JAMA  2 July 2008  Vol 300

51     The Journal of the American Medical Association makes little fuss about entering its 300^thvolume, but begins by celebrating one of the great triumphs of medicine: highly active antiviral therapy for human immunodeficiency virus. The Figure on p.56 says it all. Before 1996, HIV infection was a stepwise process towards death which occurred at about 10 years from seroconversion in 50% of those infected. Now people with HIV infection in the developed world can expect to survive much as people without infection. http://jama.ama-assn.org/cgi/content/abstract/300/1/51

71     The years from 1996 have also seen a transformation in the management of myocardial infarction and also in the terminology we use to describe it. NSTEMI and ACS are abbreviations which have only become widespread in the last decade, and the same goes for PCI. This meta-analysis of the randomised trials does a final bit of sorting out to see if there is really a subgroup of patients with non-ST elevation acute coronary syndromes who do not benefit from immediate invasive treatment. The only one they find consists of low-risk women. http://jama.ama-assn.org/cgi/content/abstract/300/1/71

NEJM  3 July 2008  Vol 359

50    As our greatest British institution reaches its sixtieth birthday, disheartened doctors moan about its imminent demise and its dismal failures, citing, for example, the lack of an integrated information technology system. We should stop being so British and celebrate. Electronic record-keeping and analysis in UK primary care are probably the best in the world. Judging from this survey of American physicians – half in primary care, the other half delivering other kinds of “ambulatory care” - it’s doubtful if the USA can catch up for decades. Only four percent have an extensive, fully functional electronic-records system, and 13% of the rest have a basic system. In other words, 83% have no electronic records. And our waiting times are coming down to match theirs. And our coverage is universal. And it is free at the point of delivery. And it costs less than half as much, because it is funded from general taxation. Rejoice in the NHS alway, and again I say rejoice. http://content.nejm.org/cgi/content/abstract/359/1/50

61    Distinguishing nature from nurture was never simple. Just as we are getting used to the gene gnomes who labour to uncover the fixed structures of our DNA, we now discover a whole brood of epi-gene-gnomes, waiting in the wings to complicate the work of their fellow-gnomes by finding out how our bodies tamper with their DNA in response to early life conditions. Epidemiologically, such work has been going on for more than a century, but the science of epigenetics is now becoming able to explain it in terms of chemical processes such as DNA methylation and histone modification. If you want a fairly readable guide to where we have got to in elucidating the effects of in-utero and early-life conditions on adult health and disease, here it is. It’s time you moved conceptually from genomic rigidity to epigenomic plasticity. http://content.nejm.org/cgi/content/extract/359/1/61

Lancet  5 July 2008  Vol 372

31     Last week you learnt from the opening paper in the NEJM that the oral factor Xa inhibitor rivaroxaban gave better protection from venous thromboembolism than injected enoxaparin after total hip replacement. This week you learn the same thing, from many of the same authors, from a nearly identical trial reported in the opening paper of The Lancet. The only significant difference is that in this trial the enoxaparin was given for a shorter period. Anyway, the fact is that we now have two effective oral anticoagulants for post-operative use, neither requiring INR monitoring but both needing long-term evaluation and direct comparison. Their names, I’m afraid, are dagibatran etexilate and rivaroxaban. http://www.thelancet.com/journals/lancet/article/PIIS0140673608608806/abstract

55    Here is a rather indigestible review of acute aortic dissection or, more accurately, acute dissection of the thoracic aorta. There is plenty of descriptive detail, but when it comes to treatment, not a shred of real evidence, for the simple reason that “no randomised trials have been reported to guide management of aortic dissection.” It’s a final bastion of old-fashioned “heroic” vascular surgery: some surgeons replace the aortic valve, a few try to mend it; most remove the arch and replace it, but there is now interest in mending it openly and then stenting it remotely; and so on. About 55% of patients return to independent living; various proportions of the rest go to the undertaker. http://www.thelancet.com/journals/lancet/article/PIIS0140673608609940/abstract

67    I described the last review as rather indigestible, but it was an ice cream smoothie compared to this account of the therapeutics of Crohn’s disease: beyond antagonists of tumour necrosis factor. And on to T-cell blockers and modifiers, and things that stop leucocytes migrating to sites of inflammation (diapedesis) and things that enhance repair or stimulate the right kind of immunity. There are some awesome tables of new and existing drug classes and compounds, with explanations in the text on the lines of: “Natalizumab and MLN-0002 bind specifically to α4 integrins, whereas the anti-cellular adhesion molecule-1(ICAM-1) anti-sense oligonucleotide ISIS-2302 (alicaforsen) blocks the endothelial cell adhesion molecules. ICAM-1 binds β2-integrin leucocyte function-associated antigen-1.”  In case you are tempted to add “no shit”; the article goes on to describe another therapeutic approach to Crohn’s disease: oral autologous colonic extracts. http://www.thelancet.com/journals/lancet/article/PIIS0140673608609952/abstract

BMJ Journals  July 2008

36      Transurethral resection of the prostate is so ancient a technique that it was already quite routine when I was a urology SHO in 1976; in fact I nearly learnt to perform it myself, in those far-off days of see-one, do-one, teach-one. The men of Lambeth had a close shave there. Then along came the holmium laser, and surely something that sounds straight out of Doctor Who must beat something that could almost be mastered by Doctor Lehman. But not so: as this systematic review demonstrates, old-fashioned TURP has yet to beaten for benign prostatic hypertrophy. http://www.bmj.com/cgi/content/abstract/337/jun30_1/a449

ADC  590   Childhood and adolescent migraine is a great curse to those who suffer from it, and therapeutic approaches to it, as so often in paediatrics, depend on a trickle-down from adult medicine. Pizotifen is an effective prophylactic in the few adults who choose to stay on it despite sleepiness and weight gain. In children it also causes weight gain, which is not predicted by drug dosage or therapeutic response, according to this case series from a West Suffolk clinic. And I bet it affects school performance too. http://adc.bmj.com/cgi/content/abstract/93/7/590

