Prognosis issue 13

The periodical of the Harley Street Medical Area Issue 13 / 2024

The Ion age How lung cancer diagnosis is being transformed by a new procedure The long goodbye Inside the ongoing battle to unravel the mysteries of long Covid Divide and conquer Prof Nicola Curtin on the research that unlocked a new approach to breast cancer treatment How does it work?

A simple guide to osteotomy

Prognosis is owned by The Howard de Walden Estate 23 Queen Anne Street London W1G 9DL 020 7580 3163 hdwe.co.uk

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54 A breath of fresh air Professor Pallav Shah of Royal Brompton & Harefield Hospitals on how a new, minimally invasive treatment is providing hope for patients with COPD

Howard de Walden contact Annette Shiel annette.shiel@hdwe.co.uk Publisher Lusona Publishing and Media Limited lusonapub.co.uk Editor Viel Richardson info@lusonapub.co.uk Editorial consultant Mark Riddaway mark@lscpublishing.com Contributers Jean-Paul Aubin-Parvu , Ellie Costigan, Gerard Gilbert, Christopher L Proctor, James Rampton, Simon Way Design and art direction Em-Project Limited 01892 614 346 mike@em-project.com

Prognosis—1

04 HSMA update Julian Best of The Howard de Walden Estate on the spirit of innovation that drives the Harley Street Medical Area 09 News New arrivals, developments and events 10 Crystal ball The evolution of treatments for multi-ligament knee injuries 11 Harley Street hero Lord Moran of Manton 12 How does it work?

Osteotomy 14 Thinking aloud The thoughts of Madalena Mendes, clinical team lead at Pharmacierge 16 Profile of a pathogen Methicillin-resistant staphylococcus aureus (MRSA) 18 How to Manage medication 20 A day in the life Reza Mirza, head of pathology at The London Clinic 24 Positive image Steve Bird of Prime Health on an imaging company that meets the changing needs of patients and clinicians 26 Healthcare in the digital age Mental health and AI

2—Prognosis

30 The big interview Professor Nicola Curtin on the ground-breaking research that has transformed the fight against breast and ovarian cancers 36 The Ion age Mr Tom Routledge of HCA Healthcare on a new procedure with the potential to transform lung cancer diagnosis 42 The long goodbye Neurologist Dr Stephen Allder on the battle to unravel the mysteries of long Covid 46 Q&A Dr Mihaela Bucur of All Points North on lifestyle psychiatry 50 Patient experience Fiona McLoughlin on how cochlear implant surgery ended a decade of progressive hearing loss 54 A breath of fresh air Prof Pallav Shah on how a new treatment is providing hope for patients with COPD

60 My Marylebone Professor Dr Christian Mehl of The Wimpole Street Dental Clinic 62 What’s on Cultural events near the Harley Street Medical Area 63 Five Places to meet friends for coffee 64 The guide Film locations close to the HSMA

Covid really raised the flag for pathology and gave the world a bit of insight into what happens behind these laboratory doors. It was a watershed moment for us.

Reza Mirza, head of pathology at The London Clinic

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HSMA UPDATE

Julian Best, executive property director of The Howard de Walden Estate, on the spirit of innovation that drives the Harley Street Medical Area

At The Howard de Walden Estate, one of our roles as stewards of the Harley Street Medical Area (HSMA) is to ensure that the buildings and facilities we provide for our healthcare operators are fit for patients and operators, while creating genuine sustainable solutions on our net-zero pathway. To do so means not only understanding our tenants’ current needs but anticipating what those needs may be in the future. And one of the key factors driving future need is innovation.

Many of the articles in this issue of Prognosis showcase innovative research, treatments and projects being led and undertaken by HSMA clinicians.

Dr Stephen Allder a consultant neurologist at Re:Cognition Health talks about leading innovative research into the causes of and possible treatments for long Covid, a condition blighting lives 4—Prognosis

across the world. Prof Pallav Shah from Royal Brompton & Harefield Hospitals shares his knowledge of a novel treatment for severe bronchial diseases, previously extremely difficult to treat effectively.

Mr Tom Routledge from HCA gives his insights into pioneering work on the Ion system, a robotic surgery technique that radically improves the possibly of early diagnosis for some lung cancers.

That spirit of innovation can be seen in some of the development works taking place in the HSMA. In a major investment, Pharmacierge has announced a 5,500 sq ft expansion of its Wimpole Street premises to install world-leading pharmacy design through cutting-edge software. This ambitious project is set to create central London’s largest robotically enabled dispensary, revolutionising the independent pharmacy pathway by

We need to not only understand our tenants’ current needs but anticipate what those needs may be in the future. And one of the key factors driving those future needs is innovation.

Orri

Prognosis—5

Seeing this drive for innovation, for raising the bar when it comes to modern healthcare, in turn drives us to constantly improve the environment we provide.

The London Clinic

Prime Health Diagnostics

utilising tech-enabled access for clinicians and patients, with traditional pharmacy values. Meanwhile, The London Clinic has opened a new pathology lab boasting state-of-the-art analytical equipment.

Our recent arrivals are showing a similar commitment to pushing their fields forward. All Points North, who started seeing patients in 2023, is at the leading edge of a new holistic field of psychiatry that takes into account patients’ lifestyle and environment.

There is also Orri, whose new HSMA facility is attaining remarkable results using innovative methods for treating people with serious eating disorders.

Seeing this drive for innovation, for raising the bar when it comes to modern healthcare, in turn drives us to constantly improve the environment we provide. At Howard de Walden, we are continually 6—Prognosis

looking for ways to foster more health tech innovation by providing an ecosystem in which it is enabled to thrive.

That was our motivation for the recent acquisition of 76-78 Portland Place, the previous offices and collaboration space of the Royal Institute of British Architects. Our aim is to transform this versatile building into a space for academics and scientists involved in research and innovation in the health-tech environment to operate and engage with each other.

We want a place that helps build strong connections between healthcare providers, clinical research facilities and universities. Plans are still at an early stage, but we have begun the process of selecting an operator to run this exciting facility for us. At the moment, we are looking for it to be open and operational

in the first quarter of 2025.

What the HSMA offers, with its wide variety of practitioners, ongoing clinical trials and some of the world’s best teaching and research hospitals on its doorstep, is the opportunity for more cohesion. We have the potential to create a more closely connected relationship between the scientists making the breakthroughs and the practitioners delivering new, more effective treatments to the patients.

This is something we see as a key role of the HSMA and we will work hard in the coming years to make sure it continues.

The Howard de Walden Estate 23 Queen Anne Street London W1G 9DL 020 7580 3163 hdwe.co.uk

EXPERIENCE THE BEST OF UK HEALTHTECH AT ARAB HEALTH 2024 29 January - 01 February 2024 ABHI hosts the largest and most visible group of UK companies at Arab Health.

Our stand is home to a busy four-day programme of live surgical simulations and dedicated partnering events. Be sure to visit us in Hall 2 to learn more about the best in UK healthcare and HealthTech.

Arab Health by numbers

17

Country Pavilions

3,450

Exhibiting companies

110,000+

Healthcare and Trade Professionals

180+

Countries Represented

NEWS

Cleveland Clinic London has become the first private hospital in the UK to be awarded HIMSS EMRAM stage 6 accreditation, which recognises excellence in the use of IT and management systems. The Electronic Medical Record Adoption Model (EMRAM) is awarded by the Healthcare Information and Management Systems Society (HIMSS), a global non-profit member-based organisation. To be validated against stage 6 standards, a hospital must demonstrate a significant level of digitalisation and integration of EMR into operations, leading to improved patient care, efficiency, data utilisation and other tangible benefits. clevelandcliniclondon.uk

The London Clinic has completed a major refit of its in-house blood sciences pathology laboratory at 120 Harley Street. Costing £4m and taking two years to complete, the redesign has resulted in the lab being fitted out with cutting-edge equipment, including ground-breaking technology for the diagnosis of cancer conditions. Supplied

by QuidelOrtho, the new equipment will provide faster and more accurate collection and analysis of results for a wide range of blood science services, including biochemistry, stem cell therapies, immunology, histology and cytology, haematology, blood transfusion and microbiology.

The London Clinic

Pharmacierge

thelondonclinic.co.uk

The Royal Marsden Private Care has announced the appointment of Mark Hawken as its new managing director. Mark Hawken joins the hospital from The London Clinic, where he has been commercial director since 2018. In this role he was responsible for building private care revenue as well as implementing new services and partnerships with clinicians and other healthcare organisations. After beginning his healthcare career as a pharmacist, Hawken has also held senior commercial roles for BUPA and Aspen Healthcare. royalmarsden.nhs.uk

Orri has opened a new state-of-the-art day treatment facility on Wimpole Street for patients seeking support for eating disorders. The new facility provides both in-person and online treatment for patients aged 16 and above. Housed in a six-storey, purpose-built space, the clinic offers an intensive day-treatment programme, facilitating individual and group therapy sessions, as well as meals and dietetic support. All programmes follow a ‘stepped approach’, meaning that treatment evolves with each individual client as they progress in recovery, blending evidence-based and innovative approaches which incorporate the latest academic research and the clinic’s own research and development. orri-uk.com

Pharmacierge, the private e-prescription app and delivery service, has announced a major expansion of its Harley Street Medical Area facilities, with the ambitious transformation of two 18th-century Georgian properties into one streamlined clinical space. The addition of an extensive new 5,500 sq ft dispensary will grow its Wimpole Street operation to over 8,000 sq ft, a tenfold increase since the company’s arrival in 2015. Among the most notable developments is a 9-metre multi-arm dispensing robot, unprecedented in central London, which will occupy one wing of the new premises, with medication chutes spiralling down through the floor to the spacious dispensary beneath.

Orri

pharmacierge.com Prognosis—9

Following rigorous processing procedures that ensure it is safe for use, bovine tendon tissue is almost indistinguishable from human tissue. The huge advantage is that this tissue is copious in volume and also very strong.

CRYSTAL BALL

Multi-ligament knee injuries Mr Adil Ajuied, consultant knee surgeon at Fortius Clinic, on a common injury for which new treatments are showing exciting possibilities State of play A multi-ligament knee injury is any knee injury where two or more ligaments have been injured. Broadly speaking, these fall into two categories: low-energy injuries caused by an isolated incident like twisting your knee while falling and high-energy injuries caused by a serious event like a motorbike accident, where it may be just one of a series of injuries. In all cases, it is crucial to rule out vascular injury to things like the tibial artery or the peroneal vessels. Missing something like this could cost the patient their leg.

You must also rule out nerve injuries and bone fractures. Once this is confirmed, you start treating the ligaments. There are four cardinal ligaments: the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial 10—Prognosis

collateral ligament (MCL), and lateral collateral ligament (LCL). The key thing to know is that the PCL and the MCL can heal very effectively on their own while the ACL and the LCL will not. If you treat the injury within two weeks, the best thing is to support the knee using a special brace. This brace supplies the right support but also pushes the tibia forwards, which takes tension off the PCL. When applied well, the brace often allows the MCL and PCL to heal completely, all by themselves. Selfhealing leads to a better outcome than any surgery can produce.

On the horizon Something I’m very excited about is a new pathway that I and brace manufacturer OSSUR developed for treating high-energy multi-ligament knee injuries. The problem is that in the initial phases of the patient’s treatment, when more severe injuries are the doctors’ priority, the knee is often either under-treated by being placed into a loose support that allows too much movement, or over-treated with supports that are too rigid.

Both situations can lead to the knee needing extensive surgery later in the patient’s recovery. With this new pathway, when the clinicians dealing with the patient initially pick up the knee injury, they place it in a special short-term splint that doesn’t disrupt MRI scans. Once the more serious injuries have been treated, the patient has a scan. This is examined by the orthopaedic team and if a multiligament injury is diagnosed, they put on a PCL brace that is dialled in to support the knee in the appropriate

way. This way, when the knee surgeon sees the patient a month or two later, those ligaments that can heal have already been doing so quite nicely.

Depending on the injury, they may have recovered to a condition where surgery is not needed at all.

In the distance The thing currently being worked on that will probably have the biggest impact on these patients from a surgical perspective is the use of xenografts.

A xenograft uses tissue from animal tendons, usually from cows, to repair damaged human ligaments. Following rigorous processing procedures that ensure it is safe for use, it is almost indistinguishable from human tissue.

The huge advantage is that this tissue is copious in volume and also very strong.

The ligament tissue in a middle-aged or late middle-aged person can be weak and stretchy, so using it to repair damage elsewhere in their body means the repair will also be weak and liable to failure, whereas the strength of the bovine material means such failure is very unlikely to happen. Also, the size of the bovine tendons means that you can replace several human ligaments using the same bovine one, making the repair consistent across the joint.

I have been involved in some nonhuman research in this area and the results are showing very exciting potential for its future use.

Fortius Clinic 17 Fitzhardinge Street London W1H 6EQ 020 72342084 fortiusclinic.com

HARLEY STREET HERO

Lord Moran of Manton 1882-1977 Physician Words: James Rampton

Everything Lord Moran of Manton did was touched with greatness. Why, he even won a camel race at the Aswan sports club in Egypt in 1912 – an honour not many doctors can claim.

At the start of the First World War, Moran (known at the time as Charles Wilson) signed up with the Royal Army Medical Corps, ascending to the rank of major. Enduring two extremely hard years on the front line, he won the Military Cross in 1916 for bravery at the Somme and was twice mentioned in dispatches. He later wrote a book, The Anatomy of Courage, about his experiences in the war and became a lecturer on the subject of courage at the Staff College at Camberley.

After leaving the army, Moran went on to become dean of St Mary’s Hospital Medical School for 25 years, while also keeping a private practice at 129 Harley Street. He was president of the Royal College of Physicians for a record-breaking nine years, and was enormously influential in the creation of the National Health Service too. His great skill at debating with the British Medical Association and the Ministry of Health earned him the nickname ‘Corkscrew Charlie’.

All that would have been enough to guarantee him a place in the history books. However, even such illustrious feats are overshadowed by Moran’s most famous achievement: he was personal physician to Sir Winston Churchill for a quarter of a century from 1940 to the politician’s death in 1965.

It was the crowning – and ultimately most controversial – accomplishment of the doctor’s life.

The doctor, who was born the son of

a GP in Skipton, Yorkshire in 1882, and the twice prime minister were lifelong friends, sharing a delight in poetry, books and history. Moran understood the prime minister’s character well, knowing exactly how to handle a patient who could often be obdurate to the point of perversity. For instance, the politician always utterly rejected any advice to cut down on alcohol and cigars.

