Tag: 8/7/22

Substantial Discrepancies found Between Estimated and Measured GFR

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A cross sectional study published in Annals of Internal Medicine uncovered substantial discrepancies between individual estimated glomerular filtration rate (eGFR) and directly measured GFR (mGFR).The authors suggest that eGFR calculations on lab reports also state this distribution of uncertainty, and also that renaming the eGFR as a population average GFR (or paGFR) merits further discussion.

GFR is the standard metric used to assess and monitor kidney function. Directly measured GFR, or mGFR, requires injecting a filtration marker and measuring plasma or urinary clearance by serial blood and urine sampling under standardized conditions is not possible for every patient. So eGFR calculated from serum creatinine is often used by clinicians to predict an mGFR. Population-level discrepancies between eGFR and mGFR are low, but individual discrepancies are much higher. It is important to understand the magnitude of these individual-level differences for clinical decision making.

Researchers calculated eGFR from serum creatinine alone and cystatin C and creatinine using the Chronic Kidney Disease Epidemiology Collaboration equations for 3223 participants and compared their eGFR to their mGFR to quantify the magnitude and consequences of the individual-level differences between the two. The authors found substantial discrepancies between directly measured GFR and estimated GFR, resulting in only about 50% agreement between CKD stages. Individual-level differences between the mGFR and the eGFR did not improve substantially using cystatin C.

The authors suggested that several factors contribute to these discrepancies: creatinine and cystatin C have non-GFR factors influencing their serum concentration; variability in the mGFR can result from normal physiology and measurement error from mGFR markers and technique; and as GFR estimation models the ratio of mGFR–body surface area as a function of serum markers, it incorporates errors in mGFR and errors in body surface area calculated from height and weight.

The authors say that their findings highlight the need to make direct GFR measurements available to patients who need them. They note that implementation studies are needed in this area, and research is needed to assess how the availability and use of mGFRs change clinical management.

Source: EurekAlert!

Scientists Prove that People Really do Get ‘Hangry’

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A new study published in the journal PLOS ONE has discovered that feeling hungry really can make us ‘hangry’, with emotions such as anger and irritability strongly linked with hunger.

Hangry, a portmanteau of hungry and angry, is a commonly used colloquialism, but the phenomenon has not been widely explored by science outside of laboratory environments.

The study’s researchers found that hunger is associated with increased levels of anger and irritability, as well as reduced levels of pleasure.

The researchers recruited 64 adult participants, who recorded their levels of hunger and various measures of emotional wellbeing over a 21-day period using a smartphone app. They made their reports with the app five times a day, allowing data collection to take place in real-world settings such as at work or at home.

Hunger was found to be linked with stronger feelings of anger and irritability, as well as lower ratings of pleasure, and the effects were substantial, even after taking into account demographic factors such as age and sex, body mass index, dietary behaviour, and individual personality traits.

Hunger was associated with 37% of the variance in irritability, 34% of the variance in anger and 38% of the variance in pleasure recorded by the participants. The research also found that the negative emotions – irritability, anger, and unpleasantness – are caused by both day-to-day fluctuations in hunger, as well as residual levels of hunger measured by averages over the three-week period.

Lead author of the study Viren Swami, Professor of Social Psychology at Anglia Ruskin University (ARU), said: “Many of us are aware that being hungry can influence our emotions, but surprisingly little scientific research has focused on being ‘hangry’.

“Ours is the first study to examine being ‘hangry’ outside of a lab. By following people in their day-to-day lives, we found that hunger was related to levels of anger, irritability, and pleasure.

“Although our study doesn’t present ways to mitigate negative hunger-induced emotions, research suggests that being able to label an emotion can help people to regulate it, such as by recognising that we feel angry simply because we are hungry. Therefore, greater awareness of being ‘hangry’ could reduce the likelihood that hunger results in negative emotions and behaviours in individuals.”

The field work was carried out by Stefan Stieger, Professor of Psychology at Karl Landsteiner University of Health Sciences. Prof Stieger said: “This ‘hangry’ effect hasn’t been analysed in detail, so we chose a field-based approach where participants were invited to respond to prompts to complete brief surveys on an app. They were sent these prompts five times a day at semi-random occasions over a three-week period.

