JAMA  3 Sep 2008  Vol 300

1027    Avoiding Alzheimer’s is one of the chief goals of “successful ageing” but this week’s journals indicate that it isn’t just a matter of taking aspirin (see BMJ p.554) and getting enough exercise. Aspirin seems downright useless for the purpose, which is odd, as there is so much diagnostic overlap between Alzheimer’s dementia and diffuse cerebrovascular disease; whereas exercise has a weak effect on some cognitive domains. This was a trial done in Western Australia, and recruited 310 individuals who reported memory problems, and got 138 of them to stay the 18-month course, randomised to an exercise programme or usual care. The exercise group showed a small benefit in three out of 8 measures. Only time will tell how many of them end up in what Dame Edna Everage caringly calls a “home for the bewildered”.

http://jama.ama-assn.org/cgi/content/abstract/300/9/1027

http://www.bmj.com/cgi/content/abstract/337/sep01_1/a1198

1069    In an otherwise uninteresting issue, JAMA features three commentaries on the relationship between the pharmaceutical industry and US medicine. By far the most trenchant and disturbing is by Marcia Angell, who says that after twenty years of editing NEJM she was forced to conclude that “physicians can no longer rely on the medical literature for valid and reliable information”. “It is self-evidently absurd to look to investor-owned companies for unbiased evaluations of their own products.” And yet the drug companies have moved in recent years towards total ownership of most major trials of new drugs, designing and ghost-writing the studies and even keeping some data secret from the so-called principal investigators. This may seem peripheral to the main agenda of reforming US health care, but unless the new Obama administration is prepared to tackle big pharma’s grip on research, it can make little progress towards providing affordable health care in the future. And not just in America. http://jama.ama-assn.org/cgi/content/extract/300/9/1069

NEJM  4 Sep 2008  Vol 359

999    Implantable cardioverter-defibrillators are now almost standard issue to many US patients with systolic heart failure and the means to pay for one. A major driver of this policy was the 23% reduction in mortality shown in a big trial (SCD-HeFT) which compared these very expensive electric shock machines with amiodarone or “state-of-the-art medical therapy”. In view of what I’ve written above I should point out that the sponsors (two drug companies and an ICD manufacturer) had no role in the design, analysis or interpretation of the quality-of-life study reported here. Anyway, it was a dead heat between the three strategies in terms of patient satisfaction. Well, perhaps “dead heat” isn’t the ideal expression, because many of the patients were in fact dead before they could give their opinion. The investigators allowed for that and still found that ICDs don’t reduce quality of life, except for about a month after they’ve gone off. http://content.nejm.org/cgi/content/abstract/359/10/999

1009    Since arrhythmias in heart failure are often a sign that cardiac myocytes are overstretched, starved of oxygen, tethered by fibroblasts and longing for death by apoptosis, they carry a gloomy prognosis. This further report from SCD-HeFT confirms that patients who experience defibrillator activation carry a substantially higher risk of death than those whose ICDs remain inactive. Nothing too shocking about that. http://content.nejm.org/cgi/content/abstract/359/10/1009

1027   Ever heard of hereditary angioedema due to C1 inhibitor deficiency? There’s no particular reason you should have, as you’ve only a one-in-five chance of coming across a case in a practice of 10,000 patients. But here I can be the boy at the back of the class and shoot my arm up and say, “Please miss, I’ve got one!” He goes all swollen from time to time and has to take stanozolol imported by special order from Spain, and whenever he has anything minor or major done to him there has to be some injectable C-1 inhibitor to hand. So instead of suggesting that you should keep a copy of this article, dear reader, I shall do so myself. This is an autosomally dominant disease first described by Osler in his Baltimore days (1888), but by a nice irony you still can’t get C1 inhibitor in the United States of America. http://content.nejm.org/cgi/content/extract/359/10/1027

1037   There are evidently readers of the New England Journal who still stoop to such humble roles as the management of acute cutaneous wounds, meaning scrapes, cuts, bites and burns. If you still do a bit of country doctoring of this kind, here’s a nice clear and well illustrated guide. Ah, it’s such a long time since I wielded needle and thread in such a cause, or indeed heated an unfolded paper clip with intent to smell burnt fingernail and dodge a fountain of pressurised blood. How it all comes back… http://content.nejm.org/cgi/content/extract/359/10/1037

Lancet  6 Sep 2008  Vol 372

807    Massive interventional trials in patients with coronary artery disease and reduced systolic function with absurd acronyms are getting less common, but here is a BEAUTIFUL example. The “acronym” here has little to do with the official designation of the study (“morbidity-mortality evaluation of the I_f inhibitor ivabradine in patients with coronary artery disease and left-ventricular dysfunction”) but you can have a beautiful time trying to find the letters hidden in it. There were 10,917 subjects and nearly as many investigators, meaning that a lot of the former and several of the latter died before it was complete. And to what avail? None at all, as far as the primary end-point was concerned; it mattered not the slightest (HR1.00) whether the patients got ivradapine or placebo in terms of hospitalisation for HF and/or death. But they did manage to find some secondary beauty in the trial: ivradapine, which reduces heart rate, reduced coronary events in patients with pulse rates over 70.

http://www.thelancet.com/journals/lancet/article/PIIS0140673608611708/abstract

http://www.thelancet.com/journals/lancet/article/PIIS014067360861171X/abstract

BMJ Journals Sep 2008

BMJ  550    In our practice before about 2003, we used to be hormone replacement enthusiasts. Just take these pills and you will sleep better, feel better, have better sex and avoid hot flushes. All sound WISDOM, as confirmed by this trial; though what we went on to say about the cardiovascular benefits has, of course, been overturned. Still, I think we may have swung too far in the anti-HRT direction, as there is absolutely nothing else that works for women with crippling vasomotor symptoms. And oddly these seem to be able to come on a long time after the menopause. http://www.bmj.com/cgi/content/abstract/337/aug21_2/a1190

