Richard Lehman’s journal review – 18 April 2011

Richard LehmanJAMA  13 Apr 2011  Vol 305
1441   The old JAMAs were comfortable: they looked good and I looked forward to getting into them – there was a nice feeling, like fluffy cotton against the skin. But sadly the old garment is getting threadbare: I report on this week’s issue more out of a sense of duty than because it’s comfortable bedwear for the generalist. Here is a perfectly decent and hardworking study of viral shedding in symptomatic and asymptomatic genital herpes infection (HSV-2). It tells us that in symptomatic infections, where there are visible, open lesions, more virus is shed than when the lesions are occult. Fair enough: but it’s like opening Meteorology and being told that rainfall tends to be higher when it is raining. I read elsewhere that JAMA is getting a new editor, and his mug shot makes him look young and fierce. Perhaps that is what this dear old journal really needs.
1460   The next study is an Ouroboros concerning Adalimumab. Adalimumab, you will recall, is not the name of a once-celebrated Assyrian horse-trainer but of a fully human monoclonal antibody against tumour necrosis factor-α. Being “fully human”, it is supposed to float unnoticed among all the other human antibodies in the bloodstream, attacking TNF-α at will and thus acting as a magic bullet against the inflammatory process in Crohn’s disease or rheumatoid arthritis. Ah, but here comes the ouroboros. This name is given to the ancient symbol of a snake eating its own tail. The undeceived fully human immune system begins to recognise adalimumab as “non-self” and makes its own antibodies to adalimumab. These neutralise the effect of the artificial antibody and reduce the clinical response in RA. And how do we detect these anti-adalimumab antibodies? Why, by creating labelled anti-anti-adalimumab antibodies. Quite an ouroboros.

1484   Some of the JAMA Commentary pieces can be excellent, so I came with high hopes to this one about Epigenetics – the Link between Infectious Diseases and Cancer. But it comes from Princeton, a university without a medical school, which should have raised suspicion from the start. This is a spectacularly important topic, but it’s rendered quite opaque by this complex account of some of the known basic mechanisms. I suspect we may have to wait another ten years for some clarity about their significance in human disease.

NEJM  14 Apr 2011  Vol 364
1385    The smart, ultra-conservative garb of the New England Journal covers some pretty lively writing these days, especially in the opening Perspective pieces. Vitamin D and Prevention of Cancer – Ready for Prime Time? is a good example. About four years ago, the journal published an enthusiastic review about vitamin D which had me taking a regular dose myself: it was talked up as the “what’s-not-to-like” vitamin that everybody in the temperate world is short of. But that depends on how you define “short of” and what you are using it for. For bony health, a serum level of 50 nmol/L is plenty. The magic cancer-reducing properties of vitamin D at higher doses are purely an extrapolation from observational studies, plus three fairly short randomised trials with different primary end-points and very mixed results. It is quite possible that high vitamin D levels may increase risk for pancreatic and oesophageal cancers.

1395   James Le Fanu’s Rise and Fall of Modern Medicine (1999) contains a gripping chapter on open heart surgery as one of the 12 definitive moments in the rise section. In the good old days, patients with valvular disease were two a penny: blood fountained over surgeons and assistants: leading surgical centres ran out of coffins (only slight poetical licence here). And then a few patients began to survive open mitral valve replacement; then more; and finally, the majority. In le Fanu’s somewhat gloomy perspective, we are now in the Fall: patients no longer have mitral incompetence much, open heart surgery has become routine, and the inventiveness of medical science produces ever smaller dividends at ever greater expense. However, if I had a leaky mitral valve, I might be rather pleased that percutaneous repair is now an option. True, 20% of patients undergoing the procedure end up requiring the open operation, but that’s 80% who don’t. For how it’s done, you’ll have to read the paper and/or watch the animation. It will be interesting to follow the progress of this innovation and how it changes practice: it may even find a place in some people with advanced heart failure and so-called “functional” mitral regurgitation. The editorial makes some sage observations on how to structure shared decision-making about this new option.

1407   The intensive care unit lies at one extreme of the human environment: you are in there because otherwise you would be dead. Everything must be clean, monitored, and designed to prevent the transmission of microbes because this is the ultimate breeding ground for antibiotic resistance. Contrast the caves and huts which our ancestors often shared with domestic animals. Cleanliness was rather late to arrive in human civilisation, and is often over-rated: but not so in the prevention of hospital transmission of MRSA, as this and the subsequent study demonstrate.

1441    Amongst all the microbes which we, and other mammals, and even reptiles evolved alongside, the mycobacteria have a special reputation for indolence and unpredictable malice. Unfortunately it is still impossible to tell a sleeping mycobacterium from one which is about to wake up, reproduce, and damage or kill its host. However, it is possible to determine which hosts it prefers to damage: this account of latent tuberculosis in the United States gives you a good table and guide to the appropriate tests, not only for the USA but also for Canada and the UK. 

Lancet  16 Apr 2011  Vol 377
1319    This week’s Lancet is devoted to stillbirth, which makes the heart sink for two reasons – the nature of the subject itself, and the way The Lancet is bound to treat it. In an opening editorial Richard Horton tells us that stillbirths are distressing and important.; moreover he commissions a whole paper to explain why stillbirths are distressing and important. As stillbirths are important (and distressing) it is important to count them properly, and distressing to see that this is not being done consistently across the globe. Well, maybe: a huge global preponderance of stillbirths occur because women do not have access to adequate pre-partum and intrapartum care. Comparative figures are only useful inasmuch as they highlight the improvements that need to be made. But at least The Lancet considers global counting and comparison as one of its chief duties, and does thoroughly and takes it seriously.

