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Take a look at a selection of our recent media coverage:
27th September 2021
Cardiovascular diseases (CVDs) cause an estimated 17.9 million deaths every year and globally, account for 32% of all mortalities. Reduced intake of fats, and in particular, saturated fats, has become a central recommendation for many years. For example, the NHS suggests that men should eat no more than 30g per day of saturated fat. In fact, reducing intake of saturated fat has been suggested as a means of reducing cardiovascular events, especially if the fat is replaced with unsaturated fats. However, in recent years, meta-analyses of randomised trials and observational studies found no beneficial effects of reducing saturated fat intake intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although studies linking fact intake and cardiovascular disease have often relied upon self-reported intake, these can be unreliable. This led an international team of researchers, led by The George Institute for Global Health, University of New South Wales, Australia, to investigate the association between serum levels of pentadecanoic acid (15:0), a biomarker for dairy fat intake and both incident cardiovascular disease (CVD) and all-cause mortality in a Swedish Cohort. The 15:0 was measured at baseline together with a series of questionnaires, between 1997 and 1999 and follow-up information was collected until December 2014. The primary outcomes of interest were incident CVD and all-cause mortality which were obtained from death registries and reported as hazard ratios. In addition, the authors included the results of their study in a systematic review and meta-analysis with a number of other studies.
The study included 4,150 adults with a mean age of 60.5 years (51% female) at baseline and who were followed for a median of 16.6 years. During this time there were 578 incident CVD events and 676 deaths (198 due to CVD). Higher serum 15:0 levels were associated with a lower incident CVD (hazard ratio, HR = 0.75, 95% CI 0.61 – 0.93, p = 0.009). However, there was no significant association of 15:0 serum levels with all-cause mortality (p = 0.38).
In the meta-analysis which included 18 studies and 42,736 participants, comparing the highest to lowest serum 15:0 levels, was associated with a 12% reduction in CVD (HR = 0.88, 95% CI 0.78 – 0.99) but as with the single study, there was no association with all-cause mortality.
The authors concluded that higher levels of 15:0, which are related to an increased intake of dairy fats, was associated with a lower risk of incident CVD and that these findings were supported by the meta-analysis. They called for further studies to ascertain the causality of this relationship and the potential role of dairy foods in CVD prevention.
20th September 2021
According to Cancer Research UK, there are around 47,800 new lung cancer cases each year and approximately 35,100 deaths, which equates to 96 deaths every day. Furthermore, Cancer Research UK estimates that 79% of lung cancer cases in the UK are preventable with 72% caused by smoking. With such a high incidence of not only cases, but more importantly, preventable cases, there is an urgent need for effective screening methods, especially among individuals who are deemed at high risk such as smokers. In a 1999 study, a low computed-tomography (CT scan) was shown to greatly improve the likelihood of detecting small, non-calcified nodules and hence lung cancer, at an earlier and hence more curable stage. Moreover, subsequent studies have also demonstrated a reduction in lung cancer mortality among those undergoing a low dose CT scan.
With the value of CT screening already firmly established, a UK-based team have published their own findings of a trial comparing the effect of a low dose CT scan compared to usual care, in high-risk patients. The UK lung cancer screening (UKLS) trial, randomised patients to low dose CT screening or usual care, i.e., with no CT scan and was undertaken at two thoracic hospitals in the UK. Eligible patients, aged 50 to 75 years, were those deemed to be at a high risk of developing lung cancer over the next 5 years defined by a risk score of at least 4.5% based on the Liverpool Lung Project risk model (LLPv2). This model includes several possible risk factors such as gender, age, smoking status, smoking duration, family history of lung cancer. Included patients were then randomised to the intervention group (CT scan) or usual care although given the nature of the intervention, blinding was not possible. The primary outcome was mortality due to lung cancer, defined as a death during the follow-up period where lung cancer was listed as an underlying cause. In an effort to provide further evidence, the researchers also undertook a meta-analysis of other recent trials and included their own data, to get a more robust estimate of the benefits of CT scanning.
A total of 1987 and 1981 individuals were randomised to the CT scan and control arm respectively and followed for a median of 7.3 years. The median age at consent was 68 years (25% female) and among the CT scan group, 38% were current smokers, of whom, 93% had smoked for more than 20 years. During the follow-up period, 76 lung cancers were detected, 30 in the CT scan arm and 46 in the control arm although this difference was not significant (relative risk, RR = 0.65, 96% CI 0.41 – 1.02, p = 0.062). Furthermore, there were no significant differences between the sexes. In addition, there were 512 deaths from any cause and again there was no significant difference between the groups (p = 0.315).
When these results were added to a meta-analysis of 9 randomised, controlled trials, low dose CT scan screening was associated with a 16% relative reduction in lung cancer mortality compared with no screening (RR = 0.84, 95% CI 0.76 – 0.92).
