Alex Nowbar’s weekly journal review—7 February 2020

Alex Nowbar reviews the latest research from the top medical journals.

The Lancet

The coronavirus 99

After several cases of pneumonia of unknown aetiology in December 2019, a novel coronavirus was identified and named 2019-nCoV. In their single centre, retrospective study, Chen et al analysed data from the first 99 cases admitted to Jinyintan Hospital in Wuhan, China. Of these 99 patients, 82 had a fever at presentation, 81 had a cough, and a third had shortness of breath. Many presented with organ failure, 17 had acute respiratory distress syndrome, and 74 had bilateral pneumonia on imaging. They all received antivirals, and most received antibiotics. By 25 January 2020, 31 had been discharged from hospital while 11 had died. From such a small sample size, few conclusions can be drawn on who is most likely to be affected, but in this study, it was mostly men, particularly those who smoked or had an underlying chronic condition.


Coronavirus—a perfect storm?

Li et al analysed the first 425 cases of 2019-nCoV pneumonia in Wuhan, specifically looking at the epidemiology. The key point from this analysis was the source of the new virus—a live animal and seafood market. The mean incubation period was five days. Critically for this epidemic, the virus is easily transmitted from human to human and has a basic reproductive number of 2.2. The basic reproductive number is the number of further cases one case generates on average during the infective period assuming an uninfected population. If this is greater than 1, it is very easy for the virus to spread. So it is no understatement that 2019-nCoV is a global emergency. More work in this area is emerging every day as the situation evolves.

A small step for acute kidney injury

Unless you are a renal physician, acute kidney injury (AKI) can make you feel impotent. We offer little else other than monitoring. This American study describes a protein with a pivotal role in the pathogenesis of AKI which one day could lead to a giant leap in prevention of this condition. The protein is called soluble urokinase plasminogen activator receptor (suPAR). High suPAR levels before coronary angiography, cardiac surgery and ITU admission were associated with AKI. The sample size tested was modest – 3827 for angiography, but only 250 for cardiac surgery and 692 for those who were critically ill. The link with high suPAR was also confirmed in their mouse model of suPAR overexpression. The animal model also revealed the mechanism of injury might be heightened energetic demand and mitochondrial superoxide generation. The distant hope is that this evidence for the role of suPAR could be used to develop a therapy to prevent and/or treat AKI.

The ugly head of cancer screening

The NELSON trial randomised 13195 men aged 50-74 years with a significant smoking history to either lung cancer screening with computed tomography (CT) or no screening. An interesting feature of the screening programme used in this study was the way indeterminate results were handled—by assessing growth rate on imaging. The headline finding was lower rates of lung cancer deaths in the screening group. The rate ratio of deaths from lung cancer in the screening group compared with the control group was 0.76. This is impressive at first glance, but is it enough? To determine whether to offer lung cancer screening in the manner trialled, we need to consider whether there is a benefit for overall survival and whether there is overall harm from the downstream testing triggered by CT findings. These data are convincing in their ability to detect lung cancers at an earlier stage, when perhaps they are more amenable to curative surgery, and this did seem to save lives from cancer. It is unclear if this offsets the harms of false positives and subsequent testing since reporting of the harms is lacking.

Pneumothorax and much-needed randomisation

Brown et al randomised 316 patients with moderate to large primary pneumothorax to either interventional or conservative management. We have essentially just been assuming intervention is the only form of management even though we would rather avoid them. Chest drains are painful and carry significant risks. The primary endpoint was complete radiographic resolution at 8 weeks. The study boldly concluded that conservative treatment was noninferior to interventional management. Before patients are denied interventional management, we must bear in mind two features of this study. First, patients were aged 14 to 50 and had unilateral pneumothorax. Second the study was unblinded and this could have biased patient and clinician behaviour thus influencing the outcome. The authors even state “Treating clinicians were more likely than the independent radiologists who were unaware of the trial-group assignments to report full radiographic resolution in the group receiving interventional management, which biased the primary-outcome findings in favour of interventional treatment.” I appreciate that placebo-controlling an intervention is very challenging but one has to randomise to test its efficacy.

Annals of Internal Medicine

Heart failure discharge services

Blum et al performed a rigorous cost-effectiveness analysis of three types of post-discharge heart failure transitional care—disease management clinics, nurse home visits, and nurse case management. These data were from observational studies as well as randomised controlled trials, so this places significant limitations on the findings. And the services assessed were diverse and varied in content and delivery. Nevertheless, compared with standard care, all types of transitional care were more effective than standard care and cost more than standard care. Nurse home visits were the most cost-effective. Readmission following a hospital stay for heart failure is a significant challenge for healthcare services and patients and this study gives credence to the idea that transitional care for heart failure should be part of standard care, an idea which in the UK is already well established.


Dropping isolated diastolic hypertension

I am always ready to delete a clinical label from the medical armamentarium. Isolated diastolic hypertension (IDH) is a great one to be able to drop because it had created a market for antihypertensive therapy that could well have done people more harm than good in terms of anxiety and pill burden. Using various observational studies set in the community, McEvoy et al assessed cardiovascular outcomes in thousands of people with isolated diastolic hypertension as defined by two guidelines (80 mm Hg and ≥90 mm Hg) compared with normotensive participants. The lower threshold was included in the most recent US guideline with little to no evidence. Using the lower threshold, the prevalence of IDH was 6.5%—that’s a lot of people to potentially medicate. By the higher threshold, the prevalence was only 1.3%. The result of this study was that IDH was not associated with increased risk of cardiovascular outcomes. This doesn’t mean that diastolic hypertension isn’t prognostically important though. These results only apply to raised diastolic blood pressure when the systolic blood pressure is in normal range.

JAMA Internal Medicine

Cardiac test clash

The common scenario of discordant test results poses the question of which test to “believe”. Daubert et al studied over 15,000 patients who had had both ECG and exercise stress echo from a single centre in the US. They were interested in the rate of major adverse cardiac events in those with positive ECG and negative stress echo compared to those with both positive ECG and positive stress echo. Negative stress echo is considered to be associated with a better prognosis so it is important to understand the significance of the positive exercise test with a negative stress echo. People with submaximal exercise tests were excluded from the analysis. The cardiac event rate in positive ECG and negative stress echo group was 14.6%, 8.5% if both tests negative and 37.4% if both tests positive. This clear stratification of risk indicates a prognostic role for abnormal exercise ECG. It also calls into question the idea that regional wall motion abnormalities abnormalities occur before ST segment changes or angina.

Risk stratification after acute kidney injury

As we simply watch the renal numbers wobble up and down in despair, Hsu et al have been busy assessing the association of post-AKI proteinuria (specifically the urine albumin to creatinine ratio) with increased risk of future loss of renal function. The ASSESS-AKI Study is a prospective matched cohort study set in 4 US centres with 5 years of follow-up. Proteinuria after AKI was found to be useful for stratifying risk of kidney disease progression. The authors conclude that proteinuria measurements after AKI should become more widespread but they acknowledge limitations of their study such as small numbers of severe AKI and lack of a validation cohort. More precise prediction of future kidney disease may not enable us to prevent it but at the very least it is useful for monitoring and planning.

Alex Nowbar is a clinical research fellow at Imperial College London

Competing interests: None declared