Richard Lehman’s journal review 29 September 2010

Richard LehmanJAMA  22-29 Sep 2010  Vol 304
   Heart failure management is supposedly a showcase for evidence-based medicine, with lots of interventional trials to guide the deployment of ACE inhibitors, angiotensin receptor blockers, beta-adrenergic blockers and so on: but in fact it is just a mess. These drugs can certainly improve prognosis in some patients but the idea that every individual should be on maximal dosages has no basis in fact, and consequently interventions aimed at making heart failure patients more adherent to treatment seldom show any benefit. This HART study is a good illustration. The investigators approached 3154 patients who bore the doom-laden label of “heart failure”. 465 of them did not meet the criteria for HF, 511 declined to take part, and nearly a thousand more had “uncertain prognosis”, “logistical difficulties” or “excessive comorbidity”. That left 902 to be randomised to receive either a basic educational package, or that plus 18 two-hour group meetings. At two years, the more intensively educated group showed a slightly higher mortality but at three years there was no difference. I think we have got as far as we can with our present conceptual framework for “heart failure” and its management.

   In all developed countries, people considered to be at increased cardiovascular risk have received much the same medication over the last decade. The REACH study recruited from 29 countries on the basis of known coronary artery disease, cerebrovascular disease, peripheral vascular disease, or a combination of risk factors without overt arterial disease. The majority of patients were taking a statin and their event rates at four years were lower by 30% than those not taking a statin. This equates to the protective effect of being Japanese. However, I suspect that the Taiwanese and Chinese groups in this study would prefer to take statins rather than rejoin the Japanese Empire. Eastern Europeans are out of luck (does that include descendants like me?) – our 28% added risk is about the same as for smoking. This applies to people from the Middle East too.

   A couple of papers in JAMA over the last few years led me to believe that we probably shouldn’t treat asymptomatic elevated TSH in elderly patients because so-called subclinical hypothyroidism is associated with greater longevity. This individual patient meta-analysis of 11 prospective cohort studies, however, rules out any actual benefit from having a high TSH if you’re over 80, but at the same time rules out any harm. In all other age groups, biochemical hypothyroidism increases the risk of coronary heart disease, especially if the TSH is above 10, but there is no effect on total mortality.

NEJM  23 Sep 2010  Vol 363
   Screening mammography was introduced following several large prospective studies done in the 1980s and 1990s, which showed an apparent reduction in breast cancer mortality of 15-23%; but the effect size and the harms of screening have been hotly debated ever since. This careful observational study of the introduction of mammographic screening to each region of Norway in the last decade gives us the best estimate of possible mortality benefit in our own era of multidisciplinary team management of breast cancer. In women over 70, who got MDT care but not mammography, breast cancer mortality fell by 8%; in women between 50 and 70, who did get screening mammography, mortality fell by 10%. So, if you screen 2,500 women aged 50 for ten years, you will prevent one death from breast cancer but generate about 1,000 false alarms and overdiagnose breast cancer in 5-15 women who will undergo needless surgery, radiation, chemotherapy or a combination. I get these figures from the admirably clear editorial on p.1276.

1222    Superficial vein thrombosis in the legs is common, painful, often recurs but is usually left to look after itself. The risk of conversion to deep vein thrombosis and/or pulmonary embolism is very low. Fondaparinux, a subcutaneously administered Factor Xa inhibitor, given for 45 days, will reduce this risk to nearly zero, but the number-needed-to-treat is 88.

Lancet  25 Sep 2010  Vol 376
   Over the last year, the fortunes of stenting for symptomatic carotid stenosis have taken a dive, with trial after trial showing that endarterectomy produces better outcomes. But the Carotid Stenting Trialists’ Collaboration is unwilling to give up without a final plea, based on a meta-analysis of individual patient data. This tries to avoid the accusation of being a post-hoc subgroup analysis by calling itself “pre-planned.” Anyway, the trialists argue that although stenting is definitely more hazardous in the over-70s, it might perhaps be as safe as endarterectomy in younger patients. But the forest plot in the editorial on page 1028 is pretty damning for the stenting option, which should probably cease to exist.

1074   We don’t really seem to know if carotid endarterectomy is worthwhile after the age of 75, but this ten-year outcomes study of the ACST-1 trial shows that it definitely reduces stroke in younger age groups, regardless of gender or medical therapy. However, it’s not an enormous benefit: the difference between 13.4% and 17.9% at 10 years.

1085   There’s been quite a bit of debate about the value of vertebroplasty in the last year too, with similar outcomes in sham and active groups in two major trials. The Vertos II investigators boldly claim that their open-label trial design is superior, because it mirrors clinical reality. Also, they selected their patients within 6 weeks of their vertebral events. While waiting 9 days for treatment, half of these patients experienced sufficient decreases in their pain scores to become ineligible for the trial. At least that is how I interpret the text. Those who went ahead with vertebroplasty experienced quicker and more lasting pain relief than those who were randomised to symptomatic treatment only. So there may be a place for this procedure; though the editorial (p.1031) written by a proponent of balloon kyphoplasty argues that this is a superior procedure. We’ll have to wait for the results of four trials comparing the two.

