Month: January 2025

Categories : Antibiotics Respiratory DiseasesTags :

Short-course Antibiotics are Game-changers for Healthcare

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Photo by Marcelo Leal on Unsplash

Antibiotic overuse is a key driver in the rise of antimicrobial resistance (AMR), a major global health crisis. Researchers from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) and Duke-NUS Medical School have provided compelling evidence that short-course antibiotic treatments can be a game-changer in tackling ventilator-associated pneumonia (VAP), a serious infection common in critically ill patients.

The findings from the landmark REGARD-VAP trial, published in Lancet Respiratory Medicine, and the accompanying economic analyses published in Lancet Global Health, highlight how prudent antibiotic use can curb resistance, effectively safeguarding patients as well as combatting the global threat of antimicrobial resistance while reducing healthcare costs.

Led by the NUS Medicine research team, the clinical trial examined over 450 patients across intensive care units (ICUs) in Singapore, Thailand, and Nepal. Results revealed that short-course antibiotics. carefully tailored to individual patients’ recovery, are just as effective as traditional longer treatments in preventing death and recurrence of pneumonia. “By shortening the duration of antibiotics, we can reduce the risks of side effects and resistance without compromising patient outcomes,” added Dr Mo Yin, Junior Academic Fellow at the Department of Medicine, NUS Medicine, and principal investigator of the clinical trial, and co-author of the economic analysis.

The economic analyses accompanying the trial were just published in the prestigious journal Lancet Global Health. They demonstrated that adopting short-course antibiotics offers significant value for healthcare systems. In Singapore, the strategy is cost-saving, reducing hospital expenditure while maintaining excellent outcomes for patients. In Thailand and Nepal, short-course antibiotics were highly cost-effective, with health gains outweighing the modest additional costs incurred. “Short-course antibiotics are a pragmatic solution that benefits patients and healthcare systems alike, particularly in resource-limited settings,” said Assistant Professor Yiying Cai, lead researcher from the Health Services and Systems Research Programme at Duke-NUS.

The REGARD-VAP study’s findings have practical implications for hospitals worldwide. Short-course antibiotics can streamline treatment in ICUs, where managing infections efficiently is vital. The approach is effective across high-income (Singapore), middle-income (Thailand), and low-income (Nepal) settings, making it a scalable solution for diverse healthcare systems. These results provide robust evidence including cost-effectiveness data for policymakers to adopt short-course antibiotics into national and institutional guidelines.

The team hopes to disseminate their findings globally to encourage the adoption of short-course antibiotics, particularly in regions with limited resources. They also advocate for integrating cost-effectiveness studies into future clinical trials to strengthen both clinical and economic decision-making processes. By reducing unnecessary antibiotic exposure, short-course treatments help preserve the effectiveness of existing drugs for future generations. Every additional day of antibiotic use increases the risk of drug resistance by 7%. Reducing treatment duration is a critical step in combating this silent epidemic. “Prudent antibiotic use is essential to combat antimicrobial resistance and optimise healthcare outcomes. Our findings make a strong case for adopting short-course antibiotics as the new standard of care,” concluded Dr Mo Yin.

Source: National University of Singapore, Yong Loo Lin School of Medicine

Categories : Mental Health Obstetrics & GynaecologyTags :

PTSD and Anxiety may Affect Reproductive Health in Female Firefighters

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Source: CC0

A new study led by University of Arizona researchers in collaboration with fire service partners and other researchers around the country through the Fire Fighter Cancer Cohort Study showed that post-traumatic stress disorder and anxiety are associated with lower levels of anti-Müllerian hormone, a marker of ovarian reserve, among women firefighters.

The ovarian reserve, a measure of fertility, is the number of healthy eggs in a woman’s ovaries that could potentially be fertilised.

“These findings highlight the negative effect that mental health conditions can have on health – specifically, reproductive health,” said first author Michelle Valenti, MPH, a doctoral student in epidemiology at the Zuckerman College of Public Health and program coordinator of the Fire Fighter Cancer Cohort Study’s Women Firefighter Studies.

