Richard Lehman’s journal review – 16 January 2012

Richard LehmanJAMA  11 Jan 2012  Vol 307
157    There’s a general feeling among cardiologists that low potasssium is a bad thing, but this interesting observational study of 38 689 patients with acute myocardial infarction shows that a high potassium can be even worse. On admission with AMI, potassium levels are normally distributed (figure 1): mortality in relation to potassium levels thereafter follows a  classic U-shaped distribution, bottoming out under 10% between 3.5 and 4.5 mmol/L but hitting an alarming 60+% by the time you reach the pretty modest level of 5.5 mmol/L. The strength of the association on both sides of the curve really is quite dramatic, which presumably is why JAMA is releasing the full text of this paper free online. What it means for clinical practice is not for me to guess: go instead to the learned editorial.

173    The only objection I have to people smoking marijuana is that it sometimes makes them a bit vague and boring; perhaps it can also unmask psychosis on rare occasions, and of course it usually involves inhaling tobacco smoke. This curiously hyped observational study looks at people who smoke pot on a median of 2-3 occasions per month. That’s an awfully tiny amount of tobacco, or indeed hemp. No wonder it has no discernible effect on pulmonary function over 20 years.

182    “So teach us to number our days, that we may apply our hearts to wisdom” (Ps 90;12) is the text I usually preach to when discussing prognostic indices for older people. Now that I’m an older person, I am increasingly unsure about what particular wisdom to apply my heart to. It’s a toss-up between the wisdom that it’s nearly all over for me, and it’s time to pack it all in and relax; or the wisdom that the world is a place that still needs some attention, and one should try one’s best for as long as possible. I certainly don’t want anyone telling me when they think I am going to die. If I did, I would ask them to measure my BNP, cystatin C, and copeptin, serially. This systematic review does not deal with biochemical tests, rather with a number of scoring instruments which are not disease-specific. Using these, you can decide whether people are still worth putting through various forms of cancer screening or being given preventive drug treatment such as statins. The patient really doesn’t get much of a look-in in this paper: presumably the idea is that doctor says to the patient, “Now look here old thing, everything points to the fact that you’re going to pop you clogs in the near future, so let’s not bother with any of this any longer, eh?” Personally, I’d rather the patient said this to the doctor.

NEJM  12 Jan 2012  Vol 366
109    I am nearing the end of Siddhartha Mukerjee’s exuberant history of cancer, The Emperor of Maladies (2010), where he is about to reach the story of “Herceptin” in the early 1990s. I am amazed that this drug, which should be called by its real name, trastuzumab, was around as long ago as that. Surely it should be off patent by now if that is the case? Anyway, long experience has taught us that given alongside docetaxel, trastuzumab provides very little worthwhile benefit in advanced metastatic HER-2 positive breast cancer. Pertuzumab is another monoclonal antibody which targets the HER-2 receptor, but by another mechanism, so the uzumabs act synergistically. This is shown to have marginal clinical benefit in this manufacturer-funded trial which randomized 808 women to either trastuzumab with paclitaxel, or to both drugs with paclitaxel. The latter group showed progression-free survival of a mean 18.5 months as compared with 12.4 months, which sounds impressive, but the overall mortality difference did not reach significance. In other words, the number needed to treat to affect survival was not determinable within the 400 randomized to this treatment, and any possible gain in lifespan would involve spectacular expenditure in the clinical setting – if indeed it is achievable at all. There are plenty of other similar agents in the pipeline, which the editorialist describes, apparently without irony, as “an abundance of riches.” For whom?

120    Do you have paroxysmal atrial fibrillation? You might, perhaps while you are asleep, or so asymptomatic that you know nothing about it. The ASSERT study found evidence of atrial tachycardias in 10% of a population fitted with pacemakers or implanted defibrillators over a period of 3 months. In the next two-and-a-half years, these people had nearly three times the risk of stroke and over five times the risk of developing permanent AF. Should we screen for it in this population? Should we offer them warfarin? Or rivaroxaban? Over to the triallists.

