In Service to Our Smallest Patients

When you work at one of the foremost hospitals in the world, there’s an expectation that you’re always moving forward. Nowhere is this truer than at Great Ormond Street Hospital (GOSH) – a facility that serves an exclusively pediatric population, and one that provides the most difficult diagnostic and treatment challenges its staff have ever encountered. How do the pathologists and laboratory medicine professionals at GOSH tackle these medical mysteries? By recognizing the unique needs of their patient population – and by working together across disciplines and specialties.

Still a Hospital for Sick Children

As pediatric pathologists, we provide the voice that children don’t have. Children can’t tell doctors what’s wrong with them, so the doctors rely on pathology services to provide that information – even more so than in any other setting. What makes GOSH unique is that our doctors receive tertiary and quaternary referrals – and that means the whole team must take on the most complex of medical problems. And that’s why I often say that there is no “routine” in our routine service. In fact, I try to avoid the word altogether. Instead, we call ourselves Pediatric Laboratory Medicine – emphasizing our focus on children’s health.

I believe the doctors here understand that they would be somewhat at a loss without pathology services – so we’re lucky to have the scope to host a range of different specialties. For instance, we have a center for lysosomal storage disorders and other enzyme deficiencies; we have areas to deal with hematology, immunology, microbiology, histopathology, and much more, all at a highly specialized level. And though it’s certainly specialist work from an outside perspective, it doesn’t always seem like that to us – unusual is our normal!

That said, it’s not all esoteric – and we actively avoid change purely for the sake of change. Not everything needs to be updated just because it can be; if something already works really well – an enzyme assay, for instance – there’s no point in spending months trying to automate it; some assays work better manually, and we use quite a lot of them. But, at the same time, we’re investing significantly in mass spectrometry, because we can use that technology to analyze a wide range of metabolites in a single sample and get a very fast response. We feel very strongly about embracing state-of-the-art technology, but it must be adopted appropriately.

We also focus heavily on translational research here; I’m a biochemist by background, but as Head of Clinical Service for Laboratory Medicine, I also oversee hematology, immunology, microbiology, histology, and every other diagnostic specialty. I can see how closely they work together, and how much they might benefit from working even more closely. And that’s what drives our desire for a “combined omics” approach to diagnostics and monitoring.

Defining combined omics

Right now, in most hospitals, laboratory specialties are somewhat in silos. There is certainly crosstalk, but at GOSH, we’re pushing for a completely integrated service. Instead of individual specialties, we want to develop our labs by technology – enzyme assays here, flow cytometry there, mass spectrometry over there – and share those technologies among all disciplines. We also want to have a unified specimen reception; at the moment, laboratories tend to have different specimen receptions depending on their disciplines, but a single receiving site would give us better control over preanalytical conditions. We want all of our specialists to have carefully controlled samples and unfettered access to tests and devices – but, even more importantly, we want to make sure that we’re sharing our knowledge base as well as our tools, so that we can begin talking to – and understanding! – one another more effectively.

With the rise of genetics in the laboratory, we’ve found that our workload has only increased. When genetic analysis first came on the scene, my colleagues said things like, “We’ll have to retrain as geneticists, because biochemists won’t be needed.” That couldn’t be further from the truth! We need functional assays more than ever. Each time we find a new variant of unknown significance (VUS), we have to ask – is it functional? Answering that question requires enzyme assays, metabolite profiling, and other biochemical tests. It’s the crux of “combined omics” – the integration of genomics, proteomics, metabolomics, and other –omic disciplines.

The Trust is investing heavily in electronic patient record systems; we no longer want just a chemistry report, a microbiology report, a pathology report… Instead, reporting scientists will be able to pull results from different areas to develop an integrated report. In my opinion, such integration is the most comprehensive – and therefore best – option for our patients, and everything we do here, we do for them.

Transitioning to combined omics

Pathology services across England are moving to a standardized hub-and-spoke model. We are currently in discussion with our network partners to explore closer working opportunities but pediatric pathology is a specialist service, so we need to ensure that the model works for our patient population and does not compromise patient safety. If you have a 120 μL blood sample from a newborn baby, you have to do all of your testing on that volume; the last thing you want to do is have to request a second blood draw. When dealing with a very sick neonate, you can’t start sending samples off-site to non-specialist laboratories because that’s not what’s right for the patient.

We’re very fortunate here because the hospital, as a whole organization, is actively engaged with the lab. Not every hospital is like GOSH; when I talk to colleagues in similar positions, they often appear quite worn down by their roles – as if they’re fighting a never-ending battle. On the other hand, I often feel like I’m being actively pushed to make positive changes for the lab. GOSH is a research-led hospital where scientific advancement is embedded into the working lives of our staff and the patients and families we treat and see. We’re looking into implementing measures like generic consent, which would allow us to use excess tissue and blood samples for future research. It’s especially valuable because we have the opportunity to use samples from a patient, conduct research, and then potentially take the results of that research directly back to benefit the same patient. I think that’s what lies ahead for us – and hopefully for other institutions, too.

