Tag: 24/2/22

Categories : Cardiovascular DiseaseTags :

CVD Risk Warning for Paracetamol That Contains Sodium

On By ModernMedia
Graphical abstract from European Heart Journal editorial: sodium hidden in medication warrants warning labels by drug companies

Clinicians have recommended avoiding effervescent, soluble paracetamol that contains sodium, following findings from a large study that shows a link with a significantly increased risk of cardiovascular disease (CVD) and mortality in people who have hypertension and even in people with normal blood pressure.

The study of nearly 300 000 patients registered with UK GPs was published in the European Heart Journal.

Sodium is often used to help drugs such as paracetamol dissolve and disintegrate in water. However, effervescent and soluble formulations of 0.5g tablets of paracetamol can contain 0.44 and 0.39g of sodium respectively. If a person took the maximum daily dose of two 0.5g tablets every six hours, they would consume 3.5 and 3.1g of sodium respectively – a dose that exceeds the WHO-recommended total daily intake of 2g a day. In 2018, 170 people per 10 000 of the population in the UK were using sodium-containing medications, with a higher proportion among women. There are alternative formulations that contain little or no sodium.

Excessive salt in the diet remains a major public health problem and is associated with an increased risk of cardiovascular disease (CVD) and death among patients with hypertension. However, there is inconsistent evidence showing an increased risk in normotensive individuals.

Professor Chao Zeng led a team which analysed data from a medical database of UK GPs’ records. They looked at 4532 hypertensive patients who had been prescribed sodium-containing paracetamol and compared them with 146 866 hypertensive patients who had been prescribed sodium-free paracetamol. They also compared 5351 normotensive patients who were prescribed sodium-containing paracetamol with 141 948 normotensive patients prescribed sodium-free paracetamol. The patients were aged 60-90 years and followed up for one year.

The researchers found the risk of heart attack, stroke or heart failure after one year for patients with high blood pressure taking sodium-containing paracetamol was 5.6% (122 cases of CVD), while it was 4.6% (3051 CVD cases) among those taking sodium-free paracetamol. Mortality risk was also higher; the one-year risk was 7.6% (404 deaths) and 6.1% (5510 deaths), respectively.

A similar increased risk was seen among normotensive patients. Among those taking sodium-containing paracetamol, the one-year CVD risk was 4.4% (105 cases of CVD) and 3.7% (2079 cases of CVD) among those taking sodium-free containing paracetamol. The risk of dying was 7.3% (517 deaths) and 5.9% (5190 deaths), respectively.

Prof Zeng said: “We also found that the risk of cardiovascular disease and death increased as the duration of sodium-containing paracetamol intake increased. The risk of cardiovascular disease increased by a quarter for patients with high blood pressure who had one prescription of sodium-containing paracetamol, and it increased by nearly a half for patients who had five or more prescriptions of sodium-containing paracetamol. We saw similar increases in people without high blood pressure. The risk of death also increased with increasing doses of sodium-containing paracetamol in both patients with and without high blood pressure.”

Prof. Zeng said that clinicians and patients should be aware of the risks associated with sodium-containing paracetamol and avoid unnecessary consumption, especially when the medication is taken for a long period of time.

“Given that the pain relief effect of non-sodium-containing paracetamol is similar to that of sodium-containing paracetamol, clinicians may prescribe non-sodium-containing paracetamol to their patients to minimise the risk of cardiovascular disease and death. People should pay attention not only to salt intake in their food but also not overlook hidden salt intake from the medication in their cabinet,” he said.

“Although the US Food and Drug Administration requires that all over-the-counter medications should label the sodium content, no warning has been issued about the potentially detrimental effect of sodium-containing paracetamol on the risks of hypertension, cardiovascular disease and death. Our results suggest re-visiting the safety profile of effervescent and soluble paracetamol.”

Being an observational study it can only show only that there is an association between salt in paracetamol and CVD and deaths, rather than that salt causes these events. Other limitations include a lack of data on dietary intake of salt and excretion of salt from urinary samples. The use of over-the-counter paracetamol was not also recorded, however by restricting the study to those over 60 who qualify for free prescriptions in the UK, the risk of this is minimised.

Source: EurekAlert!

