{"id":47319,"date":"2020-04-27T17:47:36","date_gmt":"2020-04-27T16:47:36","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=47319"},"modified":"2020-05-05T11:27:56","modified_gmt":"2020-05-05T10:27:56","slug":"richard-lehmans-covid-19-reviews-27-april-2020","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2020\/04\/27\/richard-lehmans-covid-19-reviews-27-april-2020\/","title":{"rendered":"Richard Lehman&#8217;s covid-19 reviews\u201427 April 2020"},"content":{"rendered":"<p class=\"standfirst\">In this weekly round-up, Richard Lehman looks at a personal selection of articles of relevance to clinicians dealing with covid-19<!--more--><\/p>\n<p><b>The Kung Fu of Covid<\/b><\/p>\n<p><span style=\"font-weight: 400\">One third of a year has passed since the start of the covid-19 pandemic, but there is little sense of shared global wisdom. The Chinese sage <\/span><span style=\"font-weight: 400\">K\u01d2ng Qi\u016b (551-479 BCE)<\/span> <span style=\"font-weight: 400\">would be saddened. Among the many sayings attributed to him are: <\/span><span style=\"font-weight: 400\">\u201c<\/span><i><span style=\"font-weight: 400\">All people are the same; only their habits differ<\/span><\/i><span style=\"font-weight: 400\">.\u201d China, with the largest population in the world, is the only one which has come close to eliminating covid-19 within its borders (with the possible exceptions of New Zealand and Iceland, as we go to press). Among 1.4 billion people, daily deaths are zero. Why then isn\u2019t the rest of the world rushing to adopt the habits of China? Another maxim of Confucius\/Kung Fu is \u201c<\/span><i><span style=\"font-weight: 400\">Learn avidly. Question repeatedly. Analyze carefully. Then put what you have learned into practice intelligently.<\/span><\/i><span style=\"font-weight: 400\">\u201d\u00a0<\/span><\/p>\n<p><b>Dialogue concerning the two world systems<\/b><\/p>\n<p><i><span style=\"font-weight: 400\">\u201cThe man who asks a question is a fool for a minute, the man who does not ask is a fool for life.\u201d<\/span><\/i><\/p>\n<p><span style=\"font-weight: 400\">Galileo wrote a dialogue to show you could not believe contrary things at once: either the sun revolved around the earth, or the earth revolved around the sun. Unfortunately the Pope was office-bound to believe the first, and Galileo\u2019s book made him look a fool. Mistake. The pope remained a fool for life, and Galileo remained under house arrest for life. Now, with covid-19, any containment policy either revolves around the value of individual life, or it revolves around the economy. It cannot do both at the same time. China exemplifies the first, and Britain exemplifies the second. <a href=\"https:\/\/www.gov.uk\/government\/speeches\/pm-statement-on-coronavirus-12-march-2020\">On 12 March<\/a><\/span><span style=\"font-weight: 400\"> our chief medical officer, chief scientific officer, and our prime minister Boris Johnson declared in favour of \u201cherd immunity\u201d<\/span><span style=\"font-weight: 400\">, and nothing that has happened since shows serious intent to prevent the cull which that implies. Britain has already lost ten times more people per head of population than China during the whole of its epidemic. If we had started by valuing the individual, this would not have happened. And our economy would be less ruined too. Maybe there is time to mend our ways in the second wave.\u00a0<\/span><\/p>\n<p><b>Controlled Avalanche<\/b><\/p>\n<p><i><span style=\"font-weight: 400\">\u201cDo not impose on others what you yourself do not desire.\u201d<\/span><\/i><\/p>\n<p><span style=\"font-weight: 400\">So let\u2019s say you have embraced the idea of herd immunity, without waiting for a vaccine. That means allowing the infection to spread through the population. It will kill those it is going to kill, but in a \u201ccontrolled avalanche\u201d that will be spread out to allow some to return to normal economic activity and health provision. That sounds like a good British compromise, though in fact the <a href=\"https:\/\/www.medrxiv.org\/content\/10.1101\/2020.04.12.20062687v1\">following model comes from Israel<\/a>. <\/span> <span style=\"font-weight: 400\">\u201c<\/span><span style=\"font-weight: 400\">Individuals whose probability of developing serious health conditions is low (i.e. 20-49 years old with no comorbidities) will be offered the option to be voluntarily exposed to the virus under controlled supervision, and will then be issued &#8216;immunity certificates&#8217; if they are confirmed to have developed SARS-CoV-2 antibodies.\u201d I can see that having some appeal, especially to altruistic health professionals who have already voluntarily exposed themselves to covid-19 risk through lack of protective equipment. What I can\u2019t understand is how the modellers come to the conclusion that this \u201creduces the overall mortality by 43%, reduces the maximum number of people in need for ICUs by 62%, and decreases the time required for release of 50% of the low-risk population by more than 2 months.\u201d <\/span><span style=\"font-weight: 400\">How can any controlled infection<\/span> <span style=\"font-weight: 400\">strategy reduce the virulence and case-fatality rate of the infection itself?