“This allowed us to generate intensive longitudinal data in a manner not possible with traditional laboratory-based research. Although this approach requires a great deal of effort – not only for participants but also for researchers in designing such studies – the results provide a high degree of generalisability compared to laboratory studies, giving us a much more complete picture of how people experience the emotional outcomes of hunger in their everyday lives.”

Source: Anglia Ruskin University

Vaccine Acceptance is Increasing Around the World

Image of a syring for vaccination
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COVID vaccine acceptance across much of the world increased by 3.7% between 2020 and 2021, according to a new study published in Nature Communications.

In a June 2021 survey of over 23 000 individuals across 23 countries, the researchers found that 75.2% of respondents reported vaccine acceptance, up from 71.5% one year earlier.  

The study was carried out during a year of substantial but very unequal global COVID vaccine availability and acceptance, which required new assessments of the drivers of vaccine hesitancy and the characteristics of people not vaccinated.

Vaccine hesitancy was most consistently associated with concerns about vaccine safety and efficacy and mistrust in vaccine development. Other factors associated with vaccine hesitancy varied by country and included personal experience with COVID (eg, sickness or loss of a family member) and demographic characteristics (eg, gender, education, and income).

The authors also found that vaccine hesitancy was not associated with a country’s current COVID case burden and mortality. In June 2021, vaccine hesitancy was reported most frequently in Russia (48.4%), Nigeria (43%), and Poland (40.7%), and least often in China (2.4%), the UK (18.8%), and Canada (20.8%).

“In order to improve global vaccination rates, some countries may at present require people to present proof of vaccination to attend work, school, or indoor activities and events,” said CUNY SPH Senior Scholar Jeffrey Lazarus. “Our results found strong support among participants for requirements targeting international travellers, while support was weakest among participants for requirements for schoolchildren.”

Those who were vaccine-hesitant were also less likely to express support for vaccine mandates. “Importantly, however, recommendations by a doctor, or to a lesser extent by an employer, might have an impact on a respondent’s views on vaccination in some countries,” said CUNY SPH Dean Ayman El-Mohandes.

Although some countries are currently disengaging from evidence-based COVID control measures, the disease has by no means been controlled or ended as a public health threat. The authors note that for ongoing COVID vaccination campaigns to succeed in improving coverage going forward, substantial challenges remain. These include targeting those reporting lower vaccine confidence with evidence-based information campaigns and greatly expanding vaccine access in low- and middle-income countries.

The Role of Social Networks

The researchers also held a meeting to explore vaccine messaging. According to data presented from a European survey carried out by the Vaccine Confidence Project, the population group most exposed to social networks, ie people under 24, with secondary or university studies and living in urban areas, are the most reluctant to be vaccinated. Additionally, messages that call for vaccination as a “moral obligation” are strongly rejected compared to those that call for “protection,” which are more commonly well received.

As with previous studies, humour was shown to be one of the most effective ways to convey anti-vaccine messages. Therefore, participants in the meeting agreed on the need to disseminate the benefits of vaccines using this same tool, but without making fun of those who have mistaken beliefs about vaccines. In the face of misinformation, it is important to improve information on vaccination using simple language and channels that reach the population, such as social networks, the participants concluded.

Source: CUNY Graduate School of Public Health and Health Policy

Mechanism Behind Sound and Pain Suppression Identified in Mice

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Sound is known to suppress the sensation of pain, and now scientists have identified the neural mechanisms through which sound blunts pain in mice. The findings, which could inform development of safer methods to treat pain in humans, were published in Science.

“We need more effective methods of managing acute and chronic pain, and that starts with gaining a better understanding of the basic neural processes that regulate pain,” said the director of the National Institute of Dental and Craniofacial Research (NIDCR), Rena D’Souza, DDS, PhD. “By uncovering the circuitry that mediates the pain-reducing effects of sound in mice, this study adds critical knowledge that could ultimately inform new approaches for pain therapy.”

Studies as far back as 1960, have shown that music and other kinds of sound can help alleviate acute and chronic pain in humans, including pain from dental and medical surgery, labour and delivery, and cancer. Yet the mechanism behind this remained elusive.

