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2nd May 2023
RSV infection in healthy children during the first year of life increases the risk of developing asthma at age five.
Respiratory syncytial virus (RSV) is a viral pathogen leading to acute lower respiratory infection in young children. Global estimates suggest that the virus causes 6.6 million infections in those aged 0-6 months and over 45,000 deaths.
Whether RSV infection during this crucial period of lung development could subsequently lead to asthma is uncertain. INSPIRE was a surveillance study including children with or without an RSV infection (RSVI) during infancy. Monitoring of children took place over the next five years.
The main hypothesis was that avoiding an RSVI during infancy reduces the risk of childhood asthma. The primary outcome was five-year current diagnosed asthma and finding from the INSPIRE study have been recently published.
A total of 1,741 children had available data during the first year of life. Among the entire cohort, 54% had an RSVI during that first year.
Over the next five years, not having an RSVI gave rise to a 26% lower risk of developing asthma (relative risk, RR = 0.74, 95% CI 0.58 – 0.94, p = 0.016). The authors estimated that 15% (95% CI 2.2-26.8) of current five-year asthma cases could be prevented by avoiding a RSVI.
The researchers commented that among healthy children, not being infected with RSV in the first year of life was associated with a substantially reduced risk of developing childhood asthma. However, they recognise that their study was unable to establish a causal relationship.
28th April 2023
Maternal vaccination with a single dose against RSV gave rise to a high efficacy against severe infection among infants.
RSV infection leads to a global high morbidity and mortality burden in children aged 0-60 months. Moreover, the greatest risk for hospitalisation occurs during the first six months of life.
In a recent study, RSV-associated acute respiratory infection, led to the hospitalisation of one in every 56 healthy term-born infants. Whether maternal vaccination can reduce such RSV-related infection in newborns and infants remains uncertain.
In the present, randomised, double-blind, phase 3 trial, pregnant women received a single dose vaccine or placebo, between weeks 24 and 36. The two primary efficacy endpoints were severe RSV-associated lower respiratory tract illness and medically attended, less severe illness. Assessment of these outcomes took place at 90 and 180 days after birth. A lower boundary of the confidence interval > 20% was the success criterion for vaccine efficacy.
Overall, 7,358 women received either the vaccine (3682) or placebo. There were six cases of severe RSV in the vaccinated group and 33 in the placebo arm within 90 days of birth (vaccine efficacy = 81.8% 99.5% CI 40.6% – 96.3%). Within 180 days, the vaccine efficacy against severe infection was 69.4% (97.58% CI 44.3 – 84.1%).
In contrast, vaccine efficacy was only 57.1% (99.5% CI 14.7 – 79.8) against less severe disease and did not meet the criteria for success.
Adverse events were similar in all groups within one month after injection or within one month after birth.
27th April 2023
Prostate cancer (PC) is the second most common cancer in men with over 1.4 million new cases in 2020. Findings from 2003, suggest that 5-alpha reductase inhibitors (5-ARIs) such as finasteride, prevent or delay the appearance of prostate cancer. Other work with another agent, dutasteride, also noted a lower risk of incident prostate cancer. However, in 2011, the FDA warned that 5-ARIs may increase the risk of a more serious form of prostate cancer. Despite this the available data is conflicting. For example, in one study, use of 5-ARIs led to a delay in cancer diagnosis and worsened cancer-specific outcomes in men with PC. In contrast, another could not detect an association between 5-ARI use and prostate cancer death.
In the present study, researchers undertook a meta-analysis on the association of 5-ARI use and death from prostate cancer. The primary outcome was the incidence of PC mortality among 5-alpha reductase inhibitor users and non-users.
5-alpha reductase inhibitor use and prostate cancer
There were 11 studies meeting the inclusion criteria, only one of which was an RCT and the remainder cohort studies. A total of 3,243,575 men were identified, 138,477 of whom were using a 5-ARI drug.
There was no significant association between 5-ARI use and prostate cancer death (hazard ratio, HR = 1.04, 95% CI 0.80 – 1.35, p = 0.79). In addition, there was also no association when restricting the analysis to exclude patients with a PC diagnosis at baseline (HR = 1.0, 95% CI 0.60 – 1.67, p = 0.99). When adjusting for prostate specific antigen level, there was a lower risk of prostate cancer mortality but this was non-significant (HR = 0.76, 95% CI 0.57 – 1.03, p = 0.08).