Heart  821   “Red wine, chocolate and vascular health: developing the evidence base”. Yes indeed, and bags I’m in the intervention group. This editorial does not in fact propose a randomised controlled trial, but musters the observational evidence for these excellent articles of diet, and then fades off into chemical speculations and vague puritanical caveats. http://heart.bmj.com/cgi/content/extract/94/7/821

Thorax  592   Combined inhalation therapy with a long-acting bronchodilator and a corticosteroid definitely helps many people with chronic obstructive pulmonary disease. This GlaxoSmithKline-sponsored trial adds tiotropium bromide to salmeterol and fluticasone to see if that will achieve even more benefit to people with COPD and also the GSK sales department. And so indeed it did; but this was a tiny little cross-over trial with weak end-points – not much of a basis to change practice just yet. http://thorax.bmj.com/cgi/content/abstract/63/7/592

Ann Intern Med  1 July 2008  Vol 149

1     We’re very used to the fact that diabetes can impair vision, but what about hearing? Looking at a cohort from of 5140 adults from NHaNES between 1999-2004, the investigators find that having diabetes doubles their chances of having hearing impairment, but the data are fuzzy: for example there was no distinction between type one and two diabetes. Speak up please. http://www.annals.org/cgi/content/abstract/149/1/1

33     This meta-analysis looks at 66 trials of adding salmeterol to inhaled corticosteroids on serious asthma-related events. All of them were conducted by GlazoSmithKline. The result: no effect on hospital admissions but a small effect on the use of rescue oral corticosteroids. Most trials lasted less than 13 weeks. http://www.annals.org/cgi/content/abstract/149/1/33

Plant of the Week: Hydrangea serrata ‘Shojo’

We spent the last week in France, a country where summer front gardens are dominated by what they call hortensias, in every shade of loud or dusty pink, or sometimes, the soil permitting, of washy blue. I find these kinds of hydrangea flower-head quite tiresome in their refusal to mix well with other plants or even in most cases with their own leaves.

The hortensias may be named after a certain Mlle Hortense who travelled with M. Bougainville’s botanical expedition around the world in the mid-eighteenth century. She was smuggled aboard in the guise of a young manservant to the redoubtable elderly botanist, M. Commerson, whose cabin she shared. Her true charms were accidentally discovered to the rest of the crew by a chieftain on Tahiti, who asked for her hand in marriage. Monsieur Commerson fled with her to Mauritius, and there discovered the first mophead hydrangea, which he then brought back to Paris. There, allegedly, it was acquired its popular name in honour of his manservant/mistress.

Enough of these Gallic frivolities. The best hydrangeas belong to other groups, and it was in the hope of enjoying these that we made our way to National Hydrangea Collection of France, conveniently close to our base in Dieppe. True to its name, it contains many, many more hortensias than even most Frenchmen could wish to see. But it also features a dell of recent lacecap introductions from the Far East, many of them in lovely shades of blue, thanks to the acid local soil. To our eyes the very best seemed to be a vigorous plant covered in very fetching lacecaps of a true, darkish blue. It is called “Shojo” and becomes available for the first time in the UK next month. We shall prepare a large pot for it, filled with aluminium-rich peaty compost, and keep it in the shade. In our normal soil, it would be a nasty deep pink, and that would never do.

JAMA  9 July 2008  Vol 300

173    Three weeks ago I referred to the fog that lies over the land of prostate cancer, but here is a pale glimpse of the sun. If you have localised prostate cancer you will derive no benefit from castration, either surgical (by orchidectomy) or chemical (by gonadotrophin-releasing hormone antagonists). In this cohort of 19 271 men receiving Medicare (median age 77) there was no difference in outcomes over 10 years in those who did or did not receive androgen deprivation therapy. These are observational data rather than a randomised trial, but at least something tangible to guide the treatment of this enigmatic condition. http://jama.ama-assn.org/cgi/content/abstract/300/2/173

182   Type 2 diabetes could also be described as an enigmatic condition, though the means of avoiding it are not particularly enigmatic – stay trim and take plenty of exercise from the age of 50 onwards. If only. Otherwise you may see a rise in α₂-Heremans-Schmid glycoprotein which forms part of the insulin resistance mechanism. This substance also rejoices in the name of fetuin A. We may hear more of it in time to come; on the other hand we may not. All this study tells us is that high levels are mildly predictive of new-onset diabetes in people over the age of 70, after adjustment for lots of things including fasting blood sugar and abdominal adiposity. http://jama.ama-assn.org/cgi/content/abstract/300/2/182

197   There seems to be no end to academic scraping of the barrel for additional cardiovascular risk factors, irrespective of whether most doctors really take any notice of them. The ankle brachial pressure index is at least fairly easy to measure, and this meta-analysis of population studies finds that adding ABPI to the Framingham score increases its predictive value. Perhaps we will soon find it made compulsory for cardiovascular screening in UK general practice. Or maybe the Polypill idea will win out and we won’t need to bother. In the end what matters is not the predictive accuracy of a screening test, but the extent to which adopting it affects outcomes. But don’t expect any data on that for another decade or two, if ever. http://jama.ama-assn.org/cgi/content/abstract/300/2/197

NEJM  10 July 2008  Vol 359

142    Acute cardiogenic pulmonary oedema is a familiar emergency which we used sometimes to see in general practice, though it has become rarer with the better management of chronic heart failure over recent years. Oxygenation of the heart is threatened by a cycle of poor filling of the left ventricle and the coronary arteries in diastole, plus pulmonary congestion and right heart failure as well as left; cardiac output falls, adrenergic overdrive increases, and the patient drowns. This study from 27 UK hospitals set out to discover if patients in acute heart failure do best if given oxygen by mask, or continuous positive airways pressure, or non-invasive intermittent positive-pressure ventilation. In fact all work equally well judged by short-term mortality, but non-invasive ventilation induces a more rapid improvement in respiratory distress. http://content.nejm.org/cgi/content/abstract/359/2/142

