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Mediskills Urology training models with a high degree of realism

PPPs in the Middle East Interview with Simon Leary of PwC Paxman Coolers Scalp cooling technology Focus: UK East Midlands Where bioscience thrives Aesica Pharma Market leading Formulation Development Research paper: Accelerated Bio-Ageing & Socioeconomic Status World Health Care Congress Middle East Abu Dhabi 2011 Preview

November: MEDICA 2011 Special Edition MEH award winners announced

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Editor’s intro This issue features some excellent UK companies with proucts with the potential to make a positive impact on healthcare in the Middle East. Mediskills’ urology training models, Paxman’s scalp cooling system, and Aesica’s formulation development services and pharma products are all UK success stories that are ready to expand their global exports, with the Middle East viewed as an increasingly important region. MEH speaks to Simon Leary of PwC on the growing trend for PPP hospital builds in the Middle East, and how these partnerships can benefit countires as diverse as Qatar and Egypt. We look at the bioscience hub of Nottingham in the UK. A major R&D centre of excellence driven by global research expertise based in the renowned universities of Nottingham, Loughborough, Leicester and Nottingham Trent.

The healthcare trade show season kicked off with REHACARE last month. We review the show, and preview the World Health Care Congress Middle East. Next month will be the MEDICA issue, with a preview of all the best medtech that will be on display, and we formally announce the winners of the 2011MEH awards. Guy Rowland, Editor Editor: Guy Rowland Publisher: Mike Tanousis Associate Publisher: Chris Silk MEH Publishing Limited Company Number 7059215 151 Church Rd Shoeburyness Essex SS3 9EZ United Kingdom Tel: +44 01702 296776 Mobile: +44 0776 1202468 Skype: mike.tanousis1

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COVER FEATURE Mediskills - Urology training models with a high degree of realism. Mediskills seeks to boost urology education and training in the Middle East with the latest 100% anatomically correct Advanced Scope Trainer.

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EXCLUSIVE INTERVIEW: What is driving the new trend for Public Private Partnerships in the Middle East? Middle East Hospital speaks to Simon Leary, Managing Partner at leading PPP consultants Pricewaterhouse Cooper with responsibility for Health Industries Middle East.

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Paxman Coolers - Scalp cooling technology Paxman is the leading global manufacturer and supplier of scalp cooling equipment, for the prevention of hair loss during chemotherapy.

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UK Regional Focus: East Midlands Nottingham and the East Midlands is one of the leading UK centres for medical technologies, and is a major hub for bioscience research and developlment.

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Preview: World Health Care Congress Middle East 10-13 December 2011, Abu Dhabi

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Aesica Pharma - Formulation Development specialists. Aesica is a fast-growing UK company with a global footprint, expanding into India, the US and Middle East

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Review: REHACARE 2011 A look at the highlights of last month’s show.

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Research paper: Accelerated Bio-Ageing & Socioeconomic Status - Accelerated Telomere Attrition Is Associated with Relative Household Income, Diet and Inflammation in the pSoBid Cohort.

Editor: Guy Rowland Tel: +44 01223 241307 Mobile : +44 07909 088369 guyrowland@middleeasthospital.com Features Editor: Emrys Baird Tel +44 07961391055 em@middleeasthospital.com

UAE distributor Dr Prem Jagyasi MD & CEO ExHealth, P. O. Box. 505131 Dubai HealthCare City, UAE Tel:+971 4 437 0170 Prem@Jagyasi.comm www.ExHealth.com

MEH agent for Egypt Dr.Amr Salah Millennium International Group amr.salah@migaegypt.com Tel: +2 0222736354 Mobile: +2 0122227209

Abu Dhabi & Bahrain office Ms. Pam Page Direct Phone: +971 4 329 1099 UAE Mobile: + 971 50 424 0569 USA Mobile: +617 943 0934 pam.page@worldcongress.com

MEH agent for Saudi Arabia Anwar Al-Qahtani Tejaratna Trading Tahlia Street Riyadh Saudi Arabia Tel: +966 508389039 aburakan01@gmail.com tejaratna@gmx.com For more information about the magazine contact the publisher or editor. Or email MEH at: editorial@middleeasthospital.com

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Mediskills Models - Designed by Clinicians for Clinicians Mediskills was founded in 1998 by three UK clinicians - a radiologist and two urologists to develop models for skills training in urology, interventional uroradiology and other minimally invasive procedures. John Kelly acquired the Mediskills company in 2008 having advised the founders initially on developing the business through his own and still existing consulting company Moffat Dickson Ltd [www.moffatdickson.com]. The founders started the development of the Mediskills business with the ethos to develop a range of training models suitable for their trainees to experience both anatomically correct models with a high degree of realism. John with his Team of model makers has further developed the Mediskills models to meet customer requirements in particular the Advanced Scope Trainer which has the capability to re-charge the stones into both kidneys from external ports. Under John’s direction and innovative approach Mediskills was presented with a Business Award 2011 from Medilink, a member organisation, as a Finalist in the Export Achievement category at their annual Innovation Day 2011.

The Advanced Scope Trainer

Meeting training challenges Challenges facing device and instrument manufacturers today include the evaluation of new instruments and accessories, training of sales personnel, demonstrating new products and physician education. Mediskills can assist in the conquering of these challenges by the provision of lifelike models for evaluation and training in almost all aspects of Endourology. Mr Kelly told MEH, “The long held philosophy, see one, do one, teach

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Training Models with a High Degree of Realism one, is no longer applicable in the modern teaching of practical skills. Learning on the job is unacceptable to patients and surgeons alike; in today's cost conscious health services there is pressure to use operating lists as efficiently as possible and therefore time available for skills teaching is at a premium.� Mediskills provide the opportunity to simulate endoscopic procedures as well as providing an opportunity for bench testing new products at the prototype stage by offering a range of models for percutaneous access, percutaneous nephrolithotomy and ureteroscopy. Unlike animal tissue models, there are no health and safety issues, which restrict the use of medical models. They can be used in the laboratory, hospital or commercial exhibition with complete safety. Mr Kelly added, “Mediskills is dedicated to the improvement of training and the acquisition of endoskills by trainees in all aspects of endourology and interventional uroradiology. The Mediskills team has a long experience of running practical skills courses which has enabled them to develop the models. These models possess a high degree of realism resulting from extensive discussions with fellow clinicians. The models, made in the UK, are developed from hand crafted moulds and produced from silicone based plastics. Each model is individually manufactured and undergoes rigorous quality control testing before dispatch to the customer. It is supplied ready for use with a complete set of instructions.� Benefits for industry and academic training The Mediskills Models range currently available will enable company personnel to become proficient in an extensive array of clinical procedures.

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Mediskills Models - Designed by Clinicians for Clinicians Mediskills sell to all the major endourology instrument manufacturers across the globe. Their largest market is Japan, with strong sales in Brazil, USA, Germany, France, India and Malaysia. In the Middle East the company sees great potential for the use of their products by trainee surgeons in the region’s hospitals and medical colleges. Mr Kelly will be attending the World Health Care Congress Middle East in Abu Dhabi (10-13 December) where he will be meeting with senior healthcare professionals and officials. He will also be collecting a Middle East Hospital Health and Innovation Award for the Advanced Scope Trainer; as the best new product for export to the Middle East in the training and education category. Mediskills training products The Mediskills advanced ureteroscopy trainer has been designed to meet the needs of basic and advanced training in rigid and flexible ureteroscopy.

The Advanced Scope Trainer

Mr Kelly explained, “Experience of these procedures will assist sales and marketing teams as well as engineers, by enabling them to appreciate and acquire the same endoskills used by clinicians in order to perform endourological procedures. Mediskills’ models are powerful marketing tools which may be

used by your Sales and Marketing Te a m s to demonstrate your products to b e s t e ffe ct; th e y ca n a l s o b e used as part of an educational course for the introduction of new procedures and devices for endourological management o f u r i n a r y tr a c t d i se a se .”

The Advanced Scope Trainer (AST) utilises a clear acrylic casing more suited to the actual demonstration of the properties of a flexible ureteroscope to potential customers. It incorporates features such as distensible bladder, a realistic ureteric orifice and a ureter, which follows the same anatomical course as the adult male, thus providing a realistic alternative to training in patients. At the same time this allows the trainee ureteroscopist to develop a feel for the difficulties that may be encountered during procedures in patients. In addition the AST has one enlarged kidney and a distorted ureter allowing the trainee ureteroscopist to develop a feel for

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100% Anatomically Correct Models the difficulties that may be encountered during real-life procedures in patients. The Advanced Scope Trainer provides the operative with the ability to re-charge each kidney with stones via the two external ports when the existing stones are removed or destroyed. The Standard Scope Trainer is designed for multiple uses. The distendable bladder with an anatomically correct ureterovesical junction will enable ease of access with the ureteroscope to be assessed. The reproduction of the lumbar lordosis enables the performance of rigid ureteroscopes to be evaluated along with devices for stone retrieval and disintegration.

