Month: January 2022

Categories : Diseases, Syndromes and ConditionsTags :

New AIRD Therapies Could Cut Side-effects

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Source: Pixabay

New therapies for autoimmune rheumatic diseases (AIRDs) that are designed to better regulate lipid metabolism could significantly reduce the harmful side-effects caused by conventional treatments, researchers found in a new large-scale review.

AIRDs include rheumatoid arthritis, lupus and Sjögren’s syndrome – conditions which affect millions and all with high rates of morbidity. The pathogenesis of autoimmune conditions is still ill-defined and delivering targeted therapeutic strategies is challenging.

As a result, current treatments for AIRDs are primarily designed to suppress the symptoms (inflammation), but are ‘low target’, ie may also have unintended side-effects. In this regard, AIRDs drugs often cause changes to cell metabolism (such as lipid metabolism) and function, putting patients at greater risk of co-morbidities such as cardiovascular disease (CVD).

Lead author Dr George Robinson (Centre for Rheumatology Research, UCL Division of Medicine) said: “While the mechanisms that cause rheumatic diseases are ill-defined, some recent research indicates cell metabolism may play an important role in triggering or worsening their onset or affect.

“In this review we therefore sought to understand the effect of both conventional and emerging therapies on lipid metabolism in patients with AIRDs.”

For the study, published in the Journal of Clinical Investigation, researchers reviewed more than 200 studies to assess and interpret what is known regarding the on-target/off-target adverse effects and mechanisms of action of current AIRD therapies on lipid metabolism, immune cell function and CVD risk.

Explaining the findings, Dr Robinson said: “Our review found that current AIRD therapies can both improve or worsen lipid metabolism, and either of these changes could cause inflammation and increased CVD risk.

“Many conventional drugs also require cell metabolism for their conversion into therapeutically beneficial products; however drug metabolism often involves the additional formation of toxic by-products, and rates of drug metabolism can be different between patients.”

The review noted that optimal combinations of immunosuppressive treatments to better control inflammation could lead to an improved metabolic/lipid profile in AIRDs.

However, many studies also showed that lipid lowering drugs such as statins do not sufficiently lower CVD risk in some AIRDs, possibly because they cannot completely restore the anti-inflammatory properties

Dr Robinson added: “The unfavourable off-target adverse effects of current therapies used to treat AIRDs provides an opportunity for optimal combination co-therapies targeting lipid metabolism that could reduce immune complications and potential increased CVD risk in patients.

“New therapeutic technologies and research have also highlighted alternative metabolic pathways that can be more specifically targeted to reduce inflammation but also to prevent undesirable off-target metabolic consequences of conventional anti-inflammatory therapies.”

Source: University College London

Categories : Injury & Trauma NeurologyTags :

Study Uncovers Mechanism Behind Visual Impairment in Traumatic Brain Injury

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A healthy neuron.
A healthy neuron. Credit: NIH

Traumatic brain injury can lead to long-term visual impairment, which researchers have found is caused by a dramatic drop in the number of neurons in the visual cortex. Their findings were published in Communications Biology.

Traumatic brain injury (TBI) is associated with mechanical brain damage and a wide range of neuronal abnormalities.  Injuries to the posterior occipital cortex are common in humans, and can result in visual impairment. Up to 75% of current or former soldiers live with permanent visual dysfunction or cortical blindness. 

The human brain possesses surprising neuroplasticity, which allows other areas of the brain to take over the functions of a damaged area.

Such neuroplasticity is also characteristic of the sensory areas of the visual cortex, which is final component of the visual pathway, responsible for receiving and processing visual impressions. The primary visual cortex (V1) is reached by the nerve fibres of the optic radiation, which carry nerve impulses from the retinas of both eyes.

Until now, scientists knew little about the effects of TBI on long-term visual circuit function. Using mice, a team of researchers examined how neurons respond to visual stimuli two weeks and three months after mild injury to the primary visual cortex (V1). V1 neurons normally show sensitivity to different features of a visual stimulus, such as colour or direction of movement. The preprocessed data is transmitted to subsequent areas of the visual cortex. This study showed that although the primary visual cortex remained largely intact after the brain injury, there was a 35% reduction in the number of neurons. This loss largely affected inhibitory neurons rather than excitatory neurons, which inhibit or stimulate action in the target cells, respectively.

