Antibody testing thus far

Antibody testing is probably still the number one topic of conversation at work these days. Although I suspect that this will rapidly be replaced by the impacts of children returning to school.

Based on my completely unscientific anecdotal evidence gleaned from snatches of conversations in the corridors, I have started to wonder a little bit at test performance.

My first observation from my study population of colleagues is that it is fair to say the the number of positive tests seems quite low, even in those clinical areas that were highly exposed. Does this reflect that some people simply don’t get infected or does it mean that we have superior hand washing technique or somehow desist from picking our noses?

We are also seeing a number of doctors and nurses who had a positive swab (antigen test) at the time of their symptoms, but who now have negative antibody tests. This also raises a lot of questions that I hope can be answered by those who actually get to see large numbers of patients and not just the stories in the tea room. Which test (if any) is actually correct? Are these people actually immune? Why are managers seemingly so interested in staff having antibody tests?

We have been focused on the false negatives, i.e., people who have symptoms but in whom the antigen test is negative. Interestingly, many of the patients in ITU fell into this category for reasons which we can again only speculate. Was it because many of the complications were from an over-exuberant reaction after most of the virus had been cleared from the body? Of importance, many healthcare workers had symptoms that were highly suggestive of COVID at the time, so it is difficult to write off these negatives as being true negatives. I am not currently aware of antibody testing in our intensive care patients but am sure data will emerge soon.

A last category are colleagues whose partners definitely had the virus but who themselves did not show any symptoms and who are now testing negative. Obviously this is interesting in the context of Karl Friston and others who are suggesting that the dynamics of the outbreak could be explained by a significant proportion of the population. Certainly an interesting theory, but my views on mathematical modelling as a single tool are familiar to those who have read this blog, i.e., maybe a useful adjunct but certainly not to be relied on.

What is also clear is that my surveys of other clinicians is a poor substitute for proper analysis of whole data sets. However, the high frequency of results that raise eye brows make me wonder what the test performances really are. I await these population level analyses with interest.

Grading ourselves against reality

One of the really enlightening parts of this crisis, from a medical perspective, is the emerging sense of how COVID-19 proves to be so deadly for specific patient groups. There were endless discussions during ward rounds as we sought to anchor the patterns of problems faced by our patients into presentations that we at least partially recognised and hence were able to have some rationale for our treatments.

We are now starting to get answers to some of the questions and a real sense of where we went right and where we went wrong. The lung problems were the most obvious. In the early stages we saw patients with quite ludicrously low levels of oxygen in their blood. Many of these patients were breath quickly but did not otherwise seem affected by having an oxygen level lower than someone on the top of Everest. We were all surprised by how many spoke in full sentences and did not seem the slightest confused.

Later, once the patients were on the ventilators we found COVID-19 lung a completely different beast. Lungs were filled with secretions and could be much harder to ventilate – often requiring high pressures with high concentrations of oxygen to get even barely adequate oxygen levels in the blood. We tried everything including turning the patients prone and then back again like a giant rotisserie, but many of the results were mixed and what worked in one patient didn’t generalise to others or often did not reproducibly work in the same patients. Moreover, COVID gives very distinctive radiological changes. COVID patients were clearly behaving very differently to previous patients with non-COVID-19 acute respiratory distress syndromes.

So a recent paper in the New England Journal of Medicine has taken our attention. The study authors looked at the lungs of people who had died of Coronavirus and compared this to patients dying of influenza. Many of the findings were similar, including tiny blood clots blocking vessels and damage to the air sacs that make the lung. However, one finding in COVID was the generation of new blood vessels in response to the lung inflammation – a feature not seen in acute respiratory distress syndromes caused by non-COVID insults to the lungs.

The study is small and limited by the extremely chaotic nature of lung changes, however does give us important clues that we were going along the right lines in supposing that COVID19 was causing a completely different type of pathology.

Unfortunately it is still a bit early to change our treatments, although there are already trials of drugs that would dampen over-exuberant inflammation. For now, it is certainly satisfying to see our (in hindsight quite naive) clinical suspicions prove to be founded on something real. The rapid reductions in COVID-19 make it difficult to know if there will be many future opportunities to study this disease – will it simply vanish like the flying Dutchman.

Antibody tests are here at last... hooray

This past week saw emails about the availability of antibody tests for staff. Uptake was swift. Some NHS trusts have prioritised their Black and Minority Ethnic employees (BAME). This might not have a strict logic, but does seem to be a gracious way to thank those who have taken disproportionate risks.

In medicine, we tend to only do tests if it changes our management of a patient. So it’s a natural question to ask how these tests are going to change things. Does this mean that I can stop wearing a bloody surgical mask? Does it mean that the results will be used as a de facto immunity passport? Will it mean that we can be deployed even further into the front line in the event of a second wave? Will it actually mean anything at all if the virus mutates?

Perhaps most importantly, it will mean an end to the arguments at home as to whether my job puts the family and grandparents at greater risk… now that’s the kind of immunity passport that really carries value!

Today I saw one of my colleagues access their antibody test result in front of the team… everyone was willing it to be positive. In fact we can’t really see how they could be negative given their likely exposure and what we suppose is the extraordinarily infectious nature of COVID-19. Alas a negative result – will have to try harder next time.

Can the NHS be changed?

There have been a reasonable number of positive changes in the NHS during this crisis – although these attempts to cut through the bureaucracy have been relatively minor in the overall context of the NHS. However, one thing that has struck a few folks here is the overall resistance to change in the NHS. Many fear that any incremental improvements will simply revert back at the end of the crisis.

So being slightly simplistic here, it seemed natural to contemplate a few possible explanations.

What if the NHS is stably bad?

