NEJM 22 October 2014 Vol 371
1577 The whole point about tuberculosis is that it is slow. The discoverer of its causative organism, Robert Koch, called it the fungus-germ, or Mycobacterium. It takes 20 times longer to divide than most other bacteria. It is only after years of division that it can do terrible things. The old Welsh chest physicians I once worked for called this “galloping” TB, and recalled how it had carried off some friends of their youth. But even this word, when pronounced as “gahl-lopin” in a soft south Welsh accent, had a mournful slowness about it. Three trials in this week’s NEJM show that it does not pay to take shortcuts with this slouchy beast. Several new fluoroquinolone drugs kill off Mycobacterium tuberculosis quite rapidly in the laboratory and in animal models and were thought to offer the promise of a faster cure than standard rifampicin based regimens. In the first trial, moxifloxacin was tested in a randomised trial cunningly designed by academics based in the tiny windswept town of St Andrews in the Scottish kingdom of Fife. They spread their net across four continents, but they have shown that in uncomplicated, smear positive pulmonary TB, four months of a moxifloxacin based regimen is not dependably curative.
1588 So now in the Floxacin Twins show, it’s time for Moxy to retire to the wings and for Gatty to take the stage. She is billed to perform twice. Her first act is set in Africa. Patients with newly diagnosed TB were randomised to a standard six month regimen, based on rifampicin or a four month regimen based on gatifloxacin. It’s not a showstopper. In the curious language of summarese, “Noninferiority of the four month regimen to the standard regimen with respect to the primary efficacy end point was not shown.”
1599 The second trial involving moxifloxacin was a bit different (i.e. significantly not nondissimilar), in that it mixed in another agent I had never heard of, rifapentene. Anyway, let’s get it out of the way. “CONCLUSIONS: The six month regimen that included weekly administration of high dose rifapentine and moxifloxacin was as effective as the control regimen. The four month regimen was not noninferior to the control regimen.” If you want a perfect antidote to all this not-non-language, hunt out that classic of the medical literature, The White Death: A History of Tuberculosis, by Thomas Dormandy (1999). Although English was Dormandy’s fourth language, and he was writing in his eighth decade, his prose sparkles and the book is full of astonishing facts and insights about all aspects of Western civilization, both artistic and scientific.
JAMA 21 October 2014 Vol
Parent JAMA holds no British interest this week as it is taken up with payment issues in the US health system. In the UK, we can forget about these because the CEO of NHS England, Simon Stevens, has just announced that a system free at the point of delivery and paid for by taxation is what the British people want. But he says there is an £8 billion shortfall. According to some estimates, this is less than the transaction costs generated by the existence of an internal market. And it’s this same market that prevents the integration of primary and secondary care. What could the answer be? And will the Labour party see this as their chance to put distance between themselves and the Tories and Lib Dems on health? If only they had a leader.
JAMA Intern Med October 2014
OL The battle of the paradigms in the treatment of addiction is between the abstinence preachers and the harm reducers. All my professional life I have been a convinced harm reducer, and my willingness to give people extra doses when they came up with suitable excuses was regarded as a severe moral failure by many colleagues. It was said that addicts would flock to me, but they never did. I was just trying to spare these mostly poor and hopeless people the cost of having to pay for something on the street, often by stealing. Some of them even got “clean,” but I have no idea whether my figures were any different from other people’s. I never deluded myself that I could fundamentally alter the comings and goings of their mostly chaotic lives, especially in the face of social contempt and irrational drug legislation. I can say all this out loud now because I no longer prescribe for addiction and will soon not be prescribing for anything. Don’t come to me for buprenorphine. But if you prescribe this for opioid dependence, please ensure you prescribe enough. And bear in mind that abstinence is hard and attempting it may be counterproductive. In the trial reported here, more participants in the attempted tapering off group went out to buy illicit opioids and most of them dropped out of the study, even though it only lasted 14 weeks. By contrast, most of the maintenance dose group stayed in. Consider carefully whether what you are trying to do will help these damaged fellow humans.
OL While we are on the moral low ground, let’s spare a thought for gamblers, sex addicts, and spendthrifts. Are they just defective people with no self-control? Very possibly, and the defect may lie in D3 dopaminergic overdrive. We know this from the widespread use of drugs which can cause such overdrive—aripiprazole for psychosis, and pramipexole and ropinirole for Parkinsonism, restless leg syndrome, and hyperprolactinaemia. The study here attempts to quantify the problem using an FDA database and several others, but for problems such as these, only active surveillance will suffice. As an accompanying commentary points out, not many patients are going to come in and report that since they started the tablets, they have been going to bed with everybody they’ve met and have run up massive bills on all their credit cards. I bet this is a commoner problem than people realise. I’ll stake £50K on it. And I really fancy you.