Categories : Paediatrics Respiratory DiseasesTags :

Indoor Air Pollution Linked to Pneumonia in Children

On By ModernMedia
Streptococcus pneumoniae. Credit: CDC

A new study published in The Lancet Global Health, highlights the impact indoor air pollution can have on the development of child pneumonia, showing that increases in airborne particulate matter results in greater carriage of Streptococcus pneumoniae.

Streptococcus pneumoniae is a major human pathogen causing more than two million deaths per year; more than HIV/AIDS, measles and malaria combined, but it is also part of the normal microbial community of the nasopharynx. It is the leading cause of death due to infectious disease in children under five years of age; in sub-Saharan Africa, the burden of pneumococcal carriage and pneumonia is especially high.

Household air pollution from solid fuels increases the risk of childhood pneumonia. Nasopharyngeal carriage of S. pneumoniae is a necessary step in the development of pneumococcal pneumonia. More than 2.6 billion people are exposed to household air pollution worldwide. Inefficient indoor biomass burning is estimated to cause 3.8 million premature deaths annually and approximately 45% of all pneumonia deaths in children aged younger than five years. However, a causal pathway between household air pollution and pneumonia had not yet been identified.

In order to understand the connection between exposure to household air pollution and the risk of childhood pneumonia researchers from the UK, Malawi and the United States conducted the MSCAPE (Malawi Streptococcus pneumoniae Carriage and Air Pollution Exposure) study embedded in the ongoing CAPS (Child And Pneumonia Study) trial. The MSCAPE study assessed the impact of PM2.5, the single most important health-damaging pollutant in household air pollution, on the prevalence of pneumococcal carriage in a large sample of 485 Malawian children.

Through exposure-response analysis, a statistically significant 10% increase in risk of S. pneumoniae carriage in children was observed for a unit increase (deciles) of exposure to PM2.5 (ranging from 3.9 μg/m³ to 617.0 μg/m³).

Dr. Mukesh Dherani, the study principal investigator, indicated: “This study provides us with greater insight into the impact household air pollution can have on the development of child pneumonia. These findings provide important new evidence of intermediary steps in the causal pathway of household air pollution exposure to pneumonia and provide a platform for future mechanistic studies.”

Study author Professor Dan Pope said: “Moving forward further studies, particularly new randomized controlled trials comparing clean fuels (e.g. liquefied petroleum gas) with biomass fuels, with detailed measurements of PM2.5 exposure, and studies of mechanisms underlying increased pneumococcal carriage, are required to strengthen causal evidence for this component of the pathway from household air pollution exposure to ALRI in children.”

Professor Nigel Bruce, co-principal investigator, stated: “This study provides further important evidence that emphasises the need to accelerate to cleaner fuels, such as LPG, which are now being promoted by many governments across the continent in order to meet SDG7 by 2030.”

Source: University of Liverpool

Categories : Diseases, Syndromes and ConditionsTags :

Investigating Vaping’s Impact on Gum Disease

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Photo by Chiara summer on Unsplash

A series of new studies investigates how e-cigarettes alter oral health and may be contributing to gum disease. The latest, published in mBio, finds that e-cigarette users have a distinctive oral microbiome that is less healthy than nonsmokers but potentially healthier than cigarette smokers, and measures worsening gum disease over time.

“To our knowledge, this is the first longitudinal study of oral health and e-cigarette use. We are now beginning to understand how e-cigarettes and the chemicals they contain are changing the oral microbiome and disrupting the balance of bacteria,” said co-lead researcher Prof Deepak Saxena.

While cigarette smoking is known to increase gum disease risk, much less is known about the impact of e-cigarette use on oral health, especially in the long term.

The researchers studied the oral health of 84 adults from three groups: cigarette smokers, e-cigarette users, and people who have never smoked. Gum disease was assessed through two dental exams six months apart, during which plaque samples were taken to analyse the bacteria present.

Gum health changes
All participants had some gum disease at the start of the study, with cigarette smokers having the most severe disease, followed by e-cigarette users. After six months, the researchers observed that gum disease had worsened in some participants in each group, including several e-cigarette users.

Clinical attachment loss is a key indicator of gum disease, measured by gum ligament and tissue separating from a tooth’s surface, leading the gum to recede and form pockets. These pockets are bacterial breeding grounds and can lead to worsening gum disease. In a study of the same participants published in Frontiers in Oral Health, the research team found that clinical attachment loss was significantly worse only in the e-cigarette smokers after six months.