ACD  793   The bronchiolitis season will soon be upon us, and the bleak message of this review is that there is no effective treatment in the community. Corticosteroids are useless, and ribavarin has little effect. Kids with severe bronchiolitis need to be in hospital where they may get intermittent or continuous positive airway pressure or may even need to be ventilated. After true British bronchiolitis (a more severe illness than mere Continentals and Americans label as “bronchiolitis”), kids tend to suffer crackly, wheezy reactions to viruses for several years. Respiratory syncytial virus remains the leading cause of the condition, but don’t forget human metapneumovirus (identified in 2001) and for extra points, bocavirus (2005). http://adc.bmj.com/cgi/content/abstract/93/9/793

Gut  1185    The epidemiology of inflammatory bowel disease may or may not give us clues about causation: as the authors of this lively review point out, the epidemiology of peptic ulcer disease never revealed that it was caused by a transmissible agent. So modern lifestyle takes the blame, since IBD is largely a disease of affluent Western nations or nations which adopt Western habits. Is it diet? Is it excessive hygiene in early life that unfits us to live in harmony with our gut bacteria? Could it be Mycobacterium avium subsp. paratuberculosis which is endemic in the cattle of many countries (though its prevalence in cattle bears no relation to the prevalence of IBD in humans)? Or – not mentioned in this article, but credibly proposed by an American correspondent with whom I have lost touch – is it due to defaecation in the sitting rather than the squatting position? It’s time we discovered which (if any) of these causes IBD - predominantly ulcerative colitis in the first wave of affected societies, then Crohn’s disease in later generations. http://gut.bmj.com/cgi/content/extract/57/9/1185

Heart  1105    The epidemiology of coronary heart disease is, by contrast, quite well understood – or is it? I found this editorial by Simon Capewell and Martin O’Flaherty somewhat confusing. Can the spectacular decline in CHD mortality seen in Norway, Australia, New Zealand and the UK really have anything to do with a lowered intake of saturated fat or increased exercise (which I don’t believe to have happened), or is it just due to a reduction in smoking and an increase in the consumption of alcohol and fresh fruit and vegetables? Why has Poland managed to reduce its rate so drastically while in neighbouring Ukraine it is climbing more steeply than anywhere else, with the Russian Federation not far behind? Does alcohol prevent coronary disease in Poland but increase it further East? If I had time, I’d dabble more in the papers cited here, but if there’s a take home message it is that medical advances can only account for at best a half of the drop in developed countries; and that as our populations age, so we will see more coronary deaths once again. http://heart.bmj.com/cgi/content/extract/94/9/1105

Ann Intern Med  2 Sep 2008  Vol 149

307    How are your adipokines? As their name implies, they do kinetic things in your adipose tissue, and that may determine whether or not you get type 2 diabetes. Resistin is useless, according to this study of stored sera from the Nurses’ Health Study; because despite its name, levels of resistin do not predict insulin resistance and the later development of type 2 diabetes. Adiponectin, on the other hand, is the one to go for: the more you have floating about in total or in high molecular weight form, the less likely you are to get diabetes; if you are an American nurse. http://www.annals.org/cgi/content/abstract/149/5/307

323    The association between cancer and venous thromboembolism was first described by Trousseau in 1865 and is therefore known as (the) Trousseau (‘s) Syndrome in some parts of the world. This review examines the important question of whether we should therefore look for cancer in everybody with unexplained VTE, and how hard we should look. The existing studies, none of them ideally designed, indicate that you might find occult cancer in up to one in ten patients with unexplained clots if you search hard enough. The test with the greatest yield is abdominal CT scanning. But unlike the great American physician Greg House (a.k.a. the astoundingly versatile British actor Hugh Laurie), these authors do not immediately leap into recommending total body scanning in every conceivable mode for every patient with a venous clot. They sensibly point out that we need proof from long-term prospective studies that an intensive search for cancer actually benefits the one person in ten in whom it’s found and doesn’t just render a lot of people desperately anxious for no good cause. http://www.annals.org/cgi/content/abstract/149/5/323

Fungus of the Week: Cortinarius rubellus

There must be something compellingly attractive about the Deadly Web-Cap which lures the unwary into eating it. This comeliness is referred to in its other Latin name, C speciosissimus , and in its German name, prächtiger Schleierling. I have never seen it, nor am I likely to; but I name it fungus of the week because it has featured in the British news in recent days, having nearly felled the author of The Horse Whisperer, Nicholas Evans. He is recovering in a renal unit in Aberdeen together with others of his party who ate red web-caps thinking they were chanterelles.

They were very unlucky. C rubellus is very rare in the UK, and most of the fungi that can be mistaken for chanterelles (or girolles) are harmless or indeed edible like Hygrophorus aurantiacus or Laccaria laccata. You might go away with a diminished admiration for chanterelles, but you would live to a ripe age. The Deadly Web Cap, on the other hand, kills many people on mainland Europe. In 1979 first recorded victims in the UK survived but needed renal transplantation. Oddly enough, one of them was a fellow medical student of my year at my Oxford college, a gruff Scot of few words, and the last person you would imagine going off and eating strange fungi.

The toxins in fungi include various substances familiar from physiology classes, such as muscarine, and others less familiar, like the amanitotoxins or in the case of this web-cap, orellanins. The traditional British wariness about mushrooms not selected and packaged by Messrs Sainsbury or Tesco has meant that serious fungus poisoning is a rare and newsworthy event in the UK, unlike Poland or Russia, where it is a daily occurrence. In fact there has been no well attested death from fungus poisoning in these islands. Do not be the first. Leave all fungi for me.

