The content of this website is intended for healthcare professionals only

Previous Posts

1 2 3  > 

On The Pulse - March 2018

On The Pulse

Tertius Lydgate

Friday, 23 March 2018

Add to PDP Tracker

Increasing inhaled glucocorticoids in asthma exacerbations
Two studies in the NEJM investigated the dose-related benefits of increased inhaled glucocorticoids in asthma exacerbations. The first study, which involved 254 eligible children, 5-11 years, showed that in children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose (fluticasone 220 μg per inhalation, two inhalations twice daily) at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth (−0.23 cm per year). On the other hand, a separate randomised trial involving 1,922 eligible adults and adolescents with asthma showed that a personalised self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids, when asthma control started to deteriorate, resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. In the quadrupling group, 420 participants (45%) had a severe asthma exacerbation in the year after randomisation compared with 484 (52%) in the non-quadrupling group (adjusted HR for the time to a first severe exacerbation 0.81; 95% CI, 0.71 to 0.92).

Five types of diabetes
Although diabetes is classified between type 1 and 2, type 2 has been seen to be highly heterogeneous. A data-driven cluster analysis in The Lancet involving 8,980 patients with newly diagnosed diabetes allowed researchers to identify five subgroups. These replicable clusters of patients with diabetes had significantly different patient characteristics, disease progression and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes. The authors conclude that this new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thus representing a first step towards precision medicine in diabetes.

Antidepressants more efficacious than placebo
While antidepressants are widely used for major depressive disorder, there is a long-lasting debate and concern about their efficacy and effectiveness. Researchers, writing in The Lancet, evaluated 21 antidepressants and placebo in 522 trials involving 116,477 participants. They found all antidepressants were more efficacious than placebo, with odds ratios (ORs) ranging from 2·13 (95% credible interval 1·89–2·41) for amitriptyline to 1·37 (1·16–1·63) for reboxetine. Head-to-head efficacy comparisons showed that agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were distinctly more effective than the other antidepressants; whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were less effective. When factoring for acceptability, an accompanying editorial points out that fluvoxamine, reboxetine, and trazodone had a poor profile for both efficacy and acceptability whereas agomelatine, escitalopram and vortioxetine emerged as preferable options. The authors call for further research to predict personalised clinical outcomes, e.g. early response or specific side-effects, and estimate comparative efficacy at multiple timepoints.

Fluoroquinolones and aortic aneurysm or dissection risk
Concerns have been raised in recent studies that fluoroquinolones, which are commonly-used antibiotics globally, could be associated with an increased risk of aortic aneurysm. A nationwide, register-based cohort study in Sweden looking at 360,088 treatment episodes of fluoroquinolone use (78% ciprofloxacin) and propensity score matched comparator episodes of amoxicillin use (n=360,088) showed there was a 66% increased rate of aortic aneurysm or dissection associated with oral fluoroquinolone use within a 60-day risk period from start of treatment. This result corresponded to an absolute difference of 82 cases of aortic aneurysm or dissection per 1 million treatment episodes and the association appeared to be largely driven by aortic aneurysm. The authors, writing in the BMJ, point out that although the absolute risk increase was relatively small, it should be interpreted in the context of the widespread use of fluoroquinolones. “Before the results are used to guide clinical decision making, the collective body of data on this safety issue should be scrutinised by drug regulatory authorities and weighed, together with other safety issues with this drug class, against the benefits of treatment; this will support appropriate clinical treatment recommendations,” they say.

Predicting those most vulnerable to cold weather
As NICE guidance recommends that GPs use routinely available data to identify patients most at risk of death and ill health from living in cold homes, researchers, writing in BJGP, investigated if primary care data could predict cold-related mortality. They conducted a case-crossover analysis on 34,777 patients aged ≥65 years from the Clinical Practice Research Datalink. The average three-day temperature for the 28th day before/after date of death were calculated, and comparisons were made between these temperatures and those experienced around the date of death. Lower three-day temperature was associated with higher risk of death (OR 1.011 per 1°C fall; 95% CI = 1.007 to 1.015). No modifying effects were observed for sociodemographic characteristics, clinical factors, and house energy efficiency characteristics. Analysis of winter deaths for causes typically associated with excess winter mortality (N=7,710) showed some evidence of a weaker effect of lower three-day temperature for females (ROR 0.980 per 1°C, 95% CI = 0.959 to 1.002), and a stronger effect for patients living in northern England (ROR 1.040 per 1°C, 95% CI = 1.013 to 1.066). The author concluded it is unlikely that GPs can identify older patients at highest risk of cold-related death using routinely available data, and NICE may need to refine its guidance.

