Salvation in a yoghurt – Does your gut microbiota hold the secrets to good health?

Based on a talk by the same name given by Dr Gareth Parkes – Consultant Gastroenterologist @ the RCP Update, AMEX Stadium, 2019 – 20/03/2019

Our GI Microbiotic Makeup

Ilya Mechnikov nobel.jpg

Élie Metchnikoff won the nobel prize in 1908 for his discoveries about bacteria and immunology. After this he developed the theory that aging is caused by the build up of toxins in thegut. In an attempt to live forever he drank sour milk (Bulgarian Kaffir Yoghurt) every day. Unfortunately it didn’t work and he died at the age of 71 and was buried in Paris. 

He however, is the great grandfather of this field and set about a chain reaction which leads up till today. In the 1990’s to early 2000’s we discovered that we are outnumbered 10 to 1 by our bacteria, but now what we have discovered & what a lot of people still don’t know is t

hat both our cells and the bacteria are probably outnumbered by the viruses harbored within the bacteria.


It is not yet clear what the role of these viruses are but the process of discovery so far has been much like zooming in on a google map of the Amazon. To continue the analogy we used to only be able to see the broad view of the microbiome & are only now zooming in on the roots:

Amazon Rainforest Map

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Initially we could only culture the bacteria in a petri dish. Then we developed complex immunoflourescence assays. Now we have developed methods to look at the metabolome & transcriptome to assess the immune processes going on within the bacteria. It’s not just about the bacteria you produce, but also about what is going on inside them. We are only just starting to understand the impacts of this. The next stage will be looking at the virome and it’s implications.

The impacts of these processes are truly profound and affect your neurophysiology, neurohormonal functioning and cause some disease. Let’s take a look at how this has developed over time.

Your Microbiotia & Inflammatory Bowel Disease?

One of the earliest avenues for research exploration was ? E.Coli in macrophages – could this cause Crohn’s? After lots of research it was discovered that they didn’t.

The Microbiome Diet - Healing the gut naturallySubsequent studies looking at bowel trauma and healing discovered that by re-biopsying previously biopsied colon it was possible to quantify the immunological response. In Crohn’s the healing response was subdued, unlike in UC patients or healthy controls. A similar response was found by injecting E.Coli into the arm. Healthy controls had a big peak in response, but in Crohn’s the response was subdued.

There Are More Unique Species on Earth that We Thought ...

Then several studies came out showing that the microbiota themselves become less diverse in UC/Crohn’s. This is pattern that continues throughout health – disease on a spectrum. You have low-risk individuals at one end with intact mucosal barriers, at-risk patients with perhaps a ‘leaky gut’ and other patients with Crohn’s/UC disease and complete mucosal failure asosciated with decrease in microbiomal diversity.

Other researchers have looked at whether fast food is causing the gut to become leaky? Transfats and inflammatory fats appear to disrupt this barrier and lead to dysbiosis. Dysbiosis subsequently predicts disease and biomarkers exist which can be used to map and anticipate this process to some degree.

FDA on trans fat: Halt use in U.S. food within 3 years - CNNWe have also found that in general a poor diet high in trans-fats can completely disrupt the baseline immunological state, leading to raised level of pro-inflammatory cytokines, increased baseline inflammatory response and higher risk for immune-mediated disease. This has particularly been demonstrated with high trans-fats in mice models.

But how does this apply to humans and what can we do to treat these diseases?

Modulation – Probioitic

An analogy. Imagine a football stadium like this one this talk is being delivered in and the grass is your microbiome.

Pre-biotics are like fertilizer the grass while pro-biotics are like the new grass seeds.

BIMUNO - PREbiotics for Anxiety, OCD, Depression & Overall ...

Pre-biotics include dietary influences. There is good evidence that pre-biotics & dietary changes can be effective for IBS and possibly UC, but not so much in Crohn’s.

Regarding probiotics, their origin is steeped in history. In 1917 during the first world war one particular German trench crew got dysentery. All of them died except one individual. His microbiome was cultured and grew an organism – E.Coli Nissile which appears to confer some protection to E.Coli:

Immune modulation by E. coli Nissle 1917. The probiotic E ...

Following on from this over the years many new probiotics have been created, but only few have actually developed good evidence to support them. Recently the rules have changed and without this evidence they cannot be labelled as probiotics – sorry Yakult.

Several studies have more recently followed:

  • Lactobacillus study – showed no improvement in the ability to metabolise alcohol.
  • Bifidobacterial cultures in Japan – small reduction in visceral fat
  • L.casei – Failed to improve immune responses to vaccination in healthy volunteers
  • Nematodes have been made to live longer by probiotics
  • Sad but not depressed people can possibly be helped by probiotics
  • Rotavirus infections can definitely be shortened by the use of probiotics
  • CD studies have shown no benefit for maintainence of remission
  • In UC – VSL#3 trials showed some benefit. This definitely works in chronic pouchitis and was the first probiotic to be NICE approved.