There are many examples of sub-optimal in the world that prove surprisingly stable. The QWERTY keyboard I am currently using is probably one of the most quoted examples. It was designed to stop the typewriter keys fouling each other at speed. Although I did a fairly good job of that on my father’s machine at low speed when I was younger. Anyone who watches their children learning to type can appreciate the high costs of switching such that alternative keyboard designs are difficult to even comprehend – can you name an alternative keyboard design? In essence, even a bad design can be remarkably persistent. No matter how bad some of the issues in the NHS the switching costs are very high - it is akin to trying to fix a car engine while driving along the highway. Hence fixing some elements of the NHS would probably require building a completely separate system and then moving everything across. Could this be an opportunity generated by all these new hospitals that the Government is proposing?

What if this is a big multiplayer game of prisoners dilemma?

I suspect most will be familiar with classic game theory. The basic idea is that although there are potentially better outcomes, this requires a level of cooperation between players that cannot be achieved due to lack of trust or knowledge. Instead, stakeholders behave in ways that are individually best for them but to the detriment of the overall system. This is a particular issue in the NHS where there are fixed budgets, since resources do not naturally follow patients without petitioning the centralised budget holder. In the absence of trust, people naturally do not take on additional work, especially if they believe that the resources do not accompany the burdens and someone else keeps the savings. This tribal behaviour is readily observable in the NHS.

What if no one actually wants to change?

In this scenario, the people who control the system do not actually want to change it no matter what the ‘customers’ actually want. There is plenty of evidence for this – many doctors and nurses will simply not countenance a discussion of change. To my ears the debate usually goes down the same line every single time: “we don’t want an American system” – as if there was only one alternative healthcare delivery system in the world and ignoring the fact that other western democracies fund and manage their healthcare systems differently to the NHS (including many not known for their unfettered capitalism). “We already have the best healthcare system,” they say despite multiple outcome measures pointing to the contrary. “Changing the system would make healthcare more expensive” as if the NHS is at capacity and that spending additional funds would simply result in cost inflation with no possible improvements. It is not hard to find a strong culture in the NHS that would frustrate change.

Maybe no one is actually really in charge?

Despite the national brand and ownership by the central government, power is much more diffuse in the NHS that one might first think. Since there is no market system to coordinate services with an ‘invisible hand’, management (usually non-clinicians) is required to centrally allocate resourcing. In practice, managers struggle to have a sufficient span of control to make more than minor changes. Since management roles often overlap, it is often difficult to make changes without the assent of multiple other managers. Moreover, since budgets are essentially fixed there are few if any incentives for service innovation. Top level managers struggle to make changes actually flow down into the patient facing services, lower level managers feel they don’t have the powers to make changes.

These possibilities are not mutually exclusive, but one has to question whether, in fact, the system is actually capable of change or indeed whether the various stakeholders really have an interest in change. It seems like a classic folie a deux between the public and the stakeholders who both have a strong interest in preserving the fantasy that we have the worlds best healthcare system. For now, the solution always seems to be shaking the magic money tree and throwing a few extra billion of someone else’s money.

The demographic explosion

Just a very quick thought from A&E over the past couple of days.

When I trained, it was unusual to see a 90 year old and very rare to see a 100 year old. Now we see someone that age what seems like every day. Today was no exception, with four octogenarians and four nonagenarians in the department.

Life expectancy for baby boomers born in 1951 was 66.4 for men and 71.5 years for women, according to the Office of National Statistics . For millennials born in 2001, this was 76.0 for boys and 80.6 years for girls.

This matters because much of this increase was not predicted, yet was used as a basis for pensions - many of which had a retirement age of 55 to 60 years. It is not hard to calculate that a 90 year old who went to work at the age of 16 and retired at 60 has only worked half of their lives and have been drawing pensions for a third of their lives.

Given the ratio of workers to pensioners has collapsed, it is not hard to see why the Ponzi scheme has effectively lasted only a single generation. Similarly, the health budget will always struggle to keep pace with these demographic realities. One argument often heard from baby boomers is that they “have paid into the system all their lives” - with the greatest of respect, I cannot possibly see how this could have been the case.

Breakdown of a lock down

It has been interesting to observe the end of the lock down from the hospital doors. Every day I see more folks on the road. My drive has started to noticeably lengthen.

I was pleased to see that lots of people were out over the bank holiday weekend. This resulted in the usual range of interesting injuries. A&E was hectic as we busied ourselves removing ticks to treating sprains and straightening bones. Also seeing a lot of alcohol withdrawal. It is clear that most people I meet are sick of lockdown and are quietly negotiating with themselves to justify their increasing social interactions.

Today was also interesting in the immediate aftermath of the Dominic Cummings debacle. I was able to bear witness to many fruity comments from patients. From my unofficial opinion poll of patients it was clear that, no matter the legal niceties of rights and wrongs, the great British public have made up their minds.

This whole sorry saga is being used by people as justification for the renormalisation of their lives that would likely have happened anyway. They can now articulate in a pithy way that focuses their overall frustrations of being locked down. The government has - inadvertently or not - offered itself as the lightning rod for this discharge of feelings.

The challenge of uncertainty

All PhDs are offered without subject area and are effectively the same, someone once observed. This is because the topic of a PhD is really just a vehicle for exploring the limits to knowledge. The fundamental question: how definitely can you know something?

This is similar to Sir Richard Doll’s work on the link between smoking and lung cancer. Today the link is beyond dispute. Yet it was difficult to prove at the time — and not just because of the opposition from tobacco companies. Almost all patients had strong exposures to smoke, be it from pea soup smog from burning of coal or the near ubiquitous scourge of nicotine addiction meant. It is often difficult to separate cause from effect.