The benefits of seafood (SF) intake such as fish exceed the potential risks from contaminants. In fact, an umbrella review identified the beneficial effect of fish intake for a range of chronic diseases. However, another review suggests only a small effect on cardiovascular mortality from eating fish. In addition, other and more recent work, proposes that the health benefits are only due to fatty fish, e.g., sardines, salmon etc.
In the current study, researchers wanted to tease out the benefits of a higher SF intake. They considered total servings of seafood and small fatty fish rich in omega-3 fatty acids separately. Using a self-reported questionnaire, SF intake was categorised as high (>2 servings/week) or low (≤2 servings/week) intake). Similarly, intake of small fatty acid fish was also high or low (> 1 serving or < 1 serving/week). The incidence of both non-fatal and/or fatal CVD events served as the outcomes of interest after 10- and 20-years.
Seafood intake and cardiovascular events
There were 2,020 individuals with a mean age of 45.2 years (50.2% female) with data for analysis. Furthermore, only 32.7% and 9.6% of the entire cohort had a high SF and small fish intake respectively.
Those consuming a high seafood intake, had a 27% lower risk of developing CVD over the next 10 years. However, this risk became non-significant in fully-adjusted models (hazard ratio, HR = 0.76, 95% CI 0.65 – 1.02). In contrast, the 10-year CVD-related mortality was significantly lower in those with a high SF intake (HR = 0.26, 95% CI 0.11 – 0.58). This was also true for a high intake of fatty fish (HR = 0.24, 95% CI 0.06 – 0.99). In addition, the 20-year CVD-related deaths were also lower for a high SF intake (HR = 0.76, 95% CI 0.55 – 0.98).
Therefore a high intake of seafood and particularly fish rich in omega-3 fatty acids, was associated with a lower risk of 10-year fatal and non-fatal CVD.
Citation
Critselis E et al. High fish intake rich in n-3 polyunsaturated fatty acids reduces cardiovascular disease incidence in healthy adults: The ATTICA cohort study (2002-2022) Front Physiol 2023
26th April 2023
The risk of different types of strokes is significantly lower in patients with atrial fibrillation who use who use one of the statin drugs.
Atrial fibrillation (AF) represents the most frequent cardiac arrhythmia. Data from 2017 suggests that globally, the condition affects 3.046 million people. Moreover, AF leads to a five-fold increase in stroke risk with up to 30% of these due to the arrhythmia.
In data presented at EHRA 2023, the risk of strokes was lower in AF patients using statins within a year of their diagnosis. While it is already known that statin use in AF reduces the risk of all-cause mortality. But whether the drugs reduce stroke risk is uncertain.
However, some data suggests that high intensity statins may reduce cerebral events in patients with acute ischaemic stroke and AF.
In the study at EHRA 2023, researchers from Hong Kong, examined a cohort of newly diagnosed AF patients. Individuals were either statin or non-statin users in relation to their AF diagnosis. For instance, a statin user was taking the drug before their AF diagnosis.
The primary outcome was any form of stroke, e.g., ischaemic, systemic embolism, haemorrhagic or a transient ischaemic attack (TIA).
A total of 51,472 AF patients of whom, 11,866 were receiving a statin had analysable data.
During a median follow-up of 5.1 years, among statin users, the ischaemic stroke and systemic embolism risk was 17% lower than non-users (Hazard ratio, HR = 083, 95% CI 0.78 – 0.89). The risk of a haemorrhagic stroke (HS) was 7% lower (HR = 0.93) and the TIA risk 15% lower (HR = 0.85).
Use of statins for 6 years would reduce the risk of an ischaemic stroke or system embolism by 43% compared to use for less than 2 years (HR = 0.57). This risk was also lower for the other cerebral events.
A heart healthy lifestyle reduces the risk of cancer which suggests that both conditions share risk factors. This relationship appears to be bi-directional such that cancer patients with CVD risk factors have an increased chance of an adverse cardiac event. Some evidence also points to atherosclerotic CVD itself being a risk for the development of cancer. However, whether all forms of CVD increase cancer risk and if there is a relationship with the cancer type remains unclear.
In the current study, researchers sought to investigate the association between both atherosclerotic and non-atherosclerotic cardiovascular disease with the development of cancer. In a retrospective examination of an insurance claims database, the team identified patients initially free from cancer. These individuals were then categorised as having either atherosclerotic cardiovascular disease or non-atherosclerotic disease. This latter group had for instance, valvular heart disease, arrhythmias or congenital heart disease. In their analysis, the researchers made adjustments for age, sex, diabetes, hypertension, chronic kidney disease and hyperlipidaemia.