“If you tell Sir Winston that he ought to do something, he will not listen,” Moran observed. “But if you can convince him that it is to his advantage, he will always listen.”

Writing on the Royal College of Physicians website, TC Hunt explained why Moran was so well-suited to the job of Churchill’s personal doctor: “He was in fact supremely fitted for his role, being not only a wise physician, but having the courage both to take risks when needed, and to persuade his difficult patient to follow his advice. His skill in choosing the right specialist at the right moment and in giving guidance to them in the handling of a sick and often obstructive patient was evidence of his exceptional ability in the art of medicine.”

Moran, who was knighted in 1938 and made a peer five years later, is credited with saving Churchill’s life on more than one occasion, including treating the prime minister for pneumonia in Tunis in 1943. He also rescued Churchill from his own often cackhanded attempts at diagnosis. On one occasion, the prime minister, who insisted on taking his own temperature, was shocked when it read 66 degrees.

He immediately summoned Moran who saw that Churchill had blundered; his

temperature was actually a perfectly normal 96.

Moran stirred up a furore the year after Churchill’s death when he published The Struggle to Survive, a book describing intimate details of the doctor-patient relationship.

Coming in at a weighty 877 pages, the book proved hugely contentious as it outlined in great detail how Churchill was afflicted by the “black dog” of depression and went into a rapid decline towards the end of his life. The late prime minister’s widow Clementine was furious with Moran, asserting: “I had always supposed that the relationship between a doctor and his patient was one of complete confidence.” The British Medical Association, meanwhile, published a stern warning to physicians, underscoring their obligation to maintain high ethical standards.

Some have suggested that Moran exposed these private matters in his book in grievance at Churchill’s unbending imperialist worldview.

And yet, Moran’s relationship with the politician was always very strong and mutually trusting. The doctor, who died in 1977, was one of the very few people in the country able to speak his mind to Churchill. Above all, he had a deep and abiding respect for everything Churchill achieved in saving the country from the existential threat of Nazism. As Moran’s biographer, Professor Richard Lovell, says, the physician viewed his patient as “the greatest Englishman since Chatham (William Pitt the Elder) and regarded his care of him as his wartime duty”.

In discharging that duty with outstanding finesse, Moran helped boost the health of the entire nation.

Prognosis—11

Jig A device used to guide a cutting tool in such a way that it maintains the correct position, inclination and alignment, resulting in very a precise cut.

Artificial bone A laboratory-produced, bone-like material that can be used in bone grafts to replace human bone. It can be made from several different materials, including metal or metal alloys, ceramics or polymers.

Segmental fracture A type of fracture in which one of the bones is broken in at least two places, leaving a segment of bone totally separated by the breaks.

HOW DOES IT WORK?

Osteotomy Professor Paul Lee, consultant orthopaedic surgeon at Phoenix Hospital Group, on the modern implementation of an old technique with the power to change people’s lives Interview: Viel Richardson

12—Prognosis

For me, osteotomy is the purest form of orthopaedics. It is a controlled way of breaking a bone into separate parts and then re-attaching those parts in a modified arrangement. Typically, I use osteotomy to straighten the legs of patients with congenital genu varum, popularly known as ‘bow legs’.

I sometimes use it to treat people with knock knees (genu valgum), where the bones curve inwards instead of outwards, but bow legs are more common. Using a procedure called high femur osteotomy (HTO), we change the alignment of the leg bones, which straightens the leg and re-directs the weight-bearing forces travelling through the knee joint.

Having bow legs straightened is not just a matter of aesthetics. The deformation can cause serious medical issues. With bow legs, the medial compartment on the inside of the knee is abnormally loaded, with too many of the forces supporting the body going through that area. This overloading can cause wear and tear, potentially leading to arthritis. It can also cause some people significant pain from certain movements, which restricts the activities they can undertake.

Advances in orthopaedic surgery mean both the methods of breaking the bone and the support structures we use while the bone is healing are far more sophisticated now than they used to be. One key advance is that the support is now internal. Previously, large steel plates were used to hold the bones in place, with weight-bearing support provided by an external scaffold structure. This was uncomfortable and inconvenient. Nowadays, the

internal plates and screws we use offer that weight-bearing support as well as holding the bones in place, which is much better for the patient.

While the concept is simple, HTO involves a complex series of procedures. First, there is a clinical examination, where we assess the level of deformation and discuss what the patient wants from the procedure. If there is a measure of pain relief involved, we have to ascertain precisely what is causing the pain and ensure the plan deals with it. Because HTO is focussed on the knees, we also need to know the status of the joint. Can the patient physically bend and straighten their knees? The joint needs to be supple enough for them to benefit from the procedure. If the knee is stiff, osteotomy may not be the right approach.

We then take a long leg alignment x-ray. This looks at the whole lower half of the body, with the patient standing and facing forward. Using this scan, we find the centre point at the hip and the centre point at the ankle and draw a line between them. This line shows how far the knee is deviating from the vertical axis and determines how far we need to shift it. To enable the detailed planning for the procedure, we then take a CT scan, preferably a weight-bearing one with the patient standing up. This allows us to reconstruct the bones in three-dimensional space within a computer. We then align that 3D model with the x-ray to make sure it’s an accurate representation.

The ability to prepare for the procedure using a computer model has been the biggest innovation in osteotomy. In this model, we can expose

Osteotomy

Leg vertical axis

Leg axis before procedure

Leg axis after procedure

Bone graft inserted

Gap created to straighten bone

the bones, examine them from all angles and simulate making the break using an accurate digital version of the specialised saw or drill we will use in the real procedure. We tweak aspects of the plan until we’ve dialled in the precise angles for the cuts and the placement of the plates. Once we’re happy, we’ll engineer an individualised jig that will lock the leg bones in position and guide the cuts. This planning stage is crucial because bones are not cylindrical and the shape changes along their length.

Once cut, the bone may want to slide in one of multiple directions. You want all this to happen in the computer model so you can understand and plan for it.

When you perform the actual surgery, there should be no surprises.

When you straighten a leg, you create gaps in the bone which need to

be filled. We use either an artificial bone or what we call allograft, which is bone tissue taken from another person – usually from bone removed during hip replacement surgery. We screen this material, scan it, make sure it’s free of disease and then sterilise it before use.

We always start with the intention of making one cut across the femur above the knee, because the body heals much better after just a single cut, but sometimes we have to make an additional cut in the tibia and fibula bones below the knee. When you make two cuts, extra forces come into play, so it takes longer to heal. On extremely rare occasions, we will make two cuts in the same bone, but this creates what we call segmental fracture and the factors you have to control during healing can quadruple, if not more, so this is

something we strive to avoid. Once we’ve made the cuts, we fill the gaps, then bolt on the plates to hold the bones in place.

I love seeing the difference this procedure makes to my patients. For some, after a lifetime of embarrassment, bullying and insecurity caused by their bow legs, their confidence soars. Others are moving without pain for the first time in years and are back running or cycling. An osteotomy can also delay the need for a knee replacement for at least 10 to 15 years. Some patients won’t need to have a knee replacement at all.

It really can be a life-changing surgery.

Phoenix Hospital Group 9 Harley Street London W1G 9QY 020 7079 2100 phoenixhospitalgroup.com Prognosis—13

THINKING ALOUD

Madalena Mendes, clinical team lead at Pharmacierge Interview: Ellie Costigan

One of our unique facets is that we hold a much broader range of medication than a pharmacy normally would, so can support a broad range of specialisms. As well as GP surgeries, I deal with lots of larger institutions, be it the OneWelbeck hospital, which is just adjacent to us, the HCA Healthcare primary care team, or a specialist clinic in psychiatry or menopause.

I knew from a young age that I wanted to be a healthcare professional. Lots of my mum’s family found their path in healthcare, including as pharmacists, and my grandad was a doctor.

Liaising with doctors is a very important part of my work. That includes ensuring we’ve understood their intentions if there is any ambiguity in what they’ve prescribed and helping them with alternatives if something isn’t available.

The Harley Street Medical Area has the highest concentration of private medical knowledge in the country and it’s reassuring to clinicians that we’re in and of the area. It also means that if there’s an issue with a prescription – especially one that can’t be sent electronically, such as for a controlled drug – and it’s urgent, we can walk over to the doctor ourselves to get it amended quickly.

I am from Lisbon, Portugal, and the pharmacist profession is a bit different here to back home. After Brexit, my qualification wasn’t recognised in the UK, so Pharmacierge supported me to get the equivalency here, which is a two-year online course.

Medication shortages are something we have to deal with a lot at the moment.

Our co-founder Ed’s father Leon says he’s never seen shortages this bad in his 65 years in the profession. It’s a global supply chain and with the economic and logistical upheavals of the past few years, it’s not surprising. We update many of our doctors every week so they’re best prepared treat their patients.

Being in central London, surrounded by hospitals, means we get multiple deliveries a day, from a huge range of manufacturers. It means our supply is very reliable. It also means it doesn’t take us long to get something from one side of London to the other.

14—Prognosis

For me, everything started with Leon Ungar, one of the founders of the business and a pharmacist himself. He interviewed me over the phone. From the beginning, I could tell this business was different. He talked to me how you talk to your family, and that trickles down to the rest of the team. We work together as a family and we treat our patients like they’re family, too.

Unlike other pharmaceutical companies, we all have share options in the company.

It means we are working for something that is actually ours, which makes a big difference.

Pharmacierge 8 Wimpole Street London W1G 9SP 020 7631 1269 pharmacierge.com Prognosis—15

Staphylococcus aureus A gram-positive bacterium that cause a wide variety of clinical diseases.

Penicillinase An enzyme, produced by some bacteria, capable of inhibiting the antibacterial action of penicillin and other beta-lactam antibiotics.

Impetigo A highly contagious skin infection that mainly affects infants and young children.

Usually appears as reddish sores on the face, hands and feet. Over about a week, the sores burst and develop honey-coloured crusts.

Anti-microbial The ability to kill or slow the spread of microorganisms such as bacteria, viruses, protozoans and fungi such as mould and mildew.

PROFILE OF A PATHOGEN

Methicillin-resistant staphylococcus aureus (MRSA)

Methicillin-resistant staphylococcus aureus, better known to the wider world as MRSA, is a type of staphylococcus bacteria that has become resistant to many of the antibiotics used to treat staphylococcus infections. Methicillin was the first penicillin-derived drug that could overcome the effects of penicillinase, an enzyme that disrupts the internal structure of penicillin, destroying the antimicrobial action of the drug and therefore its efficacy. Methicillin was introduced in 1959 to treat infections caused by the penicillin-resistant bacteria staphylococcus aureus and proved so effective that it quickly became established in clinical facilities across the world. Even as it was being rolled out, scientists knew that bacteria would likely develop resistance to methicillin too – and so it proved. The first culture 16—Prognosis

of staphylococcus aureus found to be resistant to methicillin was identified in a lab at Colindale Laboratories, London, by Professor Patricia Jevons on 2nd October 1960. This was followed by an outbreak of MRSA at Queen Mary’s Children’s Hospital, Carshalton only two years later.

MRSA infections can be divided into two types, hospital-associated HA-MRSA and community-associated CA-MRSA. They differ not only in clinical features and molecular biology but also to their antibiotic susceptibility and treatment, which makes them hugely difficult to tackle. The list of conditions MRSA can lead to is eye opening – they include cellulitis, folliculitis, impetigo, osteomyelitis of the spine and meningitis. HA-MRSA can cause ventilator-associated pneumonia while CA-MRSA can cause life-threatening necrotising pneumonia in otherwise healthy individuals. There are lung abscesses, empyema (internal pus sacs), serious bone and joint infections, necrotising fasciitis, diabetic foot ulcers, MRSA-associated bacterial endocarditis (an infection caused by the bacteria that enters the bloodstream and settles in the heart). The list goes on and on.

There are some medications available to treat sufferers, but whether they work will depend on the type of condition, local staphylococcus aureus resistance patterns, individual patient profiles, the availability of often expensive drugs and other factors.

Some of the least complicated infections may respond to oral antibiotics like doxycycline or clindamycin. If these are ineffective, intravenous vancomycin is the drug of choice for most HA-MRSA infections, but there have already been

sporadic cases of vancomycin-resistant MRSA. As the old saying goes, prevention is better than cure. And the most effective form of prevention is the proper implementation of infection-control protocols such as the proper washing of hands before and after contact with infected patients and the wearing of gowns, gloves and masks. Isolation spaces for MRSA patients may also be required.

Studies from across the world have identified MRSA strains adapted to survive in the hospital environment, and we are nowhere near having a comprehensive drug-based solution to the problem. As we wait for the discovery of another drug with the almost miraculous anti-microbial capabilities of the first penicillin-derived medications, the answer to combating MRSA is primarily found not in the medical establishment but in the realms of public expectations and government policy. Experience has led much of the public to expect a ‘pill’ to alleviate the symptoms of even the most minor ailments, while prophylactic antibiotic dosing is widespread in livestock production. These twin factors have led to the huge overuse of the class of drugs that underpins modern infection control. Were antibiotics to become wholly ineffective, the results would be catastrophic. Work is being done to reduce antibiotic overuse and to discover drug-based alternatives, but we are well behind the curve in dealing with this issue. It will take a great deal of political will as well as scientific endeavour to crack the problem. It is to be hoped that both are in plentiful supply.

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HOW TO MANAGE MEDICATION

Reshma Malde, superintendent pharmacist at John Bell & Croyden Interview: Jean-Paul Aubin-Parvu

When picking up our medication, what questions should we be asking the pharmacist that we maybe didn’t ask the GP? Very often, people who’ve been prescribed a new medication by their doctor haven’t had enough time to ask pertinent questions about what it does and how it works. You can ask your pharmacist if there’s anything important that you need to know. You should also read the information that comes with the medication. Ensure you know exactly how much to take, when and how often, when you should stop taking it and any precautions to be aware of. You may also want to ask what you’re supposed to notice once you start taking it, so you know that it’s working. Ask about storage. Some medicines need to be stored in certain conditions. For example, insulin needs to be kept within a specific temperature range to ensure the active ingredient is at its best.

Is there anything that we should make the pharmacist aware of when picking up our medication?

