Richard Lehman’s journal review – 29 November 2010

Richard LehmanJAMA  24 Nov 2010  Vol 304
   It’s a pleasure to start the week with a first class well-conducted study with a clear outcome that will benefit patients. The benefit in this case is the avoidance of futile thoracotomy for non small-cell lung cancer. And the way to avoid it is by using combined trans-oesophageal and endobronchial ultrasonography before proceeding to surgical mediastinoscopy. This way you can detect spread to the mediastinal lymph nodes much more accurately and reduce the number of unnecessary operations (currently about 25%) by about half.

2253  But now I’m afraid it’s back to business as usual – a diabetes trial that is too small, too short, and uses that most discredited of surrogate end-points, HbA1c. It’s no comfort at all that the intervention is non-pharmacological, because such interventions are the ones we need more than any. In this case success was achieved with a combination of aerobic and resistance exercise, as practised by one group out of four in this Louisiana trial, which recruited 262 sedentary subjects of a mean age of 56 with well-controlled type 2 diabetes, mean HbA1c 7.7%. The separate forms of exercise, or no exercise, did not produce a statistically significant drop in HbA1c but hey presto the combination reduced it by 0.34. Of much greater clinical significance, probably, was a drop in waist circumference and body fat: but we shall never know what we are really doing to our type 2 diabetic patients until we have more trials that are powered for hard outcomes.

2270   Among the metabolic diseases, gout interested doctors far more than diabetes for over 2,000 years. Children who got diabetes wasted away and died, which most children did anyway: similarly people aged 55 and over. Gout, however, tormented rich men, who were generally the only clients who mattered, especially in the second century Roman Empire. Galen observed that most of his gouty clients were male and ate and drank too much: they were also quite fond of sex. Women, on the other hand, rarely ever got gout until they stopped menstruating: and being Roman matrons rather than courtesans, they didn’t get much sex. The cure for male gout, said Galen, must likewise lie in regular bleeding and infrequent intercourse. This, together with abstention from the pleasures of the table, was what Galen recommended to his rich male clients; and perhaps they paid him with vats of garum and Falernian wine, as they wouldn’t be needing it any more. How unlike the home life of the modern American nurse! According to the Nurses’ Health Study, following 29,000 women for 22 years, their drinks are more likely to contain fructose than alcohol; and in proportion that they drink these sticky beverages, they get gout. Hand over that Pepsi, a modern Galen would insist.

2279   I always emit a short low groan when I see the letter Q in any acronym. It stands for Quality and it often means the opposite, as this excellent “Users’ Guide” to the Quality Improvement literature demonstrates. Consider the gout section in the newly discovered manuscript of the Roman Imperial Quality and Outcomes Framework (RIQOF), circa 180 AD. “An expert panel, chaired by the distinguished podagrologist, Claudius Galen MD, recommends the following quality measures and appropriate physician payments throughout the Empire, from Britannia to Syria and Africa:

  • maintaining a record of all gouty clients – 3 slaves
  • maintaining a recall system for bleeding – 4 rolls of dyed wool
  • proof of bleeding – 2 ounces of blood at least annually – one toga
  •                             – 4 ounces of blood at least annually – two togas
                                – 8 oz up to every 4 months – one villa with hypocaust

  • lifestyle advice given (by doctor or practice slavegirl), including sexual abstinence – one horse
  • depression screening questionnaire completed – one ass.

These requirements will be reviewed every century by a conclave of imperial physicians to be held at Delphi.”
It is a sobering thought that but for the decline and fall of the Roman empire, we might have had such an effective system of quality improvement in place for 18 centuries.

NEJM  25 Nov 2010  Vol 363
   Quality improvement is actually, of course, a good thing in itself, and we need better ways of doing it and better ways of studying it. High quality outcomes research, carefully reflected on, is one essential input, and there are two good examples in this week’s New England Journal. A general survey of North Carolina hospitals produces a rather gloomy view of overall improvements in patient safety, but this study of mortality from allogeneic haematopoietic-cell transplantation is very much cheerier. The period 2003-7 showed an overall mortality fall of over 40% compared with a decade earlier, driven by significant decreases in the risk of severe GVHD; disease caused by viral, bacterial, and fungal infections; and damage to the liver, kidneys, and lungs. Further details are strictly for the haematologists: but it seems they have much to congratulate themselves about.

2102   It is a truism, daily confirmed, that people who go on low-calorie diets lose weight, and then put it back on again as soon as they slacken their efforts. This important European study may have found a solution to that: of 773 participants who had managed to lose 8% of their initial weight, all that was needed to prevent regain was a modest increase in protein content and a modest reduction in glycaemic index in an otherwise unconstrained diet. There does seem to be a convergence of hard evidence now in the otherwise notoriously evidence-free area of dietary advice. Let me add my own anecdote: my wife has adopted the Atkins high-protein, ultra-low glycaemic index diet. I haven’t, though my need is greater: I eat all the nice protein with her, and throw in some bread and potatoes. She is losing weight and so am I, because the protein is more interesting, and neither of us is eating anything sugary. Easy-peasy.

2114   The evidence we have about the safety of drugs in pregnancy is almost all retrospective and observational, and so never quite definitive. But I think pregnant mums with heartburn can now be prescribed omeprazole with very little hesitation, since this comprehensive Danish survey identified over 5,000 women who received omeprazole in the first trimester and found no increase in major birth defects when they checked them with EUROCAT, the Europe-wide register of congenital abnormalities.

