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9th July 2020
In this new review, researchers challenged the rationale for dietary advice in FH, which is characterised by an elevated level of low-density lipoprotein (LDL), stating that it does not have a supportive evidence-base. They point to data illustrating how patients with FH have risk factors for CVD that are related to an insulin-resistant phenotype (for example, elevated triglycerides, blood glucose, obesity and hypertension) and that this arises because of carbohydrate intolerance. Consequently, they argue that a low-carbohydrate (LC) as opposed to a low-fat diet would be more appropriate.
Evidence cited shows that when patients with FH eat a LC diet supplemented with up to 1800mg/day of cholesterol from eggs, LDL levels remained unchanged but triglycerides levels decreased. Other factors seen in FH patients which have been shown to increase the risk of CHD, independent of LDL levels, include raised levels of fibrinogen, hypertension, abdominal obesity and hyperinsulinaemia.
The authors conclude that there is now strong evidence to support clinical trials of LC diets in patients with FH to assess the impact on cardiovascular disease outcomes.
Reference
Diamond DM et al. Dietary recommendations for familial hypercholesterolaemia: an evidence-free zone. BMJ Evidence-Based Medicine 2020;July 5. doi: 10.1136/bmjebm-2020-111412
8th July 2020
Currently, WHO advises that COVID-19 is spread through droplet infection only, that is, when a person either coughs, sneezes or speaks and because these droplets cannot travel more than 1m, this is deemed to be the minimum safe distance to prevent transmission of the virus. However, in their letter, the scientists argue that there is now strong and convincing evidence that microscopic respiratory drops released during talking and coughing can remain in the air and travel beyond 2m, citing data which demonstrates how airborne transmission of viable other coronaviruses occurs in an indoor environment.
They also note early evidence from China in which infections were recorded in a restaurant where there was no evidence of direct or indirect contact between those who became infected.
While acknowledging that airborne transmission it is not universally accepted, the authors call upon international organisations such as WHO to at least provide recommendations on control measures to mitigate this potential route of infection, especially as individuals believe that they are fully protected by following the current recommendations.
Reference
Morawska L, Milton DK. Is it time to address airborne transmission of COVID-19. Clin Infect Dis 2020; ciaa939: https://doi.org/10.1093/cid/ciaa939
7th July 2020
In April 2020, the Spanish Ministry of Health established ENE-COVID, a nationwide, longitudinal study to quantify the extent of COVID-19 circulating throughout the country. The team randomly selected and recruited 35,883 households covering the 50 Spanish provinces and tested 61,075 individuals for COVID-19 between 27 April 27 and 11 May, 2020 while Spain was in lockdown.
The results from testing found a seroprevalence of the entire country of 5% (95% CI 4.7–5.4) although this was higher in the central part of Spain including Madrid and there was no difference between the sexes. Positive tests were 1.1% in infants younger than 1 year and 3.1% in children aged 5–9 years. Interestingly, between 21.9 % and 35.8% of patients who tested positive were asymptomatic, corresponding to between 376,000 and 1,042,000 individuals.
The authors note that their findings suggest that the achievement of herd immunity to COVID-19 is very unlikely and caution that because the majority of the population are still virus naïve, it is entirely possible that it can quickly re-circulate throughout the community, leading to a second-wave once lockdown restrictions are lifted.
Unfortunately, recent media reports of a localised lockdowns in parts of the country serve to illustrate how the authors’ forecasts have come true.
Reference
Pollan M et al. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet 2020; July 6: doi.org/10.1016/ S0140-6736(20)31483-5.
It occurs due to the formation of a blood clot in the retinal vein which leads to increased vascular permeability and fluid leakage into the retina. In a new study, researchers from the Taub institute in Columbia University have discovered a potential treatment for the condition.
They discovered that an endothelial enzyme, caspase-9, which is normally present at very low levels in an uninjured eye, becomes overly active after occlusion of a retinal vein and promotes vascular dysfunction and neuronal injury. Using a mouse model, the team first induced retinal occlusion after which they observed an increased activity of caspase-9 in retinal capillary beds. Subsequently, topical application of Pen1-XBir3, a highly selective caspase-9 inhibitor was able to attenuate the neuronal injury and restore normal functioning. They also successfully tested whether use of topical Pen1-XBir3 could be scaled up to a larger eye by applying the drops to a rabbit.
