JAMA 6 Oct 2010 Vol 304
1447 “In 2005, because our evaluation of out-of-hospital cardiac arrest in Arizona revealed dismal outcomes, we established a statewide program aimed at improving survival.” I like the way the chief investigator uses the word dismal: I like his name, which is Bentley Bobrow: and I like his study too, which shows better outcomes from compression-only cardiopulmonary resuscitation when given by lay rescuers. It was a natural experiment: following a public campaign to promote simplified CPR, paramedic rescue teams were simply told to record whether any CPR had been given by bystanders and whether this included interruptions for the “kiss of life”. Other studies of more sophisticated randomised design have shown non-inferiority for CPR without rescue breathing, but this one shows significant superiority, not just in survival rates but also neurological outcomes. The kiss of life is usually the kiss of death, and “Push hard, push fast, and don’t stop” is a maxim that will improve survival of out-of-hospital cardiac arrest by 60% when applied by people with no medical training. It’s worth spreading the message, even though the survival rate in Arizona only reached 13.3%.
1480 In the last couple of years, we’ve become increasingly aware of atypical fractures as a potential complication of long-term bisphosphonate therapy. I’ve even had a spontaneous mid-shaft fracture of the femur happen to one of my patients, who subsequently died. So it does happen, but fortunately not often – so much so that this clinical case review states that large cohort studies of women taking bisphosphonates for 5 or more years can’t detect an increase. This rare but sometimes catastrophic complication is more just a shot across the bows, reminding us that it may not be a good idea to put people’s osteoclasts completely out of action for up to decade.
NEJM 7 Oct 2010 Vol 363
1410 The ADVANCE and ACCORD studies of tighter glycaemic control in established type 2 diabetes appeared in June 2008 but their lessons are still slow to percolate the glucose-fixated world of diabetology. ACCORD, you will remember, threw anything and everything to reduce HbA1c at a group of over 10,000 people with T2DM and was curtailed due to higher mortality in the intensive intervention group. ADVANCE went for a similar target of 6.5% HbA1c but used long-acting gliclazide as the preferred intervention. In both trials the interventions increased the risk of severe hypoglycaemia, especially in ACCORD where the increase was threefold. This was analysed for its relation to mortality in a BMJ paper earlier this year. Oddly enough, although a range of adverse outcomes, including death, was associated with hypoglycaemia in that study, this did not explain the higher mortality in the intensively treated group. And this ADVANCE analysis is similarly ambivalent: it seems that people who are more likely to get hypos are more likely to get sick and die for all sorts of reasons, not just from cardiovascular disease; the relationship with the hypoglycaemia is not necessarily causal. I hope I have made myself sufficiently unclear.
1438 A review of profound deafness in childhood spends most of its space explaining what cochlear implants can and cannot do. They can allow children to recognise speech and help the development of the auditory cortex, but they cannot transmit music in any meaningful way and they deprive speech of much of its tonal variety.
Lancet 9 Oct 2010 Vol 376
1225 On some yet undiscovered Sumerian clay tablet or Egyptian papyrus there must be a reference to honey as a pacifying agent for babies in pain, and I will send a piece of honeycomb to any reader who can find a suitably ancient reference to what is undoubtedly a very ancient practice. This study aims to determine whether sucrose solution really does reduce pain in neonates undergoing heel-prick blood sampling in University College London, and is described by the editorialist (p.1203) as “a laudatory mix of innovative research on cortical evoked responses to noxious stimulation and a rigorous randomised trial”. Laudatory? or laudable? Copy editing in British medical journals has become almost undetectory. And actually it’s hard to find much that’s laudable about this trial, since these seemingly impressive techniques really tell us nothing about the way neonates perceive and record pain, and the trial was only powered to detect a massive 0.9 standard deviation difference between the babes given sugar and the babes given water – small wonder that it didn’t.
1233 Here’s the Lancet piece about the CURRENT-OASIS 7 trial of standard or double dose clopidogrel prior to PCI for acute coronary syndromes which was also reported in the printed NEJM a couple of weeks ago. In that paper, the distinguished investigators concluded, without qualification, that outcomes did not differ significantly between the higher- and standard-dose groups. In this Lancet paper they state the exact opposite, in relation to the two-thirds of patients who actually underwent PCI. It’s almost too good to be true, and if you want to study the detail go to Harlan Krumholz’s brilliant analysis on CardioExchange, which concludes,”These articles earn my top rating for use in a journal club. Rarely will you witness famous authors draw such different conclusions about identical data published simultaneously in two prestigious journals. It’s a perfect opportunity for students and others to learn about interaction testing, significance levels, and subgroup selection.” Even if you don’t read the papers or care a fig about interventional cardiology, you must read this piece.
