Richard Lehman’s journal review—14 November 2016

richard_lehmanNEJM  10 Nov 2016  Vol 375

Reinventing connected medicine

A 1300 word Viewpoint article can hardly do justice to a theme as grand as “Meaning and the Nature of Physicians’ Work”, and a lot of this piece is taken up with describing the current realities of American hospital medicine for those at its coalface. But here’s a proposal we can all identify with:”Perhaps the greatest opportunity for improving our professional satisfaction in the short term lies in restoring our connections with one another. We could work on rebuilding our practices and physical spaces to promote the sorts of human connections that can sustain us—between physicians and patients, physicians and physicians, and physicians and nurses. We could get back to the bedside with patients, families, and nurses. We could get to know our colleagues from other specialties in shared lunchrooms or meeting spaces.” It’s not rocket science. But it’s certainly how the greatest rocket scientist operated. He was Sergey Pavlovich Korolev (1907-1966), who lived and worked with his teams day and night, and put the Soviet space programme way ahead of any other while he lived.

Vitamin D Deficiency — Is There Really a Pandemic?

The leading obituary of this week’s The BMJ describes the life and work of Robert P Heaney, Vitamin D advocate and a “Legend of Osteoporosis.” In 1967, he gathered 167 young nuns from 6 convents into his research unit and made an intensive study of everything that went in and out of them (“Everything, dear,” said one of them, many years later) over several days, and repeated the exercise every five years until 1992. He started out looking at calcium but ended up more interested in vitamin D, ending his life advocating for widespread high dose supplementation. A Perspective piece in the NEJM takes the opposing view. This is a highly technical piece which is of more interest to would-be experts than people like me who take the odd vitamin D tablet when we think about it. It seems to me that this strategy is as evidence-based as any other, but I may be wrong. Only long-term dosing studies will tell.

The heart failure that dared not speak its name

I got interested in heart failure in the 1990s, and for a few years I felt quite lost. I was among the first to measure B-type natriuretic peptide and compare it with echocardiography in a primary care population, and it seemed very clear that there were a lot of very symptomatic people with high BNP and normal systolic ejection fraction on echo. There was already an extensive literature in the USA using the term “diastolic heart failure,” but if I mentioned it to British cardiologists they would look at me derisively and tell me there was no such thing. Here is a Clinical Practice piece on Heart Failure with Preserved Ejection Fraction which states what is now universally accepted: “Epidemiologic studies indicate that up to 50% of patients with heart failure have a preserved ejection fraction, and this proportion has increased over time. In observational studies, rates of hospitalization and death among patients who have heart failure with a preserved ejection fraction approach those among patients who have heart failure with a reduced ejection fraction.” But cardiologists are still not interested, because they have no specific treatments to offer. At the end of this article, a Mayo clinic cardiologist suggests the following for her 73 year old patient with BMI 39: “Once her condition is stable, exercise and weight-loss programs should be commenced. Persistent symptoms or recurrent hospitalizations should prompt referral to a disease management program for patients with heart failure. She should be informed about clinical trials of therapeutic strategies for heart failure with a preserved ejection fraction.” In fact, persistent symptoms or recurrent hospitalizations will mean that she is dying. Reducing her BMI from 39 to 38 will not alter that. She may wish, out of altruism, to enlist in a trial. But if she wants good care, she needs to (a) avoid disease management programs (b) find a generalist with whom she can trust the remainder of her life (c) concentrate on what is most important to her (d) connect with everyone she loves and (e) find someone who can guide her towards a good death. These are the things that every person with advanced heart failure needs, regardless of aetiology. Yet so few can find them. And by the way, most heart failure nurses in the UK are still barred from accepting referrals for heart failure with preserved ejection fraction.

JAMA  8 Nov 2016  Vol 316

Tailor failure

For a number of reasons, I’ve spent a lot of mental energy over the last year looking at so-called “tailored” treatments for early breast cancer. I feel very much older and not at all wiser. And while the tailors deserve credit for their good intentions, I wouldn’t yet trust them with my bust measurement. In this particular trial, the dosing of chemotherapy in the “tailored” group was based on the hypothesis that short intense treatments that hammer the bone marrow will also hammer the cancer cells. Thus doses of chemotherapy were driven largely by nadir values of leucocytes and platelets at various points following each treatment cycle. Inevitably this meant that the group had to be given filigrastim to help bone marrow recovery each time: and inevitably it meant they had more adverse effects. After 5 years, overall survival and distant disease recurrence did not differ significantly between the groups.

Anakinra for pericarditis

It’s strange how some conditions are studied more in particular countries. Italy is big on coeliac disease, H pylori eradication, and pericarditis, for no reasons I can discern. Having helped to establish that colchicine is a good treatment for pericarditis, they have now moved on to anakinra. Anakinra is a recombinant version of the interleukin 1 receptor antagonist, so it does not grow free on the Apennines like the colchicum lily. So the AIRTRIP Anakinra -Treatment of Recurrent Idiopathic Pericarditis) trial only recruited patients with cochicine-resistant and corticosteroid-dependent recurrent pericarditis. Not surprisingly they could only find 21 patients at three Italian tertiary centres. Anakinra seemed to work but caused transient skin rashes in nearly all patients, and there was one case of ischaemic optic neuropathy.