JAMA  10 Sep 2008  Vol 300

1135    This week’s JAMA is devoted to issues of education and training, entirely from a US perspective. Most of it therefore isn’t of much interest to British readers, even if they are educators. However, it’s worth glancing at this initial paper on the racial and ethnic mix amongst US medical students, and the way this influences their attitudes to providing care to an increasingly diverse population. “Minority groups” will overtake the white Anglo-Saxon majority within the next 40 years in the USA, and this study strikes an optimistic note about the way that racial diversity amongst the students will prepare them for looking after a diverse mix of patients. But only a minority strongly endorsed the view that adequate health care is a universal right, and only a quarter intended to work amongst the disadvantaged. Roll on, Sarah Palin. http://jama.ama-assn.org/cgi/content/abstract/300/10/1135

NEJM  11 Sep 2008  Vol 359

1097    Surgeons are people who like to operate: give them a body cavity where something might be going wrong, and they’ll dive into it. It is the business of evidence-based medicine to curb their enthusiasm, whether the cavity be the maxillary sinus, the abdomen, or in this case, the knee joint. One of the classic trials of orthopaedic surgery was a comparison between sham arthroscopy and washout for osteoarthritis of the knee and the real thing, which featured in the NEJM six years ago: outcomes were identical. However, since sham arthroscopy for knee OA has failed to gain popularity, this trial compared arthroscopic surgery with usual care (physiotherapy, analgesia). Once again, the results were identical:

O keep the scope far hence from crumbly knees:

The only difference is the surgeon’s fees.

http://content.nejm.org/cgi/content/abstract/359/11/1097

1108    In fact most knees become crumbly as they age, whether or not they creak or hurt. This study from Framingham carried out MRI scanning of the knees of nearly one thousand randomly chosen people of 50 and over: in men of 70 and over, degenerate menisci were found in 56%. Torn or destroyed menisci are particularly common in people of both sexes with knee osteoarthritis. http://content.nejm.org/cgi/content/abstract/359/11/1108

1116    Inhibitors of the epidermal growth factor receptor (EGFR) are being tried out on many different kinds of recurrent or metastatic cancer at present, so far with very limited success. This trial used cetuximab (together with platinum-based chemotherapy) for recurrent head and neck cancer, and achieved an increase in median survival from 7.4 months to 10.1 months. For more about recent advances in head and neck cancer turn to page 1143: no overall survival figures are given, but the best median survival figure (from diagnosis, all types) seems to be 72 months, for the most successful treatment regime(n).

http://content.nejm.org/cgi/content/abstract/359/11/1116

http://content.nejm.org/cgi/content/extract/359/11/1143

1136   According to this review of gonadotropin-releasing hormone agonists for endometriosis, all women who menstruate show evidence of retrograde (i.e. tubal) menstruation but only about 10% get endometriosis. This will usually melt away with GnRH analogue treatment, but at the same time the woman is likely to get a lot of menopause-like symptoms and loss of bone mineral density. These effects can be controlled by “add-back therapy with high dose progestins or low-dose combinations of oestrogen and progestin. If GnRH agonists (goserilin or leuprolide by injection, or nafarelin by nasal spray) fail a three-month trial, there is danazol or surgery. http://content.nejm.org/cgi/content/extract/359/11/1136

Lancet   13 Sep 2008  Vol 372

871    I always flinch a bit when The Lancet turns its magisterial gaze towards primary care, as it does in this issue celebrating the thirtieth anniversary of the Alma Ata Declaration. This grand statement put primary care at the heart of providing health care for all by the year 2000. Richard Horton loves paternalism on a sweeping scale, and he has no problem with “primary care” in the sense of providing mainly preventive interventions to whole populations at grass-roots level. What he doesn’t have much insight into (or sympathy with) is the role of the generalist doctor in mediating between scientific medicine and the experience of individuals who come to doctors seeking help. This person-to-person engagement can last the best part of a lifetime and is a key element of medical practice, especially in the developed English-speaking world. But it doesn’t get any mention here, except in this short editorial from the Netherlands and the USA, which draws a useful distinction between personal care and community health care. It calls for an integration between the two, but doesn’t mention the tensions which often arise between them. The rest of the issue is devoted to “primary care” in the sense that The Lancet is most comfortable with: on-the-ground projects in low-income countries, mostly supervised by but not delivered by doctors. Fair enough. I am very aware that impersonal care is what matters most for whole populations; also that much of what is written about personal care in Britain and the USA is sentimental, self-congratulatory codswallop; but all the same I’m not entirely willing to view the whole of my working life as a pointless luxury. http://www.thelancet.com/journals/lancet/article/PIIS0140673608613768/fulltext

BMJ  13 Sep 2008 Vol 337

611  A few years ago, I made a sally into medical student teaching and was astonished to find how little stereotypes had changed over the thirty years since I had last wandered the wards and operating theatres, in order to learn wisdom and the art of communication from consultants. Mostly white male consultants of course, in 2008 still saying such things as “Some of these sweet little Asian girlies are very hard to get through to.” Or, “A little bit of fear ain’t a bad thing from where I come from. I may push someone over the edge and they’ll probably commit suicide and I’ll be terribly sorry but that’s a risk I will take…” Hah hah, that’s the way, none of your political correctness around here, thank you, this is an operating theatre, isn’t it sister? And you sweet little girlies better get used to it, though none of you will ever make surgeons because you don’t have the stamina of a large white male like me and you’ll all go off and have babies and do dermatology or public health. Or general practice if you’re thick. Forceps!http://www.bmj.com/cgi/content/abstract/337/aug18_1/a1220

616    Do you value self control? I’m not sure that it’s all it’s cracked up to be; not as a moral quality, of course, but as a research method. This study used the GP Research Database which gets a big puff in the Methods section. Patients given antipsychotics acted as their own controls and trawling through 6790 of them confirmed that all antipsychotics carry a risk of stroke, with “atypical” antipsychotics riskier than phenothiazines and the biggest risk being in patients with dementia. For more about the methodology, see the editorial on p.586.

http://www.bmj.com/cgi/content/abstract/337/aug28_2/a1227

http://www.bmj.com/cgi/content/extract/337/aug28_2/a1069

Arch Intern Med  8 Sep 2008  Vol 168

1733   British doctors can sometimes sound rather smug about the way we invented communication skills (in general practice and palliative care, mostly, because we’re so nice). The BMJ stereotype paper is a useful corrective to this, and so is this very worthwhile article about titrating guidance in the context of American hospital medicine. It’s a piece that needs to be read by all who teach the process of shared decision-making in difficult circumstances (here it’s whether to put a feeding tube into an old man with a dense stroke); and by all who actually do the business too. http://archinte.ama-assn.org/cgi/content/abstract/168/16/1733

1740   If you stick someone’s arm in freezing water and measure the rise in blood pressure using the other arm, you may be able to identify individuals who will go on to develop salt-sensitive hypertension. This is known as the cold pressor test and is the sort of unpleasantness we endured in physiology labs to help us learn better, and in this study was endured by 1906 dwellers in rural North China to see if dietary modification can prevent hypertension. In theory, it can: cold pressor positive individuals should eat less salt and take more potassium. The experiment continues, and will include genomics. http://archinte.ama-assn.org/cgi/content/abstract/168/16/1740