It is similarly not proving easy to show a link between infection with COVID and various forms of exposure. Based on previous coronaviruses, we feel confident that this germ is spread by aerosols generated by talking and coughing that ultimately find their way onto a naive host where the infection cycle starts again.

A scale exists for how we can measure the strength of medical evidence, where 1 is evidence from a meta-analysis of multiple high quality randomised control trials through to 5 which is simply an expert opinion or individual case reports. Much of the current COVID research is reliant are on level 5 opinion, often based on non-transparent datasets and judgement.

Yet for all of this apparent knowledge about transmission, it is obvious that even dedicated scientists are struggling to show the effectiveness of even simple interventions. Perhaps the most obvious is face masks, where we have seen multiple revisions of the scientific advice. We also see confusion about whether we should all be 1 metre (as the WHO recommends) or 2 metres (as the UK Government recommends) apart, or indeed the number of people who can meet safely. Perhaps the most extreme example is that of the lockdown itself, which was always going to be a blunt and socially and economically costly tool. The computer modelling used to justify the lockdown has proven a complete mess, highlighting the difficulty of modelling unpredictable of human behaviour.

The scientific community is perhaps more comfortable with the constant chopping and changing nature of a debate under a blizzard of new facts and figures. Indeed, raised voices and the ability (pretence?) of having the latest research on the tip of your tongue is in sharp conflict between the PR consultants — who are thriving on 3, 4 and 5 point plans, where all points are a tag line that starts with a verb. It is interesting to see both sides also come unstuck.

The scientists – including a professor at Imperial - do not seem to appreciate that messages must be simple, unambiguous, and not for negotiation or exception. Ultimately all of science has a strong random walk element, where the point of inquiry meanders as different results become available. In this way, it is difficult for scientists to provide leadership – especially over the hours and days time frame that characterises the news/political cycle – and stay true to their recognition of doubt.

The politicians are struggling to find a style of leadership that survives deep uncertainty, and potentially rapid changes in direction. The initial strategy has been outed as a rather crude attempt to hide behind scientists and effectively blame shift if it goes wrong. Much of politics is about the art of doable – and politicians here are in somewhat uncharted territory. Methinks they could rapidly become passengers rather than drivers.

I wonder if what has been portrayed in the broadsheets as a rejection of authority and expertise is in reality not some sort of modern Luddism. Instead, perhaps the population has been inured to level 5 evidence, having heard people in authority during the great financial crisis and the Brexit debate being grossly overconfident (wrong?).

The missing A&E patients

The media has finally picked up on the truly unbelievable reductions in A&E attendances. Although this is something that I have already covered a month or so back, I thought it would be worth some quick comments.

It is only just dawning on the public that lockdown is forcing a choice between COVID patients and patients with life threatening yet treatable diseases such as early stage cancers. The latest data shows that A&E attendances were down by 57% in April, from 2.1 million in April 2019 to 917,000 in April 2020. There is a very real risk of increased non-COVID deaths, that could offset some of the benefits of lockdown. This continues to undermine the lockdown – which is still largely based on ‘scientific advice’ that is not available for critique.

Doctors of greater standing than I are pointing to the numbers suggesting that many of these missing patients have serious conditions – if the numbers of patients and their classifications are indeed correct. My observations of the initial figures are that the number of ‘missing’ A&E patients with serious conditions is very large compared to the current excess death rate.

Put another way, most of the patients presenting to A&E with serious symptoms are not actually dying. We have no idea how many are coming to harm – however I would suspect that it is only a minority of the missing presentations. In other words, there are a large number of patients for every patient we prevent coming to harm. We should seek to quantify this ratio when the COVID plague is over. It could enable us to ascertain how many A&E attendances are in fact non-life threatening or damaging and hence not as urgent as might be first supposed.

As previously stated, it is my belief that A&E should refuse service to presentations that are neither accidents nor emergencies as judged by medical staff, not the patient. Given how resource intensive A&E is, this could free up significant resources to plough into more preventative services, or indeed not spend at all.

The stated objective of the lockdown was to ‘flatten the curve’ to avoid overwhelming the NHS, not to stop the pandemic. For my money, I do not think we can economically survive lockdown until a vaccine is found. These latest figures make this even more evident.

The ONS data

I recently had a really interesting conversation with a colleague who spent years in public health, including assembling death statistics. What an eye opener.

The speed and fluency with which he was able to disentangle the statistics was truly impressive. Despite the best efforts of an increasingly prescriptive training system, it appears that doctors still just go off the traditional training pathways and explore the world as it interests them. We are all the richer for it. I hope to do even a small amount of justice to a couple of their arguments. Also interesting just how dispassionately folks who talk about such a large number of deaths can be.

The ONS data is a couple of weeks behind due to the time taken to report deaths, but it well worth a look as it compares this year’s deaths against the 5 year average for a similar time of the year.

The first point made was that there are about 10-12,000 deaths each week in the UK, with seasonal variation due to winter cold and viruses. Death is a good endpoint because reporting is effectively universal and does not require any subjective opinion in itself, although the cause of death is up to the interpretation of the attending doctor. After initially being trepidatious in reporting COVID as the cause, many doctors are apparently more comfortable to cite COVID even where testing is negative.

The second point made was that the data show a clear increase in the death rate this year over the 5 year average. There is no denying from this data when the epidemic hit the UK. The ONS helpfully shows the official COVID-19 deaths as well, so it is easy to see that there are excess deaths over and above those attributed to the virus. The view of the doctor I spoke with is that the timing of this is such that these apparently non-COVID deaths are in fact COVID and not folks dying of other diseases because they couldn’t get to the hospital.