JAMA Intern Med  Nov 2016  Vol 175

Triglycerides, pancreatitis and MI

Two big cohort studies of adults in Copenhagen yielded a total of 116 550 people with non-fasting measurements of their triglyceride levels. Their data confirm the traditional association between high TG and the risk of pancreatitis and myocardial infarction. There is a linear increase in risk for both, so that compared to people with TG below 1mmol/L, those with a level over 5 had an increased 8-fold risk of pancreatitis and 3.4 fold increased risk for MI.

The Which? guide to aortic valves

This article begins by saying that “postmarket evidence generation for medical devices is important yet limited for aortic valve devices.” Actually it is rather good for aortic valve devices, as the authors show, while for a range of other important devices it is pretty well non-existent. There is a National Cardiac Surgery Audit which gathers data from the NHS and also from private providers, yielding nearly 58,000 aortic valve replacements to analyze here. This is a model for such analysis and identifies two specific biological valves that are outliers and give cause for concern.

Lancet  12 Nov 2016  Vol 388

Back to Bismuth for H pylori

Bismuth has been used medicinally for over two centuries, and Pepto-Bismol (bismuth subsalicylate) has been a bestseller for over a century and shows no sign of losing popularity in shops around the world. It has some immediate effects on indigestion and it can also suppress Helicobacter pylori, though seldom for long. Like many ubiquitous, semi-commensal organisms, H pylori is good at becoming resistant to antibiotics, and patterns of resistance vary geographically. I doubt whether we will ever be able to get rid of it altogether and it is not even clear whether it would be a good thing if we could. This study comes from Taiwan and shows that in places where there is high resistance to H pylori eradication using triple antibiotics alone, adding bismuth tripotassium dicitrate and keeping up a quadruple attack for 14 days can do the job better.


BMJ  12 Nov 2016  Vol 355

Ischaemic preconditioning: when the miracle fails

Remote ischaemic preconditioning is a bizarre and wonderful thing if it really exists. It means that you can occlude the blood supply to a limb for less than 5 minutes and the body will react by protecting all its organs from ischaemic damage over the next few hours. So theoretically if you put a cuff round a limb and inflate it for a few minutes to above systolic blood pressure, prior to surgery that might carry a risk for ischaemia in the heart, brain or kidney, you might prevent injury to those organs. Unfortunately this systematic review provides no clear evidence from randomised trials that this actually happens.

Gene detection to guide anti-D use in pregnancy

Please read carefully before proceeding: “In most women who are RhD negative there is a complete deletion of the RHD gene. The discovery of cell-free fetal DNA in maternal plasma during pregnancy and the feasibility of fetal RHD testing with this source of DNA presented the opportunity to restrict antenatal anti-D immunoglobulin use to only those RhD negative women carrying an RhD positive child, which optimises the use of this blood product.” Actually, it’s a lot more complicated than that, but it can be done: you can tell whether the fetus is actually D positive simply by sampling maternal blood at 27 weeks. This Dutch study shows that this is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use.

Cancer drugs, survival, and ethics

As you may have noticed, most trials of new cancer drugs give me rage fatigue. Terrible design, strange recruitment, bad comparators, stupid endpoints, biased reporting, usually followed by unwarranted hype and unconscionable licensing, deluding patients and bankrupting individuals and health systems. It really could not be worse, in every respect. Peter Wise says this much more soberly in an excellent Analysis piece. Not that he pulls his punches at the end: “Above all, the efficacy bar for approval needs to be raised for both new and existing cancer drugs —by using more meaningful statistical and disease specific criteria of risk-benefit and cost-benefit. Finally, aggressively targeting the less than ethical actions of stakeholders in the heavily veiled medical-industrial complex may be the only way forward: current market driven rather than health driven priorities and practices do not benefit cancer patients.”

Plant of the Week: Pinus sylvestris

The Scots pine is usually seen outside Scotland as a solitary tree, where it can cut a wonderful silhouette against the November sun, or if approached from the other side, can astonish with the shining grey-pink of its tall trunk.

In fact Scotland was the last part of the British Isles which this pine reached following the last glaciation. After the ice retreated northwards, it recolonized the Highlands around 8,000 BC and flourished to form the Great Caledonian Forest, of which a few remnants survive. Elsewhere in Britain, the Scots pine then died out and had to be reintroduced as single park specimens or small stands in the last 300 years.

It is hardly a tree for small gardens, but I am always grateful to see it where some Victorian grandee or churchman thought fit to plant it in a private or public space, preferably near the top of a hill.