1768    We all know (because prescribing advisors are always telling us) that old people who take sleeping tablets have a higher rate of falls. Therefore benzodiazepines cause falls and we should feel awfully guilty about prescribing them. Well, perhaps. Benzos probably do increase the risk of falls, but so does poor sleep, according to this interesting actigraphy study of sleep quality in 3,000 American women aged 70 or more. If you’re a bad sleeper, you fall more anyway. http://archinte.ama-assn.org/cgi/content/abstract/168/16/1768

1791   When a group of persecuted Swiss Anabaptists decided to take refuge in William Penn’s American colony, they little knew that they were setting themselves up for endless genetic study in the twenty-first century. The Old Order Amish no doubt expected the world to end long before then. But now they form a perfect agar plate of organisms confined to one spot and breeding with each other. Here they are studied for the light they shed on the association between common FTO gene variants and obesity and the way that exercise (much practised among the Amish, who shun all mechanical devices) modifies the genotypic effects. http://archinte.ama-assn.org/cgi/content/abstract/168/16/1791

1798   Oh GORD, not another harmful effect of hormone replacement therapy. This analysis of the Nurses’ Health Study seems to show a dose-related link between oestrogen use and symptoms of gastro-oesophageal reflux. http://archinte.ama-assn.org/cgi/content/abstract/168/16/1798

Fungus of the Week: Clitopilus prunulus

I was thinking how long it had been since I last saw this fungus when I came across a large stand of them on a little grassy bank by the Academic Building of the John Radcliffe Hospital in Oxford. I am surprised that they lasted so long on a site so regularly traversed by Middle Europeans and other fungivorous types. Anyway, I snaffled them up gratefully and took no notice of anyone staring at me as I bore an armload back to the car park.

These white fungi are easily distinguished from poisonous amanitas and other rogues by several features: the caps usually grow flattened and irregular, with very distinct margins and folds, the feel of kid leather and a shiny appearance in places. The stipes are usually short and eccentric. No ring. The gills begin nearly white but always tend towards grey and later pale brown. And above all, they smell of new meal: hence their alleged popular name, The Miller.

On examining the bank further, I made my most spectacular find: a large white fungus with a heavy cap covered in grey warts. Its flesh broke soft like a puffball’s and smelt somewhat similar; it had a large, fragile ring and pure white gills, indicating an amanita. And so it is (I think): Amanita strobiliformis (Paul. ex Vitt.) Bertillon, syn A solitaria (Bull ex Fr.). “Unknown in many areas, including Great Britain, or very rare” says my book, written by two Czechs in 1979. “As it dries, smells of honey and radishes.” It is edible, but I have foregone the unique opportunity of eating it and sent it to Kew for definitive identification.

Later I prepared the following fungus feast, to eat up the week’s other gatherings with friends:

1. Poached oysters with cream of hedgehog

Open 12 oysters, reserving the liquid. Chop a carrot finely. Take a few hedgehog mushrooms (Hydnum repandum, pieds de mouton) and chop these somewhat less finely. Cook the carrot and the mushrooms for a few minutes in the oyster jus and a little white wine. Now add the oysters and the cream of five lactating hedgehogs: failing this, a cup of double cow’s cream, together with a few tiny pieces of tomato flesh and finely chopped chives. Bring almost back to the boil. Serve – three oysters per person.

***** Perfect. Based on a dish of oysters with morels I had at the Comptoir à Huîtres, a restaurant serving nothing but molluscs and crustaceans in a scruffy backwater of Dieppe.

2. Frazzled Millers

Take four whole caps of The Miller. Fry each one separately and as quickly as possible in enough very hot olive oil to cover it. Dry any excessive oil on absorbent paper and serve each cap on a slice of Serrano or Parma ham adding black pepper, a little parsley, and a few shavings of Parmesan cheese.

** Less than the sum of its parts. The olive oil was too green and made the mushrooms bitter. Better to fry them with pancetta and sprinkle with a bit of parsley.

3. Deer of the Forest

Marinate four venison steaks in red wine with a little brandy and olive oil, salt and pepper. Dry them and fry in duck fat. Half way through add a chopped leek and a handful of autumn chanterelles (Cantharellus infundibuliformis: make sure these are not too moist, or pre-fry in butter). Remove the meat, deglaze the pan with the marinade at high heat and serve with broad beans, crushed peas, and green lentils with a little lightly cooked tomato.

**** An excellent way to eat venison, though the mushrooms had no impact. Baked beetroot might have added earthiness and brought them out more.

JAMA  17 Sep 2008  Vol 300

1303   We live in a toxic environment and we are all going to die. One of the man-made toxins I was quite unaware of is bisphenol A, which is used in lots of plastics and polymers including those which line food and drink containers. Even if you don’t use packaged foods and canned drinks, you can’t avoid it, because it’s in the water supply too. Hence your tendency to grow fat, oestrogenised and insulin resistant. Perhaps: this is a cross-sectional study (from the US population survey, NHaNES) which finds an association between urinary BPA concentrations and diabetes and cardiovascular disease, after adjusting for a number of potential confounders. It could be awfully important; or just an artefact of residual confounding: it’s hard to know how we can ever be sure. But if we could do without this stuff, we would have one less thing to worry about (see editorial p.1353). http://jama.ama-assn.org/cgi/content/abstract/300/11/1303

1311   The Pelvic Floor Disorders Network is yet another research consortium which tapped data from NHaNES, and the conclusion of their survey is that “pelvic floor disorders affect a substantial proportion of women and increase with age.” Gosh. More revelations: parity and obesity are major risk factors. http://jama.ama-assn.org/cgi/content/abstract/300/11/1311

1317   How many cusps does the aortic valve have? I had to think for a moment, because the valve called “tricuspid” is of course the one between the chambers of the right heart; which is a silly specific name because the aortic outflow valve is also tricuspid. Except, that is, when it is bicuspid. An aortic valve with two cusps is the commonest congenital cardiac anomaly in the adult population, and in this survey of young adults referred to a number of hospital clinics, it did not affect survival over a 9-year period. But in the longer term it definitely carries the risk of aortic dissection and aneurysm, and of stenosis and/or regurgitation. We need long-term follow-up studies of cases detected by whole-population screening. http://jama.ama-assn.org/cgi/content/abstract/300/11/1317