Botulinum toxin A
Authors writing in BMJ Case Reports present three cases of patients with severe Raynaud’s phenomenon in the toes, secondary to scleroderma, with associated complications such as ulceration, gangrene and possible amputation. The diagnosis of Raynaud’s syndrome and scleroderma was established according to the 2010 American College of Rheumatology and European League Against Rheumatism criteria. Patients were treated with 10 units of botulinum toxin injected into each foot. Two millilitres were injected into the base of each toe in both the left and right feet. Six weeks post-injection into the toes, patients reported an improvement of cold intolerance, colour change and frequency and severity of Raynaud’s attacks. The effects were reported to last up to five months. The authors say that, to their knowledge, these are the first reported cases of the treatment of Raynaud’s phenomenon in the toes, that is refractory to medical management, with botulinum toxin A.

NHS Health Check programme  
Research published in PLOS Medicine suggests that the current NHS Health Check cardiovascular disease prevention programme is contributing to improvements in health and reducing health inequalities, but that feasible changes in the organisation of the programme could result in more than a three-fold increase in health benefits. Using a longitudinal microsimulation model, the researchers estimated that the current NHS Health Check programme is preventing approximately 300 premature deaths (before 80 years) and resulting in an additional 1,000 people at age 80 years being free of cardiovascular diseases, dementia, and lung cancer each year in England. The benefits were greatest for people living in more deprived areas. The authors suggest however that making feasible changes to the delivery of the existing programme is likely to result in valuable improvements in health. For example, a strategy that combines extending eligibility to those with pre-existing hypertension, extending the upper age of eligibility to 79 years, increasing uptake of health checks by 30%, and increasing treatment rates amongst eligible patients 2.5-fold could result in at least a three-fold increase in benefits compared to the current programme.

Custom-made foot orthoses for heel pain
Plantar heel pain (PHP) accounts for between 11% and 15% of all foot symptoms that require medical attention in adults and for 8%–10% of all running-related injuries. There is a lack of consensus on which treatments are most effective but, despite a lack of evidence, foot orthoses are often recommended. A systematic review in the British Journal of Sports Medicine analysed 20 existing randomised controlled trial studies, investigating eight different types of foot orthoses, and involving a total of 1,756 patients with PHP. It revealed no difference for pain at short term between custom orthoses and sham orthoses (mean difference (MD) 0.22 (95% CI−0.05 to 0.50)), custom orthoses and pre-fabricated orthoses (MD 0.03 (95% CI −0.15 to 0.22)), or between pre-fabricated orthoses and sham orthoses (MD of 0.26 (95% CI −0.09 to 0.60)). Most of the studies analysed had reported a significant improvement over time in patients treated with orthoses as well as patients treated with other conservative interventions – probably due to the fact that plantar heel pain tends to improve after 12 months. The authors conclude clinicians should be reserved in prescribing foot orthoses in all patients with PHP and take factors like patient preference and adherence into account.

Author's Image

Tertius Lydgate

Originally from Northumberland, Tertius Lydgate studied medicine in Edinburgh, London and Paris. There he developed a special interest in communicable diseases and hoped to make great advances in treating and preventing them. But, after a promising start in a provincial centre of excellence in middle England, he was forced by circumstances (please, don't inquire) to abandon his high ideals. He now scrapes a living by pouring cold water on the over-enthusiastic at his private cryohydrotherapy clinic. Dreaming of the contributions he once hoped to make himself, he finds consolation in the latest medical journals and is happy to share his discoveries with his readers. He thinks that his creator, George Eliot, would have approved.
Registered in England and Wales. Reg No. 2530185. c/o Wilmington plc, 5th Floor, 10 Whitechapel High Street, London E1 8QS. Reg No. 30158470
Twitter Facebook
A Wilmington Company