The Perc Trainer

The Standard Scope Trainer

The carefully designed collecting system containing both stones and a papillary tumour together with fluoroscopic properties of the model enables the performance and manoeuvrability of flexible ureteroscopes to be assessed and demonstrated. In addition, the placement of a nephroscope through a percutaneous track can be a very powerful tool for demonstrating the properties of a flexible ureteroscope to potential customers. A unique feature of the Perc Trainer kidney model is the ability to reproduce ultrasound and fluoroscopic features of the human kidney. Re-use is limited, depending on the procedure practised; but the resealing material allows repeated needle puncture in the collecting system. However once a tract has been dilated, use is restricted to further tract dilation and endoscopic manoeuvres. www.mediskills.com

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Mediskills Models - Designed by Clinicians for Clinicians John Kelly biography For the last 35 years John has been involved in the pharmaceutical industry at Board and senior management level in a number of both Japanese and EU based companies. Latterly John was President and Board Member for the major Japanese conglomerate Kowa Company Ltd, Tokyo where he established the European subsidiary near London to head up their clinical development operation and recruited a team of over 30 staff carrying out clinical trials in Europe, US, India and Russia. During this period John has amassed a network of contacts particularly in Japan and South East Asia as well as within the EU where he has a network of pharmaceutical and biotech contacts. John’s track record of being involved in two start-up operations for Japanese pharmaceutical companies in Europe in both the commercial oncology arena launching the anti-cancer drug Mitomycin-C in Europe and in research through the clinical development sector gives him a valuable insight into the scientific and business area as well as the cultural environment within Japan which is often a challenge for client companies reaching out to this market. During his career John gained valuable contacts during this period internationally with senior oncologists and urologists and is listed as a founder member of the European Organisation for the Research and Treatment of Cancer GU Group based in Brussels (E.O.R.T.C.) jtkelly@mediskills.com www.moffatdickson.com

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Public Private Partnerships in the Middle East what is driving the new trend for Public Private Partnerships in the Middle East? Middle East Hospital speaks to Simon Leary, Managing Partner at leading PPP consultants Pricewaterhouse Cooper(PwC), with responsibility for Health Industries Middle East. The concept of PPPs has been enshrined in law in some Middle Eastern countries for over a decade. It is only much more recently, however, the governmental multi-sector PPP units and /or specific PPP deals have emerged as real contenders to develop infrastructure and social sector services. Middle East Hospital (MEH): What is your role for PwC in the Middle East? Simon Leary (SL): The UK has an increasingly close relationship with Middle East. Im here to build the multifunctional health industries PPP offering that we have in UK in the 12 countries of the Middle East. We are advising governments on setting up national health projects; for example we are currently helping to establish a national health insurance scheme in Doha which will cover everyone in Qatar, nationals and non-nationals. We are also advising on establishing a national primary care network in Qatar, and introducing the concept of an end to end medical service that starts with prevention and goes right through to long term care. Qatar is leading the charge on this in the region. We are also helping to set up what is arguably the first proper PPP in the region, in Kuwait. This is really a flagship project for PPP in the region. We help with performance improvement, not only cost, but policy and critical service, through to supporting other aspects of the broader health continuum. This is

What is a Public Private Partnership? In essence Public Private Partnerships are a collection of models. One such model is the PFI (Private Finance Initiative) model in which the private sector is contracted to rebuild or replace a public asset and maintain that asset for 20 to 30 years. However, PFIs are merely one type of PPP model. PPPs are defined as a broader partnership between private contractors and government, in which the common characteristics are that the public sector contracts (usually on a long term basis) with the private sector for the provision of a public service. During the 1990s, the United Kingdom was fertile ground for PPPs in healthcare since the government had vastly

underinvested in its National Health Service (NHS) hospitals. As a result, nearly every new hospital – approx. 100 buildings in 12 years – was built as a PPP in the UK. The concept spread to other countries, and the PFI model developed its own cadre of expertise as bidders and the public sector improved on the process. PPPs were not without criticism and some well publicised failures in Australia, Japan, Italy and other places allowed sceptics to point out the flaws in the model. However, important lessons have been learned from these failures according to the model’s advocates, and it has now been refined and altered.

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Interview with Simon Leary, Pricewaterhouse Cooper why we call our department health “industries” as opposed to health “care”. We are also looking at aspects of the pharma market, the big issue around supply chain, and also prosthetics; which are very much in demand due to the high level of road accidents. MEH: Who do you work with on these projects? SL: This work requires a multidisciplinary team, so I recruit people from both inside and outside the Middle East who have the requisite skills to tackle these issues. Our approach is very country specific due to the big differences in the healthcare systems from country to country. Requirements are very different for example in Basra than they are in Doha. Also, there are very different levels of development between the Gulf, Levant and North Africa. For example, we are doing a lot of public health and primary care outreach work in Iraq to tackle the immediate need, while also building a 500 bed hospital in Kuwait. We use resources within the region as much as possible to deliver projects. That means cutting down on fly-in resource except where outside expertise is essential, and ensuring that the bulk of the work is done by people living in the region, if not the actual country. MEH: How is the flagship Kuwait hospital project progressing? SL: The market in Kuwait is dominated by the public sector, with some private hospitals. There hasn’t been a completely new hospital build in Kuwait for 30 years. The National Rehabilitation Facility- the only hospital of its kind in the country- is currently run out of an army barracks, with 70 beds to cater for the entire country. PwC has completed the feasibility study for the Ministry of Health

Sizing the market: Health spending is expected to increase by 65.5% between 2010 and 2020

Current and projected health spending as percent of GDP in OECD, BRIC nations

and is the project sponsor. Later this year work will begin on a PPP scheme to rebuild the hospital with 500 beds. This will enable the hospital to meet new demand, and enable people currently going overseas for treatment to stay at home. The PPP will include the building, operating and managing of the hospital by the private sector on a fixed-term franchise, with the state providing the patient-facing staff

(doctors and nurses). This arrangement makes the project stand out from other PPPs currently operating in the Gulf due to the greater level of private sector involvement and the risk transfer. It is therefore a model similar to the PPP that you would find in the UK. MEH: What is the attraction of the PPP model for Middle Eastern governments? SL: It’s impossible to generalise about this region, you really need to split the market in two. Some

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Public Private Partnerships in the Middle East countries require the finance and the expertise- such as Egypt which has been very active in creating PPPs across several sectors- while others need the technical knowhow and expertise brought from outside the country. Qatar is a good example of the latter case, where the capital is the least important factor, whereas in North Africa, as in the West, the finance is the most important requirement. MEH: How do you see the future of healthcare in the Middle East? SL: The state will continue to play the major role, both due to the political nature of healthcare delivery (and this is true of all countries not just in the Middle East), and because most of the health funding is provided by the state. Citizens in the region are also accustomed to the state providing healthcare and expect to be taken care of. I do expect the healthcare landscape to change over time in the Gulf. While there is no reason to believe it will not continue to be free or heavily subsidised, there are more efficient ways of delivering and financing healthcare. Not necessarily spending less, but allocating finds more efficiently. Countries need to look at their models of care, which tend to be very inefficient. We are in the early stages of having that debate in countries such as Qatar, who recognise that healthcare as a whole needs to set up to be sustainable both financially and operationally, and not just focused on trophy projects. MEH: Will healthcare become more sustainable in the Gulf? SL: The healthcare workforce is increasingly global in nature (eg. 30% of NHS staff not born in UK). In the Gulf States, where the

majority of the population are not nationals, the health service reflects the rest of society. Forward looking countries are investing in training more of their own nationals, and we have recently been consulted on an endowment programme where nationals of one country will be sent abroad to receive medical training,

on the condition that they then return and spend a certain number of years working for the health service of that state. There needs to be much more of this kind of programme that contains an element of repatriation in order to keep those skilled workers in the country.

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Public Private Partnerships in the Middle East

Simon Leary profile Simon is a partner in Pricewaterhouse Coopers’ international health industries advisory practice and is currently the Managing Partner for our Health Industries business in the Middle East. He is also Managing Partner for PwC’s Health Research Institute (HRI) across EMEA and sits on the HRI global governing council. From 2002-2005 Simon was seconded to the UK’s Department of Health where he undertook a number of roles, latterly as Head of the national Strategy Unit. This role involved providing medium and long term strategy advice to the Prime Minister’s Office (Strategy and Delivery Units), Health Ministers and senior civil servants. From 1996-2002 he was seconded to PwC in South East Asia where he worked across the region (initially as director and then as a partner) to build a multidisciplinary business focused across those sectors being funded by international agencies and national reconstruction funds. MEH: Can the Middle East avoid the problems some other countries have had with PPPs? SL: It needs to be remembered that the PPP model in the UK has taken 20 years to develop into its current level of maturity, while this is still new in the Middle East. There will need to be a learning

process over the course of several years. While lessons can be learned from the mistakes of others, the conditions and economics for PPP can vary greatly depending on the country, so blindly following other national models that may be inappropriate.

Simon was educated at Cambridge University and London Business School. He is a Fellow of the Royal Society of Medicine (UK), an Affiliate Fellow of the Institute of Chartered Accountants in England and Wales and a member of the Royal Institute of International Affairs.