I would always recommend giving them a list of all the medications, supplements, vitamins and herbal medicines that you currently take. Let them know about any recent changes in your health or medication and inform them about any allergies or intolerances. This helps ensure that what they’re giving you today isn’t going to affect you adversely or interfere with what you’re already taking.

How important is it to take the medication correctly?

18—Prognosis

Research has allowed us to understand how certain drugs work and how to get the best out of them for different conditions. There’s a set regime that needs to be followed to to get the optimum effect. By not taking it correctly, you’re not getting the best out of the medicine. And not only can it hinder the improvement of the condition, it can get to the point where you experience undesirable effects.

Please speak to your pharmacist if something is stopping you from taking the medication correctly. We may be able to recommend a more suitable preparation that gives you the same best effect.

Is it a bad idea to ‘save some for later’ if you’re prone to the same illness returning?

We’ve all been brought up to avoid waste, so saving some for later might seem like common sense.

But if you have excess medication, that suggests you maybe haven’t used it the way it was intended. Either the medication wasn’t needed, or you’re not getting the full benefit. Perhaps you didn’t know that you can reorder this medication from your doctor.

Perhaps you’re concerned about cost, so have used the medication sparingly.

But, again, that has consequences for your health.

Some people stop taking the medication as soon as the symptoms stop. Is it always best to finish the course even if you are feeling better?

It’s really important to follow the instructions from your doctor and

pharmacist. Take the example of antibiotics. When you get an infection, the doctor will prescribe an antibiotic if appropriate. You start taking the course and after a few days the antibiotics have started to do their job.

The bacteria that caused these horrible symptoms are being killed off, so all of a sudden you start feeling better.

You think, oh that’s okay, I’m done, so you stop taking the antibiotic. But by completing the course, there’s more chance of clearing all the bacteria so that the infection doesn’t return.

What’s your view on a person giving medication to a friend suffering from the same condition?

You’re not a healthcare professional, so sharing medication with a friend could be harmful for them. They could be taking something you’re unaware of which interferes with the medicine you’ve shared. And even though that person may feel better afterwards, you’re delaying them seeking medical attention and getting their condition managed.

How should we dispose of old medication?

Please bring it back to your pharmacy.

Any pharmacy that has an NHS dispensing contract is also instructed to be able to take patient returns of old medication. It can then be collected and destroyed safely.

John Bell & Croyden 50-54 Wigmore Street London W1U 2AU 020 7935 5555 johnbellcroyden.co.uk

A DAY IN THE LIFE

Reza Mirza, head of pathology at The London Clinic Interview: Ellie Costigan Portrait: Simon Way

The more you progress within any area, the further away it takes you from bench-top work. Nowadays, my role is a combination of administrative, clinical and leadership responsibilities. My main focus as head of pathology at The London Clinic is ensuring that day-today operations are running efficiently and we’re delivering timely services.

I’m also here to make sure that the team leadership is strong and that we’re collaborating well with other clinicians outside of pathology. I deal with any issues that arise and communicate them to the rest of the clinic – I’m the glue between pathology and other departments. They will also sometimes come to me for advice when they’re looking to introduce new services and need to understand the impact it might have on pathology.

20—Prognosis

The fact that each day is different is part of the attraction for a lot of people coming into pathology. There is no such thing as a typical day in the laboratory and that’s largely because we cover around seven major disciplines. Some of these are hugely manual, reliant on the skills of the individual, honed over many years of practice. Histology, for example, involves cutting wax blocks to one-cell thickness – a really skilled job. Conversely, something like blood sciences is entirely automated.

The nature of the work often dictates the turnaround time – it could be within the hour, or it could be days – but we’re always trying to improve, in every area. If you were to boil pathology down to its basics, our role is to ensure that the right patient gets the right result, in the right timeframe – those

w Prognosis—21

There is no such thing as a typical day in the laboratory and that’s largely because we cover around seven major disciplines. Some of these are hugely manual, reliant on the skills of the individual, honed over many years of practice.

are the nuts and bolts. We perform thousands of different tests, some of which may be referred out. Our aim is to get the results of each test back to the clinician as quickly as possible so they can decide what treatment plan the patient requires.

The wait between having the test and getting the result is a crucial time for patients and often the most worrying.

We want to alleviate that worry as much as we can. At The London Clinic, we put the patient at the centre of everything we do. They should have complete assurances in our services and not be subjected to any additional anxiety at what is often a very vulnerable time in their life.

The lab has recently undergone a £4 million transformation, which happily has already started making our 22—Prognosis

services even better. It involved so much more than just taking out old machines and bringing in new. We’ve brought in state-of-the-art equipment and pieced it together to create an automated track that moves samples between analysers, without the need for a human to be present, which makes things much more efficient. We’ve changed the fabric of the building, replacing the air systems so that we’ve got much cleaner air for our staff. We’ve also introduced remote working in some areas. We’re trying to make sure we’re staying abreast of how people will want to work in the future.

For example, we’ve introduced a piece of kit that allows us to send slides remotely to a clinician’s desktop, in real time.

We had the grand opening of the transformed lab in September 2023 and there have been a couple of teething issues, as is to be expected, but we’re also seeing a lot more uptime with our equipment – fewer breakdowns and failures. The whole process has become more streamlined, which ultimately means a better service for patients.

There is always going to be a human element to our work, but we have also started to think about how AI technology can support us. There’s a lot of discussion around progressive learning, which I think can potentially advance areas such as histopathology – so cancer diagnosis. At The London Clinic, we need to make sure that we’re at the forefront of advancements – the clinicians who work for us are world renowned and they need access to the latest technologies.

As well as keeping on top of technological advancements, we also need to stay abreast of regulatory

requirements, and to that end our service is regularly accredited – we’re one of the most heavily accredited departments in the hospital. Specifically, we’re assessed by the UK Accreditation Service (UKAS), which ensures we have quality management systems, high testing standards, and competent, welltrained, knowledgeable staff. This gives our patients and doctors an assurance that we’re running a high-quality lab.

I have to say, one of the rare silver linings of Covid was that it gave people some insight into the laboratory testing side of things. People became very aware of what a PCR test is, for example, and that it was scientists who created the protections against Covid and the roadmap that helped get us out of lockdown. It really raised the flag for pathology and gave the world a bit of insight into what happens behind these doors. It was a watershed moment, globally. People had a renewed respect for the pathologists and scientists, who so often work in the background and don’t always have a name or a face.

Since I’ve been here, I like to think I’ve opened the doors to pathology.

I want to invite people in and help them understand what we do here.

I’m able to meet clients a lot more – not just the clinic’s patients, but the wider healthcare community. A lot of clientfacing activity happens here. We’ve got an exceptional team here and I’m very proud to be able to spotlight that.

The London Clinic 120 Harley Street London W1G 7JW 020 7616 7755 thelondonclinic.co.uk

“Nobody understood my eyes more than Moorfields.”

Glasses and contact lenses didn’t fit into Evgeniya’s active lifestyle, leading her to feel she was missing out. After laser surgery, she’s not missing out anymore.

“I have worn glasses ever since I was in high school, before switching to contact lenses due to my active lifestyle. But contact lenses gave me dry eyes and glasses weren’t practical for me - I wanted to be able to see better when going about my daily life.

I spoke to a number of companies offering vision correction but, due to an issue with my cornea, I didn’t feel comfortable having the procedure with them.

Then I went to see Moorfields Private.

They were able to assess my eyes and find a solution I feel I would not have found anywhere else.

My surgery has improved my quality of life incredibly.

I enjoy my daily activities more and I no longer feel like I am missing out on life.

Find us at: City Road New Cavendish Street EC1 W1 I feel a lot safer, especially when driving, as it’s improved my peripheral vision. I don’t remember ever being able to see as well in my life.

I wish I’d done it sooner.”

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POSITIVE IMAGE

Steve Bird, CEO of Medical Imaging Partnership and Prime Health, on building an imaging company that meets the changing needs of patients and clinicians Interview: Ellie Costigan

Medical Imaging Partnership and Prime Health are the same company, but with two different front doors. The business is concerned with diagnostic imaging: we provide mobile MRI and CT scanners for NHS partners, as well as running diagnostic imaging departments in independent hospitals and stand alone clinics.

Prime Health can be found on Queen Anne Street, in the Harley Street Medical Area. We offer imaging for orthopaedic, brain, prostate, cancer – anything that requires an MRI or CT scan. The centre has an excellent reputation for quality and is one of only two imaging centres in London to have recently been awarded the maximum five stars by Prostate Matters, for its mpMRI facilities and reporting.

We get a lot of referrals from 24—Prognosis

clinicians, but patients can also refer themselves, booking online at a time that suits them. It’s empowering. I think there’s a generational shift, in that sense: healthcare has become more commoditised and I think that people wanting to take care and control of their own health in a way that fits in with their work and personal life is going to become more prevalent. We want to embrace this and enable patients to take charge of their life and wellness.

As an imaging business, our work comes in at the beginning and end of a patient’s pathway. Before you go to see a surgeon, he or she will want an image or a scan to make a diagnosis. Then, once you’ve been through the surgery, an image is needed to assess whether the treatment has delivered the desired outcome.

The emotional wellbeing element of that experience shouldn’t be underestimated, but I think it often is. Waiting around either for a scan or to receive your results can be quite daunting. For some patients, the scan itself can be traumatic. Some can take up to 50 minutes and you might be in an enclosed space, as is the case with an MRI scan, with lots of noise. That can be tricky for some people. The more we can do to make that experience as smooth as possible, the better. Alongside our partners, we deliver tens of thousands of scans every year, but each patient is different and should be treated as such.

There are lots of facilities in the HSMA that offer scanning services, which means we’ve got to be competitive.

The area also has a certain reputation, with a particular clientele, and we need

We don’t just want to be an imaging factory, churning out scan after scan. We want to create a pathway for patients, providing an efficient scan and a detailed report, and using that to signpost those who need it to further treatment, helping them on the rest of their journey.

to make sure we are meeting their expectations – our services must be high quality, immediate and accessible.

We don’t just want to be an imaging factory, churning out scan after scan.

We want to create a pathway for patients, providing an efficient scan and a detailed report, and using that to signpost those who need it to further treatment, helping them on the rest of their journey.

To do that, it’s vital we have the right staff, who understand and buy into that concept. It’s our collective responsibility to find the best talent to develop the right ethos and team culture. In a challenging recruitment market, it’s important that we find technical and other staff who buy into our service aspiration. There is a shortage of healthcare professionals at the

moment – finding technically competent radiographers and technicians who also believe in holistic care can be challenging. But it’s also important to find the right leadership to ensure we can cope with changing dynamics and continue to innovate. For me, diagnostic imaging is at the heart of all healthcare.

That’s why I enjoy working in this space.

Technology is ever improving, and we need to keep up with its progress.

There are software applications that halve the scanning time for certain tests, for example, and it’s getting better all the time. The growth of AI is also a big opportunity for us, particularly in terms of interpreting images and sending appointments to patients. I believe the use of AI tools is going to benefit patients significantly in the next five years or so. It’s an interesting and

exciting time to be in the industry.

Healthcare requires investment.

The whole of the Harley Street Medical Area needs to continue its commitment to constant improvement – from the facades of the buildings, to increasing our understanding of how patients get to clinics. The area is going to look very different in five or 10 years’ time, and that will require vision and continued investment from everyone: from small businesses like Prime Health to the larger private hospitals, right up to our landlords, The Howard de Walden Estate.

Prime Health Harley Street 45 Queen Anne Street London W1G 9JF 033 0025 2100 prime-health.co.uk Prognosis—25

One interesting question being asked is whether digital techniques such as automated language processing and machine learning algorithms have the potential to assess a patient’s mental state beyond what can be measured through the patient’s self-reporting and clinical observation.

Dr Jacqueline Phillips Owen

HEALTHCARE IN THE DIGITAL AGE

The potential impact on healthcare of evolving technologies is vast.

In this series, experts from within the diverse community of the Royal Society of Medicine offer their unique perspectives on digital health

26—Prognosis

MENTAL HEALTH AND AI Dr Jacqueline Phillips Owen, child and adolescent psychiatrist and president elect of the RSM Psychiatry Section Council, and Dr Johnny Downs, senior clinical lecturer in child and adolescent psychiatry at King’s College London and leader of the CAMHS Digital Lab, King’s Maudsley Partnership, on the promise and pitfalls of integrating AI technologies into mental health practice

Dr Jacqueline Phillips Owen Traditionally, the role of the Royal Society of Medicine has been as an educational and health advocacy organisation focused on the medical community. But recently we have been expanding our remit and increasing our ability to engage with diverse groups and tackle issues of interest to the wider public. What has become increasingly clear is that both groups are becoming more aware of, and in many cases concerned about, the impact artificial intelligence (AI) and the wider world of computing will have on the field of medicine. We want to help examine this intersection of the digital and medical worlds on ethical and policy grounds as well as those of clinical practice.

As a psychiatrist who works with children with attention deficit hyperactivity disorder (ADHD), I have been involved in research into the condition. Because ADHD can be a very time-consuming condition to diagnose, there is a real interest in investigating ways of making an automated diagnosis. One interesting question being asked is whether digital techniques such as automated language processing and machine learning algorithms have the potential to assess

w Prognosis—27

a patient’s mental state beyond what can be measured through the patient’s self-reporting and clinical observation.

That is a very attractive proposition, but one I think will be very difficult achieve.

However, what researchers have discovered so far are some processes that might provide possible clinical insights through a computer’s ability to interrogate vast amounts of information. This is not the same as automated diagnoses. It is more the ability to sift out patterns of thoughts or behaviour which might help the clinician in their assessments. It is all about pattern recognition, which is something computers have been great at for decades. In fact, looking at most digital tools currently available to clinicians in my field, many cannot really be said to be using true AI. What they are doing is more traditional digital processing.

We also need to consider the wider arena within which AI is going to operate. Can the algorithms be programmed to take account of societal or cultural changes. The last few years have seen society shifting into a space where people are much more aware of the symptoms of various mental disorders. Returning to ADHD, many adults who feel they are struggling to cope, look up symptoms, do online questionnaires and self-diagnose the condition. But when a trained mental health clinician applies their experience during sessions with the patient, they may find that the issue is generalised ‘distress’. This is a state of mind that does need to be addressed, but it’s not the mental disorder it is being badged as by the patient. The problem is that patients will interpret their thoughts and feelings through the lens of their self-diagnosis, which can distort their appreciation of the situation. It takes training and experience to tease out what is actually happening in these situations.