1346    Helicobacter eradication used to be easy: three drugs for a week, and it was done. But over the last decade, success rates have fallen because the cunning little blighters have become resistant to clarithromycin and metronidazole, though interestingly not to amoxicillin, which we throw down every second patient who comes through our doors. So should we be switching to sequential therapy? It’s fiddlesome but almost certainly the strategy of the future, as this useful little article suggests. http://jama.ama-assn.org/cgi/content/extract/300/11/1346

NEJM  18 Sep 2008  Vol 359

1200  “No Place Like Home – Testing a New Model of Care Delivery”. The American College of Physicians has come up with a radical new vision for the care of people with complex chronic conditions: “The core features include a physician-directed medical practice; a personal doctor for every patient; the capacity to coordinate high-quality, accessible care; and payments that recognise a medical home’s added value for patients.” So what is this medical home of which they speak? Uncannily like the place that you and I work in, if you are a British GP in a traditional partnership.

http://content.nejm.org/cgi/content/full/359/12/1200

http://content.nejm.org/cgi/content/full/359/12/1202

1207    I have spent the last decade mulling over the way we use diagnostic tests in real life primary care, and the associated terminology of “usefulness”, “accuracy” (as in this paper), sensitivity, specificity, predictive values, likelihood ratios etc. At the workface, we don’t use a 2x2 table, or a nomogram, or a ROC curve, but some rapid, partially informed mental process to decide which tests to order, and then how to interpret them. Every working morning at 8 a.m., I scroll down so many test results that my wrist aches, and that’s before starting consultations. By the end of the day at 7 p.m., both my wrist and my head ache and I have generated the next lot. So: if my patient has had a negative CT colonogram, does that mean I can tell them they don’t have bowel cancer? Yes and no: they have a 90% chance of not having a tumour (adenoma or cancer) of 10mm or more. To me, that isn’t quite good enough: the examination was a waste of bowel preparation, time, and radiation. http://content.nejm.org/cgi/content/abstract/359/12/1207

1218   To be practically certain, the examination I want for myself or my patient is colonoscopy. Like CT colonography, this takes three days (not one, as the editorial on p.1285 claims): one to enjoy starvation and incessant diarrhoea, one for the examination, and one to recover. I speak as the patient. For the doctor, it might be a bit nicer and a bit faster to look at CT films rather than having to wield the colonoscope, but on the other hand the five year risk of having a cancer after a normal screening colonoscopy is nearly zero (95% CI 0-0.24%). http://content.nejm.org/cgi/content/abstract/359/12/1218

1225   The angiotensin II type 1 receptor blockers (ARBs, sartans) arrived on the scene a few years after the inhibitors of the angiotensin converting enzyme and they continue to fight it out with ACE inhibitors for a market share. So tell me, sartan, can you prevent recurrent stroke or cardiovascular events when compared to placebo in the two and a half years following an ischaemic stroke? The bizarre answer is no: telmisartan reduced blood pressure but did not reduce events. That shouldn’t be possible. http://content.nejm.org/cgi/content/abstract/359/12/1225

1238   Built into the same trial (PRoFESS, which recruited 20,332 patients after ischaemic stroke) was a comparison between aspirin plus dipyridamole versus clopidogrel to prevent recurrent stroke. It was a draw, both in terms of stroke events and bleeding complications. But the current price advantage is about 4 to 1 in favour of dipyridamole/aspirin.

1252   I tend to regard food allergy as a complicated subject, the province of mountebanks and immunologists. But this nice short British article makes it sound very simple. Children are often allergic to eggs and milk, but 75% of them outgrow this. They may also be allergic to nuts and seeds, but rarely outgrow these allergies; which also often present in adult life. Adults also get allergic to fish and shellfish. Skin prick testing and IgE tests are reasonably reliable. It’s just a shame that I’ve spent my whole working life without access to any effective allergy service. http://content.nejm.org/cgi/content/extract/359/12/1252

Lancet  20 Sep 2008  Vol 372 

Asthma is the oldest medical word in common use: it first appears in the writings of Hippocrates around 450 BCE and derives from a verb used by Homer. But, as The Lancet’s cover declares, “Progress in understanding asthma and its underlying mechanisms is slow; treatment can be difficult and response unpredictable; and prevention or cure is still a pipedream.” This is an exceptional issue of the journal, which deserves to be read from cover to cover, not just for the insights it offers into this frustrating disease complex but also as a showcase for the scientific processes which can help to unravel this kind of complexity: all the way from epigenetics to whether Calpol is safe for babies.

1039   So is Calpol safe for babies? Perhaps not, according to this New Zealand study of the association between the use of paracetamol in infancy and childhood, and the risk of asthma, rhinoconjunctivitis and eczema. Giving babies paracetamol in the first year of life increases the risk of later childhood asthma in a dose-dependent manner. This is an ongoing study called ISAAC, which hopefully will not sacrifice any children; after all, in New Zealand sheep outnumber people by ten to one and there is no shortage of rams stuck in thickets. But to know whether paracetamol really causes childhood asthma we need a prospective controlled trial; so far, the only one done seems to show that ibuprofen is safer, or may even prevent asthma if given early in life (see editorial p.1011). http://www.thelancet.com/journals/lancet/article/PIIS0140673608614452/abstract

1058   I was trying to take my own advice and read this Lancet from cover to cover during an out-of-hours session, but found myself prevented by a 6-hour long stream of patients including a bouncy baby of six months who had been wheezing ever since a “chest infection” at three months of age. “Do you think she has asthma, doctor?” asked her mother sensibly, while in reply I found myself waffling incomprehensibly about viruses that make babies wheeze not necessarily leading to asthma but you couldn’t be sure at this stage etc. This longitudinal study from Tucson, Texas confirms that you cannot be sure for a very long time indeed – 22 years at least. It seems that babies who wheeze persistently may be 14 times more likely to develop asthma in early adulthood. This is part of wealth of associative data which you may or may not want to explore in greater detail, taking in a European study of rhinitis (p.1049), a couple of thought-provoking editorials (pp.1012, 1014), and a valuable review of atopy in children as a predictor of asthma (1100).