The third point made to me — not shown on this data but well appreciated by those who work from these datasets — was that there is often a spike in excess deaths about ten days or so after the first cold snap of winter. This is then followed by a reduction in deaths that basically matches the excess. In other words, the first cold snap of the winter tends to bring forward deaths by a few months but these are frail people who were likely to die anyway.

There is one school of thought that at least some of the initial deaths represent very frail patients from care homes – some of whom may never have made it into the hospital. It is possible that the combination of evolving herd immunity plus the tragic early deaths of the most vulnerable citizens may tend to attenuate any second or third waves.

In the meantime, the number of non-COVID patients continues to rise. The lockdown is increasingly in name only (LINO?).

Covid has changed how we do research

Coronavirus is resetting the balance of risk and benefit for how we perform research.

Even last year it seemed to take an interminable amount of time to get even simple innovations approved — now it happens in the blink of an eye. In just the last few days the U.S. Food and Drug Administration has approved a new COVID diagnostic using the CRISPR-cas9 method with an emergency use authorisation. Perhaps we can maintain this sense of urgency when this is all over.

The fact that we had no pre-existing clinical tools meant that even relatively ineffective diagnostics and treatments have a place. Regulators and governments also now realise that there is a cost to caution and delay.

This is somewhat reminiscent of the early years of HIV-AIDS. In 1980 the first patient in the epidemic was recognised – albeit retrospectively. There are now known to be earlier victims. The virus was not identified until 1982 with the first diagnostic in 1985. It took until 1987 for the first drug — AZT — to be developed by the British company Burroughs Wellcome based on a discovery in 1962. Fascinatingly, many drugs were tried in a multi-parallel approach, and activists succeeded in getting early access in 1986 to the experimental drugs before they were approved. Compared to COVID this seems glacial - a diagnostic was developed within a few short days and vaccine candidates are already entering the clinic.

Researchers are testing a myriad of different hypotheses about COVID biology and therapeutics. Two have struck my eye this week:

Firstly, Vitamin D. People with low vitamin D seem to be worse affected than those with normal levels. Vitamin D is produced by the body in response to sun exposure which could, therefore, explain why equatorial countries and southern hemisphere countries coming out of summer — such as Australia and New Zealand have been less affected than northern hemisphere countries coming out of winter. There are potential holes in the theory — such as the impact of COVID in South America — and the relationship may not be causative, but nonetheless interesting.

Secondly, the GenOMICC study on the genetics of mortality in critical care has been extended to look for genetic markers of susceptibility. Some of these may turn out to have plausible causes of the disease, raising the possibility of new therapeutic targets to prevent people from getting unwell.

As an aside, we must be very careful about drawing linkages between different gene loci and ethnic grouping since we know that the genetic differences between ethnic groups are relatively small when compared to genetic differences within ethnicities. There is no genetic definition of ethnicity or race, and will likely never be.

These research threads indicate the sheer breadth of thinking that is sitting alongside clinical trials of existing drugs. Much of this work is not being coordinated by a central authority but is instead responding to the incentives being provided guided by Adam Smith’s invisible hand.

This provides an interesting contrast with the centralised governmental response in the UK and elsewhere. These responses have been characterised by ponderous, non-transparent thinking by politicians with no expertise. Scientific research is rapidly and brutally challenged on a time scale that could not be more different than governments which effectively change about every four years or so in most countries.

What is also noticeable is the much more pragmatic nature of the research. Previously much of the focus has been on testing specific biologic mechanisms. Only about three in 100 drugs developed this way that are put into humans survive the rigorous testing process to be approved as medicines. Almost all of those 100 drugs have a plausible mechanism yet most fail even though they apparently get to the right biological receptors in a reasonable concentration. Biology is not as logical or predictable as some of the adherents of the scientific method might suggest.

We are now seeing a more open ended approach to research. The starting point is searching within large, real-world datasets looking for associations between outcomes and specific interventions or patient characteristics. Many of these associations will be noise or could be correlated but not causative — however, the value of this starting point is the knowledge that there is a real world relationship that can then be expanded using our knowledge of biological systems.

Although I do not hold out hopes for a treatment or vaccine in the next few months, my prediction is that combining flexible and sensible medicines regulation with this ‘crowd sourced’ model of research could be effective. Focusing on what works — rather than what we can explain — will show impressive speed compared to current drug discovery paradigms.

Nothing like The Blitz

I had the huge fortune to speak with a lady in her nineties the other day. It was another quiet one so I had the chance to spend about 25 minutes discussing her life. She was kind enough to assent for me to tell some of her story.

She was in her late teens at the time of The Blitz and was living in London.

It’s rare to get time with folks from the Greatest Generation. I asked her straight out: how does COVID-19 compare to The Blitz? Her response was clear and ambiguous: coronavirus and the political response to lock down the country is nothing compared to the blitz.

She vividly recalled being bombed in her Anderson air raid shelter. She described how her neighbour was bombed just as he had finished on the WC in the back garden. As he was dug out of the rubble his first response was that he ‘just pulled the chain and didn’t expect this to create such an explosion’.

A real treat. Aside from our recent war vets - whose service I salute - we baby boomers and millennial snowflakes ain’t got nothing on this generation.

Let’s stop kidding ourselves: any comparison is simply wishful thinking.

Open for business

It is great to hear about the plans to kick start cancer screening. There have been a number of urgent cancer surgical lists.

It is difficult not to feel for some of the COVID patients – the stories have been especially desperate. There have been family members who act as carers for sick relatives, NHS colleagues, and husbands and wives both on ventilators.

