Day: April 24, 2024

Categories : AntibioticsTags :

Useless Antibiotic Prescriptions are Getting out of Hand

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Photo from Pixabay CCO

According to a massive new medical insurance database study, the U.S. is going the wrong way with antibiotic stewardship, with 1 in 4 prescriptions going to patients who have conditions that the drugs simply won’t work on. In fact, the percentage of all antibiotic prescriptions given to treat conditions they’re useless against was even higher in December 2021 than it was before the pandemic began, the study shows – increasing the rate of antibiotic resistance development.

The percentage inappropriate prescriptions actually fell slightly in the early months of the pandemic, when far fewer people sought medical care for infectious or non-infectious reasons, the new research shows. But this trend was soon reversed.

The study, published in the journal Clinical Infectious Diseases by a team from the University of Michigan, Northwestern University and Boston Medical Center, is based on data from more than 37.5 million children and adults covered by private insurance or Medicare Advantage plans from 2017 to 2021. Patients received antibiotic prescriptions from both in-person and telehealth visits.

The team looked back at any new diagnosis given to each patient on the day they received a prescribed antibiotic or in the three days before getting the prescription. If none of these diagnoses justified the use of antibiotics, they classified the prescription as inappropriate.

Key findings:

  • In all, 60.6 million antibiotic prescriptions were dispensed in the five years of the study period from January 2017 to December 2021. The share that were inappropriate rose from 25.5% to 27.1% during this period.
  • The proportion of people getting inappropriate antibiotics was 1.7% in December 2019, dipped to 0.9% in April 2020 – largely because fewer people get antibiotics in general – and returned to 1.7% by December 2021.
  • Some groups of people were more likely to receive inappropriate antibiotics. At the end of 2021, 30% of antibiotics for older adults with Medicare Advantage coverage were inappropriate, compared with 26% of antibiotics for adults with private health insurance and 17% of antibiotics for children with private insurance.
  • Among the diagnoses listed for people who received antibiotics for inappropriate reasons, “contact with and suspected exposure to COVID-19” was one of top two most common reasons from March 2020 through December 2021. There is no evidence that taking antibiotics after an exposure can reduce risk of developing COVID-19.
  • Of all the inappropriately prescribed antibiotics dispensed in the last half of 2021, 15% were for a COVID-19 infection. And COVID-19 infections accounted for 2% of all antibiotic prescribing – regardless of appropriateness – from March 2020 through December 2021.
  • Telehealth appointments accounted for 9% of all inappropriate antibiotic prescriptions in the latter half of 2021, down somewhat from 2020. There were almost no telehealth-based antibiotic prescriptions before March 2020.
  • For 28% to 32% of the antibiotic prescriptions filled by patients in the study period, there was no diagnosis available to judge appropriateness, potentially because the patient received the prescription at an appointment that didn’t get billed to their insurance, or it was a refill of a past prescription. The percentage was especially high in the first months of the pandemic.
  • 45% of all the patients in the study received antibiotics at least once in the five years, and 13% received them four or more times.

Source: University of Michigan

Categories : Ageing NeurologyTags :

Essential Tremor Increases Cognitive Impairment Risks over Time

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Photo by Matthias Zomer on Pexels

Essential tremor, a nervous system disorder that causes rhythmic shaking, is one of the most common movement disorders. A new study published in the Annals of Neurology reveals details on the increased risk of mild cognitive impairment (MCI) and dementia that individuals with essential tremor may face.

The research represents the longest available longitudinal prospective study of rates of MCI and dementia in people with essential tremor. The study enrolled 222 patients, 177 of whom participated in periodic evaluations over an average follow-up of 5 years.

Investigators observed a cumulative prevalence of 26.6% and 18.5% for MCI and dementia, respectively. They also noted a cumulative incidence of 18.2% and 11.2% for MCI and dementia, respectively. Each year, 3.9% of patients with normal cognition “converted” to having MCI, and 12.2% of those with MCI “converted” to having dementia.

