Richard Lehman’s journal review—26 January 2015

richard_lehmanNEJM 22 Jan 2015 Vol 372
331 “Approximately one in four extremely premature infants born at 22 to 28 weeks of gestation does not survive the birth hospitalization; mortality rates decrease with each additional week of completed gestation.” I am not your best guide to this topic, but for those who want to know more, a new study maps trends in the survival of these babies in the USA. The data span from 2000 to 2011 and the 22,248 babies were born in study hospitals within the US National Institute of Child Health and Human Development Neonatal Research Network. I don’t know how typical these hospitals are, but the results differ from the UK Perinatal Mortality Survey in that their deaths from infection have gone down whereas ours have gone up. In both countries, overall mortality has shown a modest fall, but deaths from necrotising enterocolitis have risen.

392 The most viewed piece in the NEJM currently is not a research paper but a letter about vaping and formaldehyde. In case your mental dictionary does not yet contain the word “vaping,” it refers to inhaling heated solutions of nicotine through e-cigarettes. These, as you know, have proved an extremely effective form of nicotine replacement therapy and in the UK at any rate they are used almost exclusively as a form of cigarette substitution. That way people avoid the combustion products of tobacco that do the damage while the nicotine keeps them addicted. This letter raises the uncomfortable possibility that the long-term effects of the chemicals produced within e-cigarettes might be even more harmful than the toxins and tars produced by burning tobacco: “If we assume that inhaling formaldehyde-releasing agents carries the same risk per unit of formaldehyde as the risk associated with inhaling gaseous formaldehyde, then long-term vaping is associated with an incremental lifetime cancer risk of 4.2×10−3. This risk is 5 times as high, or even 15 times as high as the risk associated with long term smoking. In addition, formaldehyde-releasing agents may deposit more efficiently in the respiratory tract than gaseous formaldehyde, and so they could carry a higher slope factor for cancer.” Until this is sorted, bang goes my idea that the arrival of e-cigarettes should lead to the rapid banning of all combustible tobacco products.

OL A new study, which you may have skipped past, shows that “Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed.” I just mention this because I majored on Richard III last week, mentioning his pronounced scoliosis. I hope that those who recently genotyped him will now look at his TBX6 alleles and report their findings in the Journal of Plantagenet Necrology and Genomics. Open access, of course.

JAMA 20 Jan 2015 Vol 313
255 The most puzzling aspect of evolution is why it happens at all. Why did sexual reproduction, which has no immediate advantages, triumph over simple division or budding? Why are the seas full of herring milt, and what use are the peacock feathers, the Provençal love poetry and all the other prodigal outpourings of sexual exuberance? Whenever I watch a video of one little wiggly sperm getting through the cell membrane of the egg-cell, I mourn the fate of all the 70+ million others who have wiggled in vain. Surely there must be a better way? Intracytoplasmic sperm injection is the obvious answer for men who produce sperm that don’t fertilize eggs. In American clinics using in-vitro fertilisation for male subfertility, its use has grown from 76% to 93% during 1996-2012: even in the absence of male subfertility, it is currently used in 67% of IVF procedures. Yet this study shows that in either category it adds nothing to the success of IVF. Nature is just bizarre, and rarely follows common sense, any more than a peacock or a Provençal love poem.

275 Every year brings with it the hope of some new breakthrough in the treatment of multiple sclerosis, but over the last 20 years there have just been a few treatments of small incremental benefit which may reduce relapses in some patients. So just a toot rather than a fanfare for this trial using unmanipulated stem cells taken from the patients’ own peripheral blood, after pretreatment with cyclophosphamide and alemtuzumab (22 patients) or cyclophosphamide and thymoglobulin (129 patients). “Among patients with relapsing-remitting MS, nonmyeloablative hematopoietic stem cell transplantation was associated with improvement in neurological disability and other clinical outcomes. These preliminary findings from this uncontrolled study require confirmation in randomized trials.”