http://www.thelancet.com/journals/lancet/article/PIIS0140673608614476/abstract

http://www.thelancet.com/journals/lancet/article/PIIS0140673608614464/abstract

http://www.thelancet.com/journals/lancet/article/PIIS0140673608614518/abstract

1065   Since asthma is an inflammatory process, the management of asthma should perhaps be guided by measuring a marker of inflammation (“inflammometry”, as the editorial on p.1017 calls it). The researchers’ favourite is the sputum eosinophil count, but nobody could suggest that this is a practical everyday test, so the fraction of nitric oxide in exhaled air (FE_NO) has been proposed instead. Logically, this should lead to reductions as well as increases in treatment, and so it did in a study mentioned in the editorial on p.1021, but not in the study reported here, which only provided evidence of increased corticosteroid treatment in those with a high NO fraction. The authors conclude that this test (which isn’t exactly cheap or home-based either) won’t add value to existing treatment guidelines. http://www.thelancet.com/journals/lancet/article/PIIS0140673608614488/abstract

1073   Are we about to see a lot of new treatments for asthma? Very probably, because the market is immense and the potential pharmacological targets are abundant. If you really want to know where we might be heading, you can read this review of new targets; and perhaps more profitably, the review of key pathogenic mechanisms on p.1107. But to do them justice, you’ll need to take the week off.

http://www.thelancet.com/journals/lancet/article/PIIS014067360861449X/abstract

http://www.thelancet.com/journals/lancet/article/PIIS014067360861452X/abstract

BMJ  Journals Sep 2008

BMJ  673    Does adherence to a Mediterranean diet improve health status? According to this Florentine review, it does: not just in terms of overall mortality and cardiovascular disease, but especially in relation to Alzheimers’ and Parkinson’s diseases. But adherence to anything improves health: adherent people live longer. And we are soon off to feast in Bologna, which though close to the Mediterranean sea, specialises in richly filled tortellini, stuffed pig’s trotters and the like. Does that really count? I think I’ll be taking my simvastatin with me. http://www.bmj.com/cgi/content/abstract/337/sep11_2/a1344

BMJ  676   Compared with the daily workload of intractable complex disease in patients one has grown fond of but cannot help, out-of-hours primary care can be rather refreshing. It is well-organised and has clear boundaries, but one of the most baffling features is call handling by a central agency, where earache a day after air travel can feature as “Urgent” and a generalised petechial rash come in as “Routine”. Fortunately our local service is well-doctored by experienced local practitioners who respond quickly to all incoming calls, but this Dutch study shows that poor telephone triaging is not just a local phenomenon. http://www.bmj.com/cgi/content/abstract/337/sep12_1/a1264

Gut  1315  It is no secret that we are greatly outnumbered by bacteria: not just in the global environment, but as cells in our own bodies. The overwhelming majority are of course in the large bowel, but bacteria in the small bowel may be important too, particularly in the pathogenesis of irritable bowel syndrome. It’s a difficult area to investigate, since the offending germs are probably those in the latter end of the ileum, and may be difficult to culture: but there is certainly some evidence that non-absorbable antibiotics like rifamixin can help some people with IBS, presumably due to small bowel bacterial overgrowth. If this is a topic that bugs you, here is a useful overview. http://gut.bmj.com/cgi/content/extract/57/9/1315

Thorax  758   More about asthma for those who seriously intend to take a week off. Here is an editorial on recent advances in exacerbations, which in all Northern hemisphere countries tend to peak in September and are mostly caused by viruses, especially rhinoviruses. Treat them as you normally do – there are no real recent advances. As for asthma self-management education, it’s something doctors are bad at and tend to leave to practice nurses. But why stop there? There is nothing about it that can’t be done equally well by properly selected and trained lay educators, according to a trial based in 39 GP practices in West London and Manchester (p.778).

http://thorax.bmj.com/cgi/content/extract/63/9/758

http://thorax.bmj.com/cgi/content/abstract/63/9/778 

Ann Intern Med  16 Sep 2008  Vol 149

380   Most of our patients with chronic obstructive pulmonary disease are long-term smokers who are also at high risk of cardiovascular events, and some of the drugs we give them, like β-adrenergic agonists and theophylline, are also, on the face of it, rather risky for the heart. Here’s a large case-control study form US Veterans’ hospitals looking at mortality associated with medications for recently diagnosed COPD. The drug carrying the highest risk (odds ratio 1.34) is neither of the above-mentioned, but ipratropium, the chest physicians’ favourite. http://www.annals.org/cgi/content/abstract/149/6/380

391   Several case-control studies have suggested a link between the use of proton pump inhibitors and community-acquired pneumonia, which is rather worrying as we prescribe PPIs to so many people. Here’s a study based on the prescriptions we have actually issued: it comes from the UK GP Research Database between 1987 and 2002. First the good news: overall, there was no association between current PPI use and pneumonia. Now the bad news: rates of pneumonia are six times higher in patients prescribed PPIs for the first time in the preceding two days, and this recent-initiation effect persists for two weeks. Odd. http://www.annals.org/cgi/content/abstract/149/6/391

Fungus of the Week: Creolophus cirrhatus

I was wandering the local woods with a young friend and fellow-reviewer, Druin Burch, who resembled St Christopher as he bore his baby son on his shoulders (in a safe rucksack contrivance unknown to the saint, I should add, in case any health visitors are reading this). After a long slow wander, finding nothing, we spotted a far-off oak trunk with a cut end which was sprouting several masses of white fungus, one of which was in perfect condition. I had never seen anything like it, except a clump of Hericium coralloides in the New Zealand bush near Tauranga. It was a bright slightly creamy white with caps covered in small spines and with long spines beneath instead of gills.

At home I identified it as a rare close relative of the Hericium, and edible. It was time to fry a bit in butter. My wife, who is usually sceptical, joined the experiment, which in itself is testimony to the very attractive appearance of this fungus. In fact I think it is the most beautiful fungus I have ever come across. And it tasted lovely and sweet.