However, the statistics for COVID patients in intensive care are especially grim – see my previous despatch explaining how 49% of patients in the UK survive to discharge from intensive care according to ICNARC data. This compares to invasive breast cancer where over 80% of patients survive for 5 years, or coronary artery bypass surgery where 5 year survival can be as high as 90%. Even organ transplants have a higher survival rate.

It is a little crazy that we have effectively stopped treatment of other life-threatening diseases in favour of COVID. It is probably a bit unrealistic to expect hospitals to stop treating COVID patients, but perhaps we could think of a more nuanced approach to this. One idea that certainly was considered in the early days, but seems to have been discounted, was having ‘hot’ and ‘cold’ hospitals. All COVID cases would be evacuated from specific tertiary care facilities so that they could continue business as usual for cancer chemotherapy, heart surgery and other diseases.

This idea may have to wait for wave two and three if they ever eventuate. It could even have utility for future non-COVID driven consolidation of specialist services. Barely a day is going by when I do not hear about another COVID ward being transformed back into a ‘normal’ surgical or medical ward. Every day is starting to feel like spring has arrived with a creeping sense of normality returning. There is light at the end of the tunnel. It doesn’t look like a train coming towards us.

What is the purpose of lockdown?

Prime Minister Boris Johnson officially declared last Thursday that we are past the peak. We have not, however, reached the peak of politicians and civil servants running the show.

Now that we’re at this point it begs an interesting question: what is the purpose of lockdown?

1. Protect the NHS and save lives by spreading the infection rate so that we do not overwhelm the NHS (“flattening the curve”)? This is what we were told at the start of lockdown. It implicitly this means that we expect most or at least many people to get the virus, but we can save lives by ensuring that we have the capacity to escalate their care all the way up and including intensive care. Also, implicitly, there will be some folk who get infected that will lose their lives no matter how intensive our medical interventions; or

2. Save lives by preventing infection until a vaccine is available or that infections go below some critical mass? Lives are effectively saved not by managing demand to the capacity of the NHS but by simply preventing infections through mass quarantining.

The Government has effectively pooh poohed the herd immunity strategy, and the Prime Minister is not relaxing the lockdown despite evidence that the NHS is busy but not currently overwhelmed. If there is now a change in strategy then surely we ought to be told and the basis for this change to be explained or debated.

At the risk of banging the drum, there is no vaccine on the near horizon and the virus is not about to melt away over the next 48 hours. I am not a professional economist, but enough economists talk about medicine that I feel somewhat emboldened to return the favour and give my economic assessment – I don’t think we can afford the current economic cost for much longer.

If we take the view that the NHS was never really overwhelmed by the first peak, and that the NHS is able to offer the best possible care, then it logically follows that none (few) of the current deaths are truly avoidable – they would likely happen even if the peak could have been further delayed.

The Government is now talking about the R0 numbers in pandemic models with the over familiarity of an Australian cricket commentator. I worry that the Government is effectively being reactive to short term political soundings and by implication is pushing an erroneous view that we can somehow avoid a relatively significant number of COVID deaths by continuing the economic free fall.

For my money, we need to rethink the lockdown not just because of the important notions of what it means to live in a free society, but also because they are no longer practical and there is no purpose in keeping the infection rate so far below the capacity of the NHS that it simply delays the time to herd immunity.

So that's where the customers went

Last weekend was a humdinger in A&E. It was definitely the busiest we have seen for weeks. It was also notable because there were far more patients with symptoms that had nothing to do with COVID-19.

The department was still split into a COVID side and a non-COVID side. We are still seeing suspected COVID-19 patients with plastic aprons, gloves and bare arms… plus ça change, plus c'est la même chose (“the more it changes, the more it's the same thing”).

The other side of the department was a grand assortment of injuries. The public are voting with their feet when it comes to lockdown, increasingly deciding to enjoy the sun shine. As doubt about the lockdown and its length are building, the British are quietly practising civil disobedience in the understated way that only the British can. Although the British have no constitution (apologies for the controversial view), they simply assert their rights and dare the government to disagree.

The gradual breakdown in the lockdown is also noticeable as I travel to work with a lot more traffic. We are seeing a lot more of the usual A&E fodder – injuries to ankles and wrists… especially from mountain biking.

We are also seeing some serious medical conditions that have clearly been brewing. As an example, I saw a middle-aged patient presenting with shortness of breath that turned out to be caused by a massive collection of fluid in the chest. Although any diagnosis of cancer will require biopsies, the imaging was pretty suspicious. This patient had clearly twigged that something was wrong some time ago but had chosen to sit on the symptoms with the hope that they would go away. In this sad case, the delay in presentation caused by COVID is unlikely to change the outcome but has begun to highlight the real problems of effectively closing hospitals to non-COVID patients.

For some patients, closure of screening programmes will clearly change outcomes from potential cures to palliation.

Medicine during COVID

I have been asked how medicine is practised differently under the threat of COVID. The intensive care unit is perhaps the most vivid with the department. it is split into three main areas.

The patient area that requires gowning and gloving to enter. The gowns are running out so it’s now what looks like a modified garbage bag with a plastic apron worn back to front to cover the back. The Parisian catwalk look is completed with a headcover slouched beret style over one eye and a full face visor.

The nurses are bearing the brunt. They are splitting shifts to avoid spending all day in stifling heat with waterproof clothes that do not breathe. You can barely hear when we talk masks and visors. Some put their names on the front of their gowns, however, most people are more recognisable by their eyes than you would think.

The intermediate area is a half dirty layer. Staff wear face masks to protect against aerosols generated from the patients leaking out when doors are opened. We also wear scrubs and wash our hands until they are red. You have to imagine that every surface is coated in an invisible layer of viral dust. Staff here are servicing the patient facing nurses – communicating using a walky talky or by writing onto a whiteboard outside each room. Drugs and equipment are left outside the doors which are opened and closed quickly when things are retrieved.