VSL#3 Probiotic Review - The BJJ Caveman

Modulation – Faecal Microbiota Transplant (FMT)

If probiotics are the seeds, FMT is when you lay down entirely new turf!

Historical attempts have included the Japanese drinking ‘Yellow soup’ and the Berbers eating camel dung.

There are several successful studies, showing:

  • FMT transplant in mice can make obese ones slim!
  • In C-Difficile it categorically works. So much so, that the landmark study had to be stopped early at 43 out of 102  patients planned to be recruited. Diversity of the microbiome was also shown to improve.
  • FMT doesn’t work in IBS – placebo is perhaps even better!
  • Obesity – Vrieze et al 2012 demonstrated a 75% increase in insulin sensitivity using FMT, but further research is needed about the generalisability of this result.
  • UC perhaps beneficial. Further trials are ongoing.

C. difficile infection and the role of faecal microbiota ...

Providing a World Class Inflammatory Bowel Disease Service with Fraser Cummings at University Hospital Southampton – Notes on the Gastroenterology Training Day (20/9/17)

National Standards:

  • Crohn’s and Colitis UK

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  • IBD standards 2013 update:

  • NICE – Feb 2015:

These are the 4 NICE standards:

  1. People with suspected IBD should be seen within 4 weeks.
  2. The services should be age-appropriate and supported by a multidisciplinary team.
  3. People having surgery for inflammatory bowel disease have it undertaken by
    a colorectal surgeon who is a core member of the inflammatory bowel disease multidisciplinary
  4. People receiving drug treatment for inflammatory bowel disease are monitored for
    adverse effects.

What is required to run a great service?


The commonly forgotten elements include – managerial, clerical support, Surgical, pharmacy, nutrition, pathology and psychological support. All of these and gastroenterology, IBD nurses, endoscopy access, radiology and much more are needed to set up a world-class service.

Where is the data?


Data is King! You need the data in order to get the money, and actually push forward your service.

We need to capture this to inform the patient, drive research, perform audit and benchmarking, plan the service and drive things forward at a national level.

At present we have:

  • Hospital episode statistics
  • NHS statistics
  • IBD clinical teams
  • Data from IBD patients

98 trusts are currently connected to the registry. 60 are connected to NHS digital.

This all feeds into NHS digital where it is pseudonymised. It is then passed to the IBD registry where it can be analyzed and deployed.

At present there are the following available platforms which patients can use:

  • Patient view – this has come out of the renal patient view
  • Patients Know Best
  • IBD BioResource
  • Improve Care Now – Paediatric IBD system

These above systems should hopefully help us to monitor the patients better in future.


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The specialist pharmacist’s role is to monitor for changes in the liver function tests and other blood tests.

This will help to mitigate possible delays and cancellations.

They are heavily involved in the approval/funding process. NICE approval is subject to a 90 day implementation period. This is locally commissioned and agreed. After 90 days access is granted. Occasionally NHS England will commission the drugs to be given at specialist centers.

If people don’t meet the criteria then sometimes they require an individual funding request. Eventually, however, the ‘individuals’ become a group. At that time a group agreement is required.

Commissioning pharmacists are really important people when it comes to improving the service.

The pharmacy also keeps accurate records of who is on what biologic agent.

Drugs are classified as either:

  1. Blue – Primary care only,
  2. Green – Primary and Secondary.
  3. Yellow – specialist initiated/recommended but suitable for continuation in primary care (e.g mesalazine). In these situations there may be a shared care agreement in place.)
  4. Red – is for specialist use only (ie. Biologics).

Local shared care agreements are all listed in the West Hampshire CCG website. They exist for azathioprine, mercaptopurine, methotrexate, sulfasalazine, lubiprostone, and prucalopride.

Homecare is another part of an IBD pharmacists role. Home-delivered medications (such as Humira) attract a no VAT tariff so there is an incentive to do this.


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The following criteria constitute malnutrition:

  1. BMI <18.5kg/m2 or
  2. Weight loss > 10% (indefinite of time) or > 5% in 3 months combined with either low BMI (age dependent) or low fat-free mass.

A lot of patients with IBD who are malnourished are actually BMI either normal or obese.

Nutritional deficiencies are common.

Micronutrient deficiencies are also common: magnesium and zinc, vitamin A&E, selenium and all the other common deficiencies are present in up to 30% of patients. (Vidarsdrottir et al.)

The dieticians spend some time discussing this all with the patients. A lot of patients have strictures and diet can help in preventing obstruction. Then addressing the malnutrition and maintaining the nutritional status, identifying food ‘triggers’, correcting deficiencies, reduce stomal losses (preventing dehydration), dietary treatment – liquid diets, and re-educating people about nutrition all form part of the IBD dieticians role.



Roles of imaging

Diagnosis is for:

  • Defining disease extent
  • Assessing disease activity
  • Extraluminal Manifestations

Often the first suggestion of IBD can be seen on CT scans.

