Richard Lehman’s journal review—17 July 2017

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM  13 July 2017  Vol 377

The CHIP: a new cardiovascular risk factor

In the USA, where chips are called fries, the word CHIP means Clonal Hematopoiesis of Indeterminate Potential. Like moles on the back of your hands or curly hair in your ears and nose, these are a sign of getting old. Getting old means getting nearer to death. The observational studies reported here show that if you have an expanded somatic blood-cell clone without other haematological abnormalities, you have an increased risk of blood cancer and a doubled risk of cardiovascular death. This is supported by some mouse experiments. So if you have a CHIP in your blood, you may soon have had your chips. Why not celebrate the prospect by visiting the French steak chain (Lyon or Paris) called L’Entrecote, where you will be served a mountain of the best chips in the world.

Watching for 12-20 years equals surgery for early prostate cancer

In the early era of prostate specific antigen testing, from 1994-2002, 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) were randomised to radical prostatectomy or observation. The Prostate Cancer Intervention versus Observation Trial (PIVOT) is a rare example of the right trial done at the right time. Now we have the results from a median 12.7 years of follow up, and all-cause mortality is the same in both groups. “Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years. Disease-related or treatment-related limitations in activities of daily living were greater with surgery than with observation through 2 years.” It may be that surgery confers a small overall benefit if the starting PSA is over 10. But we shouldn’t pay attention to post-hoc analyses that can’t be tested: the default option for localized PSA-detected cancer is clearly to watch and wait, unless the patient chooses otherwise. Best of all, avoid doing PSA tests under most circumstances.

JAMA 11 July 2017  Vol 318

UnBritish choices for depression

All GPs know that only about a third of people respond to the first antidepressant they are given. After that, it’s a process of trial and error. Bupropion is an antidepressant which is quite as effective as other drugs given that name. Aripiprazole on the other hand is classed as an “atypical antipsychotic.” Both drugs have potential interactions with serotonin reuptake inhibitors. So for this ordinary Brit it comes as a surprise that an American trial could randomise depressed patients who were not responding to first choice drugs (mostly SSRIs) to receive add-on bupropion or aripiprazole, or simply get switched to bupropion alone. The participants were overwhelmingly middle-aged men, since they were US Armed Forces Veterans. Add-on aripiprazole caused weight gain and/or akathisia, as expected, but helped depression in 29%, compared to 22% in the bupropion-only group, and 27% in the bupropion-augment group. But don’t try this at home in the UK: neither drug is licensed for depression over here, though it is truly strange that bupropion is only available for smoking cessation.

Does CPAP reduce CVD risk in sleep apnoea?

Continuous positive airway pressure for obstructive sleep apnoea is often wonderfully effective for reducing daytime tiredness, and for luring spouses back to the beds of snorers. The hope is that it will also reduce the cardiovascular risk associated with obstructive sleep apnoea (OSA). This may or may not be true. Pessimists say that OSA is largely due to neck obesity, which in turn is related to central obesity and the so-called metabolic syndrome, so the apnoea is just an epiphenomenon. Others argue mechanistically that CPAP reduces nocturnal hypoxaemia and blood pressure, so it must be a good thing. The randomised trials so far have not shown a cardiovascular benefit reaching statistical significance, according to this systematic review and meta-analysis, which is dominated by one large trial called SAVE. In that trial, high-risk patients only used CPAP for a mean 3.3 hours per night, so the jury remains out for other patient groups who may use their machines more effectively. I agree with the editorial which says that the question is unanswered—”it is far too soon to say.”

JAMA Intern Med  July 2017

Carry on Sharing Medicine

After my initial introductory piece last week, the Sharing Medicine series proper gets going with an illustrated example of the basic processes of shared decision making. The example is an old man with heart failure facing the choice of having an implanted cardioverter-defibrillator. The clarity of the narrative hides the real complexity of the decision, which is really about mode of death in an end-stage condition. So if you’re interested in reaching decisions with patients—which you should be, as it’s your job—read this piece carefully, and give it some thought. How can we conduct these discussions more skilfully? What knowledge resources should patients and clinicians share to inform this kind of dialogue?  Who should be the partners here—the cardiologist? The GP? The heart failure nurse? The family?