166    This review of the initial management of epilepsy offers a very wide choice of options, tabulated over 4 pages. Neurologists tend to divide between commanding officers – those who order you to try such-and-such an agent and titrate it up to a certain level, and woe betide you and the patient if they are not on it by the next outpatient appointment – or friendly advisers, who confide that you can start with such-and-such but then move on to this-and-that, or on the other hand try something else. I’m not sure which I prefer. In fact there seems little evidence to determine a first choice of broad-spectrum anticonvulsant (e.g. valproate, lamotrigine, topiramate, levitiracetam), or, in the case of focal epilepsy, between narrow-spectrum drugs such as carbamazepine, phenytoin or gabapentin. http://content.nejm.org/cgi/content/extract/359/2/166

Lancet  12 July 2008  Vol 372

117    Pegylated interferon makes no difference to survival in resected stage III melanoma: that seems to me to be the only practical message of this trial. In clinical practice, it can only make sense to spare your patients the side-effects which make a third of them discontinue the substance even in a trial setting. Sure, there was a small effect on recurrence: but I don’t think a breakthrough in melanoma treatment can really lie in this direction. The interferon used was alfa-2b, and pegylated means chemical modified with the addition of polyethylene glycol. http://www.thelancet.com/journals/lancet/article/PIIS0140673608610338/abstract

155    When I admitted in these columns that I’d never diagnosed Paget’s disease of bone in thirty years it drew critical disbelief from a reader, and from the review here I learn that it is present in about 8% of men and 5% of women over the age of 80. I must be a very unobservant doctor indeed. Most of it is limited to one site, picked up by chance biochemical measurement (raised alkaline phosphatase) and may not be clinically important, but I guess I’ve been missing more important presentations too, which should be treated with a bisphosphonate, preferably zoledronic acid. http://www.thelancet.com/journals/lancet/article/PIIS0140673608610351/abstract

164    Three of the most successful human pathogens – malaria, tuberculosis and human immunodeficiency virus – play such cunning tricks with the immune system that we have so far failed to produce an effective vaccine to any of them. Tuberculosis lies indolently in the bodies of a third of the human population, occasionally becoming invasive and killing about two million a year. Bacille Calmette Guérin has been the only vaccine on offer for the last 75 years, with a puzzling track record of becoming less effective the nearer one gets to the Equator. This review goes through the possible approaches to a new TB vaccine in very great detail, but none of them seems to offer much hope of an immediate answer. Very large long trials will be needed to demonstrate protection against this lazy old beast. http://www.thelancet.com/journals/lancet/article/PIIS0140673608610363/abstract

BMJ  12 July 2008  Vol 337

92    Do the fittest really survive? Apparently so, according to this study of Texan men whose muscle strength was assessed between 1980 and 1989. You go find yoself a real strong boy from Texas, Peggy-Lou, and he’ll take care of you a whole lot longer. http://www.bmj.com/cgi/content/abstract/337/jul01_2/a439

99   Here are some statistics about mortality from coronary heart disease in adults with diabetes from Nord-Trøndelag in Norway. This county is very Nord indeed, touching the Arctic Circle, and there as elsewhere death rates from heart disease in diabetic patients have fallen by 40-50% between the 1980s and the 1990s. They still remain twice those of the non-diabetic population however. I’d be much more interested to hear how you deliver chronic disease management in primary care to such a scattered mountain population, especially during the winter. Let alone immediate percutaneous intervention for MI. http://www.bmj.com/cgi/content/abstract/337/jul01_2/a236

103   Imported malaria is no great rarity in my practice, almost always P vivax brought back by Pakistani families visiting their native villages without taking antimalarials. We did however once have a scary case of cerebral falciparum malaria in a boy from the Sudan. This, it seems, is the shape of things to come, especially in London. Imported cases of benign vivax malaria are declining as malaria is better controlled on the Indian subcontinent, but dangerous falciparum infection is on the increase, especially among West Africans. Half of the imported cases come from Nigeria and Ghana. http://www.bmj.com/cgi/content/abstract/337/jul03_2/a120

Plant of the Week: Cornus alternifolia ‘Variegata’

You cannot go wrong with a variegated dogwood, unless you happen to dislike variegated leaves on principle. Even then you would have a hard job not admiring this one, whose small leaves are scarcely discernible from a distance, as the whole plant resembles a tiered cloud of white-green loveliness. If you want a similar effect but on a grander scale, with the individual leaves very visible, go for Cornus controversa, whose tiers are also more widely separated.

Both these plants need to be given a central space in the garden to show their true glory. Dark background plantings are desirable. Keep them uncluttered by surrounding perennials and do not even think of letting a clematis disturb their noble structure. These plants are soloists, not ensemble players.

If you do want some chamber music from variegated species of Cornus, you must look to the Roman dogwood, C mas, or the Siberian C alba. These are also lovely plants, though of quite different habit, and they are perfect as a framework for dark blue, red and purple varieties of clematis. Latinists among you will notice that Cornus is female of the fourth declension, like Morus (mulberry). I said “third” declension last time round, but Jeff Aronson soon put me right.