The authors concluded that caspase-9 plays a direct role in neuronal injury and that targeting this enzyme offers a potential valuable therapeutic option and are planning Phase I clinical trials to test the drug in patients with retinal vein occlusion.
Reference
Avrutsky MI et al. Endothelial activation of caspase-9 promotes neurovascular injury in retinal vein occlusion. Nat Comm 2020;11(1) DOI: 10.1038/s41467-020-16902-5
The study by a team the University of Georgia, followed 19,887 adults who had undertaken cognitive function tests for mental status, word recall and vocabulary at least biennially from 1996 to 2008. Based on their cognition scores throughout the study period, participants were grouped into either a low or high trajectory.
Alcohol consumption was categorised as never, former, low to moderate (<8 drinks per week for women and <15 drinks for men) or heavy (> 8 drinks for women and > 15 drinks per week for men).
The results showed that compared to the baseline group of “never” drinkers, low to moderate drinkers were significantly less likely to be associated with consistently low cognition scores (OR = 0.66, 95% CI 0.59 – 0.74. p < 0.001) and had a significantly lower rate of decline in cognitive scores over time. Alcohol consumption was found to have a U-shaped relationship with cognition scores with an optimal level of 10 to 14 drinks per week.
Interestingly the authors observed that these associations appeared to be stronger for white rather than black participants. Unfortunately, the authors were unable to explain the association between low to moderate alcohol consumption and cognition scores or the ethnic disparity.
Reference
Zhang R et al. Association of low to moderate alcohol drinking with cognitive functions from middle to older age among US adults. JAMA Netw Open 2020; Jun 1:3(6):e207922.
The ONS infection survey uses patient swab data and was established to determine the community prevalence of COVID-19 (excluding care homes and hospitals). To date, it has enrolled 17,139 households across England including 27,494 individuals. The intention is to continue monitoring over the next 12 months and to expand to all four UK nations. The most recent data covers the period 14 to 27 June 2020 and estimates that there were approximately 25,000 (confidence intervals 13,000 to 46,000) new infections per week in England, which equates to roughly 0.04% of the population of England or 1 in 2200 individuals. The study is also undertaking antibody testing and results suggest that 6.3% tested positive for COVID-19 antibodies, which equates to around 2.8 million people in England.
Although the results of the latest survey indicate that the percentage of people in England testing positive has declined since the first measurement on 26 April, it appears that the downward trend has now levelled off with the ONS report concluding that “at this point in time, we do not have evidence that the current trend is anything other than flat”.
One important area has been a description of the clinical characteristics of those infected with the virus and this information has helped government define groups of patients who are perceived as vulnerable to the virus and advised to “shield”. Several of the early studies from China identified the most common co-morbidities among those infected with COVID-19. For instance, in the first reported case series of 140 infected patients, hypertension (30%) and diabetes (12.1%)1 were the most common comorbidities and other retrospective studies came to the same conclusion.2,3 One comorbidity which is intriguingly absent from the list is asthma and in the study by Zhang et al,3 only a single patient was reported to have the condition. It is possible therefore that patients with asthma are somehow protected from COVID-19?
It is perhaps surprising that asthma does not feature as a common co-morbidity for those with COVID-19. In 2002, a study comparing the incidence of rhinovirus infection (such as those that cause the common cold), showed that while asthmatics were not particularly at a higher risk of infection, once infected, the illness occurred more frequently and was more severe than for non-asthmatics.4 Other work has also revealed that the degree of asthma control at the time of infection is also an important contributory factor in the subsequent response to infection. For instance, where a patient’s level of disease control is poor, they tend to experience a more severe exacerbation in response to a viral infection.5 A further problem which particularly affects asthmatics, is that after infection with a rhinovirus, the normal innate immune response which causes induction of interferons and an apoptotic response in virally infected cells, is severely impaired.6
It therefore seems puzzling that asthmatics are apparently note at a higher risk of infection with COVID-19. Allergic diseases such as asthma are characterised by a T helper-2 (Th2) response and enhanced expression of immunoglobulin E (IgE) and there is emerging evidence that interferons can suppress the Th2 allergic response.7 In fact, studies have suggested that interferon treatment can result in improvements in patients with severe asthma.8 However, since interferon production in asthmatics is impaired how might this serve to protect against infection with COVID-19? One theory suggests that the protective effect arises not through the suppression of interferons but precisely the opposite, that is, as a consequence of the enhanced Th2 response although the authors offer no plausible explanations as to why this might be protective.9 One possible explanation relates to how COVID-19 is believed to enter cells.