After TBI, fewer than half of the isolated neurons were sensitive to visual stimuli (32% at two weeks after injury; 49% at three months after the event), compared with 90% of V1 cells in the control group. Up to a threefold decrease in neuronal activity was seen after the brain injury, and the cells themselves had worse spatial orientation. The overall results mean that even minor, superficial brain injuries cause long-term impairment in the way visual stimuli are perceived, persisting several months after the event.

Such a deeper understanding of the functional impairments in damaged visual cortex could provide a basis for developing circuit-level therapies for visual cortex damage.

Source: Institute of Physical Chemistry of the Polish Academy of Sciences

Categories : Respiratory DiseasesTags :

Simple COPD Screening Could Benefit Millions

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The global burden of Chronic Obstructive Pulmonary Disease (COPD) could be significantly reduced with a simple health assessment available in low- and middle-income countries (LMICs), according to a large-scale international study.

The greatest burden on COPD is in LMICs, which account for around 90% of COPD related deaths. 

In high-income countries, COPD is typically caused by tobacco smoking and is diagnosed using a spirometer, the straightforward ‘gold standard’ diagnosis, and symptoms can be effectively treated.

However, in LMICs the primary cause of COPD is more varied and includes household air pollution in the form of biomass smoke for cooking and heating; other causes include impaired lung growth, chronic asthma and post-tuberculosis lung damage. Spirometry is often unavailable in LMICs. These reasons, combined with a shortage of clinicians, means COPD is commonly undiagnosed in LMICs.

In the new study, published in JAMA, researchers found that people with a high risk of COPD could be identified in 7 to 8 minutes using either a questionnaire on its own or a questionnaire combined with a Peak Expiratory Flow (PEF) assessment.

Explaining the study, lead researcher Professor John Hurst said: “Chronic Obstructive Pulmonary Disease is one of the world’s major public health issues, causing both individual and economic harm: there is a clear and pressing need to find better ways to identify people early, in all manner of settings.

“Screening tools for COPD have been shown to have reasonable diagnostic accuracy in high-income countries, but due to better population health and treatment in these settings, this has tended to identify milder disease, not requiring much intervention.

“Up until now the performance of these screening tools has not been adequately studied in LMICs; we aimed to test both the diagnostic accuracy and feasibility of simple screening tools.”

Researchers assessed three COPD screening tools (a combination of PEF and/or questionnaires) on populations in three distinct settings: semiurban Bhaktapur, Nepal, urban Lima, Peru and rural Nakaseke, Uganda.

To establish diagnostic accuracy of the tools, all participants were also given a spirometry test.    

In total 10709 adults aged 40 years or older from the three communities took part.

Study findings:

  • Prevalence of COPD varied by site, from 3% in Lima (Peru) to 7% in Nakaseke (Uganda) and 18% in Bhaktapur (Nepal).
  • 49% of COPD cases were clinically significant as defined by symptoms and or exacerbation burden, and 16% had severe or very-severe disease measured on spirometry. 95% of cases were previously undiagnosed.
  • The screening instruments performed similarly within each population setting and were feasible to deliver using trained research staff, taking an average of 7 to 8 minutes.

Commenting Professor Hurst said: “Our findings support the accuracy and feasibility of using simple screening tools to identify people affected by COPD living in diverse low- and middle-income settings.

“It is alarming that a high percentage of screen-identified COPD cases were clinically important, had severe or very severe changes in lung function, and that most were unaware of their diagnosis despite the high prevalence of symptoms and lower quality of life.

“In addition, only a minority of people had a history of smoking, further highlighting the poor conditions, exacerbated by biomass smoke, that people in low- and middle-income countries are living.”

Professor Hurst added: “Action is needed: the global health community has neglected the burden of chronic respiratory diseases for too long.  It is now time for people with chronic respiratory diseases such as COPD to be promptly identified, informed about their condition and treated – wherever they live in the world.”