1331    Which brings us closer to home: why do stillbirth rates vary in high income countries? What are the avoidable factors? Although this systematic review is very comprehensive, I am not quite clear about the answers. Smoking – avoidable; BMI above 25 – yes, but not all that likely to change; maternal age over 35 – ditto; pre-existing diabetes and hypertension – treatable but little evidence that control affects stillbirth. Primiparity, and previous stillbirth, gestational diabetes and hypertension – all important factors, but in the end the only answer is to get the baby delivered at the least sign of trouble.

1367   Maybe you thought glaucoma was something that older people got and was prevented by regular measurement of intra-ocular pressure and the use of eye drops with strange names; o sinner, turn again. Read Harry Quigley’s Seminar, and know that glaucoma may be lurking deep inside your orbits, waiting to reward your ignorance with permanent loss of sight. Take heed, complacent one! “Open-angle glaucoma often occurs at an intraocular pressure that falls in the typical range. In Asia, most patients with open-angle glaucoma have similar pressure levels as those in healthy individuals… Glaucoma is undiagnosed in nine of ten affected people worldwide and is undiagnosed in 50% of those in developed countries; thus, improved case detection is needed.” Fortunately most optometrists these days seem to know how to examine the fundus and perform proper visual field testing: which is just as well, as I am, maybe, a little deskilled. 

BMJ   16 Apr 2011  Vol 342
856   When my father was dying of heart failure in Sheffield 20 years ago, my main concern was to keep him out of hospital so he could have a reasonably good death at home. I just about succeeded, and subsequent attempts to think through the problems of palliative care for heart failure much later on brought me into correspondence with Merryn Gott, who was then in Sheffield and is now in Auckland, NZ. Here she leads a qualitative study on the barriers to transition between acute hospital care and palliative care in England. Despite the growth of a large literature and better liaison between palliative care and the acute sector, the problems remain much the same, above all an unwillingness to discuss prognosis with the patient and the family. And as teams grow larger and ever more transitory, I can’t see this getting better.

857   Traditionally, doctors look down on qualitative research as too touchy-feely and removed from the hard science that we are all so good at. Similarly, palliative care is all very well, but it’s chemotherapy that kills cancer cells and improves survival. Except that very often it isn’t, and studies of lung cancer have shown that stopping chemo and introducing palliative care can actually improve longevity as well as quality of life. And qualitative research can provide unique insights into how health professionals view choices about chemo at the end of life and how their own feelings can govern their choice of language to patients in what should ideally be a non-directive process of shared decision-making. The result is that chemo is often given or continued when neither the patient nor the doctor really believes it is worth it. When your own turn comes, or that of a loved one, you might wish doctors paid a bit more attention to the lessons of the qualitative palliative care literature.

Arch Intern Med  11 Apr 2011  Vol 171
636   Talking with Paul Glasziou a few days ago – always a treat – we strayed into the difficult territory of informed consent to screening. He suggested that there are three separate situations with population screening, and in none of them was personal decision-making the best option (above and beyond the absolute right of consent to be screened). The first is where the data demonstrate incontestable benefit from screening (e.g. phenylketonuria in the newborn). This can become public policy without detailed explanation to parents or patients. The third is where there is incontestable lack of benefit from screening (e.g. PSA for prostate cancer): this kind of screening should not be offered as public policy. It is only in the middle category, where the evidence is debatable, that any attempt at explanation should be made, and then not to individuals but to a citizen’s jury sitting for two days. Only by a process of lengthy discussion can the issues be understood sufficiently to arrive at informed consent. Apparently this process has been followed in New Zealand; but I digress. Personally I don’t believe that the UK programme of colorectal cancer screening using faecal occult blood testing is worth the candle, whereas regular sigmoidoscopy is, and colonoscopy may be nearly as good but is less feasible and more dangerous. I would favour the use of electronic prompts for the last two but not the first. This Harvard study included all three modalities of screening, and got better uptake using the prompts, but not for very long.

686   The higher the dose of opioid you prescribe for pain, the higher the risk of unintentional overdose. Those of you with a memory span of a week will be saying, “hang on, he told us this last week” (JAMA 305:1315). And so I did – but this is not a case of dual publication or a lapse of memory on my part (perish the thought): it is an entirely different study from the US-based one in JAMA, which included cancer patients. This one is from Canada and excludes cancer patients, but the message is the same. Opioids are dangerous drugs: perhaps because we are anxious to reassure patients, we hide from them (or ourselves) just how dangerous they can be.

Plant of the Week: Skimmia japonica “Rubella

I have no idea why this excellent evergreen shrub came to bear the name of a once-common childhood disease: I suppose it is because its buds are pink before they open into white flower-heads, with the loveliest scent. This is an amazingly tough and versatile plant which will grow in dense shade, slowly but inexorably. Any cutting, or even leaf, that hits the ground will take root, but you will have to wait a long time to get a proper plant. It is ideal for occupying difficult spaces. It will grow on limy clay, but do give it some iron if it gets chlorotic. And do not be fooled by its female name: it is male, and if you want berries, you must buy another form, such as “Reevesiana.”