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Richard Lehman’s weekly review of medical journals

Richard Lehman’s journal review—8 February 2016

8 Feb, 16 | by BMJ

richard_lehmanNEJM 4 Feb 2016 Vol 374
Renal altruism
411 Greater love hath no man than this, that a man lay down his life for his friends. Failing that, consider live kidney donation. In fact, the risk of you laying down your life by getting end stage failure of the other kidney is really low, especially if you are “white” rather than “black”, in the parlance of this paper. If you are a black man of 40 in the general US population with two intact kidneys, your 15 year risk of end stage renal disease is 0.24%, whereas if you are a white woman, it is 0.04%. Donating a kidney increases the risk by a factor of 3.5 to 5.3. So the extremes would be: maximum 1.72% risk for a black man donating a kidney versus minimum 0.14% for a white woman over 15 years. Quite a range, but reassuring figures for anyone thinking of being altruistic.

150 Shades of AML
422 Pathologists have always been classifiers, and the new genomics has sent them into pathology heaven. Let’s take a peep at their paradise: more…

Richard Lehman’s journal review—1 February 2016

1 Feb, 16 | by BMJ

richard_lehmanNEJM 28 Jan 2016 Vol 374
Venetoclax & CLL
311 Venetoclax is a wonderful name. I shall set up a burglar alarm company in Venice so that I can see it painted on the side of gondolas: “Protect your palazzo with VENETOCLAX.” Then, when the moony silence of the Venetian night is pierced with the affrighting wail of our klaxons, I will be able to mutter contentedly, “Another one caught. Another success for Venetoclax.” I don’t know how the name venetoclax came to be attached to a new drug for resistant chronic lymphocytic leukaemia (CLL). But here it is, attacking BCL2, a protein central to the survival of CLL cells, in a phase 1 trial. Almost every patient with relapsed or refractory CLL or small lymphocytic lymphoma showed a response. I would opine that it is much too early to predict its place in the overall management of CLL, though this is a subject which I know little more about than burglar alarm selling in Venice.

Et tu, Bruton
323 Things that I do know about CLL: it affects older people, it has hitherto been hard to treat, but the emerging standard of care seems to be ibrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK), which is slightly better than chlorambucil and costs hundreds of times as much. more…

Richard Lehman’s journal review—25 January 2016

25 Jan, 16 | by BMJ

richard_lehmanNEJM 21 Jan 2016 Vol 374
Share data or be damned
OL The most important article this week also appears on the websites of JAMA, The BMJ, Annals of Internal Medicine, and The Lancet. It’s a proposal from the International Committee of Medical Journal Editors to move towards a requirement that all published research should be accompanied, within six months of publication, by a full dataset of de-identified participant level data. I’m writing this during a brief stay at the home of the Yale Open Data Access project, which began in 2011 when this would have seemed the stuff of fantasy. We didn’t actually open champagne, though we did talk of it. One reason is that it we now will have even more work to do; another is that this is still just a proposal. If you support it, write to

Richard Lehman’s journal review—18 January 2016

18 Jan, 16 | by BMJ

richard_lehmanNEJM 14 Jan 2016 Vol 374
SDM: no looking back
104 There are two interesting Perspective pieces in this week’s NEJM, both about individualizing care. The first is about shared decision making and its difficulties. The author usefully sees these through the eyes of a physician who is just beginning her struggle with the realities of communicating risk while accepting that individuals have the right to choose, especially in the context of screening and long-term preventive medication. Shared decision making is a long journey, and it’s taking the medical community a long time even to get started. This is a reasonably good place to set off from. But beware: once you have started, you can never go back to your comfort zone. You are on a lifetime journey beyond it. more…

Richard Lehman’s journal review—11 January 2016

11 Jan, 16 | by BMJ

richard_lehmanNEJM 7 Jan 2016 Vol 374
Predicting next week’s PET
13 This week begins with a toughie. Diagnostic test studies are always tricky to analyse. What matters to you as a clinician is the downstream value of the test—how it will help your management and improve the outcomes of patients. In the PROGNOSIS study a combination of tests was used to predict the short term onset of pre-eclamptic toxaemia in women past the 24th week of gestation who were suspected of being about to get PET. The primary outcome measure was whether they did get PET. And in this study, designed and closely supervised by Roche Diagnostics, the combination test shows pretty useful predictive value for the development of PET in the coming week: it is less good for predicting PET thereafter. But what you as a clinician need to know is if this is any better than sending the patient home to rest and measure her BP and urine protein daily. And if these go up and stay up, you have a diagnosis of “PET” and therefore get her to hospital and deliver the baby when you think safest. So where does the Roche test fit into routine practice? more…

