Richard Lehman’s journal review – 13 February 2012

Richard LehmanJAMA  8 Feb 2012  Vol 307
565   There are signs that JAMA is gradually improving under its new editor, although moving its perspective pieces to the beginning of the journal doesn’t really count as progress. The BMJ has also tinkered with its order of contents, almost as if to hide the fact that they are improving at the same time. And it will certainly take a lot more than swapping chairs around to improve the Lancet. Anyway, here is a Viewpoint piece that is well worth reading if you are interested in screening and shared decision-making with patients. In a clear and well-structured piece, the authors trace the gradual path of disillusionment from the “spotting cancer early is always good” mindset to “there are harms and costs” attitudes of the present. They point out that dumping these issues on to individual clinicians to share with patients is a dubious strategy (not least in health systems where patients are called for screening independently of their normal healthcare provision). “Expert groups may dispute the ‘facts’; the science can be difficult for physicians to communicate and for patients to understand; some patients demure [sic] and want the physician to decide; physicians may lack the time, reimbursement, or motivation to engage in long discussions; and social attitudes and medicolegal pressures may influence the decision.” I particularly like their concluding sentences: “However, society’s first concern should be to confirm that screening is a net good for public health. This requires harms to be considered independently of costs. Until the reality of harms becomes more palpable to clinicians and the public, concerns about the safety of screened populations will continue to be mistaken for frugality.”

567   The next Viewpoint piece also raises an important issue in shared decision-making with patients. When we mention the potential harms of the treatment we propose – as we often must – can this interfere with its effectiveness? Again I would recommend everyone to read this article on Nocebo Effects, Patient-Clinician Communication, and Therapeutic Outcomes. This is not as coherent a piece as the previous one, but it’s good to see this discussion coming out into the open. So much simplistic talk about shared decision making ignores the extraordinary power of clinicians to instill fear and hope in their patients by the words they use and the attitudes they convey. We need to be realistic and indeed scientific about this. We have a duty to be honest, but we also have a professional and ethical duty to understand the effect we have on people in situations where they are vulnerable and we have the power to help them or harm them.

573   This study of a new polyvalent vaccine against serotype B meningococcus may mark a great moment in medical history – final victory over a horrible killer and maimer of mostly young people. The science behind it is certainly awesome: it deploys a fusion protein made up of various newly discovered antigens from different strains of type B meningococci. In this European trial the 4CMenB vaccine proves safe and moderately antigenic in infants, but how the antibody responses relate to protection from invasive disease remains to be seen. We now seem to be within sight of vaccination to neutralize the full range of pathogenic meningococci. Rejoice!

583    Bacteriologists and public health physicians in the UK try to dissuade us from using ciprofloxacin as first-line treatment for uncomplicated cystitis in young women, but in the USA the battle is already half-lost and urinary pathogens are increasingly showing resistance to fluoroquinolone antibiotics. This study examines an alternative – a third-generation cephalosporin called cefpodoxime, which seems to have been around for long enough to be available as a generic (in the UK, used by vets more than doctors). And it works: 100mg of the proxetil ester daily for 3 days works as well for simple UTI as 250mg b.d. of cipro. Possibly worth knowing.

598    Now let us praise another vaccine, this time against rotavirus. We know that this works, and saves many young lives in the developing world and hospital admissions in the USA, where it is now routinely given. What we weren’t quite sure of was whether there would an increase in intussusception following vaccination with the new pentavalent vaccine, such as caused the withdrawal of the previous trivalent vaccine. This cohort study rules that out: there was no increase in intussusception after nearly 800 000 shots given to American babies and toddlers.

NEJM  9 Feb 2012  Vol 366
489    The New England Journal alone has shown no urge to shift its contents around in the 14 years I have been reviewing it. I don’t often mention the opening Perspective pieces, but they are usually interesting and sometimes outstanding. This week you can read about the threat of untreatable gonorrhea, Medicaid battles in the Supreme Court (“All Heat, No Light” – I didn’t read further), and Preparing for Precision Medicine. The piece is co-signed by no less than Lord Darzi, once Czar Omnipotent of our humble health system, since he alone knew how to improve it. Here he sets forth a vision of medicine so perfectly guided by improved diagnostics and genomics that every intervention will achieve complete success with no harms worth speaking of. Together, we can do it! All that it will take is a little time and endless wealth. Replacing the human race would also be a good step, because as Kant said, “Out of the crooked timber of humanity, no straight thing was ever made.”