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Paxman Coolers Paxman is the leading global manufacturer and supplier of scalp cooling equipment, for the prevention of hair loss during chemotherapy. Hair loss is a well documented side effect of many chemotherapy regimes. It is often devastating and the fear of hair loss has even been known to cause patients to refuse treatment. The revolutionary Paxman hair loss prevention system is responsible for helping thousands of people worldwide keep their hair and their dignity. Paxman’s innovative system is the very latest in scalp cooling technology researched and developed in the UK over a number of years, it now has the backing of leading Oncologists from around the World. Company history Paxman Coolers was formed over ten years ago after the Managing Director’s wife lost all her hair during her cancer treatment. The family found this very distressing so using his engineering knowledge, the resources within his existing business and the help of his brother, Glenn Paxman created the Paxman Scalp Cooler. Following trials at Huddersfield Royal Infirmary, the first systems were sold into hospitals including St Mary’s Hospital, Portsmouth, Christies in Manchester and the Stoke Mandeville Hospital. The Paxman Scalp Cooler has also received the Millennium Product Award for Innovation and has had much success in many hospitals in the UK, Europe and other parts of the World. How it works Chemotherapy affects the rapidly dividing cells of the hair follicles and at any given time, 90 per cent of hair follicles are in the actively

dividing phase. Cooling the scalp during selected chemotherapy regimes has been shown to reduce or prevent otherwise inevitable total hair loss by restricting the blood flow to the hair follicles, thereby reducing the amount of chemotherapy chemicals reaching them. For many of us, one of the

most devastating side-effects of chemotherapy is the loss of our hair. However, there is a revolutionary machine that can help prevent this – the Paxman Scalp Cooler. The Paxman Scalp Cooler is unique - using a lightweight cap made out of silicone which is comfortable and provides a snug fit

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Scalp Cooling Equipment ensures an efficient use of space. As the temperature is maintained by the system, nursing staff do not need to stay with patients during the treatment. The cap is worn for approximately 30 minutes before chemotherapy infusion and continues to be worn during administration of the drugs and then for a calculated time afterwards. The cold cap is then worn for each chemotherapy session until the course of treatment is completed. The average time a patient wears the cold cap is from two to two and a half hours, this is dependent upon the toxicity of the chemo-therapy drugs being administered. Success In The Middle East Paxman Coolers Ltd was delighted to participate in The 5th Gulf Federation Cancer Congress alongside the regional representative and its new distributor, Gateway Scientific, held under patronage of H.H. Sheikah Jawaher Bint Mohammed AlQassimi, which was officially opened by Dr. Haneif Hassan, Prime Minister of Health and held at Expo Center Sharjah.

to the patient’s head. The caps are linked to a compact refrigeration unit which circulates coolant at -6°C through coolant lines and into the cooling caps. Temperature sensors ensure the cap maintains the scalp at a constant temperature throughout the treatment. Consideration and care has gone

into the design of the system in order to meet the needs of both the patient and nursing staff. The Paxman system is simple for nurses to operate as it has easy-touse touch screen displays allowing instant visual monitoring. The compact nature of the system makes it easy to manoeuvre and

The Paxman stand welcomed a large number of visitors from UAE and other gulf countries, including the Prime Minister of Health. The Friend of Cancer Patient (FOCP) Society, represented by Miss Amira Bin Karam and Dr. Sawsan AlMadhi committed to donate the Paxman systems into hospitals in UAE, thereby enabling more patients to reap the system’s benefits. Dr. Falah Al-khatib, Head of Scientific Committee, also showed his interest in the Paxman technology and plans to utilise it in his clinical practice at the City Hospital in Dubai. The President of Bahrain Cancer Society and

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Paxman Coolers Representatives of Saudi Cancer Society also attended the stand, showing great interest and promising to help hospitals with donations to purchase Paxman scalp cooling systems. At the end of the show Richard Paxman received an award on behalf of the company from H.H. Sheikh Khalid Al-Qassimi for its excellent participation in the congress. The company are looking forward to working with organisations and hospitals in the Middle East in the coming months to enable more patients the opportunity to receive scalp cooling as part of their treatment programme. Export Achievement Award In 2010 Paxman won the ‘UK Trade and Investment Export Achievement Award,’ at the Medilink Yorkshire and Humber Healthcare Business Awards. Over the past year Paxman has seen a 66% increase in export sales, as well as a 65% increase in new markets. With over 1000 scalp cooling systems now in use worldwide, they received the award as recognition for this success. Speaking at the event Managing Director of Medilink Y&H, Kevin Kiely, said: “Today’s event clearly highlights the buoyancy of the Health Technologies sector, and specifically the continued success and innovative capacity of Yorkshire Health Technology companies.” Richard Paxman, Operations Director, added: “It has been a very successful year for us, particularly in terms of our international expansion, so it’s fantastic that this hard work has been recognised. We hope to continue going from strength to strength with our export strategy and remain the world’s leading provider of scalp coolers.”

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Paxman Coolers Case study: Amy shares her experiences “After being diagnosed in January of this year I started a course of chemotherapy at a hospital in Hertfordshire. I had been given a leaflet about the Paxman by the cancer care nurse at the hospital where I was diagnosed. Initially, I was sceptical about the treatment because I had two friends who had tried the old gel ice caps, one lost her hair after the first session, and the other found the treatment so intolerable she gave up early on. “The old system uses ice caps of frozen gel which are taken straight from the freezer and placed on your head. They are unbearably cold at first, then after about half an hour, just as they begin to become tolerable, they thaw and have to be changed. I had the frozen gel ice cap during my first session of chemotherapy. It was really heavy and uncomfortable. After about half an hour it warmed up, which was a relief. As it thawed the cold water dripped down my neck and face, then the nurse appeared with a new ice-cold cap straight from the freezer and the torture began all over again! “The Paxman system which I used sub-sequently was a completely different experience. It was a little uncomfortable for the first ten minutes, then I got used to it. The Paxman cap is much lighter and much easier to tolerate than the old gel cap. I had lost a lot of hair after my first treatment using the old cooling system and I began to panic. Thankfully I was able to use the Paxman cooler for my seven subsequent treatments and whereas I experienced some thinning, my hair came out in strands rather than handfuls.

“Because I kept my hair it was not obvious that I was a chemotherapy patient and this enabled me to keep my cancer to myself. Thanks to the Paxman system I felt ‘normal’ and I was able to continue with a ‘normal’ social life. I would recommend the Paxman system to every women going through cancer treatment who wants to retain her hair and her anonymity. I wanted to choose who I told about my illness. The Paxman

enabled me to retain my hair and keep my secret.’ Amy’s personal experiences highlight not only how important it is for women actually experiencing cancer to retain their hair, but also that the Paxman system is effective and essentially life-changing for these women. The old system simply does not compare in terms of ease of use, comfort and overall effectiveness.” www.paxman-coolers.co.uk

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Regional Focus: UK East Midlands

Orthogem synthetic bone graft

This summer, several leading bioscience and healthcare companies based in Nottingham headed for London as part of a major campaign to market the Midland city to investors, financiers, businesses and potential partners. Gathered in the grand surroundings of St Pancras International Renaissance Hotel, were Medilink East Midlands, the Healthcare and Bioscience iNet, BioCity Nottingham and representative companies such as Monica Healthcare, Medibord, Sygnature Chemical Services Limited and global player Novozymes Limited. Their presence, and contribution to the event, left a lasting impression on those who attended.

Nottingham and the East Midlands is one of the leading UK centres for medical technologies, drug formulation and delivery, with the University of Nottingham’s School of Pharmacy rated the highest school in the UK. The region can also boast highest number of people working in drug delivery companies, ICT and e-health. As a result, the bioscience, pharmaceutical, med-tech and healthcare sectors are among the most attractive to potential investors and collaborators. Driven by global research expertise based in the renowned universities of Nottingham, Loughborough, Leicester and Nottingham Trent, the commercialisation of new products and services is generating high-

quality jobs and investment opportunities. A typical example of the confidence shown by Nottingham’s main public-private partners is the proposed Medipark complex adjacent to the Queen’s Medical Centre teaching hospital. The East Midlands has a long tradition of excellence in drug discovery and development, being home to Alliance Boots, AstraZeneca and 3M Healthcare. In a period of rapid investment in the region’s universities and research facilities, the life sciences sector has taken hold and has attracted some of the brightest scientific brains. University of Leicester’s Professor Sir Alec Jeffreys, the British geneticist who pioneered DNA fingerprinting and

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Where Healthcare and Bioscience Thrive profiling, and Nottingham’s Research Professor of Chemistry Martyn Poliakoff are two of the region’s leading lights who have maintained their love of the laboratory and continue to inspire new generations of scientists. However, the pipeline of new discoveries and the commercialisation of innovative products which eventually find themselves in global use take years to nurture. Without investment in research, early-stage growth and significant rounds of funding, most devices found in hospital use today or drugs patented for world-wide application wouldn’t get off the ground. The significance the East Midlands in attracting like-minded scientists and developers can’t be underestimated. Clusters of hightech firms such as those on show in London stimulate each other; they co-habit facilities such as BioCity Nottingham and collaborate in subtle forms to reach new heights of commercial success. Middle East markets are attractive to some of these new companies who seek investment partners and business opportunities to tackle new challenges. The recognition by the UK government of the important role of small and medium-sized businesses (SMEs) comes at a crucial time for those in the healthcare and bioscience sector. The pharmaceutical industry, shaken to the core by falling productivity and looming patent expiries that will shave billions off its sales figures, has changed its research and development model in recent years.