JAMA   16 July 2008  Vol 300

295    I include this paper from JAMA only out of politeness on its 125^th anniversary of continuous publication. There really isn’t much else in this issue, and this one simply reports that in the USA, levels of exercise drop sharply between the ages of 9 and 15. This is a carefully conducted cohort study from 9 locations across America, and the graph is quite startling: a smooth curve down from over 170 minutes per week of moderate-to-vigorous activity at age 9 to less than 50 minutes at 15. Kids who were running around together gradually take to spending all their time texting each other and playing video games and heaven knows what other solitary pastimes. A strange thing, puberty. http://jama.ama-assn.org/cgi/content/abstract/300/3/295

NEJM   17 July 2008  Vol 359

229    A good dietary trial is what is now called an oxymoron – a contradiction in terms. (Pedants like me reserve the word for a deliberate, rhetorical contradiction in terms: Dark with excessive bright thy skirts appeer Milt.: but usage is all) There are three commonly recommended diets for weight loss: Mediterranean, low-fat, or low carbohydrate. In real life, overweight people assign themselves to one of these, try it for a week or two, and then go back to eating what they like. In this Israeli trial, they were randomly assigned to one of the three diets and kept under fairly close supervision for two years by dieticians. The Mediterranean diet had the best results for weight loss and lipid changes, the low fat the worst. I think this is the nearest thing I have seen to a good dietary trial, oxymoron or not. http://content.nejm.org/cgi/content/abstract/359/3/229

262   I’m always amazed by the quality of population studies from Norway, a large cold mountainous place which takes very good care of its scattered population and comes up with very precise epidemiology, in this case about the long-term consequences of preterm birth. As we’ve seen from other countries, including the UK, it is best to come timely from the womb: medical and social disabilities in adulthood increased with decreasing gestational age at birth. This is a study of over 900,000 babies born alive without congenital abnormalities in Norway between 1967 and 1983 and followed up until 2003. http://content.nejm.org/cgi/content/abstract/359/3/262

274   Do British doctors cheat? I say, old chap, steady on: you can’t go asking questions like that. But a group of Mancunians went ahead and asked the question of British GPs, who were given quite an open field for cheating when pay for performance was introduced in 2004. We could “exception report” patients to avoid meeting clinical outcome quality criteria, and so boost our results and our pay. But, finds this study of 8105 GP computing systems, we didn’t. The analysis finds an astonishing lack of cheating. http://content.nejm.org/cgi/content/abstract/359/3/274

285    People often overdose on paracetamol, not always deliberately, and the antidote is acteylcysteine, given within a certain time. This case-based Clinical Therapeutics article discusses the use of acetylcysteine for both acute deliberate acetaminophen (paracetamol) OD and more chronic, unintentional overdosage. It’s certainly worth thinking about if you come across a patient like the one in the vignette, who has had a bad toothache and taken more and more painkillers, e.g. 24 paracetamol in a day. http://content.nejm.org/cgi/content/extract/359/3/285

Lancet  19 July 2008  Vol 372

207    The idea of an Alzheimer’s ward in Russia brings up chilling images from Chekhov, Bulgakov and Solzhenitsyn, and not without reason, according to the editorial on p. 179, which mentions a typical ward size of 70 patients. Here in the UK we spend a lot of money giving people with Alzheimer’s cholinesterase inhibitors which scarcely help and certainly don’t slow disease progression. In this Russian double-blinded RCT an obsolete cheap antihistamine was used instead. This is called dimebon and it had a positive effect on cognition and all other domains. The editorialists, who are the leading British researchers in the field, call for further studies of this drug and other cheap promising old drugs which may help Alzheimer’s, such as minocycline.

http://www.thelancet.com/journals/lancet/article/PIIS0140673608610740/abstract

http://www.thelancet.com/journals/lancet/article/PIIS0140673608610466/fulltext

224    INTERHEART is the huge 52-country case-control study which demonstrated that the same risk factors for coronary heart disease apply across all human populations. These are smoking, exercise, fruit and veg, alcohol, hypertension, abdominal obesity, psychosocial stress, and the apolipoprotein B100 to apolipoprotein A1 ratio. The what? Yes, the ApoB/ApoA ratio accounts for half of the population-attributable risk for myocardial infarction. So why aren’t we measuring it? Because we measure the HDL/LDL cholesterol ratio instead, which is almost the same thing. But maybe not quite as good, according to this paper. If you care deeply about this kind of thing, here are all the stats and charts you could desire. http://www.thelancet.com/journals/lancet/article/PIIS0140673608610764/abstract

234   A very useful seminar lumps together polymyalgia rheumatica and giant-cell arteritis. Now I diagnose PMR about once a month, and GCA never, but according to this paper, the ratio should be about 3 cases to 1, with about 20% cross-over. So I must be doing something wrong: and indeed I know I am, because some of the people I diagnose with PMR turn out later to have late-onset rheumatoid arthritis or other inflammatory conditions. That’s because the clinical criteria for PMR (there are three systems, usefully tabulated here) aren’t very precise and the diagnostic test (ESR>40) as imprecise as they get. The bad one to miss in the differential diagnosis, by the way, is myeloma, which is not mentioned here. As for giant-cell arteritis, I’m not sure how I’ll ever get to diagnose it, because all the temporal artery biopsies I’ve ever asked for have come back negative. http://www.thelancet.com/journals/lancet/article/PIIS0140673608610776/abstract

246   As you go through your general practice career, you will find your sessions filling up more and more with problems of psychological adjustment to chronic disease. This isn’t easy for doctors, who have to learn to be a support for people even when they have no solution to their problems; still worse, of course, for the patients, who face restricted lives, lowered earnings, loss of body image and a welter of feel-bad chemicals (cytokines) in the case of inflammatory disease. This humane and insightful review from the Netherlands uses a primarily biomedical approach, and is all the better for that. It should be compulsory reading for everyone who has ever used the word “heartsink”. http://www.thelancet.com/journals/lancet/article/PIIS0140673608610788/abstract

BMJ  19 July 2008 Vol 337

151    In a television interview the year before he died, John Betjeman was being taken over a Cornish hill in a wheelchair and asked what regrets he might have about his life. “Not having more sex” he replied, though subsequent accounts of his life have allayed any fears that he was being serious. Sex among 70-year olds is on the increase, at least in Sweden between 1970 and 2000; better still, it is more satisfying than it used to be. Betjeman would have been pleased. His late poem Senex is a lament for still-troubling lust:

Oh would I could subdue the flesh
Which sadly troubles me!
And then perhaps could view the flesh
As though I never knew the flesh
And merry misery.

To see the golden hiking girl
With wind about her hair,
The tennis-playing, biking girl,
The wholly-to-my-liking girl,
To see and not to care.

