Richard Lehman’s journal review – 11 July 2011

Richard LehmanJAMA  6 July 2011  Vol 305
45    Of all the great writers, only Chekhov captures exactly the balance of good and evil in rural life. Before his fame as a writer, he worked in a rural hospital, making the best of what support staff he had and what competencies he had acquired as a medical student in Moscow. To be a long way from specialist help was a precarious position for a doctor or a patient then, and is equally so now. Modern hospitals must have a certain critical mass to survive and be able to provide the basic range of core acute services: and which ambitious health professionals are going to choose to provide them, for the rest of their lives, on the tightest rota possible, in remote rural North Dakota? Not that Chekhov ever practised in North Dakota; but we are talking here about a study of American rural hospitals and their outcomes for myocardial infarction, heart failure, and pneumonia. Mortality is higher than for non-rural hospitals with much larger average acute bed numbers. Whether this will ever change is open to doubt: if you live in a huge country and want to enjoy the trees and sunsets described by Thoreau or Turgenev, you must not be surprised if the spectres of Chekhov and Bulgakov attend your sickbed.

53    By contrast, the down side of going to a big city hospital in America is that they will do too many things to you that don’t need doing. If you come through the doors of the hospital nearest to me in the middle of the night, you will get more investigations done before daybreak than you would get in a week lying on the average British medical ward. You will be at particular risk if an interventional cardiologist passes by and decides you need coronary angiography, because such persons tend to have a well-developed oculo-stenotic reflex – meaning that the moment they see a narrowed coronary artery, in goes a stent. By the time your bad heartburn has worn off, you will have had two of these placed in your nearly normal coronary arteries and had a dobutamine stress echocardiogram, a PET scan and an OGD. You will be home by lunch, consisting of aspirin, clopidogrel, labetalol, atorvastatin, lisinopril, and omeprazole. Quite filling. That’s my impression anyway: but the reality, as judged by this excellent study, is slightly less extreme. “In this large contemporary US cohort, nearly all acute PCIs were classified as appropriate. For nonacute indications, however, 12% were classified as inappropriate, with substantial variation across hospitals.”

NEJM  7 July 2011  Vol 365
32    About 30 years ago, it was discovered that the cardiac atria react to increased filling pressure by producing a hormone which promotes the excretion of salt and water, which was therefore called atrial natriuretic peptide (ANP). Then about 20 years ago another natriuretic peptide was isolated from pig brain and called brain natriuretic peptide (BNP). This was unfortunate, since BNP is not a significant brain hormone but a very significant cardiac hormone, almost entirely produced by the ventricles of the heart (not the brain). So nowadays we sometimes call it B-type natriuretic peptide, to avoid confusion with pig brains and British nationalist parties. Since then, various people (myself included) have been looking at ways of using circulating levels of BNP to help clinical decision-making, with mixed success. But it also occurred to pharma companies early on that by using some of the basic peptide structures common to ANP and BNP, they might be able to produce a new agent for use in acute heart failure. Nesiritide was granted a licence by the US Food & Drug Administration for use to relieve dyspnoea in AHF after a small, company-funded trial compared it with intravenous nitrates. I was amazed at the FDA decision then and I’m not in the least surprised that this large, publicly funded, placebo-controlled trial shows that it has no place in the management of acute heart failure.

62   A nice straightforward clinical review takes us through the management of glucocorticoid induced bone disease. Loss of bone occurs because steroids increase the lifespan of osteoclasts while dramatically suppressing the numbers of osteoblasts. So it’s no surprise that osteoclast-suppressing drugs are more effective than others like PTH or strontium at preventing steroid osteoporosis. If I were in the position of having to take long-term prednisolone, I think I’d opt for once yearly IV zoledronic acid rather than weekly alendronate, especially since treatment needs to continue as long as the steroids are needed.

Lancet  9 July 2011  Vol 378
129   In this diabetes-themed issue of The Lancet, here is a nice piece of pragmatic British research – and pragmatic in this case is not just a polite term for methodologically sloppy. The trial looked at what happened if you took two groups of newly diagnosed type 2 diabetics and randomised them to usual care, usual care plus an intensive diet intervention, or usual care plus the diet and extra exercise. The diet did something to lower weight, glycated Hb and blood pressure – not a lot, but possibly enough to be useful – whereas the added exercise produced no further benefit in these short term proxy measures. So it may be worth concentrating most effort on diet in this group – but I am by no means convinced that we know what the ideal diet actually is, or that exercise might not be equally or more beneficial in the long term.

