Richard Lehman’s journal review – 19 September 2011

Richard LehmanJAMA  14 Sep 2011  Vol 306
1089   In medicine, always expect the counterintuitive. For some time it has been known that removing more lymph nodes at the time of bowel cancer surgery is associated with better outcomes. This is nicely confirmed in this large cohort study – 86 394 patients, showing a one third reduction in total mortality within tight confidence intervals, for those who had more than 30 nodes removed compared with those who had 1-8 removed. The odd thing is that the extra nodes showed scarcely any additional cancer and their removal contributed nothing significant to staging and therefore to clinical management. It seems that the removal of these seemingly uninvolved lymph nodes is of major therapeutic benefit in its own right.

1104   Both of the high pressure heart valves are tricuspic, but the one on the left is called the aortic valve and in 1.3% of the population it is bicuspic. If universal echo screening at birth ever gets adopted, we will become aware of many more of these bicuspic aortic valves, and we will have to counsel a lot more parents and patients about the significance of this, the commonest congenital heart defect. Here are the data to guide us from the Olmsted County cohort study, which collected over 40,000 echocardiograms from 1980 to 1999, and identified 416 people with definite BAV. For some reason, these individuals are called “patients” and those in prison are excluded as “non-legitimate.” So what are you to say to the parent of a healthy baby who has been found incidentally to have two instead of three flaps on her aortic valve, and has not yet been locked up in an American jail? The authors of the paper don’t make this very easy. You could say that this puts the wee bairn at more than 8 times the population risk of aortic dissection, and so cause everyone a lifetime of anxiety. Or you could say that the risk of the “abnormality” causing a problem is quite small at 3.1 cases per 10 000 person-years. Unless I have got my sums wrong, this amounts to a 2.5% risk in a lifetime of 80 years.

1113   Studies of general prognostic markers drive me mad. Why do journals give space to these things, generated purely by the availability of stored sera and some new candidate chemical? Serum cathepsin S is the latest and it proves weakly predictive of death in older adults – very weakly, if you look at the tables and figures. You can’t tell this from the abstract which gives the mean OR increment per unit – and whoever knows what units cathepsin S is measured in? Now, if the Revd. Thomas Bayes, FRS (1701-1761) had given a sermon to his Presbyterian flock at Mt Sion chapel in Tunbridge Wells on the text “O Lord let me know mine end, that I may apply my heart to wisdom,” he would also have pointed out that the only value of a new prognostic marker is what it adds in predictive power to those we already have. And for those unwise enough to want to know when they are going to die, we already have telomere length, BNP, cystatin C and co-peptin. Let us apply our hearts to wisdom, and enjoy ourselves while we can.

NEJM  15 Sep 2011  Vol 365
993   When is aggression good? When it is American medical aggression, of course. Here “aggressive medical therapy” is compared with the Wingspan stent device in patients who have suffered stroke or TIA due to atherosclerosis of a major intracranial artery. The trial was stopped early when it became clear that the stent device was causing too many extra strokes in its own right. So what was this “aggressive medical therapy” that proved superior? Blood pressure lowering, aspirin and statins. Now if that counts as aggressive, we should all change our name to Dr. Genghis Khan.

1025   The NEJM has given the job of reviewing breast cancer screening to Ellen Warner, who baldly states that “screening mammography for women 50 to 69 years of age is universally recommended.” I can hear the sound of loud barking from across the Atlantic at the Nordic Cochrane Centre, as the Great Dane, Peter Gøtzsche, prepares a fulminating response. Moreover, it seems that Dr Warner holds a candle for mammography screening before the age of 50; and there is astonishingly little mention of the harms of screening and overdiagnosis. The virtue of mammography, it seems, is still a truth that Americans hold to be self evident. Be prepared for some interesting letters in the NEJM of some weeks hence.

Lancet  17 Sep 2011  Vol 378
1071   Here is a straightforward publicly funded randomised trial, which demonstrates that in patients with stenosed saphenous vein coronary grafts, drug-eluting stents are better than bare metal stents. Our thanks go to the ISAR investigators and the Deutsches Herzzentrum for this useful increment in medical knowledge. Even those doyens of Oxford cardiology, David Taggart and Adrian Banning, cannot find much else to say in their editorial, Are we Wiser after ISAR? – except to make their usual point that if you want to avoid graft stenosis, you use the internal mammary artery, not the saphenous vein.

1089  extremis malis extrema remedia is the Latin tag that gave rise to the English proverb “Desperate diseases call for desperate remedies.” There are many variations, from the first known English translation “A stronge disease requyreth a stronge medicine” (1539) to modern adaptations such as “drastic times call for drastic measures.” Does anyone know the Danish version? I ask because the paper we are considering here is a case series report of early plasma exchange used to treat haemolytic-uraemic syndrome in adults from southern Denmark. As the German plague of Shiga-toxin producing E coli spread northwards across the peninsula of Schleswig-Holstein, the Danes decided to get active at the first sign of trouble. And it paid off: all 5 patients got better within a week, with no sequelae. The authors suggest a randomised controlled trial; but if I get this disease, swap my plasma, please.

BMJ  17 Sep 2011  Vol 343
People with chronic sciatica are generally willing to try anything, and many pain clinics offer caudal steroid injections as a “worth a try” treatment option. This Norwegian multi-centre randomised trial shows that saline injections work just as well. The accompanying editorial winces like someone with radicular pain getting out of a chair: “epidural steroid injections may be an effective adjunct when used judiciously,” it pleads. Well yes, but why not use epidural saline instead?