Available Techniques with their respective pros and cons:

Fluoroscopy for the small bowel, enterography, and enteroclysis (enterography is oral and enteroclysis is via an NG tube). The barium bolus dives deep. Fistulograms and Loopograms are other options.

Fistulograms and Loopograms are other fluoroscopic techniques.

Pros: provides good luminal information at a relatively low dose.

Cons: No transmural or extraluminal assessment. The methylcellulose makes the patients feel sick. Plus, availability is limited.

CT – With or without IV or Oral contrast.

Can be enterography or often enteroclysis as well.

Pros: High spatial resolution and extra information, sensitive and reproducible.

Cons: Radiation, IBD patients are young. Not dynamic, lower contrast resolution (particularly without contrast).

MRI – Again can be with or without IV or Oral contrast.

Tends to be enterography.

Pros: Excellent contrast resolution. Different sequences, better neural detail. Reproducible. Dynamic.

Cons: Time consuming, access. (There are 5 or 6 at Southampton, but even despite this each study takes at least 30 minutes). Oral contrast is poorly tolerated. Reduced spatial resolution.


Pros: No radiation. V.high spacial resolution. Doesn’t rely on dilatation.

Cons: Operator dependent, Less reproducible, Patient dependent (obese, scarred abdomens are difficult to scan.) The propensity for missing complications – abscesses and perforations.


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A new biologic which has recently entered the IBD scene.

Most of the trials in IBD are now endoscopy based. Endoscopy + CDAI or Mayo score will be used to assess response.

If they respond then they stay on this arm of the study. If they don’t they either switch arm they go onto the open-labeled maintenance part of the study.

Lots of patients are excluded from trials because of comorbidities, a long disease duration, difficulties in treating them and fallibilities in the clinical scoring systems.

Ustekinumab is an antibody to IL-12 and IL-23. 3 trials: UNITI 1 and 2 + IM-UNITI.

UNITI 1 was for those who had failed on anti-TNF therapy.

UNITI 2 was for those who were TNF naive.

CRP’s and calprotectin’s are also improved.

Relapse studies were also done showing that those no placebo over a year are at a significantly higher risk of relapse.

The drug loading dosing should be weight based. It is administered in a similar fashion to adalimumab but there is a loading dose. Standard dosing is 12 weekly.

There are a lot of known potential side effects, as such, it is not advised as first-line biologic therapy. It is licensed for Crohn’s but not UC at present.

IBD in Pregnancy

The aim is for a:

1) Healthy Mother:

  • Pre-Conception education,
  • Control of IBD:
  • drugs,
  • Effect of IBD on pregnancy,
  • Effect of pregnancy on IBD,
  • Mode of delivery (think about long-term continence in some patients).

2) Healthy Baby:

  • Drug exposure,
  • Mode of delivery,
  • The effect of IBD on the baby.

This area causes significant anxiety.

Many patients consider voluntary childlessness, half worry that they might not be fertile, two-thirds worry about passing the disease on to their children. This is not often discussed in clinic.

Regarding the drugs used in pregnancy: See the ECCO guidelines summarised below:


Ideally, patients should be in remission 3-6 months before they conceive. The chances of having a stable pregnancy are then much higher. The converse is also true so getting patients into remission early before conception is of paramount importance.

Treating depression can help IBD patients get pregnant!

The babies will arrive slightly earlier and be slightly smaller. There is an increased risk of severe perianal Crohn’s disease in some patients and some should be referred for a c-section.

Anti-TNF should potentially be stopped in the third trimester. This needs to be an individual decision.

Note: No live vaccines must be given for six months post delivery. (BCG, rotavirus, polio) – regardless of what you do during the pregnancy.

Post delivery certain drugs are also contraindicated during breastfeeding:


Getting the Diagnosis Correct – Excluding Infection

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Rare infectious mimics –

  1. GI Schistosomiasis. Extremely difficult to diagnose, sometimes you can pick up the eggs on a colonic biopsy. Serology after about 3 months is highly reliable. Treatment is with praziquantel.
  2. HIV/Immunosuppression with other infections such as CMV, TB. Diagnosis of CMV is on PCR positivity on biopsy and viral inclusion bodies. The prognosis from CMV is poor.
  3. Other viral infections including VZV and HSV can also complicate the use of biologics and the consequences can be extremely serious. Infliximab is probably more immunosuppressing than adalimumab, which is more than others like etanercept. Particularly intracellular organisms in the first 90 days of administration. In particular septic arthritis (staph), TB, NTM, listeria, and Legionella are all associated. As are hep B, C, CMV colitis, HSV, VZV and respiratory infections. Apart from being screened for these conditions, the patients should have pneumococcal, influenza, and possibly hep B and VZV vaccination.
  4. Acute colitis can be mimicked by c.difficile and all sorts of other bacterial infections as well as some of the above viral causes and rotavirus. Near patient testing for gastrointestinal infections are currently under research.