I don’t think that automated language processing techniques and machine learning algorithms have the ability to read the subtle nuances necessary to get to the truth. It is an issue being faced in many fields of medicine as public awareness of clinical conditions grows.

I am optimistic about the possibilities of digital health – it does have huge potential – but we do need to be wise about how and where we adopt it.

We are witnessing a conceptual shift in the public’s understanding of mental health. This change is happening in ways that I think ensure the adoption of true AI-generated solutions is still some time away.

28—Prognosis

Dr Johnny Downs I think there’s a mixture of cautious optimism about the possibilities of AI and deep concern about some of the issues it raises. Mental health medicine requires a multimodal assessment of information.

Diagnoses involve assessing what patients say, their facial expressions, tone of speech, body language, personal history and other factors. Therapists synthesise all this complex data to adapt and personalise their treatment approaches. But as humans we make errors, make omissions, overlook data.

One compelling area of research is using AI techniques to help clinicians summarise this wealth of information.

This is not sexy science. It involves things like accurate auto-transcription and summarising of a session. This would free the therapist to fully focus on the patient during each session and save a lot of time deciphering scrawled notes afterwards. There may be ways to automatically input the clinician’s note into the right records in the correct format. These AI back-office functions will save time and help provide a better service to patients.

With AI-based diagnosis, we are facing a different order of problem. This involves feeding data into a series of algorithms and a diagnosis coming out the other end. How do you interrogate the nature and quality of a diagnosis made inside a black box? Can we use these particular models to more quickly and accurately identify a condition?

ADHD is an excellent example here.

Young people can be recognised quite early as having potential difficulties, but then take years to navigate mental health system to the point where they get a diagnosis. This lag is driving research into creating tools which could shorten that time considerably.

But this example throws the spotlight on the nature of the data used in these computer models. To build them we rely on huge data sets, of which there are not that many. The NHS has the largest, but there are some others around the world. This data is used to train the algorithms, but we know the data sets contain ascertainment biases. These arise when data is collected, surveyed, screened or recorded in ways that mean some members of the target population are less well represented than others. Assumptions based on ethnic background, levels of social deprivation, home circumstances and many other metrics can distort the data. Even when children get into the system, there are inherent biases that will shape their

Therapists have to synthesise a lot of complex data to make a robust diagnosis. But as humans we make errors, make omissions, overlook data. One compelling area of research is using AI techniques to help clinicians summarise this wealth of information.

Dr Johnny Downs

experiences. For example, we know that fewer people than average from a black ethnic minority background navigate the system to the point of an ADHD diagnosis. So, if you train the algorithms on the raw data, the model will assess race as being one of the key factors in the probability of the patient having ADHD, leading to it producing false negatives.

Another idea has been to combine facial emotional processing algorithms with facial recognition technology to assess the patient’s emotions during a session. In an experiment, led by colleague Magnus Boman, when the clinical psychologist was a white woman interacting with a white child the system showed promise. But when used on a black mother with her black child, we were not able to use any of these technologies in a robust way. And I could go on. The issue is: how can we reverse engineer that sort of bias out of a system? It’s a real concern. We know that unfairness is inherent in society; the challenge is to avoid building that unfairness into our digital systems.

I am actually very optimistic about the possibilities of AI. We are making progress, and small-scale systems are working within some areas. The first step in any successful project is to identify the obstacles, and I think we have really got to grips with that.

There is much to do, but if we get it right, AI could transform the experience of mental health patients for the better.

Royal Society of Medicine 1 Wimpole Street London W1G 0AE 020 7290 2900 rsm.ac.uk

“Genomic testing is a crucial tool in our efforts to understand cancer better. It enables us to identify genetic changes in individual cancers, which means we can offer improved, personalised treatments to our patients.”

Like no other Dr Angela George, Clinical Director of Genomics and Consultant Medical Oncologist in Gynaecology

To refer an international patient privately, please contact the International team.

+44 (0)20 7808 2063 int@rmh.nhs.uk royalmarsden.nhs.uk/private

THE BIG INTERVIEW Divide and conquer Professor Nicola Curtin, professor of experimental cancer therapeutics at Newcastle University, on the ground-breaking research that has transformed the fight against breast and ovarian cancers Words: Viel Richardson Portraits: Christopher L Proctor

30—Prognosis

w Prognosis—31

It became known as the Angelina Jolie gene. In 2013, the Hollywood actor, director and producer revealed in a newspaper article that she had chosen to have first her breasts and then her ovaries removed. The reason for such drastic surgical interventions was that, having lost her mother Marcheline Bertrand to ovarian cancer at the age of just 56, Jolie discovered she had a defective version of the BRCA 1 gene, the presence of which, she was told, increased her chances of getting breast cancer to over 80%. Faced with this knowledge, she took the decision to remove the organs in which the cancer was most likely to occur.

Jolie’s decision made headlines around the world, firstly because she was a woman famed for her beauty and at the height of her powers, but also for the bravery she showed in telling her story. In choosing to do so, she highlighted how little choice women at the time had when facing this situation. Fortunately, due to the work of dedicated scientists like Professor Nicola Curtin, the choices women today can make are not always so stark. In 2003, Rubraca became the first PARP inhibitor (PARPi) to enter clinical trials for the treatment of cancer. It is now used to treat high-grade cancers of the ovary, fallopian tubes and peritoneum – the membrane lining the abdomen.

“I was part of the Newcastle University Anticancer Drug Discovery Group, and the development of PARPi was one of our first projects in 1990,” says Prof Curtin, one of the foremost cancer research scientists in the

32—Prognosis

country. Poly-ADP ribose polymerase (PARP), an enzyme found in our cells, plays a key role in DNA repair.

At the time, most chemotherapy and radiotherapy worked by damaging DNA, so the rationale for developing PARPi was to overcome resistance to the therapy by blocking DNA repair.

“My first role was to establish a robust system to assess the potency of inhibitors that the medicinal chemists were producing,” says Prof Curtin. “This would help us develop a structure-activity relationship (SAR) – that is, the relationship between the chemical structure of the compound and its biological activity – such that compounds of increasing potency could be designed. Then, using the more potent compounds, I evaluated their effects on living cancer cells and determined which anticancer drugs they worked best with. This identified that the best combination was with Temozolomide, another drug – like Rubraca – developed with Cancer Research UK support. The first Phase 1 clinical trial of Rubraca in 2003 was in combination with Temozolomide.”

However, since the PARPi also prevented DNA repair in normal cells, unwelcome side effects of the combination were seen, limiting the dose that could be given. “DNA repair doesn’t exist to frustrate the attempts to treat cancer,” the professor explains. “Our DNA is continually being damaged. This can be caused by external factors, like smoking or exposure to sunlight, but most of the damage is being done by substances produced as a byproduct of the cell’s metabolism. There are lots of types of

That’s what makes this so beautiful – you are homing in on a cancerspecific vulnerability to give a truly tumourselective therapy.

DNA damage and for each type there is a corresponding repair pathway.

“The first thing to understand is that the integrity of DNA is essential for life and, as I mentioned, DNA is being damaged all the time. Therefore, every living organism from bacteria right up to humans needs to be able to repair its DNA at the same rate it is being damaged, or it will die. This constant DNA damage takes place at quite an alarming rate, for example, we think as many as 10,000 to 100,000 singlestrand breaks occur in every cell every day. Some types of damage are easy to repair, needing only a few components do the job. Others are very tricky to repair and require lots of different proteins to cut out the damage and patch up the hole left behind.”

As well as repairing the DNA, the cell also needs to stop its normal replicative cycle or any non-fatal damage will be carried on to the daughter cells. To prevent the damage from being passed on, a DNA damage response (DDR) triggers mechanisms not only to carry out repairs but also stop the cell trying to replicate the damaged DNA. “If the damage proves too extensive, the DDR can tell the cell to kill itself and starts cutting up proteins, including the PARP, that would help it repair any damage,” she says.

Cancer cells are genetically unstable, which increases their ability to survive by evolving. Prof Curtin thinks that this genetic instability may be what allowed the cancer to develop in the first place. A major cause of such instability is a defect in the cells’ DDR mechanisms. This is

Academy of Medical Sciences Professor Nicola Curtin is a Fellow of The Academy of Medical Sciences. The Academy, based on Portland Place, is an elected fellowship of medical researchers. It has over 1,300 fellows, about half of whom are clinically qualified, the other half being laboratory scientists in a range of disciplines. The Academy, which seeks to promote excellence in research,influence policy to improve health, promote careers in medical research, and foster links between academia, industry and government, is a registered charity that relies on philanthropic funding. To support its work and make a donation please visit: acmedsci.ac.uk/support

where the groundbreaking work led

by Prof Curtin and Professor Thomas Helleday, professor of translational oncology and director of the Sheffield Cancer Centre at the University of Sheffield, comes in. Together they discovered the ‘synthetic lethality’ of PARPi in cancers defective in another DNA repair pathway: homologous recombination DNA repair.

“Synthetic lethality is when you have two components or pathways that have complementary roles in completing a process – in this case, repairing damaged DNA – where the loss of either one on its own doesn’t compromise viability, but inactivating both together is fatal,” Prof Curtin explains.

The single-strand repair process with which PARP is principally involved is pretty efficient. However, if by the time the cell comes to replicate the DNA – which it needs to do so it can divide into two daughter cells – PARP hasn’t been able to repair all the DNA breaks, then those single-strand breaks will make the replication process stall, producing a singleended double-strand break. Because the accuracy of DNA replication is so important, cells have developed a sort of belt-and-braces approach to deal with DNA damage. In the case where the failure to repair the single-strand breaks has resulted in these collapsed DNA replication lesions, the cell has a back-up repair pathway known as homologous recombination DNA repair. Prof Helleday and Prof Curtin showed that PARPi are synthetically lethal in cells where the homologous recombination was defective – and this is where BRCA comes in.

Most cancer cells have some sort of defect in their DDR. Mutations in the BRCA1 and BRCA2 genes (the names of which are abbreviations of ‘breast cancer’) are responsible for most hereditary breast and ovarian cancers. “Homologous recombination is a complicated, but high-fidelity, DNA repair pathway. It involves a lot of components, but two key ones are BRCA1 and BRCA2,” Prof Curtin tells me. “So, if you inhibit PARP, thereby preventing single-strand breaks from being repaired, any cell that is replicating, such as a cancer cell, will be dependent on the homologous recombination pathway for the repair.

If that option is unavailable because of a mutation in BRCA1 or BRCA2, the cell can’t repair the damage and will die.”

The beauty of this approach is that only the tumours contain cells in which the homologous recombination pathway is defective, and the PARPi are selectively targeting the defect that caused the tumour to develop in the first place. In the case of hereditary cancer, although the patient may carry a mutant BRCA gene from their mother or father, they still have a normal functional gene from the other parent, so can repair the DNA damage when PARP is inhibited. Only the cells in the tumour have lost the remaining functional gene. Within four years of Prof Curtin and Prof Helleday’s work, published in Nature in 2005, clinical trials with PARPi showed they were effective in treating BRCA mutationassociated cancers without causing serious side effects.

This was a real paradigm shift – a completely different way of looking at

The Development of Rucaparib/Rubraca: A Story of the Synergy Between Science and Serendipity Nicola J Curtin (Cancers, 2020) pubmed.ncbi.nlm.nih.gov/32121331/ Targeting DNA damage response pathways in cancer Florian J Groelly, Matthew Fawkes, Rebecca A Dagg, Andrew N Blackford, Madalena Tarsounas (Nature Reviews Cancer, 2023) pubmed.ncbi.nlm.nih.gov/36471053/ Poly (ADP-ribose) polymerase inhibition: past, present and future Nicola J Curtin, Csaba Szabo (Nature Reviews Drug Discovery, 2020) pubmed.ncbi.nlm.nih.gov/32884152/ DNA repair dysregulation from cancer driver to therapeutic target Nicola J Curtin (Nature Reviews Cancer, 2012) pubmed.ncbi.nlm.nih.gov/23175119/

w Prognosis—33

treatment. In fact, when Prof Curtin and her colleagues initially began their research into PARP inhibitors, this was not the end use they had in mind. Instead, they had been looking for a way to block repair in cells damaged by chemotherapy and radiotherapy. “Before discovering the synthetic lethality approach, the main treatment involved blocking things that gave cancer an advantage. The key realisation was that you could exploit a tumour-specific defect – one that probably caused the cancer in the first place – without harming normal cells. That’s what makes it so beautiful.

You are homing in on a cancer-specific vulnerability to give a truly tumourselective therapy.”

However, BRCA1 and BRCA2 are not the only proteins involved in the complex, multi-component pathway that is homologous recombination DNA repair, and a defect in any one of the other components could also compromise a cell’s ability to repair their DNA by this method.

Prof Curtin had suspected that the frequency of BRCA mutations found in ovarian cancers – around 20% – underestimated the proportion of ovarian cancers where the homologous recombination pathway was defective.

“If this was true then many more ovarian cancers would be treatable with PARP inhibitors,” Prof Curtin explains. “I was lucky enough to get to work with some gynaecological oncology surgeons. We developed a way to test whether tumour samples from the patients were deficient or proficient in this key DNA repair pathway.

34—Prognosis

We were the first to show that the homologous recombination pathway was defective in 50-60% of randomly selected patients with ovarian cancer tumours. Clinical trials with Rubraca and other PARPi now also show benefit in tumours where this pathway is defective irrespective of their BRCA status.” Six PARP inhibitors (four in the USA and Europe, plus two in China) are now approved to treat several cancer types (ovarian, breast, prostate and pancreatic) associated with the homologous recombination pathway and BRCA mutations. It is likely that other tumour types will be added in the future as our ability to test for the defective homologous recombination pathway increases.

“It has been a long journey, with some remarkable bits of luck along

I admire people who fight against injustice, like Nelson Mandela, and making a difference has always been really important to me.

the way. The first was the chance rearrangement of a chemical compound while it was being synthesised that gave us a compound which was about 50 times more potent than the one we were trying to make,” Prof Curtin says with a smile. “Another was entering into collaboration with Agouron Pharmaceuticals, who did structure-based drug design. The work they did enabled the design of PARP inhibitors that were a better fit – more selective and more potent.” Possibly the most significant piece of luck, though, was the synergy between Prof Curtin and Prof Helleday with their complementary interests in translational biology and DNA repair.