I’m slightly baffled by the appearance of the next paper in the BMJ. It’s a Canadian study pointing out the danger of hyperkalaemia if you co-prescribe co-trimoxazole and spironolactone, particularly in elderly patients. Now the BMJ may be widely read in Canada and perhaps in other parts of the world where co-trimoxazole is prescribed routinely to elderly patients; but in the UK we hardly ever prescribe it except for the treatment or prophylaxis of Pneumocystis infection. So I’d have thought this was a paper for CMAJ – itself a journal all doctors should read.

When I mentioned Peter Gøtzsche earlier, I wasn’t aware that the Great Dane would make two appearances in this week’s BMJ. In this one, he joins colleagues at the Nordic Cochrane Centre to look at the effect of mammography screening on rates of breast cancer surgery in Norway. Contrary to breast cancer screening propaganda, the introduction of whole population mammography does not decrease the need to perform total mastectomies: quite the opposite. In fact there was a large surge in Norway, consistent with overdiagnosis, followed by a temporal decline which can best be explained by a universal trend towards breast conserving surgery.

The mighty Viking now turns his double-headed battle-axe to meta-analyses which use a multiplicity of data. If you mix all sorts of trial designs, patient populations, starting points, end-points, and disease definitions into your statistical software and run it over lunch, by the afternoon you can have a meta-analysis. The only problem will be that it is codswallop. But that is no reason not to publish it, of course: nobody is likely to check. Ah, but you have reckoned without the Great Dane…

I don’t usually comment on the series Easily Missed, because I helped to set it up and I still review all the contributions long before they are published. But when I first looked at a submission on Panton Valentine leukocidin associated Staphylococcus aureus infection I had the feeling that I hope you will all get from time to time in this series: “I do wish I had known about this earlier.” People unfortunate enough to carry this bug get endless recurrent boils until they are treated with a long course of rifampicin and another suitable antibiotic.

Arch Intern Med  12 Sep 2012  Vol 171
 1433   Principles of conservative prescribing is classed as a review article, but it is really a manifesto. I love it. Put these Rules on your wall:
“(1) think beyond drugs (consider nondrug therapy, treatable underlying causes, and prevention); (2) practice more strategic prescribing (defer nonurgent drug treatment; avoid unwarranted drug switching; be circumspect about unproven drug uses; and start treatment with only 1 new drug at a time); (3) maintain heightened vigilance regarding adverse effects (suspect drug reactions; be aware of withdrawal syndromes; and educate patients to anticipate reactions); (4) exercise caution and skepticism regarding new drugs (seek out unbiased information; wait until drugs have sufficient time on the market; be skeptical about surrogate rather than true clinical outcomes; avoid stretching indications; avoid seduction by elegant molecular pharmacology; beware of selective drug trial reporting); (5) work with patients for a shared agenda (do not automatically accede to drug requests; consider nonadherence before adding drugs to regimen; avoid restarting previously unsuccessful drug treatment; discontinue treatment with unneeded medications; and respect patients’ reservations about drugs); and (6) consider long-term, broader impacts (weigh long-term outcomes, and recognize that improved systems may outweigh marginal benefits of new drugs).”

1454   Cardiac resynchronization therapy can work wonders for some patients with heart failure, reducing hospital admission and death by 40%, and just as importantly, bringing immediate major improvements in quality of life. So how do you qualify for it? This meta-analysis demonstrates that the QRT duration threshold for biventricular pacing to be effective is 150 milliseconds. Less than this and CRT achieves nothing.

1463   Here is another excellent paper by Lisa Schwartz and Steven Woloshin on communicating benefit and harm to patients. Why, you may ask, do their names always appear together? Could they by any chance be more than just work colleagues at Dartmouth? I can answer this question definitively, because I was recently admiring a work of calligraphy hanging on their living room wall and discovered that it was their marriage certificate. Here they perform a “national randomised trial” by using a commercial database of randomly selected US adults to quiz about their understanding (a) of the meaning of Food and Drug Administration approval and (b) how to choose the better of two drugs. They had an excellent response rate and discovered that most Americans overrate the protection afforded to them by the FDA, and have difficulty in understanding drug choices but can be helped by simple explanations.

Plants of the Week: Mallows

When the aged Richard Strauss wrote his great Four Last Songs for soprano and orchestra, all of them meditations on autumn and death, he actually wrote a fifth song called Malven, meaning mallows. And there they are as you look through the window, glowing in the September sunshine, ready to fall victim to the first frosts which cannot be long in coming.

Every garden should have space for a few kinds of mallow. In fact, if you are starting a new garden, be sure to scatter abroad some seeds of white mallow. This is some kind of Althea or Alcea, an aggressive perennial weed which you will forever be pulling up in years to come, but really valuable for its evergreen crimped leaves and its abundance of white flower throughout the season.

Put hollyhock seed in every dry crevice you can find, and keep buying hollyhock plants in village sales until they naturalize themselves with you. Their leaves may turn brown and yellow with rust, and they may die on you repeatedly, but they are not be lived without.

Finally, spare a thought for good old Lavatera “Barnsley,” an untidy shrub which was wildly popular in the mid-1980s but is seen less and less now. It may be short lived and verge on the proletarian; though The Garden once deigned to publish an article about its origins, which lie not in the Yorkshire mining town but in a genteel Gloucestershire garden of the same name. It flowers abundantly for months and has admirable grey leaves. Cut it back annually and you have a friend for nearly the whole season. And if you want a new plant, just stick one of the autumn prunings in the ground.