 There are a few more verses in this poem, none much better, and increasingly specific.

http://www.bmj.com/cgi/content/abstract/337/jul08_3/a279

http://www.poetryconnection.net/poets/John_Betjeman/16978

164   The second part of this short review of the management of breast cancer is to my mind better than the first. The logic and benefits of oestrogen-receptor and HER-2 receptor blocking treatment are very clearly explained. Figure 3 is also useful, showing the benefit of adjuvant therapy. It is very marginal indeed. http://www.bmj.com/cgi/content/extract/337/jul11_2/a540

Arch Intern Med  14 July 2008  Vol 168

1371   I think it’s a good general principle for doctors to work hard on diseases they really hate, and for a long time I worked on heart failure, which had caused a miserable death to my father and many of my patients. That standpoint concentrates your mind on what actually helps patients, and I soon learnt that a great deal of heart failure research was not about helping patients but about making academic careers and selling drugs. Many “landmark” studies depended on atypical patient selection and composite end-points of death and hospitalisation. Most studies of service delivery were based on hospital readmission rates. Another thing I learnt was that to find papers that describe what actually happens to heart failure patients, you begin by looking for the name Harlan Krumholz in the authorship. Here Harlan My Hero looks at statistical models and patient predictors of readmission for heart failure. It’s a dog’s breakfast. His team found 941 potentially relevant articles, of which 117 met the inclusion criteria and none provided a standardised and properly validated model for patient risk stratification. http://archinte.ama-assn.org/cgi/content/abstract/168/13/1371

1387   Rapport-building, up-front agenda setting, and acknowledging social or emotional clues: does that sound familiar? I don’t know about you, but I attempt it about 30 or 40 times every full working day, and try and teach it when I can. Here’s an American account of communication skills in the medical encounter, as garnered from a huge literature search, narrowed down to 9 key papers. Good, but nothing you didn’t know if you were trained in UK general practice some time in the last 20 years. And another tip: the secret of keeping the consultation to 10 minutes is not to interrupt the patient. http://archinte.ama-assn.org/cgi/content/abstract/168/13/1387

1423   We do an awful lot more for patients with stable coronary heart disease now than we did ten years ago, and outcomes have improved accordingly: but better risk stratification might help us do even more. Inducible ischaemia can be tested for by the use of stress echocardiography and if present it doubles the risk of a future coronary event. Only 20% of patients with inducible ischaemia have clinical angina. http://archinte.ama-assn.org/cgi/content/abstract/168/13/1423

1450   Framingham is the one place where we have data that cross the various post-war eras of blood pressure management – i.e. none at all, a bit, and then more and more. Reassuringly, BP control has indeed got steadily better and the relationship between BP and mortality has become steadily more attenuated. http://archinte.ama-assn.org/cgi/content/abstract/168/13/1450

Ann Intern Med  15 July 2008  Vol 149

73    Knee arthroscopy is one of the commonest day surgery procedures, though therapeutically most of it is a complete waste of time (see the Cochrane reviews). Afterwards patients go home with compression stockings to prevent deep vein thrombosis, but this randomised trial (called KANT, for some kind of Pure Reason) shows that they would do better with low molecular weight heparin for a week. But not by much. http://www.annals.org/cgi/content/abstract/149/2/73

91    Prehypertension and coronary calcium scores are American ideas that I am less than enthusiastic about. This study links the two: all it shows is that if you happen to be at the wrong end of the distribution curve – i.e. nearer 139 systolic than 120 -  at an age between 18 and 30, you are more likely to show calcium in your coronary arteries 20 years later. And so you might get more coronary events. So BP is continuously linked with coronary risk: well who would have thought it? http://www.annals.org/cgi/content/abstract/149/2/91

Plant of the Week: Magnolia ‘Maryland’

By the sunnier walls of many of our most distinguished buildings spreads a morose tree with large leathery leaves. Occasionally, at this time of year, it bears a large goblet flower – sometimes even two – of creamy white. If this happens to be within sniffing height, you can enjoy a gulp of honey and lemon scent that will make you want to grow your own Magnolia grandiflora whatever it may take. Otherwise you will wonder why anyone bothers.

The further south you go, the more lofty these trees become, and they are seen at their very best on the North Island of New Zealand, where they can reach 30 metres. The trouble is that they then require a huge amount of space and waste their sweetness on the upper insects.

There are many cultivars of M grandiflora, but few hybrids. “Maryland” is a hybrid with M virginiana, the first American magnolia to be introduced in Britain but a great rarity now. The idea of this mix is to make a smaller, freer-flowering plant. It is certainly better for the average British garden than any of the pure grandiflora clones, however “compact” they may claim to be on garden centre labels. And it does flower quite freely some warm years, with exactly the scent you bought it for and yearn to enjoy each season. But we must wait for the genetic engineers to produce a really good compact hardy free-flowering evergreen summer magnolia for our little plots. 

JAMA  23-30 July 2008  Vol 300

395     VI*rGA at knock-down prices! Satisfy her every time. See if you can spot the difference between this JAMA paper and your spam file. Well, it was a randomised trial for a start – but then so is buying blue pills on-line, I imagine. Second, it was sponsored by Pfizer. Third it was addressed at female sexual dysfunction. Fourthly it had spotted a whole new market for sildenafil before it comes off patent in 2011: continuous prescription to all women on SRI antidepressants. The stated logic for this study is that many women give up taking SRIs due to sexual dysfunction and so suffer all the baleful effects of depression and alternative treatments. So: did this trial look at co-prescribing sildenalfil for women being started on SRIs and compare discontinuation rates? No, sir: it looked at women who had been prescribed SRIs for an average of over two years and who thought that this had spoilt their enjoyment of sex. They were then randomised to sildenafil or placebo to be taken when they anticipated sexual intercourse (not more than once a day, mind). In the 8-week trial, 20% dropped out. Those getting Viagra experienced more headaches, flushing, nasal congestion and orgasm (95% confidence interval 0.5 to 4.73). Hardly a secure foundation for what I imagine will become an enormous sales pitch. I think I’ll click the Spam button. And yes, I know I look really stupid in the shower. http://jama.ama-assn.org/cgi/content/abstract/300/4/395