The question obviously arises as to whether this work had led to treatments for genetic conditions other than cancer, but the professor is not sure. “I don’t know whether the type of DNA repair defects that PARPi exploit are found in other diseases.

However, there are other potential applications for PARPi. In normal non-dividing cells that have plenty of time to repair their DNA, too much PARP activation can actually be a real problem,” Prof Curtin explains.

“This is because it consumes the cells’ NAD stocks.” Nicotinamide adenine dinucleotide (NAD) is a coenzyme that is central to metabolic activity.

As the cell tries to make more NAD, it catastrophically depletes its energy stocks and dies. This might happen when there has been an interruption then resumption in blood flow – for example, in heart attacks, crush injury trauma, organ transplants, or with infection or inflammation, all of

which can cause an increase in oxygen radicals that cause DNA singlestrand breaks, PARP activation, NAD depletion and cell death. “Animal studies have shown that PARPi can reduce cell death and make the animals more likely to recover, so there are definitely areas in which PARPi research will prove useful.”

I ask Prof Curtin about her motivation.

When she first entered the world of science, she couldn’t have foreseen that she would play such a central role in the initial breakthrough and subsequent translation of that discovery into a medication that is helping people across the world.

What drove that initial foray into the laboratory? “I first became fascinated by biology because of how wonderfully clever it all was; for instance, how interdependent animals and plants are: one needs CO2 and releases oxygen and the other needs oxygen and releases CO2,” she replies. “I didn’t have any scientific role models or some grand plan, but I was given a deep social conscience and a desire to ‘make a difference’ by my dad. I admire people who fight against injustice, like Nelson Mandela, and making a difference has always been really important to me.

That’s why I jumped at the chance to be part of the Anticancer Drug Discovery Group at Newcastle.”

Prof Curtin demonstrated the depth of her commitment to making positive change in the lives of others when she received from Newcastle University her share of six years’ worth of royalty payments. This ran into the hundreds of thousands of

pounds, but none of it was ever likely to be spent on luxury holidays and personal treats. “It was an enormous sum, rather like winning the lottery,” she says. “But I was paid for my work, and I already have everything I need, so it just felt wrong to take it for myself.

I have had a lot of luck and I wanted to do something for people who don’t have the same opportunities as me. So, I set up the Curtin PARP Fund, which stands for Passionate About Realising your Potential at the local Community Foundation. The aim of the fund is to help people realise their potential by overcoming barriers to education and training. A little money goes a long way in the charitable sector. The first grant was just £1,000 to a young carer for a laptop, but it enabled her to get her qualifications and earn promotion at work. We have had specific calls for arts and culture, environment and conservation, and English language classes for asylum seekers and refugees.

The feedback from these projects is so great, it makes me so very happy. It’s set up as an endowment fund, meaning only the interest on the capital is used, so it will still be going when I die and my daughter takes over my role.”

Rubraca is effective in 50-60% of the cases for which it is prescribed. It means thousands of women finding themselves facing the situation Angelina Jolie did all those years ago now have more of a choice about how to proceed, while those who do develop the cancer have a greater chance of recovery. It also means that Professor Nicola Curtin can add ‘philanthropist’ to her long list of accomplishments.

The Academy of Medical Sciences 41 Portland Place London W1B 1QH 020 3141 3200 acmedsci.ac.uk Prognosis—35

Mr Tom Routledge, consultant in thoracic surgery at HCA Healthcare, on a pioneering procedure that has the potential to transform the diagnosis of lung cancer Words: James Rampton

THE ION AGE

36—Prognosis

w Prognosis—37

90% This new procedure takes away that guesswork element and allows us to offer a safe, high-accuracy – 90 plus per cent – biopsy for pretty much everybody with an abnormality in their lung, whether it’s big or small, and wherever it is within the lung.

On the wall of his office, the thoracic surgeon Mr Tom Routledge has a small but heartfelt handwritten message.

It reads simply: “Thank you, Mr Tom.” Despite being a world leader in his field, Mr Routledge is very British and self-deprecating about what he does. At one point, he jokes that his extraordinarily high-powered work is really down to “nice technology. I just sit there and turn it on.”

All the same, Mr Routledge will admit that it is very gratifying to receive such notes as the one pinned to his office wall. “Sometimes, you can’t see the wood for the trees in this job. You’re so caught up in the technicalities, you can lose track of the fact that there’s a human being there.”

However, it has been Mr Routledge’s experience that, “The more advanced I get in my career, the less I focus on the satisfaction of the technical procedures, because they become second nature, and the more I refocus on the human side of things and take my professional satisfaction from getting that right. The satisfaction of seeing somebody have a burden lifted from them is greater than everything else.”

Lately, he has felt that satisfaction more and more frequently. He has been at the cutting edge of lung cancer treatment, and his work in the area is proving truly groundbreaking.

In his role as a senior thoracic surgeon for HCA Heathcare UK, Mr Routledge – who is also chief of thoracic surgery at Guy’s and St Thomas’ NHS Foundation Trust – has helped pioneer a game-changing technology called the Ion system. Along with robotic, minimally invasive surgery, this new approach has drastically improved the prognosis for patients. The system aims to radically improve the early diagnosis of suspected lung cancer – and so far the success rate has been quite dramatic.

38—Prognosis

In the past, this cohort of patients has not been well served by medical science in Europe. Mr Routledge, who has been working out of HCA’s London Bridge Hospital, the first private hospital in Europe to offer the robotic-assisted technology, explains that before this great leap forward was made with the Ion system, the diagnosis of lung cancer was usually made by CT-guided percutaneous biopsy. “This is a procedure that involves puncturing the patient’s chest wall with a large needle while they are awake in a CT scanner.

The weaknesses of that procedure are firstly that it can only hit relatively large tumours, so it is too inaccurate to reliably biopsy small tumours. Also, it is often painful, and has a significant risk of a pneumothorax, which is a collapsed lung.”

The surgeon, who studied at both Cambridge and Oxford, adds that, “of those weaknesses, probably the greatest that this new technology addresses is that no procedure is now limited in terms of which tumours can be biopsied by their size or by their location within the lung.

Many areas were not accessible before because they were, for instance, blocked by the scapula or too high up or too deep within the lung or too close to the big blood vessels. So it was an unpleasant procedure. For many patients, maybe even the majority with a possible tumour in their lung, it just wasn’t something that could be done. We were faced with having to make a decision as to what to do based on the scan only and educated guesswork.”

But the Ion system has transformed all that, bringing about a sea change in the diagnosis of lung cancer. “This new procedure takes away that guesswork element and allows us to offer a safe, high-accuracy – 90 plus per cent – biopsy for pretty much everybody with an abnormality in their lung, whether it’s big or small, and wherever it is within

the lung. So many patients were previously sentenced either to an unpleasant procedure that had some risk or, even worse, to living with the uncertainty about what this thing in their lung was. But now we can offer them and, of course, the medical teams looking after them, the assurance of a safe and reliable diagnostic technique.”

In addition, the Ion system greatly reduces the risk of the highly dangerous “interval cancer” where the cancer spreads between scans. According to Mr Routledge, “the standard clinical pathway for somebody who had a small thing in their lung meant that there were only really two ways ahead. One was to go straight for surgery, if surgery was feasible, depending on where in the lung it was. The downside of that is you may end up having a major operation for something that could be harmless. A lot of these things turn out not to be cancers, even in patients who’ve had a previous cancer. The other, more common option was to take an interval scan. That meant doing another scan in three months’ time and seeing whether the abnormality in the lung was growing and therefore more likely to be a concern.”

The problem with that is that patients have to live with the anxiety and the uncertainty for months and months before the situation becomes clear enough to offer treatment. “This new method really removes that painful wait-and-see approach and also removes any risk during that interval of any tumour growing and spreading dangerously whilst we’re sitting on our hands.”

The surgeon goes on to detail how the Ion system actually works. “It’s a combination of two technologies, one of which is very new and another that is less new, but has not been used in synergy in this way before.” The less new technology is an

in-room CT scan which can, if necessary, perform multiple, quick, 30-second scans during a procedure to make sure that our biopsy is in the correct place.

“The new bit is the way we get to the correct place,” Mr Routledge continues. “It’s a bronchoscopy. Conventional bronchoscopy involves manually understanding the anatomy, but it can only take you so far. The airways inside the lungs are like a branching tree, and the airways are dividing all the time into two and three branches. Because of the size of the scope, and because of your ability to manually navigate by your understanding, conventional bronchoscopy can only take you out to about the second division. This new scope uses, if you like, a Google map of the tiny backroads of your lungs, taken from your CT scan. Then it computes that and it calculates an AIgenerated path to exactly where your tumour is. It shows you that path. So part of the technology is this computer-generated navigational map which allows us to navigate from inside your lungs to exactly where the tumour is.”

That is already astounding. But there is more. “Part of the new technology is the fact that this bronchoscope is very small,” Mr Routledge continues. “It has what’s called shapesensing technology. That means that as you’re navigating this scope, it takes a number of twists and turns through the lungs. And to avoid you getting lost within your own map, it has something like a GPS. It knows where it is – not from satellites, obviously, but from this shape-sensing technology.”

And so, “the endoscope understands the exact curvature and direction that it is going in and knows where it is within the map. And that combination of the shape-sensing technology, which is like the flashing GPS on Google Maps, combined with the sophistication of the map-generating software means that you can with a high degree of reliability w Prognosis—39

Maybe the greatest strength of this procedure is the removal of anxiety.

We can now relieve that stress and say: ‘Come here next week, and we’ll get an answer straightaway in the room.’

get to where you want to go.”

The success of the Ion system speaks for itself. “We have done over 20 biopsies so far,” says Mr Routledge. “Some of them have been quite technically challenging, but we have 100% success rate so far. In the past, many of those biopsies would just not have been possible. It’s not just that this success rate with conventional CT guided biopsy would have been impossible – it simply wouldn’t have been possible to even try. We would have had to arrange treatment or surveillance for them without any biopsy. And that would have meant you’re shooting in the dark and inevitably getting things wrong from time to time. So patients would have had unnecessary treatment or delayed surgery. But now that has all been avoided.”

The future possibilities of this brand-new technology are equally exciting. Mr Routledge says: “The next step is that we’ll be rolling it out towards the ability to treat tumours in the lung. So once we can navigate out and put some kind of needle into a tumour, the first thing we do is to biopsy it. But we are also looking at whether we can introduce various types of electrical or thermal treatment or even drug treatment by direct delivery into the tumour.” Another potential game-changer.

The most significant and unacknowledged upside of the Ion system, though, might be the fact that it takes away so much of the patient’s stress. In Mr Routledge’s view, “maybe the greatest strength of this procedure is the removal of anxiety. As a doctor, I’ve had this conversation with countless patients where I say: ‘Oh, there’s a little something in your lung. We don’t know what it is, but come back in three months.’ And we’ve actually become rather comfortable with that conversation because that’s what we’ve got to offer.”

40—Prognosis

But if you’re a patient, that’s a horrible thing to live with. “If you’re being followed up for bowel cancer, or breast cancer, and there’s something in your lungs, and who knows what it is, just having the doctors shrug their shoulders and say: ‘We’re not in a position to do anything now, you’ll have to come back’ – that’s a terrible uncertainty to live with. We can now relieve that stress and say: ‘Come here next week, and we’ll get an answer straightaway in the room.’ So, there’s no waiting around for the test results afterwards. That’s a huge relief of that great burden of anxiety and uncertainty.”

Doctors generally go into the profession because they want to help people by treating them. But, Mr Routledge contends: “That relief of anxiety is actually as important.

Removing the stress is an enormous benefit. The message we want to get out to doctors and patients as well is that if you’ve been told there’s something in your lungs, come and see us, and we can tell you what it is in a way that, frankly, nobody else in Europe can do at the moment. To be able to relieve that suffering in that way is a great privilege.”

Mr Routledge proceeds to reveal what the reaction of his patients thus far has been to his revolutionary treatment.

“First, they’re amazed by how well they feel afterwards. They wake up a half an hour later and go home feeling essentially completely fine. Also, the fact that they wake up, and we can give them an answer straight away, is a fairly magical thing.

Patients have woken up, and I’ve had a conversation with them saying: ‘Yes, it is a tumour, but that we can arrange an operation for you in two days’ time.’ The fact that we can take somebody from possibly facing months of uncertainty, to having an answer and having a definitive treatment, and being free of cancer again by the weekend – that’s an extraordinary change from where we were before.”

As the Ion system spreads across the world, it will undoubtedly prolong millions of lives. I wonder how that makes Mr Routledge feel. “Certainly,” he says, in a typically modest fashion, “it’s a fabulous way to earn your living.”

Could the surgeon ever imagine having done anything else? “I used to want to be an investigative journalist writing big articles in the Sunday colour supplements.”

I doubt he regrets not following that particular career path now. It’s fair to say that as a doctor helping to transform the health of humanity, he’ll be remembered rather more fondly than any journalist.

HCA Healthcare UK lungnoduleclinic@hcahealthcare.co.uk hcahealthcare.co.uk

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Boris Johnson’s reaction was succinct, but not subtle.

According to information recently disclosed at the UK Covid-19 Inquiry, when the then prime minister was handed a document in October 2020 describing the symptoms of long Covid, he replied by writing a single word across the page: “Bollocks.”

Unfortunately, this one-word response was emblematic of the official refusal to take long Covid seriously. The then prime minister was, very neatly, summing up the authorities’ disdain towards the condition.

At the public inquiry, Professor Chris Brightling, professor of respiratory medicine at Leicester University, made his feelings quite clear about Johnson’s reaction:

“I’m deeply saddened and extremely angry at the same time.” Brightling continued that Johnson’s reply was “clearly wrong because the science was already quite compelling that this was a problem. Is it bollocks to the patients because he actually didn’t really feel that they deserved a voice?”

One consequence of this blinkered attitude at the heart of power, and the subsequent lack of government funding for research into the condition, was that thousands of people in the UK suffering the brutal effects of long Covid were left feeling abandoned. There is now some cause for hope – thanks in part to Dr Steven Allder, the eminent consultant neurologist who is leading very encouraging new research into the condition at Re:Cognition Health, a

THE LONG GOODBYE

Dr Stephen Allder, consultant neurologist at Re:Cognition, on the battle to unravel the mysteries of long Covid, a condition blighting the lives of millions across the globe Words: James Rampton

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cutting-edge medical company in the Harley Street Medical Area.

