Ann Robinson’s research reviews—10 May 2019

Ann Robinson reviews the latest research from the top medical journals

Annals of Internal Medicine

Olfactory loss and higher risk of mortality

Older people often say that things don’t smell (or taste) like they used to. Poor olfaction has been linked to higher mortality. You would think that is because people who have lost their sense of smell are already in poor health, with neurodegenerative conditions such as Parkinson’s disease or dementia. But this cohort study finds that the opposite is true—poor olfaction is only an independent predictor of higher mortality among healthy people. Those in poor health are more likely to die overall, but their sense of smell doesn’t help to predict their risk. Liu et al enrolled 2289 older people and used the objective Brief Smell Identification Test. Over half of the participants had died within the 13 years of follow-up; those who had poor olfaction had a 46% higher cumulative risk of dying at year 10, and a 30% higher risk at year 13. But the increased risk was only seen among those who were in good health at enrolment, not among those who were already unwell. The mechanism is still unclear.  Olfactory loss in healthy people may prove to be an important predictor of mortality, but I’m not sure what practical benefit there is for patients in knowing that.

Heartening news?

Generations of families are affected by hypertrophic cardiomyopathy, an autosomal dominant condition caused by mutations in genes coding for sarcomere proteins in the heart. Seventy percent of hypertrophic cardiomyopathy is obstructive and causes debilitating symptoms of breathlessness on exercise, fatigue, and chest pain. Current treatments (beta-blockers, calcium channel blockers, and surgical interventions) are far from perfect. So there is interest in a brand new drug, Mavacamten, that modulates cardiac myosin in the hope of reducing left ventricular contractility. This tiny (21 patients), 12 week, pharma-funded proof of concept, open-label study  with no placebo arm, found that Mavacamten was generally effective and safe with a marked fall in postexercise left ventricular outflow obstruction measures and improvement in symptoms. Two larger studies are now underway.


Wait and see

Good news for people living with diabetes who currently have good vision but are told they have signs of macular oedema (centre-involving diabetic macular oedema). A randomised controlled trial asked whether such people would be better off being kept under observation or having intravitreal injections of aflibercept (which blocks vascular endothelial growth factor) or laser photocoagulation. There was nothing significant to choose between the three options. After two years, 16-19% of participants had a loss of visual acuity of at least five letters. They were all offered treatment with aflibercept. However, unless visual acuity worsens, observation without treatment may be a reasonable strategy, say the authors. This will be reassuring for clear sighted people with centre-involving diabetic macular oedema and may avoid unnecessary treatment.


Aortic valve replacement: the best approach

Aortic valve replacement is the only effective treatment for severe, symptomatic aortic stenosis, and there are two ways of doing it: transcatheter aortic valve replacement involving transfemoral placement of a balloon-expandable or self expanding valve, or surgical aortic valve replacement. For intermediate to high risk patients, there is not much difference in outcome. But if you are at low surgical risk, which would you opt for? Mack et al found that the patients randomised to balloon-expandable transcatheter aortic valve replacement fared better at one year in terms of the primary composite endpoint (death, stroke, or re-hospitalisation) than those who had surgery (8.5% v 15.1%). Incidentally, how useful is a composite that mashes up death rate and readmission rates?

Another study by Popma et al, published on the same day, looked at non inferiority of TAVR using a self-expanding supra-annular bioprosthesis compared to surgery in similarly low surgical risk individuals with severe aortic stenosis. There was no difference in severe stroke or death rates after two years (5.3% v 6.7%). Two caveats; women, people with bicuspid valves and poor ventricular function were under or un-represented in both trials. And the long term durability of transcatheter bioprosthetic valves is still unknown. But on the basis of these two studies, I imagine that most people, especially those over 70,  would certainly choose TAVR over surgery.

JAMA Internal Medicine

Glomerular filtration rate estimates—all methods are equal

Methods of estimating glomerular filtration rate may not be the sexiest subject, but the procedure is essential in the diagnosis and management of chronic kidney disease. It’s not practical to measure glomerular filtration rates directly using methods such as inulin clearance, so the various ways of calculating an estimated glomerular filtration rate need to be as close as possible to the true value. There are several different equations in use, and the question is whether the newer methods trump older ones. This single centre, cross-sectional study found no significant differences between four methods used in patients over 65 years old, and all were of reasonable accuracy compared with the reference methods.


Undetectable means untransmittable

Among gay couples, if one is HIV positive and taking suppressive antiretroviral therapy and the other is HIV negative, what is the risk of transmission to the seronegative partner if they have condom-less sex? This study finds that, if HIV viral load is fully suppressed, the risk of transmission to a seronegative partner is effectively zero. Any new cases of HIV infection (15 in this study) were not phylogenetically linked to the couple. This is the same result as previously found among female partners of HIV positive men. The message is neatly summed up as U=U (undetectable means untransmittable) and reinforces the need for HIV infection to be diagnosed and treated as early as possible to avoid transmission to seronegative partners.


Prematurity and kidney care

Swedish researchers looked at the records of over 4 million babies born between 1973-2014 in the sort of National cohort study that Sweden excels at. They wanted to know whether being born preterm (<37 weeks) increases the risk of developing chronic kidney disease (CKD) at a young age. Only 0.1% (4305 people) had a recorded diagnosis of CKD; being born before 28 weeks gestation increased the risk by 2-3 times (although of course the absolute risk remains very low.) Even being born a little early, at 37-38 weeks increased the risk of early CKD. The data are imperfect; there’s no information on CKD severity, the study started before ultrasound could provide accurate gestational age and follow up was up to a maximum age of 43. But it’s a useful pointer that people born prematurely need to take care of their kidneys with regular blood pressure and blood and urine checks, avoiding nephrotoxic drugs and thinking carefully before they donate a kidney altruistically.

Ann Robinson is an NHS GP and health writer and broadcaster