431    Half of patients with heart failure do not have a reduced left ventricular ejection fraction; I’ve been telling you this for years, in these columns and a BMJ editorial. The problem, well illustrated in this little commentary piece, is that we don’t know what to call them and we don’t know how to treat them. Here their condition is called HFPEF (heart failure with preserved ejection fraction) – which is not even an acronym – and we are told to treat their “co-morbidities”, such as obesity, hypertension, coronary artery disease, atrial fibrillation, diabetes and chronic kidney disease. As if we aren’t already. More work needs doing on heff-peff, not least in finding it a better name. http://jama.ama-assn.org/cgi/content/extract/300/4/431

NEJM  24 July 2008  Vol 359

339    I seldom comment on HIV studies as they lie outside the province of a very provincial GP. But I guess I should tell you that there is a new drug which interferes with HIV-1 integrase and can help to rescue patients with HIV resistant to older antiretroviral drugs. It is called raltegravir and the key trials reported here (see also p.355) are called BENCHMRK, setting a new benchmark for stupid acronyms by missing out a vowel. The reason they can’t put in an “A” is that MRK is an abbreviation of Merck. Benchmerck sounds a bit wrong; like bird droppings on a park seat in Harrogate.

http://content.nejm.org/cgi/content/abstract/359/4/339

http://content.nejm.org/cgi/content/abstract/359/4/355

366    I tell you about some highly academic cancer studies because they might be the shape of things to come. Nowadays it seems almost routine to harvest circulating tumour cells from blood by “a microfluidic device containing microposts coated with antibodies against epithelial cells”. The cells harvested here were from non-small-cell cancer, for which we now use tyrosine kinase inhibitors to block epidermal growth factor receptor (EGFR), with limited and usually transient effect. Here the investigators were able to trace the development of EGFR mutations in harvested tumour cells and correlate these with drug resistance. So – a new, immensely sophisticated tool to trace cancer cells and follow their twists and turns. Of what eventual clinical benefit, time will tell. http://content.nejm.org/cgi/content/abstract/359/4/366

391    Six years after coming up with the idea, I am still working on a possible BMJ series called “Commoner Than You Think”. Is hypoparathyroidism commoner than you think? It has to be commoner than I think, since

I have never thought about it at all. This review article proclaims its existence, names many causes, but gives no idea of its prevalence. Like many conditions – even common ones – we really don’t know how common it is. I would hazard a guess from this article that hypoPTH is very uncommon, and I may not have done my patients too much harm by my ignorance. There is in any case no readily available treatment for it. http://content.nejm.org/cgi/content/extract/359/4/391

Lancet  26 July 2008  Vol 372

293     Three weeks ago, when JAMA ran a paper on life expectancy with HIV in the era of combination antiretroviral therapy, I drew fire from a reader for loosely claiming that survival in HIV-infected people is “much as” survival in the general population. This was an overstatement caused by the very impressive Kaplan-Meyer charts in that paper: HIV before 1996 was a death sentence and is now mostly a life sentence. Here, a combination of 14 cohort studies from high-income countries shows that HIV still carries the risk of a reduced lifespan, though the figures are skewed by intravenous drug users, who have a much lower life expectancy than other HIV carriers. Overall, “the average number of years remaining to be lived at age 20 was about two-thirds that of the general population”, says the abstract rather confusingly. If you happen to carry HIV and aren’t 20, you would do much better to try and find which group you belong to and where you lie in the generously provided statistical tables. For those who aim to be HIV-literate, there are several other important papers in this week’s Lancet.

http://www.thelancet.com/journals/lancet/article/PIIS0140673608611137/abstract

http://www.thelancet.com/journals/lancet/article/PIIS0140673608611149/abstract

http://www.thelancet.com/journals/lancet/article/PIIS0140673608611150/abstract

321    If you get acute hepatitis C and become clinically ill, especially with jaundice, count yourself lucky: you are almost certain to get completely better and stand a good chance of clearing the virus permanently. The other 85% of people who acquire HCV don’t know about it at the time and often develop chronic carriage, with the risk of chronic liver damage and hepatocellular carcinoma. This interesting review article is mostly about the acute phase but provides a useful update on the epidemiology and current thinking about treatment strategies. http://www.thelancet.com/journals/lancet/article/PIIS0140673608611162/abstract

BMJ   26 July 2008  Vol 337

183    In bygone days, horse-drawn scrap iron carts would be led up and down the streets of poorer England by unkempt men who shouted “Any old iron!”  I saw the last of them as a child, together with real steam rollers and rag-and-bone men. It’s presumably to these that the cover headline of this week’s BMJ refers: “Not Any Old Iron”, it declares. I beg to differ: this is a large multinational cross-sectional dietary study (INTERMAP), claiming an association between meat derived iron and blood pressure. Personally I would get all these weak observational dietary studies out and plonk them on the scrap iron cart. http://www.bmj.com/cgi/content/abstract/337/jul15_1/a258

227   Guillain-Barré syndrome is a “never miss this” condition, and what we need are some clear red flags. But although this is a serviceable brief review of the condition, the red flags here lie crumpled and almost invisible beneath a heap of neurology-textbook prose. Now look: if a patient comes in complaining of not being able to use their arms and/or legs properly after a viral illness, get out of your chair at once and test their power, their tendon reflexes, and their cranial nerves. If there is any abnormality, or if you’re in any doubt at all, get them seen by the on-call neurologist and not a young doctor who has never seen GBS. You may have four weeks to reach the diagnosis, but don’t bank on it; their respiratory muscles may start failing later that day. This is what you need to know at the front line: the rest you can swot up at leisure. http://www.bmj.com/cgi/content/extract/337/jul17_1/a671

Plant of the Week: Malva moschata ‘Alba’

In the winter months, I destroyed a large part of our back garden in an effort to get fit and to prepare for a modest house extension. This left several areas of clay bank and bare earth, which have since been colonised by various plants, while the process of getting the builders to start proceeds with slug-like alacrity. It’s an interesting exercise in garden ecology, from which my respect for the competitive toughness of this plant –already considerable – has emerged even greater. The white mallow is an invader that means business and holds its own with any wide-seeding weed. Moreover it is beautiful enough to carry a Royal Horticultural Society Award of Garden Merit and white enough to shine on the dullest English summer day. All over the clay and the other spaces of bare earth, there are clumps of brilliant white mallow flowers.