The clean area is furthest from the patients and is ‘sealed’ off by the plastic curtains that we used to see at butchers in the old days. They are cleaned frequently but everyone hates going through them as they psychologically feel dirty because everyone has to touch them. Also, no matter how you try to squeeze through them, they drape all over you like a dead octopus. Once through, we really only have the staff round to unwind.

Each day starts with a handover round where the night team hands over to the day team – each patient is well known by now so only the ‘highlights’ are shared.

The board round follows. Doctors sit with pharmacists, specialist nurses and dieticians going through each patient laboriously. Intensive care is about detail but also trying to join up the picture from multiple perspectives. In trying to help one organ system, it is common to create problems for another organ. Today this leads to yet another debate over how ‘wet’ to run the patients – or in other words how much fluid to give them. Walky talkies are used to relay observations from bedside doctors, and orders from the clean side team who use specialist software and telemetry to build a complete picture of the patient. Because these are civilian radios, we need to use bed numbers to refer to patients. The junior staff have ‘given’ everybody code names. Today these are in the style of top gun. X-Men is another favoured cultural reference.

The unit is full so the ward round finishes at about 14.00. Time for a quick bite of all the donated food – today is a delicious Thai green curry and an unhealthy quantity of Easter egg. The afternoon is soon filled with calls to patient relatives – always difficult although most of the staff have spoken to each family more than a few times. The main topic of conversation today seems to be how to get mobile phones to patients who simply cannot be visited. We aren’t sure whether patients will really be able to respond or if their obvious confusion will simply alarm rather than comfort relatives.

The late afternoon is typically filled with procedures. These can include central lines that feed into the large veins leading into the heart and allow multiple medicines to be given simultaneously; arterial lines that directly measure the blood pressure second on second; and tracheostomies which are breathing tubes that patients can tolerate without needing sedation and hence enable patients to move off ventilators. The afternoon also sees many of the transfers to and from other units to balance capacity – some units ran out of dialysis machines and proper intensive care ventilators early. Almost everybody is ventilating some patients using machines from operating theatres.

We finish off the afternoon by updating our handover sheet and handing back over to the night shift. These meetings are typically filled with humour and there is a comforting family-like atmosphere since there are only two shifts and the people you took over from in the morning are now slept and ready for another night.

The drive home is fantastic. The weather is good. There is NO traffic. Windows down, stereo on.

What's the exit strategy?

What is the exit strategy for all of this?

Some things have been obvious for some time:

1. We are in economic free fall – I don’t believe the exact numbers from the economists. Their track record is poor – very poor. Do people not remember the great financial meltdown Despite figures in the media, we cannot begin to estimate the size of economic hit. Even if we could, would it even be relevant to individual circumstances such as the loss of a job or business?

2. We have already missed the boat on testing - Tests can currently only identify the virus while a person is actively infected – not after the fact. The failure to mass test has denied ourselves the opportunity to identify those who have previously been infected. We also assume people cannot be reinfected – an assumption we should perhaps return to in the future.

3. The cavalry is not coming (anytime soon) – Tests to identify that a person has developed an immune reaction to the coronavirus do not yet exist. After the initial hype, all seems to have gone quiet as the reality of how difficult it is to provide a test really hits home. Vaccines also take at least 12-24 months, absolute minimum. To create something new it helps to have a starting point – the spoiler is that we didn’t really have a starting point on which to base a vaccine.

We have to decide how much economic pain we can endure and how we balance that against the inevitable additional deaths that will occur due to stopping the lockdown. Eventually, the infection will die out or at least dramatically decrease as herd immunity builds – remember how the government assured us that herd immunity was not their strategy… hmmm. 

For my money, I think we are about to witness just how little value is placed on life. This may shock the general population but is a well established branch of health economics. The National Institute of Clinical Excellence (NICE) in the UK has a threshold for whether it will fund a treatment. This threshold is not a fixed published number, but a value of £50,000 per year of fully enjoyed life – is arguably well above the level used by NICE. I will leave it for others to do the back of envelope calculation about the value placed on life that officials might actually be balancing against the economic costs of lockdown.

From this humble doctor can I suggest a classic playbook based on the past form of various politicians?

Classic ‘Goldilocks’ exit: neither too soon nor too late. Many eyes will be watching countries that are the first to exit lockdowns. Trump’s strategy is interesting here – easy to castigate and hence difficult to follow even if the US ultimately succeeds.

Leading from behind: try to seem ahead of events but in reality end a lockdown when it feels like the mood of the country has shifted sufficiently to being nearly bankrupt or simply bored of lockdown.

Shades of grey: move from complete lockdown to partial lockdowns of particular demographic groups – creates plausible deniability if it all goes horribly wrong.

Try to seed a popular potential exit strategy without being overly associated with it: use well placed individuals who are nonetheless not members of the government to suggest exit points to see if they are politically feasible. Suggested forms could be ending the lockdown “once we are over the peak”, “once we have NHS capacity”, “when deaths are below xx per day for a certain period of time”.

Find an expert to blame later: find an overly confident or glory seeking scientist to propose an exit. If possible one that can be based on a ‘scientific model’ that simple folk wouldn’t understand. Explain loudly that your role as a government is to be guided by experts.

Downplay the testing and vaccines as part of any exit: stop talking about tests of any sort as part of exit. Refer to past pronouncements as evidence of the government’s commitment to being led by the scientific evidence, and that they were always only ever part of the longer term strategy.