Ann Intern Med  11 July 2017 

Coffee: wake up and smell the confounding

Two big observational studies suggest that coffee drinking is associated with longevity. You drink coffee, and would like to believe good things about coffee. So your first instinct, as you sip the aromatic liquid and feel the caffeine buzz, is to rejoice. But you are a scientist: look closer. The first study is of the EPIC cohort, where E stands for European. Over half a million Europeans recorded their coffee consumption on one occasion. Those who claimed to drink the most had a slightly higher rate of survival at 16.4 years than those who said they did not drink coffee. There was a markedly lower rate of death from gastrointestinal causes. Epidemiologically, it’s quite intriguing, but I defy anyone to conduct a randomised trial for a sufficient length of time. So at best we can say that coffee drinking is unlikely to be harmful. The same message emerges from a study of 185 855 Americans of mixed ethnicity, after adjustment for confounders. The coffee drinkers were a bit less likely to die over a period of 16 years, compared with non-coffee-drinkers. Don’t let your coffee get cold while you muse on these matters. Observational evidence is observational evidence and will never be anything more.

The Lancet 15 July 2017  Vol 390

The global burden of childhood RSV

Human respiratory syncytial virus (RSV) is among the most tiresome of germs. Pretty well everybody gets it in the first two years of life, but it provokes such a weak immune response that it’s even possible to get it twice in the same season. And in some children—especially small babies—it can cause severe bronchiolitis, and even lead to death. In others it provokes a response that leads to wheezing and crackling with every cold they encounter. This global survey estimates that in 2015, RSV resulted in about 3·2 million (2·7–3·8) hospital admissions, and 59 600 (48 000–74 500) in-hospital deaths in children younger than 5 years. These figures are based on extrapolation and may be some way out, but the fact remains that there’s nothing more that we can do for RSV now than when I worked on the paediatric wards 40 years ago. Producing an effective and lasting vaccine is an urgent challenge—especially since the harm that RSV causes is not confined to children.

Men B vaccine reduces gonorrhoea

Neisseria meningitidis is closely related to Neisseria gonorrhoeae, and they share 80-90% of the same genetic material. A record linkage study from New Zealand shows that after the introduction of an outer membrane vesicle meningococcal B vaccine (MeNZB) for young New Zealanders, rates of gonorrhoea fell by 30%. This is good news, because gonorrhoea is getting increasingly difficult to treat, and if even this rate of protection continued, it would decline rapidly. Following the development of a really effective gonococcal vaccine, a diplococcus emerging from the urethra could become as unlikely as a diplodocus.

The BMJ 15 July 2017  Vol 358

High blood pressure in pregnancy and after

When faced with blood pressure measurements, I get increasingly tetchy with age. I avoid the term “hypertension,” which sounds like a disease, and I even have trouble with “elevated” and “high.” Here’s a prime example of the confusion these terms can cause: “In the year after delivery, women with a hypertensive disorder of pregnancy had 12-fold to 25-fold higher rates of hypertension than did women with a normotensive pregnancy. Rates in women with a hypertensive disorder of pregnancy were threefold to 10-fold higher 1-10 years postpartum and remained twice as high even 20 or more years later.” These are population statistics from Denmark.

They give relative figures for risk of a risk factor. What I’m looking for are absolute figures for events. We surmise that lifetime blood pressure is related to risk of cardiovascular events, especially for stroke and heart failure in late life. We know something about how this added risk is lowered (though not abolished) by certain types of treatment. How do we guide individuals through choices of intervention? The next article gives us a rough clue. It’s from the Nurses’ Health Study and it shows that weight control is linked with a lowered risk of “chronic hypertension” after a rise in blood pressure during pregnancy (HDP). Apart from BMI control, “There was no clear evidence of effect modification by physical activity, DASH diet, or sodium/potassium intake on the association between HDP and chronic hypertension.” But then the conclusion states: “This study suggests that the risk of chronic hypertension after HDP might be markedly reduced by adherence to a beneficial lifestyle.” No it doesn’t. It just suggests “don’t get fat.”

Plant of the Week: Clematis integrifolia

To a gardening beginner, the idea of a non-clinging clematis may seem bizarre. With so many different ones that support themselves, why buy ones that don’t? The answer is to do with blueness and beauty, and the time of flowering.

Look at your garden now. The lawn is a bit yellow in places and the borders are full of plants that need a bit of clipping. There are some white flowers, and some yellows, and an increasing number of oranges and reds. Apart from the odd hydrangea (good luck with those), the shrubs are all leaf and no flower. There is little freshness anywhere.

Now go to a specialist clematis nursery. If you are lucky, you will see a variety of herbaceous plants in full flower. One of the best has twisted clear azure flowers and—with a little help from the odd tie—it’s ready to clamber up any medium sized subject that is getting past its best. This is the plain form of C integrifolia. Such blue flowers tumbling out of a medium sized shrub give a unique and wonderful effect in the middle of summer. It comes in a white form too, and a new pink variety called Carol Klein, which looks lovely in pictures. All gardens need these.