A unique microbiome
Analysis of the bacteria in plaque samples showed that e-cigarette users had a different oral microbiome than smokers and nonsmokers, in line with their earlier results.

While all groups shared roughly a fifth of the types of bacteria, the bacterial makeup for e-cigarette users had strikingly more in common with cigarette smokers than nonsmokers. Several types of bacteria, including Selenomonas, Leptotrichia, and Saccharibacteria, were abundant in both smokers and vapers compared to nonsmokers. Several other bacteria – including Fusobacterium and Bacteroidales, linked to gum disease – were particularly dominant in the mouths of e-cigarette users.

When plaque samples were gathered and analysed in the six-month follow-up, the researchers found greater diversity in bacteria for all groups studied, yet each group maintained its own distinct microbiome.

“Vaping appears to be driving unique patterns in bacteria and influencing the growth of some bacteria in a manner akin to cigarette smoking, but with its own profile and risks to oral health,” said Fangxi Xu, study co-first author.

An altered immune response
The researchers found that the distinct microbiome in e-cigarette users was correlated with clinical measures of gum disease and changes to the host immune environment. In particular, vaping was associated with different levels of cytokines. Certain cytokines are linked to an imbalance in oral bacteria and can worsen gum disease by making people prone to inflammation and infection.

TNFα, a cytokine that causes inflammation, was significantly elevated among e-cigarette users. In contrast, cytokines IL-4 and IL-1β were lower among e-cigarette users; because IL-4 tends to be reduced in people with gum disease and increases after treatment, it suggests that certain bacteria in the mouths of e-cigarette users are worsening inflammation.

The researchers concluded that the distinct oral microbiome of e-cigarette users elicits altered immune responses, which along with clinical markers for gum disease illustrate how vaping presents its own challenge to oral health.

“E-cigarette use is a relatively new human habit,” said Scott Thomas, study co-first author. “Unlike smoking, which has been studied extensively for decades, we know little about the health consequences of e-cigarette use and are just starting to understand how the unique microbiome promoted by vaping impacts oral health and disease.”

Source: New York University

Categories : Lab Tests and Imaging Neurodegenerative DiseasesTags :

Blood Test for Alzheimer’s Proves Highly Accurate

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Plaques and neurons. Source: NIAH

A study in the journal Neurology has shown that a less expensive blood test to detect Alzheimer’s is highly accurate at early detection, providing further evidence that the test should be considered for routine screening and diagnosis. 

“Our study shows that the blood test provides a robust measure for detecting amyloid plaques associated with Alzheimer’s disease, even among patients not yet experiencing cognitive declines,” said senior author Professor Randall J. Bateman, MD.

“A blood test for Alzheimer’s provides a huge boost for Alzheimer’s research and diagnosis, drastically cutting the time and cost of identifying patients for clinical trials and spurring the development of new treatment options,” Prof Bateman said. “As new drugs become available, a blood test could determine who might benefit from treatment, including those at very early stages of the disease.”

Developed by Prof Bateman and colleagues, the blood test assesses whether amyloid plaques have begun accumulating in the brain based on the ratio of the levels of the amyloid beta proteins Aβ42 and Aβ40 in the blood.

The gold standard PET scan evaluation requires a radioactive brain scan, at an average cost of $5000–$8000 (R75 000–R120 000) per scan. Another common test, which analyses levels of amyloid-beta and tau protein in cerebrospinal fluid, costs about $1000 (R15 000) but requires a spinal tap process.

This study estimates that prescreening with a $500 (R7500) blood test could halve both the cost and the time it takes to enrol patients in clinical trials that use PET scans. Using only blood testing for screening could be done in under six months, a tenth or less of the cost. The test is currently only available in the US and Europe.

The current study shows that the blood test remains highly accurate, even when performed in different labs following different protocols, and in different cohorts across three continents.

Scientists didn’t know if small differences in sampling methods (such as anticoagulant use) could have a big impact on test accuracy because results are based on subtle shifts in amyloid beta protein levels in the blood. Subtle interfernece in these amyloid protein ratios could have triggered a false negative or positive result.

To confirm the test’s accuracy, researchers tested blood samples from current Alzheimer’s studies in the United States, Australia and Sweden, each of which uses different protocols for the processing of blood samples and related brain imaging.

