Richard Lehman’s journal review – 26 April 2011

Richard LehmanJAMA  20 Apr 2011  Vol 305
   Chronic kidney disease, pre-diabetes, subclinical hypothyroidism, vitamin D insufficiency, attention deficit disorder, asymptomatic systolic dysfunction, borderline personality disorder, early chronic obstructive pulmonary disease, pre-hypertension, Barrett’s oesophagus: you may think you’re healthy, but how do you know you haven’t got any or all of these? Wake up! Have the tests and get a depressing medical label! Stop enjoying the spring sunshine and start thinking of death. And don’t forget to take the tablets and see your doctor regularly.

A few years ago pathology labs in the UK started estimating the glomerular filtration rate from every sample sent to measure serum creatinine. Overnight , a twelfth of the British public acquired chronic kidney disease; GPs chasing QOF points were then supposed to convey this news to them and get a urine sample to measure the urinary albumin/creatinine ratio. In the USA, referrals to renal physicians went up fourfold. Now readers of this column will be aware that there is a much more accurate blood test for estimating renal function and GFR: cystatin C. This does not vary with how much meat you had last night and how much fluid you’ve been taking. And this study shows that cystatin C based GFR is far more predictive of end stage renal failure and death than creatinine-based eGFR. The study after this, on p.1553, shows that you improve on creatinine by factoring in serum phosphate, calcium, albumin and bicarbonate; but cystatin C is still better overall. So what should we doing for patients whose creatinine-based eGFR comes back under 60? You could argue that you should measure their urinary albumin and try and get a cystatin C assay (good luck). Or you could argue that you should keep quiet and save the CKD label for people with eGFRs under 30. The facing-both-ways editorial on these studies (p.1593) begins by stating that “Effective treatments for chronic kidney disease are available but underused”, but ends by saying that we need “studies that demonstrate that using better risk prediction tools will lead to clinically meaningful benefit for patients.” Boy, do we need these studies: why not suspend the whole of QOF until someone has actually done them?

1560  I’m in the middle of 25 hours of out-of-hours primary care work and some time soon I am bound to hear the dreaded words, “They shouldn’t have let her out of hospital so soon, doctor.” Early discharge sometimes goes wrong, and that’s when we hear about it. But a lot has gone right in the last 20 years as well: this huge study of Medicare episodes of total hip arthroplasty shows that since 1991, mean hospital stay for THR has fallen from 9.1 to 3.7 days; perioperative mortality has been halved despite a small increase in the mean age of patients; many more patients are receiving rehabilitation in the community; and the only downside is an increase in readmission rates from 5.9% to 8.5%. Tough on those affected, but good news for most patients.

NEJM  21 Apr 2011  Vol 364
  Relieving pressure within the cranium is one of the most ancient goals of medicine – or at any rate one of the easiest to spot, since skulls with holes drilled in them count as neat archaeological evidence. In most cases we no idea what the trephination (or trepanning) was supposed to cure: demonic possession, epilepsy, headache, depression perhaps. Diffuse traumatic brain injury causes raised intracranial pressure, neurological damage and death: merely drilling a hole won’t relieve that, so a group of Antipodean trauma centres have been running a randomised trial of decompressive craniectomy since 2002. A desperate remedy for a desperate situation: but although the procedure releases pressure, it doesn’t help patients. In fact, they do worse.

1523   In England, we look down on ticks. Foreigners may get diseases like typhus, Rocky Mountain fever, Rift Valley fever and so forth but all we allow ourselves is the odd dubious case of Lyme disease. However, the latest tickborne disease comes from temperate north-eastern China and the tick that probably carries it is pretty ubiquitous among domestic animals throughout the world. So we may need to look out, though the novel bunyavirus that the ticks carry is still rare, even in China. The emergence in 2009 of a mysterious haemorrhagic fever in several rural hospitals in Hubei and Henan, with a mortality of 30%, led to an impressive detective exercise, funded by the China Mega-Project for Infectious Diseases. I hanker for the days when it might have been called the Glorious People’s Battle Cadre against Disease-Foes of the Peasants and Workers. Initially they suspected infection with Anaplasma phagocytophilum – well you would, wouldn’t you – but using an array of sophisticated techniques they found the RNA of the culprit virus. It is named for the disease it causes – SFTS – severe fever with thrombocytopenia syndrome. In their discussion the 46 authors (one deceased) modestly confess that they have not fully satisfied Koch’s postulates, but this paper is nonetheless a classic of the infectious diseases literature, free on the NEJM website.

1533   Amongst all the wonderful things you learnt about in school biology, few were more amazing than cilia. So tiny, so tireless; and in fact quite ubiquitous, since the centrosome that forms cilia also forms the spindle in mitosis, and ciliated organisms appear very early in evolution, so that the ciliary mechanisms of a green alga and the human bronchus are remarkably similar. And this means that when cilia go wrong, the results can be drastic. In this earnest and recondite review of the ciliopathies, you will learn about a lot of rare genetic disorders affecting the primary cilia. Bad luck, though, if your biology lessons had led you to think only about motile cilia: they lie “beyond the scope of this review”. Well, I’m very disappointed: in my opinion, nothing could be sillier.