“We know from related research that the presence of cognitive impairment in patients with essential tremor has meaningful clinical consequences. For example, patients with essential tremor who are diagnosed with dementia are more likely to need to use a walker or wheelchair, to employ a home health aide, and to reside in non-independent living arrangements than are patients with essential tremor without dementia,” said corresponding author Elan D. Louis, MD, MS, of the University of Texas Southwestern Medical Center. “With this in mind, the findings of the present study highlight the importance of cognitive screening and monitoring in patients with essential tremor. Early detection of impairment may provide opportunities for interventions that may slow further cognitive decline and improve the quality of life of patients and their families.”

Source: Wiley

Categories : Metabolic DisordersTags :

Study Links Emulsifiers and Type 2 Diabetes Risk

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Photo by Amit Lahav on Unsplash

Emulsifiers, commonly used additives for improving the texture of food products and extending their shelf life, may be associated with the onset of type 2 diabetes, according to a large cohort study of over 100 000 people in France.

Researchers from Inserm, INRAE, Université Sorbonne Paris Nord, Université Paris Cité and Cnam, as part of the Nutritional Epidemiology Research Team (CRESS-EREN), studied the possible links between the dietary intake of food additive emulsifiers and the onset of type 2 diabetes between 2009 and 2023. They analysed the dietary and health data of 104 139 adults participating in the French NutriNet-Santé cohort study, specifically evaluating their consumption of this type of food additive using dietary surveys conducted every six months. The findings suggest an association between the chronic consumption of certain emulsifier additives and a higher risk of diabetes. The study is published in Lancet Diabetes & Endocrinology.

In Europe and North America, 30 to 60% of dietary energy intake in adults comes from ultra-processed foods. An increasing number of epidemiological studies suggest a link between higher consumption levels of ultra-processed foods with higher risks of diabetes and other metabolic disorders.

Emulsifiers are among the most commonly used additives. They are often added to processed and packaged foods such as certain industrial cakes, biscuits and desserts, as well as yoghurts, ice creams, chocolate bars, industrial breads, margarines and ready-to-eat or ready-to-heat meals, in order to improve their appearance, taste and texture and lengthen shelf life. These emulsifiers include for instance mono- and diglycerides of fatty acids, carrageenans, modified starches, lecithins, phosphates, celluloses, gums and pectins.

As with all food additives, the safety of emulsifiers had been previously evaluated by food safety and health agencies based on the scientific evidence that was available at the time of their evaluation.
However, some recent studies suggest that emulsifiers may disrupt the gut microbiota and increase the risk of inflammation and metabolic disruption, potentially leading to insulin resistance and the development of diabetes.

For the first time worldwide, a team of researchers in France has studied the relationships between the dietary intakes of emulsifiers, assessed over a follow-up period of maximum 14 years, and the risk of developing type 2 diabetes in a large study in the general population.

The results are based on the analysis of data from 104 139 adults in France (average age 43 years; 79% women) who participated in the NutriNet-Santé web-cohort study (see box below) between 2009 and 2023.

The participants completed at least two days of dietary records, collecting detailed information on all foods and drinks consumed and their commercial brands (in the case of industrial products). These dietary records were repeated every six months for 14 years, and were matched against databases in order to identify the presence and amount of food additives (including emulsifiers) in the products consumed. Laboratory assays were also performed in order to provide quantitative data. This allowed a measurement of chronic exposure to these emulsifiers over time.

During follow-up, participants reported the development of diabetes (1056 cases diagnosed), and reports were validated using a multi-source strategy (including data on diabetes medication use). Several well-known risk factors for diabetes, including age, sex, weight (BMI), educational level, family history, smoking, alcohol and levels of physical activity, as well as the overall nutritional quality of the diet (including sugar intake) were taken into account in the analysis.

After an average follow-up of seven years, the researchers observed that chronic exposure – evaluated by repeated data – to the following emulsifiers was associated with an increased risk of type 2 diabetes:

  • carrageenans (total carrageenans and E407; 3% increased risk per increment of 100 mg per day)
  • tripotassium phosphate (E340; 15% increased risk per increment of 500 mg per day)
  • mono- and diacetyltartaric acid esters of mono- and diglycerides of fatty acids (E472e; 4% increased risk per increment of 100 mg per day)
  • sodium citrate (E331; 4% increased risk per increment of 500 mg per day)
  • guar gum (E412; 11% increased risk per increment of 500 mg per day)
  • gum arabic (E414; 3% increased risk per increment of 1000 mg per day)
  • xanthan gum (E415; 8% increased risk per increment of 500 mg per day)

This study constitutes an initial exploration of these relationships, and further investigations are now needed to establish causal links. The researchers mentioned several limitations of their study, such as the predominance of women in the sample, a higher level of education than the general population, and generally more health-promoting behaviours among the NutriNet-Santé study participants. Therefore caution is needed when extrapolating the conclusions to the entire French population.