Two nights of broken sleep ensued as I contemplated the commercial opportunities opening up. Here was an edible fungus which grew on wood, and would therefore be easy to propagate – perhaps as easy as the oyster mushroom, which you can grow on sawdust or even lavatory paper. It looks lovely and tastes nice and could be marketed by the ton as Queen Coral Mushroom ©. All it would need is a bacteriologically clean room to isolate and propagate spawn, a large production shed with controlled levels of heat, humidity and carbon dioxide, a distribution system, a marketing manager…

I was saved all this anxiety by a repeat tasting after two days storage in the refrigerator. “Nah – tastes of paint,” was my wife’s comment, and I had to agree. The Dulux Fungus ® may never make my fortune, or Druin’s. Back to writing.

JAMA  24 Sep 2008  Vol 300

1471   Humankind is genetically more diverse in Africa than anywhere else, but the slaves who were snatched and traded in the New World (if they survived the journey) were mostly from a relatively small area of Western Africa. Their descendants, after many generations of mixture, are now extensively studied as “African-Americans” or, in this paper, just as “black men and women”. Political correctness apart, this is genetic science at its crudest: but I guess that it is useful to know that “black” Americans have a higher risk of colon cancer and that this is reflected in the prevalence of polyps larger than 9mm detected by screening colonoscopy, which is slightly higher in black American men and considerably (60%) higher in black American women.

http://jama.ama-assn.org/cgi/content/abstract/300/12/1417

1423   Out-of-hospital resuscitation for cardiac arrest is usually unsuccessful, but that doesn’t mean it shouldn’t be attempted. Or indeed abandoned when it is totally futile. So we need (a) to understand the reasons why success in resuscitation varies so much and (b) have robust criteria for discontinuing it. These are the topics of two papers here: the first simply demonstrates the huge variation in success rates across a variety of North American locations – from 3.0% to 16.3%. Possible reasons are discussed in the editorial on p.1462: the main one is location. The second study (p.1432) validates two different rules for discontinuing out-of-hospital cardiac arrest procedures, one devised by the Canadian OPALS group for basic life support (BLS) and the other for advanced life support (ALS). In this case series of 5505, the overall survival for OOH arrest to hospital discharge was 7.1%, but in those who met the BLS discontinuation criteria it was 0.2%, and in those who met the ALS discontinuation criteria it was zero.

http://jama.ama-assn.org/cgi/content/abstract/300/12/1423

http://jama.ama-assn.org/cgi/content/abstract/300/12/1432

1439   It was only last week that I became aware that there was a question mark over the use of inhaled anticholinergics for chronic obstructive pulmonary disease. That was from a case-control study in US Veterans’ Hospitals (Ann Intern Med p.380) looking at ipratropium bromide only, whereas this is a meticulous systematic review of 17 trials involving both ipratropium and tiotropium. Use of these muscarinic agonists is associated with a definite increase in major adverse cardiovascular events, and an increase in total mortality which just escapes statistical significance (95% CI 0.99-1.61). Therapeutic advance in COPD seems to be drifting backwards; even long-acting bronchodilator/steroid combinations carry a danger of increased pneumonia (TORCH trial).

http://jama.ama-assn.org/cgi/content/abstract/300/12/1439

NEJM  25 Sep 2008  Vol 359

1317  In the enthusiastic editorial which accompanies this paper (p.1393), a Californian neurologist reports asking his trainees the question: if a patient presents 30 minutes after the onset of a hemispheric stroke, how long do you have to initiate thrombolysis? The correct answer is one minute. The effectiveness of alteplase declines with every passing moment, though it is not quite lost by four hours, as this large European trial (ECASS III) demonstrates. But only just. It falls panting across the statistical finishing line –  95% CI for global benefit 1.00-1.65, as an odds ratio with placebo.  http://content.nejm.org/cgi/content/abstract/359/13/1317

1330   So which really is the best stent following myocardial infarction? Bare metal or coated? Oh, how we long to know. This follow-up study from Massachusetts favours the coated, but not by much, and by retrospective analysis of matched pairs rather than prior randomisation. So the Stent Wars can go on and on, in all sorts of fascinating statistical arguments, which I know you will want to follow. http://content.nejm.org/cgi/content/abstract/359/13/1330

1357   Given that quite a few patients with really high cholesterol levels can’t tolerate statins, we would like to celebrate the arrival of ezetimibe, but people (in the SEAS trial – see p.1343) have spoilt the party by saying it might cause cancer. Here various acquaintances and luminaries from the Oxford Clinical Trial Support Unit try to ride to the rescue with data from large unpublished trials which they are running. According to these, use of ezetimibe is probably not associated with increases in cancer. At least in the short term. And we know that it lowers cholesterol. Now all we need is proof that it has any meaningful benefit.

http://content.nejm.org/cgi/content/abstract/359/13/1357

http://content.nejm.org/cgi/content/abstract/359/13/1343

1367   The molecular origins of cancer are hardly the stuff of light reading: genomics mixed with complex biochemistry mixed with speculation. But this account of the origins of lung cancer pulls off the feat of being lucid, readable and even engrossing, if you skip past all the immensely technical paragraphs at the start. It comes from Houston, which even I know is in Texas: unlike Tucson, which I relocated in that state last week, but which I am informed still belongs to Arizona.

http://content.nejm.org/cgi/content/extract/359/13/1367

Lancet   27 Sep 2008  Vol 372

1163   As sirolimus gets nearer the end of its patent life, what is going to make us buy more olimusses? Biolimus, perhaps: it may be the marketing answer, though it’s just sirolimus with a slight chemical tweak. And that means it can be incorporated in a whole lot of new expensive drug-eluting stents and the Stent Wars can continue for ever. But even The Lancet begins to wonder why – see the editorial on p.1126. http://www.thelancet.com/journals/lancet/article/PIIS0140673608612441/abstract

1174   The manufacturers of the angiotensin receptor blocker telmisartan aren’t having much luck with the studies they’ve financed in the hope of showing that the cardiovascular benefits of their drug equal those of an angiotensin converting enzyme inhibitor. This trial recruited people with high cardiac risk who would normally be given ACE inhibitors, but could not tolerate them. It showed that telmisartan had virtually no detectable benefit. So far from telling me to prescribe this sartan, it makes me wonder if it less effective than, say, candesartan.