Evidence suggests that COVID-19 uses angiotensin-converting enzyme 2 (Ace-2) as its cellular receptor.10 In a study examining whether Ace2 expression was reduced in airway cells from patients with asthma and respiratory allergy, it was found that such patients did indeed have lower levels of Ace-2.11 Additionally, some data suggest that the enhanced Th2 inflammation in asthma also reduces expression of Ace-2 leading to better outcomes in those infected with COVID-19.12 Alternatively, it might be due to the effects of treatment with some preliminary and yet to be reviewed data, indicating that the inhaled corticosteroid, ciclesonide, blocks coronavirus replication.13
In summary, the evidence to date indicates that asthma is not an independent risk factor for COVID-19 infection because of a possible protective role that arises from the Th2 inflammation which downregulates Ace-2 expression. Nevertheless, asthmatics should not consider themselves immune from infection as witnessed by a large UK study in which 14.5% of 17,535 patients hospitalised for COVID-19 were asthmatic.15 With a potential protective effect against COVID-19 from inhaled corticosteroids, patients with asthma should continue to use their regular treatments to help maintain disease control.
References
3rd July 2020
What’s more, dementia was diagnosed around 7 years earlier in people with IBD than it was in those without this gut condition, the findings of this large population-based study show.
Mounting evidence suggests that communication between the gut, its microbiome, and the central nervous system (gut-brain axis) is implicated in various aspects of health and disease.
While the cause of IBD is not clear, it is thought to develop from an impaired immune response to changes in the gut microbiome.
And recently published research suggests that IBD may have a role in the development of another neurodegenerative disorder, Parkinson’s disease. But it’s not clear if IBD may also be linked to a heightened risk of dementia.
To explore this further, the researchers drew on data for 1742 people aged 45 and above who had been diagnosed with either ulcerative colitis or Crohn’s disease between 1998 and 2011, and registered with the Taiwan National Health Insurance programme. This was set up in 1995 and is compulsory for all Taiwanese residents.
Their cognitive health was tracked for 16 years following their IBD diagnosis and compared with that of 17,420 people who were matched for sex, age, access to healthcare, income, and underlying conditions, but who didn’t have IBD.
During the monitoring period, a larger proportion of those with IBD developed dementia (5.5%), including Alzheimer’s disease, than those without (1.5%).
Additionally, people with IBD were diagnosed with dementia an average of 7 years earlier (76) than those without IBD (83).
After taking account of potentially influential factors, including age and underlying conditions, people with IBD were more than twice as likely to develop dementia as those without.
Of all the dementias, the risk for Alzheimer’s disease was greatest: those with IBD were six times as likely to develop this as were those without IBD.
Neither sex nor type of IBD had any bearing on the findings. But the risk of dementia seemed to be associated with increasing length of time a person had had IBD.
This is an observational study, and as such, cannot establish cause and effect. Nor were the researchers able to gather information on potentially influential lifestyle factors, such as diet and exercise, or assess the impact of anti-inflammatory drugs prescribed.
But they point to previously published research, indicating chronic inflammation and an imbalance in gut bacteria as potential contributors to cognitive decline.
And they conclude: “The identification of increased dementia risk and earlier onset among patients with IBD suggest that [they] might benefit from education and increased clinical vigilance,” to slow cognitive decline and improve quality of life.
1st July 2020
Leaving hospital can be a confusing and sometimes risky time for patients who take medication, with an estimated 44% experiencing medicine-related problems once they get home.
New research from the University of Bath in the UK suggests the most helpful and timely medicine-related support is provided by hospital pharmacists, yet few patients are aware that they can turn to their NHS Trust to allay confusion and stay safe.
The Bath study explored the experiences of 40 patients or their carers using various hospital-based telephone medicines information services. It found that patients who have called a service regard it as uniquely placed to answer medication queries arising after hospital discharge. After using the service, patients said the helpline service was quicker to access than their GP and often more helpful.