147    If I go for a pre-operative check, that means I intend to have an operation; if I have a pre-prandial blood test, that means I intend to have a meal; but if somebody tells me I have pre-diabetes, that means I shall probably never get diabetes. Welcome to the whacky world of disease mongering, where you are a living disaster area just waiting to happen. It’s a wonder that any of us get out of this place alive, as Sir Richard Doll once said. “Pre-diabetes” and “pre-hypertension” means that you don’t have a defined risk factor now but you have an increased risk of it in the future, just because of your place on a normal distribution curve. So, according to this Japanese study looking at the predictive value of various levels of HbA1c and fasting blood sugar, you should be “targeted.” For what? Some new intervention with a NNT of 500, perhaps: I can feel them inventing it now. For heaven’s sake, there are already 400 million people in the world with real diabetes who have difficulty accessing the treatments they need.

156   Our evidence base for the treatment of type 2 diabetes is not exactly one of the glories of medical science, but at least we can be fairly sure from the UKPDS and STENO studies that early intensive treatment of both glycaemia and cardiovascular risk will improve long-term outcomes. The ADDITION-Europe trial was led from British primary care by Simon Griffin and powered to show a decrease in real adverse hard end-points based on event rates in past T2D trials. The aim was to demonstrate the benefits of early target-driven intensive management in patients with T2DM detected by screening, but it failed to reach significance. “Usual care” for type 2 diabetes in Europe is now so good – as evidenced by much lower event rates than expected – that “intensive” care doesn’t add anything.

169   Learning time at The Lancet tends to be a heavy affair, as learned authors parade their knowledge and attempt to distil the content of a vast array of references (140 in this case). This three-author piece on type 2 diabetes across generations is certainly weighty but also fascinating, as it explores the various theories of T2DM pathogenesis. Early life nutrition seems to be their favourite hypothesis, in which case there’s not a lot we can do to stop the rise of the diabetes pandemic in present adult generations. This well-illustrated overview is well worth accessing and keeping to read properly on some rainy day: unfortunately the weather is hot and sunny in New England today and I need to take some exercise to get rid of abdominal fat and lower my fasting blood sugar.

182   The next magisterial overview concerns the Management of type 2 diabetes: new and future developments in treatment. Gosh this is exciting; and complicated; and depressing. So much astonishing ingenuity and painstaking discovery; so many promising leads; so little hard evidence. If you are to give drugs to 400 million people, perhaps for the rest of their lives, you have to be very very certain that you are doing more good than harm. The good you do must consist of a reduction in cardiovascular disease, in blindness, in amputations, and in kidney failure. If the blood sugar goes down too, that’s nice, and easy to measure. But the real end-points that we must know in order to practise safely take many years to measure, and until we know them we may be doing patients more harm than good – a situation positively encouraged by the present drug licensing systems both in Europe and the USA. Just look at the table of new drugs on pp.184-5 and see how often “Unknown long-term safety” features prominently in the right hand column. The sad fact is that therapeutic progress in type 2 diabetes must take longer and be better scrutinized if it is ever going to be safer, or more effective – see the piece on rosiglitazone (Avandia) on p.113.

BMJ  9 July 2011  Vol 343
“Do I have blood pressure, doctor?” You should never reply, “Well, you appear to be alive,” because doctors are in no position to be clever about such things. Most people who are on BP lowering drugs will never get any benefit from them and we have scant means of finding out who will. The only way to determine whether it is better to treat according to BP measured in the office, the home, or with an ambulatory monitor is by carefully constructed, very long-term interventional trials based on the three types of measurement. But then again, the more people you treat, the more cardiovascular events you will prevent: it’s just that the NNT/NNH ratio will become ever more unfavourable. This systematic review simply takes ABPM as the reference standard and compares this with office and home measurements. The latter tend to be higher: so is ABPM “better”? No, it is just lower.