The paper was published in the Journal of Women’s Health.

Firefighters are exposed to high stress and traumatic situations in addition to chemical exposures and have a higher prevalence of PTSD compared with the general population. Previous research showed that women firefighters have lower levels of anti-Müllerian hormone compared with women who are not firefighters; however, the reason why was unknown.

The research team, which included personnel at the Zuckerman College of Public Health’s Center for Firefighter Health Collaborative Research, led this analysis to determine whether anxiety, depression or PTSD were associated with anti-Müllerian hormone levels. They found that clinical diagnoses of PTSD and anxiety among women firefighters were associated with reductions in anti-Müllerian hormone levels of 66% and 33%, respectively.

These findings highlight a potential mechanism through which adverse mental health conditions could lead to adverse reproductive outcomes. Further research is needed to identify potential areas for intervention.

“The work of this AMH study within the broader context of the FFCCS is imperative to taking care of all of our firefighters,” said Captain Caitlin St. Clair of the Puget Sound Regional Fire Authority. “These findings provide scientific leverage to fire departments to implement programs to reduce stress and improve the lives of our firefighter women.”

The Women Firefighter Study, a subgroup of the Fire Fighter Cancer Cohort Study, aims to identify causes of stress, cancer and adverse reproductive health effects in women firefighters that would inform effective interventions to mitigate these conditions.

“This study demonstrates the power of the Fire Fighter Cancer Cohort Study’s Women Firefighter Study to evaluate exposures that lead to adverse gynaecologic conditions,” Valenti said. “The Women Firefighter Study would not be possible without our amazing fire service partners who have championed women firefighter research.”

Source: University of Arizona Health Sciences

Categories : Diseases, Syndromes and Conditions Obstetrics & GynaecologyTags :

Human Papillomavirus Infection Kinetics Revealed in New Longitudinal Study

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Improved understanding of why some infections persist could improve treatment, screening, and vaccination strategies for HPV infection

Non-persistent human papillomavirus (HPV) infections are characterized by a sharp increase in viral load followed by a long plateau, according to a study published January 21st in the open-access journal PLOS Biology by Samuel Alizon of the National Centre for Scientific Research (CNRS), France, and colleagues.

Chronic HPV infection is responsible for more than 600 000 new cancers each year, including nearly all cervical cancers. Infection among young women is common, impacting nearly 20% of women 25 years of age. Fortunately, the vast majority of these infections clear within two years without symptoms. Still, a better understanding of why some infections clear while others persist could improve treatment, screening, and vaccination strategies for HPV-associated diseases.

To monitor the dynamics of HPV infection, the PAPCLEAR cohort study in France followed 189 women aged 18 to 25 years for up to 24 months. Researchers followed participants every two months, collecting information on viral kinetics and immune markers.

By frequently monitoring participants, the researchers achieved unprecedented temporal resolution on viral and immune kinetics. They found that non-persistent infections are characterised by a plateau in HPV viral load that starts around 2 months after infection and lasts for 13 to 20 months before rapidly declining. Additionally, they found a strong correlation between a population of immune cells in between innate and adaptive immunity, namely TCRγδ cells, and the total amount of viruses produced.

The study is limited by the fact that many of the infection follow-ups were truncated, meaning that the participants were already infected when enrolled or were lost to follow-up before infection clearance. Furthermore, only 4 out of 76 infected participants were followed for 18 months or more. Therefore, differences between chronic and acute infections will have to wait for longer studies.

The authors add, “Asymptomatic genital infections by human papillomaviruses (HPVs) display striking dynamics at the frontier between acute and chronic infections. HPV infections appear to be associated with specific patterns of the innate and adaptative local immune response.”

Provided by PLOS

Categories : Mental HealthTags :

New Research Reveals Recent Trends in ADHD Diagnoses

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Source: Paul, et al. 2024, Psychiatric Research and Clinical Practice

New research has identified differing trends in attention-deficit/hyperactivity disorder (ADHD) diagnoses among adolescents and adults, including an increase among adults from 2020 to 2023. The study, published in the American Psychiatric Association Journal Psychiatric Research and Clinical Practice, found a significant downward trends in ADHD incidence among adults from 2016 to 2020 and adolescents from 2016 to 2018. The ADHD incidence rate remained stable for adolescents in subsequent years.