Medibord radiotherapy material

The largest companies who have been reducing their internal R&D capabilities, in part through site closures, now rely much more heavily on external partners – often SMEs and universities – for early product development. Innovation,

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Regional Focus: UK East Midlands or the successful exploitation of new ideas, means taking risks, so external support is usually crucially important. East Midlands-based life science firms can draw on the particular expertise of the Medilink East Midlands Healthcare and Bioscience iNet, an impartial advisory organisation inspired by the regional development agency and part-funded by European Regional Development Fund. The organisation has helped more than 500 innovative SMEs over the past three years. BioCity Nottingham-based Orthogem is one of those helped by the iNet. The company has developed a novel manufacturing method for the production of a highly porous synthetic bone graft for use in patients with spinal degeneration and injury. The advantage of this synthetic bone is that its exceptionally high porosity encourages the patient’s own bone cells to grow into it and its ability to be completely reabsorbed by the patient’s own metabolic processes mean that it is ultimately being replaced with real bone. Before the synthetic bone can be applied, the material may be blended with an extract of the patient’s own bone marrow or blood to create a wet granular mixture. Orthogem recognised that it could gain further competitive advantage by developing an all-in-one sterile device that blended and delivered the material to the site of damaged bone in a single continuous operation. This would make the synthetic bone easier to handle and quicker to use - and help the surgeon save precious time in the operating theatre. As with any novel product entering a competitive market, the synthetic bone had to gain clinical

acceptance so it was vital to get the applicator onto the market quickly. The iNet adviser helped the company work through the options and highlighted possible sources of funds. Orthogem decided to apply for an iNet innovation support grant because it could be accessed

quickly. As a result, Orthogem was able to design the applicator, secure regulatory approval and launch the applicator in under a year. Another company which has benefited from being part of the East Midlands ‘cluster’ is Medibord. Formed in 2009 as a result of a

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Where Healthcare and Bioscience Thrive positioning devices, is currently being used by the NHS in MRI, CT, LINACS and Tomotherapy applications. “Our geographical location has played a major part in the Medibord success story,” states Jonathan Richards, founder and CEO; “our core competence is the development of sustainable composite solutions to a number of industrial sectors, but this was our first entry into medical devices. We immediately contacted BioCity in Nottingham who introduced us to Medilink East Midlands and the Healthcare and Bioscience iNet. With their assistance we were able to produce prototypes, commission a detailed market research survey as well as guiding us through the legislative issues’. As a direct a result of this assistance and support, Medibord have won the MEH Awards for Innovation in Export, presented by Lord Darzi as well as the prestigious Da Vinci Award. They have been contacted by and are working with a number of the scanner and radiotherapy manufacturers as well as identifying resellers and strategic partners both on a local and global level. Many other companies like Orthogem and Medibord in the healthcare and bioscience sector have taken advantage of the Medilink East Midlands sectorfocused workshops, seminars and lectures as well as networking events that aim to support innovation. development project with the Nottingham University Hospital Trust City Campus oncology department, the company has responded to the increased requirement for accuracy of diagnostic imaging to aid radiotherapy planning for the treatment of cancerous

tumours. Oncologists need to be able to fuse both MRI and CT images to enable them to locate and track tumours and ensure that only the affected areas are treated without damage to surrounding tissue and organs. Medibord developed a non-conductive flat couch top which, together with its

The relationships formed between academic partners, suppliers, customers and intermediaries such as professional and trade associations are particularly important in developing new collaborations that have been demonstrated to improve a company’s capacity for innovation.

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Regional Focus: UK East Midlands

East Midlands Healthcare and Bioscience iNet Innovation is a key strategic priority for East Midlands Development Agency (emda). Four sector specific Innovation Networks (iNets) funded by emda and the European Regional Development Fund, including the Healthcare and Bioscience iNet, have been established to help turn innovative ideas in to business opportunities. The iNet concept was developed by emda and East Midlands Innovation (the region's innovation council) to bring together businesses, colleges, universities, public sector representatives and individuals with a shared interest in a market or the technology that underpins it. A key aim of iNet is to provide a sector-specific focus that enables organisations to exchange knowledge and form collaborations to exploit new ideas. It supports individuals and organisations through the Innovation, Advice and Guidance and Collaborative Research and Development initiatives. The support offered includes grants and funding advice. The Healthcare and Bioscience iNet is based at BioCity in Nottingham (its 'iHub'), a renowned life science industry centre of excellence, but it covers the whole region, and is operated by Medilink East Midlands on behalf of a consortium of partners. www.eminnovation.org.uk/health

Much of the work of Medilink East Midlands and the Healthcare and Bioscience iNet is directed at building bridges between organisations to stimulate innovation and expanding the network of support to SMEs with the long term aim of creating a highprofile cluster that attracts investments and people to the East Midlands. Th e c o m p a n i e s m e n ti o n e d i n this article have commented on the unexpected levels of growth achieved with the support of Medilink and its iNet advisers, and their pivotal role in helping them to achieve success in global markets. Middle East investors would do well to take a look at the growing levels of a c t i v i t y, and c o n f i d e n c e , i n t h e UK East Midlands healthcare sector.

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World Health Care Congress Middle East Launched in 2010, the World Health Care Congress Middle East, is the premier conference to feature global health care innovation. It attracts more than 600 senior health care thought leaders from all industry sectors, including hospitals, health systems, employers, government agencies, pharma, biotech and industry suppliers. WHCC Middle East is organized with sovereign partners the Health Authority-Abu Dhabi (HAAD) and the Abu Dhabi Tourism Authority (ADTA). Additional sponsorship is currently provided by The Abu Dhabi Health Services Company (SEHA) www.seha.ae and Children’s National Medical Center www.childrensnational.org. More than 600 health care executives representing 25 countries will share their perspectives on best practices for health care delivery; with the Conference to be held at new Abu Dhabi National Exhibition Centre (ADNEC) from 11-13 December 2011. Organized Under the Patronage of H.H. General Sheikh Mohammed Bin Zayed Al Nahyan, Crown Prince of Abu Dhabi and Deputy Supreme Commander of the United Arab Emirates’ Armed Forces and in collaboration with sovereign partners the Health Authority-Abu Dhabi (HAAD) and the Abu Dhabi Tourism Authority (ADTA), the World Health Care Congress Middle East is the most prestigious health care event, convening global thought leaders and key decision makers from all sectors of health care to promote health care through global best practices. Key topics for WHCC Middle East 2011 include: Middle East and

World Health Care Congress has announced the return of Al Jazeera International television host Riz Khan [right] as a featured panel moderator. The international TV news veteran will reprise his role from last year’s WHCC Middle East, leading several panel discussions with global health care executives. He will join a distinguished roster of 90 presenters from nearly 30 countries. Mr. Khan served as a presenter and reporter at the BBC for eight years and was the first mainstream Asian newsreader for the outlet’s international network. He later worked extensively for CNN. In 2005, he authored his first book: “Al-Waleed: Businessman Billionaire Prince,” published by Harper Collins.

Northern Africa (MENA) Health Authority Dialogue - Health Care Strategies for the Future and Evidence-Informed Health Policies Hospital/Health System CEO Debate on Global Health Care Models; How Provider Systems

and Technology Companies are Responding to the Implementation of Electronic Health Records (EHR) Systems; Building Strategic Public Private Partnerships (PPPs); The Promotion of Healthy Lifestyles.

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11-13 December 2011, Abu Dhabi

Featured presenters at WHCC Middle East H.E. Prof. Mohamed Jawad Khalifeh, Minister of Health, Ministry of Health; President, Arab Health Ministers Council, Beirut, Lebanon Hanan S. Al Kuwari, PhD, Managing Director, Hamad Medical Corporation, Doha, Qatar Rt Hon Prof the Lord Ara Darzi of Denham KBE, Paul Hamlyn Chair of Surgery; Head, Division of Surgery; Honorary Consultant Surgeon, Imperial College Hospital NHS Trust and the Royal Marsden Hospital; Chair, Surgery, Institute of Cancer Research; Chairman, Institute of Global Health Innovation, United Kingdom

Dr. Manar Al Moneef, Director General, Health Care and Life Sciences, Saudi Arabian General Investment Authority (SAGIA), Riyadh, KSA Zaid Al Siksek, CEO, Health Authority-Abu Dhabi (HAAD), Abu Dhabi, UAE Dr. Najeeb Al Shorbaji, Director, Knowledge Management, The World Health Organization (WHO), Geneva, Switzerland Dr. Cristian Baeza, Director of Health, Nutrition and Population, The World Bank, Washington, DC, USA Prof. Abdallah S. Daar, Professor, Public Health Sciences; Professor, Surgery, University of Toronto, Canada Jeff Goldsmith, PhD, President, Health Futures, Inc., Charlottesville, Virginia, USA Anne Milton, MP, Parliamentary Under Secretary of State for Public Health, Department of Health, London, UK

TV host George Kurdahi will be master of ceremonies for the event. Best known as host of the Arabic version of Who Wants to Be a Millionaire? (Man sa yarbah al-malyoon), which airs on MBC 1 television, Mr. Kurdahi will preside over the WHCC Middle East’s opening ceremony on 11 December. Mr. Kurdahi came to Millionaire following a long and distinguished broadcasting career. After working for the Lebanese newspaper Lisan Elhala, Kurdahi moved to Télé Liban, then in 1979 to Radio Monte Carlo. After thirteen years, he became Head of News at Radio Orient, then General Manager of MBC FM.