The study is nevertheless based on a large sample size, and the researchers have accounted for a large number of factors that could have led to confounding bias. They also used unique, detailed data on exposure to food additives, down to the commercial brand name of the industrial products consumed. In addition, the results remain consistent through various sensitivity analyses, which reinforces their reliability.

“These findings are issued from a single observational study for the moment, and cannot be used on their own to establish a causal relationship,”explain Mathilde Touvier, Research Director at Inserm, and Bernard Srour, Junior Professor at INRAE, lead authors of the study. “They need to be replicated in other epidemiological studies worldwide, and supplemented with toxicological and interventional experimental studies, to further inform the mechanisms linking these food additive emulsifiers and the onset of type 2 diabetes. However, our results represent key elements to enrich the debate on re-evaluating the regulations around the use of additives in the food industry, in order to better protect consumers.”

Among the next steps, the research team will be looking at variations in certain blood markers and the gut microbiota linked to the consumption of these additives, to better understand the underlying mechanisms. The researchers will also look at the health impact of additive mixtures and their potential ‘cocktail effects.’

They will also work in collaboration with toxicologists to test the impact of these exposures in in vitro and in vivo experiments, to gather more arguments in favour of a causal link.

Categories : Hospitals PaediatricsTags :

Refurbished School for Paediatric Patients Bridges Critical Learning Gaps

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Photo by Mary Taylor on Pexels

April 16 2024 – The Chris Hani Baragwanath Hospital School officially opened in its new location today, marking a key milestone in the partnership between Wits University and the academic hospital. The school caters for all learners in need of longer-term and chronic treatment for various paediatric conditions. Learners between Grades R and 12 are taught.  

“Sick children have multiple needs, and it’s our duty to ensure that they don’t miss out on any schooling. Everyone deserves the right to be educated and to contribute meaningfully to their communities as adults,” said Professor Shabir Madhi, Dean of the Wits Faculty of Health Sciences. 

Professor Madhi noted that the previous school building will be used as a campus for medical students and to grow the university’s teaching and learning footprint at Chris Hani Baragwanath Academic Hospital.  

The school district representative for Johannesburg Central, Ronica Ramdath, said that often sick children forfeit their education, which can be mitigated through the correct teaching approach and through supportive facilities. “When I first came to the school some years back, I was amazed at the teachers’ dedication. I remember seeing a teacher load all their educational resources in a bag and walk to the paediatric ward to teach sick children. Today, these children all benefit from such support,” she said.  

The Wits Faculty of Health Sciences heads of schools were present, together with hospital and teaching representatives.  

Meanwhile, Professor Madhi said that the university’s wifi is available at Chris Hani Baragwanath Hospital, underpinning Wits’ commitment to invest in a world-class academic hospital facility. “We are very proud of our footprint at the hospital and hope to continue to add value through research and clinical work,” he said. 

Source: University of the Witwatersrand – Faculty of Health Sciences

Categories : Immune SystemTags :

How Glucocorticoids Reprogram Immune Cells to Slow them Down

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Scanning electron micrograph of a T cell lymphocyte. Credit: NIH / NIAID

Cortisone and other related glucocorticoids are extremely effective at curbing excessive immune reactions. But previously, astonishingly little was known about how they exactly do that. A team of researchers have now explored the molecular mechanism of action in greater detail. As the researchers report in the journal Nature, glucocorticoids reprogram the metabolism of immune cells, activating the body’s natural “brakes” on inflammation. These findings lay the groundwork for development of anti-inflammatory agents with fewer and less severe side effects.