<\/span><span style=\"font-weight: 400\">\u00a0<\/span><\/p>\n<p><b>Face value<\/b><\/p>\n<p><i><span style=\"font-weight: 400\">\u201cIf you make a mistake and do not correct it, this is called a mistake.\u201d<\/span><\/i><\/p>\n<p><span style=\"font-weight: 400\">When you put on a mask in public, you lose a lot of face. You also stop a lot of droplets. But this is at the cost of adopting a habit that many people in English-speaking countries seem to find repellent. I think they lose more face by insisting on randomised controlled trial evidence than they ever would by just putting on a mask. No RCT is ever going to be as good for detecting harms as a natural experiment involving 2 billion people. No cluster randomised trial of sufficient scale is going to be able to adjust for confounders any better than an observational comparison. Every population observation we have favours masking. Then triangulate this with some simple, common sense physical experiments, such as this<\/span><span style=\"font-weight: 400\">: \u201c<\/span><span style=\"font-weight: 400\"><a href=\"https:\/\/www.medrxiv.org\/content\/10.1101\/2020.04.19.20071779v1\">We found that most home fabrics substantially block droplets, even as a single layer. With two layers, blocking performance can reach that of surgical mask without significantly compromising breathability. Overall, our study suggests that most double-layered cloth face coverings may help reduce droplet transmission of respiratory infections<\/a>.\u201d <\/span><span style=\"font-weight: 400\">I do wish that some EBM-loving friends would admit that some ideas that have face validity are in fact valid until proven otherwise. On faces, even.<\/span><\/p>\n<p><b>Ventilator Mortality<\/b><\/p>\n<p><i><span style=\"font-weight: 400\">\u201cTo know what you know and what you do not know, that is true knowledge.\u201d<\/span><\/i><\/p>\n<p><span style=\"font-weight: 400\">A month ago the question on everyone\u2019s mind was how many very sick covid-19 patients would have to be turned away from ventilators. For some of us older people, there was also the question of whether it was worth going on to a ventilator at all. In fact it seems that very few ventilator rationing decisions have had to be made in the UK, and thanks to the <a href=\"https:\/\/www.icnarc.org\/Our-Audit\/Audits\/Cmp\/Reports\">brilliant work of ICNARC <\/a><\/span><span style=\"font-weight: 400\">we know that the mortality of ventilated patients in the UK is 67%. This is based on a <a href=\"https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/2765184\">much larger sample than from any other country<\/a>. <\/span><span style=\"font-weight: 400\">A more pertinent question may be: which patients really need ventilation and which might do better with a non-invasive strategy? Since continuous positive airways pressure was first proposed as an alternative, surprisingly little seems to have appeared about it in the clinical literature. Meanwhile, <a href=\"https:\/\/www.uchicagomedicine.org\/forefront\/coronavirus-disease-covid-19\/uchicago-medicine-doctors-see-truly-remarkable-success-using-ventilator-alternatives-to-treat-covid19?fbclid=IwAR1OIppjr7THo7uDYqI0njCeLqiiXtuVFK1znwk4WUoaAJUB5BHq5w16pfc\">high flow nasal cannulas <\/a><\/span><span style=\"font-weight: 400\">are making an appearance. I hope someone sorts all this out before I arrive on an ICU.<\/span><\/p>\n<p><b>Natural History<\/b><\/p>\n<p><i><span style=\"font-weight: 400\">\u201cNo matter how busy you make think you are you must find time for reading, or surrender yourself to self-chosen ignorance.\u201d<\/span><\/i><\/p>\n<p><span style=\"font-weight: 400\">I may have been reading the wrong journals, but so far I\u2019ve found little about the varied natural histories of the illness called covid-19. For sure, there have been plenty of symptom lists and time-course diagrams and so forth, but nothing that\u2019s helped me understand the transition from what I\u2019ve called benign covid into malignant covid. Now a very comprehensive review of the <a href=\"https:\/\/www.medrxiv.org\/content\/10.1101\/2020.04.19.20071548v1\">world literature has appeared in medRxiv.<\/a>\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">This divides covid-19 into three stages: \u201c<\/span><span style=\"font-weight: 400\">the time of infection (Stage I), sometimes progressing to pulmonary involvement (Stage II, with or without hypoxemia) and less frequently to systemic inflammation (Stage III).\u201d The hard-working authors go on to attempt to map therapy on to each stage. That is certainly the central challenge, though it seems hardly addressable in the present state of ignorance.\u00a0<\/span><\/p>\n<p><b>PM Question Time<\/b><\/p>\n<p><i><span style=\"font-weight: 400\">\u201cThe essence of knowledge is, having it, to use it.