493    Neonatal screening for hypothyroidism has relegated the word ‘cretin’ to an archaic term of abuse, but an association persists between high levels of thyrotropin (TSH) in pregnancy with impaired cognitive development in children. This largely British trial looked at the effect of screening for high TSH and low free T4 at less than 16 weeks’ gestation, and giving levothyroxine at a starting dose of 150 mcg to half of the mothers with evidence of hypothyroidism and matched placebo to the other half. The (questionable) end-point was IQ in the offspring at the age of 3. There was no difference between the groups.

511    As a coffee-drinker with little interest in alternative therapies, I was under the impression for several years that tai chi was some kind of herbal tea, but apparently it is another of those things where you put your legs apart and wave your arms about, often to the accompaniment of an out-of-tune bamboo flute. Here it was compared with resistance training or stretching exercises for mild-to-moderate Parkinson’s disease. Tai chi was better than either at improving balance and reducing falls. Perhaps in Western cultural settings, it should next be compared with slow disco dancing. Like bamboo flute music, this has also been shown to foster supportive relationships, particularly amongst those trying to escape.

520    Another week, another therapy which prolongs progression-free survival in advanced breast cancer. This time it is everolimus, a derivative of what used to be called rapamycin and is now called sirolimus; and the subgroup of patients in this trial (BOLERO-2) are those with hormone receptor positive cancer who are taking exemestane. The Abstract gives two figures for the primary end-point, indicating a benefit of either 4 months or 6.5 months according to who judged “progression-free” survival. The end-point that really matters, which is overall survival, is not yet “mature,” according to the investigators: so far the absolute difference between groups is less than 2%, with far more adverse effects in the everolimus group. I think the sentences you need to read here are “In summary, we report a phase 3 trial in patients with HR-positive advanced breast cancer showing that the addition of everolimus to endocrine therapy results in an improved clinical outcome.” Note the singular use of “outcome” – these patients have 8 times the rate of stomatitis, 4 times the rate of anaemia and fatigue and ran a risk of pneumonitis which was absent with exemestane alone. The second sentence you need to read is: “Supported by Novartis, including funding for medical editorial assistance with the manuscript.”

Lancet  11 Feb 2012  Vol 379
521    This analysis of birth outcomes following assisted conception looks at 124,128 cycles of IVF that resulted in 33,514 live births, and the results are intriguing: women aged over 40 have the best outcomes. This seems counter-intuitive, and if this is a subject that interests you, you definitely need to get hold of this paper and pore over the figures. Here the bottom line will have to suffice: “Transfer of three or more embryos at any age should be avoided. The decision to transfer one or two embryos should be based on prognostic indicators, such as age.”

547   Many years ago, I put off a 3 a.m. visit to a 3-day old baby who was sleepy and reluctant to feed. Two days later he was dead from fulminating group B streptococcal disease. Hardly a day has gone by since when I have not thought of that mistake which may have cost a baby’s life, and which could and perhaps should have ended my medical career. Most general practitioners in the UK will never encounter this disease, especially in neonates, since antibiotic prophylaxis before birth is now the rule. But those who do have one chance to get it right: so any child with a hint of sepsis in the first three months of life must go straight to the paediatricians. This systematic review tries to determine the incidence of disease due to Streptococcus agalactiae in this age group, from wherever there are data: it is probably around 0.53 per 1,000 live births. The investigators add the rider that “A conjugate vaccine incorporating five serotypes (Ia, Ib, II, III, V) could prevent most global group B streptococcal disease.” I hope so.

BMJ  11 Sep 2012  Vol 344
Antibiotic prescribing in British primary care is the subject of endless debate and investigation, much of which I have found quite unpersuasive. Here is a notable exception: a real-life cluster-randomized trial of an educational intervention which really worked, albeit modestly. It is called STAR, which stands for Stemming the Tide of Antibiotic Resistance. In fact past interventions which have reduced antibiotic prescribing in primary care have shown little effect on antibiotic resistance, and it is not even a secondary end-point in this trial. Introducing the STAR programme in Welsh practices resulted in a 4.2% reduction in antibiotic dispensing. This is discussed in an outstandingly useful editorial by James McCormack and Michael Allan, which should be discussed in every training practice in the UK – and elsewhere. I particularly like the last paragraph, advising that patients should stop their antibiotics as soon as they feel better, and also that they should be told what to do if they don’t.