Researchers say more work is needed to assess whether COPD screening can be implemented in routine LMIC healthcare settings; if screening for COPD is of benefit to those testing positive, and it is cost-effective, for a given population, to implement COPD screening in LMIC settings.  

Source: University College London

Categories : Antibiotics Diseases, Syndromes and ConditionsTags : 1 Comment

AMR Caused Over 1.2 Million Deaths Globally in 2019

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Methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Credit: CDC

Globally, infections by antimicrobial-resistant (AMR) bacteria caused more than 1.2 million deaths worldwide in 2019, according to a study published in The Lancet. It is the largest and most comprehensive one to date of this critical issue.

Lower-income countries are worst affected but antimicrobial resistance remains a global threat, the researchers wrote.

The researchers emphasised that investment in new drugs is urgently needed, as well as vaccination and better antimicrobial stewardship.

The estimate of global deaths from AMR, is based on the researchers’ analysis of 204 countries, assuming the counterfactual that the bacteria responsible would be antibiotic-susceptible.

Of the 4.95 million deaths in which AMR played a role, 1.27 million were directly attributable to it. In 2019, 860 000 deaths were estimated from HIV and 640 000 from malaria.

Most of the AMR-related deaths resulted from lower respiratory infections, such as pneumonia, and bloodstream infections, which can lead to sepsis.

Deaths from AMR were estimated to be highest in sub-Saharan Africa at 23.7 deaths per 100 000, and lowest in North Africa and the Middle East at 11.2 per 100 000. Young children are at most risk, with about one in five deaths linked to AMR being among the under-fives.

The researchers also noted that “resistance is high for multiple classes of essential agents, including beta-lactams and fluoroquinolones.”

MRSA (methicillin-resistant Staphylococcus aureus) was particularly deadly, while E. coli, K. pneumoniae, S. pneumoniae, A. baumannii, and P. aeruginosa were associated with high levels of resistance. The researchers wrote that “each of these leading pathogens is a major global health threat that warrants more attention, funding, capacity building, research and development, and pathogen-specific priority setting from the broader global health community.”

They also recommend that immunity to these pathogens be built up by vaccination, and since currently only S. pneumoniae has a vaccine readily available, these will need to be developed and deployed as a matter of urgency. They noted several limitations to their study, the first being the sparsity of data drawn from low- and middle-income countries, which may in fact lead to an underestimate of the prevalence of AMR. Secondly, there is the possibility of multiple sources of bias inherent in combining datasets from different providers. Finally, there may be bias in surveillance, eg if cultures are drawn only if a patient is unresponsive to antibiotics, leading to an overestimate.

Source: The Lancet

Categories : COVID HospitalsTags :

Little COVID Viral Contamination Risk in Hospital Rooms

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Source: Martha Dominguez de Gouveia on Unsplash

A study found that hospital rooms where COVID patients were treated had little to no active virus contaminations on surfaces. The finding, published in Clinical Infectious Diseases, concluded that contaminated surfaces in the hospital environment are unlikely to be a source of indirect transmission of the virus, contrary to earlier views.

“Early on in the pandemic, there were studies that found that SARS-CoV-2 could be detected on surfaces for many days,” said the study’s senior author, Professor Deverick Anderson. “But this doesn’t mean the virus is viable. We found there is almost no live, infectious virus on the surfaces we tested.”

The researchers tested a variety of surfaces in the hospital rooms of 20 COVID patients at Duke University Hospital over several days of hospitalisation, including on days 1, 3, 6, 10 and 14.

Samples were collected from the patients’ bedrail, sink, medical prep area, room computer and exit door handle. A final sample was collected at the nursing station computer outside the patient room.

PCR testing found that 19 of 347 samples gathered were positive for the virus, including nine from bedrails, four from sinks, four from room computers, one from the medical prep area and one from the exit door handle. All nursing station computer samples were negative.

Of the 19 positive samples, most (16) were from the first or third day of hospitalisation.