Dare to be different! Why sticking out from the crowd means you might be on to something


Matt Stammers, Clinician Software Developer, Gastroenterology specialist registrar, healthtech entrepreneur and founder of Clinical Developers – an organisation that supports the cross-fertilisation of medicine and computer science – writes about the mental outlook and cutting edge skills it takes to change the face of healthcare. He wants to get you inspired

medical innovators

As Mark Twain once wrote, ‘whenever you find yourself on the side of the majority, it is time to pause and reflect.’ It’s not always good to go with the flow. 

And here’s a good example. In 1985, young maverick Australian doctor Barry Marshall drank a broth containing helicobacter bacteria. It was an act of defiance that brought years of condemnation from the establishment. At that time, he had been working on this bacterium for two years following advice he received from a senior histopathologist colleague. Despite many attempts to culture it in animals, he had failed. Their theory was that this bacterium was the cause of stomach ulcers. But, like several others before him, they had been unable to prove it in the lab.  

Taking the poison 

Fortunately, Barry Marshall was not like most other doctors. Out of sheer desperation, he tricked an endoscopy colleague into performing a gastroscopy on him in order to prove he did not have the bacteria. Without ethical approval – and without even informing his wife – he drank the bacterial broth in secret. At the time he thought he would probably develop an ulcer in a year or two. In fact, it only took a few days for him to be admitted to hospital with severe gastritis.  

Barry Marshall

Many others had tried (and failed) to prove that helicobacter was the cause of stomach ulcers. They failed because the medical institution and big pharma at the time had no interest in such a discovery. Such a ‘cure’ would end the need for a whole generation of ‘ulcer surgeons’, and the vast quantities of drugs that treated but didn’t actually cure the disease. 

But why did Barry succeed where others failed? Many have asked and attempted to answer this question over the years. Was he smarter than the others? Was he more ambitious? Or foolish? Was he just lucky? The answer isn’t straightforward, and to reduce the answer to just one word would constitute ambitious folly itself. However, I’m convinced that Barry Marshall possessed some key components that none of the others had:  

  1.  He was fully, personally invested in the success of the project 
  2.  He was ‘different’ – while surrounded by ambitious colleagues, he was personally driven by the desire to find the answer above everything else 
  3.  He was fearless! 

In short, he was completely invested in solving this problem. Unlike all the others who had gone before, Barry Marshall drank his own poison because he was more invested in it, cared more about it, and was totally committed to the project, not himself. In that moment he acted selflessly – something the others couldn’t and wouldn’t countenance. 

Is he a one-off? 

We see this pattern again and again throughout history. Would Ignaz Semmelweis have discovered the cause of ‘childbed fever’ had he not lost a colleague to sepsis and then chosen to take selfless action? We owe the discovery of modern medical hand hygiene to this selfless Hungarian. Ignaz Semmelweis suffered heavily for his selfless convictions – roundly derided and rejected during his lifetime for his work, he gave us what couldn’t have been discovered in any other way and latterly became known as the ‘saviour of mothers’. Many of us owe our lives to him. 

John Snow

Would John Snow have isolated the Broad Street pump as the cause of cholera had his heart not gone out to the people dying all around him from the disease? This generous man put himself in jeopardy in order to discover the cause of cholera. While all his colleagues were fleeing London he stayed, and because he was so personally invested in the problem he saved many lives, founding the field of modern epidemiology in the process.  

So my summoning call to readers is this: become invested in the problems you face daily. And do the work for the sake of the work, not for ambition or any other reason. Take positive action and commit to solving a problem that is meaningful to both yourself and others. 

Why don’t more people do this? It’s because there’s a high price to pay. It requires learning new skills to solve problems, plus not buying into the falsehood that only ‘professionals’, big companies or others can solve these problems. The truth is they can’t. Only you can solve the problems you are uniquely positioned to solve, and you might just create a new field of science in the process. 

Barry Marshall was just a Gastroenterology registrar (like me) when he made his discovery. It is only now, with hindsight, that he’s recognised as a great example of the ‘clinician scientist’ – a now well-recognised phenomenon. It cost him his reputation – for many years he was rejected and mistreated by colleagues and industry alike. Only in 2005 was he finally awarded a Nobel Prize for his work, and today he is considered a medical hero.

Ignaz Semmelweis

Ignaz Semmelweis, the father of modern hygiene, only became so because he was curious about something he observed. Where many would have let the unexplained death of a colleague go, Semmelweis couldn’t: he was intrigued. Intrigue led to discovery, which led to conviction, which led to commitment in the face of adversity, which ultimately led to breakthrough. He received little glory for his work during his lifetime.

The modern field we now know as Epidemiology did not exist before John Snow. Through his commitment he drew the first epidemiological map and began to turn the tide on cholera. He was one of only very few physicians in London at the time and so one of only very few people who could actually have made the discoveries he did. He worked out where he fit in the world, and he ran with it. 