Dr Allder – also, one suspects, quite angry – begins by assessing Johnson’s crude and ill-informed dismissal of the very idea of long Covid. “It’s all about denial. The downstream implications of the pandemic, and everything that’s happened from it, are huge. I think the compassion and empathy which that requires of a leader is just way beyond Johnson’s capacity – which is why he said long Covid is bollocks.”

The neurologist, whose main focus has been on traumatic brain injury (TBI), and functional neurological disorders (FND), underlines the sheer scale of the problem: “The numbers are terrifying. In March 2023, there were 650 million people infected with Covid

w Prognosis—43

worldwide, of whom the researchers think 10% have got brain fog, a common symptom of long Covid. That’s 65 million people globally.” The current population of the United Kingdom stands at around 67 million.

These figures make such derision about the existence of long Covid appear even more wrong-headed.

“When you think about it,” Dr Allder says, “there’s no other medical problem that exists on the scale of this, potentially. It’s bit like climate change.

It’s so big that you can’t acknowledge it. Were you to acknowledge it, the existential grief would be hard to grapple with.”

He adds: “You hear on the news that the post-pandemic NHS waiting list stands at 7 million people. I would make graphs predicting all the scenarios that the NHS faced in 2011. I never would have imagined it could have got to this state by 2023.

But what that means is that if Johnson wanted to take long Covid seriously, he would have had to acknowledge that his administration had overseen the biggest degradation of the health service in the UK’s history. It’s just completely inadequately positioned to rise to this new challenge.”

All is not lost, however. At Re:Cognition Health, Dr Allder has thrown his considerable expertise into attempting to overcome the immense difficulties posed by long Covid.

It was the challenge involved in unravelling such medical mysteries that first drew Dr Allder to the field of neurology. “I did a brilliant medical rotation; we did heart, lungs, bowels, etcetera, but generally, it became quite predictable,” he says. “You know that people get chest pain when they walk up a hill and that they cough when there’s more pollen in the air. Most of those specialities quickly became quite technical and surgical. Whereas with the brain and neurology, it was just fascinating. It was like getting paid for playing Sherlock Holmes!”

He came to be involved in researching long Covid through his enduring fascination with the stillcontroversial field of chronic fatigue syndrome (CFS). “I’ve always been very interested in chronic fatigue syndrome, and I was looking at all the evidence for it. And it was then that I realised how polarised the world is. It’s very contested. Some people are saying: ‘It’s all psychological.’ And other people

are saying: ‘It’s biological.’ It is very difficult for people in that field trying to synthesise the information into a firm position because whichever conclusion you draw, you upset one group or the other.”

Dr Allder, who is also the primary investigator on several global Phase 3 studies relating to Parkinson’s disease, continues: “The symptoms of chronic fatigue manifest because of biological changes in the person’s brain.

It’s not that the person is weak-willed or anything like that. A set of circumstances have shaped the brain in a way that means it’s now generating these genuine symptoms. So, I’ve got absolutely no sympathy for the argument that people are making stuff up. These people are genuine, and they deserve the same amount of support as someone who’s got MS or Parkinson’s disease. To my mind, there is no difference.”

His expertise in CFS helped Dr Allder spot the similarities when long Covid appeared. He reflects: “When long Covid came along, it was scary for all of us. I could immediately see the same polarised camps emerging.

So, one camp insisted: ‘This is all psychological, everybody’s stressed.’

And the other camp said: ‘No, this has

I found a group in Australia that had been doing serial scans looking at the connectivity of the brain.

They were absolutely clear that the problems caused by long Covid are located in the control centres of the brain.

Certain things there are not working. When you see it through that lens, it makes perfect sense.

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got a more biological basis.’”

Very rapidly, the doctor realised that, like CFS, Covid had a very severe neurodegenerative impact on people.

“As the disease emerged, I could see how serious it was. I thought, oh my god, this is really terrifying. It quickly became clear it had multi-system effects on the lungs, heart, the whole body. But it also became obvious relatively quickly that Covid itself could produce two things that from a neurological perspective were really quite nasty. It could cause major neurological complications, like encephalitis or venous strokes. But there was also this condition we’re calling long Covid, with fatigue and brain fog as its signature features. Importantly, this was even affecting people who had only had a mild infection.”

In co-operation with a series of international partners, Dr Allder has swiftly made great strides in identifying that residual virus in the brain may well be contributing to long Covid. He explains: “We’re at a point now where we’ve got a pretty good idea of what may be happening. We’ve got an embryonic idea of what model of testing would be optimal. We’re also trying to work out what treatment options there are and how best to

deliver them. Do you deliver it on a named-patient basis? Or do you try to link with people doing clinical trials, which at Re:Cognition is our day-today bread and butter?

“When I started investigating, I found a group in Australia that had been doing serial scans looking at the connectivity of the brain in patients with CFS. Their work inspired me to look at the possibility of an equivalent problem in long Covid. A French group using PET imaging found a very similar problem in long Covid. The doctors discovered a similar pattern of brain stem involvement was present in patients with long Covid. When you see it through that lens, it makes perfect sense of the symptoms that patients complain of.”

Dr Allder goes on to detail what possible treatments for long Covid he and his team may be able to find: “The brain fog is the core ongoing symptom. If you take poor old monkeys and you give them Covid, and you follow them every week for about seven weeks, and you scan their whole body, all of them have a brain full of virus and inflammation in the first few days. That builds up to about day seven, and then goes down.”

It is clear, he says, that the virus is triggering brain inflammation in the majority of people. “The reason why people are getting long Covid symptoms in a subgroup with brain fog and fatigue is probably because they have got residual chronic brain inflammation.” In other words, the brain inflammation caused by Covid simply does not go away as the patient recovers.

Dr Allder has been concentrating on how the systemic immune system responds to the disease. After a person has had Covid, he asks, “does the immune system then become abnormal going forward? Does it fail to clear the virus, so you get left with little sumps of virus that are triggering problems?

Does that immunological change lead to little micro clots that are still hanging around, or even make your blood vessels generally much more irritable than they should be?”

The good news is, there may be hope on the horizon. The neurologist’s prognosis is that, depending on which variant of Covid you have had, “we may be able to give you a short course of a monoclonal antibody that fixes your antibody hole and allows you to clear the virus and get better”.

There’s more. “If you have got micro clots, there are various blood-thinning

treatments you could try. Looking at the brain inflammation, there’s quite an exciting finding that shows there is one particular cytokine [small proteins that play an important role in how cells communicate with each other], which seems to be particularly elevated.

We are developing a blood test for this and thinking about the best way to tackle it.”

There is now a growing understanding that finding effective treatments for long Covid is of urgent importance both to the individuals it affects and to wider society. According to Dr Allder, “researchers are starting to look at workforce numbers and saying that the peak age to get long Covid is 36 to 50, so it’s hitting people in the prime of their life.” As a result, “there are a lot of entrepreneurial people who have been affected and are banding together to try to move towards treatment trials.

You have to try and link everybody together.” Creating those links is central to his role at Re:Cognition: “It’s extremely complicated, it’s very multidisciplinary and the current systems are very siloed. I head up neurological clinical services, so I’m the person who’s coordinating with our various partners to try to move the research forward.”

Before we part, Dr Allder pauses to consider what makes his job so satisfying. “It’s wonderful to feel you can contribute to a project like this.

But the best bit is being able to sit with people and let them know that you’re actually listening to them and taking them seriously. Even if I don’t know the answer, or no one knows the answer, or you can’t do very much on a clinical level, being in an environment where you’ve got the time to really engage with a person and their family is great.

It makes them feel seen.

“If you can then move to defeating or solving the problem, then that’s pretty cool. However, there’s so much in medicine where that isn’t the case. But I’ve been amazed at what a difference it makes just to listen and let the person speak and tell their story without being interrupted, without being rushed.

That has such a massive impact on people. I have found it incredibly rewarding to be able to do that.”

Re:Cognition Health 77 Wimpole Street London W1G 9RU 020 3355 3536 recognitionhealth.com Prognosis—45

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Q+A

Lifestyle psychiatry Dr Mihaela Bucur, consultant psychiatrist at All Points North, on an emerging field of psychiatry that provides a more holistic view of mental health treatment Interview: Viel Richardson Images: Christopher L Proctor First things first, what is lifestyle psychiatry?

Lifestyle psychiatry is a newly emerging field in the area of mental health which focuses on the interface between lifestyle and mental health.

As such, it has real implications for prevention, which is so important in psychiatry. It focuses on the connections between mental health and physical wellbeing. It is an extra approach to be used alongside more established traditional treatments like medication and psychotherapy. Patients, particularly those with severe mental illness like schizophrenia, statistically have a lower life expectancy, with higher risk of developing cardiovascular diseases or difficulty maintaining healthy lifestyle habits. As we

increase our understanding of the complex relationships between the mind and body, there is huge scope for improving a patient’s mental and physical health with lifestyle interventions.

Can you expand a little on the word ‘lifestyle’?

We are part of the wider movement of lifestyle medicine that increasingly acknowledges the real impact of factors such as physical activity, diet, sleep, relationships and stress management on our physical and mental health. Lifestyle factors such as these could impact the treatment plans psychiatrists recommend for different conditions, particularly chronic conditions. Lifestyle psychiatry refers to the use of lifestyle interventions to Prognosis—47

w

We now have a much wider understanding of how all aspects of our daily lives – our relationships, environment, working conditions and physical health – are interconnected with our mental wellbeing.

manage mental health conditions and promote wellbeing.

What is the underlying philosophy of lifestyle psychiatry?

The American College of Lifestyle Medicine codified six interconnected ‘pillars’ that support a healthy body and mind. These are nutrition, physical activity, restorative sleep, stress management, avoidance of risky substances, and positive social connections. The lifestyle psychiatry approach acknowledges the interconnectivity of these six pillars.

It looks holistically at a person without separating mental health and physical health.

This means understanding, and acting upon, each patient’s uniqueness and individuality.

In more traditional types of psychiatry, patients have a more passive role, being the recipients of a certain intervention from the healthcare professionals who recommend a form of treatment to reverse or stabilise a symptom.

The difference in lifestyle psychiatry is the much more collaborative nature of the relationship between clinician and patient, which is vital in increasing the probability of the treatment plan being fully engaged with. As clinicians, we are of course responsible for any medical advice, but we also have a coaching role in helping navigate any lifestyle modifications or interventions.

How does this differ from the traditional approach in psychiatry?

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I have practiced psychiatry for more than two decades and have worked in all areas, from acute in-patient settings to community work and primary care. I saw that a lot of the time the care is disjointed. You have a symptom, you see a therapist, you get a diagnosis and usually some medication, then you see whether the symptom disappears. After that, it stops, most of the time. With a lot of patients, aspects of their lifestyle have played a significant role in the development of their depression, anxiety, phobia or other issues, but there’s been a lack of acknowledgement that supportive interventions could have had a real positive impact. Also, the majority of the patients I see have physical health issues which are dealt with on completely separate treatment pathways. It shouldn’t be like this.

As a lifestyle-focused psychiatrist, I act as medical expert and coach and should be able to assess the social, psychological and biological predispositions that drive a patient’s lifestyle behaviours and the resulting health outcomes. I also develop strong collaborations with general practitioners and other colleagues from different medical disciplines.

What is driving this field forward?

What need is it meeting?

Although healthcare has transformed considerably over the past decade, in psychiatry our approach to care hasn’t changed that much. But we have a much wider understanding of how all aspects of our daily lives – our relationships, environment,

working conditions and physical health – are interconnected with our mental wellbeing. There is a need for a more holistic approach. There is a rapidly increasing body of evidence on the impact of lifestyle choices on certain mental health conditions.

Take physical activity: there is no medication in the world that can match the combined positive effects of physical activity on a person’s body, soul and mental wellbeing.

The National Institute for Health and Care Excellence (NICE) now lists physical activity as a treatment option for depression in its clinical guidance. Emerging studies on the positive impact of Mediterranean diet show that aspects of the culture such as family meals being eaten together around a table are just as important as the food itself. Sleep is of paramount importance. Simply improving the quality of sleep can significantly reduce symptoms in several conditions. Some studies have suggested that loneliness, particularly in the older population, can be as harmful as smoking. The drive is to try to bring treatments of the six pillars under one umbrella to focus on whole health. The key is integration.

What can the patient expect from this form of treatment?

It starts with the same comprehensive assessment you would do with any patient: their medical history, developmental history, family circumstances, and so on. In addition to this I strive to understand their lifestyle at that particular moment: their engagement in physical activity,

the impact of stress and any stress management techniques, their eating habits, their sleep habits, their social connections at work and at home.

Understanding all of this, I can design a lifestyle treatment plan together with the patient that may include more traditional treatments such as medication and other specific forms of therapy but also an integrated lifestyle plan. Here at All Points North, I am fortunate to work with an amazing multidisciplinary team and we have established a joint approach to care. I work every week with our nutritionist, our head of fitness therapies, addiction specialists and others to ensure we are creating a well thought-through plan, tailored to each patient.

How would developing that lifestyle plan work?

Let’s take physical activity as an example. We know that the NICE guidance for depression is to do about 150 minutes of moderate activity per week. I would talk to the patient about how we might reach that. We would make a plan to get there over a certain period of time. Together, we define how that intervention will work for them. When are they going to do it?

Will someone do it with them? What will the barriers be? If it’s rainy, will they still go outside? If they feel tired or low in mood, what will help ensure they still do some activity? You want to build a structure that will help the patient maintain the new behaviours.

The most important aspect is the level of confidence they have that they can maintain the changes. We

underpin our planning by using our understanding of the basic principles of how behaviour changes. We will take the same approach to diet, sleep, social interactions and other aspects of the patient’s life.

How involved are other clinicians in developing the plan?

We work very closely as a lifestyle psychiatry team to provide a comprehensive approach that addresses the patients’ mental health needs and supports lifestyle changes for improved mental wellbeing. The team, which typically consists of professionals from various disciples such as psychiatrists, therapists, nutritionists, fitness instructors among others, also plays a crucial role in monitoring progress and adjusting treatment plans as needed. Each week we review the patient, checking in on their progress. Are they engaging with sleep hygiene measures, or doing well with stress management? Can we tweak their plan to be more supportive in places where they are struggling with engagement? If the patient has had substance misuse issues, we will work very closely with our addiction counsellors and other therapists to provide specialist advice in this area.

How do you define success?