But although 52% of NHS Trusts currently provide a medicines helpline, few discharged patients seem to know of their existence, resulting in extremely low usage.
Matt Williams, the Bath PhD student who led the research said: “A typical hospital that discharges over 100 patients every day will have 30 to 40 patients with a potential need to call the helpline, yet they might get just one call a day.
“If people don’t know the service exists, they either do nothing when problems arise or they go to their GP, use the emergency services or turn to the people around them or Google for non-expert and potentially unreliable advice. Yet they could resolve their problem with a simple phone call, which is quicker and easier for both the person and the NHS.”
Dr Matthew Jones, lecturer in pharmacy practice at the university, explained that patients often experience big changes to their medicine regimen when they are discharged from hospitals, and it’s common for them to find there are gaps in their knowledge.
He said: “They might have questions about side effects, correct dosage or potential interactions between medications. Getting the right information can help them avoid harm. It can also draw attention to mistakes that have been made with their medicines.”
Helplines have been established to help meet the NHS’s priority to improve patients’ transitions of care, so people can better manage their own health. Study participants called for their local helpline to be extended to cover evenings and weekends.
A second study from the Bath team finds that hospital pharmacists who provide a hospital medicines helpline service are aware that it is a valuable resource for patients but regard it as under-resourced.
“There is concern among pharmacists that if they advertise the service more widely, they will not be able to cope with the influx of enquiries. This is completely understandable at a time when NHS staff are so stretched. To benefit as many patients as possible, pharmacists need guarantees they will be given time to help everyone who calls,” said Dr Jones.
According to the results of research commissioned in 2018 by the UK Department of Health and Social Care, 237 million medication errors occur in the NHS in England every year. Of these, 66 million are of potential clinical significance. Avoidable adverse drug reactions cause around 700 deaths per year and cost the NHS an estimated £98.5m per year.
A study in 2017 found that discharged patients were not reliably warned of possible problems that could arise from their medications. Of the people involved in the NHS Patient Survey Programme, 43% said a member of staff did not tell them about any side effects to look out for.
Some discharged patients also experience medicines-related errors, such as prescribing mistakes and incorrect or missing information on discharge summary documents. As a result, 26% of discharged patients seek help relating to their medication, mainly from their GP.
Dr Jones said: “It’s important that all patients discharged from hospital can easily get timely and expert advice about their medicines. Different areas currently do this in different ways, which is one reason why the public doesn’t know about the services that are there to help them.
”In addition, the government recently announced a new Discharge Medicines Service, which will allow people to seek help from their community pharmacy. The NHS should decide what is the best way to help discharged patients and then ensure that this is provided and advertised by every hospital.”
For this new systematic review and network meta-analysis, a team from the clinical research and evidence-based medicine unit, Thessaloniki, Greece, provided a comprehensive overview of the current literature. Their analysis included 453 trials with 320,474 patients which assessed 21 different anti-diabetic interventions from 9 drug classes.
There were 134 randomised controlled trials examining monotherapy, 296 exploring treatment “add-ons” to metformin and finally 23 trials which compared monotherapy to add-on metformin therapy. There were several outcomes measured including reductions in HbA1C levels, all-cause mortality, cardiovascular death, diabetic retinopathy and amputation. The results showed that in drug naïve patients, all medications except dipeptidyl peptidase-4 inhibitors (for example, sitagliptin) were as effective as metformin in reducing HbA1C levels but the combination of metformin with specific-glucagon-like peptide-1 receptor agonists (GLP-1 RA) (for example, exenatide) and insulin provided the greatest reduction. For patients at an in-creased cardiovascular risk, combining metformin with sodium-glucose co-transporter-2 agents (SGLT-2) (for example, empagliflozin) or liraglutide (a GLP-1 RA) reduced cardiovascular death and all-cause mortality.
The authors also noted that for patients at a low risk of cardiovascular disease, none of the treatments differed with respect to vascular outcomes.
Reference
Tsapas A et al. Comparative effectiveness of glucose-lowering drugs for type 2 diabetes. Ann Intern Med 2020; June 30; doi:10.7326/M20-0864
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