Tag: 21/1/22

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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Photo by Mockup Graphics on Unsplash

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