http://www.thelancet.com/journals/lancet/article/PIIS0140673608612428/abstract

BMJ  Journals Sep 2008

BMJ  729   Debate has reached fever PITCH about whether to use paracetamol, ibuprofen or both together to bring down children’s temperatures. In response to the PITCH study reported here, Anthony Harden contributes a lucid and sensible editorial summarising the evidence (p.701) of various trials of antipyretics, and concluding that if you are going to use anything, you might as well use ibuprofen because it lasts longer. But this is not good enough for fundamentalists who insist that recommending any antipyretic for children is a sin. Send in your own Rapid Responses to the BMJ, remembering the First and Second Laws of Inverse Outrage. (The First Law states that the heat of argument should increase in inverse proportion to the importance of the topic, and the Second Law states that the weaker your evidence, the louder you should assert it). http://www.bmj.com/cgi/content/abstract/337/sep02_2/a1302

Gut  1207   Proton pump inhibitors are now so cheap and effective that we rarely think about referring patients with gastro-oesophageal reflux for endoscopic surgery, which has become simpler and safer of late and carries the acronym LARS (laparoscopic anti-reflux surgery). A Swedish trial randomised 554 patient to either esomeprazole or LARS (total fundoplication), and reports that at 3 years, the two groups have similar outcomes, except that the surgical group had quite a lot of post-operative discomfort. http://gut.bmj.com/cgi/content/abstract/57/9/1207

Gut  1246  Getting inflammatory bowel disease is bad enough, but this Dutch study confirms that it also carries a risk for early colorectal cancer which is not addressed by current colonoscopy screening guidelines. They did a national pathology database search and found 149 patients with IBS and colorectal cancer, and found that 17-28% of the cancers would have been missed had the recommended colonoscopy intervals been followed. http://gut.bmj.com/cgi/content/abstract/57/9/1246

Heart  1141  In a long and tedious effort to save our local hospital, I have scoured the literature for studies on the effect of transit times between home and hospital for a number of conditions, though not myocardial infarction, which is the subject of this paper. It establishes that there is indeed prima facie evidence of a link between transit time to hospital and outcome in MI. And since the study comes from Tayside, I shall have to revive a great tradition of local poetry in its honour:

It is always a serious matter when a man has a heart attack,

And if he happens to be far from Dundee’s great hospital he may never come back.

W. McGonagall (op posth) http://heart.bmj.com/cgi/content/abstract/94/9/1141

Thorax  791  I am quite a regular referrer to physiotherapy though I can’t think of a study which has ever shown it to be of benefit for anything. But at least it helps patients feel that something is being done while they get better. I’m sure the same principle has lead to the continuing use of physio for children in hospital with acute pneumonia. If it doesn’t do any good, it can’t do any harm: except that this study from Brazil suggests that it might. Kids who got physio for pneumonia had a longer duration of coughing and kept their chest crackles longer too. http://thorax.bmj.com/cgi/content/abstract/63/9/791

Arch Intern Med  22 Sep 2008  Vol 168

1853   Patients with cancer live from one hospital appointment to another, hanging on every word the doctor has to say, and then forgetting most of it or finding that the doctor had nothing much to say; which they then often ask us as GPs to remedy. Like as not, we don’t have the clinic letter or it doesn’t contain anything more helpful. If it’s any consolation (and it shouldn’t be) things are probably even worse in America. This study – which as far as I know is unique – recorded the clinic encounters of patients with lung cancer and looked for empathic opportunities, i.e. signals from the patient to indicate that understanding or explanation were being sought. Out of 384 such moments, clinicians were deemed to have responded appropriately in 39 – a 10% empathy score. Greg House would be proud of them. http://archinte.ama-assn.org/cgi/content/abstract/168/17/1853

1867   Here is a long-term trial of tight control of type 1 diabetes which actually seems to say something important – that keeping the HbA_1c low may prevent hypertension. Or perhaps, given that we have so little control over the way our patients manage their condition, this should be expressed the other way round: that hyperglycaemia is a risk factor for developing hypertension. This is a 15.8 year follow-up study of 1441 patients, sufficiently powered to be believable.

http://archinte.ama-assn.org/cgi/content/abstract/168/17/1867

 
Fungus of the Week: Phallus impudicus

Yes, a common woodland fungus really does carry this official Latin name, and it looks uncannily like one. John Gerard the Elizabethan herbalist called it the “pricke mushroom” or fungus virilis penis effigie. One German name is Hirschbrunst, which implies that these woodland erections belong to ardent male deer. But there is a tribe in New Guinea which attributes them to fallen tribesmen, who will chase you through the forest if you are so foolish as to touch their aroused membrum virilis. John Parkinson in 1640 – a time of maritime rivalry between Britain and the Netherlands – calls them “Hollanders workingtooles”. And so on. I am sure you will be relieved to learn that their modern English name is The Stinkhorn.

The stink of these phalloids really is something remarkable, resembling rotten flesh and attracting insects from far and wide. The sticky glans of a newly emerging one is always covered in flies. Within a day all the covering – consisting of a tenacious mucoid substance full of spores - has gone. This is a really effective dispersal mechanism and you will find these fungi in every wood around this time of year: or at least you will smell them. For this reason, I have come to rather like the smell, because it means that the mushroom season is properly under way. Call me perverted.

All the books tell you that the “egg” (oeuf de diable) from which the mushroom (satyre puant) emerges is edible, and naturally it is credited with aphrodisiac properties. I found about 2 kilos of them the other day and decided to put this to the test – the edibility, I mean. First you remove the white outer skin to reveal a mass of translucent tenacious slime. You do your best to remove this, though it is almost as difficult as removing slug slime. Then you cut the inner egg in two, revealing the little protophallus surrounded by a grey-green mass of immature spores. Lovely. If you are well-versed in the ways of phallus-egg-eating, you are supposed to fall on the raw middle bit and declare that it has a delicious taste of radishes. But lacking this advice, I just proceeded to slice it and fry it in butter. It tastes of nothing. Moreover I can think of few things less calculated to arouse the amorous propensities - especially those of a sceptical onlooker.