JAMA Intern Med Jan 2015 Vol 175
Many studies have described how health behaviours spread through social networks, and the tightest social network is the person you live with. Here is a study using prospective data from married and cohabiting couples (n= 3722) participating in the English Longitudinal Study of Ageing who were over 50 and who confessed to smoking, being physically inactive, or overweight/obese. For all these domains, they found that people were 2-3 times more likely to change their behaviour if their partner did so.

I have been contemplating writing a blog on salt for the UK Cochrane Collaboration to mark the appearance of the latest Cochrane review of reduced dietary salt for the prevention of cardiovascular disease.

The review concludes that current evidence does not confirm clinically important effects of dietary advice and salt substitution on cardiovascular mortality in normotensive or hypertensive populations. In August, the NEJM published the PURE studies which showed that an estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. This latest paper in JAMA Intern Med is a cohort study of people aged 71-80 and concludes that in older adults, food frequency questionnaire-assessed sodium intake was not associated with 10-year mortality, incident CVD, or incident HF. So the Salt Reduction Emperor turns out to have few clothes on, if any. But rather than tackle the blushful dictator full-on, we should perhaps allow him the favour of a curtain to hide behind whilst he adjusts his underwear. There are some residual uncertainties, of course we should encourage people to prepare fresh food, more potassium is good too, and so on. It will all take an awfully long time, and I imagine that “healthy eating” guides will still repeat rubbish about vitamins, minerals, antioxidants, and reducing salt for as long as I live. “It is difficult to get a man to understand something when his salary depends on not understanding it” as Upton Sinclair once said. The irony is that the word salary comes from the allowance of salt which was an essential of health in the Roman army.

Ann Intern Med 20 Jan 2015 Vol 162
123 I am an old man in a hurry, which is why I am almost entirely sedentary. Not only do I suffer from Muir Gray’s Walking Deficiency Syndrome but I am also at risk of Bottom Based Morbidity. Gone are the days of the itinerant preacher who walked from town to town like John Bunyan in order to stir up a turbulent, seditious, and factious people. You have to do it sitting at a keyboard now, and sitting is perilous, according to this systematic review and meta-analysis. “Prolonged sedentary time was independently associated with deleterious health outcomes regardless of physical activity,” say the investigators, while noting that “there was marked heterogeneity in research designs and the assessment of sedentary time and physical activity.” I wonder how many sitting hours it took for the seven authors to analyze the data in 47 studies and come up with this systematic review.

100 That said, I’m actually for as little turbulence, sedition, and factiousness as possible: I’m only using these words because I so enjoyed Christopher Hill’s book of that name, describing John Bunyan and his Church.

If we are ever to reach the millennium when Christ and His Saints shall reign over a thousand years of person centred medicine, we will all have to join efforts to link everything, from analyzing individual participant data from randomized trials to improving the dynamics of decision making with each individual—and all the way back round again, in a Great Cycle. There have been some fantastic recent developments, especially the Overdiagnosis Group of GPs and the Choosing Wisely initiative within the Academy of Medical Royal Colleges. We’re hoping to learn many lessons from the American and Canadian Choosing Wisely groups. I would say that where wasteful medical practices are concerned, non-adoption is better than de-adoption. A permanently cash strapped NHS has not saved us from many foolish adoptions, but at least tilt tables and other useless investigations for syncope remain relatively rare in the UK. Not so in the USA, according to a survey of hospitalists there: when given simulated cases of syncope, or routine pre-operative evaluation, they reported overuse in 52% to 65% of the preoperative evaluation vignettes and 82% to 85% of the syncope vignettes.

Lancet 24 Jan 2015 Vol 385
371 A Lancet review of vesicoureteric reflux in children may be a story of massive overdiagnosis and overinvestigation, due to a basic misunderstanding of what is normal. Reflux of urine from the bladder into the ureters in children has been viewed for several decades as an important risk factor for febrile urinary tract infections and postinfection scarring. But “micturition urethrocystogram data from 102 urologically normal infants and children from 1967 showed that as many as 65% of the infants displayed reflux in the first six months of life. The rate gradually decreased until at the age of five years none of the investigated children showed vesicoureteric reflux.” But this horrible investigation (MCUG) still gained vogue after that date and led to a big increase in surgical intervention. This article is a real gem: a perfect case report of enthusiastic over-adoption followed by reluctant de-adoption, with evidence ignored or considered inadequate to guide practice. “Open surgery has largely been replaced by the injection of a bulking agent close to the ureteric orifice in the bladder. Although studies have shown no benefits of surgery over prophylactic antibiotics, the injection method has only been compared with prophylaxis in one trial. Antibiotic prophylaxis yielded better results, but further investigation is warranted.” It’s now 48 years since the 1967 imaging study. Our continued ignorance is a dereliction of our responsibility to these children.