“Human brain imaging studies have implicated certain areas of the brain in music-induced analgesia, but these are only associations,” said co-senior author Yuanyuan (Kevin) Liu, PhD, at NIDCR. “In animals, we can more fully explore and manipulate the circuitry to identify the neural substrates involved.”

The researchers first exposed mice with inflamed paws to three types of sound: a pleasant piece of classical music, an unpleasant rearrangement of the same piece, and white noise. Surprisingly, all three types of sound, when played at a low intensity relative to background noise (about the level of a whisper) reduced pain sensitivity in the mice. Higher volume had no effect on their pain sensitivity.

Researchers discover how sound reduces pain in mice
Inhibition of auditory cortex inputs to the thalamus drives sound-induced analgesia. Credit: Conghuan Ye

“We were really surprised that the intensity of sound, and not the category or perceived pleasantness of sound would matter,” Dr Liu said.

To explore the brain circuitry underlying this effect, the researchers trace connections between brain regions using fluorescent protein-tagged viruses. They identified a route from the auditory cortex to the thalamus, which relays sensory signals, including pain, from the body. In freely moving mice, low-intensity white noise reduced the activity of neurons at the receiving end of the pathway in the thalamus.

Without sound, suppressing the pathway with light- and small molecule-based techniques mimicked the pain-blunting effects of low-intensity noise, while turning on the pathway restored animals’ sensitivity to pain.

Dr Liu said it is unclear if similar brain processes are involved in humans, or whether other aspects of sound, such as its perceived harmony or pleasantness, are important for human pain relief.

“We don’t know if human music means anything to rodents, but it has many different meanings to humans – you have a lot of emotional components,” he said.

The results could give scientists a starting point for studies to determine whether the animal findings apply to humans, and ultimately could inform development of safer alternatives to opioids for treating pain.

Source: National Institutes of Health

Hyaluronic Acid of Little Value in Knee Osteoarthritis

Knee pain
Source: CC0

Treating knee osteoarthritis with hyaluronic acid injections (known as viscosupplementation) makes almost no difference to pain or functioning and might raise risk of adverse events, suggests a review of 50 years of literature on the procedure.

Viscosupplementation has been used to treat knee osteoarthritis since the 1970s, but there are long-standing questions over its safety and efficacy.

Some 560 million people worldwide suffer from knee osteoarthritis, which involves inflammation and structural changes of the joints, resulting in joint pain and limitations to physical movement.

National and international guidelines vary in their recommendations, but most advise against the use of viscosupplementation. Researchers therefore set out to review 50 years’ worth of studies to evaluate the safety and efficacy of viscosupplementation. The studies compared viscosupplementation to placebo or no treatment.

Published in The BMJ, the main analysis of this review found that viscosupplementation was associated with a small reduction in pain compared with placebo, but the difference was tiny and was described as “clinically irrelevant.”

Their analysis showed that since 2009, there has been conclusive evidence that viscosupplementation and placebo treatment have led to the same clinical result in terms of pain reduction, meaning there is no point to having the injections.

They also found from 15 large trials on 6462 randomised participants that viscosupplementation was linked to a 49% higher risk of serious adverse events than placebo.

The authors say that based on their analysis of the studies between 2009 and 2021 alone, more than 12 000 patients were arguably unnecessarily subjected to these injections in viscosupplementation trials, which raises ethical concerns.

The study has some limitations in that it represents summary estimates and does not necessarily exclude the possibility that selected patient populations could benefit from viscosupplementation. Also, the researchers looked at adverse events that emerged rather than adverse events directly and clearly related to treatment.

However, strengths include the fact that this is the largest collection of randomised trials on viscosupplementation reported to date, which significantly decreases the risk of bias influencing the results.

As such, the authors conclude: “There is strong, conclusive evidence that among patients with knee osteoarthritis, viscosupplementation, compared with placebo, is associated with a clinically irrelevant reduction in pain intensity and with an increased risk of serious adverse events.

“The findings do not support broad use of viscosupplementation for the treatment of knee osteoarthritis.”

Source: The BMJ