All 19 positive samples were screened for infectious virus via cell culture with only one sample, obtained on day three from the bedrails of a symptomatic patient with diarrhoea and a fever, demonstrating the potential to be infectious.

“While hospital rooms are routinely cleaned, we know that there is no such thing as a sterile environment,” Prof Anderson said. “The question is whether small amounts of viral particles detected on surfaces are capable of causing infections. Our study shows that this is not a high-risk mode of transmission.”

Prof Anderson said the findings reinforce the understanding that SARS-CoV-2 primarily spreads through person-to-person encounters via respiratory droplets in the air. He noted that people should concentrate on known anti-infection strategies such as masking and socially distancing to mitigate exposures to airborne particles.

Source: Duke University

Categories : HospitalsTags :

Standard Saline as Effective as Specialised Intravenous Fluids in ICU

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New research on intravenous fluids used in intensive care shows that commonly used saline is as effective at keeping people alive and their organs functioning as more expensive balanced solutions.

The results not only provide doctors with greater certainty about the safety and benefits of saline solution, but also have broader implications for treatment availability and costs around the world.

“Just about every patient admitted to the Intensive Care Unit (ICU) will receive intravenous fluids for resuscitation or as part of standard treatment,” said Professor Simon Finfer AO, an ICU physician and senior researcher at The George Institute.

“However, the best choice of fluid has been a longstanding issue of debate as some fluids were approved and licensed for use based on trials in small numbers of patients looking only at short term outcomes.”

Plasma-Lyte 148® is a type of intravenous fluid that more closely matches the body’s normal levels of certain minerals, known as balanced multi-electrolyte solutions, or BMES. Use of BMES has risen since concerns were raised about increased rates of kidney injury and death associated with saline, although this had not been proven in clinical trials.

To address this issue, the Plasma-Lyte 148® versUs Saline (PLUS) study recruited over 5000 patients across 53 sites in Australia and New Zealand.

Participants were adult patients admitted to ICUs in need of intravenous fluid resuscitation for their underlying medical condition. The patients were followed for a period of 90 days after treatment as previous research had shown around one in four would be at risk of dying within this timeframe.

At 90 days after the treatment, the same number of patients who had received BMES or saline had died.

Other outcomes including days of mechanical ventilation, kidney dialysis, patient survival time in the ICU and in hospital, as well as major measures of healthcare costs were similar between the groups.

“We found no evidence that using a balanced multi-electrolyte solution in the ICU, compared to saline, reduced risk of death or acute kidney injury in critically ill adults,” said Prof Finfer.

ICU is one of the most expensive aspects of healthcare and ICU resources are in high demand. Even a small difference in outcomes may result in important clinical and economic effects at the population level.

In the early 1990s, up to one in seven people were dying in ICUs across Australia and New Zealand, prompting George Institute researchers to start investigating intravenous fluid resuscitation – one of the most commonly used treatments in intensive care settings.

This started a program of fluid resuscitation research conducted in ICUs that no-one previously thought possible which has resulted in major changes to clinical treatment guidelines worldwide, preventing harmful practices and saving many lives.

The results from this study were published in the New England Journal of Medicine.

Source: EurekAlert!

Categories : Mental HealthTags :

Suicidal Ideation in Adolescents Linked to Risky Driving

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Suicide and motor vehicle traffic accidents are two of the most common forms of death among adolescents. A new study published in JAMA Pediatrics found that adolescents who reported at least one suicide attempt within the last year, compared to those reporting no attempts, were also more likely to report infrequent seat belt use and driving with a drunk driver. There were also over twice as likely to report driving drunk.

The researchers analysed data from over 13 500 U.S. high school students who participated in the 2019 Youth Risk Behavior Survey, and found that 19% of the sample reported suicidal ideation. Texting or e-mailing while driving was the most commonly reported form of risky driving behaviours.

Study lead author Kyle T. Ganson, PhD, assistant professor at the University of Toronto, said: “The findings from this study emphasise the need for mental health support for adolescents experiencing suicidality as a means of increasing safety for themselves and their communities, as accidental injury deaths via car accidents were the leading cause of death among adolescents in 2019.”