ADHD is a neurodevelopmental disorder involving inattention and/or hyperactivity and impulsivity that interferes with a person’s functioning and ability to perform daily activities, including at school or work. ADHD is often viewed as a condition primarily impacting childhood and adolescence; however, it can also affect adults. Research on the prevalence of ADHD in adults remains limited, with findings varying considerably.

The large retrospective cohort study, conducted by researchers at Saint Louis University and SSM Health, involved more than 140 000 adolescents and adult patients who used services with a large healthcare system located in four states. New ADHD diagnoses were identified using patient charts. Regression analysis was used to determine incidence rates and trends in ADHD diagnoses by age group.

They found a significant downward trend in ADHD incidence among adults from 2016 to 2020 and an upward trend from 2020 to 2023. Among adolescents, a significant downward trend was observed between 2016 and 2018, and the incidence rate remained stable between 2018 and 2023.

“Fluctuations in incidence rates are likely due to a complex interplay of various factors,” the authors write. For example, increased awareness and destigmatisation of ADHD can lead to more diagnoses. Changes in diagnostic criteria, such as the expansion of ADHD criteria in the DSM-5 compared to previous editions, may have contributed to an increase in diagnoses. Variations in diagnostic practices and assessment methods can contribute to differences in incidence rates. In addition, there are some indications, the authors note, that the COVID-19 pandemic may have contributed to new ADHD diagnoses and worsening symptoms.

The authors suggest that this research can support future efforts to identify modifiable risk factors, ensure sufficient treatment resources, develop targeted interventions, and address diagnostic disparities.

Source: American Psychiatric Association

Categories : Cardiovascular DiseaseTags :

Divorce during Childhood Increases Odds of Stroke in Later Life

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Data on 13 205 adults suggests an increased risk of later life stroke among people who had experienced parental divorce in childhood

Photo by cottonbro studio

People whose parents divorced during their childhood may be at a greater risk of stroke later in life, according to a new study published January 22, 2025 in the open-access journal PLOS One by Esme Fuller-Thomson of University of Toronto, Canada, and colleagues. 

Each year, approximately 795 000 individuals in the U.S. have a stroke. Previous work has established many sociodemographic risk factors for stroke, as well as connections between adverse childhood events and stroke. In the new study, researchers looked specifically at the impact of childhood parental divorce among adults with no history of childhood abuse. They used data on 13 205 adults aged 65 and over from the 2022 Behavioral Risk Factor Surveillance System.

The study found that people who had experienced parental divorce before they were 18 years old had 1.61 times higher odds of having a stroke when compared to respondents who did not experience parental divorce (AOR=1.61, 95% CI=1.15-2.24). The association did not vary by sex, and remained even after controlling for known risk factors such as diabetes, depression, and small social support networks.

The current study was not designed to analyse the potential mechanism of this association, nor to prove causation. The conclusions may not be generalisable to younger generations, who have experienced overall higher rates of parental divorce. In addition, several potential confounding factors – including blood pressure, cholesterol, contraceptive use, age at parents’ divorce, and types of strokes – were not available in the data.

However, the authors say that their data supports an association between parental divorce during childhood and increased stroke risk, even in the absence of childhood abuse and other trauma. 

Senior author Esme Fuller-Thomson adds: “It is extremely concerning that older adults who grew up in divorced families had 60% higher odds of stroke, even after excluding those who had been physically or sexually abused as children. The magnitude of the association between parental divorce and stroke was comparable to well-established risk factors for stroke such as male gender and having diabetes.”