OL “Zotarolimus-eluting durable-polymer-coated stent versus a biolimus-eluting biodegradable-polymer-coated stent in unselected patients undergoing percutaneous coronary intervention (SORT OUT VI): a randomised non-inferiority trial.” Hey, I hear you say, you told us about this Lancet paper a few weeks ago. Nope, that was “Ultrathin strut biodegradable polymer sirolimus eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial.” You clearly aren’t paying attention.

OL Resistant hypertension is a slippery thing. You may remember that there was a renal nerve ablation device that showed spectacular reductions in an open label study. Then Medtronic bought it up and ran a proper double blinded randomized trial which showed it was little better than a sham procedure. A device company called ROX medical has now come up with a cunning little device which creates a small anastomosis between the iliac artery and vein. In an open label trial, 20% of participants were rewarded with a swollen leg, so that may be a glitch that needs sorting. Some huge reductions in BP were observed, averaging 26.9/13.5mm Hg SBP/DBP. Long-term results including adverse effects like device migration, high output heart failure etc? We have no idea. We’ll need a sham-controlled RCT of long duration.

BMJ 24 Jan 2015 Vol 350
There has been a lot of publicity for this cohort study of 1126 patients presenting with “suspected acute coronary syndrome” to the Edinburgh Royal Infirmary over a three month period. The use of high sensitivity troponin testing made little difference to the diagnosis rate in men but doubled the number of women diagnosed with myocardial infarction. This is an important and well reported study and I think it calls for an immediate change in practice followed by a series of further studies. I think we are still some way short of knowing how best to diagnose and treat MI in women.

Using high sensitivity troponin testing appropriately can also help in the early rule-out of MI in patients presenting with suggestive symptoms, according to a systematic review and meta-analysis of studies using a different diagnostic product—the Elecsys Troponin T high-sensitive assay.” The results indicate that a single baseline measurement of the Elecsys Troponin T high-sensitive assay could be used to rule out acute myocardial infarction if lower cut-off values such as 3 ng/L or 5 ng/L are used.” But pay attention to all the basic principles of using diagnostic tests—the pre-test probability in each individual, the likelihood ratio, and the importance of timing.

When I first met Rosamund Snow, the new patient editor at The BMJ, I knew she would produce something novel and challenging, and she hasn’t disappointed. There is a horrible Calvinist in most doctors, always ready to preach at patients, as much to demonstrate our own status among the Elect as to turn sinners from their wickedness. Fat people know they are fat. Smokers know that they smoke. But how we love to tell them every time they turn up. And how few brands we actually pluck from the burning: how many more just go away muttering “sod off you prat, I never want to see you again.” Here Emma Lewis tells it like it is from the point of view of somebody who is obese despite keeping wonderfully active. Learning point: if you must tell somebody who is fat to take more exercise, find out how active they are already. Or better still, just shut up.

Plant of the Week: Helleborus “Penny’s Pink”

I have never come across a hellebore as good as this—it is one of the ericsmithii offspring I talked about a week or two ago. We first fell in love with it in Bob Brown’s nursery garden at Cotswold Garden Flowers in Badsey. It was June and everything was in flower and looking beautiful, but his clumps of this winter plant filled us with desire: incomparable foliage with still fascinating flowers, dried out and fading as they were by now. Asking at the shop, we were told that they sold out the moment that they arrived in early spring, and we would be lucky to get any even in the coming year.

Actually, when we returned late the following spring, they still had several. So we bought a couple and they are just now the most beautiful things in the garden.