These three heroes share threads of commonality. None of them were entirely alone in their endeavours (even Semmelweis and Snow had communities of support), all of them were ‘square pegs’, all of them were fully committed, all of them had to learn new skills, all of them did the best with what they had, and all of them acted selflessly. 

Enter the clinician developer 

I came up with this name by mistake. I was trying to explain to some colleagues what kind of doctor I wanted to become, and the name popped up. Not that the name is important. Indeed, it may well change. What is important is what it stands for – which is the ‘builder’ clinician. Traditional pathways for clinical staff have generally been: clinician ‘specialist’, ‘generalist’, ‘manager’, ‘teacher’, ‘scientist’ or more recently ‘entrepreneur’. All of these pedigrees (apart from the entrepreneur) have very long histories and the routes to becoming on are well established. However, I’m convinced that the time has now come for a seventh type of clinician – the ‘clinician developer’ or builder.  

In a sense all clinical staff are builders – from writing protocols or business plans to conducting research. However, what I’m referring to is a particular kind of clinician who has their feet in two different worlds. They straddle the world of the clinician with all its arcane knowledge and tradition, and the world of the software developer with all its flux and change, constant upgrades and machine intelligence. I believe that the fusion of these two worlds is the future. I believe that both worlds can learn a lot from one another, that they fit together hand in glove. 

Medicine has become an increasingly complex domain, so complex in fact that my brain physically aches every day as I try to assimilate and sort vast quantities of information. Humans do not do this very effectively. As Daniel Kahneman points out in 2011’s Thinking Fast and Slow we tend to oscillate between two types of thought – Type 1 (fast, automatic, frequent, emotional, stereotypic, subconscious) and Type 2 (low, effortful, infrequent, logical, calculating, conscious). As healthcare requires much more Type 2 than Type 1, this poses a significant problem for us as clinicians, and sometimes proves dangerous to our patients. We need software solutions that can help ease this Type 2 burden, but so far they don’t exist. In fact, most of the IT solutions we currently have are very good at collecting and presenting vast quantities of information… just not in a way that helps us as humans or healers. 

Software developers and data scientists alone cannot help us. Even when a clinician works in close proximity with a developer (a combination that can work) success is not guaranteed. Granted, you can make progress – but this is where I come back to my original point. The issue is one of selfless investment. The software developer or data scientist doesn’t actually have to deal with the problem themselves, so therefore they are not fully invested in it, and they’re probably not acting selflessly.   

We easily forget nowadays that these problems are by their very nature extremely difficult to solve and some are effectively intractable. Therefore, it’s only someone who is possessed of several skillsets and is fully selflessly invested in solving the problem that can actually solve it. All the heroes listed above needed to be both deeply involved in the problem and to have the technical skills to solve it.  

Yes, teams are incredibly important in scaling and bringing products to market. But that first spark – that initial burning ember of innovation – is formed in the fire of heavy individual investment. These clinician developers are one such catalyst, and I believe that without them healthcare technology will continue to lag 15+ years behind every other industry. 

That’s why we formed Clinical Developers. We’re just getting started, but together we are determined to accelerate one another towards success. If you have the skills and determination, now’s the time to start solving the difficult problems only you can selflessly solve. We’d love to help.

PWC Teach at #NHSClinEnt PitStop 7 on the Financial Journey of a Startup

Adnan Zaheer and Lynell Peck are both Finance Partners at PWC.


Adnan was the formal financial director at Arena Flowers and Smart Pension. He is experienced in building up small businesses into medium-sized ones. Now both working for PWC.

Lynelle trained as a speech and language therapist but then pivoted to accounting.

Most companies don’t have a great system for fulfilling their legal obligations financially.

Filing late impacts your company in terms of fines. It also impacts your companies credit rating and it can also damage your own personal credit rating.

The monster can grow very big, very fast and sometimes it can get really really ugly.

When should you hire a finance director?


Adnan would advise that you get a finance director earlier on rather than later.

Tony suggested getting an accountant – otherwise, mistakes will be made. You need someone to keep you on the straight and narrow. It will keep you from getting into trouble.

You cannot withdraw dividends unless a company is making a profit. The articles of the company will stipulate what one can and cannot do from the start, however, these have to be within the law.

They would recommend you find someone who you can talk to and build a relationship with over time. However, if you want your company to grow rapidly then you will need a bigger firm.

PWC will be launching an application for SME’s soon.

Randeep Grewal then talked about cash flow from the back of the room. Does your business generate cash flow in a positive way? (ie. the working capital is negative eg. Tesco). He again emphasised the importance of a decent finance director.

Adnan again – SEIS and EIS schemes are enormously helpful in stimulating investment in SME’s in the UK.

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All you need is an assurance certificate. SEIS is up to 150k. EIS is £100k – 5 million. There needs to be UK taxpayer in there to get the tax relief. SEIS – people can even invest in themselves. You have to incorporate within 2 years to get SEIS.