Lancet  23 Apr 2011  Vol 377
   “There are few subjects that polarise cardiologists like vascular access for coronary angioplasty does.” Such is the first sentence of a generally very good editorial by two authors with Italian names, discussing a study of radial versus femoral access for coronary angiography.  Now a gentle copy editor might have stepped in and improved the English here, but  Richard Horton was no doubt too busy writing “Offline”, in which we find such gems as ” Although she was extremely praiseworthy of the support given to her work by the Wellcome Trust, she also pointed out…” Praiseworthy! Come here Horton! You will rewrite this thing in decent English five times and see me after Assembly tomorrow.  Now, class: the randomised RIVAL study was conducted in 158 hospitals in 32 countries, so it is probably as representative as we are going to get. It found that in procedures carried out for acute coronary syndromes, there were generally fewer local vascular complications using radial artery access, but the variable anatomy of the upper limb arteries meant that conversion to femoral access was occasionally needed. Horton, what did I just say? Are you paying attention? I shall set you a little test, you know.

BMJ  23 Apr 2011  Vol 342

906   I was introduced to the pleasures of sailing 21 years ago, on a cold and misty San Francisco bay where I fell to talking to the boat owner, a Silicon Valley millionaire I had never met before. He told me he had just invented a miniature gizmo for continuously measuring blood glucose, and I suggested that this would need to be linked to a continuous insulin delivery system to create an artificial pancreas by real-time feedback. He seemed a bit crestfallen: talk moved on to spinnakers and forthcoming races; it was too cold to fall asleep and this big piece of wood kept threatening to knock one into the sea. I never saw the millionaire again, and have avoided sailing ever since; but the artificial pancreas has finally arrived, and naturally the main worry is that it will cause hypoglycaemia and the main hope is that it will achieve near-normal glucose control. Here the feedback system is tested in a nocturnal cross-over trial with a conventional continuous insulin pump system. The results favour the closed loop (artificial pancreas) system, after meals with or without alcohol. But long-term outcomes need to be watched closely before these devices go to the market.

908  I’ve already commented once on the disparity between the summary and the conclusions of this 20-year follow-up study of PSA prostate cancer screening in the entire male population aged between 50-69 in the city of Norrköring in Sweden. The results are more consistent with an increase in prostate-related mortality than a decrease, but you can argue either way, and people do in the Rapid Responses. You may just be thoroughly bored with this issue and want to move on: or you may wish to spend an hour or two discussing the paper and responses with students and colleagues, in which case you also need to buy Overdiagnosis by Gilbert Welch with Lisa Schwartz and Steve Woloshin (2011) – a great read, with Ch 4 all about PSA.

Ann Intern Med  19 Apr 2011  Vol 154

541    In this week’s JAMA, we saw an editorial alleging that the early detection of “chronic kidney disease” and proteinuria offers the prospect of “effective treatment”. Here’s a lengthy systematic review going over the evidence that relates to the effect of tighter blood pressure control in people with CKD and various levels of albuminuria. The three best trials recruited subjects with stage 3-4 renal disease and compared BP control aimed at 125-130/75-80 as opposed to 140/90. The trials reached their targets for BP but the results are inconclusive. There are too few hard outcomes such as death or end-stage renal failure. There are no diabetic patients in these trials. In a word, we don’t know.

554   Ever since Fiona Godlee encouraged me to put my head above the parapet two years ago, and ask in a BMJ editorial why diabetologists were ignoring the evidence against tight glycaemic control in longstanding type 2 diabetes, I have been hoping that somebody somewhere might be hiding away a good summary of the trial data that would allow us to share informed decision-making with individual diabetic patients. It’s been a wonderful quest in many ways, though the dispiriting fact is that much of the evidence we need is simply not there. However, the search has put me in contact with a number of personable and brilliant people who have been looking for and collating the existing data, and my heart leapt when I read the title of this piece, Individualizing Glycemic Targets in Type 2 Diabetes Mellitus: Implications of Recent Clinical Trials. But actually it’s not so much individualizing sugar or HbA1c  targets that we need as individualizing preferences for outcomes and the whole package of lifelong management.  In corresponding with a number of friends about this paper, I have discovered two resources which are helpful towards this goal: from David Aron (Veterans Administration) I learn of Management of Diabetes Mellitus in Primary Care guidelines, and from Victor Montori (Mayo Clinic) I learn of the Decisions Aids page.

Both are more useful than the NICE guidelines, and make the one-size-fits-all approach of QOF look downright silly.

Plant of the Week: Syringa vulgaris

It is lilac time. It is also wisteria time, peony time, cherry-blossom time, apple-blossom time, iris time even. The early magnolias are flowering with the late; gardens are carpeted with flowers; every tree is covered with shimmering new foliage, the air is full of scent and birdsong: there has never been an English April like it.

But among all these delights, we’re finding that giving us the most pleasure is our sprawling common lilac tree. Its flower heads are of the deeply unfashionable colour favoured for the felt hats of maiden aunts – lilac. The scent is such as came from the Christmas presents of the 1950s – bath salts and cold cream. But at the same time, lilac carries springtime and freshness. And in the evening, the scent turns to languid summer in the air: young men in Chekhov stories feel urges that they later regret.

Nor do lilac bushes need to be scrawny messes for the rest of the year. The least you can do is keep them tidy and run a late flowering clematis into them for summer interest. By good fortune ours grows on a shady bank, with its top in the sunshine. Here it has formed mossy, corrugated trunks with Japanese curves. All year round, it looks venerable and beguiling.