ICU patient outcomes from COVID-19

There are are a lot of numbers bandied about estimating the outcomes of patients in intensive care with COVID. Data from overseas is probably pretty accurate. It’s just that by the time you think about potential differences in admission criteria and standards of care, you subconsciously begin to discount its relevance.

In the UK the best source is the Intensive Care National Audit and Research Centre (INARC). Despite the effectively universal coverage of intensive care in the UK, it is worth noting that the published data only covers patients with positive COVID tests. We are also relatively early in the process, so the outcomes of many patients are still not known even though some may have been ventilated for four plus weeks.

The dataset is interesting because it also compares COVID to non-COVID pneumonia. The numbers from 18 April give some pretty sobering top level messages from an already large cohort of patients - so far 2396 have had outcomes reported (i.e. the patient has been discharged from intensive care or is dead). A similar number of patients are still receiving medical treatments. 

One quick caveat – this data only covers admissions to intensive care not all patients in the hospital. There is a myriad of reasons why patients may not get to intensive care and hence will appear under-represented. Many older patients with multiple comorbidities are likely to have respect forms where they express their wish not to receive invasive and potentially futile medical interventions. There are estimates that only about 1 in 10 patients getting to a hospital are admitted to intensive care.

Men are disproportionately affected compared to ‘normal’ viral pneumonia: 72% of patients admitted to critical care are men. Men are also more likely to die (53%) compared to females (45%). Of note, this disparity is far more pronounced than for non-COVID pneumonia where males mack up 54% of patients. What is it about COVID?

Half of the patients die even after receiving intensive care - We like to think of intensive care as a panacea, yet overall 51% of patients admitted to intensive care with COVID die. However, the old are affected far more than the young – 67% of patients over 80 die compared with only 22% of patients under 40.

Older patients are more affected – Despite the prominence of media reports of young patients dying, only 226 patients making it to discharge or death are aged under 40 years and so far 50 of these patients have died. Regardless of age, most patients were previously able to live without assistance in daily activities which indicates that highly dependent patients are simply not admitted to intensive care in the UK. It is still worth noting that COVID is more deadly for the younger population than ‘normal’ non-COVID viral pneumonia.

Patients of black and Asian heritage are disproportionately affected: According to the 2011 census, Asian ethnic heritage makes up 7.5% of the UK population but comprise 15% of COVID cases admitted to intensive care; black ethnic heritage makes up 3.3% of cases but over 11% of COVID cases admitted to intensive care. It is worth noting that this contrasts sharply with non-COVID viral pneumonia admissions where people of black and Asian heritage are slightly under-represented in intensive care admissions. We wonder is it because these groups have higher rates of diabetes and other serious diseases, or are there other fundamental reasons? 

Severe previous disease is a clear risk factor: A no-brainer really, but patients without commodities face a 50/50 chance of recovery sufficient to be discharged from intensive care. Patients with severe previous diseases – for instance – metastatic cancer, immunocompromise from steroids or HIV, kidney dialysis, or liver cirrhosis – the chances fall to only 39% recovering sufficiently to make it out of intensive care. Death rates in the morbidly obese are about 9% greater than in patients with a normal weight. This last group is really difficult since it is difficult or impossible to nurse these patients in prone positions which seems to be especially advantageous in COVID.

Requiring advanced respiratory support or kidney replacement therapy are especially poor prognostic signs – Again a no-brainer but I admit to being slightly surprised that the statistics were as good as reported here. Requiring advanced respiratory support – i.e., intubation and ventilation - has a mortality of 67% versus only 20% of patients requiring lower levels of respiratory support, such as oxygen by face mask or CPAP. 80% of patients requiring dialysis die. Clearly ventilation has a role, but we also need to be realistic that it is not a case of ventilating patients until they clear their lungs – based on these numbers most of these patients will die.

For those who have made it this far, the summary is short: if you need admission to intensive care then it is 50/50 whether you survive to get discharged back to a ward. In reality, we expect many patients with severe COVID to be left with permanent damage to their lungs, as was seen with other coronavirus diseases SARS and MERS.

For those interested in reading further, this data is from the ICNARC Case Mix Programme Database. The Case Mix Programme is the national clinical audit of patient outcomes from adult critical care coordinated by the Intensive Care National Audit & Research Centre (ICNARC). For more information on the representativeness and quality of these data, please contact ICNARC.

Clinical limbo and the end of the road

The intensive care unit is full during my latest shift. The slow drip drip drip of cases day by day has filled the unit.

The doctors have spent the past few weeks rebuffing soft and speculative referrals – professional relationships are surviving, even thriving despite the sometimes fraught conversations.

Many of the patients have now been on the unit for two or three weeks. Since these patients have developed respiratory problems two weeks after contracting COVID most of these poor folks are now effectively a month after they got infected. Most of the patients are surprisingly young – forties and fifties. They have a mix of co-morbidities, especially diabetes, smokers’ lung, obesity or kidney disease. After this long many of these patients are facing the end game.

About half the patients have managed to recover sufficiently to ‘earn’ a tracheostomy and be weaned off the ventilator. The damage to their lungs makes us all wonder if any will avoid being respiratory cripples. Despite this recovery, COVID is also leading to profound neurological dysfunction. Some patients are agitated and confused but for a significant proportion, the lights are on but no one is home. We wonder how families will react to their loved ones being different people.

Many patients are in a clinical limbo – not getting worse – but also not going forwards. The daily conversations with relatives are variations of the same theme trying to emphasise that in the big picture their relatives are critically unwell and that almost nothing can be read into the slight changes in oxygen or ventilation pressures. Relatives are clearly reading up on their medicine, clinging to every possible indication of improvement however unrealistic. Others are putting their faith in the divine – this is all God’s will.