The authors concluded that while their trial had not demonstrated a statistically significant reduction in lung cancer mortality, when their data was combined with other studies, the pooled estimate was significant and provided further support for lung cancer screening via a low dose CT scan.
Field JK et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. Lancet Regional health Europe 2021
7th May 2021
Psoriasis is now considered to be an immune-mediated, chronic inflammatory disease which can affect both the skin and joints. There is no cure for the disease and while treatments are able to provide satisfactory control, long-term management is required. Although most patients have mild to moderate disease which can be controlled with topical therapies, around 20–30% of patients have moderate to severe disease, that requires systemic treatment. Oral therapies include ciclosporin, methotrexate, acitretin, apremilast and fumaric esters. In addition, there are now several biological therapies available and which have revolutionised the treatment of more severe disease. These have been broadly categorised based on their mode of action, e.g., anti-interleukin -17 (IL-17), e.g., secukinumab, ixekizumab and brodalumab, anti-IL-12/23, e.g., ustekinumab, anti-IL-23, e.g., guselkumab and anti-tumour necrosis factor (TNF), e.g., infliximab, adalimumab, etanercept. In the absence of direct head-to-head trials, a network meta-analysis (NMA), which uses both direct and indirect information, is invaluable to identify the relative efficacy of the available treatments. This was the method used by a team responsible for a Cochrane review of systemic treatments in psoriasis. The authors included only randomised trials in adults (18 years and over) with moderate-to-severe psoriasis in comparison to placebo and set the primary outcome as the proportion of participants achieving a psoriasis area and severity index (PASI) score of 90. The PASI is a measure of disease severity, ranging from 0 to 72 and with higher scores representing more severe disease. A PASI90 indicates that participants achieved a 90% improvement in disease severity from baseline.
The analysis included 158 studies with 57,831 participants (67.2% male) with an average age of 45 years and a mean baseline PASI of 20. At a class level, the anti-IL-17, anti-IL12/23, anti-IL23 and anti-TNF agents were all significantly more effective at achieving a PASI90 compared to the non-biologics. The NMA showed that infliximab, ixekizumab and secukinumab were the most effect biologics and with a similar clinical effectiveness.
The authors noted that a limitation was how the evaluations were limited to induction therapy, i.e., from 8 to 24 weeks after randomisation which was insufficient to assess the longer-term outcomes.
They also commented that the data did not help identify which patients were more suited to the smaller molecules and how in future pragmatic trials that involve switching between treatments, dosage adjustments, are needed to evaluate these drugs in clinical practice.
Sbidian E et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Sys Rev 2021
14th December 2020
It is fairly well established that a route out of the restrictions imposed on individuals because of COVID-19 would be through widespread vaccination once a suitable product becomes available. Early in the pandemic, several studies sought to ascertain people’s perceptions on whether they would be willing to receive a vaccination against the virus. Such information is of vital importance because it is believed that a large proportion of a country’s population needs to be vaccinated for the program to be fully effective. The earliest data was positive, with a large majority of those surveyed, stating that they were likely to want to be vaccinated. However, given the pace with which vaccines have entered developed, there has been a good deal of misinformation circulated on social media, leading to potential mistrust in the safety of vaccines which has been produced and tested in such a short space of time than normal.
Given this potential uncertainty, a team led by researchers from the Department of Psychology, University of Liverpool, set out to systematically review all the available studies undertaken to examine the percentage of the population intending to be either vaccinated or intending to refuse it once available. Included studies were required to have used a nationally representative sample (e.g. based on age, gender, education level etc) and having a sample size greater than 1000 participants from the same country though any studies from non-general public samples e.g., healthcare professionals, students, were excluded. In addition, all eligible studies had to include a question that measured willingness to use a vaccine for COVID-19 once available and these studies had to report the outcome for each option, e.g., yes vs no, or willing vs unsure vs unwilling.
A total of 20 articles reporting on 28 samples were included which were undertaken in 13 different countries. The size of each sample varied from 1,000 to 7,547 with a median of 1,198. In addition, samples were collected in the early phase of the pandemic (March – May 2020) or later (June 2020 and onwards). Interestingly, the proportion of respondents willing to be vaccinated decreased over time (79% early phase studies vs 60% later studies), whereas the proportion not willing to be vaccinated increased (12% early studies vs 20% later studies). In contrast, the proportion of individuals who stated that they were unsure did not change over time. There was also a persistent trend relating to vaccination intentions: being female, younger, of lower income/education level or belonging to an ethnic minority were all associated with a reduced likelihood of wanting to be vaccinated.
The authors called for an urgent need to address vaccination hesitancy to promote widespread uptake of the vaccine.
Robinson E et al. International estimates of intended uptake and refusal of COVID-19 vaccines: a rapid systematic review and meta-analysis of large nationally representative samples. MedRxiv 2020 doi.org/10.1101/2020.12.01.20241729