130    The Greek word for fennel is marathon, and it was on a fennel covered field that the Greeks repulsed the army of Persia – a most regrettable encounter which has retarded the progress of civilization to this day. To quote Wikipedia: “The traditional story relates that Pheidippides (530 BC–490 BC), an Athenian herald, was sent to Sparta to request help when the Persians landed at Marathon, Greece. He ran 240 km (150 mi) in two days. He then ran the 40 km (25 mi) from the battlefield near Marathon to Athens to announce the Greek victory over Persia in the Battle of Marathon (490 BC) with the word “Νενικήκαμεν” (Nenikékamen, “We have won”) and collapsed and died on the spot from exhaustion.” Serves him right: it was a very foolish thing for a forty-year old man to do. Moreover, if he was so out of breath, he did not need to use the reduplicative aorist. Male marathon runners continue to drop dead at an increasing rate (2 per 100,000), and this study identifies the chief causes as atherosclerotic coronary disease in the older runners and hypertrophic cardiomyopathy in the younger. If only the Persians had won: we might have a world free of marathons, Olympic games and unhelpful Greek medical terms like hypertrophic cardiomyopathy (or such really exotic examples as paragonimiasis).

Lancet  14 Jan 2011  Vol 379
123    Idrabiotaparinux is a word which belongs to no known human language: it is made up of “idraparinux” (perhaps inspired by the characters in Astérix, as this is a French drug) and biotin, sometimes known as vitamin H (a Greek root sneaks back in here). You will, I am afraid, have to memorise this word, because idrabiotaparinux marks a breakthrough in anticoagulation. It is a safe, effective anticoagulant which inhibits factor Xa : it has a terminal half-life of 66 days and a simple antidote in the form of avidin (an egg-derived substance). In this study, it was given by weekly subcutaneous injection, but there seems no reason why that could not be monthly. Patients with acute symptomatic pulmonary embolism were started on enoxaparin and then allocated (with complex blinding) either to idrabiotaparinux or to INR-adjusted warfarin. As usual in The Lancet, the manufacturers are allowed to sneak statistically non-significant claims for their product into the abstract: but the fact remains that idrabiotaparinux is non-inferior to warfarin in preventing VTE following PE, and probably a lot more convenient for most patients.

136    Paris became the world’s chief centre for medical education around 1800, just after the Revolution, when the city’s main hospitals were secularized and integrated into a massive teaching unit. Here students from America and all over Europe could question and examine thousands of inmates and then discover the causes of their illness in post-mortem examinations. A few patients had the temerity to survive, but the rest were invariably dissected. Now, alas, there are but few corpses on the pathologists’ slabs: the modern doctor may make fewer mistakes, but she or he can bury or burn them with greater impunity. Pathologists from Manchester and Oxford demonstrate here that scanning is no substitute for prosection – CT is better than MRI but still inadequate in a third of cases. Imaging is particularly inaccurate in determining the cause of sudden death. If we are to get at the truth, we need to become more like the post-revolutionary French. Vive la morgue!

153   I guess most of my readers have never seen measles, and this punchy review will not help them to recognize it the way we used to, as a febrile, spotty, red eyed child came coughing into the consulting room. The nearest you get is a rather ancient illustration of Koplik’s spots. Hopefully doctors in generations to come will never need to recognize the disease at all, as it does not exist outside humans and is a prime target for global eradication. At present it still kills more than 100,000 people a year and is one of the most contagious diseases of all – it can propagate even if less than 10% of the population is susceptible. Keep vaccinating.

165    Unlike measles, the great majority of chronic kidney disease is totally invisible. So invisible, in fact, that most people with it never experience anything. They are silently suffering from a form of organ failure so subtle that, left alone, they will die of something else without ever being aware of it. I skimmed this review dutifully to see if I was missing some deep reason why we should awaken our elderly patients from this blissful state of ignorance, but found none. The authors are particularly emphatic that most long-term interventional trials in “CKD” are inadequate to form the basis of a population strategy.