The event will also include the 2nd Annual WHCC Middle East Health Innovations Poster Exhibit and Awards Program, which will be on display throughout the conference. The poster exhibit is part of the WHCC Health Innovations Initiative, a year-round program that features health care innovations that improve health care while reducing costs. To submit an innovation for display at the conference and award consideration, visit www.worldcongress.com/middlee ast/posters www.worldcongress.com/me

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Aesica Pharma Aesica is a fast-growing UK company with a global footprint. When four year old R5 Pharma was bought out by Aesica in June 2010 Aesica Formulation Development was created. Aesica FD are Formulated Product Specialists. Their expertise lies in the ability to offer custom manufacturing services to customers from preclinical stage to leading to full commercial supply (from Aesica Formulated Products) . Their manufacturing facilities meet the highest standards according to regulatory and customer audits. They strive to deliver efficient manufacturing processes to customers and are equipped to produce high volumes of sterile and non-sterile liquid and solid dosage forms. With highly secure facilities authorised to handle up to schedule 2 controlled substances, they also have a high containment suite to manufacture products in the Safe Bridge Category 3 level of potency. Their teams of experts focus on delivering the highest quality outputs with an unrivalled level of customer service. FD Specialists Aesica are fully equipped to develop and manufacture new medicines and clinical trial materials for Phase I and Phase II clinical trials through their Formulation Development Business Unit. Their team of experts ensures seamless transfer and scale-up of manufactured products using stateof theart facilities and careful processes. In-house analytics expertise and services support the entire manufacturing process. Aesica are able to manage full scale and complex formulation manufacture with rigorous quality

assurance and regulatory processes in place, and offer a range of packaging technologies for solid and liquid dosage forms including bottle and blister packaging. Their artwork design service provides a full range of coding and labelling if required. Paul Titley, Managing Director of Aesica FD, told MEH, “With a keen understanding of early stage development and clinical trial requirements, we guide customers through the processes of new medicine and material development for Phase Iand Phase II clinical trials.

“At Aesica FD, we have a singleminded vision to provide market-leading formulation development, analytics and GMP services to the global biotech and pharmaceutical industries. And that vision is fast becoming reality, as we are already acknowledged as the leading provider of clinical pharmaceutical dosage form development in Europe. Our expertise lies in the ability to offer custom manufacturing services to customers from pre-clinical stage to full commercial supply.� Aesica FD do business in Australia, New Zealand, North America and

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Market Meading Formulation Development

across Europe, and are now looking to expand further into the USA and India. The Middle East is as yet an untapped market for the company and this is something Mr Titley wants to change, which is why he is attending the World Health Care Congress in Abu Dhabi (11-13 December) to meet potential new clients from the region. “We have the ability and experience to develop and manufacture almost all dosage forms. Typical dosage forms we work with include tablets, capsules, liquids, suspensions, creams, ointments, inhaled and sterile pharmaceuticals. Companies approach us from all over the world to create pharmaceuticals and so we are delighted to be able to showcase our services to the healthcare community of the Middle East in Abu Dhabi, and find out what they need from us”, said My Titley.

Mitovie Specialist Medicines Developed and manufactured by Aesica FD Magnesium Glycerophospahte Oral Solution 1mmol/ml, 200 ml bottles Midazolam Oral liquid 1mg/ml, 10 ml bottle including 4 oral syringes Midazolam Oral liquid 1mg/ml in Prefilled Oral Syringe, 4 syringes/pouch. 1.0ml, 0.75ml, and 0.5ml PovidoneIodine 5% (sterile) in 15ml dropper bottle Supply chain management Aesica’s extensive supply chain management experience – including cold chain – means that they can securely store and supply your products worldwide. The experienced Regulatory Affairs Team is ready to support customers with all aspects of their regulatory submissions, including preparation of dossiers, variations, renewals and line extensions.

hey offer a range of quality services covering GLP/GMP audits and validation through to supporting your post-marketing surveillance. Aesica’s investment in and expansion of state-of-the-art facilities, equipment, laboratories and support services play a critical part in our continuing growth and success. They fully appreciate that an investment in hardware alone is no guarantee of continued prosperity.

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Aesica Pharma Mitovie Pharma Mitovie Pharma is a pioneering privately held global pharmaceutical company which develops and commercializes innovative medicines to meet real clinical needs. Headquartered in the UK, its portfolio of available medicines spans several therapy areas as a result of the company’s strategy of problem solving where there are real medical challenges. This is reflected in the company’s pipeline of late stage development drugs which offer first in class treatment options for millions of patients worldwide. Mr Titley told MEH, “Our relationship with Mitovie attaches their expertise in solving medical challenges with our ability to deliver products. They know what physicians need and have the scientific knowledge to market our products effectively.” The company is led by the Mitovie Pharma Executive Management Team (MPEMT) which reports to the Mitovie Group Board of Directors (MGBD). Mitovie has established a strong UK operation which includes R&D, Medical, Sales, Marketing & Support Functions. Currently it partners for distribution globally. The company distributes its medicines to full GDP including cold chain supply, direct to patient, hospital, retail pharmacy and wholesaler from a purpose built 2500m² MHRA approved facility in the UK. The company’s near term plan is to establish its infrastructure in the key European territories and other selected geographies. It intends to augment its existing portfolio through in house development and in-licencing/acquisition of innovative medicines. www.aesica-pharma.co.uk

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Philips Healthcare Royal Philips Electronics provided clinicians from across the globe with a glimpse of future innovations designed to advance cardiac care, including the current management of cardiovascular disease (CVD) and associated cardiac conditions, during the 2011 Congress of the European Society of Cardiology (ESC), which took place in Paris. Cardiovascular disease remains the main cause of death in the European Union, claiming more than two million lives each year and costing the economy more than €100 billion annually. “Philips has been a consistent game-changer in the area of healthcare for almost 100 years, developing innovative and integrated patient-focused solutions, including some of the earliest X-ray technologies,” commented Joris van den Hurk, general manager, Cardiology Care Cycle, for Philips Healthcare. “At this year’s ESC, we highlighted our vision of how future innovation will enable care-givers to transform the way cardiovascular disease is managed at each stage - from early detection and diagnosis, to hospital treatment and health care at home, in order to reduce the burden of cardiac disease for patients, doctors and society at large.” The future of cardiac care Solutions that will transform detection, diagnosis and treatment This vision of future innovation is exemplified by the launch of the world’s first sleep apnea mobile application (“app”) designed specifically for cardiologists, and aiding early detection and diagnosis amongst their patients. It’s estimated that over 100 million people worldwide are suspected to have Obstructive Sleep Apnea (OSA), of which more than 80% remain undiagnosed.2

OSA is particularly prevalent amongst people diagnosed with CVD and heart failure, and if untreated can contribute to the development of high blood pressure, diabetes, heart attack and stroke. The new app, called Sleep & Cardio aims to help expand cardiologists’ knowledge of sleep apnea and CVD, providing simple steps for identifying patients who are at risk, a summary of existing guidelines and access to the latest clinical information and training. From diagnosis to treatment, Philips’ commitment to the

advancement of CVD care was also being showcased at the ESC in the area of heart modeling - technology that is in development and aims to produce highly accurate and detailed models of a patient’s heart structure. Through ongoing research and development, the hope is that this future technology can provide information to clinicians quickly; to support them in planning and refining the execution of complex interventions based on an individual’s specific anatomy; and that it can calculate the likelihood of a successful outcome while reducing overall procedure time.

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REHACARE 2011: Review

Interest in aids and topics revolving around rehabilitation and care is growing. This was reflected over the course of REHACARE 2011, International Trade Fair and Congress for SelfDetermined Living, that closed its doors on Saturday, 24 September after the four-day event in Düsseldorf. “REHACARE Düsseldorf is the right venue for tabling the current challenges for rehabilitation and care and for highlighting ways for people with disabilities, special care needs as well as age-related

restrictions to cope with their everyday routines as independently as possible,” said Joachim Schäfer, Managing Director at Messe Düsseldorf, summing up the event. “We have struck a nerve here, especially with the REHACARE Congress – dedicated this year not only to senior-friendly living concepts but also to the widespread condition of dementia. There is quite clearly a great need for information and awareness here amongst patients, family members and even amongst experts.” REHACARE 2011 attracted over 47,000 international trade visitors

and affected individuals – as personal experts in this field – who came here to gather information on the innovative auxiliary means and new findings from science and research presented at the fair by 747 exhibitors from 29 countries. In line with the event’s thematic schedule this year REHACARE once again presented a range comparable with that of 2009. Back then the trade fair and congress counted 48,000 visitors. Barbara Steffens, Minister for Health, Emancipation, Care and the Aged in North Rhine-Westphalia, underlined the importance of

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Congress for Self Determined Living REHACARE during her visit here on 22 September 2011. With its focal themes “Dementia” and “Senior Living” the trade fair, she said, had picked up on two topics Germany urgently needed to address. Such an established event like REHACARE could make a key contribution here, said the Minister. Praise was also directed at exhibitors and partners of REHACARE 2011. Dr Martin Danner, National Head of the German self-help association BAG SELBSTHILFE (Federal Self-Help Association for People with Disabilities and Chronic Illness and their Families) delighted at the high number of visitors at the stands of self-help groups. “The REHACARE trade fair offers a range of products spanning solutions suited to everyday use through to smart assistance systems – thereby providing insight into the future of rehabilitation and care,” explained Dr Danner. “And this picks up on the key themes of today. For affected individuals the trade fair is far more than an exhibition – it is the most important forum for exchanging experience and tabling topical issues relating to the disabled and health policy.” At the focus of visitor interest at REHACARE were walking and mobility aids, vehicles, wheelchairs, aids for daily living aids and care. For Heiko Keuchel, Managing Director of the Bremervörde-based company Thomashilfen für Behinderte, trade fair participation was a resounding success: “We are very satisfied and have definitely met our trade fair objectives. As a company oriented to development we seek dialogue with affected individuals. REHACARE offers us great opportunities in this respect. And the trade fair is also successfully broadening its horizons in terms of care issues.

