1 to 26%, and 2 to 78%, respectively. For head CT, the differences were less spectacular (with the range of mean effective doses less than 1.5 times and the share of high dose exams ranging from 8 to 27%.

Achievable and universal standards
However, when the UCSF group adjusted for technical parameters, that is, in terms of the way CT scanners were used by medical staff, the variations in doses nearly disappeared.
The researchers conclude that it is possible to optimize doses to a “single set of achievable quality standards” and apply this “to all hospitals and imaging facilities.” They also noted that the choice of “appropriate CT protocol parameters might be less complex than widely believed.” The key to protocol optimization lies in updating physician awareness and recalibrating expectations about what constitutes a diagnostic CT scan. The latter will be based on a better alignment of CT protocol parameter choices with diagnostic image quality requirements.
One interesting finding was that institutions with lower average doses shared scanning approaches. These institutions tended to limit the number of protocols, with each relying on the minimum dose required to answer the clinical question. They used multiple CT scanning infrequently, had lower settings for tube current and tube potential, and used higher pitch for most, if not all, imaging indications.

The way ahead
The road to CT dose reduction and standardization will vary by type of institution and country. This is due to differences in the make and model of CT scanners as well as medical cultures, in terms of radiologist preferences and personnel support. There are case studies of protocol overhauls taking a year or more, and needing to be kept up-to-date with new CT software and scanner upgrades. Examinations with higher radiation exposure generally give more acceptable images than those where exposure is lower. The challenge is to optimize a ‘correct’ minimum dose for different patient sizes, ages and conditions. Continuing improvements in scanning technology will undoubtedly also be part of the process of optimizing protocols. On their side, some companies have been experimenting with artificial intelligence algorithms to position patients correctly in a CT scanner. Off-centre CT scans can expose patients to much higher levels of radiation
than necessary.

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