Richard Lehman’s journal review – 27 July 2015

richard_lehmanNEJM  23 Jul 2015  Vol 373

307   Four summers ago I found myself dabbling in the early history of outcomes research. I was astonished to find that surgeons over a century ago were reflecting on much the same issues as they do today. In cancer, for example, there was lively debate about the place and timing of radiotherapy in relation to surgical procedures. Here’s a study of regional node irradiation in early-stage breast cancer, which recruited between the years 2000 and 2007. Ionizing radiation was first used to treat cancer in 1896 and this trial shows that we are still learning how to use it. The median follow-up here is 9.5 years, and irradiating the regional lymph nodes as well as the breast made no difference to the primary outcome, which was overall survival. It did, however, reduce the recurrence rate of breast cancer by an absolute margin of 5%, at the cost of a small difference in the occurrence of lymphoedema (absolute increase 3.9%) and pneumonitis (1%).

317   A second trial recruited 4004 early breast cancer patients between 1996 and 2004. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P=0.06). Statistically speaking, still a draw. The benefit in breast cancer specific mortality has a better claim to significance, but only just: 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P=0.02). And then you have to consider the bigger picture, since breast cancer therapy is a rapidly changing field, and rates of local recurrence have fallen markedly in the last decade with much wider and more individualised use of drug therapies.

This is discussed – though not resolved – in a linked editorial.

328   And now for a really nice example of observational surgical outcomes research. The investigators identified nearly 40,000 matched Medicare patients who underwent either open elective repair of an abdominal aortic aneurysm or endovascular repair. The overall perioperative mortality was 1.6% with endovascular repair versus 5.2% with open repair (P<0.001). But to set against that, in the following 8 years, aneurysm rupture occurred in 5.4% of patients after endovascular repair versus 1.4% of patients after open repair. Intriguingly, over the seven years studied, there was an improvement in outcomes from endovascular compared to open repair, so that these figures probably can’t be used with confidence to create a decision aid which would be accurate in 2015.

373   In my trawl through early uses of the word “outcome” in medical literature, I came across a report of gallbladder procedures in an American city hospital from around 1899. The mortality rate was over 50%. It’s a reminder of the agonies that must have been endured by people with gallstones before operative treatment became standardized and safe. Not completely safe, though: I remember a few deaths in our locality as surgeons trained to do open cholecystectomies climbed the laparoscopic learning curve in the late 1980s. And even in experienced surgeons, video re-runs of laparoscopic procedures commonly reveal all sorts of technical infelicities. Here’s an illustrated review of all the techniques now available, including mini-laparotomy, Natural Orifice Transluminal Endoscopic Surgery (NOTES), percutaneous cholecystostomy, transpapillary drainage of the gallbladder, and transmural endoscopic ultrasound-guided gallbladder drainage. A few pictures, no videos.

JAMA  21 Jul 2015  Vol 314

247   I suppose it’s the experience of sitting through endless sectarian sermons as a child that has led to my distrusting things in proportion to how earnestly they are preached. Out-of-hospital cardiopulmonary resuscitation is an example. The odds of it working are not quite as small as Jesus coming in clouds descending, but in most circumstances they aren’t very much better. And yet. Some people who drop dead in the street may be revivable and may want to be revived (you can’t know this), and if you go all out to revive them they stand a better chance than if you don’t. In Japan, citizens have received increasing tuition in (chest compression-only) CPR and defibrillators have been liberally scattered around public locations. There was a paper about the same thing in Sweden in NEJM five weeks ago . The more bystanders try, and the quicker they do it, the more chance people with a cardiac arrest have of neurologically good survival. In Japan between 2005 and 2012, the percentage rose from 3.3% to 8.2%.

255   And now to North Carolina. Here there were “statewide initiatives to improve bystander and first-responder efforts from 2010-2013.” As North Carolingians rallied to the call, the combination of bystander CPR and first-responder defibrillation increased from 14.1% in 2010 to 23.1% in 2013. Neurologically favourable survival moved from 7.1% to 9.7%.

JAMA Intern Med  July 2015

Online   Splanchnic vein thrombosis. I don’t suppose you’ve ever come across it. If you ever do, you may want to read this international collaboration report describing management and outcomes. I just like writing the word splanchnic.


There was a boy called Nicholas

Who kept on making such a fuss

His parents grew quite splanchnic,

So finally they spanked Nick.


Now this is most deplorable

For Nick is quite adorable

And it is wrong to spank Nick

Because you’re feeling splanchnic.


So kindly parents must desist

And never use their hand or wrist,

But rather seek to thank Nick

When he is not being splanchnic.


The key to life’s whole mystery

Is to avoid splanchnicity

And live with all felicity

In tranquil domesticity.

Online   Guidelines often make me splanchnic because they encourage over-investigation and overtreatment. But they can sometimes try to operate in the opposite direction. In the US system, physician income is related directly to activity and guidelines can attempt to act as a restraint. A research letter about upper GI endoscopy in Massachusetts finds that nearly 40% of procedures are done outside the recommendations of the American College of Physicians.

Joe Ross comments that this is a good topic for a Choosing Wisely initiative. “Guidelines and recommendations are not enough. Practices need to change at the point of care.”