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REHACARE 2011: Review

Increases in the number of visitors interested in geriatric products and solutions are clearly noticeable and we very much welcome this.” Dick J. van der Pijl – in charge of research and development at Tilburg-based Dutch firm FOCAL Meditec specialised in smart solutions for people with limited mobility of the arms – described REHACARE as a key contact exchange for meeting and taking on international sales partners and for exchanging ideas with specialists from the fields of science and technology. “This is the sixth consecutive year we have attended REHACARE and we are very satisfied.”

The REHACARE Congress with its lecture series on “Senior Living” and “Dementia” posted excellent attendance figures. 630 specialists and affected family members gathered a great deal of information on senior-friendly living concepts, the symptoms of dementia, preventative measures and support options. Once again meeting with great interest was the Wohn(t)raum theme park with its range of barrierfree building and living options located in Hall 3. The North Rhine-Westphalia disabled sports association (BSNW) delighted visitors with the REHACARE Sport Centre

providing information on the opportunities for staying fit and healthy even with disabilities. Recreational athletes, world champions and Paralympic champions celebrated their annual festival in Hall 9 of the exhibition centre. BSNW Managing Director Herbert Kaul was delighted by the event’s success: “For us REHACARE is the most important event for showcasing the wide range of sports for the disabled to the general public.” The next REHACARE will be held in Düsseldorf from 10 to 13 October 2012.

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Congress for Self Determined Living

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Research paper: Accelerated Telomere Attrition Is Associated with Relative Household Income, Diet and Inflammation in the pSoBid Cohort Authors: Paul G. Shiels, Liane M. McGlynn, Alan MacIntyre, Paul C. D. Johnson, G. David Batty, HarryBurns, Jonathan Cavanagh, Kevin A. Deans, Ian Ford, Alex McConnachie, Agnes McGinty, Jennifer S. McLean, Keith Millar, Naveed Sattar, Carol Tannahill10, Yoga N. Velupillai, Chris J. Packard Abstract Background: It has previously been hypothesized that lower socio-economic status can accelerate biological ageing, and predispose to early onset of disease. This study investigated the association of socio-economic and lifestyle factors, as well as traditional and novel risk factors, with biological-ageing, as measured by telomere length, in a Glasgow based cohort that included individuals with extreme socio-economic differences. Methods: A total of 382 blood samples from the pSoBid study were available for telomere analysis. For each participant, data was available for socio-economic status factors, biochemical parameters and dietary intake. Statistical analyses were undertaken to investigate the association between telomere lengths and these aforementioned parameters. Results: The rate of age-related telomere attrition was significantly associated with low relative income, housing tenure and poor diet. Notably, telomere length was positively associated with LDL and total cholesterol levels, but inversely correlated to circulating IL-6. Conclusions: These data suggest lower socio-economic status and poor diet are relevant to accelerated biological ageing. They also suggest potential associations between elevated circulating IL-6, a measure known to predict cardiovascular disease and diabetes with biological ageing. These observations require further study to tease out potential mechanistic links. Introduction Gompertz (1825) first described ageing as an increase in the likelihood of mortality with increasing chronological age [1]. In man, this equates to a corresponding, progressive loss of metabolic and physiological functions, though the trajectory for this is not uniform, indicative of underlying inter-individual variation in the biology of ageing [2]. Variation in the rate of biological ageing reflects the cumulative burden of genetic, metabolic and environmental stressors, resulting in oxidative damage and elevated inflammatory processes [3]. This is of particular interest in Glasgow, because of the exceptional gradient of socio-economic status (SES) in this city and the associated variation in mortality and morbidity. The latter is reflected in the large difference in life expectancy for men, between the most and least deprived areas of the city, which is 28.7 years [4]; a difference which is one of the largest in the developed

world. We investigated potential mechanisms for such gradients as part of the psychological, social, and biological determinants of ill health (pSoBid) study cohort [5], the characteristics of which have been described in depth elsewhere [6]. Briefly, the pSoBid study was designed to investigate the factors linking social circumstances, mental wellbeing, and biological markers of disease. Participants were selected from the least and most deprived areas in the NHS Greater Glasgow Health Board area. We have hypothesised that such a difference in life expectancy might be reflected in the biological age of individuals. In turn we considered whether deprivation-related measures correlated to accelerated telomere attrition and also determined interactions with inflammatory status. Suitable and validated biomarkers for analysing biological ageing in this context are limited in number. Despite cell cycle inhibitor transcript

levels providing an accurate indication of organ and T cell biological age [7–9] the overwhelming majority of studies employ determination of telomere length in peripheral blood leukocytes (PBLs) in a clinical context [10–12]. However, there are many equivocal reports regarding how useful this marker is when applied in epidemiological studies [13,14]. Telomeres are nucleoprotein complexes at chromosome ends, consisting of (TTAGGG)n direct repeats bound to a range of proteins involved in maintaining cellular stability and viability (reviewed in [3]). Typically, in larger mammals, the telomeric DNA component shortens with successive cell divisions. This arises from what has been termed the end replication problem [15]. Telomere attrition is thought to represent a molecular clock, at least at the cellular level, where it has been hypothesised to act as an anti-neoplastic mechanism [16],

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Figure 1. Regression analysis plots that highlight household income, housing tenure, and diet score were associated with steeper agerelated decline in telomere length. Faster rates of agerelated telomere attrition were observed in individuals with an average income less than £25,000 (7.7% vs 0.6% reduction per decade, p = 0.024, (A)), home tenants (8.7% vs 2.2%, p = 0.038 (B)) and a diet score among the lower 50% of scores (7.7% vs 1.8%, p = 0.05 (C)).

proposed to function by countering the accumulation of mutations over successive cell divisions, which potentially could produce neoplastic cells. Although telomere length is inversely related to chronological age in humans, there is considerable inter-individual variation in telomere length at any specific age [17]. Thus estimates of the effects of chronological age as a covariable in regression models have relatively wide confidence intervals, making detection of significant effects of age-related diseases more difficult: it may be unclear how much of the residual variance is explained by the disease and how much is attributable to error in the estimate of an age effect. This has been discussed in detail eleswhere [18,19].

Recent human data have now established telomere attrition as a major risk factor for numerous diseases, including cardiovascular disease (CVD), hypertension, diabetes and end stage renal disease [11,20–22] as well as being associated with elevated psychological stresses [23]. Many such pathologies, showing an association with increased telomere attrition rates, are predominant in deprived communities where there is a higher prevalence of classical risk factors for disease, but this explanation does not account totally for these variations in disease incidence [10,24,25]. One hypothesis for the increased disease prevalence in these communities is underlying chronic inflammation (elevated CRP or IL-

6), a known component and predictor of CVD and diabetes [26,27], that is linked to a diverse range of pathologies. A possible contributory factor to generating an increased pro-inflammatory state, is accelerated biological ageing. Both telomere attrition and CDKN2A expression have been reported to show association with IL-6 levels in disease [11] and ostensibly ‘healthy’ populations [9]. Such associations are intuitive, as senescent cells upregulate and secrete pro-inflammatory cytokines as part of the senescent secretosome [28]. A link between accelerated biological ageing and socioeconomic status has previously been reported by some [29], but not by others [30,31]. The reasons for this equivocacy remain

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Accelerated Bio-Ageing & Socioeconomic Status to be proven, but may be attributable to methodological differences [13]. Any putative link, however, may be weak and open to multiple confounders, such as parental telomere length and epigenetic effects [32]. We have chosen to evaluate the contribution of socio-economic factors to biological age, as measured by telomere length, in thethis in turn affects risk factors for ill health. Results Socio-economic and lifestyle factors Telomere lengths were determined in PBLs by Q-PCR for 382 individuals. The SES and lifestyle factors investigated are shown in Table S1, as are the median telomere lengths within subgroups of these factors, overall and by three age groups. The relationship between age, gender and biological ageing was investigated by estimating the percentage change in telomere length associated with a decade increase in age and male gender.

average income less than ÂŁ25,000 (7.7% vs 0.6% reduction per decade, p = 0.024), a diet score among the lower 50% of scores (7.7% vs 1.8%, p = 0.05), and home tenants (8.7% vs 2.2%, p = 0.038). Figure 1 highlights differences in telomere attrition with income, housing tenure and diet score. We investigated the extent to which the associations between telomere attrition and household income, housing tenure, and diet score were independent by adjusting for these interactions. All three interactions were attenuated to a similar degree and were no longer significant, suggesting that these three interactions are correlated but no single factor is driving these interactions.