Many of the patients are also on haemodialysis to replace kidneys which have failed. Now patients have not passed urine for weeks – each day makes it more and more unlikely that the kidneys will ever recover. Hence, in reality, these patients are clinically deteriorating, but this is hidden by the layers of medical intervention.

A few patients in this unit are now at the end of the road – changes are effectively like rearranging the deck chairs on the Titanic. Every day the ward round tries another attempt to reduce the level of support – usually resulting in a deterioration that leaves the later shift the work of reversing our changes. Today, another patient dies weeks into treatment – the oxygen level in their blood suddenly decreases – but with the patient already paralysed, on 100% oxygen and maximal pressure support there is nowhere else the clinical team can go.

The end is quick, quiet and peaceful and there is nothing else the team can do but to gown and glove to confirm life extinct.

Sunday Read: Where are the usual customers?

Another day with few patients except for those with COVID. Which all begs the questions: where are the usual customers?

Two patient groups of particular interest seem to have disappeared without a trace.

The first group is are patients with serious sounding symptoms or known serious diseases. This group includes patients with bowel obstruction, chest pain with known heart disease, head injuries in patients on blood thinners, and suspected fractured hips. These patients need to be expeditiously investigated on the day of presentation. Although many of these patients turn out to be not as serious as first thought, a good proportion need admission for observation, specialist opinions, and alterations to therapies. A sizeable number of these patients also require assessments for social care. Many patients will have significant medical interventions – coronary stents, hip prostheses, or the diagnosis of new cancers.

Some of these patients are still attending – after all you cannot walk on a fractured hip. However, there has been a distinct reduction in the number of these patients. Talking with others, we are slightly suspicious of the consequences of the stoicism that is often seen in these patients. They often say things like “we weren’t sure whether it was serious so didn’t want to bother you”. There is genuine concern that when normality returns we will find a number of patients who now have significant and irreversible impairments to their health – for instance, a cancer that has now spread, or coronary artery disease that has now caused a heart attack and actual scarring of the heart.

The other group we are talking about are the “worried well” who should normally see their GP about minor complaints including sore throats, skin rashes, constipation and such like. Many patients attend A&E instead of their GP because they do not have a GP or claim not to be able to get an appointment. Being seen within 4 hours in A&E is often preferred by patients of working age as they can attend out of hours and do not have to compete with elderly patients or children who will always tend to get priority at the GP, and who also have more flexibility to attend the GP. The availability of specialists, blood tests and imaging also means that patients get a relatively thorough workup.

Unfortunately, A&E doctors do not know these patients so must start from scratch for each patient. Many A&E doctors are also relatively junior so each attendance takes significantly longer than an experienced GP – often as long as 45 minutes to an hour.

The exact number of these patients is always a little contentious when I discuss them with my colleagues – although it is fair to say that even as few as 5% (1 in 20) adds a distinct burden in a system that is creaking. Because A&E departments do not routinely turn these patients away, and the doctors and nurses are (nearly) invariably polite, there is little to dissuade these patients from effectively bypassing the primary care system. Not all of these patients have malign motives for attending A&E – most simply don’t know what is serious and what is not, and everything feels serious in the middle of the night with only the wonderful interweb to create a further sense of panic.

When this crisis is over – if anyone is listening who deals with these things -it would be much appreciated if we could find a better mechanism for dealing with these attenders. They are ultimately a symptom of a deeper issue in the NHS: how do we fund patient care?

In simplistic terms, the current system uses a fixed budget as the starting point. Service obligations require the NHS to see all patients that turn up. Great idea if the budget matches the demand - the Government gets to set a consistent budget and also claim politically that it has paid for the healthcare that voters have asked for.

Reality is somewhat more complex. The budgets are not matched to demand.

Some of the problem is demographic. We have a population that is both growing but also ageing. There has been little recognition that costs will rise much faster than the rate of inflation. Moreover, not all health costs are fixed costs. Many costs scale with the number of patient care episodes – for instance each hip operation requires an expensive prosthesis. NHS trusts have no option but to go into deficit since they are not allowed to deny patients care, even if it is simply impossible to provide it for the money that is being given. Although there are likely to be NHS trusts that are not well managed, the majority of deficits are likely to be simply where budgets have not adequately allowed for the service provision demanded.

These fixed budgets are then cascaded down to the various healthcare providers. The current system effectively assumes that patients will choose the right care environment. Even with Google and the increasing number of diagnostic apps, it is more difficult than is readily appreciated to understand if symptoms are serious or not, or whether they should be seen by a GP or other service.

Ultimately the NHS is ‘free at the point of use’ but it is not free. We need to think again about how we resource health care. The answer is surely to make the costs of each patient care episode more transparent and effectively to move toward event driven reimbursement mechanisms. These are widely used across the globe and which give patients greater freedom to choose when and when they access healthcare. These mechanisms enable funds to follow the patient, no longer do we need to care whether we have been given the resources to deal adequately with demand.

Where are all the patients

Wow… that was a quiet day.

Started quietly then a two hour rush of ambulances – all slightly ominously from care homes – all elderly patients with COVID. Through the grapevine it sounds like some rest homes residents have been hit really hard – difficult to gauge whether the numbers get exaggerated like the game of Chinese whispers.

Always humbling to see this generation face unbelievable odds – despite the grim statistics confirming the various risk factors some of these folks just seem to float serenely above it all. Not confused and just accepting it all as part of the rich tapestry of life. Asked one of them what they made of all this – they simply mentioned that they did their best to live a life without regrets. Spend more time with your family, they tell me.

No one regrets having not done more work. Hmmm…. Think I just got schooled.

And then as soon as the rush seemed to start, the patient flow all dried up leaving us with more doctors than patients. Weird day.