Richard Lehman’s journal review—24 October 2016

richard_lehmanNEJM  20 Oct 2016  Vol 375

Fainting and pulmonary emboli


O Padua, sidus praeclarum,          O Padua, brilliant star,
hocce nisa fulgido                         
luminous model
virtutum regula morum                  
of virtues and manners,
serto refulgens florido,                  
resting on this radiant wreath of flowers,

te laudat juris sanctio,                    you receive praise from jurisprudence,
philosophiae veritas                      
from philosophical truth,
et artistarum concio,                      
from the artistic community
poematum sublimitas.                  
and from the sublimity of poetry.

So begins Johannes Ciconia’s three part motet from around the year 1400. By this time, medicine had already been taught in Padua for about two centuries. The city’s greatest medical glory was to come 140 years later, when Vesalius gave his famous anatomical lectures there and produced De humani corporis fabrica. A pupil of Vesalius, Realdo Colombo, was the first person in the western world to describe the pulmonary circulation. This week Padua and the pulmonary circulation get their place in the NEJM with a cross-sectional study (funded by the University of Padua) of the prevalence of pulmonary embolism in patients presenting with syncope and admitted to 11 Italian hospitals. The startling conclusion reads, “Pulmonary embolism was identified in nearly one of every six patients hospitalized for a first episode of syncope.”

Blimey. Can that possibly be true? Should we be doing Wells scores and D-dimers on everyone who passes out in the street? The short answer is no, as explained in a terrific short blog that Rory Spiegel, an American ER physician, wrote soon after the paper appeared. The key paragraph reads: “Furthermore, it is important to note, this is not a cohort of 97 pulmonary embolisms in 560 patients as it will inevitably be portrayed. Rather this was 97 (3.8%) radiographic pulmonary embolisms in 2584 patients presenting to the emergency medicine for a syncopal event. Only the patients admitted to the hospital after an emergency department workup for syncope were enrolled into the PESIT cohort. The majority of patients presenting to the emergency department were discharged home without further workup. This means one in 26 patients presenting to the emergency department will have a pulmonary embolism found on imaging. The large majority of these will be incidental findings and the remainder will be clinically obvious.”

What Padua really needs to give us is a new Realdo Colombo-like dissertation “On the Lungs as Sieves” (De pulmonibus sicut cribra, 2017). The Paduans need to do CT angiograms on all their newly presenting ER patients—I suspect the baseline figure for PE would be about 3.8%. The lungs pick up all sorts of stray debris from the venous circulation all the time. And by the way, it wasn’t really a Paduan who first described the pulmonary circulation, but Ibn Nafis (1213–1288), a Syrian born physician who spent most of his life in Cairo. He refuted Galen’s idea of a permeable cardiac septum in his Commentary on the Anatomy of the Canon of Avicenna.

Not that any of this can detract from the true glory of this beautiful North Italian town, as Ciconia concludes:

Tuae laudis preconia                               Renown marks the proclamation
per orbem fama memorat                       
of your praise throughout the world,
que Johannes Ciconia                             
which Richard Lehman re-echoes
canore fido resonat.                                
with his faithful song.


JAMA  18 Oct 2016  Vol 316
Mending incisional hernias
The journals are offering me little to bite on this week. Here is an observational study from Denmark on the five year outcomes of abdominal wall incisional hernia repair according to whether it was performed with or without mesh. I am afraid that I cannot pad out this section with any references to early Danish motets or quotations from Hamlet. The simple fact is that mesh repair provided better early results, but over five years the stuff can move about, become infected, or otherwise cause nuisance—partly offsetting its advantages. This is another surgical study that needs turning into a decision aid.

Oxygen in ICU
After the Brexit vote, we need to reassert the British ownership of oxygen. With so few things to trade in, we should insist that foreigners pay us Priestley Duty on every litre of dephlogisticated air, which its discoverer described as “five or six times better than common air for the purpose of respiration, inflammation, and, I believe, every other use of common atmospherical air.” We altogether reject the claims of foreigners like Scheele or Lavoisier: it was our Joseph who found it. Shame that he then had his house and laboratory burnt down by a mob of xenophobes and obscurantists and had to flee to America, where he was miserable for the rest of his life. Some fine English traditions die hard. As for oxygen, we continue to revere the therapeutic benefits of this dangerously reactive gas. Here’s a prematurely terminated trial from the University Hospital of Modena in Italy, which randomised ICU patients staying longer than 72 hours to conventional amounts of oxygen or a conservative oxygen regimen. Survival was better in those who got less oxygen. As for Modena, don’t get me started. Everyone should visit this North Italian city once in their lives, to sample the architecture of its tiny but sublime Romanesque cathedral and the cookery of Massimo Bottura at the Osteria Francescana.

JAMA Intern Med  Oct 2016  Vol 175
Quality of outpatient care in the US
Every now and again, I dip back into the works of Avedis Donabedian, who published three books and a dozen key papers on the assessment of quality in medical care, and refused to come up with any simple solution. How right he was. Here is a study that is supposed to describe how the quality of outpatient care has changed in the US between 2002 and 2013. There were some small shifts in categories of “appropriateness” of treatment and advice about screening. Overall, nothing much changed. I suspect nothing much will ever change until a new medical workforce appears, taught from the start how to conduct better dialogues with patients and use their goals and experiences as the main metric for quality. This will probably be the work of two generations, and it’s the greatest challenge for the medicine of our century. But, as Gandhi would have said, you can start right away with yourself.