It’s really important to get buy-in from all staff. In science, it can be hard to get people working together across the bench – let alone across the building. It’s not the only challenge, though; once you have your staff on board, you have to work out how to implement change without compromising service; and how to ensure that everything is not only fit for purpose, but kept to an ISO standard as well. I think aspects of our work here make it easier to move to combined omics and to provide greater opportunities for our staff group. If we do not continue to move forward, we’re doing our patients a disservice by looking at every result in isolation. Our highly specialized pediatric investigations will certainly benefit from a more integrated approach.

Collaborating to improve care

I’m the Head of Laboratory Medicine at GOSH, but I’m also the Head of the Neurometabolic Unit at the National Hospital next door – so we’ve been working in partnership for quite a while, with a number of joint contracts and other arrangements that allow free movement between the two organizations. We’re scientists at heart – and scientists are often good at networking and collaborating!

Here at GOSH, we compare ourselves to institutions like the Mayo Clinic, the Children’s Hospital of Philadelphia, and Toronto’s Hospital for Sick Children. Like them, we’re hoping to become a sort of pediatric laboratory medicine supermarket, offering a broad range of specialist tests to other providers who may lack the facilities themselves. We have a great network with those institutions; we’re constantly in touch with them for consultations, second opinions, and advice. What we haven’t done yet is share operational details – aspects such as funding, organizational structure, and increasing efficiency – but it’s something I hope to investigate in the future.

I never hesitate to raise the profile of laboratory medicine to the wider Trust to highlight why we exist and our essential role in patient care. The training of the next generation is also embedded within our strategic plan. It will be news to no one that pathology is struggling to recruit new graduates.  With limited resources for recruitment and retention, we need to come up with new ways to attract new graduates and train them in our highly specialized areas. At the moment, there’s a traditional training route to which all new NHS scientists must conform – but we’ve got to look at ways to customize training to suit different educational and career needs.

Industry partnerships also help us move forward. In my own interest area, metabolic disorders, we have healthy relationships with the companies that produce treatments – enzyme replacement therapies for lysosomal storage disorders, for instance. We collaborate with those companies to develop new assays in the laboratory, and the collaboration benefits the companies because it means that more patients are diagnosed faster and progress to the treatments they provide. More importantly, because the longer diagnosis is delayed, the worse the outcome in metabolic disorders, the collaborations allow us to identify patients in need of treatment so that we can improve or even save their lives.

Preventing preanalytical variation

Preventing preanalytical variation is a key priority here at GOSH, and one I think is under-recognized in pathology and laboratory medicine – Carolyn Compton raised the issue wonderfully in “Garbage In, Garbage Out” in The Pathologist last month. We’re working on a number of initiatives to prevent preanalytical error; for instance, the Trust invested in a dedicated member of staff for one year initially to reduce preanalytical error.

The staff member will focus on the development of practice, policy and procedures to reduce preanalytical error rates for clinical samples. They will be an integral part of the laboratory quality management team and, within this structure, will oversee the implementation, development and coordination of improved preanalytical quality processes.

They will provide leadership and direction on quality improvement processes linked to the collection and delivery of samples and will advise on sample quality issues, developing a team approach and encouraging sharing of best practice to meet the requirements of a patient-focused service, which is vital for our children and their families.

Getting the right samples to the right place at the right time isn’t as “sexy” as new tests and fancy machines, but getting the basics right is truly important. The last thing any hospital, parent or child wants is for their sample to end up in the wrong department. Eliminating preanalytical variation is very dear to our hearts, so we’re working hard to achieve that goal.

A move to mass spectrometry

At GOSH, what we have right now is a virtual facility – with machines distributed around the department. We have just acquired a new system, and we’re planning to acquire more as we increase our test volume and move toward more quantitative assays.

We use mass spectrometry a lot – newborn screening, vitamin D assays, metabolic analyses – which is why we are so eager to expand and improve those facilities. Mass spectrometry is powerful and relatively cheap (aside from the initial system purchase), so we want to move as many tests as possible onto that platform – appropriately. As I mentioned, not every assay needs to be conducted via mass spec – but many can and should be. For instance, we measure glycosaminoglycans in urine to diagnose and monitor lysosomal storage disorders. At the moment, we use two-dimensional electrophoresis, which takes quite a long time; with a mass spectrometer, you can do it all in a single run, and it becomes fully quantitative instead of just semi-quantitative.

We’re also running more enzyme assays on the mass spec. Instead of running one long assay that yields a rate of change, we can perform up to 10 different enzyme assays on a single dried blood spot – we add all the different substrates, incubate, and then have the mass spectrometrist separate out the products. It’s a great way of doing lots of enzyme assays at once – and it uses the skills of the scientist in new ways. I anticipate that mass spec will develop in many other areas – histopathology (where they’re already looking at proteins from embedded blocks), immunology (for instance, by looking at cytokines), microbiology… For these applications, I consider the use of mass spec a no-brainer.

In Service to Our Smallest Patients

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