“The more severe the suicidality, the stronger the association with risky driving behaviours,” Dr Ganson continued. “Adolescents who reported a suicide injury, such as a poisoning or overdose needing to be treated by a medical professional, had the highest likelihood to report all four risky driving behaviors we examined.”

The researchers stress the importance of the implications their findings have to protect the health and well-being of adolescents. “Health care professionals should consider discussing risky driving behaviours with teens who report suicidality,” said co-author Jason M. Nagata, MD, MSc, assistant professor at the University of California, San Francisco.

Source: News-Medical.Net

Categories : COVID Expert OpinionTags :

SA Scientists Criticise Developed Nations’ ‘Scepticism’ over Omicron

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South African scientists have criticised developed nations for ignoring early evidence that Omicron was “dramatically” milder than the previous strains of the coronavirus, an attitude which could be construed as “racism”.

“It seems like high-income countries are much more able to absorb bad news that comes from countries like South Africa,” said Prof Shabir Madhi, vaccinologist at Wits University.

“When we’re providing good news, all of a sudden there’s a whole lot of scepticism. I would call that racism.”

Prof Salim Karim, former head of the South African government’s COVID advisory committee and vice-president of the International Science Council concurs.

“We need to learn from each other. Our research is rigorous. Everyone was expecting the worst and when they weren’t seeing it, they were questioning whether our observations were sufficiently scientifically rigorous,” he said, though he acknowledged that Omicron’s high number of mutations may have led to an overabundance of caution.

But by early December, anecdotal evidence was already indicating that Omicron caused far fewer hospitalisations than the Delta Wave, despite being more transmissible.

“The predictions we made at the start of December still hold. Omicron was less severe. Dramatically. The virus is evolving to adapt to the human host, to become like a seasonal virus,” said Prof Marta Nunes, senior researcher at the Vaccines and Infectious Diseases Analytics department at Wits

“It didn’t take even two weeks before the first evidence started coming out that this is a much milder condition. And when we shared that with the world there was some scepticism,” Prof Karim added.

While some have argued that Africa’s pandemic experience is different due to factors such as its younger population, any advantage South Africa has is outweighed by poor health, with excess deaths during COVID at 480 per 100 000, one of the highest in the world. Prof Madhi points out a high prevalence of comorbidities such as obesity and HIV.

A majority of those excess deaths are probably due to the pandemic, many SA scientists believe. Half occurred during the Delta wave, but only 3% transpired during the Omicron wave so far, Prof Madhi pointed out.

The government chose not to tighten restrictions during the fourth wave, and criticised the reimposition of travel bans coming from South Africa. South African scientists have mostly welcomed this, even though the WHO continues to warn that Omicron should not be considered “mild”.

“We believe the virus is not going to be eradicated from the human population. We must now learn how to live with this virus and it will learn how to live with us,” said Prof Nunes.

The low death rate from Omicron indicates a different phase of the pandemic. “I’d refer to it as a convalescent phase,” said Prof Madhi. The government has already effectively stopped quarantining and contact tracing.

Source: BBC News

Categories : COVID PaediatricsTags :

COVID is Turning Some Children into ‘Fussy Eaters’

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More and more children could be turning into ‘fussy eaters’ after a bout of COVID, according to smell experts at the University of East Anglia and Fifth Sense, a charity for people affected by smell and taste disorders.

This is because they may be suffering parosmia – a symptom where people experience strange and often unpleasant smell distortions. Once-loved foods like chicken may taste like petrol, for example, making it hard for children to eat those foods and maintain a healthy diet – or even take in enough calories to maintain their weight.

Together, Fifth Sense and leading smell expert Professor Carl Philpott from University of East Anglia, are launching guidance to help parents and healthcare professionals better recognise the disorder.

Prof Carl Philpott said: ”Parosmia is thought to be a product of having less smell receptors working which leads to only being able to pick up some of the components of a smell mixture. It’s a bit like Eric Morecambe famously said to Andre Previn – ‘it’s all the right notes but not necessarily in the right order’.