There are also R&D tax credits – particularly web/system development side. If making a loss in that year you can get up to 33.5% money back on your web development. If you make a profit you get 22.5% back. Nifty is PwC’s platform for this.

You have to offer a pension to your employees. (Auto-enrollment). There should also be benefits packages.

Regulatory audits have to be done when you have more than 50 staff. Due diligence, tax health checks, cyber-security health check, restructuring support and risk assurance / corporate governance all need to come in after this.

Finally, people need to tax-plan for their business exit.

Types of Finance Advisor

Book-keepers manage payable accounts at about £10-12/ hour. A management accountant will probably be at least partially qualified and can do some analysis – put it into a reporting form (ie. cash flow forecast.) Accountants will be fully qualified and chartered.

Finance directors come in 3 different types:

  • Accountants – who will do tax and reporting.
  • Strategic Partners – sit on the board and have relationships with external investors.
  • Catalysts – they do the ops and strategy but they also drive the business (normally they are number 2 to the CEO.

My finance partner (PwC app) helps you with all the different levels here. They also have My Lawpartner, My Tax partner.

Raising money


Thanks Anna Vital for this


  1. In the beginning you with incorporate. Then you will raise family and friends money, angel – SEIS or EIS, crowdfunding, startup loans, grants, (innovation grand, r&d tax rebates, Innovation Vouchers, Regional Growth Funds, Mayor of London etc.). Pension-led, incubators and accelerators.
  2. Next around the time of Series A: Business angel investors, family offices/corporate venturing, VC (professional option), Crowdfunding, Business Growth Funds, Loans (Bank, Asset financing, invoice financing, Mezzanine Finance [where the debt turns into equity if it is not paid], Bank Referral Scheme).
  3. Finally in additional rounds or either as the company nears exit: Private equity, VC, Debt Finance (from  both banks and non-banks), Mini-bonds (Loans from small-scale investors), Alternative debt financing.)

Will they invest?

  1. Debt is cheaper than equity – investors will lose interest later on.
  2. Previous success
  3. The investor’s confidence is high (market forces have a massive effect).
  4. Investors will look for the right team, idea and execution and exit plan.

You have to pre-plan – it takes 9 months for the average round to be closed.

Get someone impartial to do the negotiating for you – as the entrepreneur, you are too close to the project to get the best deal.

Digital Health and Inter-operability in the NHS


Choluteca Bridge – 1998. The bridge stayed up but the river moved following a storm! Why is this here? Read to the end and you’ll find out.

First talk of the Interoperability summit based on the talk by Robert Watcher – writer of the Watchter report

Watchter – The four stages of health IT are:

  1. Digitizing the clinical record.
  2. Connecting all the parts
    1. Enteprise system to enterprise system
    2. Third-party apps to enterprise
    3. Patient-facing systems to enterprise systems, and to one another
  3. Gleaning meaningful insights from the data
  4. Converting these insights into action that improves value.

Things get really interesting when you connect things – the intercontinental railway connecting up in the middle was the beginning of great innovation and trade in the US. Traditional enterprise is one set of those tracks (EHR’s, Epic, Cerner etc). The second part is consumer-facing IT (big data, apps, sensors, etc.) When these two combine great things will be possible.

Unfortunately in America, the situation of: ‘No electronic medical record’ in a hospital is now seen as a selling point in the US.

You see, because of huge efforts spent on data entry – the US then digitized the system first without thinking about the people and their work in a deep enough way. This resulted in technical maladaption.

According to Ronal Heifitz there are two kinds of changes in work – adaptive vs technical changes. Technical changes think only about how the technology changes; Adaptive changes consider the people involved and how it might impact them – people are both the problem and the solution all at the same time. Healthcare technology must be adaptive – that is why we have managed to get it wrong in the past.

Erik Byrnjolfsson talks about the productivity paradox of health IT. In industry after industry, digitilization was supposed to bring improvement; however, these changes often actually produced more problems and productivity plummeted. “You can see the computer age, in everything except the productivity statistics”. It takes 10-15 years at least for the productivity to follow.

We are at the beginning of becoming a primarily digital industry.

Solving the productivity paradox: Improve the technology and re-imagine the work itself! Both have to happen in order for success to follow! We need to move towards collaborative charting – this is the only way to succeed.

Features of the Wachter report:

Implementation needs to move at an appropriate speed – staged approach, including global exemplars will be necessary.

We need to give local trusts authority to buy best system for them – and not just follow NP-fit which failed as it tried to centralise everything.

We need to build and nurture the clinical-informatics workforce – we must see health IT as change management, not just a technical project. We need chief clinical information officers and a national lead – currently: Prof Keith McNeil

Interoperability is crucial to success and Leaders must...

  1. Connect the digital pieces, learn to use data for improvement and build decision support.
  2. Build skills, culture, governance to re-imagine the work not just digitise it.