The glucocorticoid cortisone is naturally present in the body as the stress hormone cortisol, which is released to improve the body’s responses to stress. Cortisol intervenes in sugar and fat metabolism and affects other parameters, including blood pressure and respiratory and heart rate. At higher doses, it also inhibits immune system activity, making it it useful for medical purposes. Due to their excellent efficacy, synthetic glucocorticoid derivates that inhibit inflammation even more strongly are used to treat a wide range of immune-mediated inflammatory diseases.

Glucocorticoids affect not only genes, but also cellular energy sources

Glucocorticoid-based medications come with side effects, especially at higher doses and when administered for longer periods. These side effects are related to the other effects of the body’s own cortisol, and include hypertension, osteoporosis, diabetes, and weight gain. With the aim of developing anti-inflammatory agents with fewer and less severe side effects, a team of researchers from from Charité – Universitätsmedizin Berlin, Uniklinikum Erlangen and Ulm University has now conducted a closer study of how the immunosuppressive effects of glucocorticoids exactly works.

Lead researcher Prof Gerhard Krönke, director of the Department of Rheumatology and Clinical Immunology at Charité, explains: “It was previously known that glucocorticoids activate a number of genes in different cells of the body. But through this mechanism, they mainly activate the resources present in the body. This does not adequately explains its strong immunosuppressive effect. In our study, we have now been able to show that glucocorticoids affect more than just the gene expression in immune cells. It also affects the cell´s powerhouses, the mitochondria. And that this effect on cell metabolism is in turn crucial to the anti-inflammatory effects exerted by glucocorticoids.”

Swords to plowshares

For the study, the research team focused on macrophages, a type of immune cell responsible for eliminating intruders such as viruses and bacteria. These cells can also play a role in the emergence of immune-mediated inflammatory diseases. In a mouse model, the researchers studied how these immune cells responded to inflammatory stimuli in a laboratory setting and what effects additional administration of a glucocorticoid had. The researchers observed that in addition to its effect on gene expression, glucocorticoids had a major effect in reversing changes in the cell metabolism that had been initiated by the inflammatory stimuli.

“When macrophages are put into ‘fight’ mode, they redirect their cellular energy into arming for a fight. Instead of supplying energy, their mitochondria produce the components needed to fight intruders,” Krönke says, describing the processes involved. “Glucocorticoids reverse the process, switching the ‘fight’ mode back off and turning swords into plowshares, so to speak. A tiny molecule called itaconate plays an especially important role in this.”

Itaconate mediates anti-inflammatory effect of glucocorticoids

Itaconate is an anti-inflammatory substance that the body naturally produces inside its mitochondria. Macrophages produce it early on when they are activated so that the inflammatory reaction will subside after a certain period. Generation of this natural immune “brake,” however, requires sufficient fuel. When the cell´s powerhouses are arming up for a fight, that is no longer the case, so itaconate production dwindles to a halt after a while. With normal, short-term inflammation, this timing is effective because the immune response has also subsided in the meantime.

“With a persistent inflammatory stimulus, the drop-off in itaconate production is an issue because there is then no immune ‘brake’ even though the immune system is still running on all cylinders, eventually contributing to chronic inflammation,” explains Dr Jean-Philippe Auger, a scientist at the Department of Medicine 3 – Rheumatology and Immunology at Uniklinikum Erlangen and the first author of the study. “This is where glucocorticoids intervenes. By reprogramming the mitochondrial function, they ramp up the formation of itaconate in the macrophages, restoring its anti-inflammatory effect.”

The search for new active substances

Using animal models for asthma and rheumatoid arthritis, the researchers showed how much the anti-inflammatory effect of glucocorticoids depends on itaconate. Glucocorticoids had no effect in animals unable to produce itaconate. So, if itaconate mediates the immunosuppressant effect of cortisone, what about administering itaconate directly, instead of glucocorticoids?

“Unfortunately, itaconate isn’t a particularly good candidate as an anti-inflammatory drug, because it’s unstable, and due to its high reactivity, it could cause side effects if administered systemically,” Krönke explains. “Aside from that, we assume the processes in humans to be a bit more complex than those in mice. So our plan is to look for new synthetic compounds that are just as effective as glucocorticoids at reprogramming the mitochondrial metabolism inside immune cells, but have fewer and less severe side effects.”

Source: Charité – Universitätsmedizin Berlin