  “In a study of 10 North Carolina hospitals, we found that harms remain common, with little evidence of widespread improvement.” Not what you want to hear, but backed up by careful analytic methodology and illustrated by six graphs, showing the results of internal and external reviewers. They generally wiggle downwards and then go up again between 2006-7. “Achieving transformational improvements in the safety of health care will require further study of which patient-safety efforts are truly effective across settings and a refocusing of resources,
regulation, and improvement initiatives to successfully implement proven interventions.” I have my own ideas about this, based on the systematic encouragement of kindness, professionalism and adaptivity, but I don’t think I will live to see them validated in this way.

2135   Two ophthalmologists take you through everything you need to know about retinal vein occlusion, very clearly and authoritatively. Odd that arterial risk factors such as hypertension play a bigger role than venous thrombotic risk factors such as oestrogen or Leiden V mutations. A major complication of branch retinal vein occlusion is neovascularisation, so as well as laser treatment, intra-ocular injections of VEGF inhibitors (ranibizumab, bevacizumab) have been shown to improve visual outcomes in randomised trials.

Lancet  27 Nov 2010  Vol 376
   When the H1N1 influenza epidemic broke on the UK in the summer of 2009, the Chief Medical Officer was Liam Donaldson, co-author of this survey of paediatric mortality related to H1N1 infection. He names this as a “Conflict of Interest” at the end of the paper, and so it is, because this paper is notable not so much for what it contains, but for what it leaves out. I have every sympathy for his position in the eye of this storm, and I can understand why he over-reacted and set up a system for mass access to antiviral drugs; but the really radical and dangerous step he also took was to hand over the triage of all febrile illness to unqualified people going through a checklist at the end of a telephone line. Very few GPs will remember a child dying of H1N1 flu in this pandemic, because the mortality rate was 6 per million; but most GPs will remember cases of pneumonia and other sepsis, sometimes including meningitis, which presented late because the lay telephone triage system. There’s another study that needs doing here, and best by people without a conflict of interest.

BMJ  27 Nov 2010  Vol 341
   One reason that long-serving GPs like me are reluctant to intrude into serious emergency situations is that we might be called upon to do something that only real doctors can do, like intubate. Meaning the trachea rather than the oesophagus in the first place, and not in a main bronchus either. This neat Viennese study looked at the best way to detect and avoid endobronchial intubation. Simple measurement is pretty reliable: 20-21cm in women, 22-23cm in men. If you’re not in a noisy helicopter or in freezing darkness, it’s also a good idea to listen for the breath sounds and see if both sides of the chest are moving.

1144   Thrombolysis for acute occlusive stroke has been shown to be marginally beneficial in several RCTs, but the number of people over 80 in these trials is minuscule, whereas in real life, 30% of strokes occur in this age group. There is a presumption that the hazards of thrombolysis will be greater and the outcome difference less. This European registry study indicates that neither is true: thrombolysis remains beneficial for stroke beyond the age of 80. But please let me die of mine.

   I don’t really know whether I count as having entered retirement, but at least I can get up at a time of my own choosing most days, which is about an hour later than previously. I also get a pension, so I have to work less, and as a result I have indeed experienced a marked reduction in mental and physical fatigue, just as it says in this paper from France (the GAZEL study). But retirement does not reduce either the incidence or progression of chronic disease. I have that to look forward to.

1146   As an enthusiastic regular drinker of wine, I am delighted to note the PRIME study which confirms that by doing so I halve my chance of myocardial infarction. I suppose I also increase my chance of pancreatitis, cancers of the GI tract and stroke. Perhaps liver disease too, though the literature is surprisingly obscure at levels of intake below about 100u/week. The thing not to do is binge drink, which is a common pattern in Northern Ireland, and probably increases your baseline risk of MI. I think the further north you travel, the more dysfunctional alcohol use becomes, as warm oblivion becomes ever more desirable. As if to illustrate this point, a review of frostbite finds that nearly half of it is associated with alcohol use. I bet that means vodka or whisky in most cases, and wine alone hardly ever.

Arch Intern Med  22 Nov 2010  Vol 170
   The great musician Adolf Busch is reported to have said, “I don’t know much, but I do know that Mozart is a good composer.” (If you want to know everything about Busch, treat yourself to the wonderful, zany two-volume biography by Tully Potter that has just appeared, a snip at £75; but if strapped for cash, buy the recordings instead.) Similarly, I could say that I don’t know much about type 2 diabetes, but I do know that metformin is a good drug. Here’s an analysis of the REACH study which looked at outcomes in nearly 20,000 patients with T2DM and established atherothrombosis followed up for two years. Those taking metformin showed a mortality reduction of about a third, which applied at least equally to those with alleged contraindications to the drug, such as heart failure or moderate renal impairment. In fact there might be a case for redefining the type 2 diabetes threshold as the level of blood sugar at which metformin conveys a risk reduction for major vascular disease. We need a massive prospective study: please recruit me to the arm that is also randomised to drink at least 3 glasses of wine a day.

1926   In studies of drugs that put people into hospital, warfarin usually comes near the top. This study looks at how combined platelet inhibition with aspirin plus clopidogrel compares in emergency department visits for haemorrhage-related events. The score is 2-1: 2.5 events per 1000 prescriptions of warfarin as compared with 1.2 events for aspirin/clopidogrel.

Confucius for the Week
: Something to Look Forward To

At fifteen my heart was set upon learning; at forty I was no longer perplexed; at fifty I understood Heaven’s Decree; at sixty I was attuned to wisdom; at seventy I could follow my heart’s desires without overstepping the mark.

Kong Fuz, died 479 BCE.