It’s very important to discuss with the patient right from the beginning what good looks like to them in six months, one year, three years from now. Where do we need to shine the light, where do we want to get to?

Those are always important questions in psychiatry, but particularly in

lifestyle psychiatry, as we need to define together what success looks like. Do we mainly look at reducing symptoms like low moods or are we looking to bolster a sense of wellbeing with the lifestyle interventions as well. Achieving these aims might lead to a reduction in the medication they need to manage depression, for example. Is this a primary objective or a nice-to-have, with finding a sense of balance and wellbeing being the primary aim? Success will look different for each patient and may change over time, so it is important to keep this at the forefront of any treatment plan.

What is it about lifestyle psychiatry that gets you so energised?

It is the whole-life approach. That is such an important aspect. It gives the work more meaning for me as a clinician. It has also shaped my relationship with my own lifestyle and I want to share this with my colleagues in healthcare. I enjoy working with and learning from so many disciplines within psychiatry. Working at the interface of psychology, nutrition, public health medicine and the many different aspects of mental health treatment is very exciting.

It’s part of the story of the evolution of psychiatry, and I want to be part of that.

All Points North 12 Upper Wimpole Street London W1G 6LD 020 7193 1128 apn.co.uk Prognosis—49

50—Prognosis

Patient experience Fiona McLoughlin on how cochlear implant surgery ended a decade of progressive hearing loss Interviews: Gerard Gilbert

Eleven years ago, I was working flat out in my job at a software company in Dublin but noticing increasing difficulty with my hearing. On my 36th birthday, I decided I really needed to do something about it.

So, I took myself for a hearing test.

I was sure it was wax or fluid on the ear. I certainly wasn’t thinking of hearing loss. But the chap doing the test informed me that I was moderately to severely deaf.

I just couldn’t believe it. I’d been functioning well enough.

He explained that it was a particular form of hearing loss known as ‘cookie bite’ – on the audiogram it looks like somebody’s taken a bite out of your chart. It’s a type that gets progressively worse and never stabilises. I’m 47 now and over the past decade I’ve probably owned six pairs of hearing aids. I kept having to get bigger ones because they couldn’t handle the deepening progression of my hearing disability.

I couldn’t hear things that were pitched at a particular level. So, I could hear the birds singing in the trees, but I couldn’t hear conversation. As a result, I was missing all the fun.

Alongside your hearing, another thing that goes is your confidence. I’m the vice-president of marketing in my organisation. If you can’t participate on calls, it’s really debilitating. My boss paid someone for six months to transcribe phone calls for me. While everyone was bantering on the call, she was typing furiously! Even your social life goes down the tube, because people insist on meeting up in pubs or other public places. You don’t want to go out, so you start getting really down on yourself.

Every time I went to get assessed in Ireland, people said: “You’re fine… you’re coping… you can lip read.”

I was told that I’d spent so long lip-reading, I didn’t even know I was doing it anymore. It was then that I realised that for me it was a case of

either getting cochlear implants or going completely deaf.

In Ireland we don’t have a private route for getting cochlear implants – there’s only public funding for 15 to 20 adults every year. I was really lucky because I’d been at the software company for a while and had health insurance, so I was able to go private in the UK using that.

I reached out to Advanced Bionics, the company that does cochlear implant systems, and they recommended OneWelbeck. I had an initial consultation with Mr Jeremy Lavy and then in November 2021, right in the middle of Covid, I stayed in London for two weeks.

I went in on the Monday and had a couple of tests before being given a general anaesthetic. I then had an implant placed in my right ear. I was discharged an hour after coming round. Having had a bite to eat, my nephew walked me back to the apartment. There were no real Prognosis—51

w

Audiologist A healthcare professional who identifies, assesses and manages disorders of hearing, balance and other neural systems.

Pure-tone audiogram A test used to measure hearing sensitivity, testing both the peripheral and central auditory systems.

Cochlea A fluid-filled, spiral-shaped cavity found in the inner ear, which plays a vital role in the sense of hearing.

Ear drum The colloquial name for the tympanic membrane: a thin, cone-shaped membrane that separates the outer ear from the middle ear. The membrane vibrates when struck by sound waves, beginning the process that converts the sound wave into a nerve impulse that travels to the brain.

side effects – a couple of standard painkillers were all I needed to dull any discomfort. A few days later I got a bit of vertigo, but that was all.

When you first switch the implants on, all you can hear is a series of beeps.

I was kind of disappointed because I hadn’t understood that this was what to expect. Then I started doing speech therapy with a therapist who OneWelbeck had recommended – it involved a lot of repeating. I also listened to audiobooks. At the start, everything sounded very mechanical, like listening to a robot read to you.

But over time, you start recognising different accents and then the implant starts formulating near-natural sounds.

I was so pleased with the results that a year later I had my left ear done. When I put the two of them on together, the sound was amazing – much richer. It’s so beautiful. I couldn’t listen to music with just the one – I could hear it, but it didn’t resemble the tunes that I remembered.

It’s been really life changing.

Having the implants doesn’t preclude me from doing anything, so I’m still working. Without the implants I definitely wouldn’t be working today. I have a great social life. I can’t recommend it enough. I know a lot of people are really nervous about going for an implant, but I say – what have you got to lose? Otherwise, you’re on a one-way ticket to nothingness, to isolation, to loneliness, to depression.

I’m now mentoring people who are considering implants. It may not be 100% perfect but I couldn’t live without it.

52—Prognosis

WHAT IS A COCHLEAR IMPLANT?

Mr Jeremy Lavy, consultant ear surgeon at OneWelbeck

Fiona originally saw me two years ago, at which point she had had a nine-year history of progressive hearing loss. This affected both ears. She used hearing aids, which she’d worn since the first diagnosis.

While working full time, she had gone through progressive loss to the extent that, when she initially saw me, the hearing in her right ear had dropped so much that she was really getting no benefit from the hearing aid.

The first thing we do with patients struggling with their hearing aids is arrange a visit to our audiologist, who will attempt to re-programme the hearing aids to ascertain their maximum benefit.

But when people are getting towards severe hearing loss, it can be difficult to re-programme the aids to any meaningful effect.

Audiologists will also make an assessment using a pure tone audiogram, a standard procedure where you sit there with headphones on and they play a series of beeps at differing frequencies and you press the button when you hear it. We also do tests that assess the patient’s ability to understand speech – for most people, that is the thing they most want to be able to hear.

We wouldn’t consider a cochlear implant until we’d exhausted all the noninvasive treatments. Before we operate, we check the anatomy of the ears – so Fiona underwent both CT and MRI scanning. This gives us a view not just of the cochlea itself, which is where we’re going to put the implants, but also of the nerves that come out of the cochlea and into the brain. We want to be sure that they’re all normal and nothing untoward is happening.

The operation itself involves making a cut behind the ear and then drilling through the mastoid, which is the bone behind the ear. You drill in parallel to the ear canal, deep enough that you’re behind the eardrum. Then you drill forward, find the cochlea and insert the implant. The reason for that approach is that all the mechanics are protected behind bone. This means if you put something down your ear you don’t scratch it.

There is also a stimultor / receiver package that is placed beneath the skin behind the ear. This communicates with the external device , which is worn on the ear and has a coil that is magnetically attracted to the implant.

There are a lot of the clever electronics in this device that will take the sound and break it down into its different frequency components.

We can do the procedure in less than an hour and the patients come and go in less than a day. It’s a fairly straightforward operation, but one that demands an extraordinary amount of precision. With all cochlear implants, you’re drilling within about 1mm of the facial nerve – the nerve that provides all the movement to your face. You’re drilling between that nerve and the nerve at the front of your tongue that gives you taste.

Because of that, there’s no room for error.

For Fiona, the procedure has worked extremely well. It’s really satisfying that she’s so pleased with the results.

Welbeck Health Partners 1 Welbeck Street, London W1G 0AR 020 3653 2000 onewelbeck.com

Receiver

Transmitter Microphone

Speech processor

Prognosis—53

A BREATH OF FRESH AIR Professor Pallav Shah of Royal Brompton & Harefield Hospitals on how a new, minimally invasive treatment is providing hope for patients with chronic bronchitis Words: Gerard Gilbert

54—Prognosis

w Prognosis—55

Coughing throughout the day can be really rather debilitating, and there’s no medical treatment to stop a cough at the moment. We can make it easier to clear the mucus, but we can’t stop the mucus production.

Chronic obstructive pulmonary disease (COPD) is a group of illnesses that include emphysema and chronic bronchitis. The common thread is that all of them cause airflow blockage and breathing-related problems that are notoriously difficult to treat. If the patient develops an infection as a result of COPD, this can be treated with antibiotics. But until recently there has been no effective method of dealing with the underlying condition itself.

This is set to change, thanks to a minimally invasive method of treating COPD that involves using a metered cryospray technology called RejuvenAir. Professor Pallav Shah, a leading consultant physician in respiratory medicine, has been using this innovative method with COPD patients at the Royal Brompton & Harefield Hospitals, part of Guy’s & St Thomas’ Specialist Care. But what actually causes the condition and how would he define it?

“The best way to describe COPD is a constellation of conditions due to smoking,” says Prof Shah. “There are some other causes for it, like toxic exposure and air pollution.

For example, in Asia, people use a lot of indoor coal cooking stoves and constant exposure to that, or to the high levels of pollution seen in developing economies, could cause problems.

But the main cause of these conditions is cigarette smoking.”

Cigarettes, he continues, contain tar and nicotine, polonium (a highly radioactive element only harmful to humans if it’s inhaled or comes into contact with an open wound), hydrocarbons and all sorts of other toxins. “As part of our lungs’ defence mechanisms, whenever we’re exposed to any toxins or viruses our airways produce extra mucus.

The aim is for the mucus to stick to any toxic particles, then the cilia [tiny hairlike structures] in our airways waft that mucus away. It’s a protective mechanism.”

56—Prognosis

In its earliest manifestation, COPD sees patients creating a lot more mucus than is normal in healthy people. They also experience inflammation of the airways, which causes spasms that can lead to wheezing and breathlessness. As COPD advances, the patient will be prone to suffering more and more infections, and the flow through the airways will become irregular. And at the far end of the COPD spectrum is emphysema, where the air sacs in the lungs are damaged.

“The main symptoms are coughing and phlegm,” says Prof Shah. “Coughing throughout the day can be really rather debilitating, and there’s no medical treatment to stop a cough at the moment. We can make it easier to clear the mucus, but we can’t stop the mucus production. On the whole, there is currently no way of treating the cough of chronic bronchitis using traditional medicine.”

During the new procedure, which is carried out under general anaesthesia, a narrow tube with a light and camera at the tip – known as a bronchoscope – is inserted into the patient’s airways. Liquid nitrogen is then introduced into the patient in very specific doses by way of a special catheter.

This liquid nitrogen sprays the surface of the airway, freezing it to -196C, which destroys the top layer of the bronchial mucosa. This minimally invasive treatment targets the goblet cells, which are found in the top layer of airway tissue (the epithelium) and produce excessive amounts of mucus in patients with chronic bronchitis.

“It basically kills a very fine layer, about half a millimetre,” says Prof Shah. “That then stimulates the mucosa to regenerate from the stem cells. This newly regenerated mucosa may have fewer of the mucus-making goblet cells than the cells present in the patient at the time they were smoking. Basically, you’re just trying to destroy the upper

w Prognosis—57

In dermatology, people have skin peels where a chemical solution is applied to the skin to remove dead and damaged skin cells and stimulate the growth of new healthy ones.

Think of this procedure as doing the same in the deep airways of the lung.

layer and leave it so that you’ve only got this cleaner airway mucosa there.”

To help illustrate the concept, he provides a simple analogy. “In dermatology, people have skin peels where a chemical solution is applied to the skin to remove dead and damaged skin cells and stimulate the growth of new healthy ones. The aim is to restore the skin to a more useful condition.

Think of this procedure as doing the same in the deep airways of the lung. The real skill is in being able to control the liquid nitrogen. When it expands to form a gas, which it does instantly, the liquid nitrogen freezes whatever it touches to -196C, but the nitrogen expands to 700 times its volume.

So as you can see, you must release the nitrogen in a very specific way.”

There are some risks involved, such as the potential for a punctured lung if the gas doesn’t have an escape route. “But if you take care and do it properly, that risk should be minimised,” says Prof Shah, who has treated over 100 patients without any complications. “We haven’t experienced that problem to this point.”

The treatment is delivered over two sittings. The right lung is treated in the first sitting and then, four to six weeks later, the left lung is treated, along with the windpipe.

Each procedure takes about 45 minutes, with patients able to go home on the same day after recovering in the unit for between four and five hours. Are their symptoms completely gone after the procedure? “Not completely gone, but dramatically better,” says Prof Shah. “A lot of patients find they’re coughing a lot less, they’re producing less mucus, and they’re less breathless. Generally, they feel much better.”

One really pleasing aspect of the procedure is that it is repeatable. “We don’t know how long the effect lasts,” he says.

“It may last for many years, or it may be that people only need it once. My own suspicion is that over time the abnormal cells will start to come back again and we will probably need to repeat the procedure. But at the moment I’ve got patients who were treated three or four years ago who are not showing any 58—Prognosis

signs of needing to have the procedure repeated.”

While there is insufficient data to state categorically that this new treatment leads to fewer infections, Prof Shah believes that it will do so. He says: “Our intuition is that patients should be prone to fewer infections, but we haven’t proven it yet because the only way to do so is by comparing groups over a long time-period in much larger numbers than we have available now.

“To show a difference in infection rates between patients who are treated and patients who are not treated, you need data on around 5,000 patients. The studies done so far have been on smaller numbers – one study included something like 28 patients and we’ve just done another study on 32 patients.

We’re now conducting a larger study between us and North America with 240 patients.”

Prof Shah says that the treatment is better suited for people with mainly cough and sputum symptoms, and less so for patients who have reached the emphysema stage of the condition. “It’s more for the patient group that has the bronchitis type of COPD,” he says. “It may also be good for treating intractable cough but again we need to study that as well. We have some patients who basically just cough their lungs out – they have really quite severe coughing spells; they can’t control it and there’s no medication that’s been able to control it. And in that group of people, this might also be quite a clever and useful therapy that we may be able to use.

“We do a number of different procedures and this is just one in our armoury. I don’t think it’s a solution to everything but it tries to address a problem that is very difficult to solve at the moment, which is the chronic cough and mucus. It’s one very effective part of our toolkit.”