Ann Intern Med 21 October 2014 Vol 161
562 Do Clinicians Know Which of Their Patients Have Central Venous Catheters?: A Multicenter Observational Study. What a shame the authors submitted this to the Annals—it would have been so good for the Christmas BMJ. A forlorn hope, I guess, when you can’t even mention the word “Christmas” in the United States, let alone allow the mask of seriousness to drop for one second in an American medical journal. In three large US academic hospitals, clinicians are oblivious of the presence of central lines in about 20% of cases. “Further study of mechanisms that ensure that clinicians are aware of these devices so that they may assess their necessity seems warranted.” I suggest a trial of special hair ribbons that twinkle and tinkle at the approach of doctors. This would almost certainly get into the Christmas BMJ. They could also be sold in retail outlets during the Holiday season.
568 Golly. Here is a systematic review that shows human behaviour can be changed by an intensive intervention, or, to be more accurate, by a range of intensive interventions. Their aim was to reduce cardiovascular disease in high risk people. This is a really thorough review of 74 trials, done for the US Preventive Services Task Force. The effect sizes found for intermediate outcomes are small, except for preventing diabetes, and few trials report long term cardiovascular outcomes data. But this may be an area where people can benefit from being motivated through suitable exhortation and support. Do I mean getting fitter? Yes, that and reporting proper endpoints in trials.
579 Because the Americans have let general practice largely die out, they are having to reinvent it from first principles. “A Practical and Evidence Based Approach to Common Symptoms: A Narrative Review by Kurt Kroenke, MD” describes how at least a third of symptoms have no distinguishable cause; history and examination alone can get you far enough in 90% or more of clinical situations. Lots of things get better on their own, but it’s important to address those that don’t: and much more in a similar vein. Some enterprising British GP trainer should go on a preaching tour of the United States.
Lancet 25 October 2014 Vol 384
OL Here’s what a trial should look like. It was well designed and conducted and paid out of public funds, except for carotid stents, which were donated by Sanofi. As a result, we know that carotid endarterectomy and carotid stenting for symptomatic stenosis have very similar long term outcomes. It’s taken a while—the trial started in 2001—but it’s been worth the wait to get a wealth of long term data. Both procedures have possible harms but they are well balanced. On the basis of this trial, patients can have a very clear conversation with health professionals about which treatment to have.
OL Fashions in stroke medicine come and go, although the discipline itself is only about 20 years old. We’ve known for ages that high blood pressure is associated with bad outcome after stroke. So is it best to lower blood pressure as much as possible after an ischaemic stroke? Or to desist, on the basis that the brain needs all the perfusion pressure it can get while it is recovering? The ENOS trial also began in 2001, and as a result we can say that it really doesn’t matter what you do, or whether you use glyceryl trinitrate patches as well. Outcomes were the same whether pre-stroke blood pressure lowering drugs were stopped or continued, and although the GTN patches were well tolerated and lowered blood pressure, they too made no difference to functional outcome.
The BMJ 25 October 2014 Vol 349
As usual, this week’s The BMJ is a good read in many parts, although I could not get excited about the research articles. Like most retired GPs, I know I could get seriously boring on the subject of the future of general practice, so I tend to avoid the subject for the sake of my listeners, and also to reduce my risk of stroke. But I would like to flag up my approval of the idea of breaking down the barriers between primary and secondary care. With GPs in the lead. Stephen Gillam’s editorial is a little too cautious I think. Maybe too worried about having a stroke.
While I’m meandering through The BMJ, I’ll pause to encourage you to read a typically excellent review of the diagnosis and management of hiatus hernia, which goes quite a bit into the causation too. I must lose some fat, or buy a looser belt.
Finally, I’m impressed that The BMJ has managed to rush onto their website Margaret McCartney’s excellent condemnation of the preposterous £55 bribe to GPs for diagnosing dementia. I can only hope this is a turning point in the whole sticks-and-carrots game between governments and primary care. Everything about it is deeply wrong.
Fungus of the Week: Boletus edulis
Perhaps the most potent reason that this mushroom is so prized among hunters is the welcome it receives when you bring it home. The male hunter gatherer experiences deep atavistic pleasure when his spousal partner, nay, the whole tribal group, actually appreciates the stuff he brings back in his bag. On most occasions, when I empty my bag of wild fungi onto newspapers on the kitchen table, I am told to make sure it doesn’t go anywhere near things that people are actually going to eat. In vain do I protest that everything I bring home is not only edible, but delicious. The handsome brown capped cep not only escapes such censure, but elicits something approaching congratulation.
And so it should. Most people who eat “wild” mushrooms in restaurants have no idea of how long and random a hunt is required to find the best sorts. The weather has to have been right, and the fungi have to be at the right stage of maturation—a day or two can be critical—and you have to know where to look. Even so, you can spend two hours finding nothing. This boletus grows mainly in symbiosis with the roots of oak and beech, but I have been hunting it for 30 years among these trees and never found it fruiting in exactly the same place twice.
Today I found four with my elder son. I let him have the two bigger ones. They were all fresh and free of larvae. They were not soggy from rain. In a word, they are perfect. In an hour or so, we will slice them quite thinly and eat them raw, lightly seasoned with salt and pepper, and sprinkled with olive oil and shavings of parmesan. Unless you have done this yourself on the day of picking, you can never hope to understand what the fuss is about ceps.