CVD and cancer risk
There were a total 27,195,088 individuals with data for analysis. Those with CVD had a 12% higher risk of developing cancer than those without the disease. (Hazard ratio, HR = 1.12, 95% CI 1.11 – 1.13). This risk was elevated for both atherosclerotic disease (HR = 1.20) and non-atherosclerotic disease (HR = 1.11).
Both forms of cardiovascular disease also linked to a higher incidence of a number of cancers. For example, atherosclerotic cardiovascular disease increased the risk of lung cancer more than two-fold (HR = 2.78). But this was slightly lower for non-atherosclerotic CVD (HR = 1.73).
Citation
Bell CF et al. Risk of Cancer After Diagnosis of Cardiovascular Disease. J Am Coll Cardiol CardioOnc. 2023
25th April 2023
Data for 2021 suggests that globally, 537 million were living with diabetes. In addition cardiovascular disease (CVD) is the main cause of death in those with type 2 diabetes (T2D). Moreover, sugar-sweetened and artificially sweetened beverages increase all-cause and CVD-related mortality. Nevertheless, the effect of different beverages on either all-cause mortality or CVD risk in those with T2D is largely unknown. There is also a lack of clarity on whether changes to beverage intake following a T2D diagnoses effects CVD risk.
In a recent BMJ study, researchers set out to investigate the relationship between beverage intake and all-cause mortality in T2D. They also considered if a change in what people drank following their T2D diagnosis affected their subsequent CVD risk. Data were collected from two large US prospective studies (the Nurses’ Health Study and Health Professionals Follow-Up Study). The researchers set the primary outcome as all-cause mortality. Secondary outcome measures were CVD incidence and mortality.
Beverages and all-cause mortality
There were 15,486 men and women with a mean age of 61.3 years (73.6% female) who had a diagnosis of type 2 diabetes at baseline. These individuals were followed for an average of 18.5 years. During this time, 22.3% developed incident CVD and 49.3% died.
When comparing the highest and lowest drink intake, there was a 20% greater all-cause mortality risk for those drinking sugar-sweetened drinks (hazard ratio, HR = 1.20, 95% CI 1.04 – 1.37). In contrast, the all-cause mortality risk was significantly lower in those drinking higher amounts of coffee (HR = 0.74, 95% CI 0.63 – 0.86). This relationship was also apparent for tea (HR = 0.79), plain water (HR = 0.77) and low-fat milk (HR = 0.88). Higher intake of coffee also significantly lowered the risk of CVD incidence (HR = 0.82).
The researchers also considered the effect of changes to beverage intake after an individual had their T2D diagnosis. For example, replacing one serving/day of a sugar sweetened drink with coffee, gave rise to an 18% lower risk of all-cause mortality. Similar trends occurred with tea, plain water and low-fat milk.
Tralokinumab targets interleukin-13 (IL-13) and appears to be both effective and tolerable in adolescents aged 12-17 with moderate-to-severe atopic eczema.
Adolescent atopic eczema gives rise to a negative impact on patient’s quality of life. There is already good evidence to suggest that IL-13 creates inflammation in atopic eczema.
Tralokinumab specifically neutralises IL-13 and therefore reduces inflammation. Previous work has demonstrated efficacy for the drug adults with moderate-to-severe atopic eczema. However, it remains uncertain whether tralokinumab is effective for adolescents with moderate-to-severe disease.
The current randomised, double-blinded, placebo-controlled enrolled adolescents aged 12-17 years with moderate-to-severe atopic eczema. Individuals received monotherapy with tralokinumab either 150 mg or 300 mg, or matching placebo, every two weeks for 16 weeks.
The primary endpoint was an Investigator’s Global Assessment (IGA) score of 0 or 1 (clear/almost clear) at week 16.
An alternative primary endpoint was a 75% or higher improvement in EASI (i.e. an EASI 75). Those meeting the primary outcome at week 16 continued in a maintenance phase until week 52.
There were 289 participants with a median age of 15 years (51.6% male). Some 97 participants were given 150 mg of tralokinumab, and 98 were assigned to 300 mg of tralokinumab.
At week 16, significantly more patients receiving tralokinumab had an IGA of 0 or 1 than placebo: 21.4% (150 mg) and 17.5% (300 mg) vs 4.3% for placebo (p < 0.01 and p = 0.002 respectively).
In addition, 28.6% of tralokinumab 150 mg patients had an EASI75, as did 27.8% of the tralokinumab 300 mg group. Only 6.4% of those in the placebo arm achieved EASI75.
Larger improvements were seen for both doses of the drug compared to placebo for itch and quality of life scores.