Royal Brompton & Harefield Heart & Lung Care 77 Wimpole Street London W1G 9RU 020 3553 9648 rbhh-specialistcare.co.uk

THE HARLEY STREET BUSINESS IMPROVEMENT DISTRICT Harley Street BID will be supporting Arab Health 2024 with a presence in the UK Pavilion and at keynote events.

We look forward to seeing you in Dubai.

The Harley Street BID has been established to promote the area and represent the exciting mix of businesses here.

In November 2021 the business community were invited to vote in the ballot to develop a business improvement district and there was an overwhelming “yes” for a BID to be established from the businesses. The BID term runs from April 2022 to March 2027. With the investment that will be made through the BID this provides opportunities to deliver projects across the key themes which are set out below.

STRATEGIC THEMES We have implemented and devised projects across our themes, identifying key priorities and building our steering group membership with our partners. Our 4 steering groups are set out below and we have a specific Medical Board in place for our business community.

PUBLIC REALM AND WAYFINDING

INTERNATIONAL MARKETING

BUSINESS SUSTAINABILITY AND CONNECTIVITY

SAFETY AND BUSINESS RESILIENCE

GET IN TOUCH If you would like more information on the newly developed business improvement district please do not hesitate to contact Nicki Palmer. Email: nicki@harleystreetbid.com Telephone: 07944 386903.

Follow us on social media:

@Harleystreetbid

Harley Street Business Improvement District

www.harleystreetbid.com

MY MARYLEBONE

Eat I’ve been to Fischer’s, and that’s really good. The food is outstanding. It has a Viennese menu that reminds me of my time in Munich and Austria. I adore the Kaiserschmarrn, which means ‘Emperor’s mess’. It’s a delicious kind of scrambled pancake. I also love the pubs in Marylebone. I especially like The Cavendish. It has great food and drink. I always start with the cider and then move on to the beer. I really like the lived-in quality of the old English pubs. I love their sticky carpets! Then, if I want a bit of feeding up, I go to Tommi’s Burger Joint. It’s just really nice, messy, simple food. Of course, I have all the toppings, from cheese and pickle to bacon. I’d rather live a short and happy life than a long and miserable one!

Professor Dr Christian Mehl, principal dentist at The Wimpole Street Dental Clinic

Fischer’s

Work At The Wimpole Street Dental Clinic, we’re working right in the heart of the medical district. We’re based on Queen Anne Street, right between Harley Street and Wimpole Street. I think Queen Anne Street is a bit of a secret – not as busy as the streets either side, and with very little through traffic.

It’s a great location for us.

Our dental clinic provides all the dental services you can imagine, from cleaning and whitening to really complex cases and even oral medicine, cancer treatment and aesthetics. We have three directors. I am the biggest shareholder and one of the directors.

Together with one of my colleagues, Dr Costa, I am the principal dentist.

I have always loved this area. It was always my absolute dream to come to Marylebone to practice dentistry, and now I have achieved my dream.

60—Prognosis

Shops I have to admit, I’m not a great shopper. I do love to stroll around the area, but normally it’s when I’m heading to the pub. So, while I’m not too bad on the pubs, I’m useless on the shops!

My wife does most of my shopping for me, especially my clothes. But I know that the shops are a great attraction in Marylebone. A lot of our patients travel from quite a long way off – from Wales, Scotland, Hong Kong or even further away – and they always combine dental visits with some shopping, which they adore. I may not go into the shops, but they do look fantastic. The buildings round here are amazing. In Marylebone, you really are immersed in history.

Culture I love the Wigmore Hall. It’s such a wonderful building and an iconic concert venue.

The interior is stunning. In London it always astonishes

me that the buildings look beautiful on the outside, but when you go in there’s often a whole other world behind their doors. I’m drawn to the Wigmore Hall because without music, my life would be much more miserable.

My favourite composer is Bach. I love his mathematical precision. I like numbers.

I like the universe to be in order – and look at the world right now! Bach always gives me the feeling that everything is going to be alright. When we listen to his music, we can understand the world a bit better. I grew up with classical music. My father was a professional musician. Everyone in my family is either a doctor or professional musician. As a teenager, I played the cello, but to become a professional musician at that stage you have to practice between six and eight hours a day.

But I was too lazy and not talented enough, so I had to choose dentistry instead!

Community I was born in a small village in Germany, and when I came to London in 2007, I fell in love with the city.

It’s like that moment when you meet a woman and you instantly fall in love with her. London had the same effect on me. Coming to a city that has such a long history, stretching back to before the Roman era, was just extraordinary. I love it to this day, specifically the Marylebone area. It teaches me new things every day. I love the fact that in this area there is so much medical knowledge and so many good colleagues. I’ve never seen anything like it.

It’s unique. But what I love above all else is how warm the people are in Marylebone.

England is the friendliest country in the world by a big margin. It is the most welcoming, accommodating nation on earth. Full stop.

THE WIMPOLE STREET DENTAL CLINIC 38 Queen Anne Street London W1G 8HZ 020 3745 7455 wimpolestreetdental.clinic

Wigmore Hall

Prognosis—61

WHAT’S ON MUSIC

EXHIBITION

EXHIBITION

SPOKEN WORD

THE AFRICAN CONCERT SERIES 17 February Wigmore Hall 36 Wigmore Street, W1U 2BP wigmore-hall.org.uk

WIDE-ANGLE VIEW Until 24 February RIBA Architecture Gallery 66 Portland Place, W1B 1AD architecture.com

THE LEISURE CENTRE Until summer 2024 The Brown Collection 1 Bentinck Mews, W1U 2AF glenn-brown.co.uk

REVOLUTION EARTH 7 – 8 March Marylebone Theatre Rudolf Steiner House 35 Park Road, NW1 6XT marylebonetheatre.com

Created by pianist Rebeca Omordia, The African Concert Series celebrates music and musicians from Africa, as well those of African heritage. In three concerts across a single day, double bass player Leon Bosch joins Rebeca for a wideranging selection of spirituals, pianist William Chapman Nyaho and percussionist Richard Olatunde Baker explore numerous piano works, and cellist and kora player Tunde Jegede teams up with the Lagos-based NOK Orchestra and percussionist Mohamed Gueye to perform a programme of African chamber music.

In the late 1960s, the Architectural Review magazine created a bold new approach to architectural journalism, photography and graphic design, the influence of which still pervades today. This free exhibition in RIBA’s Architecture Gallery shows off over 70 original photographs from the magazine’s groundbreaking Manplan series, which ran from 1969 to 1970.

The series, which included the work of renowned photographers such as Ian Berry, Patrick Ward and Tony Ray-Jones, explored architecture’s profound impact on society, religion, health and education.

RIBA

62—Prognosis

Based in a beautiful Marylebone mews house, The Brown Collection shows the work of contemporary British artist Glenn Brown, who appropriates forms and subjects from historic artworks and melds them together to create something distinctive and new. This exhibition combines Glenn’s own paintings and sculptures with those of artists past and present whose paintings and sculptures have become part of his personal collection. The title, he says, questions not so much what a leisure centre is but where the centre of our leisure might be found.

The Brown Collection

Poet and novelist Sir Ben Okri joins choreographer and dance artist Charlotte Jarvis to present a dramatic collision of poetry and movement, responding to the ecological catastrophe facing humanity.

Along the way, they explore themes of history, the secret lives of women, the passions of motherhood, and the toughness of hope.

Sir Ben Okri

WATCHHOUSE 32-34 New Cavendish Street London W1G 8UE watchhouse.com

EXHIBITION RANJIT SINGH: SIKH, WARRIOR, KING 10 April – 20 October The Wallace Collection Manchester Square, W1U 3BN wallacecollection.org

Five places to meet friends for coffee

HAGEN 82 Marylebone High Street London W1U 4QN thehagenproject.com

The Wallace Collection’s major exhibition for 2024 explores the life and personality of the great Sikh leader Ranjit Singh (1780–1839), who in the early 19th century conquered the Punjab, a region in northern India that today encompasses Pakistan, and became its undisputed Maharaja.

Through over 100 exquisite artworks, including jewellery and weaponry, the exhibition explores how Ranjit Singh’s reign brought about a golden age of trade, art and military might.

The Wallace Collection

With its modern design aesthetic, WatchHouse offers its customers the full contemporary coffee experience, with names like the Slayer Steam LPx espresso machine and the 3Temp Hipster brewer familiar to those on the cutting edge of the speciality coffee scene. Seasonal beans are roasted and brewed in ways chosen to showcase their unique characteristics.

A full brunch menu is available seven days a week to eat in and take away, as well as bakery goods, sandwiches, salads and more.

WatchHouse

In Denmark there is a notion of the ‘coffee pause’, which involves slowing down to celebrate friendship in a relaxed atmosphere with great coffee. Hagen’s Danish founder Tim Schroeder has created a cafe that, with its calm vibes and communal tables, evokes those two elements: coffee and friendship. Among its signature coffee varieties is Taplejung, one of the first speciality coffees made in Nepal, all profits from which go directly to the farmers.

They in turn ensure that their processing systems are sustainable, helping Hagen fulfil its aim to be carbon neutral at source.

ARRO COFFEE 67 Chiltern Street London W1U 6NJ arrocoffee.com Arro is a cafe that celebrates the Italian love of food and culture and acts as a haven for people who want to experience the flavour and feel of Italy. Its owners, who consider coffee an Italian

national treasure, offer a wide variety of coffees, from classic espresso to more creative styles. Gathering over food is a huge part of Italian culture and at Arro you will find a warm and inviting space to do just that. Enjoy authentic Italian pastries, sandwiches, salads and pastas made according to traditional recipes.

31 BELOW 31 Marylebone High Street London W1U 4PP 31below.co.uk This cafe and bar in the heart of Marylebone offers a small plates menu and an outdoor terrace on Marylebone High Street – a spot to sit and people-watch while enjoying a coffee on a sunny afternoon. The venue is dog friendly, so furry friends are also welcome. It can be a great place to catch up on emails during work hours and then shut down for the day and hang out with friends for the evening. As the night progresses, head on down to the basement bar to keep the fun going with a wide variety of cocktails.

LINA STORES 13-15 Marylebone Lane London W1U 2NE linastores.co.uk A recent addition to the area, Lina Stores has fast become a firm favourite with Marylebone residents and visitors alike. Housed on the corner of Marylebone Lane and Wigmore Street and set over two floors, it features a spacious all-day restaurant, fully stocked delicatessen and downstairs bar. Lina Stores is ideal for leisurely breakfasts or lunchtime catch-ups with friends over black angus beef carpaccio, bruschetta con acciughe e capperi, or linguine con granchio e limone. There is also a full range of highquality coffees available, including all the espressobased Italian classics.

Prognosis—63

a posh West End hotel, the Majestic, which is actually the Wallace Collection’s Hertford House building in Manchester Square.

Remarkably, the Wallace Collection manages to pull off a far more convincing impression of a hotel than Rea does of an actor.

Chandos House

THE GUIDE

FILM LOCATIONS CLOSE TO THE HSMA

REDS (1981) The magnificent Chandos House, one of the Georgian masterpieces of the Adam brothers, was done up as a Greenwich Village townhouse for Warren Beatty’s hugely ambitious Reds. The legendary Hollywood libertine wrote, directed and starred in this epic portrait of the radical leftwing journalist John Reed. In the film Beatty, playing Reed, dances with Diane Keaton, playing Reed’s lover Louise Bryant, in one of Chandos House’s grand reception rooms.

PARTING SHOTS (1998) For Parting Shots, Michael Winner gathered together the stellar talents of John Cleese, Oliver Reed, Ben Kingsley, Bob Hoskins, Diana Rigg and Joanna Lumley and somehow managed to create one of the worst films ever made. At one point, the film’s main character, played by singer Chris Rea, holes up in 64—Prognosis

In Reds, Warren Beatty dances with Diane Keaton in one of Chandos House’s grand reception rooms.

THE ITALIAN JOB (1969) In The Italian Job – the 1960s original, not the execrable 2003 remake – the most truly memorable scenes take place in Turin, where the Minis wreak havoc, and Crystal Palace where to the dismay of a young Micheal Caine, managing to look mismatched dressed in a disturbing variety of browns, more than the bloody doors get blown off. But Marylebone has a small supporting role: after taking a break from his incarceration at Wormwood Scrubs, Noel Coward’s dapper villain Bridger takes a stroll down Harley Street for a checkup with an expensive doctor.

THE 39 STEPS (1935) Alfred Hitchcock’s adaptation of John Buchan’s The 39 Steps. In the book, mining engineer Richard Hannay lives in an apartment at 122 Portland Place, from where he gets sucked into a terrifying world of spies and killers.

For Hitchcock’s film the building’s exterior was recreated in a studio, with the famously wide road dramatically reduced in scale. But there are also genuine shots of Marylebone, not least the beautiful sweep of Park Crescent East where Hannay (played by Robert Donat) abandons a horse and cart at the start of the picture.

A HARD DAY’S NIGHT (1964) In The Beatles’ first film, Marylebone station manages to play two different roles.

At the start, the Fab Four leave on a train from Marylebone, which is masquerading as Liverpool station. They travel through Paddington, and arrive at…

Marylebone. This time, there are huge crowds waiting for them, and they have to run away to prevent themselves from being torn limb from limb by sobbing baby-boomers. In Billy Liar, released the previous year, the station had shown admirable versatility by pretending to be Bradford.

It went on to play itself in Julian Temple’s The Great Rock ‘n’ Roll Swindle.

WITHNAIL & I (1987) Regent’s Park has been a frequent film location. Most gloriously, the Gloucester Gate entrance, which was once home to an enclosure filled with wolves, provides the backdrop for the closing scene of the peerless Withnail & I. Richard E Grant, playing the tired and emotional Withnail, serenades the lurking wolves with a heart-rending passage from Hamlet as the rain pours down around him.

The park also plays host to a memorable scene from David Lean’s masterpiece Brief Encounter (1945) where Alec, played by Trevor Howard, gets his tweeds wet when he falls into the boating lake.

THE LONG GOOD FRIDAY (1980) The site now occupied

by Cavita restaurant at 60 Wigmore Street was the setting for one of the many cracking scenes that make up The Long Good Friday – the film that makes any other London gangland thriller look like a laughable mockney pastiche.

Gangster Jeff, played by Derek Thompson, gets spat on by a relative of one of his victims while conducting a clandestine meeting with the corrupt Councillor Harris.

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