Ann Robinson’s research reviews—6 March 2020

Ann Robinson reviews the latest research from the top medical journals

Annals of Internal Medicine

Should breast cancer screening be extended to older age groups?

One in eight women in developed countries will develop breast cancer and for most, it will be a disease of old age. One third of breast cancer deaths are in women who are first diagnosed after the age of 70, but in the UK, we only offer routine mammography screening from 50-70 years (though a trial is underway to investigate extending it to 47-73 year olds.) In this important study, García-Albéniz and colleagues used observational data to model the impact of screening in over 1 million US women aged 70-84 who had a life expectancy over 10 years and had never had breast cancer. They found a modest benefit in screening women aged 70 to 74 years (-1 breast cancer death/1000 women over 8 years compared to women who no longer had screening) but not in older women. The design of this study relied on observational data but a prospective randomised trial would be expensive, time consuming and possibly unethical given that mammography screening is now widely, though not universally, accepted as routine.


Interferon doesn’t help ARDS

Acute respiratory distress syndrome (ARDS), a life threatening form of respiratory failure, can be a complication of infections such as covid-19. There is no specific treatment for ARDS, so this multicentre European study into a potential role for interferon (IFN-β-1a) is timely. Unfortunately, in adults with moderate or severe ARDS, six days of treatment with intravenous IFN-β-1a resulted in no significant difference in a composite score that included death and number of ventilator-free days over 28 days, compared to placebo. Interferon has a plausible role as it increases extracellular adenosine that regulates endothelial cell permeability which is a key feature of ARDS. So why didn’t it work? It could be that the study was underpowered to show clinical improvement or that the effect of interferon was inhibited by the extensive use of steroids in the trial. Or it just doesn’t work and the quest for an effective treatment for ARDS lies elsewhere.

Which type of screening is best for dense breasts?

What’s the best method of screening to detect invasive breast cancer in women with dense breasts? Comstock et al conducted a cross-sectional study with longitudinal follow-up of 1444 women at average risk of breast cancer. The participants had abbreviated breast magnetic resonance imaging (MRI) and digital breast tomosynthesis (DBT), which is a form of 3-D mammography. The study found that abbreviated breast MRI detected substantially more invasive cancers (11.8 per 1000 women) than DBT (4.8 per 1000 women). Adding DBT to MRI screening didn’t confer any advantage; no invasive cancer was identified by DBT alone or as interval cancer during follow-up. The study has limitations: there’s no evidence about mortality or overdiagnosis as that would need larger randomised controlled trials with follow up of 15-20 years. Surrogate endpoints such as tumour stage at diagnosis or interval cancer rates can give us proxy data. MRI appears to be better for women with dense breasts and DBT doesn’t seem to add much other than cost, radiation, and hassle.


Covid-19: rapid spread of research

The rapid spread of covid-19 is being matched by a proliferation of published research. This report of over 1000 patients treated in Chinese hospitals with laboratory-confirmed covid-19 shows that the median age was 47, 6% needed ventilation, and 1.4% died. One quarter had no contact with Wuhan or its residents. Median incubation period was 4 days. The most common symptoms were fever (over 37.5 degrees C) and cough, but around a fifth didn’t develop a fever and a third didn’t have a cough. 83% had a low lymphocyte count and 56.4% had an abnormal CT chest with ground glass opacity. I was interested that more than half were given intravenous antibiotics and over a third received oseltamivir (Tamiflu) which is of unproven efficacy against this new virus. The data in this study come from people who came to hospital, and so may well represent more severe cases than those who are  out and about without ever realising that they are harbouring and spreading the virus.

JAMA Internal Medicine

Toppling prescribing cascades

Here’s a curious question; are older (over 66 years) adults who start on a calcium channel blocker more likely to be subsequently prescribed a loop diuretic within the next three months than those who began taking other medications such as an ACE inhibitor? In this Canadian study of over 40,000 people with hypertension, the answer was “yes”. Presumably the diuretics were usually added to counter the ankle swelling that so often results from a calcium channel blocker. Around double of those who started on calcium channel blocker’s like amlodipine were then prescribed a loop diuretic compared to the control group, although absolute rates were still only 1.4% in the CCB group. (Yet another example of the shock horror effect of a relative risk sounding much less sexy when stated as an absolute risk.) Perhaps more telling was the fact that most of those given loop diuretics in addition to amlodipine, were still on them a year later. It’s so much easier to start a drug than stop it. This example of a “prescribing cascade” with the associated harms of polypharmacy needs to be recognised and avoided, say the authors.


Chronic kidney disease: a worldwide challenge

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. Most data on the impact of CKD come from high income countries. The Global Burden of Diseases, Injuries and Risk Factors study (GBD) is a major attempt to quantify the global, regional and national prevalence and impact of CKD which affects 9.1% of the global population. It’s becoming a growing cause of death because of ageing, hypertension, and diabetes. Actions required include raising awareness among the public and healthcare providers, educational programmes, better management of early stage CKD and treatment facilities for end-stage kidney disease, especially in low and middle income countries. Some challenges for this study are that countries with the highest burden of CKD often have the poorest data collection, prevalence rates may be overestimated as the diagnosis is often made on the basis of a one off measurement of eGFR (ideally it should be rechecked over 3 months) and finding the cause of CKD is often difficult. 

Ann Robinson is an NHS GP and health writer and broadcaster