Alex Nowbar’s journal reviews—21 May 2021

Alex Nowbar reviews the latest research from the top medical journals

Ovarian cancer screening is out

The UK Collaborative Trial of Ovarian Cancer Screening is a randomised trial comparing annual screening with no screening in hundreds of thousands of women. There were two screening arms (transvaginal ultrasound and multimodal) and one non-screening arm. The main finding was that screening was not associated with a reduction in deaths due to ovarian cancer. Ovarian cancer is known to be particularly hard to catch early and is deadly; so screening seemed a natural approach, but it wasn’t effective. This is such crucial evidence because cancer screening is a popular and emotive concept, but if, in such a large sample, it didn’t reduce death then it should not be introduced. That’s not to say that screening doesn’t have the potential to save lives—it would just need to detect the disease earlier to allow treatment that would have a chance to be curative. This trial underscores the importance of randomised trials prior to implementation.

Lancet doi:10.1016/S0140-6736(21)00731-5


Nurse to patient ratios

No one would argue that higher nurse-to-patient ratios are not better for patient care. But you could argue that it doesn’t make sufficient difference to be worth the cost, and the minimum standard is unknown. Unfortunately, this Australian study isn’t a randomised trial comparing nurse-to-patient ratios. Instead it’s an observational study comparing the change in mortality, length of hospital stay, and readmission rates over time between some hospitals that implemented minimum nurse-to-patient ratios and some hospitals that didn’t. Hospitals were not randomly allocated to implement the minimum ratios. This study design means the differences between intervention and comparison hospitals cannot be definitively attributed to the minimum ratios. However, putting that to one side, the findings were that minimum ratios were better for outcomes. I’m all for minimum ratios, but this study design isn’t great for assessing the effect of an intervention even after adjustment for patient and hospital characteristics because it is impossible to exclude unmeasured confounders as the reason for the better outcomes.

Lancet doi:10.1016/S0140-6736(21)00768-6

A new monoclonal antibody for asthma

Tezepelumab has arrived. It blocks “thymic stromal lymphopoietin.” Don’t worry, no one else knows what any of that means either. Suffice to say, thymic stromal lymphopoietin is an inflammatory cytokine implicated in asthma. Tezepelumab reduced asthma exacerbations (the primary endpoint) in a large double-blind randomised trial of people with severe uncontrolled asthma. It also did that rather pleasing thing of improving the secondary outcomes as well, such as lung function and health related quality of life. When an intervention is good on both the primary and secondary outcomes, it really strengthens the findings because it suggests the drug is working how it was expected to work.

N Engl J Med doi:10.1056/NEJMoa2034975

Tympanostomy tube trial

Tympanostomy tubes are yet another intervention assumed to be beneficial. Hoberman and colleagues randomised 250 children with recurrent acute otitis media to tympanostomy tube placement or medical management in a randomised (but open label) trial. There was no difference between groups in rates of acute otitis media at two years (the primary outcome). The medical management group was diluted a fair bit by many undergoing tympanostomy tube placement further down the line, but per-protocol analysis is hard to rely on because it loses the advantages of randomisation. These data do not support the use of the tube, and yet I think we won’t be saying a goodbye to them, as operators and parents alike will still find them mechanistically appealing when a child keeps getting otitis media. This study also provides useful data on the relative adverse effects in the two groups, such as more otorrhoea in the tympanostomy tube group.

N Engl J Med doi:10.1056/NEJMoa2027278

Antibiotics in idiopathic pulmonary fibrosis

It’s gratifying to see the evidence base finally catching up with clinical practice. Prophylactic antibiotics have often been used in idiopathic pulmonary fibrosis. The catching up has now been done in the form of a 513 patient, randomised trial looking at the effect of adding co-trimoxazole or doxycycline to usual care on rates of respiratory hospitalisation and death. Antibiotics didn’t improve outcomes, and the trial was stopped for futility. You could see this as a shame because it means that we aren’t able to improve outcomes. But you could also see it as a blessing that the evidence base has been established now to enable patients not to be prescribed antibiotics (and the accompanying burden thereof) under the false impression that they are protective. You could argue that in the right patients (perhaps those with an increased imbalance in gut bacteria) antibiotics would have helped, but this hypothesis hasn’t been tested and there is little reason to think it would be true. The best feature of this trial is the use of clinically relevant endpoints (as opposed to lung function, which is only a surrogate).

JAMA doi:10.1001/jama.2021.4956

Alex Nowbar is a clinical research fellow at Imperial College London.