1094   There have been major advances in the diagnosis and management of rheumatoid arthritis in the last decade, but a great deal remains to be learnt – not least what causes the condition, something skipped over by the authors of this seminar. They claim that we’re on the verge of curing RA in the way that tuberculosis was cured in the 1950s, but I don’t think the analogy holds. It’s more like the treatment of syphilis with mercury and arsenicals before Treponema pallidum and penicillin were discovered. At least we now have a slightly better diagnostic test – antibodies to citrullinated peptides (ACPA) – and a range of biological agents which will only come into their own once their patents expire and they cost less than the current £10K per annum.

BMJ  25 Sep 2010  Vol 341

As I neared the end of my time in mainstream general practice, I followed the general trend of my colleagues and local psychiatrists in adding in a bit of olanzapine or some other atypical antipsychotic when failing to help people with agitated depression. In doing so, we double the risk of venous thromboembolism over the first few weeks of treatment, according to this case-control study based on QResearch database in UK primary care. That might be acceptable if these drugs actually worked, but in my experience they merely add weight gain to the miseries of depressed people locked in social hopelessness. And using “mild” antipsychotics actually carries the highest risk for VTE.

The BMJ’s new Spotlight feature reminds me of the days when I tried to improve the palliative care of people with non-cancer diagnoses, specifically people with heart failure. In the course of putting together the first book on palliative care for HF, I came across a number of the authors of this section. It reminds me of how well they write, but also shows how little progress seems to have been made in the last few years. For example, I pointed out then that you could probably predict the death of a patient with heart failure to within weeks or days by serial measurements of BNP, but nobody actually does this. Everyone instead complains that futile treatment continues to the very last days and hours. In the book I also avoided any discussion of assisted dying, though this is what many patients with HF specifically ask for; it was too sensitive a topic to raise amongst palliative care doctors, whose views about this contradict those of most of the people they treat. “Raising public knowledge of issues surrounding death, dying, and bereavement risks raising expectations we cannot yet meet or sending an unrealistic message that death can always be managed well. But such activity is a vital part of generating a sense of wider responsibility for the dying and promoting social justice for all those living towards the end of their life.” In other words, we need to give dying people some real choice about the place and time of their death. A doctors’ group within Dignity in Dying will be launching an initiative about this in a couple of weeks.

Ann Int Med  21 Sep 2010  Vol 153
   Severe oral mucositis is a common effect of cancer chemotherapy which can sometimes lead to cessation of treatment. The drug firm Amgen has developed a recombinant human keratinocyte growth factor which rejoices in the name of palifermin and reduces mucositis when given as a single dose before each cycle of chemotherapy. It thickens the oral mucosa of everyone who gets it. Further trials will determine how useful it is in allowing potentially curative continuation of chemotherapy.

378    Clinical pharmacologists long ago suggested a potential interaction between clopidogrel and proton pump inhibitors, through inhibition of CYP-mediated metabolism. Then some studies showed that this seemed to be happening. But this Danish study suggests something quite other, and rather alarming: PPIs themselves increase cardiovascular risk following myocardial infarction. Very simply: following MI in Denmark, 43% of patients received clopidogrel and the rest presumably just received aspirin. Take the risk of further cardiovascular events in this group as 1. Now compare the group who were taking PPIs as well. Their risk of a CV event was 1.29, whether or not they were getting clopidogrel. So no evidence of an interaction here, just a potential 29% harm from taking PPIs.

Fungus of the Week: Boletus edulis

In the woods where I forage every year, this choice edible fungus appears every three or four years, and this is one of them. If it reaches a farmer’s market in England, it commands prices like £55 per kilo. In the market at Cracow, however, where I bought a few yesterday morning, it sells at about £8 per kilo, or half that for poorer specimens.

The Italians are particularly fond of their funghi porcini and buy in lots from Eastern Europe, recycling them at exorbitant prices as “Italian” dried ceps. These are good for flavouring things like soups, stews and risotti, but there’s no substitute for the real thing, young and fresh. Rub or cut off any soil, slice your little beauty very finely and add slivers of best parmesan and a generous drizzle of olive oil. A little salt and pepper.

Somewhat older, flabbier specimens benefit from treatment à la bordelaise. Part the cap from the stem (stipe) and put it, pores down, into a pan well covered with sizzling olive oil. Chop the stem into the oil around it. Now turn the cap over, and chop some garlic over the pores. The pores will have gone a bit slimy, but do not fear. Add salt and pepper and then spoon the pieces of stem on top of the cap and place on a plate with some of the hot oil poured over. Add chopped parsley and serve.

Now if you had enough ceps, you could compile a feast of four or perhaps five courses celebrating them, including combinations with oysters and quails. Perhaps even with a chocolate and nut tart…