Finally. Why is the bridge at the top of the article? Well the Choluteca Bridge in Honduras was a technical masterpeice. It withstood an enormous storm in 1998 and all the engineers congratulated themselves. Except there was one problem… The river had moved. If we are not careful our digital bridge could look the same. That’s why we need to make the solution people-centric!

Ten Top Tips for Clinical Entrepreneurs in Media Land #NHSClinEnt

Based on a talk to the #NHS Clinical Entrepreneurs by Vivienne Parry – Science writer and broadcaster.

1. People like:

  • Royals, celebs, cute dogs, drama.
  • Something new, surprising, quirky, counter intuitive.
  • Conflict.
  • Human stories – personal journey’s.

Make of this what you will – but these are the things media-land tend’s to look for.

2. Have things to hand:

Great pictures, top factoids – a nugget that is unforgettable – quote on, quote off.

3. Don’t ramble:

Have a beginning, middle and an end to the story.

Typically people start in the middle – without a context (and therefore the story doesn’t work).

4. There needs to be a clear need:

Otherwise people won’t get it. Show me patient’s who have benefited. It needs to be clear and easily understood!

5. Know the difference between good morning and newsnight

One of them is very relaxed and the other is very formal. If you’re sitting on the couch with Piers Morgan you don’t need any training. Newsnight you do! Always watch the show before you go on it.

6. News and features are really different animals.

On the news they will not tell you to comb your hair. If you look like a mess they won’t tell you. Features you’ll have makeup etc – apparently this is essential.

Know the style of the programme, magazine or paper. Know what makes a good piece for each.

7. Rate journalists

Pitch to the ones you like and are in sympathy with. The ones you resonate with are the kinds of ones you should approach yourself as the interview is likely to work much better

8. Horizon scan – what’s coming next?

Understand what events make news. – If you’re the top ligament guy you may need to wait until Wayne Rooney busts his ligament. Then is you’re chance to pounce.

If you don’t get anything – don’t be disappointed. Everything has a time to shine and it may not be dictated by the factors you consider most important.

9. Media people live in a totally different time-zone and world!

They will have to meet their deadlines. It needs to be now (tomorrow is not ok). The average online journalist has to get a story out in 24 minutes! Return those calls fast. Now or never – return and leave a message if you can – at least they will remember you.

It is not an oral examination. Don’t use acronyms or jargon. Use and practice analogy in your area. Simple analogies that people can get win the day.

Establish what the journalist knows. If you don’t ask them to repeat it back they will fill in the dots otherwise and get it wrong. If you think they didn’t get it ask them to repeat what you said and explain it back. If they can’t do that then you need to go over it again. Same with quotes, ask them to quote them back to you.

Re-frame the questions: ie. Is this available in the NHS? If not then say that’s a very good point, we need to raise awareness of this and try to get it into the NHS nationally!

Check: Is it live or recorded? Studio or OB (outside broadcast)?

10. Lights, Camera, Action…

News? Feature or documentary? Documentary you’ll get lots of time setup etc, feature in the middle, news they really don’t care – if you look a wreck they won’t tell you. Who am I on with? What to wear – don’t wear black or white? No small checks, patterns, strong colours, not fussy, no dangly earrings and brush your hair!

You need makeup – DO NOT refuse it! You will regret it.

Never look at the camera – look at the interviewer. When you look away from the camera you lose trust! Also, don’t flap around.

People often look at the monitor – this is because they suddenly get distracted by being on television. Say what you want to say. Write down 3 things that you absolutely have to say in that interview. Note: (The interviewer might distract you with some other irrelevant questions – just say what you need to say!)

Understand that the interviewer won’t have read your departmental briefing or any of your papers. The researcher may not have told the presenter much. If you have something to hand and can, do your innovation in a speedy way or use 5 quick and easy phrases. Help people out if you need to, and don’t ever get angry.

Be relaxed. Breathe out, smile.

Be authorative: stillness, clarity of message, sincerity. Breathe out – then you have a very lovely sexy voice to the voiceovers with.

To be authoratative – STOP! Be still and then speak – you will come across as a very serious person to be taken seriously. Make your message crystal clear.

Be interesting – record yourself and then mark out every word you think should be significant in bold. Vary speed and tone of what you say, use limited hand gestures, smile. Make it sound like a ham Spakespearean actor – on screen this comes across well apparently… Vary the tone and the speed!

If you have a tic – train it out!! They can be very off-putting.

11. Bonus – When dealing with print and radio:

Understand deadlines, ask journalists to read back quotes, offer to look at the science copy but don’t alter grammar or style.

Always say yes to radio – has enormous reach and is a great way to practice.

Ask ‘is it live or is it recorded?’ Who are the other guests?

You don’t need notes – you’re the expert – (if you need to, write it on the palm of your hand, don’t wear bracelets, don’t bang the table [apparently people do].)

Practice with your auntie and try it with kids – but don’t start with 14 year olds.

Start with local radio and TV (great practice).

Pour yourself a large drink and watch yourself back! Note things down in a notebook. Change the things you can. In a mirror remember you are looking at a mirror image of yourself. On TV you see the reverse! Unless you watch it you will never improve.