Why do we prescribe non-steroidal anti-inflammatory drugs so freely? They burn holes in the upper GI tract, precipitate heart failure, and most of them increase myocardial infarction by the same amount as smoking. The trouble is that they work a bit, and patients and doctors simply haven’t many alternatives. As people get older, they take more NSAIDs and they get more atrial fibrillation. Are they by any chance related? Yes, says this Danish case-control study: the additional risk of AF is 40-70% in new users.

“QOF Must Be Abolished” is a slogan you will be familiar with if you are fortunate enough to receive e-mails from Chris Johnstone, a Scottish GP. Do you need persuading? Well, just read Tim Dornan’s paper here: as we already knew with diabetes, so it is with all these indicators – GPs were on a steady upward trend before 2004 but once QOF came in, performance slackened to match the top of the target range. Gaming between government and the BMA set in, and irrational new targets (e.g for HbA1c, “chronic renal disease” detection) were devised. By 2007, some detriment to non-QOF care was already detectable: how much more now? QOF must be abolished.

Plant of the Week: Allium cepa Aggregatum group

A couple of days ago we bought our first “purple scallions” in the tiny Farmer’s Market by New Haven Green. These resemble enormous spring onions and are wonderful in salads: they might be worthy of eating as a dish on their own, perhaps seethed in a little olive oil and dressed with balsamic vinegar. We shall try next week, when we buy some more. “Scallions” in modern New England are probably just the sprouts of the familiar European Allium cepa, grown huge since it was first brought here by the Pilgrim Fathers, who need not have bothered since America abounds in edible allium species.

The word “scallion” has died out in England and so we looked it up, thinking it must be of Norman French origin. How wrong we were. It is the same word as “shallot,” and both derive from the ancient Greek word askalonion. (Although this word, found in Theophrastus, ends in onion, the modern English word onion probably has an entirely different etymology.) Now askalonion bears a remarkable resemblance to the name of a Canaanite town, Askalon, now Ashkelon, one of the most ancient and fought-over of coastal settlements in human history. And the scallion is indeed named after this port, because it was from there that the Greeks traced the origin of the best onions.

Ashkelon has a long and often tragic history. Its remains date back to Neolithic times and it was successively occupied by Canaanites, Philistines, Israelites, Assyrians, Babylonians, Greeks, Phoenicians, Romans, Persians, Egyptians and even by Richard 1 of England on his Crusade, who built a castle on its ruins. The Mamluks finished the job, and under the Ottoman Turks it was just a poor village. In 1948 its 11,000 Palestinian residents were expelled and it is now an entirely Israeli city.

But the lasting resonance of the name Askelon comes from the Bible in David’s great lament for Saul and Jonathan in 2 Sam v 17-27. You will not need to chop scallions to weep over this passage, one of the greatest things in world literature:

17And David lamented with this lamentation over Saul and over Jonathan his son
 18(Also he bade them teach the children of Judah the use of the bow; behold, it is written in the Book of Jasher):
 19″The beauty of Israel is slain upon thy high places! How are the mighty fallen!
 20Tell it not in Gath, publish it not in the streets of Ashkelon, lest the daughters of the Philistines rejoice, lest the daughters of the uncircumcised triumph.
 21″Ye mountains of Gilboa, let there be no dew, neither let there be rain upon you, nor fields of offerings. For there the shield of the mighty is vilely cast away, the shield of Saul, as though he had not been anointed with oil.
 22″From the blood of the slain, from the fat of the mighty, the bow of Jonathan turned not back, and the sword of Saul returned not empty.
 23″Saul and Jonathan were lovely and pleasant in their lives, and in their death they were not divided; they were swifter than eagles, they were stronger than lions.
 24″Ye daughters of Israel, weep over Saul, who clothed you in scarlet, with other delights, who put on ornaments of gold upon your apparel.
 25″How are the mighty fallen in the midst of the battle! O Jonathan, thou was slain in thine high places.
 26I am distressed for thee, my brother Jonathan; very pleasant hast thou been unto me. Thy love to me was wonderful, passing the love of women.
 27″How are the mighty fallen, and the weapons of war perished!”