Caffeine & heart failure
Needless to say, I am writing this with a mug of coffee by my side. If I developed heart failure, would I need to give up this daily essential? Probably not, judging from a simple human experiment conducted in Brazil, still the largest producer of coffee in the world. Patients with systolic heart failure and at high risk of arrhythmia were recruited from a clinic in Porto Alegre and given 100mg of caffeine or placebo in addition to decaffeinated coffee every hour for five hours. During this time they were monitored for arrhythmias, and the experiment was repeated one week later. The high doses of caffeine provoked no arrhythmias in these high risk patients. I hope they were rewarded with many bags of real coffee beans.

Lancet  22 Oct 2016  Vol 388
From nose to knee
From this Lancet article, I learn that the chondrocytes of the human nasal septum are of a higher quality than their sister cells which live in joints.
“Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects.” The investigators at University Hospital Basel decided to try out lab enhanced nose cartilage to repair full thickness cartilage injuries in the knees of 10 patients. “No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage.” So another somewhat promising phase 1 trial of an orthopaedic technique. Now we’ll just have to wait and see what bigger trials show.

Avoiding whole brain radiotherapy for lung cancer
Whole brain radiotherapy (WBRT) has predictable effects. Your hair will fall out and you will feel sick and lethargic while you’re having it and often for weeks afterwards. And then, in the case of the patients in the QUARTZ trial, you will die: over half were dead within eight weeks, all but a handful by a year. They had non-small cell lung cancer with brain metastases. I must say I shuddered when I read this paper.
It describes how, on the basis of observational evidence and one hopelessly inadequate 48 patient trial from 1971, an entire population of dying patients has been exposed to unnecessary treatment for half a century. Not just that, but WBRT has undergone all sorts of futile refinements, which increasingly include neurosurgery, stereotactic radiosurgery, and systemic treatments. This trial, conducted in 69 centres in the UK and three in Australia, conclusively shows that dexamethasone alone provides exactly the same survival rates with or without WBRT. It wasn’t until a Cochrane review in 2012 that people started to question the practice, which for all I know continues to be standard treatment. This is a horrible example, which should be included in every lecture on evidence based medicine. Set against it should be the landmark paper from 2010, in which Temel et al demonstrated that “Among patients with metastatic non–small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival.”

Expensive monitoring dies hard
This week sees the official launch of the UK Academy of Medical Royal Colleges’ Choosing Wisely campaign. While I was on its steering committee, I tried to nudge it away from a negative agenda of practices that ought to be discouraged towards a positive agenda of sharing decisions with patients. For example, if you are 75 or over and taking an antiplatelet agent such as prasugrel because you’ve been given a drug eluting stent, do you really want to have two lots of blood tests to monitor your platelet function when they contribute nothing to clinical outcomes? To ban the practice would be one way, but in some clinical areas this is going to look like rationing by stealth. However, here is a clear statement that is all the stronger for coming from the manufacturers of prasugrel and platelet tests, following a randomised trial in France:
“Platelet function monitoring with treatment adjustment did not improve the clinical outcome of elderly patients treated with coronary stenting for an acute coronary syndrome. Platelet function testing is still being used in many centres and international guidelines still recommend platelet function testing in high risk situations. Our study does not support this practice or these recommendations.”

The BMJ  22 Oct 2016  Vol 355
GLP-1 analogues & breast cancer
For decades, drugs have been licensed for human use on the basis that there will be surveillance for harms over ensuing years. In the UK, “Yellow Card” reporting has been the traditional method, but provides few statistical clues about prevalence or causality. It surprises me that there has been no massive revolution in this area. With whole population databases like those in Taiwan and some Nordic countries, associative data about drugs (and maybe devices too) should be rolling off the presses by the stack. Here is a neat, thoughtful study from McGill University, which uses data from the UK Clinical Practice Research Database to compare the breast cancer risk for women newly taking either glucagon-like peptide-1 (GLP-1) analogues or dipeptidylpeptidase-4 (DPP-4) inhibitors.
Contrary to concerns raised by the US Food and Drug Administration, there is no signal for an increase in breast cancer related to GLP-1 analogues. There are lots of papers like this that need writing, and if you’re thinking of doing so, you could do a lot worse than follow the template of this one. And then go on to examine all the other big databases.

Fungus of the Week: Clitocybe dealbata
This is the time of year when lawns tend to sport little fungi that appear and disappear within a day or two. Most people would not think of collecting them for the table, except for the fairly long lived fruits of Marasmius oreades, the fairy ring mushroom. Unfortunately, there are two small fungi of roughly similar size and appearance, which are lethally poisonous. These are Clitocybe dealbata and C rivulosa.

I’ve often seen them on lawns where children play and I’ve then wondered whether to point out their deadly properties or to remain silent, in case any child might be tempted to feed them to a sibling in a fit of pique. The happy fact seems to be that British children, at least, don’t seem very keen to pick or eat toadstools of any kind, especially drab looking little ones. There has never been an attested death from clitocybe poisoning in the UK.

So the best safety advice is to ignore all lawn growing fungi. If you want to know what these clitocybes look like, go online or consult a book—several books, in fact, since their appearance varies and often isn’t very well captured on a single photograph.

Editor’s note: The section on caffeine and heart failure was updated shortly after publication to clarify the amount of caffeine given to participants.