Ask your mum to keep cuttings and records of phone numbers and who you have spoken to. Use a contact management system to keep records of your contacts.

Further hints… Be committed

Passion, Enthusiasm and Knowledge are key!

There is always that moment when the mouth is moving and the brain has stopped. Just stop talking: I’m really sorry that was rubbish can I start again. Short soundbites are all they want – they will cut out any ramble.

That concludes her whistlestop tour of media training for the NHS clinical entrepreneurs.


Branding: Adam Devey-Smith #NHSClinEnt

How do clients build brands?


The One Off (Top 10 agency). They are idea agitators. Their team is broad with multiple people across disciplines working together. They live by their promises. The biggest one is respect – you have to respect your client and your customers.

How will AI affect consumer behaviour – people are not dumb. They get what is going on and they will vote with their feet. Your brand has to stay ahead. The branding has to fit with the product.

Things they have learned:

  • Manage Risk – evolve and collaborate
  • Listen all the time
  • Don’t hang out with the wrong people
  • Well research your ideas and market
  • Good branding and communications

Don’t assume that you know what the competition are doing.

  • What’s your secret. Your story? Vision, mission, values.
  • What are your promises? (Give them something to believe it).
  • Why should I believe you? (Do something compelling).
  • How do you tell your story?
  • Where should you tell/sell it?

Is it sustainable? It needs to be more than just you and the product. Vision and love – do you fall in love with the idea?

Just GYSD – ‘Get your shiz done’

Q&A, actions, age breakdown. Ask everyone what do you think? Why you? What are your competition doing?

Big Promises: Align the vision/brand promise with the behaviour of the company – have a really strong passion!

Little Promises: ‘By 10:30 AM’ – that’s crap don’t do that.

Brand Matrices – Get these nailed down!

Do the groundwork – why are the customers here! Go back to basics and the history of ‘what the company is about’.


  • Don’t get hung up on your brand logo early on. Do get hung up on the name and vision.
  • Vision and Brand Values
  • Articulate your brand promises and belief points across all media.
  • Your logo does not need to do everything
  • Align your business to your brand – branding is a promise.
  • This will build a brand map.

What is your BHAG – Big Hairy Audacious Goal – Anita Roddick, Body Shop

The tech, fashion and sports industries are the most demanding. They want an idea now – if you can crack those industries you can iterate really quickly and build great stuff.

Spend at least a day doing this – sit down with others and beat around each others’ ideas. It is important – a VC will be looking for a sustainable business.


Make sure your pitch is understandable by investors, customers and colleagues.

You will succeed when you identify a problem that needs solving. Listen to 5 good people and your customers. When you see this as a journey you never give up!

When you get the team and customers behind you… really understanding, believing and loving your brand. (Not just you and not just your product.)


300 people, 4 centres round the world. Collaborations to build great products.

They are excited about what can be done in health.


It’s so important to be authentic. Ctrl group – Wearables, Babylon Health, Echo – hacking the service to get prescriptions delivered locally, Dr Focused – to minimise the amount of note taking in order to focus more on patient care.

‘Move fast and break things’ – but this has to be adapted in health as ‘breaking’ things definitely has limits. Patients, clinicians and designers together can achieve great things.

It’s not easy but by building bridges is key. Collaboration is more than just joint stakeholders – it’s sharing all the problems. Everyone has to care equally about each aspect.



They wanted to help people to cope with their mental health better. Depression may become the number one cause of mental disability by 2030. This is something they are passionate about.

The biggest challenge of any health app is to ‘hide the vegetables in the meal.’ This is what Ustwo did with Moodnotes. They managed to build the products in a very quick timescale.

iWantGreatCare – Neil Bacon shares a few predictions

download-17 iwantgreatcare

He explained that patient ratings are directly related to outcomes, patient satisfaction, absenteeism and cost.

Transparency drives performance. Relative’s ratings of cleanliness in hospital predicts MRSA and C-diff rates.

In 5 years time your professional reputation will be determined by what Google says about you.

Your colleagues will be threatened by your ambitions. He had to sell his house in order to start and then invested all the money he got from in iWantGreatCare. It is going well but taking time to scale. Watch this space.

Proximie – An NHS Clinicial Entrepreneur Startup


Proximie – augmented reality platform that allows surgeons/clinicians to collaborate in a AR platform.

Secure system – cloud based telesurgery. Allows you to work together locally and internationally. Crowdsourcing knowledge. Hardware agnostic. Virtually hands-on. Surgeons can reach the poorest from the richest areas.

AR is growing massively. What do the surgeons actually need? What does a consultant at home actually need?

They have now got some really diverse partnerships and have won some great awards.

She co-founded with a technical person and when they realised they were on to something they brought in a chairman and a director to make the team start to scale. It’s only when you have the idea, traction and team (with the right vision) that you can start to scale the business. They are now 25 strong! Good job!