We were first given this plant by a lady whose garden we had stopped to admire. She turned out to be a haematologist and warned us that it would spread. It has indeed turned out to be a sort of garden leukaemia – cells of white turning up everywhere – but fortunately very easily controlled by simply uprooting the many plants that emerge where you don’t need them. In this respect it’s like Viola labradorica, an early spring plant of opposite colouring which also becomes a nuisance through self-seeding, but is nonetheless an essential for every garden. These are garden plants that become weeds, as opposed to weeds which become garden plants, like self-sown foxgloves and valerian. Although I hate weeding, I wouldn’t be without any of them.

NEJM  31 July 2008  Vol 359

463    Although the HIV pandemic may have peaked, we still badly need cheap, simple and effective ways of blocking its transmission. A cellulose sulphate gel was thought a likely candidate for reducing vaginal HIV transmission; but like so many cheap simple solutions, it was not only ineffective but may have made the problem worse. This was a randomised double-blind placebo-controlled trial conducted in India and Africa (1398 women) and ended with 25 new infections in the cellulose sulphate group and 16 in the placebo group: not statistically significant but distinctly unpromising. We need a better understanding of why vaginal transmission is common in these countries but relatively rare in the developed world. http://content.nejm.org/cgi/content/abstract/359/5/463

473    Nowadays we make enormous efforts to restore an oxygen supply to half-asphyxiated myocardial cells, but as well as saving some myocytes, acute reperfusion can kill others and/or trigger fatal arrhythmias. In animal models, acute reperfusion injury can be attenuated by cyclosporine and this pilot trial looked at giving the drug at the same time as percutaneous intervention for myocardial infarction. The main outcome measure was infarct size measured by MRI at 5 days, and the results were promising. Bigger trials with long-term, patient-important outcomes are needed. http://content.nejm.org/cgi/content/abstract/359/5/473

482    On the 1^st of April 2006, British television screens were filled with pictures of wrathful Scotsmen puffing on cigarettes outside pubs which they had previously been at liberty to fill with tarry smoke. Bar-owning Scots could be heard saying things like “It’ll be the death of us”. Quite the opposite. This observational study notes a drop of 17% in the number of people entering hospital with acute coronary syndromes in the 10 months after the public smoking ban. Two-thirds of them were non-smokers, which can be seen as a priori evidence of the importance of passive smoking. The investigators made an attempt to quantify their exposure to tobacco smoke before and after the legislation, and while I doubt that this would convince any true-bred smoking Scottish empiricist, the trend has been similar in all places where smoking bans have been studied. http://content.nejm.org/cgi/content/abstract/359/5/482

503    Malignant gliomas in adults are still lethal: within 15 months for glioblastomas and 2-5 years for anaplastic gliomas. This thorough review concludes that “recently there has been important progress in the treatment of malignant gliomas”, but a “selected” list of investigational treatments with over 50 entries (Table 2) suggests guesswork and a certain amount of desperation. Malignant brain tumours are likely to remain very bad news for some time yet. http://content.nejm.org/cgi/content/extract/359/5/492

Lancet  2 Aug 2008  Vol 372

375    Rheumatology is a frustrating discipline, and most of the patients I send  to our local clinic have vague symptoms and uncertain diagnoses. Even when patients have rheumatoid arthritis, their course (thank goodness) is mostly mild and unpredictable rather than classical and severe. But in this study (COMET), the team at Leeds - funded by Wyeth (who also wrote up the study) - managed to collect 542 patients with early moderate-to-severe rheumatoid, and randomise them to either standard-dose oral methotrexate alone or methotrexate combined with etanercept. The latter group did better, as everyone (including Wyeth) expected. But as the editorial on p. 347 points out, most rheumatoid patients follow a more indolent course, and if they get flare-ups we increase their methotrexate or give it by injection rather than continue a standard (small) oral dose. This trial may improve sales of etanercept, but it does not shed much light on its place in the management of most patients with RA. http://www.thelancet.com/journals/lancet/article/PIIS0140673608610004/abstract

383    Now combine the difficulties of doing a trial in rheumatology with the difficulties of doing a trial in children. The result: a study of abatacept in juvenile rheumatoid arthritis that is roundly condemned in an editorial (p.348) by Thomas Lehman - who is not my son of that name, but with whose every word I agree. The Lancet has put itself in the position of publishing a paper which its own commentator shows to be scientifically unsound and probably unethical. “Paediatric rheumatologists should consider the countervailing responsibility not to unnecessarily enter children into studies that subject them to placebo control with the possibility of flare and worsening their condition, when the studies are inadequately designed or powered to provide convincing proof of efficacy and safety.” For “possibility” read “near certainty”, and to paediatric rheumatologists add sponsors (Bristol-Myers Squibb) and high profile medical journals. http://www.thelancet.com/journals/lancet/article/PIIS0140673608609988/abstract

392    A recent editorial in Gut labelled Helicobacter pylori an “amphibiont” – not quite a parasite not quite a symbiont, but a bacterial companion that can be harmless or nasty by turns. The nastiest thing it does is cause gastric cancer. Until the antibiotic era, gastric cancer was quite common in Western countries and H pylori carriage was universal in humans, as it is in all mammals. Now we try to eradicate it whenever we find it, and often bump it off accidentally when we give patients antibiotics, particularly at the same time as PPIs. In this Japanese trial, patients with early gastric cancer were randomised to open-label H pylori eradication or put in a control group. At 3 year follow-up, the treated patients showed far fewer metachronous gastric cancers than those who were left untreated. In this instance, the editorial (p.350) doesn’t debate the ethics of this study but advocates a universal screen-and-eradicate policy for H pylori in countries where gastric cancer remains common. http://www.thelancet.com/journals/lancet/article/PIIS0140673608611599/abstract