Provided by PLOS

Categories : NeurologyTags :

Sex Differences are Also Seen in Brain Immune Cells

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Image of an astrocyte, a subtype of glial cells. Glial cells are the most common cell in the brain. Credit: Pasca Lab, Stanford University
NIH support from: NINDS, NIMH, NIGMS, NCATS

New research from the University of Rochester finds that microglia function may not be as similar across sex as once thought. This discovery could have broad implications for how diseases like Alzheimer’s and Parkinson’s are approached and studied, and points to the necessity of having gender-specific research. It is already known that more women are diagnosed with Alzheimer’s and more men are diagnosed with Parkinson’s, but it’s unclear why.

Microglia are the immune cells of the central nervous system, clearing toxins in the brain. But if they are overactive, they can damage neurons instead and, in some cases, have been found to promote the progression of neurodegenerative diseases like Alzheimer’s and Parkinson’s. Although there are known sex-related differences in how microglia function, it was thought to be less variation in how they behave in adulthood. The new study showied how microglia respond differently in adult male versus female mice when given an enzyme inhibitor to block its microglia survival receptor.

“It is a fortuitous finding that has repercussions for what people are doing in the field, but also helps us understand microglia biology in a way that people may not have been expecting,” said Ania Majewska, PhD, professor of Neuroscience and senior author of the study in Cell Reports. “This research has a lot of ramifications for microglia biology and as a result all these diseases where microglia are important in a sex-specific manner.”

Pexidartinib or PLX3397 is an enzyme inhibitor commonly used to remove microglia in the lab setting to help researchers better understand the role of these cells in brain health, function, and disease. PLX3397 is also used to treat the rare disease tenosynovial giant cells tumours (TGCT), a condition that causes benign tumours to grow rapidly in the joints.

Researchers in the Majewska Lab were using PLX3397 in male versus female experiments but continued to run into difficulties, so they decided to take a different approach with the inhibitor. Instead of using it to ask other questions, they decided to better understand how microglia were responding to the drug in males versus females.

First author Linh Le, PhD (‘24), currently a Research Scientist, SetPoint Medical Corp, was a graduate student in the Majewska Lab when she found the expected response from microglia to PLX3397 in male mice: it blocked the receptor that signals microglial survival and depleted the microglia. However, Le, et al, were surprised to find that female microglia responded with a different signalling strategy that resulted in increased microglial survival and less depletion.

“These findings are crucial in the rapidly emerging field of developing disease-modifying therapies that target microglia,” said Majewska. “We do not yet know why the microglia are acting differently in the two sexes. I think we’d like to understand how the signaling through this receptor is regulated in different conditions, such as hormonal changes, basal state, inflammatory, or an anti-inflammatory state.”

Source: University of Rochester Medical Center

Categories : Diseases, Syndromes and ConditionsTags :

Sleep Apnoea Treatment Reduces Risk of Getting into Car Accidents

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Photo by Why Kei on Unsplash

Sleepiness at the wheel is a significant contributing factor to motor vehicle accidents. A new analysis published in Otolaryngology–Head and Neck Surgery reveals that for people with sleep apnoea, getting surgery for their condition may lessen their risk of such accidents compared with using a Continuous Positive Airway Pressure (CPAP) device at night or receiving no treatment.

In the analysis of data on 2 832 437 patients with obstructive sleep apnoea, 3.4% of patients who underwent surgery were in a car accident at any point following their diagnosis, compared with 6.1% of those using a CPAP and 4.7% of those not receiving any treatment.

Patients receiving no treatment had 21% higher odds of motor vehicle accidents compared with the surgery group. The surgery group had 45% lower odds compared with the CPAP group.

Patients with obstructive sleep apnoea who experienced accidents were more likely to have comorbidities such as hypertension, diabetes, and heart failure following the accident.

“Our findings underscore the profound impact that inadequately managed obstructive sleep apnoea can have on individual health and public safety,” said corresponding author Elliott M. Sina, BA, a medical student at the Sidney Kimmel Medical College at Thomas Jefferson University. “This work adds to the growing body of evidence supporting surgical interventions such as hypoglossal nerve stimulation as an effective alternative treatment for select patients with obstructive sleep apnoea.”