He said that as COVID swept through classrooms in the UK, there has been a growing awareness that it is affecting children too. “In many cases the condition is putting children off their food, and many may be finding it difficult to eat at all.

“It’s something that until now hasn’t really been recognised by medical professionals, who just think the kids are being difficult eaters without realising the underlying problem. For Prof Philpott, he is seeing teenage patients with parosmia for the first time in his career.

Fifth Sense Chair and founder Duncan Boak said: “We’re hearing anecdotal evidence that children are really struggling with their food after covid.

“If children are suffering smell distortions – and food smells and tastes disgusting – it’s going to be really hard for them to eat the foods they once loved.

“We’ve heard from some parents whose children are suffering nutritional problems and have lost weight, but doctors have put this down to just fussy eating. We’re really keen to share more information on this issue with the healthcare profession so they’re aware that there is a wider problem here.”

Together with Prof Philpott, Fifth Sense have put together guidance for parents and healthcare providers to help recognition and understanding of the problem.

The guidance shows that children should be listened to and believed. Parents can help by keeping a food diary noting those that are safe and those that are triggers.

“Establishing what the triggers are and what tastes ok is really important,” said Prof Philpott.

“There are lots of common triggers – for example cooking meat and onions or garlic and the smell of fresh coffee brewing, but these can vary from child to child.

“Parents and healthcare professionals should encourage children to try different foods with less strong flavours such as pasta, bananas, or mild cheese – to see what they can cope with or enjoy.

“Vanilla or flavour-free protein and vitamin milkshakes can help children get the nutrients they need without the taste. And it may sound obvious, but children could use a soft nose clip or hold their nose while eating to help them block out the flavours.”

‘Smell training’ has emerged as a simple and side-effect free treatment option for various causes of smell loss, and is a final option to consider.

Prof Philpott said: “Smell training involves sniffing at least four different odours – for example eucalyptus, lemon, rose, cinnamon, chocolate, coffee, or lavender – twice a day every day for several months.

“Children should use smells that they are familiar with and are not parosmia triggers. In younger children this might not be helpful, but in teenagers this might be something they can tolerate.”

Source: University of East Anglia

Categories : Medical Research & TechnologyTags :

Why Public ‘Big Data’ Initiatives Failed to Deliver on COVID

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Source: Pixabay

Experts from a data-driven initiative to aid the COVID response have outlined major obstacles to making successful use of new data released by technology companies in times of crisis. Harvard University’s Caroline Buckee and colleagues presented these views in the open-access journal PLOS Digital Health.

Technology companies collect vast amounts of data on their users, including their geographic locations. During the COVID pandemic, many companies made some of their user data available in order to aid public health efforts, such as monitoring the impact of social distancing policies or travel restrictions. However, Buckee and colleagues note, many efforts to harness these “data for good” failed to make a significant impact.

The authors are part of Crisis Ready, in which epidemiologists help policy makers understand and use insights from human mobility data released by technology companies. In this capacity, they have now identified challenges that hinder other efforts to use novel forms of data as part of disaster response.

Firstly, data-sharing agreements between researchers and technology companies were hastily arranged during the pandemic. They recommend pre-established agreements that will be ready for implementation in future crises.

Buckee and colleagues also observed that a lack of standardisation, interoperability, and clarity on uncertainties or biases in novel datasets resulted in the need for highly specialised professionals to process this data. To address this challenge, data access and characteristics can be negotiated prior to a disaster.

The authors also call for global investment in training more professionals that can analyse complex data to provide information in a disaster. In addition, they strongly emphasise the need for local response agencies to collaborate closely with regional scientists.

Without such efforts, no amount of data donated by technology companies will be useful in a crisis.

“It is still very difficult to translate the vast amounts of digital data that are owned by companies into useful public health tools, despite their incredible potential for transforming decision-making during health emergencies,” said Buckee. “We need to build a global cohort of data scientists and epidemiologists who can support local governments, and put in place the data pipelines and analysis tools before disasters hit, so that local responders have context-specific information when they need it most.”

Source: News-Medical.Net