\u201d<\/span><\/i><\/p>\n<p><span style=\"font-weight: 400\">Now let\u2019s look at the few who die. Remember that modern medicine was not built on numbers but on observation: living patients reviewed on a daily basis, and then examined <\/span><i><span style=\"font-weight: 400\">post mortem <\/span><\/i><span style=\"font-weight: 400\">should they get unlucky. Autopsy just means seeing for yourself. I am baffled that medicine today should employ so many statisticians and so few gross pathologists. <a href=\"https:\/\/www.medrxiv.org\/content\/10.1101\/2020.04.19.20054262v1\">A new article tells us<\/a> about the lung findings in 38 patients from Northern Italy. <\/span><a href=\"https:\/\/www.sciencemag.org\/news\/2020\/04\/how-does-coronavirus-kill-clinicians-trace-ferocious-rampage-through-body-brain-toes\"><span style=\"font-weight: 400\">Terminal covid-19 is a systemic disease, <\/span><\/a><span style=\"font-weight: 400\">but I guess it\u2019s better to know about the lungs than about nothing. They are a mess, of course. \u201c<\/span><span style=\"font-weight: 400\">The features of the exudative and proliferative phases of Diffuse Alveolar Disease (DAD) were found: capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia, platelet-fibrin thrombi.\u201d There is lots about those thrombi in small arterial vessels, confirming that coagulopathy often dominates the end-stage of covid-19. In 4 patients, there were multiple small lung abscesses caused by bacterial infection.\u00a0\u00a0<\/span><\/p>\n<p><b>Silver lining<\/b><\/p>\n<p><i><span style=\"font-weight: 400\">\u201cSuccess depends upon previous preparation, and without such preparation there is sure to be failure.\u201d <\/span><\/i><span style=\"font-weight: 400\">Two and a half millennia later, this Confucian saying reappeared on the lips of Louis Pasteur (1822-95) as \u201cFortune favours the prepared mind\u201d. Pasteur\u2019s experiments with yeast and cotton wool had prepared his mind to discover that infectious diseases were transmitted by filterable micro-organisms. Before long, other people discovered that certain infectious diseases, like smallpox, were spread by organisms that seemed to be invisible and pass through filters. Subsequently, with better filters and stronger microscopes, these viruses appeared in their full glory. The image of a blob covered in a mass of collar studs that you see everywhere is a triumph of cumulative science. Forget post-modernism. This represents knowledge that is certain and will never go away. Soon it will lead us to an effective vaccine. There is no reason to doubt that: the only question is when and <a href=\"https:\/\/www.nature.com\/articles\/d41573-020-00073-5\">which of the 115+ candidate vaccines it will be<\/a>. <\/span><span style=\"font-weight: 400\">\u00a0And then it will all seem so straightforward. <\/span><span style=\"font-weight: 400\">\u201c<\/span><i><span style=\"font-weight: 400\">Anyone can find the switch after the lights are on.<\/span><\/i><span style=\"font-weight: 400\">\u201d<\/span><\/p>\n<p><span style=\"font-weight: 400\">No, Confucius did not really say that. There is no record that he invented the electric light in 500 BCE. Yet you can find it in a <a href=\"http:\/\/www.quoteambition.com\/famous-confucius-quotes\/\">list of his sayings on Google<\/a>.\u00a0<\/span><\/p>\n<p><a href=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/07\/richard_lehman2.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignleft size-thumbnail wp-image-42626\" src=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/07\/richard_lehman2-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" \/><\/a><em><span style=\"font-weight: 400\"><strong>Richard Lehman<\/strong> is professor of the Shared Understanding of Medicine at the University of Birmingham.<\/span><\/em><\/p>\n<p><em><strong>Competing interests<\/strong>: None declared<\/em><\/p>\n<p><strong>Email<\/strong>: <a href=\"mailto:r.lehman@bham.ac.uk\" target=\"_blank\" rel=\"nofollow noopener noreferrer\">r.<span class=\"il\">lehman<\/span>@bham.ac.uk<\/a><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><em><span style=\"font-weight: 400\">Articles from MedRxiv get special prominence in these reviews. MedRxiv is a completely free site for the rapid exchange of knowledge which was launched last year as a joint initiative by <\/span><span style=\"font-weight: 400\">The BMJ<\/span><span style=\"font-weight: 400\">, Cold Spring Harbor Laboratory and the Yale University Open Data Access project. All MedRxiv articles carry the caveat: <\/span><a href=\"https:\/\/www.medrxiv.org\/content\/what-unrefereed-preprint\"><span style=\"font-weight: 400\">This article is a preprint and has not been certified by peer review. It reports new medical research that has yet to be evaluated and so should <\/span><span style=\"font-weight: 400\">not<\/span><span style=\"font-weight: 400\"> be used to guide clinical practice.<\/span><\/a><span style=\"font-weight: 400\"> This review is intended as a quick source of information in a readable form. While every effort has been made to be accurate, the opinions are those of the author and should not be relied on without reading the full articles cited in the context of current NHS guidance.<\/span><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>In this weekly round-up, Richard Lehman looks at a personal selection of articles of relevance to clinicians dealing with covid-19 [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/bmj\/2020\/04\/27\/richard-lehmans-covid-19-reviews-27-april-2020\/\">More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":46950,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[111],"tags":[],"class_list":["post-47319","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-richard-lehmans-weekly-review-of-medical-journals"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - 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