Online  “Large population-based studies can inform us on the prevalence, incidence, natural history, treatment, correlates, and associations of disease, as well as the pattern of health care utilization. A special type of large population study encompasses the population of an entire nation. Advantages include enormous sample size and lack of selection and participation bias. These advantages are enhanced further when the databases are rich in clinical, personal, and risk factor information and when different pieces of information are linked to permit joint analysis. Once the process for data accessing is established, vast amounts of information can be obtained at minimal cost, especially when additional collection and update of information is carried out routinely for purposes inherent in medical care and/or insurance coverage and reimbursement.” Ann Hsing and John Ioannidis go on to praise the populous island where this is already being done. It is called Taiwan. Weep, Britons, weep. In this week’s issue The BMJ, Lord Darzi writes that ” We must convince the public that researchers need access to medical records”.

But as several respondents have pointed out, it’s just this lordly “we” versus “the public” attitude that ensures it won’t happen. The public are perfectly aware that great tranches of confidential data have already been made available to insurers and industry without any safeguards at all. Trust has been destroyed and may never recover. For the kind of data analysis and real-time feedback that the NHS should be leading the world in providing, researchers may now have to look to Taiwan.

Online   The Taiwanese studies which drew this praise are firstly a nationwide survey of adverse reactions to allopurinol, and secondly a similarly huge study of familial aggregation and heritability of SLE and the relative risks of other autoimmune diseases in relatives of patients with SLE.

These are great studies and yield clinically significant information – for example, the danger of serious allopurinol reactions seems greatest in patients whose hyperuricaemia is asymptomatic and caused by treatment for other conditions. They need replication in European and other populations. So perhaps the UK can get its act together and dig through its second-best databases such as the CPRD.

Lancet  25 Jul 2015  Vol 386

341   This article on stone-expelling treatments reminds me that like San Francisco awaiting its next earthquake, I await my next ureteric stone, knowing it’s overdue but not wanting to think about it. I must check the expiry date on the diclofenac suppositories. I now know that nifedipine and tamsulosin will do nothing whatever to help the stone move down the ureter: the evidence comes from this randomised trial. Lovely clear publicly funded research addressing an important clinical question, and The Lancet has made it open access: it makes you proud to be British, for a change.

360   At the other end of the spectrum is a trial of intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency. “The funder [CSL Behring, manufacturer of the intervention] had a role in oversight and management of data collection. JME, LH, and ZY, who are employees of the funder, participated in data analysis, data interpretation, and writing of the report.” 99% of participants in both the active and placebo groups had adverse reactions. One surrogate measure of emphysema progression showed an effect from the intervention whereas two others did not. “These findings should prompt consideration of augmentation treatment to preserve lung parenchyma in individuals with emphysema secondary to severe α1 antitrypsin deficiency.” says the last sentence in the abstract. Isn’t there a “not” missing somewhere?

369   I am very much a Goldilocks person where ambient temperatures are concerned. The present English summer is suiting me perfectly: just one stifling day above 30, and the rest hovering around or below 20C. But it is not heat but cold that kills, according to a big (open access) survey funded by the Medical Research Council (MRC). I hate the winter here though daytime temperatures are seldom below freezing. In the MRC sample of 13 countries, only three have really cold winters: Canada, Sweden and the USA. But that doesn’t stop about 15 times as many deaths being due to cold than to heat. The Anglo-Saxons were constantly referring to this in their poetry. Wintres wōma: the death cry of winter. My translation from The Wanderer. Nobody quite knows what woma means: something to do with noise.


The BMJ  25 Jul 2015  Vol 351

This week has seen The BMJ at its most brilliant, not in primary research but in advocacy. Trevor Jackson sums up most of it in his opening commentary “Confronting medicine’s flaws.”

Alas, one of medicine’s flaws is the idea that every question can be solved by more research. The first of the invited editorials asks “Without proper research funding, how can medical education be evidence based?” My question would be, “Even with proper research funding, can medical education ever be evidence-based?” and my answer would be no, because there will always be too many confounding factors and a lack of meaningful, long-term metrics.

And the first of the research papers is an attempt to trawl through studies of self-reported soft drink intake to prove that habitual consumption of sugar sweetened beverages is associated with a greater incidence of type 2 diabetes, independently of adiposity. It even calculates a population-attributable fraction. I’m sorry, this is hard work conscientiously done, but it can never prove causality and is based on data that hardly deserve the effort.

And yet this really is a brilliant issue of The BMJ. The final editorial challenges Rory Collins to get proactive about arranging an independent review of individual participant data from all the statin trials about which he has been so vocal.

Margaret McCartney finds time amongst all her other activities to do a personal investigation of the way that employees of pharma “help” GP practices in the UK by identifying patients who need extra treatments to achieve QOF points. These people are given a free run of confidential patient information while we turn a blind eye.

And then she squeezes in the best and quickest refutation of the mad hype surrounding Eli Lilly’s “breakthrough drug” for Alzheimer’s, solanazemab.

Plus her usual column, pithily deconstructing the Hunt plan for making people feel guilty about using pricey drugs – such as solanezumab (should it ever appear).

An Analysis piece by two authors from New Zealand examines why, after much evidence of lack of benefit and some of harm, tens of millions of women are still encouraged to take regular supplements of calcium and vitamin D. It’s as if there were market forces at work against evidence based medicine.

Plant of the Week: Rosa “Jacqueline Du Pré”

I once carried Jacqueline du Pré’s cello on a London bus. It was only her second cello, mind, though still a Strad. I never met her in person: I just happened to know a friend to whom she’d lent her instrument.

I did hear her playing though. Her rose is contrastingly subtle, sweet and restrained, but  with a touch of Jacqui’s own generosity. The flowers are nearly white, shading to almost imperceptible delicate orange-pink. The stamens are wispy and beautiful, like those of “White Wings”. The scent is heady and wonderful.

The only problem was that our garden didn’t have room for another rose. But now it has.