BMJ  14 Jan 2012  Vol 344
The Hypertension in the Very Elderly Trial (HYVET) recruited 3845 subjects over the age of 80 using a huge team of investigators from 11 countries, dominated by Bulgaria, Tunisia, and China, between 2000 and 2003. Indapamide was the main intervention used to get the systolic BP under 160mm Hg – a strange choice since there are so many other thiazide diuretics that cost practically nothing. The second-line drug was perindopril, also made by the co-sponsor of the trial, Servier. Oh well: there are no doubt plenty of people still taking these drugs in the centres chosen. And they continue to benefit, as the BMJ shows us in this paper about an open-label follow-up cohort; though I imagine the subject who was 105 at the start may no longer be among them.

An intriguing study of the UK General Practice Research Database suggests that taking bisphosphonates doubles the lifespan of joint replacements. This could be an immensely important discovery, though it clearly needs to be replicated in prospective trials. It is all the more remarkable since people taking bisphosphonates – due to osteoporotic fracture, long-term steroid use or severe osteopenia – are just the ones you would expect to need the most revision of joint replacements. Just imagine if a cheap, well-tolerated annual infusion could halve the rate of revision joint surgery in future health systems.

Arch Intern Med  9 Jan 2012  Vol 172
41    Having been so dismissive about chronic kidney disease, I was eager to be enlightened by these follow-up data on progression to end-stage renal failure according to blood pressure in the cohort (mean age 69) from the Kidney Early Evaluation Program (KEEP). According to the authors, “The KEEP is a health screening program that attempts to raise awareness of CKD in the population.” They then demonstrate that serious kidney failure occurs at a rate of about 14% in this elderly cohort over a period of 10 years if the systolic BP is above 150 (one measurement). “Findings did not materially differ when limited to persons with eGFR lower than 60 mL/min/1.73 m2 and macroalbuminuria (ACR   300 mg/g).” From which one might conclude that one should attempt to reduce awareness of eGFR and albumin excretion. The label of CKD does nothing to inform treatment: just aim to reduce the systolic BP in your elderly patients, and you will help to prevent a lot of strokes, some heart failure, a few myocardial infarctions and a little bit of kidney failure.

Plant of the Week: Foeniculum vulgare “Purpurea”

Mention of the Greek word marathon for fennel reminds me of the excellence of this garden plant, especially in the winter months, when frost gives a magical appearance to its tufts of thread-like leaf. These plumes of icy gossamer may herald the death of the plant, which is none too hardy in cold British clay, though it has become a perennial weed wherever the summers are hot and the soil is light, as in many parts of Europe and the USA.

The bronze-leaved version is the one to grow, unless you want big bulbs to eat raw in salads or cooked in Italian dishes. It is a wonderful foliage plant, up to the point that it throws up its flower-stalks and goes to seed. The seeds should be used for fish dishes and the stalks should be kept and dried.

Fish and fennel are made for each other. It is a more delicate herb than dill, and is a superior substitute for dill in most situations, for example in making gravadlax. This is extraordinarily simple and only requires a filleted cheap salmon, salt and sugar, plenty of fennel fronds and a suitable kind of spiritous liquor, such as rum, brandy or whisky.

When cooking sea-bass in butter and wine, you should consider adding fennel-seeds (which are actually fruits); and fennel leaves make a fine decoration for the served fish.

Prometheus used dried fennel stalks to bring fire from the gods to men, and Elizabeth David waxes sternly lyrical about the Mediterranean habit of burning dried fennel stalks under grilled fish to impart flavour. I have never tried this, though I once dried a lot of fennel in readiness. The Supreme Instructress warns that the cook should exert strict control over the process, so as to avoid serving guests fish that is covered in bits of burnt fennel. Just to be awkward, I think I shall make this a special feature of the Sea-Bream “Prometheus” which I intend to serve at summer barbecues this year.