Alex Nowbar’s weekly review—15 November 2019

Alex Nowbar reviews the latest research from the top medical journals

Annals of Internal Medicine

Favour faecal transplant

Faecal transplant is an established treatment for recurrent clostridium difficile infection. But does it reduce the risk of bloodstream infections? C diff is thought to increase the risk of bloodstream infections through use of vancomycin disrupting intestinal bacteria or by directly impacting the microbiota. So restoring the faecal microbiota with tranplant could theoretically modify this risk. Ianiro et al used a cohort design to compare the incidence of bloodstream infection between those treated with transplant (109 patients) and those treated with antibiotics (181 patients) in one unit in Italy over 5 years. There was a much lower incidence in the former. They used clever matching techniques to try to adjust for confounding. With the caveat that they are not from a randomised study, these data suggest that faecal transplant reduces the risk of bloodstream infections. 


Open-angle glaucoma gene

GWAS is an acronym that strikes fear into my heart (fear of people finding out I don’t know anything about genetics). It stands for genome wide association study. It’s less terrifying than it sounds. It’s an observational study comparing the human genome for single nucleotide polymorphisms in people with and without the condition (in this case people over age 40 with and without primary open-angle glaucoma). Using a “discovery set” of 2320 people with the condition and 2121 without, Hauser et al identified variants at amyloid-β A4 precursor protein-binding family B member 2 as being associated with primary open-angle glaucoma. They then confirmed this on a “validation set” of 6937 affected individuals and 14 917 unaffected individuals. The association was only present in people of African ancestry which could be useful in assessing risk in different populations. Perhaps more interestingly, the association of this amyloid-β allele suggests that clearance of amyloid-β may have a role in the development of glaucoma, thus presenting a new therapeutic avenue for exploration.

Chronic kidney disease risk prediction

On the surface this study sounds exciting and game-changing and all of that. But what is so special about an equation to predict 5-year risk of chronic kidney disease? How is it clinically useful? Refining risk prediction is only useful if knowing the risk more accurately helps to improve the outcome. While this study’s design is impressive (such as millions of patients, comparisons with existing models), it puts the cart before the horse by delivering a mechanism for identifying those at risk when we have not established why this is good. And even if there was an intervention to reduce the risk, this study only looks at eGFR reduction when patients and clinicians are likely to be more interested in risk of kidney failure, cardiovascular disease or death.


Vaping related lung injury

E-cigarette users and clinicians have been quite alarmed by the “outbreak” of vaping related acute lung injury in the US with almost 2000 identified cases in just over 6 months. Understanding of this condition is evolving. Blagev et al prospectively analysed 60 cases across 13 hospitals or outpatient clinics in Utah between June and October 2019. Affected people were young and without comorbidities. By definition, they had had vaping exposure to nicotine, tetrahydrocannabinol, or both. They presented with respiratory, gastroenterological and constitutional symptoms. Thirty three of them were admitted to intensive care and ten received mechanical ventilation. There were two deaths although the lung injury was probably only contributory not the cause of death. On the other hand, six were treated as an outpatient. Self reported amounts of vaping exposure were very varied and the types of e-liquid used also varied although almost all used pre-filled cartridges. Most patients received antibiotics, steroids, and oxygen but it was steroids that their clinicians believed to be the effective treatment. Pneumothorax and pneumomediastinum were also quite common features. This study also describes an admirable approach to managing the outbreak using an integrated health system, formation of a specialised task force, and centralisation of data collection and reporting mechanisms to accumulate experience across centres.

Tricuspid valve repair

From the makers of MitraClip, TriClip has arrived. Eighty five patients with at least moderate tricuspid valve regurgitation and symptoms received a TriClip in this study. TriClip is a minimally invasive transcatheter tricuspid valve edge-to-edge repair system. This study tells us that the technique is feasible in that it reduces the amount of regurgitation (although regurgitation itself isn’t what matters clinically) and doesn’t seem unsafe based on six month data. There were no strokes for example. No conclusions can be drawn about efficacy for symptoms or other endpoints without a comparator group. Clinical and imaging criteria to receive this device seem quite niche, for example, the co-aptation between the valve leaflets could not be greater than 10mm. This begs the question of how many patients are going to be eligible in real life. This could make a substantial randomised controlled trial challenging. 

JAMA Internal Medicine

Enhancing group medical visits for diabetes

Yancy et al performed a randomised controlled trial of group medical visits plus intensive weight management versus group medical visits alone for glycaemic control and weight loss in 263 people with type 2 diabetes mellitus. Group medical visits are groups of patients meeting to receive education and self-management training of a common chronic condition and have already been shown to lower HbA1c, primarily by medication intensification. This study found that adding weight management (involving a dietician, more frequent visits, low-carbohydrate nutrition, physical activity, and weight management counseling) produced better glycaemic control and weight loss and a reduction in diabetes medication use at 48 weeks. This model may be worth pursuing.


Reducing ventilator-associated pneumonia after cardiac arrest

This double-blind randomised controlled trial of 198 patients at 16 units in France addresses a pertinent intensive care question. Does a two day course of co-amoxiclav upfront (within six hours of return of spontaneous circulation) reduce the rate of ventilator-associated pneumonia? Yes. It reduced the rate from 34% to 19% making it a positive trial for its primary outcome. However it did not improve the number of ventilator-free days, length of stay or 28-day mortality. Neurological outcomes were also no different. Taken together the data support the use of the antibiotic if you assume that reducing ventilator-associated pneumonia is likely to be beneficial. It was probably underpowered to look at these secondary outcomes (event rates were much lower than they anticipated in their sample size calculation). It is also worth noting that the population studied were people who had a cardiac arrest with an initial shockable rhythm, were being treated with targeted temperature management (32 to 34 degrees), were not on ongoing antibiotic therapy and were not colonised with multidrug-resistant bacteria. In other words, these were not allcomers to intensive care.

Anti-itching drug in haemodialysis

Difelikefalin is the new unpronouncable kid on the block. It was compared to placebo in 378 patients in the double-blind randomised controlled trial KALM-1 for treating moderate to severe uraemic pruritus. This condition is debilitating, but hard to treat. Difelikefalin showed a promising reduction in itch intensity and itch-related quality of life although side effects included diarrnoea, dizziness, and vomiting. So what is difelikefalin? Why, it’s a peripherally restricted, selective kappa opioid receptor agonist of course! Ok so what have opioids got to do with pruritus? Well, one possible mechanism for the itch in chronic kidney disease is dysregulation of the body’s internal opioid system. This drug is designed not to access the central nervous system. This peripheral restriction is achieved with a hydrophilic small-peptide structure preventing it from passively diffusing across membranes. Therefore the drug should mostly be activating kappa opioid receptors on peripheral neurones. Amazingly it worked within a week and the effect persisted to the end of the study at 12 weeks. This is excellent news for patients with this distressing condition.

Alex Nowbar is a clinical research fellow at Imperial College London