Biomarkers Associations between biomarkers investigated and telomere length are reported in Table 2. Individuals with longer telomereshad increased levels of total cholesterol (2.4% increase in total cholesterol per one SD increase in log telomere length, p= 0.027) and LDL cholesterol (3.7%, p =0.027). Conversely, shorter telomeres were associated with increased levels of IL-6 (7.2% decrease in IL6 levels per one SD increase in log telomere length, p = 0.022, Tabl). Further analysis, adjusting for deprivation, income, diet and smoking status, maintained the positive association between telomere length and cholesterol (p =0.033) and LDL cholesterol (p= 0.026). Interestingly,

Age was strongly negatively associated with telomere length, each decade predicting a 4.8% decrease in telomere length (p =0.002). No significant difference in telomere length was observed between males and females. There was also no difference between affluent and deprived groups either in telomere length or age-related telomere attrition. All subsequent analyses were adjusted for age, gender and deprivation. Of the SES and lifestyle factors investigated, only cigarette smoking was associated with an overall reduction in telomere length (6.6% reduction, p= 0.050). However, household income, housing tenure, and diet score were associated with steeper agerelated decline in telomere length. Faster rates of agerelated telomere attrition were observed in individuals with an

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the significant association between telomere length and IL-6 was weakened whenadjusted for these SES factors. Analyses were performed to establish which individual factors had an impact on IL-6 expression (Table 3). The significant association between shorter telomeres and higher levels of IL-6 was lost when analyses were adjusted for age and gender, or for smoking status deprivation, income and diet (Table 3). Discussion It has been hypothesized that socio-economic deprivation can accelerate biological ageing, resulting in shorter telomeres in deprived individuals in comparison to more affluent-aged matched controls. Five previous studies examining this relationship reportpositive [29], null [30,33,34] and negative associations [31]. The equivocacy between these reports is possibly due to methodological differences, variations inherent in individual cohorts and in the veracity of subject answers relating to SES data, such as income, which may be confounded by undeclared income. The present study has examined the relationship between

biological ageing, SES and disease in participants in Glasgow, a city with an extreme socioeconomic gradient, with documented health issues associated with social deprivation. Interestingly, in the light of possible confounders relating to the veracity of SES data, employment status (men who reported being out of work) was reported to associate significantly with shorter telomeres [34], in a large cross sectional study from an overlapping demographic

area (the WOSCOPS cohort). Surprisingly, despite the prevalence of CVD in this cohort and its proven association with SES, there were no other associations found with other markers of SES (including educational attainment, employment status, area-based deprivation and physical stature measured as a proxy for early life social circumstances). Our data are not incongrous with previous reports, as we observed no associations with area based

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Accelerated Bio-Ageing & Socioeconomic Status deprivation and employment. However, we have demonstrated a direct link between accelerated biological ageing, low income and poor diet. Furthermore, we have observed a relationship with a measure of adiposity, namely waist/hip ratio (Table 1), a predictive measure for CVD and diabetes as well as all cause mortality in prospective studies [35]. These observations are intuitive and in keeping with the Marmot findings [36,37] who indicated that relative health inequalities are associated with SES. It is reasonable to assume that a low relative income means a decreased likelihood of being able to afford a good quality diet, leading to an acceleration in biological ageing. Poorer quality, fat and sugar rich diets, are known to result in the production of more reactive oxygen species, which directly cause DNA breaks that lead to gene malfunction, telomere attrition and disease [38,39]. Notably, these observations indicating an interaction between biological ageing and SES are reinforced by the finding that telomere length, in the pSoBid cohort, associates positively withLDL cholesterol levels, a strong and unambiguous causal risk factor in CVD. In our study, telomere attrition was associated with increasing IL-6 levels, an emerging risk factor for CVD, which may predict fatal events more strongly than non-fatal events [40]. The association of IL-6 with biological age is in keeping with recent observations indicating that senescent cells up-regulate and secrete IL-6 [9,11]. It would be expected, as a consequence of increased telomere attrition, that this group would have more senescent cells present and thus higher IL-6 levels and have an elevated risk of a range of

conditions, if indeed IL-6 is causally related to CVD and diabetes. The association between accelerated biological ageing and increased IL6 levels has been previously been reported to be linked with disease [11], general health [9] and social deprivation [41]. These observations are congruent with more extant inflammatory conditions in the most deprived, a situation exacerbated by increasing age. Our findings suggest the unadjusted association between telomere length and IL-6 is strong, and it is still marginally significant with adjustment for age and gender. This association is only partially weakened by further adjusting for smoking but subsequent addition of deprivation, income and diet does not appear to weaken the IL-6telomere association further (Table 3). In simple terms, these observations suggest that varying upstream factors drive both telomere shortening and elevated IL-6 levels. However, we cannot exclude the possibility that part of the mechanism for elevated IL-6 is via telomere shortening. Future studies need to explore this potential further, particularly as IL-6 is attracting increasing interest in the diabetes and CVD arenas [27,40]. Of the four previous studies in this field [29–31,34] only two have indicated an association with SES. These comprised an analysis of female twins, where non manual workers had longer telomere lengths than manual workers [29]. However, in analyses in which the authors used a more comprehensive range of SES categories, no evidence of a relationship was observed with biological age. The other, analysed Chinese men and indicated men with higher self-rated socioeconomic status have shorter telomeres [31]. This was postulated as possibly being mediatedthrough

psychosocial, rather than lifestyle factors, or the presence of chronic disease. These authors also argue that there may be significant cultural, ethnic and age-related differences in social determinants of health. The Q-PCR methodology employed in the present study yielded similar telomere length data in keeping with other reports [10,33,42] using the same methodology. Our observations must also be viewed with reference to the fact that any differences reflect that PBL telomere length is neither an absolute, nor precise measure of biological ageing. The telomere lengths measured are an average and reflect a range of lengths in cells. A better measure may be an absolute marker of cellular growth arrest, such as CDKN2A [7–9]. The use of such a marker would avoid the potentially confounding effects of differences in telomere length measurement methodology, that currently beset the field [14]. The difference in observations using telomere length as a marker of biological ageing, that have been reported by different groups have been elegantly summarised by Nordfjall et al [39]. Our observations find consensus with those using a similar methodology, when applied to age, BMI, smoking, insulin, triglycerides and glucose. Our observations on the effect of smoking, however, maybe limited by lack of detailed information on smoking history. We differ in the detections of associations with total and LDL cholesterol, though these have previously been reported to be associated with telomere length in a disease setting [11], along with IL6 [7,9]. These observations were also in keeping with concomitant elevation of DNA damage (as measured by 8-0H dG levels) in a

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specific disease cohort. However, our observations are consistent with previous biochemical analysis of the pSoBid cohort [5], which demonstrated that total cholesterol and LDL were inversely associated with deprivation. This is congruent with more extant inflammatory conditions in the most deprived, a situation exacerbated by increasing age. It is thus also in keeping with the observed elevation of IL-6 correlating with short telomeres.Our observations provide an intuitive link between proven socioeconomic drivers of disease [5,36,37] and a biological phenomenon underlying any predisposition, or extant disease, namely cellular ageing. The tendency of our data to show faster ageing in those with lower socio-economic status, is indicative of this and reflects ‘more miles on the clock’ for these individuals. This study may be limited by its size and cross sectional nature. Indeed, the social gradient in Glasgow is so extreme that a ‘survivor effect’ among the most deprived cannot be excluded. This merits a larger, longitudinal study to look at the relative impacts of further markers of SES and potential SE and lifestyle interventions. Such interventions are not without precedence and appear to show direct benefit to biological ageing. A recent intervention study in men with prostate cancer, reported that changing lifestyle, primarily via better diet and increased exercise leads to increased telomerase activity and deceleration of telomere attrition rate [43]. A similar result in the pSoBid cohort would be expected to have significant health benefits. In summary, we show convincingly that factors associated with lower socio-economic status and poor diet are relevant to accelerated biological ageing in a cohort

representing extremes of social class. Our findings also suggest potential associations of elevated circulating IL-6, a measure known to predict CVD and diabetes, with biological ageing, observations which require further study to tease out potential mechanistic links. Materials and Methods Ethics Statement The study was approved by the Glasgow Royal Infirmary Research Ethics Committee and all participants gave written informed consent. Participants The design of the psychological, social, and biological determinants of ill health (pSoBid) study has been described elsewhere [6]. In brief, participants were ranked on the basis of multiple deprivation indicators to define the least and most deprived areas in the NHS Greater Glasgow Health Board area, using criteria established in the Scottish Index for Multiple Deprivation (SIMD). Sampling was stratified to achieve an approximately equal distribution of the 666 participants across males and females and age groups (35– 44, 45–54 and 55–64 years) within the most (bottom 5% of SIMD score) and least deprived areas (top 20% of SIMD score). Participants undertook a physical examination (including measurement of blood pressure, body mass index (BMI), and waist hip ratio (WHR)) and lifestyle questionnaires as detailed previously [6]. A total of 382 blood samples were available for telomere analysis. Analytical parameters Measurement of biochemical parameters have been described in detail elsewhere [5]. In brief, cholesterol and triglyceride concentrations were determined by enzymatic colorimetric assays on a Roche Hitachi 917 analyser (Roche