Findings from this study confirmed that the Aβ42/Aβ40 blood test using a high-precision immunoprecipitation mass spectrometry technique developed at Washington University provides highly accurate and consistent results for both cognitively impaired and unimpaired individuals across all three studies.

When blood amyloid levels were combined with another major Alzheimer’s risk factor – the presence of the genetic variant APOE4 – the blood test accuracy was 88% compared to brain imaging and 93% when compared to spinal tap.

“These results suggest the test can be useful in identifying nonimpaired patients who may be at risk for future dementia, offering them the opportunity to get enrolled in clinical trials when early intervention has the potential to do the most good,” Prof Bateman said. “A negative test result also could help doctors rule out Alzheimer’s in patients whose impairments may be related to some other health issue, disease or medication.”

Source: Washington University School of Medicine

Categories : NeurologyTags :

Scientists Unravel Neurological Origins of the Placebo Effect

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Researchers at Massachusetts General Hospital (MGH) have discovered a network of brain regions activated by the placebo effect overlaps with several regions targeted by brain-stimulation therapy for depression.

The findings of this study, published in Molecular Psychiatry, will help in understanding the neurobiology of placebo effects and could inform how brain stimulation trial results are interpreted. In addition, this could provide insights on how to harness placebo effects for the treatment of a variety of conditions.

The placebo effect occurs when a patient’s symptoms improve because they expect a therapy to help (due to a variety of factors), but not from the specific effects of the treatment itself. Recent research indicates that there is a neurological basis for the placebo effect, with imaging studies identifying a pattern of changes that happen in certain brain regions when a person experiences this phenomenon.

The use of brain-stimulation techniques for patients with depression that doesn’t respond adequately to medication or psychotherapy has gained wider use in recent years. Transcranial magnetic stimulation (TMS) delivers electromagnetic pulses to the brain, and its effect on brain activity has been established over the last three decades in animal and human research studies, with several TMS devices approved by the Food and Drug Administration for treating depression. In addition, for treatment depression, deep brain stimulation (DBS, which requires an implanted device) has shown some promise.

Senior author Emiliano Santarnecchi, PhD, saw studies of brain stimulation as a unique opportunity to learn more about the neurobiology of the placebo effect. Santarnecchi and his co-investigators conducted a meta-analysis and review of neuroimaging studies involving healthy subjects and patients to create a “map” of brain regions activated by the placebo effect. They also analysed studies of people treated with TMS and DBS for depression to identify brain regions targeted by the therapies. The team found that several sites in the brain that are activated by the placebo effect overlap with brain regions targeted by TMS and DBS.

Dr Santarnecchi and his colleagues believe that this overlap has critical importance in interpreting the results of research on brain stimulation for conditions such as depression. In clinical trials, a significant portion of depression patients receiving brain stimulation improve — but so do many patients receiving placebo (sham) treatment, in which no stimulation is administered, which has led to confusion over the therapy’s benefits.

A possible explanation is “that there is a significant placebo effect when you do any form of brain stimulation intervention,” said Dr Santarnecchi. TMS involves a clinical setting, with loud clicks as the pulse is delivered. “So the patient thinks, ‘Wow, they are really activating my brain’, so you get a lot of expectation,” said Dr Santarnecchi.

Elevated placebo effects associated with brain stimulation may create problems when studying the intervention, said first author Matthew Burke, MD, a cognitive neurologist. If brain stimulation and the placebo effect overlap in activating the same brain regions, then those circuits could be maximally activated by placebo effects, which could make it difficult to show any additional benefit from TMS or DBS, said Dr Burke. If so, this could explain the disparity of results in neurostimulation treatment of depression. Screening out placebo from brain stimulation’s direct impact on brain activity will help in designing studies where the real potential of techniques such as TMS will be more easily quantified, thus improving the effect of treatment protocols.

The findings from this study also suggest broad applications for the placebo effect, said Dr Santarnecchi. “We think this is an important starting point for understanding the placebo effect in general, and learning how to modulate and harness it, including using it as a potential therapeutic tool by intentionally activating brain regions of the placebo network to elicit positive effects on symptoms,” he said.

Dr Santarnecchi and his colleagues are currently designing trials that they hope will “disentangle” the effects of brain stimulation from placebo effects and offer insights about how they can be leveraged in clinical settings.

Source: Massachusetts General Hospital