At week 52, 62.9% of all tralokinumab participants maintained their IGA score of 0 or 1 with doses administered either every two or four weeks. The drug was tolerable with a similar proportion of adverse events in all three arms.
The researchers concluded that tralokinumab therefore appears effective for adolescents with moderate-to-severe atopic eczema.
Citation
Paller AS et al. Efficacy and Safety of Tralokinumab in Adolescents With Moderate to Severe Atopic Dermatitis: The Phase 3 ECZTRA 6 Randomized Clinical Trial. JAMA Dermatol 2023.
Type 2 diabetes increases the risk for developing dementia. Both elevated HbA1c levels and diabetic complications also linked to an increased dementia risk. Moreover, intensive glycaemic control does not seem to reduce cognitive decline. But how long-term glycaemic control affects the risk of dementia is uncertain and was the subject of the current study.
Using a large US healthcare database, researchers looked at type 2 diabetics older than 50 with HbA1c levels recorded over time. Researchers categorised HbA1c measurements as < 6%; 6% to < 7%; 7% to < 8%, 8% to < 9%, 9% to < 10% and 10% or more. They also identified those diagnosed with dementia during follow-up.
HbA1c levels and development of dementia
There were 253,211 eligible participants with a mean age of 61.5 years. The participants were followed for a mean of 5.9 years. During this time, participants with the majority (i.e., > 50%) of HbA1c measurements between 9 and 10%, had an increased the risk of dementia (hazard ratio, HR = 1.31, 95% CI 1.15 – 1.51). Similarly, with most measurements of 10% or above, the risk was also significantly higher (HR = 1.74, 95% CI 1.62 – 1.86).
In contrast, among participants with more than 50% of HbA1c measurements that were less than 6%, the dementia risk was lower (HR = 0.92, 95% CI 0.88 – 0.97). This also held true for HbA1c levels of 6 to 7% and between 7 and 8%. Thus in type 2 diabetics, keeping cumulative HbA1c levels below 8% was associated with a lower risk for developing dementia. The researchers called for further research to determine if these associations were causal.
Citation
Moran C et al. Glycemic Control Over Multiple Decades and Dementia Risk in People With Type 2 Diabetes. JAMA Neurol 2023
Psychological therapy that improves a patient’s depression could also reduce their risk of developing cardiovascular diseases in the future, according to new research.
In the first-of-its-kind study, published in the European Heart Journal, researchers retrospectively examined a cohort of 636,955 individuals who had completed the Improving Access to Psychological Therapy (IAPT) primary care programme for depression.
Individuals were free of cardiovascular disease (CVD) before entry into the IAPT and over 45 years of age, with a mean age of 55. Some 58.6% showed an improvement in their depression. Regression models then estimated the association between improvement of depression and the risk of subsequent CVD events.
In fully adjusted models, those whose depression symptoms improved after psychological therapy were 12% less likely to experience a cardiovascular event than those who did not, over an average three-year follow up.
Indeed, improving depression symptoms gave rise to a significant lowering in the risk of any new onset of CVD (hazard ratio, HR = 0.88, 95% CI 0.86 – 0.89). This was true for coronary heart disease (HR = 0.89), stroke (HR = 0.88) and all-cause mortality (HR = 0.81).
This reduction in CVD risk and risk of death from all causes was higher in those aged under 60, with 15% and 22% decreased risk respectively. Those over 60 years of age had a 5% decreased risk of developing CVD and 14% decreased risk of death from all other causes.
The authors suggest that management of depression with psychological therapies might therefore reduce the risk of subsequent CVD, but more research is needed to understand the causality of these associations.
Commenting on the study, lead author Celine El Baou, PhD candidate from UCL Psychology & Language Sciences, said: “The findings are important as they suggest that the benefits of psychological therapy may extend beyond mental health outcomes and to long-term physical health. They stress the importance of increasing access to psychological therapy to under-represented groups, for example minority ethnic groups who may be more at risk of experiencing cardiovascular disease.”
The authors also noted that previous studies have shown that people who experience depression are around 72% more likely to develop cardiovascular disease in their lifetime.
A study published earlier in 2023 also highlighted that depression and poor mental health among young adults is more likely to lead to premature CVD and suboptimal cardiovascular health. The researchers concluded that prioritising mental health might help to reduce CVD risk and improve cardiovascular health in young adults.
In 2021/22, 1.24 million referrals accessed the Improving Access to Psychological Therapies (IAPT) programme (now renamed NHS Talking Therapies for anxiety and depression) compared to 1.02 million the previous year, according to latest NHS Digital statistics.
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