Source: Wiley

Categories : Diet and Nutrition Metabolic DisordersTags :

In Obesity or Not, Individuals Prefer High-calorie Food

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Calorie content drives food preference despite similar taste in individuals with and without obesity

Source: Pixabay CC0

Higher calorie foods were preferred among individuals with and without obesity despite similar taste and texture, according to a study published December 17th in the open-access journal PLOS Biology by Albino Oliveira-Maia from the Champalimaud Foundation, Portugal, and colleagues.

Eating sends signals to the brain with information about a food’s energy content, which can influence food preferences irrespective of flavor. People with obesity often have impairments in areas of the brain where dopamine is released, which may drive reward-related eating and a preference for energy-dense foods rich in fat and sugars. Weight loss due to bariatric surgery has been associated to a normalization of reward-related eating with a shift of preferences toward healthier options, but the underlying mechanisms are not well understood.

In this study, after examining a large group of healthy volunteers, researchers compared food preferences in three groups: 11 individuals with obesity, 23 post-bariatric surgery patients, and 27 non-obese control subjects. They gave participants sweetened low-fat yogurt with and without maltodextrin (a carbohydrate that adds calories to the yogurt with no impact on taste or texture). Participants ate the yogurt at home, alternating between the maltodextrin-containing and -free yogurt. All three groups ate more of the maltodextrin-containing yogurt, despite rating both as equally pleasant. Somewhat unexpectedly, the effects of maltodextrin on yogurt consumption were similar in individuals with obesity relative to their non-obese counterparts.

The study also used radioactive iodine labelling and single photon emission computed tomography to visualise dopamine receptors in the brain. Consistent with previous studies, individuals with obesity had lower dopamine receptor availability than non-obese controls. Dopamine receptor availability was similar in the surgical and non-obese groups and was associated with more restrained eating. These results suggest that obesity-related brain changes can be reversed after bariatric surgery, potentially impacting the amount of food consumed but not necessarily the types of food preferred.

The authors add, “We were very intrigued that, while behaviour was guided towards eating yoghurts with higher energy-content, this did not seem to be a result of explicit choices, since consistent changes in pleasantness of flavours enriched with carbohydrates were not found. Importantly, this behaviour was maintained in patients with obesity and after weight-loss surgery, even though there were important differences in their brain dopaminergic system.”

Provided by PLOS

Categories : GeneticsTags :

DNA Damage can Stay Unrepaired for Years

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The findings are set to change our understanding of genetic mutation

Photo by Sangharsh Lohakare on Unsplash

In a paradigm shift in how we view mutations, researchers uncover forms of DNA damage in healthy cells – most particularly in blood stem cells – that can persist unrepaired for years.

While most known types of DNA damage are fixed by our cells’ in-house repair mechanisms, some forms of DNA damage evade repair and can persist for many years, new research shows. This means that the damage has multiple chances to generate harmful mutations, which can lead to cancer.

Scientists from the Wellcome Sanger Institute and their collaborators analysed family trees of hundreds of single cells from several individuals. The team pieced together these family trees from patterns of shared mutations between the cells, indicating common ancestors.

Researchers uncovered unexpected patterns of mutation inheritance in the trees, revealing that some DNA damage persists unrepaired. In the case of blood stem cells, this can be for two to three years.

The research, published in Nature, changes the way we think about mutations, and has implications for understanding the development of various cancers.

Throughout our life, all of the cells in our body accumulate genetic errors in the genome, known as somatic mutations. These can be caused by damaging environmental exposures, such as smoking, as well as the everyday chemistry occurring in our cells.

DNA damage is distinct from a mutation. While a mutation is one of the standard four DNA bases (A, G, T or C) in the wrong place, similar to a spelling mistake, DNA damage is chemical alteration of the DNA, like a smudged unrecognisable letter. DNA damage can result in the genetic sequence being misread and copied incorrectly during cell division, in a process known as DNA replication. This introduces permanent mutations that can contribute to the development of cancers. However, the DNA damage itself is usually recognised and mended quickly by repair mechanisms in our cells.