In my recent experience of general practice (increasingly geriatric on both sides), about half of gout is brought on by diuretics. So it’s no surprise that this trawl through the UK GP Research Database to find associations between blood pressure lowering drugs and gout points the finger most clearly at thiazides. What is slightly less expected is that beta-blockers increase the risk of gout by around a half and ACE inhibitors blockers and angiotensin II blockers increase it by about a quarter. Except for losartan, which decreases gout risk by about 20%, as do calcium channel blockers.

Surgery is like violin-playing: most people can learn how to scratch out a tune; many can learn enough to play in a band; a few learn to sound nice all the time; and a tiny handful become great musicians. Most of the great ones, like Heifetz and Milstein, did a lot of practice every day; others like Kreisler and Busch did not, and you can tell the difference technically, though they were arguably greater musicians. We all also know there are great surgeons, good surgeons, and bad surgeons: also perfectly hopeless non-surgeons, such as ourselves, who are reduced to joking about the rest. And we know perfectly well – by analogy and instinct – that this is not just a matter of case-load and experience. All learning curves do not eventually rise to the same line. This study of French thyroid surgeons does not tackle this problem of individual variation head-on, but instead related rates of damage to the parathyroids and the recurrent laryngeal nerve with number of years in post. The middle years see fewest mistakes. “Optimum individual performance in thyroid surgery cannot be passively achieved or maintained by accumulating experience. Factors contributing to poor performance in very experienced surgeons should be explored further.” Mais non: c’est la vie, mon ami. Laissez tranquilles les pauvres vieillards. Add Gallic shrug and outstretched hands.

The generally high standard and practical focus of the BMJ’s Clinical Review series is well exemplified in this week’s offering on Raynaud’s Phenomenon. It’s great to see a team of young trainee doctors coming up with a product of such quality.

Ann Intern Med  7 Feb 2012  Vol 156
173   Rooting about in the library of the Robert Wood Johnson Scholars at Yale, I was surprised to come across a copy of Epidemiology in Country Practice (1937) by William Pickles. This is the founding text of British academic general practice, though it comes from a world that has now disappeared, where a pair of doctors watched day and night over a whole Yorkshire dale. In John Pemberton’s Will Pickles of Wensleydale (1970), you can read how Pickles and his taciturn Scottish partner kept track of every case of infectious disease in their rural domain, cut off from the outside world but for a railway line to the end of the valley. When influenza struck, Pickles and his wife plotted a great chart of its progress on their kitchen wall: he had his wife drive him to the village school (he hated driving himself) and ordered that classes be suspended immediately. Alas, too late: a teacher had already spread the contagion, which moved inexorably up the dale. Most of the schoolchildren went down with it: I can’t remember how many dalesmen died. Now let’s switch to Canada, some 80 years later. An epidemic of H1N1 flu strikes Alberta, and schools are closed. Infection rates in children drop quickly. Then schools are reopened; and infection rates show a second peak. Somewhere from a moorland grave, I can hear Pickles muttering, “I bloody told you so.”

Violinist of the Week: Fritz Kreisler (1875-1962)

Many doctors are excellent violinists, but there is only one doctor amongst the greatest. As a teenager, Kreisler showed outstanding ability as a violinist and toured Europe and even America, but when he failed to get a place in the Vienna Philharmonic Orchestra, he decided to train as a doctor. He qualified, and sought career advice from one of the faculty. “Well, my boy, you can progress and become a third rate doctor, or go back and carry on being a great violinist,” he was told. Sound advice.

Kreisler was a complete natural, and his mode of playing was unique. He introduced the practice of almost continuous vibrato to his playing, which had a magical tonal and expressive power in his own hands. Unfortunately it had a generally disastrous effect on most twentieth century violinists. Because he never strove to keep up his technique (saying that “practice is just a bad habit”), his playing deteriorated with age. To get a full idea of his musicianship and mastery, listen to his recordings of the Beethoven and Brahms concertos with Blech and the Berlin Philharmonic from the earliest years of electrical recording, together with the Bach G minor Adagio (which served as a fill-up side on the 78s). To understand why nobody could resist his charm, go for the many recordings he made of his own salon pieces and imitation Baroque movements, prior to 1930. Magical, inimitable.