BMJ 9 Oct 2010 Vol 341
762 Most medical research is clinically useless, and so, sadly, are most systematic reviews and meta-analyses. This paper explores some of the reasons, especially those that are innate in the way that evidence is generated. The authors use TNF blocking agents as their example of drugs rarely compared with the best current treatment, and bevacizumab for cancers as an example of small treatment effects never meta-analysed with sufficient breadth and in the context of clinical practice. It’s depressing reading, so you probably won’t read it, excusing yourself that you’re merely a clinician. But you should: because until clinicians seize evidence-based medicine by the scruff of its neck and demand that it gives us better evidence, this glut of futility will merely get worse.
767 Take this meta-analysis of the relationship between low glomerular filtration rate and stroke. It’s a perfectly decent piece of work by a team from Taiwan and Los Angeles. Yes, there is a linkage between an eGFR under 60 and the risk of stroke, as you’d expect given that there are common pathophysiological pathways. Like both organs having arteries. The clinical question – made pertinent to British GPs by the QOF payment system – is whether picking out people with a mildly impaired eGFR is a useful exercise in cardiovascular prevention, or whether traditional risk factors suffice for this purpose. I’ve never seen a good analysis of that. Meanwhile, the hapless Taiwanese and American researchers sit in air-conditioned rooms going through 1754 abstracts, 83 full papers, and then fully meta-analysing 22 to get themselves a paper in the BMJ telling us what we already knew.
768 The next paper uses a population study from Iceland to tell us much the same thing, except that it ranges across all of major cardiovascular disease and uses a very confusing distinction between lowered eGFR with and without “chronic kidney disease” – based on albuminuria, I think.
770 As GPs, we face a winter of dealing with respiratory infections, often causing wheezy episodes in small children. We will be using our clinical judgement (not to mention how late we are running) to determine which kids have viruses so that their parents need persuading to take them home and sit it out a bit longer, and which have bacterial infections and so simply need the printer to issue forth amoxicillin. Actually, the majority have both, and whether they get better with or without an antibiotic is largely determined by other factors. Bacteriological analysis will only tell you what organisms are there, not what they are doing. Which is the problem with this excellent and thought-provoking paper from the Copenhagen Prospective Study on Asthma in Childhood. Airways aspirates were analysed for bacteria and viruses every six months routinely in kids under 3, and additionally whenever there was a wheezy episode. It seems that bacteria are associated with exactly the same number of wheezy episodes as viruses. How this should influence management is a question that needs an interventional trial, and it’s high time we had one.
772 The clinical review section of the BMJ usually maintains an impressive standard, so I had high hopes of this article on the difficult subject of chronic pelvic pain in women. It’s probably in the nature of the topic that I was disappointed. The summary points in the box make that clear, but Fig 2 showing a “biopsychosocial model of chronic pelvic pain” has its triangles completely the wrong way round. It’s the social context that envelops everything, then within that the psychological, and within that the physical. Here we must realise our limitations and admit that we can only really help the physical, much as we would like to address the rest.
Ann Intern Med 5 Oct 2010 Vol 153
435 If you are sleep deprived and calorie restricted, you feel hungrier and oddly enough you burn up protein in preference to fat. So, as the title of this study says, insufficient sleep undermines dietary efforts to reduce adiposity. This is a good old-fashioned study, using 10 overweight, sedentary, healthy volunteers in a cross-over study involving them in spending two fortnights confined to a sleep laboratory in Chicago. During one period they were allowed 5.5 hours of sleep with no naps, and during the other they could sleep for 8.5 hours, all the while receiving a diet of 90% of their resting metabolic rate. More sleep produced more fat loss.
Plant of the Week: Coronilla valentina subsp glauca “Variegata”
Thanks to late-season sunshine and the absence of frost, the garden remains full of life and colour, but we know that will be gone within a week or two. Then it will be time for a few treasured stalwarts to see us through the cold dark ugly months of winter. Most lively among these, though not most hardy, is this climbing, sprawling little shrub which bears bright yellow pea flowers right throughout the dead season. These have a delicious sharp scent even on frosty days. In the variegated form, which is the one you’re most likely to find, the flowers are set off by pretty little leaves of grey-green edged with cream white. Wall protection and a bit of support will help to keep it alive and handsome all the year round.