If researchers can better understand the causes and mechanisms of mutations, they may be able to intervene and slow or remove them.

In a new study, Sanger Institute scientists and their collaborators analysed data in the form of family trees of hundreds of single cells from individuals. The family trees are constructed from patterns of mutations across the genome that are shared between cells – for example, cells with many shared mutations have a recent common ancestor cell and are closely related.

The researchers collated seven published sets of these family trees, known as somatic phylogenies. The data set included 103 phylogenies from 89 individuals,1 spanning blood stem cells, bronchial epithelial cells and liver cells

The team found unexpected patterns of mutation inheritance in the family trees, revealing that some DNA damage can persist unrepaired through multiple rounds of cell division. This was particularly evident in blood stem cells, where between 15 to 20 per cent of the mutations resulted from a specific type of DNA damage that persists for two to three years on average, and in some cases longer.

This means that during cell division, each time the cell attempts to copy the damaged DNA it can make a different mistake, leading to multiple different mutations from a single source of DNA damage. Importantly, this creates multiple chances of harmful mutations that could contribute to cancer. Researchers suggest that although these types of DNA damage occur rarely, their persistence over years means they can cause as many mutations as more common DNA damage.

Overall, these findings change the way researchers think about mutations, and have implications for understanding the development of cancer.

Source: Wellcome Trust Sanger Institute

Categories : Metabolic DisordersTags :

Treatment for Children with Obesity has Lasting Effect

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Photo by Patrick Fore on Unsplash

When children with obesity undergo weight-loss treatment, the effects have repercussions later in life and the risk of serious health problems and premature death is lower as they reach young adulthood. However, this is not the case for depression and anxiety, a study from Karolinska Institutet published in JAMA Pediatrics reports.

The study shows that children and adolescents who respond well to obesity treatment are less likely to develop obesity-related diseases, such as type 2 diabetes, hypertension and dyslipidaemia as young adults.  

The treatment studied involved support for children with obesity and their families designed to motivate healthy diets, exercise and sleep habits – what is known as “behavioural lifestyle therapy”.  

“The results are very good news,” says the study’s last author Emilia Hagman, principal researcher at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet. “Whether or not the treatment of obesity in childhood has long-term health benefits have been debated, since weight-loss is hard to maintain.”

Higher risk of dying as young adults

The study shows that children with obesity who respond to treatment also run a lower risk of premature death. A previous study, published in PLOS Medicine by the same research group, has shown that children with obesity have a much higher mortality risk in early adulthood, and were much more likely to die from suicide and somatic conditions. Just over a quarter of deaths were obesity-related.

“This emphasises the importance of providing early treatment, as we know that timely intervention increases the likelihood of success and helps mitigate the long-term health risks associated with obesity,” says Dr Hagman.

Depression and anxiety are not affected

However, the risk of depression and anxiety was not affected by the treatment outcomes in childhood, the JAMA Pediatrics paper shows. No matter the outcome of obesity treatment in childhood, the risk of anxiety and depression was unchanged in young adulthood.

“It has been believed that weight loss could decrease symptoms of depression and anxiety, but we can now show that it’s not the case,” says Dr Hagman. “Even though there’s a link between the two comorbidities, they must be treated in parallel.”

The study included over 6700 individuals who had received treatment for obesity during childhood identified via the BORIS register (the Swedish Childhood Obesity Treatment Register) and who were then followed up as young adults in the Swedish Patient Register, the Prescribed Drugs Register and the Cause of Death Register. A control group from the general population was also used, matched by age, sex and place of residence.

GLP1 analogues, which have become popular obesity drugs in recent years, were not part of the study as they were yet approved when the study participants were being treated for obesity. As Dr Hagman points out, it is still uncommon for this type of drug to be administered to children.

“I’m in favour of their use as these drugs eases feelings of hunger, which is something that some children struggle with” she says. “That said, lifestyle therapy is still the foundation of all treatments for childhood obesity.”

The research group will now be trying to identify therapy options that are most effective for different individuals and the health/risk markers that are significant for future health.

Source: Karolinska Institutet