398    For a couple of decades I remained a sceptic about influenza vaccination but I was gradually half-won-over by a large body of evidence – none of it grade A – that it has some benefits in the elderly. I am more convinced of its benefits in the young. But who am I to bandy words with my paymasters? We give the jabs and take the cash. We have been led to believe that it protects oldies from community-acquired pneumonia, but this nested case-control study finds that if you are careful to control for potential confounders such as smoking, lung and heart disease, and general frailty, there is no proof that it does. http://www.thelancet.com/journals/lancet/article/PIIS0140673608611605/abstract

406    Diacritical signs are a pain: ask anyone who has owned a Polish typewriter. Meniere’s disease here appears shorn of its acute and grave accents, for reasons unspecified but very understandable. At least its discoverer, Prosper Ménière, is allowed both his accents whenever he is named.  And although the authors are American, they allow him to possess his disease in the genitive case. The condition itself remains something of an enigma, and in this thorough review I can’t find anything that amounts to proof that it is caused by endolymphatic hydrops, still less that it can be effectively treated either medically or surgically. Evidence-based medicine seems to have deprived ENT surgeons of many ineffective treatments but it hasn’t given them many new and effective ones. http://www.thelancet.com/journals/lancet/article/PIIS0140673608611617/abstract

BMJ Journals July 2008

Gut   1004   Of the making of many books there is no end, wrote the author of the book of Jewish wisdom we call Ecclesiastes (or Kohelet) in about 250 BCE. Medical guidelines only really took off in the 1980s, but of the making of them there is no conceivable end as long as medical science continues. This one on the management of common bile duct stones is an excellent example: very thorough, covering all common clinical situations, based on immense reading carefully sifted and graded. Ten or fifteen years ago surgeons were damaging the CBD in their early attempts to learn laparoscopic surgery and physicians were doing the same on their learning curve to ERCP: now, thank goodness, we have clear training protocols and standards for volume and quality, as well as a good evidence base for managing most situations where stones get trapped. http://gut.bmj.com/cgi/content/abstract/57/7/1004

Heart   930    Antibiotic prophylaxis against infective endocarditis is a hallowed medical custom, the subject of countless telephone calls from dentists and final paragraphs in cardiology clinic letters. But has it finally fallen victim to evidence-based medicine? The British NICE guideline goes further than any other national guideline to date. Although there is no good evidence that prophylaxis against gut-borne bacteria works, prophylaxis is still recommended for vulnerable patients undergoing “dirty” gut-related procedures. But for dental procedures, it is abandoned, on the basis that we send far more mouth bacteria into our bloodstream when we brush our teeth than when we have them taken out.

http://heart.bmj.com/cgi/content/extract/94/7/930

http://heart.bmj.com/cgi/content/extract/94/7/931

Thorax  584   Using immunosuppressant drugs for corticosteroid-refractory asthma is not new: I seem to remember a promising trial of azathioprine some years ago. But etanercept is a relatively new drug with its patent intact and here again Wyeth sponsored the study, though in this case they did not design it or write it up. This TNFα blocker had very modest effects in a 12 week trial which randomised 39 patients with refractory asthma to get it or placebo once a week. The editorial on p.571 usefully discusses the general problem of refractory asthma and the end-points which need to be looked at in the search for better treatments.

http://thorax.bmj.com/cgi/content/abstract/63/7/584

http://thorax.bmj.com/cgi/content/extract/63/7/571

Arch Intern Med  28 July 2008  Vol 168

1493    When in Norfolk, remember to eat plenty of fruit and vegetables, and you will avoid diabetes. This is the lesson drawn by the EPIC investigators from the finding that the highest quartile of plasma vitamin C helps you fall in the lowest quintile of diabetes risk: though the figures aren’t very convincing when adjusted for other factors (95% CI odds ratio 0.6-1.0). http://archinte.ama-assn.org/cgi/content/abstract/168/14/1493

1531    Colesevelam is a bile-acid sequestrant which was designed to lower low density lipoprotein cholesterol (LDL-C) but was found also to have a mild glucose-lowering action in people with type 2 diabetes. The main outcome measure in this trial was HbA_{1c ,}though at 16 weeks’ duration it was only just long enough to detect a difference, and the difference it did detect was small (0.5%). The choice of patient group was rather odd; it was tried in those who were already on insulin plus other oral hypoglycaemic agents as necessary. However, it was well tolerated and it did have favourable effects on lipids. http://archinte.ama-assn.org/cgi/content/abstract/168/14/1531

Plant of the Week: Lonicera similis var delavayi

No garden can have too much honeysuckle. Much of ours comes from birds’ bottoms and consists of self-sown varieties of the native British honeysuckle L periclymenum which is abundant in the local woods. This drapes itself over lilac and crab-apple trees, but for a bare wooden fence one needs an evergreen climber, and we hit on this one visiting a nursery last year. It has not disappointed, trebling in size and filling the back of the garden with a marvellous spicy scent in the evening.

It is one of innumerable plants first described by Jean Marie Delavay (1834-95), a Jesuit missionary who worked without help and collected 200,000 plant specimens in Yunnan, all meticulously preserved and annotated. It is difficult to imagine how he found time to care for the souls of an equal number of the Yunnanese heathen. He survived bubonic plague in 1888, but never fully recovered. For some reason, he has never become as celebrated as his fellow-missionary Père David (1826-1900), though he introduced fully as many fine plants: the specific names delavayi and davidii  being practical guarantees of quality. The third French missionary-plantsman was Paul Guillaume Farges (1844-1912), though his introductions tend to be less important and a little bit tender for the English climate. If you want a really spectacular tree, for example, plant Paulownia fargesii, but don’t be surprised if it dies after a few years.