Richard Lehman’s journal review—4 January 2016

4 Jan, 16 | by BMJ

richard_lehmanNEJM 24 & 31 Dec 2015 Vol 373
Second cancers after Hodgkin’s cure
2499 Hodgkin’s disease was one of the first cancers to move from invariably fatal to routinely curable. It happened about 50 years ago, and we have long known that the price for this was an increase in risk for later cancers, due to the treatment modalities used—extensive radiotherapy and highly toxic chemotherapy. But surely, with better targeted treatments over the decades, this risk has diminished? Alas, there is no evidence of this from a study of 3905 persons in the Netherlands who survived for at least 5 years after the initiation of treatment for Hodgkin’s lymphoma between 1965 and 2000. With a median follow-up of 19.1 years, the risk of a second cancer remained high across the board, with a cumulative incidence of a second cancer in the study cohort at 40 years of 48.5%. This paper expresses the risk as a standardized incidence ratio (SIR), which had me looking on Google. The SIR was 4.6 (95% confidence interval 4.3 to 4.9) in the study cohort as compared with the general population. And yes, unless I am mistaken, that means over 4 times higher than the population average.


Richard Lehman’s journal review—21 December 2015

21 Dec, 15 | by BMJ

richard_lehmanNEJM 17 Dec 2015 Vol 373
Chilling brain trauma
2403 Traumatic brain injury is the commonest cause of permanent disability in Europeans under the age of 40, and its incidence is rising. After the trauma, many people show an increase in intracranial pressure above 20mm Hg. One way to reduce it is to cool the whole patient using infusions of refrigerated normal saline until the core temperature reaches 32C or the intracranial pressure falls below 20. This is standard practice in some European ICUs, though a review of previous trials shows mixed results. This 47 centre European trial is definitely negative: “therapeutic hypothermia plus standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone.” At Cochrane, we’re constantly debating at what point absence of evidence becomes evidence of absence. It seems to me that this trial, taken together with previous ones, shows that we’ve passed the tipping point with this type of treatment for head injury.


Richard Lehman’s journal review—14 December 2015

14 Dec, 15 | by BMJ

richard_lehmanNEJM 10 Dec 2015 Vol 373
Pacific treatments for scabies
2305 Wow. Here is the ultimate cluster randomised trial: an island randomised trial. First find your islands in the vastness of the Pacific Ocean. Make sure they are big enough for your power calculation, and that they have a similar prevalence of your target condition: in this case, endemic scabies and secondary impetigo. The ocean will keep them separate. By now you are itching to go, and you are a mite excited because you will be starting from scratch. So you allocate one island group to standard care involving the administration of permethrin to affected persons and their contacts (standard-care group), the next to mass administration of permethrin (permethrin group), and the third to mass administration of ivermectin (ivermectin group). Your primary outcome is the change in the prevalence of scabies and of impetigo from baseline to 12 months. Burrowing into the data at the end of the trial, both the whole-population treatment strategies proved effective at reducing scabies and impetigo, with ivermectin the overall winner. Maybe there are other conditions endemic on Pacific islands that might get under the skin of researchers and provoke a rash of similar studies.


Richard Lehman’s journal review—7 December

7 Dec, 15 | by BMJ

richard_lehmanNEJM 3 Dec 2015 Vol 373
CPR with or without breaks
2203 Cardiopulmonary resuscitation for cardiac arrest outside hospital carries a mortality risk of more than 90%. It is usually assumed that the death rate would otherwise be 100%, but trials of CPR don’t ever include a non-intervention arm, so we don’t really know. In this huge US trial, emergency medical service groups were cluster randomised to give either continuous chest compressions without breaks for ventilation, or to have a ventilation break after every 30 compressions. There was no significant difference in outcome: 9-9.7% of patients survived to be discharged from hospital and 7-7.7% had “favourable neurologic function” at discharge.

Paracetamol and fever outcomes
2215 A double-blinded trial of paracetamol (acetaminophen) in ICU patients with fever raises the old question of whether fever helps you fight off serious infection and therefore if suppressing it is a bad idea. more…

Richard Lehman’s journal review—30 November

30 Nov, 15 | by BMJ

richard_lehmanNEJM 26 Nov 2015 Vol 373
“Artificial cell” for diabetes
2129 “Home use of an artificial beta cell in type 1 diabetes” conjures up a vision of some huge cellular blob taken home in a glass tank and connected up with the circulation, probably by Peter Cushing in a white coat and half-moon spectacles. In fact the artificial beta cell is just a fanciful name for a closed loop insulin pump driven by a glucose sensor. It’s the device we’ve been waiting for for decades. The trial recruited 33 adults from the UK, Germany, and Austria, and 25 children and adolescents from the UK. The comparator was a sensor augmented pump. The closed-loop system produced overall better control and less nocturnal hypoglycaemia over 12 weeks, provided it was connected properly with a working battery: when not, it caused three episodes of significant hypoglycaemia. So a promising start for a device that would be used for a whole lifetime, and a great opportunity to do an international collaborative follow-up study, in which all the data and device modifications are shared in real time to achieve the quickest route to an effective, safe, and affordable system. Come on guys, you can do this. more…

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