Diagnostics Ltd, Burgess Hill, UK). Lipid fractions were measured using ultracentrifugation and precipitation methods. Glucose was measured by hexokinase and glucose-6-phosphate dehydrogenase assay on an Abbott c8000 analyser (Abbott Diagnostics, Maidenhead, UK). Insulin was measured by ELISA (Mercodia AB, Uppsala, Sweden and ALPCO Diagnostics, Salem, NH, USA, respectively). Creactive protein levels were determined by an immunoturbidimetric assay (Roche Diagnostics Ltd). High sensitivty interleukin-6, von Willebrand factor and intercellular adhesion molecule 1 weree22521 measured by ELISA (R&D Systems Europe Ltd, Abingdon, UK and DAKO UK Ltd, Ely, UK). Fibrinogen was measured on an automated coagulometer (MDA-180; Organon Teknika, Cambridge, UK). D-dimer was measured by ELISA (Hyphen, Neuville-sur-Oise, France). Indices of dietary intake A diet score for the consumption of fruit and vegetables was calculated from subjects self-reported food frequency questionnaire responses. Participants were asked on average how often they consumed a range of food categories (21 food categories listed). Responses for each question ranged from daily consumption (number of portions per day) to weekly and monthly consumption. Participants selected one response per food category. For the purposes of the present analysis, responses to four questions from the food frequency questionnaire relating to fruit and vegetable intake were aggregated to give an overall indicative diet score (i.e. frequency of intake of fresh fruit, cooked green vegetables (fresh or frozen), cooked root vegetables (fresh or frozen) and raw vegetables or salad (including tomatoes)). Monthly diet scores were calculated on the basis of a 28 day month. The maximum possible

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Accelerated Bio-Ageing & Socioeconomic Status total diet score was 672 (6 portions per day x 28 days per month x 4 food category questions). Telomere length determination DNA was extracted from PBLs following standard procedures and telomere lengths in the DNA samples were determined by QPCR, following the method of Cawthon [44] as described previously [11,33]. Telomere length determination was performedus ing a Roche Light Cycler LC480. Telomere length analyses were performed in triplicate for each sample, using a single-copy gene amplicon primer set (acidic ribosomal phosphoprotein, 36B4) and a telomere-specific amplicon primer set [7]. Quality control parameters employed for the amplifications comprised using a cut off 0.15 for the standard deviation (SD) of the threshold cycle (Ct) for sample replicates. At a SD above 0.15 the sample was reanalysed. The average SD across plates was 0.05. Relative telomere length was estimated from Ct scores using the comparative Ct method after confirming that the telomere and control gene assays yielded similar amplification efficiencies. This method determines the ratio of telomere repeat copy number to single copy gene number (T/S) ratio in experimental samples relative to a control sample DNA. This normalised T/S ratio was used as the estimate of relative telomere length (Relative T/S). The interassay variation was assessed by comparing the relativ telomere estimates (T/S ratio) across assays for the positive controls, which were assayed on every assay plate. The average inter-assay coefficient of variance was 0.3% for telomere and 0.1% for 36B4 plates. Statistical analyses Associations between telomere length and participant characteristics

were investigated in linear regression models. Sampling was stratified by age, gender and deprivation group, and all models were adjusted for these factors. Because telomeres are expected to shorten gradually with age, age was represented in models as a continuous rather than categorical covariate. When investigating factors that might influence ageing such a SES and lifestyle, telomere length was modelled as an outcome. Biomarkers, on the other hand, may be viewed as downstream of ageing, motivating their modelling as outcomes with telomere length as a covariate. Telomere length and biomarkers were log-transformed for regression analysis to satisfy the assumption of normally distributed residuals. Regression coefficient estimates were therefore multiplicative when transformed back to the original scale. For example, a regression coefficient for a binary characteristic back-transormed to 1.1 implies the characteristic is associated with a 10% difference in the outcome. Thus, where log telomere length was the outcome, regression coefficients are presented as the percentage change in telomere length associated with each patient characteristic. Where telomere length was a covariate, a telomere length z-score was used so that the backtransformed regression coefficients could be interpreted as the percentage change in biomarker level associated with a one standard deviation increase in telomere length. The telomere length z-score was calculated by standardising log telomere length to have a mean of zero and standard deviation of one. We hypothesised that the effects of telomereshortening factors accumulate over time, therefore the largest

differences between exposed and unexposed participants would be expected among the oldest participants. We investigated this hypothesis by testing for interactions between participant characteristics and age. Supporting Information Table S1 Median (interquartile range) telomere length within subgroups of socioeconomic status and lifestyle factors, overall and by age group. (DOC) Table S2 Percentage change (95% CI) in telomere length associated with a 10-year increase in age within subgroups of socioeconomic status and lifestyle factors, predicted from linear regression models adjusted for significant main effects and interactions. All models were adjusted for age, gender and deprivation group. Interactions were investigated by testing the null hypothesis of homogeneity of age effects across subgroups. (DOC) Author Contributions Conceived and designed the experiments: PGS LMM A. MacIntyre PJ GDB HB JC KAD IF A. McConnachie A. McGinty JSM KM NS CT YNV CJP. Performed the experiments: LMM A. MacIntyre PGS. Analyzed the data: LMM PGS PJ A. McConnachie. Contributed reagents/materials/analysis tools: PGS LMM A. MacIntyre PJ GDB HB JC KAD IF A. McConnachie A. McGinty JSM KM NS CT YNV CJP. Wrote the paper: PGS LMM A. MacIntyre PJ GDB HB JC KAD IF A. McConnachie A. McGinty JSM KM NS CT YNV CJP. www.plosone.org

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Citation: Shiels PG, McGlynn LM, MacIntyre A, Johnson PCD, Batty GD, et al. (2011) Accelerated Telomere Attrition Is Associated with Relative Household Income, Diet and Inflammation in the pSoBid Cohort. PLoS ONE 6(7): e22521. doi:10.1371/journal.pone.0022521 Editor: Daniela Cimini, Virginia Tech, United States of America Received April 20, 2011; Accepted June 22, 2011; Published July 27, 2011 Copyright: 2011 Shiels et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by the Glasgow Centre for Population Health, a partnership between NHS Greater Glasgow and Clyde, Glasgow City Council and the University of Glasgow, supported by the Scottish Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: Paul.Shiels@glasgow.ac.uk

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Philips Healthcare Philips introduces unique backup fetal and maternal monitoring solution during pregnancy, labor and delivery Last month Royal Philips Electronics announced the global availability of Avalon Smart Pulse, the first technology to provide a new source for automatically detecting situations where maternal pulse may be confused with the fetal heart rate without the need to apply additional electrodes or sensors. The only company to offer this technology, Philips developed Smart Pulse to help clinicians make more informed decisions about delivering a baby. Smart Pulse is now available for customers in the Middle East and U.S. after being introduced to international markets in May 2010. Electronic fetal and maternal monitoring is used during pregnancy, labor and delivery to monitor the mother’s and baby’s heart rate, uterine activity and fetal movement, among others. Obstetricians use fetal monitoring because it is one of the few solutions that can be used before the baby is born to help evaluate the baby’s well-being. Traditionally, clinicians rely on two methods to measure maternal pulse: ECG and SpO2. In most pregnancies, however, these are not routinely monitored. In situations where ECG and SpO2 data is not collected, Smart Pulse automatically kicks in to provide the maternal pulse reading. Smart Pulse technology is built into the Toco MP transducer, the new uterine activity transducer, which is then routinely placed on the mother’s abdomen to record uterine contractions during labor and delivery. Using a heart rate comparison technique known as “coincidence detection,” the

maternal pulse is continuously compared with the fetal heart rate and provides an important backup to the traditional ECG electrodes or SpO2 sensors, which may become disconnected or are often not used at all. Since Smart Pulse is part of routine monitoring and is “always on” by continuously calculating without the need for additional wires or sensors, it provides comfort for mothers. “During conventional fetal monitoring, physicians can often experience confusion between the fetal heart rate and maternal pulse, which can threaten the life of the baby if it goes unnoticed,” said Roger Freeman, M.D., professor of Obstetrics and Gynecology, University of California at Irvine School of Medicine, Long Beach Memorial Medical Center, Children's Hospital. “An accurately monitored fetal heartbeat is crucial to improving the likelihood of a safe, healthy outcome for mother and baby. Smart Pulse is providing a much-needed backup that clinicians really need. It allows

coincidence detection of heart rates to continue in cases when it previously would not have been possible.” With Smart Pulse, two maternal pulse sensors under the plastic surface of the Toco MP transducer scatter infrared light through the bottom layer of the transducer. This light is reflected by tissue and blood vessels. The pulsating diameter of small arteries causes changes in the reflected light. The measured light changes are evaluated and a maternal pulse is displayed and recorded. “This is an important advancement in electronic fetal monitoring that will enhance clinician confidence that fetal heart rate and maternal pulse are not being confused,” said David Russell, general manager, Mother and Child Care, for Philips Healthcare. “This is also about making a difference in the lives of mothers and babies. We are committed to developing solutions that help put these patients on the healthiest path possible.”

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Middle East Hospital Magazine September 2011