NEJM 17 July 2014 Vol 371
203 Niacin is an abundant natural B vitamin, which lowers bad cholesterol and raises good cholesterol. What’s not to like? Well, niacin, unfortunately. In doses that make any difference to lipid levels, it is very likely to make you feel sick, get flushes and/or rashes, and/or feel muscle pains. So Merck decided to market it in combination with laropripant, a prostaglandin antagonist that is meant to combat its unpleasant effects. Even so, a third of people who were recruited to the present trial could not continue past the run-in phase with the active combination. And now that the full results are out, we have confirmation that this dual agent definitely does not offer any cardioprotection despite its “favourable” effect on lipids. Worse still it causes bleeding, raises blood sugar, and shows a tendency to increase mortality in those who can tolerate taking it for three years. The Clinical Trials Support Unit (CTSU) at Oxford did a great job of running this trial with funding from Merck, following its usual rules of independence. In doing so, it provides a great illustration of the fact that lipid fractions are very unreliable surrogates for cardiovascular outcomes. But we knew that already, and it seems a great pity to me that many superb researchers were tied down for so long on a project that has made such a small contribution to clinical knowledge, whatever it may have contributed to the funds of CTSU.
213 When I started writing these notes on the journals for a few friends and colleagues, I would have gone straight past a title like “Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia” in the NEJM. Nothing is more certain than that I will never initiate treatment with ibrutinib or ofatumumab in previously treated chronic lymphoid leukaemia. But I’m really pleased that someone has discovered ibrutinib because it will save lots of lives. One of the pleasures of reading the journals is to see discoveries like this pop up from time to time. The “brut” in ibrutinib comes from Ogden Bruton (1908-2003), whose name was given to an important kinase expressed in several blood cancers; and the “inib” simply refers to inhibition. Ibrutinib lives up to its name, and by inhibiting Bruton’s kinase it stops chronic lymphoid leukaemia when nothing else can. A medical advance of this magnitude deserves a poem called Lehman’s Brut, in imitation of Laʒamon’s Brut. This epic work was written around 1190, and it ran to 16 095 lines of Early Middle English. I must get started at once.
JAMA 16 July 2014 Vol 312
240 To improve the management of your patients with chronic pain, why not set up a nurse-led system of supervision over the telephone? You could call it Telecare Collaborative Management of Chronic Pain in Primary Care. If you followed the model of this trial, you might find that it produced slightly better results than usual care, with less of an increase in opioid prescribing. Or you could just try improving usual care.
249 Primary Sjögren’s syndrome is a systemic autoimmune disease characterised by dryness, pain, and fatigue. Despite the advances of rheumatology in the last two decades, there is no evidence based treatment for it that alters the course of the disease. Hydroxychloroquine is widely used, but that may stop following this French trial that compared it with placebo. The two produced the same results after 24 weeks.
Lancet 19 July 2014 Vol 384
OL Both the Lancet and The BMJ have important papers about whooping cough this week, but you have to look online to find the Lancet study. It charts the success of the English pertussis vaccination programme for pregnant women. Something strange happened to the epidemiology of Bordetella pertussis in 2011, when there was a sudden spike in infections in babies under the age of 3 months in England. In 2012, there were 14 infant deaths from whooping cough. In October that year, a vaccination programme was introduced for pregnant women in England. The success of this is clear from figure 2 in this paper: unless it was just a return to normal from a glitch. Whatever the cause, only three infants died from pertussis in the first nine months of 2013, all to mothers who had not received the vaccine.
OL The arrival of drug-eluting stents signalled a bonanza not just for device manufacturers, but for makers of anti-platelet drugs and platelet testing kits too. The small superiority of the new stents over the old bare metal ones depended on using clopidogrel or a similar agent in addition to aspirin for an initial period, now fixed by tradition at 12 months. An extension of the French ARCTIC-Monitoring trial sought to find out whether there might be additional benefit from continuing dual anti-platelet treatment for longer than a year. The answer is no: in fact this just increases the potential for harm from bleeding events.
The BMJ 19 July 2014 Vol 348
I first became aware of how common whooping cough is when my primary care practice took part in research that Anthony Harnden was conducting in the early 2000s. We turned up pertussis IgG levels suggesting recent infection in almost a quarter of saliva samples in schoolchildren and adults with chronic persistent cough. After the study was over, we were denied access to pertussis serology on the grounds that the condition was untreatable: a curious insight into how our masters understand the use of diagnostic tests. This experience had one very useful outcome, because it led me to ask Anthony to join me in proposing a series called “Commoner Than You Think” to The BMJ. This then became “Easily Missed,” which has been running for over five years. Anthony, meanwhile, continues to base himself in real life practice, while producing a series of excellent studies and papers of immediate relevance to clinical care from his base in Oxford University. This one, led by Kay Wang, is an update of the earlier study. It shows that pertussis is still common in schoolchildren with a chronic cough that is typically paroxysmal and sometimes severe. Acellular-only vaccine regimens are not very durable in their effect, and the search for better protection needs to continue.
As I’ve just told you, pertussis vaccine given to pregnant women seems to have been very successful in snuffing out a min-epidemic which was killing a number of English babies. Here is a paper looking at what effect it had on maternal and pregnancy outcomes. It seems to have been without any detectable harms.
A common assumption is that cerebral palsy is due to some form of brain injury at birth, but often it is not. There is a strong familial element, as demonstrated by this national cohort study from Norway. Risk of cerebral palsy is associated with how close the child is related to others with the condition. For example, in families with an affected singleton child, risk was increased 9.2 fold in a subsequent full sibling and 3.0 fold in a half sibling. This is another awesome piece of work from a comprehensive Nordic database.
Plant of the Week: Lavatera x clementii “Mary Hope”
Twenty years ago, a shrub bearing hollyhock flowers of white flushed with rose-pink was planted in every second garden in England. It achieved this popularity even though its name suggested a public toilet in South Yorkshire. Lavatera x “Barnsley” then seemed to vanish as quickly as it had arrived. It is a fairly short lived plant, and perhaps when it died after its usual lifespan of about 10 years, people decided to go on to try something else.
What a good plant it is though. It is actually named after Barnsley House in Wiltshire, which was then celebrated for the garden of a renowned plantswoman of aristocratic mien, Rosemary Verey. This latest tree mallow is nearly indistinguishable, but bears the name of one Mary Hope, with whom I lack acquaintance. It is spreading around garden centres under her name, though the designation is not yet official. I suspect it will behave exactly like the late Ms Verey’s hybrid, flowering abundantly and prettily for months in any reasonably sunny spot, and looking best if cut back hard in the spring. It has a rather softer flush of raspberry pink in the centre of its flowers. The leaves are greyish and lobed.
As I grow old, I am frustrated that plant breeders don’t get on and create all sorts of lovely new intergeneric hybrids in the mallow family. If they did a bit of fiddling about with hollyhocks and lavateras, I am sure they could easily produce shrubs with all the lovely hollyhock colours from pale lemon yellow to an inky purple that approaches black. This year we happen to be blessed with those colours of hollyhock, but by next year they may be gone. If they were to appear on a lavatera, we could be sure of them forever, because nothing is easier than to propagate from the pithy branches of these shrubs: just pull one off and stick it in the ground.